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Sample records for 3p 5q 17p

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    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.

  3. RECENT ADVANCES IN THE 5Q- SYNDROME

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    Andrea Pellagatti

    2015-05-01

    Full Text Available 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.

  4. Genetics Home Reference: 5q minus syndrome

    Science.gov (United States)

    ... for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood. 2011 Mar ... U, List A, MacBeth KJ. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic ...

  5. Main: 1B5Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5Q トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...EESRRIEQQSDEQTKAEIMQVLRKMFPGKDVPDATDILVPRWWSDRFYKGTFSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B5Q.jpg ...

  6. Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

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    Sugimoto Yuka

    2012-03-01

    Full Text Available Abstract Background While lenalidomide (LEN shows high efficacy in myelodysplastic syndromes (MDS with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. Design and methods We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN, MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML without del[5q] by metaphase cytogenetics (MC who underwent therapy with LEN. Results Fluorescence in situ hybridization (FISH or single nucleotide polymorphism array (SNP-A-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8% additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08 and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11. However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Conclusions Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Levitt, R.C.; Meyers, D.A. [Johns Hopkins Medical Institutions, Baltimore, MD (United States); Bleecker, E.R. [Univ. of Maryland, Baltimore, MD (United States)] [and others

    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.

  8. Síndrome 5q-: um relato de caso

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    Marcelo Gil Cliquet

    2015-10-01

    Full Text Available As síndromes mielodisplásicas (SMD se caracterizam por hematopoiese ineficaz, citopenias, distúrbios qualitativos de uma ou mais linhagens de células do sangue periférico, anormalidades cromossômicas e uma predileção variável de evolução para leucemias mielóides agudas. As anormalidades mais freqüentemente observadas incluem a deleção do braço longo do cromossomo 5 (5q-. O tratamento com novas drogas vem mudando as perspectivas de tratamento. A lenalidomida é um fármaco que fica reservada para o tratamento das síndromes mielodisplásicas 5q- e mieloma múltiplo. Objetivo: Relatar o uso do fármaco lenalidomida por um paciente portador de SMD com a síndrome 5q-, avaliando o impacto na necessidade transfusional. Relato de caso: Paciente de 64 anos, sexo masculino, encaminhado por apresentar anemia (8,2g/dl macrocítica (VCM=109fl. Série branca e plaquetária normais. Após investigação para hemólise, carência de B12, ácido fólico e Ferro sem anormalidades, foi solicitada avaliação de medula óssea que revelou hipercelularidade (relação G/E=4/1, aumento de mieloblastos e prómielocitos, e cariótipo mostrando 46XY del(5(q15q33{6} e 46XY{14}. Prescrito Lenalidomida (10mg VO/dia em ciclos de 21 dias com intervalo de uma semana. Desde a primeira consulta até o início do tratamento, o paciente recebeu 16 unidades de concentrados de hemácias. Após dois ciclos, observou-se elevação da hemoglobina, sem transfusões, chegando a 12,3g/dl. Apresentou, no entanto, redução de neutrófilos (970/mm³ e de plaquetas (107.000/mm3. Conclusão: O uso do fármaco pode melhorar a qualidade de vida e a sobrevida dos pacientes portadores da síndrome 5q-, tendo em vista a redução de transfusões de sangue, evitando, assim, a sobrecarga de ferro e ainda pode diminuir a taxa de transformação em LMA.

  9. Síndrome 5q-: um relato de caso

    OpenAIRE

    Marcelo Gil Cliquet; Fábio Moreira Campos; Gabriel Murad Takao; Ricardo Hiroshi Murashita Fujiki; Thays Brunelli Pugliesi; Guilherme Cliquet

    2015-01-01

    As síndromes mielodisplásicas (SMD) se caracterizam por hematopoiese ineficaz, citopenias, distúrbios qualitativos de uma ou mais linhagens de células do sangue periférico, anormalidades cromossômicas e uma predileção variável de evolução para leucemias mielóides agudas. As anormalidades mais freqüentemente observadas incluem a deleção do braço longo do cromossomo 5 (5q-). O tratamento com novas drogas vem mudando as perspectivas de tratamento. A lenalidomida é um fármaco que fica reservada p...

  10. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP of the European Society for Blood and Marrow Transplantation (EBMT

    Directory of Open Access Journals (Sweden)

    Xavier Poiré

    2017-01-01

    Full Text Available Abstract Background Acute myeloid leukaemia (AML with 17p abnormalities (abn(17p carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT appears as the only potential curative option. Methods To address outcomes after allo-SCT in patients with abn(17p, we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. Results One hundred thirty-nine patients with confirmed abn(17p have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1. Median age was 54 years old. Abn(17p was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q- in 55%, monosomy 7 (-7 in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59% had a reduced-intensity conditioning regimen. The 2-year overall survival (OS and leukaemia-free survival (LFS were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM was 15%, and 2-year relapse incidence (RI was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age. Conclusions In contrast to the dismal prognosis reported for AML patients harbouring abn(17p undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.

  11. Microdeletion in distal 17p13.1

    DEFF Research Database (Denmark)

    Zeesman, Susan; Kjaergaard, Susanne; Hove, Hanne Buciek;

    2012-01-01

    Array comparative genomic hybridization has led to the identification of new syndromes by identifying genomic imbalances not detectable by standard karyotyping methods and by allowing correlations with physical findings. Deletions in the 17p13.1 region have been reported in patients with dysmorph...

  12. PP2A: The Achilles Heal in MDS with 5q Deletion

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    David eSallman

    2014-09-01

    Full Text Available Myelodysplastic syndromes (MDS represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q (del(5q is pathologically and clinically distinct. Patients with del(5q MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14 gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to AML and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα. PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell cycle arrest and apoptosis in del(5q cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q MDS develop resistance to lenalidomide over time associated with PP2Acα overexpression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del(5q MDS.

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

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, R.; Bauer, J. M.; Mainzer, A. K.; Masiero, J. R. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, MS 183-427, Pasadena, CA 91109 (United States); Kramer, E. A. [Department of Physics, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816 (United States); Grav, T., E-mail: Rachel.A.Stevenson@jpl.nasa.gov [Planetary Science Institute, 1700 East Fort Lowell, Suite 106, Tucson, AZ 85719-2395 (United States)

    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.

  14. Water outburst activity in Comet 17P/Holmes

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    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.

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

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    Fries, M.H.; Reilly, P.A.; Williams, T.C. [Keesler Medical Center, MS (United States)] [and others

    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.

  16. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide.

    Science.gov (United States)

    Mortensen, Thomas Bech; Frederiksen, Henrik; Marcher, Claus Werenberg; Preiss, Birgitte

    2017-01-04

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed. This suggests that lenalidomide may be a viable treatment option for ITP in the presence of del(5q) not responding to standard treatments.

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

    Science.gov (United States)

    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

    2015-07-09

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Stallard, R.; Zurcher, V.; Schwartz, S. [Case Western Reserve Univ., Cleveland, OH (United States)

    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.

  19. Interstitial deletion of 5q33.3q35.1 in a boy with severe mental retardation

    OpenAIRE

    Lee, Jin Hwan; Kim, Hyo Jeong; Yoon, Jung Min; Cheon, Eun Jung; Lim, Jae Woo; Ko, Kyong Og; Lee, Gyung Min

    2016-01-01

    Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cas...

  20. [Lenalidomide treatment in myelodysplastic syndrome with 5q deletion--Czech MDS group experience].

    Science.gov (United States)

    Jonášová, Anna; Červinek, Libor; Bělohlávková, Petra; Čermák, Jaroslav; Beličková, Monika; Rohoň, Petr; Černá, Olga; Hochová, Ivana; Šišková, Magda; Kačmářová, Karla; Janoušová, Eva

    2015-12-01

    Myelodysplastic syndrome (MDS) is a common hematological disease in patients over sixty. Despite intensive research, the therapy of this heterogeneous blood disease is complicated. In recent years, two new therapeutic approaches have been proposed: immunomodulation and demethylation therapy. Immunomodulation therapy with lenalidomide represents a meaningful advance in the treatment of anemic patients, specifically those with 5q- aberrations. As much as 60-70% of patients respond and achieve transfusion independence. We present the initial lenalidomide experience of the Czech MDS group. We analyze Czech MDS register data of 34 (31 female; 3 male; median age 69 years) chronically transfused low risk MDS patients with 5q- aberration treated by lenalidomide. Twenty-seven (79.4%) patients were diagnosed with 5q- syndrome, 5 patients with refractory anemia with multilineage dysplasia, 1 patient with refractory anemia with excess of blasts 1, and 1 patient with myelodysplastic/myeloproliferative unclassified. Response, as represented by achieving complete transfusion independence, was achieved in 91% of patients. A true 5q- syndrome diagnosis in most our patients may be responsible for such a high response rate. Complete cytogenetic response was reached in 15% of patients and partial cytogenetic response in 67%, within a median time of 12 months. TP53 mutation was detected in 15% (3 from 18 tested) and 2 of these patients progressed to higher grade MDS. The majority of patients tolerated lenalidomide very well. Based on this albeit small study, we present our findings of high lenalidomide efficacy as well as the basic principles and problems of lenalidomide therapy.

  1. LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

    Institute of Scientific and Technical Information of China (English)

    Zhang Guoling; Yang Huijian; Xu Kaili; Zhou Jin; Qin Ruidi; Lu Minghua

    1998-01-01

    Objective:To identify the loss of heterozygosity (LOH) on chromosome 17p13.3 in ovarian cancer and cervical cancer. Methods: The frequency of LOH on chromosome 17p13.3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non-malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ.22. Results:LOH on 17p13.3 was found in 12 of 24 (50.0%) ovarian cancers (including a borderline mucinous cystadenoma), 4of 9 (44.4%) cervical carcinomas, and 1 of 13 (7.7%) nonmalignant gynecological diseases, which was cervical intraepithelial neoplasm HI (CIN Ⅲ) (P<0.01).Conclusion: These results show that LOH on 17p13.3 is associated with ovarian cancer and cervical cancer,suggesting that detection of LOH on 17p13.3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Amelung, P.J.; Panhuysen, C.I.M.; Postma, D.S. [Univ. of Maryland, Baltimore, MD (United States)]|[Beatrixoord Hospital (Netherlands)

    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.

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

    Science.gov (United States)

    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. Bilateral radial agenesis with absent thumbs, complex heart defect, short stature, and facial dysmorphism in a patient with pure distal microduplication of 5q35.2-5q35.3

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    Jamsheer Aleksander

    2013-01-01

    Full Text Available Abstract Background A partial duplication of the distal long arm of chromosome 5 (5q35-- > qter is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome. Clinical spectrum of this disorder mainly consists of mental retardation, microcephaly, short stature, skeletal anomalies, and craniofacial dysmorphism featuring flat facies, micrognathia, large, low-set dysplastic ears, hypertelorism, almond-shaped, down-slanted palpebral fissures, epicanthal folds, small nose, long philtrum, small mouth, and thin upper lip. Less frequent remarkable findings include craniosynostosis, heart defect, hypoplastic phalanges, preaxial polydactyly, hypospadias, cryptorchidism, and inguinal hernia. In most patients with a partial duplication of 5q the aberration occurred due to an inherited unbalanced translocation, therefore the phenotype was not reflective of pure trisomy 5q. Case presentation We report on a 9.5-year-old boy with some feature of Hunter-McAlpine syndrome including short stature, complex heart defect (dextrocardia, dextroversion, PFO, bilateral cryptorchidism, hypothyroidism, and craniofacial dysmorphism. Additionally, bilateral radial agenesis with complete absence of Ist digital rays, ulnar hypoplasia with bowing, choroidal and retinal coloboma, abnormal biliary vesicle were identified, which have never been noted in 5q trisomy patients. Karyotype analysis, sequencing and MLPA for TBX5 and SALL4 genes were unremarkable. Array comparative genomic hybridization detected a duplication on 5q35.2-5q35.3, resulting from a de novo chromosomal rearrangement. Our proband carried the smallest of all previously reported pure distal 5q trisomies encompassing terminal 5.4-5.6 Mb and presented with the most severe limb malformation attributed to the increased number of distal 5q copies. Conclusions We postulate that a terminal distal trisomy of 5q35.2-5q35.3, which maps 1.1 Mb telomeric to the MSX2 gene is causative for both

  7. Interstitial deletion of 5q33.3q35.1 in a boy with severe mental retardation.

    Science.gov (United States)

    Lee, Jin Hwan; Kim, Hyo Jeong; Yoon, Jung Min; Cheon, Eun Jung; Lim, Jae Woo; Ko, Kyong Og; Lee, Gyung Min

    2016-11-01

    Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cases, it is the most common feature described in patients who present the 5q33.3q35.1 deletion. Here, we report a case of a de novo deletion of 5q33.3q35.1, 46,XY,del(5)(q33.3q35.1) in an 11-year-old boy with mental retardation; to the best of our knowledge this is the first case in Korea to be reported. He was diagnosed with severe mental retardation, developmental delay, facial dysmorphisms, dental anomalies, and epilepsy. Chromosomal microarray analysis using the comparative genomic hybridization array method revealed a 16-Mb-long deletion of 5q33. 3q35.1(156,409,412-172,584,708)x1. Understanding this deletion may help draw a rough phenotypic map of 5q and correlate the phenotypes with specific chromosomal regions. The 5q33.3q35.1 deletion is a rare condition; however, accurate diagnosis of the associated mental retardation is important to ensure proper genetic counseling and to guide patients as part of long-term management.

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

    Science.gov (United States)

    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.

  9. CHROMOSOME 17P MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

    Institute of Scientific and Technical Information of China (English)

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君

    2002-01-01

    Objective: To investigate whether deletion of chromosome 17 is involved in the carcinogenesis of primary glioblastoma multiforme and to localize the possible common deletion region in the aforementioned chromosome. Methods: Polymerase chain reaction-based microsatellite analysis was used to assess loss of heterozygosity (LOH) on chromosome 17 in 20 primary glioblastoma multiforme (GBM). Fifteen fluorescent dye-labeled polymorphic markers were used. Results: Thirteen of twenty (65%) GBM displayed LOH on at least one marker of chromosome 17p. Two tumors showed either LOH or non-informativeness on all markers tested. The most frequent LOH was observed at loci including D17s799 (53.3%), Dl7s1852 (53.8%), Dl7s938 (63.20/o), Dl7s831 (55.6%). The loci D17s831 (on 17pl3) and D17s799(Dl7sl852 (17p11.2(pl2) are distal and proximal to p53 respectively. The frequencies of LOH at all loci examined on chromosome 17q were relatively low (<30%). None of informative loci exhibited microsatellite instability in this study. Conclusion: Loss of genetic material on chromosome 17p may play an important role in the pathogenesis of GBM. Besides the well-known TSG p53 on 17p, other unknown TSCs associated with GBM may be present on the chromosomal regions 17pl3 and 17p11.2(pl2, which are distal and proximal to p53 respectively.

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

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, C.A.; Holmgren, A. [Karolinska Inst., Stockholm (Sweden); Bajalica, S.; Lagercrantz, J. [Karolinska Hospital, Stockholm (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiang; Wang Jabs, E.; Hawkins, A.L.; Griffin, C.A. (John Hopkins School of Medicine, Baltimore, MD (United States)); Wise, C.A.; Lovett, M. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)); Le Paslier, D. (CEPH, Paris (France)); Pittler, S.J. (Univ. of South Alabama College of Medicine, Mobile, AL (United States))

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Prenatal Diagnosis of 17p13.1p13.3 Duplication

    Directory of Open Access Journals (Sweden)

    Kirsi Kiiski

    2012-01-01

    Full Text Available We present here the first prenatal diagnosis of 17p13.1p13.3 duplication. 17p13.3 duplication has recently been defined as a new distinctive syndrome with several diagnosed patients. In the current case prenatal chromosome analysis (G-banding performed on cultured amniocytes revealed additional material in chromosome 19p. This was further defined as a chromosome 17p13.1p13.3 duplication by FISH and genomic microarray analysis (GMA. In addition Prenatal BACs-on-Beads (PN_BoBs assay was performed, which detected the duplication clearly. This enables rapid prenatal diagnosis of the duplication for this family in the future.

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

    Science.gov (United States)

    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

  15. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 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...

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

    Directory of Open Access Journals (Sweden)

    J Gustav Smith

    2016-05-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. A Patient with Interstitial 5q21 Deletion, Familial Adenomatous Polyposis, Dysmorphic Features, and Profound Neurologic Dysfunction

    Directory of Open Access Journals (Sweden)

    Manoochehr Karjoo

    2017-01-01

    Full Text Available Familial adenomatous polyposis (FAP is a hereditary autosomal dominant cancer syndrome, results from germ line mutation or deletion of the Adenomatous Polyposis Coli (APC gene on chromosome 5q21. Patients with FAP suffer from multiple polyps mainly at the colorectal region as well as other parts of the gastrointestinal tract, which has propensity to transform into carcinoma. FAP has also been well described in association with various syndromic extra-gastrointestinal manifestations. Less commonly, patients with FAP present with varying degrees of cognitive dysfunction and developmental delay, though the reason for the association is unclear. Herein, we report the case of a male patient born with an interstitial deletion of chromosome 5q, 46,XY, del(5 (q14q23, presenting with familial adenomatous polyposis (FAP, profound developmental delay, cognitive dysfunction, and multiple congenital anomalies including talipes equinovarus, agenesis of the corpus callosum, and dysmorphic facial features.

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

    Science.gov (United States)

    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

  20. The association between DNA copy number aberrations at chromosome 5q22 and gastric cancer.

    Directory of Open Access Journals (Sweden)

    Pei-Chien Tsai

    Full Text Available BACKGROUND: Gastric cancer is common cancer. Discovering novel genetic biomarkers might help to identify high-risk individuals. Copy number variation (CNV has recently been shown to influence risk for several cancers. The aim of the present study was sought to test the association between copy number at a variant region and GC. METHODS: A total of 110 gastric cancer patients and 325 healthy volunteers were enrolled in this study. We searched for a CNV and found a CNV (Variation 7468 containing part of the APC gene, the SRP19 gene and the REEP5 gene. We chose four probes targeting at APC-intron8, APC-exon9, SRP19 and REEP5 to interrogate this CNV. Specific Taqman probes labeled by different reporter fluorophores were used in a real-time PCR platform to obtain copy number. Both the original non-integer data and transformed integer data on copy number were used for analyses. RESULTS: Gastric caner patients had a lower non-integer copy number than controls for the APC-exon9 probe (Adjusted p = 0.026 and SRP19 probe (Adjusted p = 0.002. The analysis of integer copy number yielded a similar pattern although less significant (Adjusted p = 0.07 for APC-exon9 probe and Adjusted p = 0.02 for SRP19 probe. CONCLUSIONS: Losses of a CNV at 5q22, especially in the DNA region surrounding APC-exon 9, may be associated with a higher risk of gastric cancer.

  1. A Turkish patient with large 17p11.2 deletion presenting with Smith Magenis syndrome.

    Science.gov (United States)

    Tug, E; Cine, N; Aydin, H

    2011-01-01

    Smith-Magenis syndrome (SMS), which occurs as a result of an interstitial deletion within chromosome 17p11.2-p12, is a disorder that presents itself with minor dysmorphic features, brachydactyly, short stature, hypotonia, delayed speech, cognitive deficits and neurobehavioral problems including sleep disturbances and maladaptive repetitive and self-injurious behavior. We present a girl with full SMS phenotype. G-banding cytogenetic analysis showed normal 46,XX karyotype. Whole-genome array comparative genomic hybridization (CGH) was performed due to the severity of the phenotype and the unusual features present in the patient. An interstitial deletion in 17p11.2-p12, approximately 4.73 Mb in size was determined. Characteristic physical and behavioral phenotype strongly suggested SMS. This, to the best of our knowledge is the first patient with SMS reported in Turkey. We emphasize the need for whole genome analysis in multiple congenital abnormalities/mental retardation disorders with unusual and severe phenotypes.

  2. Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p deletion.

    Science.gov (United States)

    Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Ferrajoli, Alessandra; Burger, Jan; Faderl, Stefan; Tambaro, Francesco Paolo; Jain, Nitin; Wierda, William G

    2014-08-01

    Although uncommon in treatment-naive patients with chronic lymphocytic leukemia, deletion 17p is a high-risk disease characteristic. We analyzed and reported outcomes for 63 patients with deletion 17p chronic lymphocytic leukemia who received first-line therapy at our institution; at time of first treatment, 81% had unmutated immunoglobulin heavy chain variable gene and 58% had complex karyotype. Forty-nine patients (76%) received first-line fludarabine, cyclophosphamide, rituximab-based therapy, 6 (11%) received rituximab-based and 8 (13%) received lenalidomide-based treatment. Overall, the complete plus nodular partial remission rate was 33%; on multivariable model, higher complete plus nodular partial remission rate was observed in patients with less than 50% cells positive for deletion 17p, and a higher probability of achieving at least a partial remission was observed with fludarabine, cyclophosphamide, rituximab-based treatment. After a median follow up of 33 months (range 1-89 months), the estimated median progression-free survival was 14 months (95% confidence interval 10-18) and estimated median overall survival was 63 months (95% confidence interval 43-83). In multivariable analysis, factors independently associated with longer progression-free survival were response to treatment and absence of complex karyotype. Achievement of complete plus nodular partial remission rate and mutated immunoglobulin heavy chain variable gene were independently associated with longer overall survival in multivariable model. Complex karyotype was associated with increased risk for Richter's transformation. New first-line strategies and agents must aim at both improving response and maintaining remission in patients with deletion 17p, particularly in the presence of complex karyotype.

  3. Allelic imbalance and fine mapping of the 17p13.3 subregion in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Hoff, C; Mollenhauer, J; Waldau, B;

    2001-01-01

    .3. This region is suspected to harbor another tumor suppressor gene. In order to get more information concerning the pattern of AIs in 17p13.3, we performed analysis of AI of 49 breast carcinomas at 6 polymorphic loci in 17p13.3. Eighty-six percent of the tumors present AI at least at one marker in 17p13...

  4. Analysis of the efficacy of lenalidomide in patients with intermediate-1 risk myelodysplastic syndrome without 5q deletion.

    Science.gov (United States)

    Yang, Yan; Gao, Sujun; Fan, Hongqiong; Lin, Hai; Li, Wei; Wang, Juan

    2013-09-01

    The aim of this study was to evaluate the efficacy and adverse effects of lenalidomide in the treatment of intermediate-1 risk non-5q deletion [non-del (5q)] myelodysplastic syndrome (MDS). A total of 30 patients with MDS were classified through G-banding chromosome karyotype analysis and fluorescence in situ hybridization (FISH). According to the International Prognostic Scoring System scores, among the 30 patients, 23 and seven cases had scores of 0.5 and 1.0, respectively. Lenalidomide (Revlimid(®)), 10 mg/day) was administered for 21 days every 28 days. All 30 cases were treated with lenalidomide for at least three cycles, including 20 cases with four cycles. The patients did not require erythropoietin, cyclosporine or iron chelation treatments. Statistical analysis was performed using SPSS statistical software version 13.0, and comparisons among groups were conducted using a t-test. The efficacy of lenalidomide was demonstrated in patients with intermediate-1 risk non-del (5q) MDS. Peripheral blood cell counts were improved following treatment, and absolute neutrophil, haemoglobin and platelet counts increased following 2-4 cycles of treatment. All patients became stable having undergone three cycles of treatment; however, 17 patients with chromosomal abnormalities had no cytogenetic response to the treatment, as confirmed through the FISH test. Patients with intermediate-1 risk non-del (5q) MDS treated with lenalidomide did not achieve complete haematological remission, although they demonstrated haematological improvement.

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

    NARCIS (Netherlands)

    Saft, L.; Karimi, M.; Ghaderi, M.; Matolcsy, A.; Mufti, G.J.; Kulasekararaj, A.; Gohring, G.; Giagounidis, A.; Selleslag, D.; Muus, P.; Sanz, G.; Mittelman, M.; Bowen, D.; Porwit, A.; Fu, T.; Backstrom, J.; Fenaux, P.; MacBeth, K.J.; Hellstrom-Lindberg, E.

    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 de

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

    Energy Technology Data Exchange (ETDEWEB)

    Juyal, R.C.; Figuera, L.E.; Hauge, X. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1996-05-01

    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 (1) FISH analysis, (2) PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (3) 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. 49 refs.

  7. Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ubol Chuensumran; Sopit Wongkham; Chawalit Pairojkul; Siri Chauin; Songsak Petmitr

    2007-01-01

    AIM: To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients.METHODS: DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned, sequenced, and identified by comparison with known nucleotide sequences in the genome database (www.ncbi.nlm.nih.gov). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by x2-test.The Kaplan-Meier method was used to analyze survival rates.RESULTS: From 33 primers, an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification, while 7 (13%) showed allelic loss. Interestingly, DNA amplification on chromosome 17p13.2 was associated with a good prognosis, median survival time (wk) of amp vs no amp was 44.14 vs 24.14,P = 0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis, median survival time (wk) of loss vs no loss was 18.00 vs 28.71, P =0.019). Moreover, Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNA amplification, allelic loss, and normal was 44.14 wk,18.00 wk, and 24.29 wk, respectively (P = 0.005).CONCLUSION: Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangiocarcinogenesis, and could be used as a prognostic marker in the treatment of ICC patients.

  8. Comet 17P/Holmes in Outburst: The Near Infrared Spectrum

    CERN Document Server

    Yang, Bin; Bus, Schelte J

    2009-01-01

    Jupiter family comet 17P/Holmes underwent a remarkable outburst on UT 2007 Oct. 24, in which the integrated brightness abruptly increased by about a factor of a million.We obtained near infrared (0.8 - 4.2 micron) spectra of 17P/Holmes on UT 2007 Oct. 27, 28 and 31, using the 3.0-m NASA Infrared Telescope Facility (IRTF) atop Mauna Kea. Two broad absorption bands were found in the reflectance spectra with centers (at 2 micron and 3 micron, 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 micron 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 micron has a color temperature of 360 +/- 40 K (corresponding to a superheat factor of ~ 2.0 +/- 0.2 at 2.45 AU). This is too hot for these grains to be icy. The detection ...

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

    Science.gov (United States)

    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.

  10. Near-Nucleus Photometry of Outbursting Comet 17P/Holmes

    CERN Document Server

    Stevenson, Rachel

    2012-01-01

    Comet 17P/Holmes underwent the largest cometary outburst in recorded history on UT 2007 Oct. 23, releasing massive quantities of dust and gas. We used the Canada-France-Hawaii telescope to obtain wide-field images of 17P/Holmes on 15 dates over a period of 3 months following the outburst and employ them here to examine the subsequent activity of the nucleus and the nature of the ejecta closest to the nucleus. Through aperture photometry we observed the in- ner coma (within 2500 km of the nucleus) to fade from an apparent magnitude of 11.7 mag to 17.6 mag, corresponding to absolute magnitudes of 8.1 mag and 12.4 mag, between UT 2007 Nov. 6 and 2008 Feb. 12. A second much smaller outburst occurred on UT 2007 Nov. 12, three weeks after the original outburst, suggesting that the nucleus remained unstable. The surface brightness profile of the inner coma was consistently shallow relative to the expected steady-state profile, and showed a persistent brightness enhancement within ~ 5000 km of the nucleus. We propose...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. Thermoelastic properties of Zn3P2

    DEFF Research Database (Denmark)

    Gerward, Leif; Olsen, J. Staun; Waśkowska, A.

    2011-01-01

    The bulk modulus and thermal expansion of Zn3P2 has been investigated at pressures up to 21GPa and temperatures down to 100K. The experimental zero-pressure bulk modulus is 80.7 ± 1.8GPa, in accordance with the bulk modulus scaling and lattice properties of the related compound Cd3P2. A tetragonal...... to orthorhombic phase transformation occurs above 11GPa with a relative volume change of-7.1%. Values for the thermal expansion coefficient are reported at 293, 200 and 100K....

  14. Definition of 5q11.2 Microdeletion Syndrome Reveals Overlap with CHARGE Syndrome and 22q11 Deletion Syndrome Phenotypes

    NARCIS (Netherlands)

    Blok, Charlotte Snijders; 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

    2014-01-01

    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 pati

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

    NARCIS (Netherlands)

    D.M. Glubb (Dylan); M. Maranian (Melanie); K. Michailidou (Kyriaki); K.A. Pooley (Karen); K.B. Meyer (Kerstin); S. Kar (Siddhartha); A.F.C. Carlebur; M. O'Reilly (Marian); J.A. Betts (Joshua); K.M. Hillman (Kristine); S. Kaufmann (Susanne); J. Beesley (Jonathan); S. Canisius (Sander); J.L. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); M.K. Schmidt (Marjanka); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.E. van der Schoot (Ellen); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); M. Ruebner (Matthias); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); P.D.P. Pharoah (Paul D.P.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); B. Burwinkel (Barbara); F. Marme (Federick); R. Yang (Rongxi); H. Surowy (Harald); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); Y.-D. Ko (Yon-Dschun); T. Brüning (Thomas); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); H. Tanaka (Hideo); T. Dörk (Thilo); N.V. Bogdanova (Natalia); S. Helbig (Sonja); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-Chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); D. Lambrechts (Diether); H. Zhao (Hui); C. Weltens (Caroline); E. van Limbergen (Erik); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); P. Seibold (Petra); P. Radice (Paolo); P. Peterlongo (Paolo); M. Barile (Monica); F. Capra (Fabio); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo; C.H. Yip (Cheng Har); M.-H. See (Mee-Hoong); B.K. Cornes (Belinda); C.-Y. Cheng (Ching-Yu); M.K. Ikram (Kamran); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); K. Czene (Kamila); D. Klevebring (Daniel); H. Darabi (Hatef); M. Eriksson (Mikael); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); J.M. Collee (Margriet); P. Hall (Per); J. Li (Jingmei); K. Humphreys (Keith); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y.-T. Gao (Yu-Tang); H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); M. Shah (Mitul); M. Ghoussaini (Maya); D. Kang (Daehee); J.-Y. Choi (J.); S.K. Park (Sue); D-Y. Noh (Dong-Young); M. Hartman (Mikael); X. Miao; W.-Y. Lim (Wei-Yen); A. Tang (Anthony); U. Hamann (Ute); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); C. Olswold (Curtis); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); P.-E. Wu (Pei-Ei); J-C. Yu (Jyh-Cherng); M.-F. Hou (Ming-Feng); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Jones (Michael); G. Pita (G.); M.R. Alonso (M Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); M. Brown (Melissa); B.A.J. Ponder (Bruce A.J.); G. Chenevix-Trench (Georgia); D. Thompson (Deborah); S.L. Edwards (Stacey); D.F. Easton (Douglas); A.M. Dunning (Alison); J.D. French (Juliet)

    2015-01-01

    textabstractGenome-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 indiv

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

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Masateru; Kim, Yoonyoung; Warjurkar, Dhanraj S.; Ham, Ji-Beom [Department of Physics and Astronomy, Seoul National University, Gwanak, Seoul 151-742 (Korea, Republic of); Kim, Junhan [Department of Astronomy and Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Usui, Fumihiko [Department of Astronomy, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Vaubaillon, Jeremie J. [Observatoire de Paris, I.M.C.C.E., Denfert Rochereau, Bat. A., F-75014 Paris (France); Ishihara, Daisuke [Department of Physics, School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602 (Japan); Hanayama, Hidekazu [Ishigakijima Astronomical Observatory, National Astronomical Observatory of Japan, Ishigaki, Okinawa 907-0024 (Japan); Sarugaku, Yuki; Hasegawa, Sunao [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 252-5210 (Japan); Kasuga, Toshihiro; Watanabe, Jun-ichi [National Astronomical Observatory, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Pyo, Jeonghyun [Korea Astronomy and Space Science Institute, Daejeon 305-348 (Korea, Republic of); Kuroda, Daisuke [National Institutes of Natural Sciences, Okayama Astrophysical Observatory, Kamogata-cho, Okayama 719-0232 (Japan); Ootsubo, Takafumi [Astronomical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Sakamoto, Makoto; Narusawa, Shin-ya; Takahashi, Jun [Nishi-Harima Astronomical Observatory, Center for Astronomy, University of Hyogo, Sayo, Hyogo 679-5313 (Japan); Akisawa, Hiroki, E-mail: ishiguro@astro.snu.ac.kr [Himeji City Science Museum, Himeji, Hyogo 671-2222 (Japan)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  19. A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.

    Science.gov (United States)

    Barlow, Jillian L; Drynan, Lesley F; Hewett, Duncan R; Holmes, Luke R; Lorenzo-Abalde, Silvia; Lane, Alison L; Jolin, Helen E; Pannell, Richard; Middleton, Angela J; Wong, See Heng; Warren, Alan J; Wainscoat, James S; Boultwood, Jacqueline; McKenzie, Andrew N J

    2010-01-01

    The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for human 5q- syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74-Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. These effects were associated with defective bone marrow progenitor development, the appearance of bone marrow cells expressing high amounts of the tumor suppressor p53 and increased bone marrow cell apoptosis. Notably, intercrossing with p53-deficient mice completely rescued the progenitor cell defect, restoring common myeloid progenitor and megakaryocytic-erythroid progenitor, granulocyte-monocyte progenitor and hematopoietic stem cell bone marrow populations. This mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q- syndrome.

  20. Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria

    Directory of Open Access Journals (Sweden)

    Tsuchiya Naoyuki

    2009-10-01

    Full Text Available Abstract Background It has been previously demonstrated that a single nucleotide polymorphism (SNP in the IL13 promoter region, IL13 -1055T>C (rs1800925, was associated with susceptibility to severe malaria in Thais. In the present study, fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13 on chromosome 5q31 was conducted using the same malaria subjects to refine the region containing a primary variant or a haplotype susceptible to severe malaria. Methods A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in 368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe malaria patients. Results Only rs1881457 located in the promoter region of IL13, which is in linkage disequilibrium with rs1800925 (r2 = 0.73, showed a significant association with severe malaria after adjusting for multiple testing (P = 0.046 by permutation test. This SNP was in a haplotype block spanning 97 kb (from rs2069812 to rs2240032. The detected haplotype block contained the RAD50 gene and the promoter of IL13, but not the other genes. Conclusion A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.

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

    Directory of Open Access Journals (Sweden)

    Dubchak Inna

    2005-12-01

    Full Text Available Abstract Background Evolutionarily conserved sequences likely have biological function. Methods To determine whether variation in conserved sequences in non-coding DNA contributes to risk for human disease, we studied six conserved non-coding elements in the Th2 cytokine cluster on human chromosome 5q31 in a large Hutterite pedigree and in samples of outbred European American and African American asthma cases and controls. Results Among six conserved non-coding elements (>100 bp, >70% identity; human-mouse comparison, we identified one single nucleotide polymorphism (SNP in each of two conserved elements and six SNPs in the flanking regions of three conserved elements. We genotyped our samples for four of these SNPs and an additional three SNPs each in the IL13 and IL4 genes. While there was only modest evidence for association with single SNPs in the Hutterite and European American samples (P IL4 gene (P IL13 gene was strongly associated with total IgE (P = 0.00022 and allergic sensitization to mold allergens (P = 0.00076 in the Hutterites, and more modestly associated with sensitization to molds in the European Americans and African Americans (P Conclusion These results indicate that there is overall little variation in the conserved non-coding elements on 5q31, but variation in IL4 and IL13, including possibly one SNP in a conserved element, influence asthma and atopic phenotypes in diverse populations.

  2. Dramatic response in the dependency to transfusion after low doses of lenalidomide treatment in a 5q-syndrome patient: a case report.

    Science.gov (United States)

    Dogu, Mehmet Hilmi; Sari, Ismail; Hacioglu, Sibel; Keskin, Ali

    2014-01-01

    5q-syndrome is a special subgroup of myelodysplastic syndrome in terms of follow-up and treatment. Lenalidomide is an immunomodulatory drug that is frequently used in the treatment of multiple myeloma. Some clinical studies have shown that lenalidomide treatment is effective in 5q syndrome and significantly decreases the transfusion dependency in these patients. In this paper, we would like to share a dramatic response of lowered transfusion dependency after treatment with low-dose lenalidomide in a patient who received myelodysplastic syndrome diagnosis and isolated 5q anomaly in our clinic.

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

    CERN Document Server

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

    2015-01-01

    This paper 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 degree beyond the field of view of the Kiso Wide Field Camera, i.e., >0.2 degree eastward and >2.0 degree 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 field of view, C= (2.3 +/- 0.5)x10^10 m^2. From the position angle, morphology and the 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. The velocity was more than one order of magnitude fast...

  4. Monitoring Observations of the Jupiter-Family Comet 17P/Holmes during 2014 Perihelion Passage

    CERN Document Server

    Kwon, Yuna Grace; Hanayama, Hidekazu; Kuroda, Daisuke; Honda, Satoshi; Takahashi, Jun; Kim, Yoonyoung; Lee, Myung Gyoon; Choi, Young-Jun; Kim, Myung-Jin; Vaubaillon, Jeremie J; Miyaji, Takeshi; Yanagisawa, Kenshi; Yoshida, Michitoshi; Ohta, Kouji; Kawai, Nobuyuki; Fukushima, Hideo; Watanabe, Jun-ichi

    2015-01-01

    We performed a monitoring observation of a Jupiter-Family comet, 17P/Holmes, during its 2014 perihelion passage to investigate its secular change in activity. The comet has drawn the attention of astronomers since its historic outburst in 2007, and this occasion was its first perihelion passage since then. We analyzed the obtained data using aperture photometry package and derived the Afrho parameter, a proxy for the dust production rate. We found that Afrho showed asymmetric properties with respect to the perihelion passage: it increased moderately from 100 cm at the heliocentric distance r_h=2.6-3.1 AU to a maximal value of 185 cm at r_h = 2.2 AU (near the perihelion) during the inbound orbit, while dropping rapidly to 35 cm at r_h = 3.2 AU during the outbound orbit. We applied a model for characterizing dust production rates as a function of r_h and found that the fractional active area of the cometary nucleus had dropped from 20%-40% in 2008-2011 (around the aphelion) to 0.1%-0.3% in 2014-2015 (around the...

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

    Energy Technology Data Exchange (ETDEWEB)

    Goliath, R.; Janssens, P.; Beighton, P. [Univ. of Cape Town (South Africa)] [and others

    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.

  6. Early lenalidomide treatment for low and intermediate-1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence.

    Science.gov (United States)

    Oliva, Esther N; Lauseker, Michael; Aloe Spiriti, Maria Antonietta; Poloni, Antonella; Cortelezzi, Agostino; Palumbo, Giuseppe A; Balleari, Enrico; Sanpaolo, Grazia; Volpe, Antonio; Ricco, Alessandra; Ronco, Francesca; Alati, Caterina; D'Errigo, Maria Grazia; Santacaterina, Irene; Kündgen, Andrea; Germing, Ulrich; Latagliata, Roberto

    2015-12-01

    Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136), TI with hemoglobin (Hb) ≥10 mg/dL (n = 88), or TI with Hb lenalidomide (10 mg/day) in 12 patients with TI del(5q) MDS and Hb lenalidomide (+12.5; P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide.

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

    Science.gov (United States)

    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

  8. Congenital diaphragmatic hernia in Smith-Magenis syndrome: a possible locus at chromosome 17p11.2.

    Science.gov (United States)

    Sanford, E F; Bermudez-Wagner, K; Jeng, L J B; Rauen, K A; Slavotinek, Anne M

    2011-11-01

    We report on a 7-month-old girl with Smith-Magenis syndrome (SMS) due to a 4.76-Mb deletion of 17p12-17p11.2 detected by array comparative genomic hybridization. She was also affected with a left-sided congenital diaphragmatic hernia (CDH) and cardiac anomalies including an atypical atrioventricular canal defect and a cleft mitral valve. To our knowledge, this is the first reported case of a patient with both SMS and CDH. There are numerous chromosomal regions in which duplications, deletions, inversions, or translocations have been associated with CDH, but none have previously been reported at or close to 17p11.2. We discuss candidate genes for the diaphragmatic defect in this patient. Our case demonstrates that it is important to consider the possibility of SMS in non-isolated cases of diaphragmatic hernia.

  9. High level of full-length cereblon mRNA in lower risk myelodysplastic syndrome with isolated 5q deletion is implicated in the efficacy of lenalidomide.

    Science.gov (United States)

    Jonasova, Anna; Bokorova, Radka; Polak, Jaroslav; Vostry, Martin; Kostecka, Arnost; Hajkova, Hana; Neuwirtova, Radana; Siskova, Magda; Sponerova, Dana; Cermak, Jaroslav; Mikulenkova, Dana; Cervinek, Libor; Brezinova, Jana; Michalova, Kyra; Fuchs, Ota

    2015-07-01

    Downregulation of cereblon (CRBN) gene expression is associated with resistance to the immunomodulatory drug lenalidomide and poor survival outcomes in multiple myeloma (MM) patients. However, the importance of CRBN gene expression in patients with myelodysplastic syndrome (MDS) and its impact on lenalidomide therapy are not clear. In this study, we evaluate cereblon expression in mononuclear cells isolated from bone marrow [23 lower risk MDS patients with isolated 5q deletion (5q-), 37 lower risk MDS patients with chromosome 5 without the deletion of long arms (non-5q-), and 24 healthy controls] and from peripheral blood (38 patients with 5q-, 52 non-5q- patients and 25 healthy controls) to gain insight into, firstly, the role of cereblon in lower risk MDS patients with or without 5q deletion and, secondly, into the mechanisms of lenalidomide action. Patients with 5q- lower risk MDS have the highest levels of CRBN mRNA in comparison with both lower risk MDS without the deletion of long arms of chromosome 5 and healthy controls. CRBN gene expression was measured using the quantitative TaqMan real-time PCR. High levels of CRBN mRNA were detected in all lenalidomide responders during the course of therapy. A significant decrease of the CRBN mRNA level during lenalidomide treatment is associated with loss of response to treatment and disease progression. These results suggest that, similar to the treatment of MM, high levels of full-length CRBN mRNA in lower risk 5q- patients are necessary for the efficacy of lenalidomide.

  10. $^3P_2$ Superfluids Are Topological

    CERN Document Server

    Mizushima, Takeshi

    2016-01-01

    We clarify the topology of the $^3P_2$ superfluidity which is expected to be realized in the cores of neutron stars and cubic odd-parity superconductors. The phase diagram includes the unitary uniaxial/biaxial nematic phases and nonunitary ferromagnetic and cyclic phases. We here show that the low-energy structures of all the phases are governed by different types of topologically protected gapless fermionic excitations: Surface Majorana fermions in nematic phases, single itinerant Majorana fermion in the ferromagnetic phase, and a quartet of itinerant Majorana fermions in the cyclic phase. Using the superfluid Fermi liquid theory, we also demonstrate that dihedral-two and -four biaxial nematic phases are thermodynamically favored in the weak coupling limit under a magnetic field. The mass acquisition of surface Majorana fermions in nematic phases is subject to symmetry.

  11. Physical and transcriptional mapping of the 17p13.3 region that is frequently deleted in human cancer

    DEFF Research Database (Denmark)

    Hoff, C; Seranski, P; Mollenhauer, J;

    2000-01-01

    suppressor gene that has also been suggested to play a role in the pathogenesis of Miller-Diecker syndrome (MDS). However, single-gene isolation efforts have retrieved additional genes from 17p13.3 that could play a role in tumorigenesis. This indicates that the full potential of this chromosomal region...... with respect to disease-related genes has not yet been exhausted and that there may exist still unknown genes that contribute to tumorigenesis or to the complex MDS phenotype. To provide a basis for the systematic isolation and evaluation of such genes, we established a physical map over 1.5 Mb of 17p13...

  12. Prenatal diagnosis of interstitial deletion of 17(p11.2p11.2) (Smith-Magenis Syndrome)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-01-15

    Interstitial deletion of 17p11.2 is associated with Smith-Magenis syndrome. This is a recognizable chromosomal deletion syndrome, characterized by brachycephaly, midface hypoplasia, growth and mental retardation, behavioral problems, and ocular abnormalities. Molecular analysis indicates it is a contiguous gene syndrome. Over 50 patients have been reported since the deletion was first described by Smith et al. [1982]. Cases include one with mosaicism and a familial example. None were prenatally diagnosed. The authors report on the prenatal detection of interstitial deletion of 17p11.2. 11 refs., 1 fig.

  13. DETECTION OF REMNANT DUST CLOUD ASSOCIATED WITH THE 2007 OUTBURST OF 17P/HOLMES

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Masateru; Kim, Yoonyoung; Kwon, Yuna G. [Department of Physics and Astronomy, Seoul National University, Gwanak, Seoul 151-742 (Korea, Republic of); Sarugaku, Yuki [Kiso Observatory, Institute of Astronomy, Graduate School of Science, The University of Tokyo, Mitake, Kiso-machi, Kiso, Nagano 397-0101 (Japan); Kuroda, Daisuke; Maehara, Hiroyuki [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Asakuchi, Okayama 719-0232 (Japan); Hanayama, Hidekazu [Ishigakijima Astronomical Observatory, National Astronomical Observatory of Japan, 1024-1 Arakawa, Ishigaki, Okinawa 907-0024 (Japan); Takahashi, Jun [Nishi-Harima Astronomical Observatory, Center for Astronomy, University of Hyogo, Sayo, Hyogo 679-5313 (Japan); Terai, Tsuyoshi [Subaru Telescope, National Astronomical Observatory of Japan, Hilo, HI 96720 (United States); Usui, Fumihiko [Department of Astronomy, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Vaubaillon, Jeremie J. [Observatoire de Paris, I.M.C.C.E., Denfert Rochereau, Bat. A., F-75014 Paris (France); Morokuma, Tomoki; Kobayashi, Naoto [Institute of Astronomy, Graduate School of Science, The University of Tokyo, 2-21-1 Osawa, Mitaka, Tokyo 181-0015 (Japan); Watanabe, Jun-ichi [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan)

    2016-01-20

    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, C{sub FOV} = (2.3 ± 0.5) × 10{sup 10} m{sup 2}. 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{sup −1}. The velocity was more than one order of magnitude faster than that of millimeter–centimeter grains from typical comets around a heliocentric distance r{sub h} of 2.5 AU. We considered that sudden sublimation of a large amount of water-ice (≈10{sup 30} mol s{sup −1}) would be responsible for the high ejection velocity. We finally estimated a total mass of M{sub TOT} = (4–8) × 10{sup 11} kg and a total kinetic energy of E{sub TOT} = (1–6) × 10{sup 15} J for the 2007 outburst ejecta, which are consistent with those of previous studies that were conducted soon after the outburst.

  14. Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome.

    Directory of Open Access Journals (Sweden)

    Emily Outwin

    2011-08-01

    Full Text Available A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR. Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrino, J.E.; Spinner, N.B.; Zackai, E.H. [Childrens Hospital of Philadelphia, PA (United States)] [and others

    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. A novel unbalanced de novo translocation der(5t(4;5(q26;q21.1 in adult T-cell precursor lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kjeldsen Eigil

    2012-05-01

    Full Text Available Abstract We here describe a novel unbalanced de novo translocation der(5t(4;5(q26;q21.1 in a 39-year-old male diagnosed with acute T-cell lymphoblastic leukemia. Bone marrow (BM was massively infiltrated with 85 % highly proliferative polymorphic T-cell precursors. Immunologically, the malignant cells stained positive for CD7, CD34, intracytoplasmic CD3+, TdT + and negative for CD3 and CD5. G-banded chromosome analysis of BM cells showed the normal karyotype 46,XY[25] whereas BAC-based aCGH analysis revealed partial gain of 4q and partial loss of 5q. Multicolor karyotyping confirmed the presence of an unbalanced der(5t(4;5 as the sole structural abnormality. Subsequent high-resolution oligonucleotide-based aCGH analysis showed that the der(5t(4;5(q26;q21.1 resulted in partial trisomy of 4q26qter (117,719,015-190,613,014 and partial monosomy of 5q21.1qter (100,425,442-180,857,866 and that there was no indication of any gene disruptions resulting from the breakages. Interphase FISH analysis using BAC-based specific probes for 4q26 and 5q21.1 confirmed the breakpoints and revealed approximately 80 % abnormal cells accordingly. At 4q26 the MIR1973 gene is located centromeric to the breakpoint in the copy number neutral region and the TRAM1L1 gene is located within the gained region. At 5q21.1 the genes ST8SIA4 and MIR548p are located centromeric to the breakpoint and no known genes up to approximately 1 Mb telomeric to the breakpoint in the copy number loss region. Interestingly, only the gene ST8SIA4 at 5q21.1 have been implicated in T-cell regulation as it encodes one of the key enzymes for polysialysation of surface proteins on dendritic cells which are important regulators for T-cell proliferation. The der(5t(4;5 is thought to play a crucial role in the pathogenesis of acute T-ALL due to either gain of 4q, the loss of 5q, or deregulation of genes in proximity to the breakpoints.

  18. Fluorescence in situ hybridization for del(5q) in myelodysplasia/acute myeloid leukemia: comparison of EGR1 vs. CSF1R probes and diagnostic yield over metaphase cytogenetics alone.

    Science.gov (United States)

    Sun, Yang; Cook, James R

    2010-03-01

    To determine the clinical utility of FISH for del(5q) in MDS/AML, we first compared FISH for 5q31 (EGR1) and 5q33 (CSF1R) in 51 myeloid neoplasms containing del(5q) by metaphase cytogenetics. Next, EGR1 FISH was compared to metaphase cytogenetics alone in 269 cases of known or suspected MDS/AML. These studies show that while metaphase cytogenetics alone can detect del(5q) in most cases, FISH is particularly useful in cases with suboptimal growth. EGR1 FISH detects del(5q) in a broad variety of myeloid neoplasms, including at least most cases of 5q- syndrome, while studies for CSF1R add little to the diagnostic yield.

  19. Two patients with duplication of 17p11.2: The reciprocal of the Smith-Magenis syndrome deletion?

    Energy Technology Data Exchange (ETDEWEB)

    Brown, A. [Greenwood Genetic Center, SC (United States)]|[Clemson Univ., SC (United States); Phelan, M.C.; Rogers, R.C. [Greenwood Genetic Center, SC (United States)] [and others

    1996-05-17

    J.M. and H.G. are two unrelated male patients with developmental delay. Cytogenetic analysis detected a duplication of 17p11.2 in both patients. The extent of the duplicated region was determined using single copy DNA probes: cen-D17S58-D17S29-D17S258-D17S71-D17S445-D17S122-tel. Four of the six markers, D17S29, D17S258, D17S71, and D17S445, were duplicated by dosage analysis. Fluorescent in situ hybridization (FISH) analysis of H.G., using cosmids for locus D17S29, confirmed the duplication in 17p11.2. Because the deletion that causes the Smith-Magenis syndrome involves the same region of 17p11.2 as the duplication in these patients, the mechanism may be similar to that proposed for the reciprocal deletion/ duplication event observed in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Charcot-Marie-Tooth Type 1A disease (CMT1A). 30 refs., 3 figs., 1 tab.

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

    Science.gov (United States)

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

    2015-01-01

    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. PMID:26242244

  1. Prognostic Impact of del(17p and del(22q as assessed by interphase FISH in sporadic colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    María González-González

    Full Text Available BACKGROUND: Most sporadic colorectal cancer (sCRC deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 1, 7, 8, 13, 14, 17, 18, 20, and 22 by iFISH in 58 sCRC patients: thirty-one non-metastatic (54% vs. 27 metastatic (46% disease. From a total of 18 probes, significant differences emerged only for the 17p11.2 and 22q11.2 chromosomal regions. Patients with liver metastatic sCRC showed an increased frequency of del(17p11.2 (10% vs. 67%;p<.001 and del(22q11.2 (0% vs. 22%;p = .02 versusnon-metastatic cases. Multivariate analysis of prognostic factors for overall survival (OS showed that the only clinical and cytogenetic parameters that had an independent adverse impact on patient outcome were the presence of del(17p with a 17p11.2 breakpoint and del(22q11.2. Based on these two cytogenetic variables, patients were classified into three groups: low- (no adverse features, intermediate- (one adverse feature and high-risk (two adverse features- with significantly different OS rates at 5-years (p<.001: 92%, 53% and 0%, respectively. CONCLUSIONS/SIGNIFICANCE: Our results unravel the potential implication of del(17p11.2 in sCRC patients with liver metastasis as this cytogenetic alteration appears to be intrinsically related to an increased metastatic potential and a poor outcome, providing additional prognostic information to that associated with other cytogenetic alterations such as del(22q11.2. Additional prospective studies in larger series of patients would be required to confirm the clinical utility of the new prognostic markers identified.

  2. Spectra and oscillator strengths of 3p63d9-3p53d10 and 3p63d9-3p63d84p transitions for cobalt-like Sn23+ ion

    Institute of Scientific and Technical Information of China (English)

    Chen Ming-Lun; Yu Xiao-Guang

    2009-01-01

    This paper calculates the spectra and oscillator strengths for highly ionized cobalt-like Sn23+ ions 3p63d9-3p53d10,3p63d9 - 3p63d84p transitions by using a multi-configuration self-consistent field method program together with the proposed fitting formula. The calculations have a good agreement with observations.

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

    Science.gov (United States)

    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.

  4. 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

    NARCIS (Netherlands)

    H.M. Sluimer-Blommestein (Hedwig); N. Armstrong (Nigel); S. Ryder; S. Deshpande (Sohan); G. Worthy (Gill); C. Noake; R. Riemsma; J. Kleijnen (Jos); J.L. Severens (Hans); M.J. Al (Maiwenn)

    2016-01-01

    textabstractThe 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 abnormali

  5. Multivariate time-dependent comparison of the impact of lenalidomide in lower-risk myelodysplastic syndromes with chromosome 5q deletion.

    Science.gov (United States)

    Sánchez-García, Joaquín; Del Cañizo, Consuelo; Lorenzo, Ignacio; Nomdedeu, Benet; Luño, Elisa; de Paz, Raquel; Xicoy, Blanca; Valcárcel, David; Brunet, Salut; Marco-Betes, Victor; García-Pintos, Marta; Osorio, Santiago; Tormo, Mar; Bailén, Alicia; Cerveró, Carlos; Ramos, Fernando; Diez-Campelo, María; Such, Esperanza; Arrizabalaga, Beatriz; Azaceta, Gemma; Bargay, Joan; Arilla, María J; Falantes, José; Serrano-López, Josefina; Sanz, Guillermo F

    2014-07-01

    The impact of lenalidomide treatment on long-term outcomes of patients with lower risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)) is unclear. This study used time-dependent multivariate methodology to analyse the influence of lenalidomide therapy on overall survival (OS) and acute myeloblastic leukaemia (AML) progression in 215 patients with International Prognostic Scoring System (IPSS) low or intermediate-1 risk and del(5q). There were significant differences in several relevant characteristics at presentation between patients receiving (n = 86) or not receiving lenalidomide (n = 129). The 5-year time-dependent probabilities of OS and progression to AML were 62% and 31% for patients receiving lenalidomide and 42% and 25% for patients not receiving lenalidomide; differences were not statistically significant in multivariate analysis that included all variables independently associated with those outcomes (OS, P = 0·45; risk of AML, P = 0·31, respectively). Achievement of RBC transfusion independency (P = 0·069) or cytogenetic response (P = 0·021) after lenalidomide was associated with longer OS in multivariate analysis. These data clearly show that response to lenalidomide results in a substantial clinical benefit in lower risk MDS patients with del(5q). Lenalidomide treatment does not appear to increase AML risk in this population of patients.

  6. Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions

    NARCIS (Netherlands)

    Mutsaers, Henricus A M; Levtchenko, Elena N; Martinerie, Laetitia; Pertijs, Jeanne C L M; Allegaert, Karel; Devriendt, Koenraad; Masereeuw, Roos; Monnens, Leo A H; Lombès, Marc

    2014-01-01

    CONTEXT: Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties. Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hy

  7. Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Qiu, Xiangning; Søgaard, Alexandra;

    2012-01-01

    Deletions of chromosome 5q are associated with poor outcomes in acute myeloid leukemia (AML) suggesting the presence of tumor suppressor(s) at the locus. However, definitive identification of putative tumor suppressor genes remains controversial. Here we show that a 106-nucleotide noncoding RNA...

  8. 31 CFR 30.5 - Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that...

    Science.gov (United States)

    2010-07-01

    ... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.5 Q-5: How does a TARP recipient comply with the... recipient's senior risk officers any risks (including long-term as well as short-term risks) that the TARP... encourage behavior focused on short-term results and not on long-term value creation. The...

  9. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q

    NARCIS (Netherlands)

    Fenaux, P.; Giagounidis, A.; Selleslag, D.; Beyne-Rauzy, O.; Mufti, G.; Mittelman, M.; Muus, P.; Boekhorst, P. Te; Sanz, G.; Del Canizo, C.; Guerci-Bresler, A.; Nilsson, L.; Platzbecker, U.; Lubbert, M.; Quesnel, B.; Cazzola, M.; Ganser, A.; Bowen, D.; Schlegelberger, B.; Aul, C.; Knight, R.; Francis, J.; Fu, T.; Hellstrom-Lindberg, E.

    2011-01-01

    This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day o

  10. Lenalidomide: a review of its use in patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndrome associated with 5q chromosome deletion.

    Science.gov (United States)

    Syed, Yahiya Y; Scott, Lesley J

    2013-07-01

    Lenalidomide (Revlimid(®)), a thalidomide analogue, is an orally administered second generation immunomodulator with anti-angiogenic, antineoplastic, anti-inflammatory and pro-erythropoietic properties. It is approved for the treatment of patients with transfusion-dependent anaemia due to International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome (MDS) associated with either chromosome 5q deletion [del(5q)] with or without additional cytogenetic abnormalities (US, Japan and Switzerland etc.), or with an isolated del(5q) cytogenetic abnormality when other therapeutic options are insufficient or inadequate (EU) [featured indication]. In a randomized, double-blind, multicentre, registrational trial (MDS-004; n = 205) in this patient population, a significantly higher proportion of lenalidomide recipients than placebo recipients achieved red blood cell transfusion independence for ≥26 consecutive weeks (primary endpoint for efficacy) and cytogenetic responses. The erythroid response to lenalidomide was accompanied by an increase in the haemoglobin levels. These efficacy outcomes are generally consistent with those seen in an earlier noncomparative registrational trial (MDS-003; n = 148). In MDS-004, lenalidomide also significantly improved health-related quality of life compared with placebo at 12 weeks. Retrospective analyses that compared outcomes between lenalidomide-treated patients with low- or intermediate-1-risk del(5q) MDS and multicentre registry cohorts showed that lenalidomide treatment did not appear to increase the risk of progression to acute myeloid leukaemia. Lenalidomide had a manageable safety profile in the registrational trials, with ≤20 % of patients discontinuing treatment because of adverse events. The most common adverse events (incidence ≥20 %) occurring in lenalidomide recipients were thrombocytopenia and neutropenia, which were generally managed by dosage reductions and/or interruptions, and

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

    Energy Technology Data Exchange (ETDEWEB)

    Balciuniene, J.; Holmgren, G.; Forsman, K. [University Hospital, Umea (Sweden)] [and others

    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.

  12. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... show that high expression of 5q14 genes and low levels of TNFR2 pathway genes were associated with poor survival in basal-like cancers. Furthermore, low expression of 5q33 genes and interleukin-12 pathway genes were associated with poor outcome exclusively in ERBB2-like tumors. Conclusion...

  13. 5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

    Science.gov (United States)

    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.

  14. Diagnosing Smith-Magenis syndrome and duplication 17p11.2 syndrome by RAI1 gene copy number variation using quantitative real-time PCR.

    Science.gov (United States)

    Truong, Hoa T; Solaymani-Kohal, Sara; Baker, Kevin R; Girirajan, Santhosh; Williams, Stephen R; Vlangos, Christopher N; Smith, Ann C M; Bunyan, David J; Roffey, Paul E; Blanchard, Christopher L; Elsea, Sarah H

    2008-03-01

    Smith-Magenis syndrome (SMS) and duplication 17p11.2 (dup17p11.2) syndrome are multiple congenital anomalies/mental retardation disorders resulting from either a deletion or duplication of the 17p11.2 region, respectively. The retinoic acid induced 1 (RAI1) gene is the causative gene for SMS and is included in the 17p11.2 region of dup17p11.2 syndrome. Currently SMS and dup17p11.2 syndrome are diagnosed using a combination of clinically recognized phenotypes and molecular cytogenetic analyses such as fluorescent in situ hybridization (FISH). However, these methods have proven to be highly expensive, time consuming, and dependent upon the low resolving capabilities of the assay. To address the need for improved diagnostic methods for SMS and dup17p11.2 syndrome, we designed a quantitative real-time PCR (Q-PCR) assay that measures RAI1 copy number using the comparative C(t) method, DeltaDeltaC(t). We tested our assay with samples blinded to their previous SMS or dup17p11.2 syndrome status. In all cases, we were able to determine RAI1 copy number status and render a correct diagnosis accordingly. We validated these results by both FISH and multiplex ligation-dependent probe amplification (MLPA). We conclude that Q-PCR is an accurate, reproducible, low-cost, and reliable assay that can be employed for routine use in SMS and dup17p11.2 diagnosis.

  15. A mitotic recombination map proximal to the APC locus on chromosome 5q and assessment of influences on colorectal cancer risk

    Directory of Open Access Journals (Sweden)

    Clark Susan

    2009-06-01

    Full Text Available Abstract Background Mitotic recombination is important for inactivating tumour suppressor genes by copy-neutral loss of heterozygosity (LOH. Although meiotic recombination maps are plentiful, little is known about mitotic recombination. The APC gene (chr5q21 is mutated in most colorectal tumours and its usual mode of LOH is mitotic recombination. Methods We mapped mitotic recombination boundaries ("breakpoints" between the centromere (~50 Mb and APC (~112 Mb in early colorectal tumours. Results Breakpoints were non-random, with the highest frequency between 65 Mb and 75 Mb, close to a low copy number repeat region (68–71 Mb. There were, surprisingly, few breakpoints close to APC, contrary to expectations were there constraints on tumorigenesis caused by uncovering recessive lethal alleles or if mitotic recombination were mechanistically favoured by a longer residual chromosome arm. The locations of mitotic and meiotic recombination breakpoints were correlated, suggesting that the two types of recombination are influenced by similar processes, whether mutational or selective in origin. Breakpoints were also associated with higher local G+C content. The recombination and gain/deletion breakpoint maps on 5q were not, however, associated, perhaps owing to selective constraints on APC dosage in early colorectal tumours. Since polymorphisms within the region of frequent mitotic recombination on 5q might influence the frequency of LOH, we tested the 68–71 Mb low copy number repeat and nearby tagSNPs, but no associations with colorectal cancer risk were found. Conclusion LOH on 5q is non-random, but local factors do not greatly influence the rate of LOH at APC or explain inter differential susceptibility to colorectal tumours.

  16. Association between Alcoholism and the Genetic Polymorphisms of the GABAA Receptor Genes on Chromosome 5q33-34 in Korean Population

    OpenAIRE

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-01-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute...

  17. Assignment of human sprouty 4 gene to chromosome segment 5q32∼33 and analysis of its pattern of expression

    Indian Academy of Sciences (India)

    Hua Liu; Jin-Zhong Chen; Shao-Hua Gu; Jian-Liang Dai; En-Pang Zhao; Lu Huang; Wang-Xiang Xu; Yi Xie; Yu-Min Mao

    2003-04-01

    The human sprouty 4 (SPYR4) gene was localized to chromosome band 5q32∼33 by screening the Stanford radiation hybrid G3 panel using a SPRY4-specific primer pair for PCR. Northern blot analysis revealed two different mRNAs (5 kb and 2 kb) in liver, skeletal muscle, heart, lung, kidney, spleen, placenta and small intestine. Reverse transcriptase-PCR analysis showed that SPYR4 was expressed in all tested tissues to different levels.

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

    Energy Technology Data Exchange (ETDEWEB)

    Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Roller, M.L.; Camper, S.A. [Univ. of Michigan Medical School, Ann Arbor, MI (United States)] [and others

    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.

  19. A novel mechanism for outbursts of Comet 17P/Holmes and other short-period comets

    CERN Document Server

    Miles, Richard

    2007-01-01

    A mechanism is proposed to explain the outburst of comet 17P/Holmes based on; (a) oxidation of water within the porous surface of the comet nucleus to form hydrogen peroxide (H2O2) through exposure to UV radiation, to energetic solar-wind particles and to cosmic radiation, (b) concentration of the H2O2 component through solid-, liquid- and gas-phase processes involving sublimation, evaporation, fractional crystallization, diffusion, supercooling, capillary wetting and migration in voids within the nucleus, and (c) rapid exothermic decomposition of aqueous H2O2 liberating oxygen gas via a surface catalytic reaction through interaction with finely-dispersed transition metals, metal compounds and minerals, in particular those containing Fe, localised within a differentiated multi-component comet nucleus. An accelerated release of gaseous oxygen, concomitant self-heating and volatilisation of hydrocarbons within the nucleus results in its explosive disruption. This mechanism may also explain the observation of a ...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Blancato, J.; Precht, K.; Meck, J. [Georgetown Univ., Hospital, Washington, DC (United States)] [and others

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Finucane, B.; Jaeger, E.R. [Elwyn, Inc. PA (United States); Freitag, S.K. [Jefferson Medical College, Philadelphia, PA (United States)

    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.

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

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki

    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 an...

  4. Where are $\\chi_{cJ}(3P)$?

    CERN Document Server

    Chen, Dian-Yong

    2016-01-01

    In the present work, we propose the $Y(4140)$ as the $\\chi_{c1}(3P)$ state by studying the $\\chi_{c1} \\pi^+ \\pi^-$ invariant mass spectrum of the $B\\to K \\chi_{c1} \\pi^+ \\pi^-$ process. In the $D\\bar{D}$ invariant mass spectrum of the $B\\to K D\\bar{D}$ process, we find a new resonance with the mass and width to be $ (4083.0 \\pm 5.0) $ and $ (24.1 \\pm 15.4) $ MeV, respectively, which could be a good candidate of the $\\chi_{c0}(3P)$ state. The theoretical investigations on the decay behaviors of the $\\chi_{cJ}(3P)$ in the present work support the assignments of the $Y(4140)$ and $Y(4080)$ as the $\\chi_{c1}(3P)$ and $\\chi_{c0}(3P)$ states, respectively. In addition, the $\\chi_{c2}(3P)$ state is predicted to be a very narrow state. The results in the present work could be tested by further experiments in the LHCb and forthcoming Belle II.

  5. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

    Science.gov (United States)

    Toma, A; Kosmider, O; Chevret, S; Delaunay, J; Stamatoullas, A; Rose, C; Beyne-Rauzy, O; Banos, A; Guerci-Bresler, A; Wickenhauser, S; Caillot, D; Laribi, K; De Renzis, B; Bordessoule, D; Gardin, C; Slama, B; Sanhes, L; Gruson, B; Cony-Makhoul, P; Chouffi, B; Salanoubat, C; Benramdane, R; Legros, L; Wattel, E; Tertian, G; Bouabdallah, K; Guilhot, F; Taksin, A L; Cheze, S; Maloum, K; Nimuboma, S; Soussain, C; Isnard, F; Gyan, E; Petit, R; Lejeune, J; Sardnal, V; Renneville, A; Preudhomme, C; Fontenay, M; Fenaux, P; Dreyfus, F

    2016-04-01

    After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.

  6. Diagnosis of del(5q MDS, 14 years after JAK-2 positive PV appearance: complete remission of both diseases with lenalidomide monotherapy

    Directory of Open Access Journals (Sweden)

    Antonella Vaccarino

    2016-10-01

    Full Text Available This is the report of the clinical case of a patient who presents the association of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q- myelodysplastic syndrome, developed after about 14 years from the first diagnosis. Patient’s symptoms had rapidly worsened, and she became transfusion-dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly, and completely brought white cells counts, haemoglobin and platelets back to normal.  After more than one year from start, blood cell count is still normal. As far as we know this is the first case of an effective treatment with Lenalidomide reported in this clinical setting.

  7. Diagnosis of del(5q) MDS, 14 Years after JAK-2 Positive PV Appearance: Complete Remission of both Diseases with Lenalidomide Monotherapy.

    Science.gov (United States)

    Vaccarino, Antonella; Dogliotti, Irene; Marletto, Fabio; Demarchi, Andrea; Bazzan, Mario

    2016-01-01

    This is the report of the clinical case of a patient who presents the association of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q- myelodysplastic syndrome, developed after about 14 years from the first diagnosis. Patient's symptoms had rapidly worsened, and she became transfusion-dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly and completely brought white cells counts, haemoglobin, and platelets back to normal. After more than one year from the start, blood cell count is still normal. As far as we know, this is the first case of an effective treatment with Lenalidomide reported in this clinical setting.

  8. The promoter analysis of the human C17orf25 gene, a novel chromosome 17p13.3 gene

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The human C17orf25 gene (Accession No. AF177342) is one of thirteen genes cloned from a regiondisplaying a high score of loss of heterozygosity within chromosome 17p13.3 in human hepatocellular car-cinoma in China[1]. To unveil the underlying mechanisms for the transcription regulation of this gene andunderstand its implication to the hepatocellular carcinogenesis, we looked into the relevant aspects by bothbioinformatic and experimental executions. We found: 1, The abundant expression of the C17orf25 genewas evident in all the cell lines and tissue samples tested, showing little hepatoma-selectivity; 2, Its tran-scription starts at a single site, locating at -60 from the translation initiation codon; 3, A 58 bp fragmentcontaining the transcription start, extending from -112 to -55, represents the minimal promoter; 4, Theconsensus sequence within this fragment recognized by SP1 contributes predominantly to the activity of theminimal promoter; 5, The bioinformatic analysis suggests that the C17orf25 gene may encode a protein inthe family of the glyoxalase. Our data has provided some deep insight into both function and regulation ofthe C17orf25 gene in the context of the normal liver and hepatocellular carcinoma.

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

    Science.gov (United States)

    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.

  10. Hypoventilation in REM sleep in a case of 17p11.2 deletion (Smith-Magenis syndrome).

    Science.gov (United States)

    Leoni, Chiara; Cesarini, Laura; Dittoni, Serena; Battaglia, Domenica; Novelli, Antonio; Bernardini, Laura; Losurdo, Anna; Vollono, Catello; Testani, Elisa; Della Marca, Giacomo; Zampino, Giuseppe

    2010-03-01

    We describe a 2-year-old baby affected by Smith-Magenis syndrome (SMS), due to 17p11.2 deletion, who presented repeated episodes of hemoglobin desaturation during REM sleep. The boy, aged 14 months, presented a phenotype characterized by psychomotor delay, right posterior plagiocephaly, telecanthus, strabismus, upslanting palpebral fissures, broad hypoplastic nasal bridge, short philtrum, deep ring shaped skin creases around the limbs, proximal syndactyly, bilateral hypoacusia. Polysomnographic (PSG) recording showed episodes of REM-related hypoventilation (hemoglobin desaturations without apneas or hypopneas). Sleep disorders are present in almost all the cases of SMS, but very few reports describe the sleep-related respiratory patterns. The finding of REM hypoventilation in SMS does not allow an unequivocal interpretation. It could reflect a subclinical restrictive respiratory impairment or, alternatively, an impairment of central respiratory control during REM sleep. In SMS children, respiratory abnormalities during sleep, and in particular during REM sleep, may cause sleep disruption, reduction of time spent in REM sleep, and daytime sleepiness. We therefore suggest that some sleep abnormalities described in SMS could be consequent to Sleep Disordered Breathing, and in particular to REM hypoventilation. Sleep studies in SMS should include the recording of respiratory parameters.

  11. Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)].

    Science.gov (United States)

    Goldman, Alica M; Potocki, Lorraine; Walz, Katherina; Lynch, Jennifer K; Glaze, Daniel G; Lupski, James R; Noebels, Jeffrey L

    2006-02-01

    Smith-Magenis syndrome is a multiple congenital anomalies/mental retardation syndrome associated with a heterozygous deletion of chromosome 17p11.2. Seizures have not been formally studied in this population. Our objectives were to estimate the prevalence of seizures and electroencephalographic (EEG) epileptiform abnormalities in patients with Smith-Magenis syndrome with defined chromosomal rearrangements and to describe the spectrum of abnormal EEG patterns. Prolonged video-EEGs were obtained in 60 patients. Eighteen percent of patients reported a seizure history; however, abnormal EEGs were identified in 31 of the 60 subjects and 27 of 31 were epileptiform. Generalized epileptiform patterns were the most common (73%). Most patients with either small or large deletions had an abnormal EEG (83%; 75%) in contrast to those with a common deletion (49%). Our results indicate that epileptiform EEG abnormalities are frequent in patients with Smith-Magenis syndrome. Considering that close to one third of individuals with Smith-Magenis syndrome with epileptiform abnormalities also had a history of clinical seizures, cortical hyperexcitability and epilepsy should be considered an important component of the Smith-Magenis syndrome clinical phenotype.

  12. 人膀胱移行细胞癌染色体17p13区域杂合性缺失精细作图

    Institute of Scientific and Technical Information of China (English)

    郑闪; 张建军; 等

    2002-01-01

    目的:明确染色体17p13区域等位基因杂合性缺失(LOH)在人膀胱移行细胞癌(TCC)中的发生频率和最小缺失区域,为膀胱TCC相关抑癌基因的定位克隆提供线索。方法:应用位于17p13区域的13个微卫星标记,分期的关系,结果:44例患者中,35例(79.5%)的膀胱TCC组织中存在至少1个微卫星标记的LOH,缺失频率最高的微卫星标记是位于17p13.2的D17S513,达41.4%(12/29),其次为位于17p13.3的D17S1308,为40.5%(17/42);最低为位于17p13.1的D17S261,为14.3%(4/28)LOH主要集中于三个区域;位于17p13.3的D17S695-D17S1308,位于17p13.2的D17S1533-D17S831,以及位于17p13.1区域的TP53。所检测微卫星标记中仅TP53的LOH与膀胱TCC病理分级(χ2=5.104,P<0.05),和分期(χ2=5.382,P<0.05)呈正相关,结论:在17p13区域除TP53基因以外,还可能存在两个与膀胱TCC相关的抑癌基因,分别位于17p13.3的D17S695-D17S1308和17p13.3的D17S1533-D17S831,TP53的LOH是膀胱TCC发展的晚期事件,而17p13.3和17p13.2区域的LOH则可能是膀胱TCC发生的早期事件。

  13. De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability and obesity.

    Science.gov (United States)

    Kuroda, Yukiko; Ohashi, Ikuko; Tominaga, Makiko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Masuno, Mitsuo; Kurosawa, Kenji

    2014-06-01

    17p13.1 Deletion encompassing TP53 has been described as a syndrome characterized by intellectual disability and dysmorphic features. Only one case with a 17p13.1 duplication encompassing TP53 has been reported in a patient with intellectual disability, seizures, obesity, and diabetes mellitus. Here, we present a patient with a 17p13.1 duplication who exhibited obesity and intellectual disability, similar to the previous report. The 9-year-old proposita was referred for the evaluation of intellectual disability and obesity. She also exhibited insulin resistance and liver dysfunction. She had wide palpebral fissures, upturned nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation. Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the insulin-responsive glucose transporter 4 (GLUT4) associated with insulin-stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1 duplication may represent a clinically recognizable condition characterized partially by a characteristic facial phenotype, developmental delay, and obesity.

  14. [17p13.3 duplication as a cause of psychomotor developmental delay in an infant - a further case of a new syndrome].

    Science.gov (United States)

    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.

  15. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1.

    Science.gov (United States)

    Ryan, A W; Thornton, J M; Brophy, K; Daly, J S; McLoughlin, R M; O'Morain, C; Abuzakouk, M; Kennedy, N P; Stevens, F M; Feighery, C; Kelleher, D; McManus, R

    2005-02-01

    Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, M.J.; Dixon, J. (Univ. of Manchester (United Kingdom)); Houseal, T.; Klinger, K.; Landes, G.M. (Integrated Genetics, Inc., Framingham, MA (United States)); Bhatt, M.; Ward, D.C. (Yale Univ. School of Medicine, New Haven (United States))

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Saltman, D.L.; Dolganov, G.M. (Genelabs Inc. Redwood City, CA (United States)); Warrington, J.A.; Wasmuth, J.J. (Univ. of California, Irvine (United States)); Lovett, M. (Univ. of Texas Southwestern Medical Center, Dallas (United States))

    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.

  18. Identification of a rare de novo three-way complex t(5;20;8(q31;p11.2;p21 with microdeletions on 5q31.2, 5q31.3, and 8p23.2 in a patient with hearing loss and global developmental delay: case report

    Directory of Open Access Journals (Sweden)

    Bejjani Bassem A

    2009-01-01

    Full Text Available Abstract Background Complex chromosome rearrangements (CCRs, which involve more than two breakpoints on two or more chromosomes, are uncommon occurrences. Although most CCRs appear balanced at the level of the light microscope, many demonstrate cryptic, submicroscopic imbalances at the translocation breakpoints. Results We report a female with hearing loss and global developmental delay with a complex three-way unbalanced translocation (5;20;8(q31;p11.2;p21 resulting in microdeletions on 5q31.2, 5q31.3, and 8p23.2 identified by karyotyping, microarray analysis and fluorescence in situ hybridization. Discussion The microdeletion of bands 8p23.2 may be associated with the hearing impairment. Furthermore, the characterization of this patient's chromosomal abnormalities demonstrates the importance of integrated technologies within contemporary cytogenetics laboratories.

  19. L-Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q- syndrome in a TP53-independent way.

    Science.gov (United States)

    Narla, Anupama; Payne, Elspeth M; Abayasekara, Nirmalee; Hurst, Slater N; Raiser, David M; Look, A Thomas; Berliner, Nancy; Ebert, Benjamin L; Khanna-Gupta, Arati

    2014-11-01

    Haploinsufficiency of ribosomal proteins (RPs) and upregulation of the tumour suppressor TP53 have been shown to be the common basis for the anaemia observed in Diamond Blackfan anaemia and 5q- myelodysplastic syndrome. We previously demonstrated that treatment with L-Leucine resulted in a marked improvement in anaemia in disease models. To determine if the L-Leucine effect was Tp53-dependent, we used antisense MOs to rps19 and rps14 in zebrafish; expression of tp53 and its downstream target cdkn1a remained elevated following L-leucine treatment. We confirmed this observation in human CD34+ cells. L-Leucine thus alleviates anaemia in RP-deficient cells in a TP53-independent manner.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  2. The gene for calcium-modulating cyclophilin ligand (CAMLG) is located on human Chromosome 5q23 and a syntenic region of mouse chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Bram, R.J.; Valentine, V.; Shapiro, D.N. [St. Jude Children`s Research Hospital, Memphis, TN (United States)]|[Univ. of Tennessee, Memphis, TN (United States)] [and others

    1996-01-15

    The CAMLG gene encodes a novel cyclophilin B-binding protein called calcium-modulating cyclophilin ligand, which appears to be involved in the regulation of calcium signaling in T lymphocytes and other cells. The murine homolog, Caml, was localized by interspecific backcross analysis in the middle of chromosome 13. By fluorescence in situ hybridization, this gene was localized to human chromosome 5 in a region (q23) known to be syntenic to mouse chromosome 13. These results provide further evidence supporting the extensive homology between human chromosome 5q and mouse chromosome 13. In addition, the results will provide a basis for further evaluation of cytogenetic anomalies that may contribute to inherited defects in calcium signaling or immune system function. 15 refs., 2 figs.

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

    Directory of Open Access Journals (Sweden)

    Musto P

    2014-06-01

    Full Text Available Pellegrino Musto,1 Vittorio Simeon,2 Roberto Guariglia,3 Gabriella Bianchino,4 Vitina Grieco,4 Filomena Nozza,4 Francesco La Rocca,2 Gioacchino Marziano,1 Anna Vittoria Lalinga,5 Emiliano Fabiani,6 Maria Teresa Voso,6 Patrizia Scaravaglio,7 Cristina Mecucci,8 Giovanni D'Arena31Scientific Direction, 2Laboratory of Preclinical and Translational Research, 3Unit of Hematology and Stem Cell Transplantation, 4Laboratory of Clinical Research and Advanced Diagnostics, 5Pathology Unit, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; 6Department of Hematology, Universita Cattolica del Sacro Cuore, Rome, Italy; 7Laboratory of Internal Medicine and Hematology, S Luigi Gonzaga Hospital, Orbassano, Italy; 8Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, ItalyAbstract: 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.Keywords: myelodysplastic syndromes, myeloproliferative neoplasms, lenalidomide, del(5q, JAK2, World Health Organization

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

    Energy Technology Data Exchange (ETDEWEB)

    Jabs, E.W.; Li, Xiang; Coss, C.; Taylor, E. (Johns Hopkins School of Medicine, Baltimore, MD (United States)); Lovett, M. (Univ. of Texas Southwestern Medical Center, San Antonio, TX (United States)); Yamaoka, L.H.; Speer, M.C. (Duke Univ. Medical Center, Durham, NC (United States)); Cadle, R.; Hall, B. (Univ. of Kentucky, Lexington, KY (United States)); Brown, K. (Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY (United States)) (and others)

    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.

  5. A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population.

    Science.gov (United States)

    Yasui, Takahiro; Okada, Atsushi; Urabe, Yuji; Usami, Masayuki; Mizuno, Kentaro; Kubota, Yasue; Tozawa, Keiichi; Sasaki, Shoichi; Higashi, Yoshihito; Sato, Yoshikazu; Kubo, Michiaki; Nakamura, Yusuke; Matsuda, Koichi; Kohri, Kenjiro

    2013-09-01

    A previous genome-wide association study (GWAS) reported three novel nephrolithiasis-susceptibility loci at 5q35.3, 7p14.3 and 13q14.1. Here, we investigated the association of these loci with nephrolithiasis by using an independent Japanese sample set. We performed case-control association analysis using 601 patients with nephrolithiasis and 201 control subjects. We selected seven single-nucleotide polymorphisms (SNPs): rs12654812 and rs11746443 from 5q35.3 (RGS14-SLC34A1-PFN3-F12); rs12669187 and rs1000597 from 7p14.3 (INMT-FAM188B-AQP1); and rs7981733, rs1170155, and rs4142110 from 13q14.1 (DGKH (diacylglycerol kinase)), which were previously reported to be significantly associated with nephrolithiasis. rs12654812, rs12669187 and rs7981733 were significantly associated with nephrolithiasis after Bonferroni's correction (P=3.12 × 10(-3), odds ratio (OR)=1.43; P=6.40 × 10(-3), OR=1.57; and P=5.00 × 10(-3), OR=1.41, respectively). Meta-analysis of current and previous GWAS results indicated a significant association with nephrolithiasis (P=7.65 × 10(-15), 7.86 × 10(-14) and 1.06 × 10(-9), respectively). We observed a cumulative effect with these three SNPs; individuals with three or more risk alleles had a 5.9-fold higher risk for nephrolithiasis development than those with only one risk allele. Our findings elucidated the significance of genetic variation at these three loci in nephrolithiasis in the Japanese population.

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

    DEFF Research Database (Denmark)

    Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan

    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 wit...

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

    Science.gov (United States)

    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

    2014-02-01

    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.

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

    Science.gov (United States)

    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

  9. Analysis of mutations in 17p 11.2 region in patients with Charcot-Marie-Tooth type 1 disease and patients with tomaculose neuropathy

    Directory of Open Access Journals (Sweden)

    Zamurović Nataša

    2002-01-01

    Full Text Available Charcot-Marie-Tooth type 1Α disease (CMT1A and hereditary neuropathy with liability to pressure palsies (HNPP are common inherited disorders of the peripheral nervous system associated with duplication and deletion respectively, of the 17p11.2 segment including the gene of peripheral myelin protein 22. We studied 48 subjects belonging to 29 families with clinical and electrophysiological signs of definite CMT1, 20 patients with suspected CMT phenotype, and 17 patients and healthy members of their families with HNPP. Blood sampling and DNA isolation, PCR, restriction analysis, southern blotting were performed using standard procedures. Of 48 patients with diagnosis of definite CMT1 in 25 (52% we found a 1.5 Mb tandem duplication in chromosome 17p11.2. These duplications were not found in any of 20 sporadic cases with the clinical phenotype of CMT but without reliable electrophysiological data. Only 13 (44.8%of 29 unrelated CMT1 patients from the first group had 17p11.2 duplications. Three of 4 sporadic cases (75% with definite CMT1 had 17p11.2 duplications. Of 17 patients from 6 families with HNPP deletion of 17p11.2 segment was found in 15 (88.2%, as well as in 5 (83.3% of six unrelated cases. Detection of CMT1A/HNPP recombination hotspot is a simple and reliable DNA diagnostic method, which is useful only for the patients with clinically already verified CMT1, and HNPP for further genetic counseling of patients and members of their families.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Thierry Vilboux

    Full Text Available 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.

  12. 伴有t(3;5)(q25;q34)的骨髓增生异常综合征急性髓系白血病变患者的分子特征%Molecular characterization of t (3;5)(q25;q34) in a case of acute myeloid leukemia secondary to myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    张悦; 邵英起; 薛永权; 王一; 张美荣; 刘旭平; 郑以州; 肖志坚

    2006-01-01

    目的 研究t(3;5)(q25;q34)的分子特征.方法 R显带染色体核型分析和染色体涂染分析确定t(3;5)(q25;q34)存在.RT-PCR法检测患者NPM-MLF1融合基因、MLF1基因表达.PCR联合序列分析检测NPM基因突变.实时定量RT-PCR(Real-time PCR)检测Evi-1,MDS1/Evi-1表达.免疫组化染色确定MLF1和NPM-MLF1蛋白细胞定位分布.Western blot法检测bcl-2蛋白表达.结果 染色体核型分析和涂染分析均证实存在染色体t(3;5)(q25;q34),NPM-MLF1融合基因阳性,经诱导治疗获得完全缓解后转为阴性.患者白血病细胞仅表达MLF1基因非编码蛋白剪接体,不表达Evi-1基因,弱表达MDS1/Evi-1.无NPM基因突变,未检出bcl-2蛋白表达.MLF1蛋白定位于细胞质,而NPM-MLF1则主要定位于胞核.结论 t(3;5)(q25;q34)是髓系肿瘤的一种少见的染色体易位,该染色体易位导致形成NPM-MLF1融合基因是其发病的分子学基础.

  13. Infantile spasm associated with 5q14.3 microdeletion syndrome: clinical and genetic characterization of a core family%5q14.3微缺失综合征导致婴儿痉挛症一家系的临床及遗传学研究

    Institute of Scientific and Technical Information of China (English)

    俞冬熠; 李朔; 姜楠

    2015-01-01

    目的 分析婴儿痉挛症患儿的临床特征,并对患儿及其父母进行遗传学检测.方法 分析2014年3月接诊的1例婴儿痉挛症患儿面部特征、体格和智力发育状况.实验室检查采用常规G显带分析患儿及父母外周血染色体核型,单核苷酸多态性(SNP)基因芯片技术检测染色体微小改变,荧光原位杂交技术(FISH)验证结果,并对其父母染色体中期分裂象进行FISH检测.结果 患儿女,7岁,语言、运动、语言发育严重迟滞,生后4个月出现癫痫发作,临床诊断为“婴儿痉挛症”.体检见消瘦,面容特殊,存在刻板样不自主动作.头颅CT平扫提示“硬膜下积液”.脑电图检查提示:痫样放电频繁;高度失律.患儿及其父母常规染色体核型分析(400条带)均显示为正常核型.SNP微阵列技术检测显示该患儿染色体5q14.3区段微缺失,缺失片段为2.03 Mb,分子核型为arr5q14.3(87 538 430 ~ 89 565 757)× 1,该区段包含MEF2C基因.选择区域特异性RP11-293 L20探针,应用FISH技术对芯片结果进行验证,确认患儿5q14.3区域存在杂合缺失.父母染色体核型正常,无5q14.3区域缺失,无插入突变.结论 患儿染色体5q14.3区段发生缺失为婴儿痉挛症的病因.患儿为新发生的5q14.3微缺失综合征,父母再次生育时,建议选择SNP芯片技术进行产前诊断.%Objective To characterize the clinical feature of a child with infantile spasm,karyotype and molecular cytogenetic analyses were performed to investigate the cause of disease and choose a suitable prenatal diagnostic method for the couple with the child.Method Routine G-banding was performed to analyze the karyotype of the patient and her parents,and molecular karyotyping was performed using SNP array.Confirmation and segregation studies were performed by fluorescence in situ hybridization (FISH).Result The patient presented with severe psychomotor retardation,epilepsy,muscular hypotonia,stereotypic behavior and

  14. Gluon fragmentation into {sup 3} P{sub J} quarkonium

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.P.

    1995-10-01

    The functions of the gluon fragmentation into {sup 3}P{sub j} quarkonium are calculated to order {alpha}{sup 2}{sub s}. With the recent progress in analysing quarkonium systems in QCD it is possible show how the so called divergence in the limit of the zero-binding energy, which is related to P-wave quarkonia, is treated correctly in the case of fragmentation functions. The obtained fragmentation functions satisfy explicitly at the order of {alpha} {sup 2}{sub s} the Altarelli-Parisi equation and when z {yields} 0 they behave as z{sup -1} as expected. 19 refs., 7 figs.

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

    Science.gov (United States)

    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

    2015-01-08

    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.

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Thermoelectric properties of polycrystalline NiSi3P4

    Science.gov (United States)

    May, Andrew F.; McGuire, Michael A.; Wang, Hsin

    2013-03-01

    The Hall and Seebeck coefficients, electrical resistivity, and thermal conductivity of polycrystalline NiSi3P4 were characterized from 2 to 775 K. Undoped NiSi3P4 behaves like a narrow gap semiconductor, with activated electrical resistivity ρ below room temperature and a large Seebeck coefficient of ˜400 μV/K at 300 K. Attempts to substitute boron for silicon resulted in the production of extrinsic holes, yielding moderately doped semiconductor behavior with ρ increasing with increasing temperature above ˜150 K. Hall carrier densities are limited to approximately 5 × 1019 cm-3 at 200 K, which would suggest the solubility limit of boron is reached if boron is indeed incorporated into the lattice. These extrinsic samples have a Hall mobility of ˜12 cm2/V/s at 300 K, and a parabolic band equivalent effective mass of ˜3.5 times the free electron mass. At 700 K, the thermoelectric figure of merit zT reaches ˜0.1. Further improvements in thermoelectric performance would require reaching higher carrier densities, as well as a mechanism to further reduce the lattice thermal conductivity, which is ˜5 W/m/K at 700 K. Alloying in Ge results in a slight reduction of the thermal conductivity at low temperatures, with little influence observed at higher temperatures.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji [Kyoto Prefectural Univ. of Medicine, Kyoto (Japan)] [and others

    1997-03-31

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

  20. The human granzyme A (HFSP, CTLA3) gene maps to 5q11-q12 and defines a new locus of the serine protease superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Fink, T.M.; Lichter, P. (Institut fuer angewandte Tumorvirologie, Heidelberg (Germany)); Wekerle, H.; Zimmer, M.; Jenne, D.E. (Max-Planck-Institut fuer Psychiatrie, Planegg-Martinsried (Germany))

    1993-11-01

    Human granzyme A (HFSP, Hanukah factor serine protease; CTLA3, cytotoxic T-lymphocyte-associated serine esterase-3), a homodimeric, trypsin-like serine protease of 60 kDa found in granules of cytolytic T cells and natural killer cells, is implicated in lymphocyte-mediated target cell lysis. It contributes to DNA fragmentation in perforin (PRF1)-lysed target cells through an unknown mechanism. The authors have isolated a cosmid clone for the functional gene of human granzyme A and established its complete exon-intron map of 10 kb. Using an 11-kb subfragment of the cloned genomic DNA as a probe, they have identified the chromosomal position of human granzyme A on 5q11-q12. Thus, the human granzyme A gene falls into a region of homology between human chromosome 5 and mouse chromosome 13, band D, where the mouse granzyme A gene has been located previously. The granzyme A gene is not linked to known members of the large superfamily of serine proteases. 20 refs., 2 figs.

  1. Long-Term Response in a Patient with del(5q Myelodysplastic Syndrome Who Discontinued Lenalidomide and Obtained a Good Response and Tolerance to Rechallenge

    Directory of Open Access Journals (Sweden)

    Francesco Pisani

    2014-04-01

    Full Text Available Background: The introduction of the immunomodulatory drug lenalidomide has revolutionized the treatment of patients with myelodysplastic syndromes (MDS and deletion of the long arm of chromosome 5. Treatment with lenalidomide results in transfusion independence in the majority of patients, but some questions remain unresolved, among them the duration of treatment. Moreover, a number of unexpected long-term remissions in patients who stopped lenalidomide for various reasons have been observed. Case Report: We report the case of a 60-year-old Caucasian male with deletion of the long arm of chromosome 5 and International Prognostic Scoring System (IPSS-defined low-risk MDS who was treated with lenalidomide, achieving complete cytogenetic remission and erythroid response. After tapering off and interrupting the treatment, the patient relapsed and showed a new response by lenalidomide retreatment. Six years after the initial treatment, we registered a durable erythroid long-term response and good tolerance, but there was no evidence of a very profound cytogenetic response compared to using lenalidomide as a first-line treatment. Cytogenetic and fluorescence in situ hybridization together with hemoglobin level, mean corpuscular volume (MCV and vitamin B12 level helped us to monitor the patient response; during the various phases of lenalidomide treatment, MCV and vitamin B12 normalization correlated with good response. Conclusion: Lenalidomide interruption and rechallenge in some 5q- MDS patients, with low risk according to the IPSS, is safe and feasible but does not result in a profound cytogenetic response.

  2. Association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population.

    Science.gov (United States)

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-06-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene and alcoholism. The GG genotype of the GABAA alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABAA beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABAA alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

  3. Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage.

    Science.gov (United States)

    Sobol, Maria; Raykova, Doroteya; Cavelier, Lucia; Khalfallah, Ayda; Schuster, Jens; Dahl, Niklas

    2015-09-01

    Induced pluripotent stem cells (iPSCs) have brought great promises for disease modeling and cell-based therapies. One concern related to the use of reprogrammed somatic cells is the loss of genomic integrity and chromosome stability, a hallmark for cancer and many other human disorders. We investigated 16 human iPSC lines reprogrammed by nonintegrative Sendai virus (SeV) and another 16 iPSC lines generated by integrative lentivirus for genetic changes. At early passages we detected cytogenetic rearrangements in 44% (7/16) of iPSC lines generated by lentiviral integration whereas the corresponding figure was 6% (1/16) using SeV-based delivery. The rearrangements were numerical and/or structural with chromosomes 5 and 12 as the most frequently involved chromosomes. Three iPSC lines with chromosome 5 aberrations were derived from one and the same donor. We present in this study the aberrant karyotypes including a duplication of chromosome 5q13q33 that restricts a candidate region for growth advantage. Our results suggest that the use of integrative lentivirus confers a higher risk for cytogenetic abnormalities at early passages when compared to SeV-based reprogramming. In combination, our findings expand the knowledge on acquired cytogenetic aberrations in iPSC after reprogramming and during culture.

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

    Science.gov (United States)

    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

    2012-02-01

    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.

  5. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. A 1.5-Mb deletion in 17p11.2-p12 is frequently observed in Italian families with hereditary neuropathy with liability to pressure palsies

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzetti, D.; Pandolfo, M. [Istituto Nazionale Neurologico, Milan (Italy)]|[Baylor College of Medicine, Houston, TX (United States); Pareyson, D.; Sghirlanzoni, A.; Di Donato, S. [Istituto Nazionale Neurologico, Milan (Italy); Roa, B.B.; Abbas, N.E.; Lupski, J.R. [Baylor College of Medicine, Houston, TX (United States)

    1995-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies. A 1.5-Mb deletion in chromosome 17p11.2-p12 has been associated with HNPP. Duplication of the same 1.5-Mb region is known to be associated with Charcot-Marie-Tooth disease type 1 (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity (NCV). The CMT1A duplication and HNPP deletion appear to be the reciprocal products of a recombination event involving a repeat element (CMT1A-REP) that flanks the 1.5-Mb region involved in the duplication/deletion. Patients from nine unrelated Italian families who were diagnosed with HNPP on the basis of clinical, electrophysiological, and histological evaluations were analyzed by molecular methods for DNA deletion on chromosome 17p. In all nine families, Southern analysis using a CMT1A-REP probe detected a reduced hybridization signal of a 6.0-kb EcoRI fragment mapping within the distal CMT1A-REP, indicating deletion of one copy of CMT1A-REP in these HNPP patients. Families were also typed with a polymorphic (CA){sub n} repeat and with RFLPs corresponding to loci D17S122, D17S125, and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, providing an independent indication for deletion. Furthermore, pulsed-field gel electrophoresis analysis of SacII-digested genomic DNA detected junction fragments specific to the 1.5-Mb HNPP deletion in seven of nine Italian families included in this study. These findings suggest that a 1.5-Mb deletion on 17p11.2-p12 is the most common mutation associated with HNPP. 51 refs., 5 figs., 1 tab.

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

    Science.gov (United States)

    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.

  11. Health-related quality of life outcomes of lenalidomide in transfusion-dependent patients with Low- or Intermediate-1-risk myelodysplastic syndromes with a chromosome 5q deletion: results from a randomized clinical trial.

    NARCIS (Netherlands)

    Revicki, D.A.; Brandenburg, N.A.; Muus, P.; Yu, R.; Knight, R.; Fenaux, P.

    2013-01-01

    We report health-related quality of life (HRQL) outcomes assessed using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) among 167 RBC transfusion-dependent patients with IPSS Low-/Intermediate-1-risk del5q31 MDS treated with lenalidomide versus placebo in a randomized phase 3 clinical t

  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

    NARCIS (Netherlands)

    A. Giagounidis (Aristoteles); G.J. Mufti (Ghulam); M. Mittelman (Moshe); G. Sanz (Guillermo); U. Platzbecker (Uwe); P. Muus (P.); D. Selleslag; O. Beyne-Rauzy (Odile); P.A.W. te Boekhorst (Peter); C. del Cañizo (Consuelo); A. Guerci-Bresler (Agnes); L. Nilsson (Lars); M. Lübbert (Michael); B. Quesnel (Bruno); A. Ganser (Arnold); D. Bowen (David); B. Schlegelberger (Brigitte); G. Göhring (Gudrun); T. Fu (Tommy); B. Benettaib (Bouchra); E. Hellström-Lindberg (Eva); P. Fenaux (Pierre)

    2014-01-01

    textabstractObjective: 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 lenalidomid

  13. Cloning of a New Gene/s in Chromosome 17p3.2-p13.1 that Control Apoptosis

    Science.gov (United States)

    2005-04-01

    Burk, F.G. Barr, B.S. Emanuel, Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors . Cancer Res., 52...previous work of our laboratory shown LOH in the transformed cell line BP1E [18]. The tumor suppressor gene TP53 is located in l7p13.1 at 1.5cM centromeric...profiling 1 has been suggested as a tumor suppressor gene in breast cancer cells (69). By RT-PCR, no differences were found in TP53 and PFN1 expression

  14. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.

    Science.gov (United States)

    Svobodova, Karla; Zemanova, Zuzana; Lhotska, Halka; Novakova, Milena; Podskalska, Lucie; Belickova, Monika; Brezinova, Jana; Sarova, Iveta; Izakova, Silvia; Lizcova, Libuse; Berkova, Adela; Siskova, Magda; Jonasova, Anna; Cermak, Jaroslav; Michalova, Kyra

    2016-03-01

    Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and

  15. Four novel Loci (19q13, 6q24, 12q24, and 5q14 influence the microcirculation in vivo.

    Directory of Open Access Journals (Sweden)

    M Kamran Ikram

    2010-10-01

    Full Text Available There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652. All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP spread across five loci were significantly associated (p<5.0×10(-8 with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61×10(-25, within the RASIP1 locus, rs225717 (6q24; p = 1.25×10(-16, adjacent to the VTA1 and NMBR loci, rs10774625 (12q24; p  =  2.15×10(-13, in the region of ATXN2,SH2B3 and PTPN11 loci, and rs17421627 (5q14; p = 7.32×10(-16, adjacent to the MEF2C locus. In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular

  16. A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q.

    Science.gov (United States)

    Clément, K; Dina, C; Basdevant, A; Chastang, N; Pelloux, V; Lahlou, N; Berlan, M; Langin, D; Guy-Grand, B; Froguel, P

    1999-02-01

    As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.

  17. Smith-Magenis syndrome and Moyamoya disease in a patient with del(17)(p11.2p13.1).

    Science.gov (United States)

    Girirajan, Santhosh; Mendoza-Londono, Roberto; Vlangos, Christopher N; Dupuis, Lucie; Nowak, Norma J; Bunyan, David J; Hatchwell, Eli; Elsea, Sarah H

    2007-05-01

    Chromosomal rearrangements causing microdeletions and microduplications are a major cause of congenital malformation and mental retardation. Because they are not visible by routine chromosome analysis, high resolution whole-genome technologies are required for the detection and diagnosis of small chromosomal abnormalities. Recently, array-comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) have been useful tools for the identification and mapping of deletions and duplications at higher resolution and throughput. Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome caused by deletion or mutation of the retinoic acid induced 1 (RAI1) gene and is often associated with a chromosome 17p11.2 deletion. We report here on the clinical and molecular analysis of a 10-year-old girl with SMS and moyamoya disease (occlusion of the circle of Willis). We have employed a combination of aCGH, FISH, and MLPA to characterize an approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in this patient, with the proximal breakpoint within the RAI1 gene. Further, investigation of the genomic architecture at the breakpoint intervals of this large deletion documented the presence of palindromic repeat elements that could potentially form recombination substrates leading to unequal crossover.

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

    Energy Technology Data Exchange (ETDEWEB)

    Juyal, R.C.; Shaffer, L.G.; Lupski, J.R.; Greenberg, F.; Baldini, A.; Patel, P.I. [Baylor College of Medicine, Houston, TX (United States)] [and others

    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.

  19. Reciprocal deletion and duplication of 17p11.2-11.2: Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome.

    Science.gov (United States)

    Lee, Cha Gon; Park, Sang-Jin; Yun, Jun-No; Yim, Shin-Young; Sohn, Young Bae

    2012-12-01

    Deletion and duplication of the -3.7-Mb region in 17p11.2 result in two reciprocal syndrome, Smith-Magenis syndrome and Potocki-Lupski syndrome. Smith-Magenis syndrome is a well-known developmental disorder. Potocki-Lupski syndrome has recently been recognized as a microduplication syndrome that is a reciprocal disease of Smith-Magenis syndrome. In this paper, we report on the clinical and cytogenetic features of two Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome. Patient 1 (Smith-Magenis syndrome) was a 2.9-yr-old boy who showed mild dysmorphic features, aggressive behavioral problems, and developmental delay. Patient 2 (Potocki-Lupski syndrome), a 17-yr-old boy, had only intellectual disabilities and language developmental delay. We used array comparative genomic hybridization (array CGH) and found a 2.6 Mb-sized deletion and a reciprocal 2.1 Mb-sized duplication involving the 17p11.2. These regions overlapped in a 2.1 Mb size containing 11 common genes, including RAI1 and SREBF.

  20. Measurement of the spin-forbidden decay rate (3s3d)1D2¿(3s3p)3 P2,1 in 24Mg

    DEFF Research Database (Denmark)

    Therkildsen, K. T.; Jensen, Brian Bak; Ryder, C. P.;

    2009-01-01

    We have measured the spin-forbidden decay rate from (3s3d)D12¿(3s3p)P32,1 in M24g atoms trapped in a magneto-optical trap. The total decay rate, summing up both exit channels (3s3p)P31 and (3s3p)P32 , yields 196±10s-1 in excellent agreement with resent relativistic many-body calculations of Porsev...

  1. Association of Serum MiR-142-3p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation

    Science.gov (United States)

    Sukma Dewi, Ihdina; Hollander, Zsuzsanna; Lam, Karen K.; McManus, Janet-Wilson; Tebbutt, Scott J.; Ng, Raymond T.; Keown, Paul A.; McMaster, Robert W.; McManus, Bruce M.; Gidlöf, Olof; Öhman, Jenny

    2017-01-01

    Background Identifying non-invasive and reliable blood-derived biomarkers for early detection of acute cellular rejection in heart transplant recipients is of great importance in clinical practice. MicroRNAs are small molecules found to be stable in serum and their expression patterns reflect both physiological and underlying pathological conditions in human. Methods We compared a group of heart transplant recipients with histologically-verified acute cellular rejection (ACR, n = 26) with a control group of heart transplant recipients without allograft rejection (NR, n = 37) by assessing the levels of a select set of microRNAs in serum specimens. Results The levels of seven microRNAs, miR-142-3p, miR-101-3p, miR-424-5p, miR-27a-3p, miR-144-3p, miR-339-3p and miR-326 were significantly higher in ACR group compared to the control group and could discriminate between patients with and without allograft rejection. MiR-142-3p and miR-101-3p had the best diagnostic test performance among the microRNAs tested. Serum levels of miR-142-3p and miR-101-3p were independent of calcineurin inhibitor levels, as measured by tacrolimus and cyclosporin; kidney function, as measured by creatinine level, and general inflammation state, as measured by CRP level. Conclusion This study demonstrated two microRNAs, miR-142-3p and miR-101-3p, that could be relevant as non-invasive diagnostic tools for identifying heart transplant patients with acute cellular rejection. PMID:28125729

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

    Science.gov (United States)

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

    2012-08-13

    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.

  3. Treatment of refractory anemia with ring sideroblasts associated with marked thrombocytosis with lenalidomide in a patient testing negative for 5q deletion and JAK2 V617F and MPL W515K/L mutations

    Directory of Open Access Journals (Sweden)

    Ryan Keen

    2016-11-01

    Full Text Available Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T is a hematologic malignancy that often results in transfusion dependency and a hypercoagulable state. This rare disease currently lacks formal guidelines for treatment; however, various case reports have demonstrated efficacy in the use of lenalidomide. This immunomodulatory drug has shown promise in patients with 5q deletions, with reports of achieving transfusion independence and normalization of platelet counts. Herein we present the case of a 68-year-old African American woman with RARS-T who tested negative for 5q deletion and JAK2 V617F and MPL W515K/L mutations. Her treatment with lenalidomide therapy resulted in a five-year durable complete clinical response.

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

    Science.gov (United States)

    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.

  5. Cystic Dilation of the Aqueductus Sylvii in Case of Trisomy 17p11.2—pter with the Deletion of the Terminal Portion of the Chromosome 6

    Directory of Open Access Journals (Sweden)

    Emese Horváth

    2010-01-01

    Full Text Available Since the 1970s, about 30 cases of partial or complete trisomy 17p have been presented in the literature. Partial trisomies of the short arm of chromosome 17 are somewhat more common, but complete trisomy is quite rare. Most of these cases were described in infants and newborns; and to our knowledge only 3 cases of trisomy 17p have been detected intrauterine. Phenotypic features of trisomy 17p in fetuses are intrauterine growth retardation, ventriculomegaly, cleft lip and cleft palate, micrognathia, horseshoe kidneys, single umbilical artery, and congenital heart defects. The sonographic and foetopathologic findings of a pregnancy trisomy 17p11.2—pter with the deletion of the terminal portion of the chromosome 6 due to paternal balanced translocation are described in this case report.

  6. Syntenic homology of human unique DNA sequences within chromossome regions 5q31, 10q22, 13q32-33 and 19q13.1 in the great apes

    Directory of Open Access Journals (Sweden)

    Vallente-Samonte Rhea U.

    2000-01-01

    Full Text Available Homologies between chromosome banding patterns and DNA sequences in the great apes and humans suggest an apparent common origin for these two lineages. The availability of DNA probes for specific regions of human chromosomes (5q31, 10q22, 13q32-33 and 19q13.1 led us to cross-hybridize these to chimpanzee (Pan troglodytes, PTR, gorilla (Gorilla gorilla, GGO and orangutan (Pongo pygmaeus, PPY chromosomes in a search for equivalent regions in the great apes. Positive hybridization signals to the chromosome 5q31-specific DNA probe were observed at HSA 5q31, PTR 4q31, GGO 4q31 and PPY 4q31, while fluorescent signals using the chromosome 10q22-specific DNA probe were noted at HSA 10q22, PTR 8q22, GGO 8q22 and PPY 7q22. The chromosome arms showing hybridization signals to the Quint-EssentialTM 13-specific DNA probe were identified as HSA 13q32-33, PTR 14q32-33, GGO 14q32-33 and PPY 14q32-33, while those presenting hybridization signals to the chromosome 19q13.1-specific DNA probe were identified as HSA 19q13.1, PTR 20q13, GGO 20q13 and PPY 20q13. All four probes presumably hybridized to homologous chromosomal locations in the apes, which suggests a homology of certain unique DNA sequences among hominoid species.

  7. Evaluation of chromosome 5 aberrations in complex karyotypes of patients with myeloid disorders reveals their contribution to dicentric and tricentric chromosomes, resulting in the loss of critical 5q regions.

    Science.gov (United States)

    Herry, Angèle; Douet-Guilbert, Nathalie; Morel, Frédéric; Le Bris, Marie-Josée; Morice, Patrick; Abgrall, Jean François; Berthou, Christian; De Braekeleer, Marc

    2007-06-01

    Dicentric chromosomes have often been observed in complex karyotypes in previously reported studies of therapy-related myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Fluorescence in situ hybridization (FISH) has now made the characterization of these rearrangements much easier. Dicentric and tricentric chromosomes were identified in 21 patients (9 MDS and 12 AML) among the 133 consecutive MDS/AML patients (17%) who had a structural or numerical aberration of chromosome 5 using conventional cytogenetic analysis. One third (7/21) of the patients had received alkylating drugs for a previously diagnosed cancer or chronic myeloproliferative disease. Loss of 5q material was identified in all 21 patients. One copy of the EGR1 (5q31) or the CSF1R (5q33 approximately q34) genes was lost in 20 of the 21 patients. Dicentric and tricentric chromosomes involving chromosome 5 are frequently observed in complex karyotypes among patients with de novo or therapy-related MDS/AML. They lead to deletions of various parts of the long arm of chromosome 5.

  8. A FISH comparison of variant derivatives of the recurrent dic(17;20) of myelodysplastic syndromes and acute myeloid leukemia: Obligatory retention of genes on 17p and 20q may explain the formation of dicentric chromosomes.

    Science.gov (United States)

    MacKinnon, Ruth N; Patsouris, Cris; Chudoba, Ilse; Campbell, Lynda J

    2007-01-01

    The dic(17;20) is a recurrent unbalanced translocation occurring rarely in myelodysplastic syndromes and acute myeloid leukemia. We have studied eleven cases with the dic(17;20) or a more complex derivative, all of which showed deletion of 17p and 20q material. The tumor suppressor gene TP53 was not always lost, supporting a more distal gene as the target of these 17p deletions. All derivatives could be interpreted as having initially been formed as a dicentric chromosome, those with a larger amount of material between the centromeres having undergone further rearrangement to stabilize the chromosome while retaining proximal 17p and proximal 20q material. We propose that critical sequences on both 17p and 20q proximal to the sites of deletion must be retained during the critical 17p and 20q deletions. This would explain the excess of dicentric chromosomes resulting from 17;20 translocation, and the apparent stabilization of the unstable derivatives by further rearrangements which preserve 17p and 20q material.

  9. Interface reactions in Mg/Zn3P2 solar cells

    Science.gov (United States)

    Kazmerski, L. L.; Ireland, P. J.; Catalano, A.

    1981-05-01

    The composition and chemistry of the Mg/Zn3P2 interface was studied using surface analysis techniques. For higher carrier concentrations (p 10 to the 17th power/cu cm), a heterojunction occurs by the chemical interaction of the Mg with Zn3P2 to form Mg3P2. For lower carrier concentrations this reaction does not take place, and Mg diffuses into the Zn3P2. Diffusion coefficients of Mg in Zn3P2 are determined. Grain (crystalline) and grain boundary components of the diffusion coefficient are evaluated. These data compare very well with that reported using electron beam induced currents and spectral response measurements.

  10. A balanced t(5;17 (p15;q22-23 in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

    Directory of Open Access Journals (Sweden)

    Wijers-Koster Pauline

    2009-11-01

    Full Text Available Abstract Background Chondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH. Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases. Results A balanced t(5;17(p15;q22-23 was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17 translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5α1 (SRD5A1 gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase × (CA10 gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases. Conclusion We report a novel t(5;17(p15;q22-23 translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-05-15

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

  12. Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Using a combination of hybridization of PAC to a cDNA library and RACE technique, we isolated a novel cDNA, designated as C17orf25 (Chromosome 17 open reading frame 25, previously named it HC71A), from the deletion region on chromosome 17p13.3. The cDNA encodes a protein of 313 amino acids with a calculated molecular mass of 34.8 kDa. C17orf25 is divided into 10 exons and 9 introns, spanning 23 kb of genomic DNA. Northern blot analysis showed that the mRNA expression of C17orf25 was decreased in hepatocellular carcinoma samples as compared to adjacent noncancerous liver tissues from the same patients. The transfection of C17orf25 into the hepatocellular carcinoma cell SMMC7721 and overexpression could inhibit the cell growth. The above results indicate that C17orf25 is a novel human gene, and the cloning and preliminary characterization of C17orf25 is a prerequisite for further functional analysis of this novel gene in human hepatocellular carcinoma.

  13. Review of disrupted sleep patterns in Smith-Magenis syndrome and normal melatonin secretion in a patient with an atypical interstitial 17p11.2 deletion.

    Science.gov (United States)

    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

    2009-07-01

    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-hr melatonin secretion patterns in two independent SMS cohorts (US and 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 ( approximately 6Mb; cenTNFRSFproteinB) of chromosome band (17)(p11.2p11.2) 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.

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

    Science.gov (United States)

    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.

  15. Energetics and Dynamics of the Reactions of O(3P) with Dimethyl Methylphosphonate and Saria

    Science.gov (United States)

    2009-09-15

    a SN2 -like transition geometry, Figure 3c, the axial O-C-H bond angle is slightly bent more for reaction 4, Figure 3d. The products of reaction 4 are...Energetics and Dynamics of the Reactions of O(3P) with Dimethyl Methylphosphonate and Sarin Patrick F. Conforti and Matthew Braunstein* Spectral...calculations were performed on the reaction systems O(3P) + sarin and O(3P) + dimethyl methylphosphonate (DMMP), a sarin simulant. Transition state

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

    Science.gov (United States)

    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.

  17. Mosaic microdeletion of 17p11.2-p12 and duplication of 17q22-q24 in a girl with Smith-Magenis phenotype and peripheral neuropathy.

    Science.gov (United States)

    Goh, Elaine Suk-Ying; Banwell, Brenda; Stavropoulos, Dimitri James; Shago, Mary; Yoon, Grace

    2014-03-01

    We report on a girl with a de novo mosaic derivative chromosome 17 involving a 7.4 Mb deletion of chromosome region 17p11.2 to 17p12 and a duplication of a 12.35 Mb region at 17q22 to 17q24. She was ascertained because of developmental delay, peripheral neuropathy, brachydactyly and minor anomalies. The derivative chromosome was present in approximately 12% of lymphocytes based on FISH studies, and was detected by array comparative genomic hybridization. To our knowledge, this is the third case of mosaicism involving deletion of the 17p11.2 region and the lowest level of mosaicism reported in a patient with Smith-Magenis syndrome (SMS).

  18. miR-410-3p suppresses breast cancer progression by targeting Snail.

    Science.gov (United States)

    Zhang, Ya-Feng; Yu, Yue; Song, Wang-Zhao; Zhang, Rui-Ming; Jin, Shan; Bai, Jun-Wen; Kang, Hong-Bin; Wang, Xin; Cao, Xu-Chen

    2016-07-01

    miR-410-3p acts as an oncogene or tumor-suppressor gene in various types of cancer. However, its role in breast cancer remains unknown. In the present study, expression of miR-410-3p in 30 breast cancer and paired adjacent normal tissues was detected by RT-qPCR. The expression of miR-410-3p was downregulated in 76.7% of the breast cancer samples. To further validate the expression of miR-410-3p in breast cancer, we analyzed miR-410-3p expression profiling data set from The Cancer Genome Atlas (TCGA) including 683 breast cancer and 87 normal breast tissues. We observed that the expression of miR-410-3p was downregulated in breast cancer tissues. Next, we investigated the influence of miR-410-3p on cell proliferation by transiently transfecting the miR-410-3p mimic or inhibitor, as well as their corresponding controls in the MDA-MB-231 and MCF7 cell lines. miR-410-3p overexpression reduced cell growth, colony formation and the number of EdU-positive cells in the MDA-MB-231 cells. In contrast, inhibition of miR-410-3p in the MCF7 cells resulted in a higher proliferation rate as assessed by MTT assay, plate colony formation and EdU assays. Furthermore, miR-410-3p inhibited epithelial-mesenchymal transition. In addition, Snail was found to be a direct target of miR-410-3p based on a luciferase assay. Overexpression of Snail was able to rescue the effect of miR-410-3p in breast cancer cells. Moreover, miR‑410-3p was inversely expressed with Snail in breast cancer samples. Our data provide new knowledge regarding the role of miR-410-3p in breast cancer progression.

  19. Sizeable beta-strength in 31Ar (beta 3p) decay

    DEFF Research Database (Denmark)

    T. Koldste, G.; Blank, B.; J. G. Borge, M.

    2014-01-01

    We present for the first time precise spectroscopic information on the recently discovered decay mode beta-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow-Teller strength distribution from the decay of 31Ar revealing that as ...

  20. Terminal 3p deletions in two families--correlation between molecular karyotype and phenotype.

    NARCIS (Netherlands)

    Pohjola, P.; Leeuw, N. de; Penttinen, M.; Kaariainen, H.

    2010-01-01

    The 3p deletion syndrome is a rare disorder caused by deletions of different sizes in the 3p25-pter region. It is characterized by growth retardation, developmental delay, mental retardation, dysmorphism, microcephaly, and ptosis. The phenotype of individuals with deletions varies from normal to sev

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

    Science.gov (United States)

    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.

  2. Electronic and Rovibrational Quantum Chemical Analysis of C$_3$P$^-$: The Next Interstellar Anion?

    CERN Document Server

    Fortenberry, Ryan C

    2015-01-01

    C$_3$P$^-$ is analogous to the known interstellar anion C$_3$N$^-$ with phosphorus replacing the nitrogen in a simple step down the periodic table. In this work, it is shown that C$_3$P$^-$ 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, C$_3$P$^-$ has a valence excited state that may lead to further stabilization of this molecule, and C$_3$P$^-$ has a larger dipole moment than neutral C$_3$P ($\\sim 6$ D vs. $\\sim 4$ D). As such, C$_3$P$^-$ is probably a more detectable astromolecule than even its corresponding neutral radical. Highly-accurate quantum chemical quartic force fields are also applied to C$_3$P$^-$ and its singly $^{13}$C substituted isotopologues in order to provide structures, vibrational frequencies, and spectroscopic constants that may aid in its detection.

  3. Orientation of Zn3P2 films via phosphidation of Zn precursors

    Science.gov (United States)

    Katsube, Ryoji; Nose, Yoshitaro

    2017-02-01

    Orientation of solar absorber is an important factor to achieve high efficiency of thin film solar cells. In the case of Zn3P2 which is a promising absorber of low-cost and high-efficiency solar cells, (110)/(001) orientation was only reported in previous studies. We have successfully prepared (101)-oriented Zn3P2 films by phosphidation of (0001)-oriented Zn films at 350 °C. The phosphidation mechanism of Zn is discussed through STEM observations on the partially-reacted sample and the consideration of the relationship between the crystal structures of Zn and Zn3P2 . We revealed that (0001)-oriented Zn led to nucleation of (101)-oriented Zn3P2 due to the similarity in atomic arrangement between Zn and Zn3P2 . The electrical resistivity of the (101)-oriented Zn3P2 film was lower than those of (110)/(001)-oriented films, which is an advantage of the phosphidation technique to the growth processes in previous works. The results in this study demonstrated that well-conductive Zn3P2 films could be obtained by controlling orientations of crystal grains, and provide a guiding principle for microstructure control in absorber materials.

  4. Evolution of a system sensitive to stochastic noise: P3.p cell fate in Caenorhabditis.

    Science.gov (United States)

    Pénigault, Jean-Baptiste; Félix, Marie-Anne

    2011-09-15

    The C. elegans cell lineage is overall invariant. One rare instance of variability concerns P3.p, the most anterior vulva precursor cell, which may either fuse with the epidermis without dividing, or remain competent to form vulval tissue and divide. Here we examine the evolutionary properties of this stochastic variation in P3.p fate. In the Caenorhabditis genus, high P3.p competence is ancestral and reduction in P3.p competence and division frequency occurred in C. sp. 14 and in a clade of nine species. Within this clade, the frequency of P3.p division further varies within and among species, being intermediate in C. elegans and low in C. briggsae. P3.p fate frequency is sensitive to random mutation accumulation, suggesting that this trait may evolve rapidly because of its sensitivity to mutational impact. P3.p fate depends on LIN-39/Hox5 expression and we find that the peak of LIN-39/Hox5 protein level is displaced posteriorly in C. briggsae compared to C. elegans. However, P3.p fate specification is most sensitive to the dose of EGL-20 and CWN-1, two Wnts that are secreted in a long-range gradient from the posterior end of C. elegans larvae (accompanying article). A half-dose of either of these Wnts is sufficient to affect division frequency in C. elegans N2 to levels similar to those in C. briggsae. Symmetrically, we show that an increase in Wnt dose rescues anterior competence in C. briggsae. We propose that evolutionary variation in the concentration or interpretation of the long-range Wnt gradient may be involved in the rapid evolution of P3.p fate in Caenorhabditis.

  5. Sizeable beta-strength in {sup 31}Ar (β3p) decay

    Energy Technology Data Exchange (ETDEWEB)

    Koldste, G.T. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Blank, B. [Centre d' Études Nucléaire de Bordeaux-Gradignan, CNRS/IN2P3 – Université Bordeaux I, F-33175 Gradignan Cedex (France); Borge, M.J.G.; Briz, J.A.; Carmona-Gallardo, M. [Instituto de Estructura de la Materia, CSIC, E-28006 Madrid (Spain); Fraile, L.M. [Grupo de Física Nuclear, Universidad Complutense, CEI Moncloa, E-28040 Madrid (Spain); Fynbo, H.O.U. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Giovinazzo, J. [Centre d' Études Nucléaire de Bordeaux-Gradignan, CNRS/IN2P3 – Université Bordeaux I, F-33175 Gradignan Cedex (France); Johansen, J.G. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Jokinen, A. [Department of Physics, University of Jyväskylä, FIN-40351 Jyväskylä (Finland); Jonson, B. [Fundamental Fysik, Chalmers Tekniska Högskola, S-41296 Göteborg (Sweden); Kurturkian-Nieto, T. [Centre d' Études Nucléaire de Bordeaux-Gradignan, CNRS/IN2P3 – Université Bordeaux I, F-33175 Gradignan Cedex (France); Nilsson, T. [Fundamental Fysik, Chalmers Tekniska Högskola, S-41296 Göteborg (Sweden); Perea, A.; Pesudo, V. [Instituto de Estructura de la Materia, CSIC, E-28006 Madrid (Spain); and others

    2014-10-07

    We present for the first time precise spectroscopic information on the recently discovered decay mode β-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow–Teller strength distribution from the decay of {sup 31}Ar revealing that as much as 30% of the strength resides in the β3p-decay mode. A simplified description of how the main decay modes evolve as the excitation energy increases in {sup 31}Cl is provided.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kononenko, Oleksiy [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    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.

  7. Elevation of circulating miR-210-3p in high-altitude hypoxic environment

    Directory of Open Access Journals (Sweden)

    Yan eYan

    2016-03-01

    Full Text Available 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.

  8. Oscillator strength for 3s{sup 2}3p{sup 5}-3s3p{sup 6} in Cl-like ions

    Energy Technology Data Exchange (ETDEWEB)

    Berrington, K.A.; Waldock, J.A. [School of Science and Mathematics, Sheffield Hallam University, Sheffield (United Kingdom); Pelan, J.C [Gatsby Computational Neuroscience Unit, University College, London (United Kingdom)

    2001-07-14

    Recent experiments have revealed discrepancies between calculated and experimental lifetimes in the lowest excited level of some chlorine-like ions. New ab initio oscillator strengths using the Breit-Pauli R-matrix method are provided for the 3s{sup 2}3p{sup 5} {sup 2}P{sup o}{sub 3/2,1/2}-3s3p{sup 6} {sup 2}S{sup e}{sub 1/2} transition in Cl-like Ar II through to Cu XIII. Our calculated lifetimes for these twelve ions are respectively 5.507, 2.077, 1.177, 0.784, 0.569, 0.438, 0.350, 0.287, 0.241, 0.206, 0.178 and 0.156 ns, and are more consistent with experiments than other calculations. (author). Letter-to-the-editor.

  9. Isotope shifts of the (3s3p) 3P0,1,2-(3s4s) 3S1 Mg I transitions

    DEFF Research Database (Denmark)

    He, Ming; Therkildsen, Kasper T.; Jensen, Brian B.;

    2009-01-01

    We report measurements of the isotope shifts of the (3s3p)P30,1,2-(3s4s)S31 Mg I transitions for the stable isotopes M24g (I=0) , M25g (I=5/2) , and M26g (I=0) . Furthermore, the M25g S31 hyperfine coefficient A(S31)=(-321.6±1.5)MHz is extracted and found to be in excellent agreement with state...

  10. The Application of 3P+MYSQL Technology of Dynamic Website Design%3P+MYSQL技术在动态网站设计中的运用

    Institute of Scientific and Technical Information of China (English)

    周悦; 朱小社

    2004-01-01

    在Windows2000 Server平台下分别利用ASP、PHP、JSP这三个动态网站技术,使用可以跨Windows和Linux平台的MYSQL数据库,采用三种连接数据库的方法,在三种不同特点的WEB服务器环境下,给出了动态网站设计中3P+MYSQL技术的运用.

  11. Surface and interface properties of Zn3P2 solar cells

    Science.gov (United States)

    Kazmerski, L. L.; Ireland, P. J.; Catalano, A.

    1981-03-01

    The compositional properties of Zn3P2 thin films are studied using surface analysis techniques. Relative sensitivity factors of S(Zn sub LMM) = 0.29 and S(P sub LMM) = 0.34 are determined for this semiconductor with the aid of Auger electron spectroscopy standard spectra. The interfacial properties of the Mg/Zn3P2 thin-film solar cell are studied using Auger electron spectroscopy depth-compositional profiling in conjunction with complementary secondary ion mass spectroscopy and X-ray photoelectron spectroscopy data. Evidence is adduced for the formation of Mg3P2 at the metal-semiconductor interface. It is noted that this compound has a bandgap near that of Zn3P2. Attention is given to the possible formation of a heterojunction as a result of the interfacial reaction.

  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

    Science.gov (United States)

    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.

    Science.gov (United States)

    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. Photoionization cross sections of the excited 3s3p 3Po state for atomic Mg

    Science.gov (United States)

    Wang, Guoli; Wan, Jianjie; Zhou, Xiaoxin

    2017-01-01

    The photoionization cross sections of the excited levels (3s3p 0,1,2,o 3P) of atomic Mg have been studied theoretically using both the nonrelativistic and fully relativistic R-matrix method. For the threshold cross sections, as previous nonrelativistic studies, present calculations show significant differences (a factor of 3) from former experimental values. Large discrepancies with experiment calls for additional measurements of the photoionization cross sections from the excited states of Mg.

  15. Determination of diffusion, reflection and deexcitation coefficients of metastable excited Ne(3P2) atom

    Science.gov (United States)

    Suzuki, S.; Itoh, H.

    2016-05-01

    The diffusion coefficient of the metastable excited Ne(3P2) atom in neon, the reflection coefficient of Ne(3P2) at the surface of an electrode and the rate coefficient of Ne(3P2) for collisional quenching by Ne(1S0) were determined from the gas pressure dependence of the effective lifetime of Ne(3P2). The effective lifetime of Ne(3P2) was measured from the transient current after turning off the Ultraviolet (UV) light in a Townsend discharge. The observed transient current waveform was analysed by solving the diffusion equation for the metastable excited Ne(3P2) atom using the third kind of boundary condition. The rate coefficient of Ne(3P2) for collisional quenching by Ne(1S0) and the reflection coefficient were determined by a nonspectroscopic method for the first time in neon to the best of our knowledge and were (3.2  ±  0.4)  ×  10-16 cm3 s-1 and 0.10  ±  0.04, respectively. The obtained diffusion coefficient at 1 Torr was 177  ±  17 cm2 s-1, which is consistent with the value reported by Dixon and Grant. Moreover, the present results are compared with the results of Phelps and were found to be in good agreement. We also discuss the deexcitation rate of Ne(3P2) at pressures of up to 60 Torr in comparison with previously reported values.

  16. Misregulation of Scm3p/HJURP Causes Chromosome Instability in Saccharomyces cerevisiae and Human Cells

    OpenAIRE

    Prashant K. Mishra; Wei-Chun Au; John S. Choy; P Henning Kuich; Baker, Richard E.; Foltz, Daniel R.; Basrai, Munira A.

    2011-01-01

    The kinetochore (centromeric DNA and associated proteins) is a key determinant for high fidelity chromosome transmission. Evolutionarily conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast. Overexpression of HJURP, the mammalian homolog of budding yeast Scm3p, has been observed in lung and breast cancers and is associated with poor prognosis; however, the physiological relevanc...

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

    Science.gov (United States)

    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.

  18. Microduplications of 3p26.3p26.2 containing CRBN gene in patients with intellectual disability and behavior abnormalities.

    Science.gov (United States)

    Papuc, Sorina M; Hackmann, Karl; Andrieux, Joris; Vincent-Delorme, Catherine; Budişteanu, Magdalena; Arghir, Aurora; Schrock, Evelin; Ţuţulan-Cuniţă, Andreea C; Di Donato, Nataliya

    2015-05-01

    We report on the clinical data and molecular cytogenetic findings in three unrelated patients presenting with intellectual disability and behavior abnormalities. An overlapping microduplication involving 3p26.2-26.3 was identified in these patients. All three aberrations were confirmed and proven to be parentally inherited. The sizes of the duplications were different, with a common minimal region of 423,754 bp containing two genes - TRNT1 and CRBN. Here, we hypothesize that the copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability.

  19. Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Takeshi Chiyomaru

    Full Text Available Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs. In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1 and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as 'Pathways in cancer', 'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3' UTR of several target genes (such as RAC1, EGFR and EP300 that are components of 'Pathways in cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.

  20. Quark structure of the X(3872) and χb(3P) resonances

    Science.gov (United States)

    Ferretti, J.; Galatà, G.; Santopinto, E.

    2014-09-01

    We discuss the nature of the χb(3P) and X(3872) mesons. Are the χb(3P)'s standard bb¯ mesons or bb¯ states with a significative continuum component? Is the X(3872) a cc¯ state with continuum coupling effects or a meson-meson molecule? To do that, we compare quark model and unquenched quark model results for the mass barycenter and splittings of the χb(3P) multiplet. Future and more precise experimental results will discriminate between the two interpretations. In the case of the X(3872), we interpret it as a cc¯ core plus higher Fock components due to the coupling to the meson-meson continuum, and thus we think that it is compatible with the meson χc1(2P), with JPC=1++. The JPC=1++ quantum numbers are in agreement with the experimental results found by the LHCb collaboration. In our view, the X(3872)'s mass is lower than the quark model's predictions because of self-energy shifts. We also provide an estimation of the open charm/bottom strong decay modes of the X(3872) and χb(3P) mesons, such as X(3872)→DD¯* and χb2(3P)→BB¯, and radiative transitions.

  1. Magnetic Properties of Quantized Vortices in Neutron $^3P_2$ Superfluids in Neutron Stars

    CERN Document Server

    Masuda, Kota

    2015-01-01

    We discuss quantized vortices in neutron $^3P_2$ superfluids, which are believed to realize in high density neutron matter such as neutron stars. By using the Ginzburg-Landau free energy for $^3P_2$ superfluids, we determine the ground state in the absence and presence of the external magnetic field, and numerically construct $^3P_2$ quantized vortices in the absence and presence of the external magnetic field along the vortex axis (poloidal) or angular direction (toroidal). We find in certain situations the spontaneous magnetization of the vortex core, whose typical magnitude is about $10^{7-8}$ Gauss, but the net magnetic field in a neutron star is negligible because of the ratio of the vortex core size $\\sim 10$fm and the intervortex distance $\\sim 10^{-6}$m in a vortex lattice.

  2. Doubly excited 2s2p 1,3p1 resonances in photoionization of helium

    Institute of Scientific and Technical Information of China (English)

    Wan Jian-Jie; Dong Chen-Zhong

    2009-01-01

    The multi-configuration Dirac-Fock (MCDF) method is implemented to study doubly excited 2s2p 1,3P1 resonances of the helium atom and the interference between photoionization and photoexcitation autoionization processes.In order to reproduce the total photoionization sprectra,the excited energies from the ground ls2 1 S0 state to the doubly excited 2s2p 1'3P1 states and the relevant Auger decay rates and widths are calculated in detail. Furthermore,the interference profile determined by the so-called Fano parameters q and p2 is also reproduced. Good agreement is found between the present results and other available theoretical and experimental results. This indeed shows a promising way to investigate the Fano resonances in photoionization of atoms within the MCDF scheme,although there are some discrepancies in the present calculations of the 2s2p 3P1 state.

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

    Science.gov (United States)

    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.

  4. A new form of Ca3P2 with a ring of Dirac nodes

    Directory of Open Access Journals (Sweden)

    Lilia S. Xie

    2015-08-01

    Full Text Available We report the synthesis and crystal structure of a new high-temperature form of Ca3P2. The crystal structure was determined through Rietveld refinements of synchrotron powder x-ray diffraction data. This form of Ca3P2 has a crystal structure of the hexagonal Mn5Si3 type, with a Ca ion deficiency compared to the ideal 5:3 stoichiometry. This yields a stable, charge-balanced compound of Ca2+ and P3−. We also report the observation of a secondary hydride phase, Ca5P3H, which again is a charge-balanced compound. The calculated band structure of Ca3P2 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.

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

    Science.gov (United States)

    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.

  6. 乳腺癌与其癌前病变染色体16q22、17p13、6q16—q23杂合性缺失的研究%Loss of heterozygosity at 16q22, 17p13 and 6q16-q23 in breast carcinoma and precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    赵文丽; 李欣影; 朱淑玲

    2008-01-01

    目的:探讨染色体16q22、17p13、6q16-q23杂合性缺失在乳腺癌发生机制中的作用及其临床病理学意义.方法:采用显微切割、PCR扩增、聚丙烯凝胶电泳及银染色等方法,检测40例乳腺癌、29例癌前病变和18例良性增生微卫星位点D16S398、TP53、D6S404杂合性缺失情况.结果:乳腺癌组上述3个位点的LOH率均高于癌前病变组,差异有统计学意义(P<0.05);癌前病变组D16S398位点LOH率高于良性增生组,差别有统计学意义(P<0.05);癌前病变组TP53、D6S404位点的LOH率亦高于良性增生组,但差异无统计学意义(P>0.05);TP53位点的LOH与乳腺癌的组织学分级、淋巴结转移和TNM分期相关(P<0.05).结论:染色体16q22杂合性缺失是乳腺癌发生的始动因素之一,TP53、D6S404可能是检测乳腺癌较为敏感的位点,TP53 LOH与乳腺癌的恶性进展相关.

  7. Domain architectures of the Scm3p protein provide insights into centromere function and evolution

    OpenAIRE

    Aravind, L.; Lakshminarayan, M. Iyer; Wu, Carl

    2007-01-01

    Recently, Scm3p has been shown to be a nonhistone component of centromeric chromatin that binds stoichiometrically to CenH3–H4 histones, and to be required for the assembly of kinetochores in S. cerevisiae. Scm3p is conserved across fungi, and displays a remarkable variation in protein size, ranging from ~200 amino acids in Saccharomyces cerevisiae to ~1300 amino acids in Neurospora crassa. This is primarily due a variable C-terminal segment that is linked to a conserved N-terminal, CenH3-int...

  8. Autism spectrum disorder, Klinefelter syndrome, and chromosome 3p21.31 duplication: a case report.

    Science.gov (United States)

    Stuart, Scott W; King, Casey H; Pai, G Shashidar

    2007-12-18

    Autism spectrum disorders are heterogeneous in nature with idiopathic and genetic origins. We present a 7-year-old boy with a long history of multiple behavioral concerns, poor school performance, repetitive/compulsive tendencies, poor social skills, and language delays. A multidisciplinary evaluation concluded that the patient met full criteria for autism. A genetic evaluation demonstrated Klinefelter syndrome 47, XXY karyotype with concurrent duplication of 3p21.31 by microarray analysis. Maternal genetic analysis demonstrated the same 3p21.31 duplication. The potential implication with regard to autism spectrum disorders has not been previously discussed in the literature.

  9. The infinite order point on Y~2=X~3-p~3

    Institute of Scientific and Technical Information of China (English)

    张绍伟

    1995-01-01

    The parameterization of the elliptic curve Y2=X2+1 is given by using the modular forms of X(12) Then using class field theory over imaginary quadratic field and Shimura reciprocity, an infinite order point on the curve y2- = x3-p3 is constructed, for prime p=7 (mod 24).

  10. miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation

    DEFF Research Database (Denmark)

    Qiu, Weimin; Kassem, Moustapha

    2014-01-01

    Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC) differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate many aspects of osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling...... in hMSC. We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast differentiation of hMSC as evidenced by reduced alkaline phosphatase...... activity, gene expression and in vitro mineralized matrix formation. Bioinformatic studies, Western blot analysis and 3'UTR reporter assay demonstrated that cell division cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of CDC25A inhibited hMSC proliferation and osteoblast...

  11. Construction of a consistent YAC contig for human chromosome region 3p14.1

    NARCIS (Netherlands)

    Bardenheuer, W; Michaelis, S; Lux, A; Vieten, L; Brocker, F; Julicher, K; Willers, C; Siebert, R; Smith, DI; vanderHout, AH; Buys, C; Schutte, J; Opalka, B

    1996-01-01

    Chromosomal deletions and translocations of human chromosome region 3p14 are observed in various human malignancies and suggest the existence of a tumor suppressor gene locus within this region. Tumors most frequently affected by these aberrations are small-cell lung cancer and renal-cell carcinoma.

  12. Baryonic {sup 3}P{sub 2} superfluidity under charged-pion condensation with {delta} isobar

    Energy Technology Data Exchange (ETDEWEB)

    Takatsuka, T.; Tamagaki, R. [Iwate Univ., Morioka, Iwate (Japan)

    1999-08-01

    We study the baryonic {sup 3}P{sup 2} superfluidity under charged-pion condensation with isobar ({delta}) degrees of freedom. After a remark on motivations of the present study, the outline of theoretical framework is briefly described, typical results of the superfluid critical temperature are shown, and the possibility of coexistence of the superfluid with charged-pion condensation is discussed. (author)

  13. Using P3P in a web services-based context-aware application platform

    NARCIS (Netherlands)

    Zuidweg, M.; Goncalves Filho, J.; Sinderen, van M.J.; Halasz, E.; Lukovszki, C.; Marosits, T.

    2003-01-01

    This paper describes a proposal for a privacy control architecture to be applied in the WASP project. The WASP project aims to develop a context-aware service platform on top of 3G networks, using web services technology. The proposed privacy control architecture is based on the P3P privacy policy d

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

    Science.gov (United States)

    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.

  15. Evidence for locus heterogeneity in acrocephalosyndactyly: A refined localization for the Saethre-Chotzen syndrome locus on distal chromosome 7p-and exclusion of Jackson-Weiss syndrome from craniosynostosis loci on 7p and 5q

    Energy Technology Data Exchange (ETDEWEB)

    Herwerden, L. van; Rose, C.S.P.; Reardon, W.; Malcolm, S.; Winter, R.M. (Institute of Child Health, London (United Kingdom)); Brueton, L.A. (Northwick Park Hospital, Harrow (United Kingdom)); Weissenbach, J. (Human Genome Research Centre, Evry (France))

    1994-04-01

    Craniosynostosis (premature fusion of the skull sutures) occurs as a clinically heterogeneous group of disorders, frequently involving digital abnormalities. The authors have previously provisionally assigned the gene for one such condition, Saethre-Chotzen syndrome (ACS III), to chromosome 7p. Linkage analysis is now reported between ACS III and dinucleotide repeat loci on distal 7p. The maximum lod scores, Z[sub max], were 5.57 at a recombination fraction of .05, with D7S488, and 4.74 at a recombination fraction of .05, with D7S493. Only weak linkage, not reaching significance, was found with distal markers (D7S513 and afm281vc9) and a proximal marker (D7S516). Multipoint analysis shows that the disease locus lies between D7S513 and D7S516. Analysis of individual recombinants shows that the most likely position is between D7S493 and D7S516. Linkage data in regard of Jackson-Weiss syndrome demonstrate that this autosomal dominant form of acrocephalosyndactyly does not map to the ACS III region on 7p or to the acrocephalosyndactyly locus on 5q (Boston type). These findings underline the genetic heterogeneity among the different clinical conditions manifesting with acrocephalosyndactyly. 20 refs., 3 figs., 2 tabs.

  16. Evidence for locus heterogeneity in acrocephalosyndactyly: a refined localization for the Saethre-Chotzen syndrome locus on distal chromosome 7p--and exclusion of Jackson-Weiss syndrome from craniosynostosis loci on 7p and 5q.

    Science.gov (United States)

    van Herwerden, L; Rose, C S; Reardon, W; Brueton, L A; Weissenbach, J; Malcolm, S; Winter, R M

    1994-04-01

    Craniosynostosis (premature fusion of the skull sutures) occurs as a clinically heterogeneous group of disorders, frequently involving digital abnormalities. We have previously provisionally assigned the gene for one such condition, Saethre-Chotzen syndrome (ACS III), to chromosome 7p. Linkage analysis is now reported between ACS III and dinucleotide repeat loci on distal 7p. The maximum lod scores, Zmax, were 5.57 at a recombination fraction of .05, with D7S488, and 4.74 at a recombination fraction of .05, with D7S493. Only weak linkage, not reaching significance, was found with distal markers (D7S513 and afm281vc9) and a proximal marker (D7S516). Multipoint analysis shows that the disease locus lies between D7S513 and D7S516. Analysis of individual recombinants shows that the most likely position is between D7S493 and D7S516. Linkage data in regard of Jackson-Weiss syndrome demonstrate that this autosomal dominant form of acrocephalosyndactyly does not map to the ACS III region on 7p or to the acrocephalosyndactyly locus on 5q (Boston type). These findings underline the genetic heterogeneity among the different clinical conditions manifesting with acrocephalosyndactyly.

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

    Science.gov (United States)

    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

  18. Energetics and Dynamics of the Reactions of O(3P) with Dimethyl Methylphosphonate and Sarin

    Science.gov (United States)

    Conforti, Patrick F.; Braunstein, Matthew; Dodd, James A.

    2009-10-01

    Electronic structure and molecular dynamics calculations were performed on the reaction systems O(3P) + sarin and O(3P) + dimethyl methylphosphonate (DMMP), a sarin simulant. Transition state geometries, energies, and heats of reaction for the major reaction pathways were determined at several levels of theory, including AM1, B3LYP/6-311+G(d,p), and CBS-QB3. The major reaction pathways for both systems are similar and include H-atom abstraction, H-atom elimination, and methyl elimination, in rough order from low to high energy. The H-atom abstraction channels have fairly low barriers (˜10 kcal mol-1) and are close to thermoneutral, while the other channels have relatively high energy barriers (>40 kcal mol-1) and a wide range of reaction enthalpies. We have also found a two-step pathway leading to methyl elimination through O-atom attack on the phosphorus atom for DMMP and sarin. For sarin, the two-step methyl elimination pathway is significantly lower in energy than the single-step pathway. We also present results of O(3P) + sarin and O(3P) + DMMP reaction cross sections over a broad range of collision energies (2-10 km s-1 collision velocities) obtained using the direct dynamics method with an AM1 semiempirical potential. These excitation functions are intended as an approximate guide to future hyperthermal measurements, which to our knowledge have not yet examined either of these systems. The reaction barriers, reaction enthalpies, transition state structures, and excitation functions are generally similar for DMMP and sarin, with some moderate differences for methyl elimination energetics, which indicates DMMP will likely be a good substitute for sarin in many O(3P) chemical investigations.

  19. 乳腺浸润性导管癌染色体8p22、11p15、17p13区杂合性缺失的研究%Invasive ductal carcinoma of the breast is prevalence of loss of heterozygosity at 8p22,11p15 and 17p13

    Institute of Scientific and Technical Information of China (English)

    李志刚; 周晓军; 孔庆兖; 易龙; 孟奎

    2004-01-01

    目的:观察乳腺浸润性导管癌中8p22、11p15、17p13三个染色体区的杂合性缺失(LOH)及其与临床病理参数之间的关系. 方法:从石蜡包埋的存档标本中选取34例肿瘤组织和其对应的自身正常对照组织,用PCR方法扩增位于此三个染色体区域的三个微卫星位点D8S136、D11S988、TP53,扩增产物用6%聚丙稀酰胺凝胶电泳,银染显色后进行LOH的判定.用免疫组化方法观察ER、PR、P53和c-erBb-2在乳腺癌中的表达情况. 结果:34例乳腺癌中有12例(35.29%)D8S136位点发生LOH, D11S988和TP53两个位点分别发现5例(14.71%)LOH.D11S988和TP53两个位点的LOH与临床病理参数之间无明显相关性,而D8S136发生LOH的肿瘤平均直径明显高于LOH阴性的肿瘤(P=0.0049). 结论:染色体8p22区域有较高的LOH发生率,位于此区域的肿瘤抑制基因的失活可能与乳腺癌的迅速生长有关.

  20. Photoelectric characteristics of CH3NH3PbI3/p-Si heterojunction

    Science.gov (United States)

    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).

  1. Verifier-based Password Authenticated 3P-EKE Protocol using PCLA keys

    Directory of Open Access Journals (Sweden)

    Archana Raghuvamshi

    2016-06-01

    Full Text Available This paper endeavors to present a novel framework for the generic structure of a verifier-based password authenticated Three-Party Encrypted Key Exchange (3P-EKE protocol which yields more efficient protocol than the ones knew before. A previous framework presented by Archana and Premchand is more secured against all types of attacks like password guessing, replay, pre-play, man-in-the-middle attack etc. But unfortunately, this protocol does not solve the problem of a server compromise. These proofs help as inspiration to search for another framework. The framework we offer produces more efficient 3P-EKE protocol, and, in addition, delivers perceptive clarification about the existing attacks that do not solve in the previous framework. Moreover, it allows direct change from a class of verge private-key encryption to a hybrid (symmetric & Asymmetric one without significant overhead.

  2. Mechanism and kinetics for the reaction of O(3P) with DMSO: A theoretical study

    Science.gov (United States)

    Mandal, Debasish; Bagchi, Sabyasachi; Das, Abhijit K.

    2012-11-01

    Mechanism and kinetics for the reaction of DMSO with O(3P) have been investigated by M06-2X/MG3S, CBS-QB3 and G4MP2 methods. Four possible reaction pathways are identified. Among them, the O(3P) addition to S-atom followed by CH3 elimination is almost exclusive. Four pre-reactive complexes have been located. AIM theory is used to determine the nature of interactions in these complexes. Considering the formation of pre-reactive complex, the rate constant for major pathway is calculated using transition state theory applied to a two-step mechanism. Enthalpies of formation at 298.15 K (ΔfH°298.15) have been calculated using the composite CBS-QB3, G4MP2 and G3B3 methods.

  3. Multi-reassortant G3P[3] group A rotavirus in a horseshoe bat in Zambia.

    Science.gov (United States)

    Sasaki, Michihito; Orba, Yasuko; Sasaki, Satoko; Gonzalez, Gabriel; Ishii, Akihiro; Hang'ombe, Bernard M; Mweene, Aaron S; Ito, Kimihito; Sawa, Hirofumi

    2016-10-01

    Group A rotavirus is a major cause of diarrhoea in humans, especially in young children. Bats also harbour group A rotaviruses, but the genetic backgrounds of bat rotavirus strains are usually distinct from those of human rotavirus strains. We identified a new strain of group A rotavirus in the intestinal contents of a horseshoe bat in Zambia. Whole genome sequencing revealed that the identified virus, named RVA/Bat-wt/ZMB/LUS12-14/2012/G3P[3], possessed the genotype constellation G3-P[3]-I3-R2-C2-M3-A9-N2-T3-E2-H3. Several genome segments of LUS12-14 were highly similar to those of group A rotaviruses identified from humans, cows and antelopes, indicating interspecies transmission of rotaviruses between bats and other mammals with possible multiple genomic reassortment events.

  4. Ge{sub 0.83}Sn{sub 0.17} p-channel metal-oxide-semiconductor field-effect transistors: Impact of sulfur passivation on gate stack quality

    Energy Technology Data Exchange (ETDEWEB)

    Lei, Dian; Wang, Wei; Gong, Xiao, E-mail: elegong@nus.edu.sg, E-mail: yeo@ieee.org; Liang, Gengchiau; Yeo, Yee-Chia, E-mail: elegong@nus.edu.sg, E-mail: yeo@ieee.org [Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117576 (Singapore); Zhang, Zheng; Pan, Jisheng [Institute of Material Research and Engineering, A*STAR (Agency for Science, Technology and Research), 3 Research Link, Singapore 117602 (Singapore); Tok, Eng-Soon [Department of Physics, National University of Singapore, Singapore 117551 (Singapore)

    2016-01-14

    The effect of room temperature sulfur passivation of the surface of Ge{sub 0.83}Sn{sub 0.17} prior to high-k dielectric (HfO{sub 2}) deposition is investigated. X-ray photoelectron spectroscopy (XPS) was used to examine the chemical bonding at the interface of HfO{sub 2} and Ge{sub 0.83}Sn{sub 0.17}. 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 Ge{sub 0.83}Sn{sub 0.17} 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 D{sub it} at the high-k dielectric/Ge{sub 0.83}Sn{sub 0.17} interface from the valence band edge to the midgap of Ge{sub 0.83}Sn{sub 0.17}, as compared with a non-passivated control. The impact of the improved D{sub it} is demonstrated in Ge{sub 0.83}Sn{sub 0.17} p-channel metal-oxide-semiconductor field-effect transistors (p-MOSFETs). Ge{sub 0.83}Sn{sub 0.17} p-MOSFETs with sulfur passivation show improved subthreshold swing S, intrinsic transconductance G{sub m,int}, and effective hole mobility μ{sub eff} as compared with the non-passivated control. At a high inversion carrier density N{sub inv} of 1 × 10{sup 13 }cm{sup −2}, sulfur passivation increases μ{sub eff} by 25% in Ge{sub 0.83}Sn{sub 0.17} p-MOSFETs.

  5. Molecular analysis of two patients with a duplicated 17p11.2 indicates that this entity may be the reciprocal of the deletion seen in Smith-Magenis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Brown, A.; Schwartz, C.; Rogers, R.C. [Greenwood Genetic Center, SC (United States)] [and others

    1994-09-01

    J.M. and H.G. are two unrelated patients that presented at an early age with developmental delay and failure to thrive. Clinical features specific to J.M. include unusual facies, global developmental delay, and clinodactyly of the fifth toe. A cytogenetic analysis of H.G. was performed on amniocytes obtained due to a low MSAFP conducted as part of a routine screening. In both J.M. and H.G., a duplication of chromosome 17p11.2 was discovered. The extent of the duplicated region was determined using single copy DNA probes: cen-D17S58-D17S29-D17S258-D17S71-D17S445-tel. All of the markers were found to be duplicated by dosage analysis except for D17S58. FISH analysis of H.G., using the Smith-Magenis diagnostic probe obtained from ONCOR, also detected a duplication in 17p11.2. The chromosome containing the duplication could be the result of unequal crossing over due to a misalignment of the two chromosomes during meiosis I. It has been shown that the markers deleted in Smith-Magenis syndrome (SMS) patients are the same as those markers duplicated in J.M. and H.G. Therefore, the chromosomal duplication in 17p11.2 observed in these two patients could be the reciprocal of the chromosomal deletion seen in Smith-Magenis syndrome patients. Interestingly, a similar reciprocal duplication/deletion event is observed for CMT1A and HNPP (hereditary neuropathy with liability to pressure palsies) just distal to the SMS region.

  6. Whole-arm translocation of der(5;17)(p10;q10) with concurrent TP53 mutations in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): A unique molecular-cytogenetic subgroup.

    Science.gov (United States)

    Hong, Ming; Hao, Suyang; Patel, Keyur P; Kantarjian, Hagop M; Garcia-Manero, Guillermo; Yin, C Cameron; Medeiros, L Jeffrey; Lin, Pei; Lu, Xinyan

    2016-05-01

    Der(5;17)(p10;q10) is a recurrent but rare aberration reported in myeloid neoplasms (MNs). We report 48 such patients including 19 acute myeloid leukemia (AML) and 29 myelodysplastic syndrome (MDS), to characterize their clinicopathological features. There were 29 men and 19 women, with a median age of 61 years (range, 18-80). 62.5% patients had therapy-related diseases (t-MNs), 70.8% had multilineage dysplasia and 83.3% showed complex karyotypes. In 39 patients tested, FLT3, NPM1, CEBPA, KIT were all wild type and NRAS, KRAS, IDH1, APC, TET2 mutations were detected in single case(s) respectively. TP53 mutations were identified in 8 of 10 cases (80%) tested. Median disease-free survival (DFS) and overall survival (OS) were 3 and 10 months, respectively and did not differ between AML or MDS cases, or between de novo versus therapy-related cases, or between the groups with or without complex karyotypes. In 19 patients who achieved complete remission after chemotherapy, and in 9 patients who underwent stem cell transplantation, the OS was better (14 and 17.5 months, P = 0.0128 and P = 0.0086, respectively). The der(5;17)(p10;q10) represents a unique molecular-cytogenetic subgroup in t-MNs and, associated with complex karyotypes. TP53 inactivation, resulting from 17p deletion coupled with TP53 mutation, likely contributes to the poor clinical outcome of these patients.

  7. LiNbO3/p+n diode surface acoustic wave memory correlator

    Institute of Scientific and Technical Information of China (English)

    张朝; 水永安; 印建华

    1997-01-01

    A detailed theoretical analysis of strip-coupled LiNbO3/p+ n diode surface acoustic wave (SAW) memory correlator in the parametric mode is presented. The influence of some important factors on correlation output is analyzed and calculated, including the amplitudes of reference, read and write signal, duration of write signal and doping density of the diode array. The conclusions can be employed for the design of improved strip-coupled SAW memorycorrelators.

  8. Fracture toughness of Al-4%Mg/Al{sub 2}O{sub 3}p composites

    Energy Technology Data Exchange (ETDEWEB)

    Pestes, R.H. [Hewlett-Packard, Camus, WA 98607 (United States); Kamat, S.V. [Mechanical and Materials Engineering Department, Washington State University, Pullman, WA 99164-2920 (United States); Hirth, J.P. [Mechanical and Materials Engineering Department, Washington State University, Pullman, WA 99164-2920 (United States)

    1994-12-20

    Fracture toughness tests were carried out on Al-4%Mg/Al{sub 2}O{sub 3}p composites containing different sizes and volume fractions of alumina particulates. The results indicated that the fracture toughness was dependent on the interparticle spacing provided the particulate size was below a critical size. The critical particle size corresponds to the situation wherein the energy release rate on particulate cracking is sufficient to trigger dynamic unstable crack extension. ((orig.))

  9. Configuration interaction calculations of positron binding to Be({sup 3}P )

    Energy Technology Data Exchange (ETDEWEB)

    Bromley, M.W.J. [Department of Physics, San Diego State University, San Diego, CA 92182 (United States)]. E-mail: mbromley@physics.sdsu.edu; Mitroy, J. [Faculty of Technology, Charles Darwin University, Darwin, NT 0909 (Australia)]. E-mail: jxm107@rsphysse.anu.edu.au

    2006-06-15

    The configuration interaction method is applied to investigate the possibility of positron binding to the metastable beryllium (1s{sup 2}2s2p {sup 3}P ) state. The largest calculation obtained an estimated energy that was unstable by 0.00014 Hartree with respect to the Ps + Be{sup +}(2s) lowest dissociation channel. It is likely that positron binding to parent states with non-zero angular momentum is inhibited by centrifugal barriers.

  10. The Participative Design of an Endoscopy Facility using Lean 3P.

    Science.gov (United States)

    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.

  11. miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.

    Science.gov (United States)

    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.

  12. $^3P_2$-$^3F_2$ Pairing in Dense Neutron Matter The Spectrum of Solutions

    CERN Document Server

    Zverev, M V; Khodel, V A

    2003-01-01

    The $^3P_2$-$^3F_2$ pairing model is generally considered to provide an adequate description of the superfluid states of neutron matter at densities some 2-3 times that of saturated symmetrical nuclear matter. The problem of solving the system of BCS gap equations expressing the $^3P_2$-$^3F_2$ model is attacked with the aid of the separation approach. This method, developed originally for quantitative study of S-wave pairing in the presence of strong short-range repulsions, serves effectively to reduce the coupled, singular, nonlinear BCS integral equations to a set of coupled algebraic equations. For the first time, sufficient precision becomes accessible to resolve small energy splittings between the different pairing states. Adopting a perturbative strategy, we are able to identify and characterize the full repertoire of real solutions of the $^3P_2$-$^3F_2$ pairing model, in the limiting regime of small tensor-coupling strength. The P-F channel coupling is seen to lift the striking parametric degeneracie...

  13. Ypq3p-dependent histidine uptake by the vacuolar membrane vesicles of Saccharomyces cerevisiae.

    Science.gov (United States)

    Manabe, Kunio; Kawano-Kawada, Miyuki; Ikeda, Koichi; Sekito, Takayuki; Kakinuma, Yoshimi

    2016-06-01

    The vacuolar membrane proteins Ypq1p, Ypq2p, and Ypq3p of Saccharomyces cerevisiae are known as the members of the PQ-loop protein family. We found that the ATP-dependent uptake activities of arginine and histidine by the vacuolar membrane vesicles were decreased by ypq2Δ and ypq3Δ mutations, respectively. YPQ1 and AVT1, which are involved in the vacuolar uptake of lysine/arginine and histidine, respectively, were deleted in addition to ypq2Δ and ypq3Δ. The vacuolar membrane vesicles isolated from the resulting quadruple deletion mutant ypq1Δypq2Δypq3Δavt1Δ completely lost the uptake activity of basic amino acids, and that of histidine, but not lysine and arginine, was evidently enhanced by overexpressing YPQ3 in the mutant. These results suggest that Ypq3p is specifically involved in the vacuolar uptake of histidine in S. cerevisiae. The cellular level of Ypq3p-HA(3) was enhanced by depletion of histidine from culture medium, suggesting that it is regulated by the substrate.

  14. miR-342-3p affects hepatocellular carcinoma cell proliferation via regulating NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Liang; Zhang, Yubao, E-mail: zhyb880077@sina.com

    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.

  15. MiR-490-3p sensitizes ovarian cancer cells to cisplatin by directly targeting ABCC2

    Science.gov (United States)

    Tian, Jing; Xu, Yan-Ying; Li, Lian; Hao, Quan

    2017-01-01

    Cisplatin (CDDP) resistance becomes a large obstacle of the beneficial therapy for patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of multiple genes’ expression and have been reported to be involved in multi-drug resistance. The purpose of this study was to determine the roles and molecular mechanism of miR-490-3p in the CDDP resistance in ovarian cancer. We found that miR-490-3p was downregulated in CDDP-resistant OVCAR3/CDDP and SKOV3/CDDP cells, which was due to the hypermethylation of miR-490-3p promoter. Functional studies demonstrated that miR-490-3p increased the cell response to CDDP in OVCAR3, SKOV3 and CDDP-resistant cells, while miR-490-3p inhibition resulted in opposite effects. Luciferase assay, real-time PCR and Western blot as well as immunohistochemistry validated that ABCC2 was a direct target of miR-490-3p and miR-490-3p downregulated ABCC2 expression via binding to its 3’UTR. Importantly, silencing of ABCC2 alleviated CDDP resistance induced by miR-490-3p inhibition, while ABCC2 overexpression restored CDDP resistance inhibited by miR-490-3p. In vivo study showed that miR-490-3p enhanced the cytotoxicity of CDDP. Finally, we found that miR-490-3p was downregulated in CDDP-resistant ovarian cancer tissues, while ABCC2 was upregulated. In conclusion, our data indicate that miR-490-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ABCC2 expression, and suggest that delivery of miR-490-3p might be a potential therapeutic strategy for patients with CDP-resistant ovarian cancer.

  16. Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) Founder Mutation: Clues from Haplotyping of Short Tandem Repeats on Chromosome 17p

    Science.gov (United States)

    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

  17. Duplicación 5q34q35.3 que involucra el gen NSD1: región delimitada por microarreglos de hibridación genómica comparativa. A propósito de un caso

    Directory of Open Access Journals (Sweden)

    AR Vázquez del Campo

    2016-09-01

    Full Text Available La duplicación de la región 5q34q35.3 se ha asociado a un fenotipo inverso de síndrome de Sotos, por contener el gen NSD1 en doble dosis. Se presenta a una paciente con retraso global del desarrollo, peso y talla bajos y dismorfias. Cuenta con antecedente de corrección quirúrgica por defectos de septación auriculoventricular (CIA y CIV, así como remodelación por antecedente de cráneo en trébol. El cariotipo con bandas G mostró un resultado 46,XX,add(5(q35, y para confirmar el origen del material adicional se utilizó sonda de FISH WCP para el cromosoma 5 [46,XX,add(5(q35.ish dup(5(q35(wcp5+]. Para definir puntos de ruptura y realizar correlación genotipo fenotipo se realizó microarreglo CytoScan HD de Affymetrix, que confirmó la duplicación intersticial de novo de 14Mb 46,XX,add(5(q35. arr[hg19] 5q34q35.3(163,110,984-177,227,216x3,177,259,401- 179,330,764x3,179,346,465 180,719,789x3dn, que contiene 80 genes (USCS genome browser, NCBI36/hg19. La descripción de este caso es importante para complementar la delineación del fenotipo, mediante la correlación con la región de la duplicación a nivel de nucleótidos. Cabe resaltar que la paciente demuestra la importancia y la utilidad de las nuevas técnicas de citogenética molecular, con las cuales es posible el análisis detallado de los genes localizados en la región 5q involucrada, así como su correlación con las manifestaciones clínicas.

  18. 75 FR 23574 - Airworthiness Directives; CFM International, S.A. CFM56-5B1/P, -5B2/P, -5B3/P, -5B3/P1, -5B4/P...

    Science.gov (United States)

    2010-05-04

    ..., S.A. CFM56-5B1/P, - 5B2/P, -5B3/P, -5B3/P1, -5B4/P, -5B5/P, -5B6/P, -5B7/P, -5B8/P, -5B9/P, -5B1/2P... Docket Operations office between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The... CFM International, S.A. CFM56-5B1/P, - 5B2/P, -5B3/P, -5B3/P1, -5B4/P, -5B5/P,......

  19. The dielectronic satellites to the 2s-3p Ne-like krypton resonance lines

    Energy Technology Data Exchange (ETDEWEB)

    Khakhalin, S.Ya. (MISDC, NPO ' ' VNIIFTRI' ' , Mendeleevo (Russian Federation)); Dyakin, V.M. (MISDC, NPO ' ' VNIIFTRI' ' , Mendeleevo (Russian Federation)); Faenov, A.Ya. (MISDC, NPO ' ' VNIIFTRI' ' , Mendeleevo (Russian Federation)); Fiedorowicz, H. (Inst. of Optoelectronics, Warsaw (Poland)); Bartnik, A. (Inst. of Optoelectronics, Warsaw (Poland)); Parys, P. (Inst. of Plasma Physics and Laser Microfusion, Warsaw (Poland)); Nilsen, J. (Lawrence Livermore National Lab., Livermore, CA (United States)); Osterheld, A. (Lawrence Livermore National Lab., Livermore, CA (United States))

    1994-08-01

    We present an analysis of dielectronic satellite spectra of 2p[sup 6]-2s2p[sup 6]3p Ne-like krypton resonance lines. The satellite structure was registered with high (better than [lambda]/[Delta][lambda] > 3500) spectral resolution in the emission of a laser irradiated gas puff target. We perform an unambiguous identification of satellite lines caused by radiative transitions from autoionizing states of sodium-like krypton ions. A total of about 20 spectral features are identified, most of them for the first time. Very good agreement between the satellite structure calculations and experimental emission spectra is obtained. (orig.).

  20. Absolute frequency measurement of the 1S0 - 3P0 transition of 171Yb

    CERN Document Server

    Pizzocaro, Marco; Rauf, Benjamin; Bregolin, Filippo; Milani, Gianmaria; Clivati, Cecilia; Costanzo, Giovanni A; Levi, Filippo; Calonico, Davide

    2016-01-01

    We report the absolute frequency measurement of the unperturbed transition 1S0 - 3P0 at 578 nm in 171Yb realized in an optical lattice frequency standard. The absolute frequency is measured 518 295 836 590 863.55(28) Hz relative to a cryogenic caesium fountain with a fractional uncertainty of 5.4x10-16 . This value is in agreement with the ytterbium frequency recommended as a secondary representation of the second in the International System of Units.

  1. Pulsar Spin-Down by 3P2 Superfluid Neutron with Field Decay

    Institute of Scientific and Technical Information of China (English)

    LUO Xin-Lian; PENG Qiu-He; CHOU Chih-Kang

    2003-01-01

    To describe pulsar spin-down, we present a simple combined torque model that takes into account both the standard magnetic dipole radiation and the electromagnetic radiation from the 3P2 superSuid vortex neutrons inside neutron star. Using an ordinary exponential model for the magnetic field decay, we derive an analytical formulae for pulsar evolution tracks. The pulsar evolution on the P-P diagram is quite different from that of the standard magnetic dipole radiation model, especially when the supernuid torque or Geld decay becomes dominant.

  2. Phase transitions in Cd3P2 at high pressures and high temperatures

    DEFF Research Database (Denmark)

    Yel'kin, F.S.; Sidorov, V.A.; Waskowska, A.;

    2008-01-01

    The high-pressure, high-temperature structural behaviour of Cd3P2 has been studied using electrical resistance measurements, differential thermal analysis, thermo baric analysis and X-ray diffraction. At room temperature, a phase transformation is observed at 4.0 GPa in compression....... The experimental zero-pressure bulk modulus of the low-pressure phase is 64.7(7) GPa, which agrees quite well with the calculated value of 66.3 GPa using the tight-binding linear muffin-tin orbital method within the local density approximation. Tentatively, the high-pressure phase has an orthorhombic crystal...

  3. MicroRNA-409-3p inhibits osteosarcoma cell migration and invasion by targeting catenin-δ1.

    Science.gov (United States)

    Wu, Shifeng; Du, Xinjie; Wu, Manwu; Du, Hechun; Shi, Xiaoliang; Zhang, Tao

    2016-06-10

    Osteosarcoma is the most common primary bone cancer which is associated with early metastatic potential and poor prognosis. However, the molecular mechanisms underlying osteosarcoma progression are not well characterized. Here, we investigated the role of miR-409-3p in osteosarcoma metastasis. Osteosarcoma tissue showed decreased expression of miR-409-3p compared to adjacent non-tumorous tissue. The expression level of miR-409-3p was negatively correlated with osteosarcoma metastasis. Overexpression of miR-409-3p in osteosarcoma cells (U2OS) inhibited cell migration and invasion. Bioinformatics analysis showed that catenin-δ1 (CTNND1, p120-catenin) is a direct target of miR-409-3p. Overexpression of miR-409-3p repressed the expression of catenin-δ1 in U2OS cells at both mRNA and protein levels. Meanwhile, miR-409-3p repressed the activity of luciferase reporter containing the 3'-untranslated region (3'UTR) of CTNND1 gene. Furthermore, expression of catenin-δ1 rescued the inhibitory effect of miR-409-3p on cell migration and invasion. Altogether, these results indicated that miR-409-3p targets catenin-δ1 to repress osteosarcoma metastasis.

  4. Metalloid tolerance based on phytochelatins is not functionally equivalent to the arsenite transporter Acr3p.

    Science.gov (United States)

    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.

  5. MicroRNA-27a-3p Inhibits Melanogenesis in Mouse Skin Melanocytes by Targeting Wnt3a.

    Science.gov (United States)

    Zhao, Yuanyuan; Wang, Pengchao; Meng, Jinzhu; Ji, Yuankai; Xu, Dongmei; Chen, Tianzhi; Fan, Ruiwen; Yu, Xiuju; Yao, Jianbo; Dong, Changsheng

    2015-05-14

    MicroRNAs (miRNAs) play an essential role in the regulation of almost all the biological processes, including melanogenesis. MiR-27a-3p is nearly six times higher in white alpaca skin compared to brown skin, which indicates that miR-27a-3p may be a candidate regulator for melanogenesis. Wnt3a plays an important role in promoting melanoblasts to differentiate into melanocytes and melanogenesis. To confirm the function of miR-27a-3p to melanogenesis in mammals, miR-27a-3p mimic, inhibitor and their negative control were transfected into mouse melanocytes. As a result, miR-27a-3p inhibits melanogenesis by repressing Wnt3a at post-transcriptional level. A significant decrease in Wnt3a luciferase activity was observed in 293T cells co-transfected with the matched luciferase reporter vector and pre-miR-27a. Furthermore, the presence of exogenous miR-27a-3p significantly decreased Wnt3a protein expression rather than mRNA and reduced β-catenin mRNA levels in melanocytes. The over-expression of miR-27a-3p significantly increased the melanin content of melanocytes. However, miR-27a-3p inhibitor performs an opposite effect on melanogenesis. Wnt3a is one target of miR-27a-3p. MiR-27a-3p could inhibit Wnt3a protein amount by post-transcriptional regulation and melanogenesis in mouse melanocytes. Previous studies reported that Wnt3a promoted melanogenensis in mouse melanocytes. Thus, miR-27-3p inhibits melanogenesis by repressing Wnt3a protein expression.

  6. MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.

    Directory of Open Access Journals (Sweden)

    Jie Ding

    Full Text Available Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2 is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.

  7. Unified interpretation of Hund's first and second rules for 2p and 3p atoms.

    Science.gov (United States)

    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

  8. A 1.5 Mb submicroscopic deletion in 17p11.2-p12 is frequently observed in Italian families with hereditary neuropathy with liability to pressure palsies

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzetti, D.; Roa, B.B.; Abbas, N.E. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies that was recently associated with a 1.5 Mb deletion in chromosome 17p11.2-p12. Duplication of the same region is known to be associated with Charcot-Marie-Tooth disease type 1A (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity. The CMT1A duplication and HNPP deletion are reciprocal recombination products involving a repeat element (CMT1A-REP) which flanks the 1.5 Mb region involved in the duplication/deletion. Patients from 9 unrelated HNPP Italian families were clinically, electrophysiologically and histologically evaluated. Families were typed with a polymorphic (CA){sub n} repeat and with RFLPs corresponding to loci D17S122, D17S125 and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, suggesting the presence of deletion. Southern blot analysis of EcoRI digested genomic DNA from HNPP patients and control subjects was performed using a probe mapping within the CMT1A-REP elements. A reduced hybridization signal of a 6.0 kb EcoRI fragment, mapping within the distal CMT1A-REP, was observed in all HNPP patients suggesting the loss of one copy of this fragment in the HNPP-deleted chromosome. PFGE analysis of SacII digested genomic DNA from selected HNPP subjects showed the presence of a junction fragment which has previously been found in association with the 1.5 Mb HNPP deletion. Evidence for deletion could be demonstrated in all 9 families suggesting that the 17p11.2-p12 deletion is commonly associated with HNPP.

  9. CHARACTERIZATION AND CHROMOSOMAL ASSIGNMENT OF YEAST ARTIFICIAL CHROMOSOMES CONTAINING HUMAN 3P13-P21-SPECIFIC SEQUENCE-TAGGED SITES

    NARCIS (Netherlands)

    MICHAELIS, SC; BARDENHEUER, W; LUX, A; SCHRAMM, A; GOCKEL, A; SIEBERT, R; WILLERS, C; SCHMIDTKE, K; TODT, B; VANDERHOUT, AH; BUYS, CHCM; HEPPELLPARTON, AC; RABBITTS, PH; UNGAR, S; SMITH, D; LEPASLIER, D; COHEN, D; OPALKA, B; SCHUTTE, J

    1995-01-01

    Human chromosomal region 3p12-p23 is proposed to harbor at least three tumor suppressor genes involved in the development of lung cancer, renal cell carcinoma, and other neoplasias. In order to identify one of these genes we defined sequence tagged sites (STSs) specific for 3p13-p24.2 by analyzing a

  10. Product lambda-doublet ratios for the O(3P) + D2 reaction: A mechanistic imprint

    CERN Document Server

    Jambrina, P G; Aldegunde, J; Brouard, M; Aoiz, F J

    2016-01-01

    In the last decade, the development of theoretical methods have allowed chemists to reproduce and explain almost all of the experimental data associated with elementary atom plus diatom collisions. However, there are still a few examples where theory cannot account yet for experimental results. This is the case for the preferential population of one of the $\\Lambda$-doublet states produced by chemical reactions. In particular, recent measurements of the OD($^2\\Pi$) product of the O($^3$P) + D$_2$ reaction have shown a clear preference for the $\\Pi(A')$ $\\Lambda$-doublet states, in apparent contradiction with {\\em ab initio} calculations, which predict a larger reactivity on the $A"$ potential energy surface. Here we present a method to calculate the $\\Lambda$-doublet ratio when concurrent potential energy surfaces participate in the reaction. It accounts for the experimental $\\Lambda$-doublet populations via explicit consideration of the stereodynamics of the process. Furthermore, our results demonstrate that...

  11. Superplasticity in an Aluminum Alloy 6061/A12O3p Composite

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The superplasticity of an Al2O3p/6061Al composite, fabricated by powder metallurgy techniques,has been investigated. Instead of any special thermomechanical processing or hot rolling, simple hot extrusion has been employed to obtain a fine grained structure before superplastic testing.Superplastic tensile tests were performed at strain rates ranging from 10-2 to 10-4 s-1 and at temperatures from 833 to 893 K. A maximum elongation of 200% was achieved at a temperature of 853 K and an initial strain rate of 1.67×10-3 s-1. The highest value obtained for the strain rate sensitivity index (m) was 0.32. Differential scanning calorimeter was used to ascertain the possibility of any partial melting in the vicinity of optimum superplastic temperature. These results suggested that no liquid phase existed where maximum elongation was achieved and deformation took place entirely in the solid state.

  12. Mechanisms and Kinetics of Radical Reaction of O(1D,3P) + HCN System

    Institute of Scientific and Technical Information of China (English)

    HUANG Yu-Cheng; DU Jin-Yan; JU Xue-Hai; YE Shi-Yong; ZHOU Tao

    2008-01-01

    The reaction of HCN with O(1D, 3P) radical has been investigated by density functional theory (DFT) and ab initio methods. The stationary points on the reaction paths(reactants, intermediates and products) were optimized at the (U)B3LYP/aug-cc-pVTZ level.Single-point calculations were performed at the (U)QCISD(T)/aug-cc-pVTZ level for the optimized structures and all the total energies were corrected by zero-point energy. It is shown that there exist three competing mechanisms of oxygen attacking nitrogen O→N, oxygen attacking carbon O→C and oxygen attacking hydrogen O→H. The rate constants were obtained via Eyring transition-state theory in the temperature range of 600~2000 K. The linear relationship between lnk and 1/T was presented. The results show that path 1 is the main reaction channel and the product of NCO + H is predominant.

  13. Narrow-linewidth cooling of $^{6}$Li atoms using the 2S-3P transition

    CERN Document Server

    Chen, Hao-Ze; Wu, Yu-Ping; Liu, Xiang-Pei; Wang, Xiao-Qiong; Chen, Yu-Ao; Pan, Jian-Wei

    2016-01-01

    We report on a narrow-linewidth cooling of $^{6}$Li atoms using the $2S_{1/2}\\to 3P_{3/2}$ transition in the ultraviolet (UV) wavelength regime. By combining the traditional red magneto-optical trap (MOT) at 671 nm and the UV MOT at 323 nm, we obtain a cold sample of $1.3\\times10^9$ atoms with a temperature of 58 $\\mu$K. Furthermore, we demonstrate a high efficiency magnetic transport for $^{6}$Li atoms with the help of the UV MOT. Finally, we obtain $8.1\\times10^8$ atoms with a temperature of 296 $\\mu$K at a magnetic gradient of 198 G/cm in the science chamber with a good vacuum environment and large optical access.

  14. MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Haihua; Yang, Tao; Fu, Shaozi; Chen, Xiaofan; Guo, Lei; Ni, Yiming, E-mail: ni_yiming@hotmail.com

    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.

  15. H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression

    Science.gov (United States)

    Li, Xing-Hui; Xue, Wen-Long; Wang, Ming-Jie; Zhou, Yu; Zhang, Cai-Cai; Sun, Chen; Zhu, Lei; Liang, Kun; Chen, Ying; Tao, Bei-Bei; Tan, Bo; Yu, Bo; Zhu, Yi-Chun

    2017-01-01

    The aims of the present study are to determine whether hydrogen sulfide (H2S) is involved in the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production, and to identify the role of microRNA-455-3p (miR-455-3p) during those processes. In cultured human umbilical vein endothelial cells (HUVECs), the expression of miR-455-3p, eNOS protein and the NO production was detected after administration with 50 μM NaHS. The results indicated that H2S could augment the expression of miR-455-3p and eNOS protein, leading to the increase of NO level. We also found that overexpression of miR-455-3p in HUVECs increased the protein levels of eNOS whereas inhibition of miR-455-3p decreased it. Moreover, H2S and miR-455-3p could no longer increase the protein level of eNOS in the presence of proteasome inhibitor, MG-132. In vivo, miR-455-3p and eNOS expression were considerably increased in C57BL/6 mouse aorta, muscle and heart after administration with 50 μmol/kg/day NaHS for 7 days. We also identified that H2S levels and miR-455-3p expression increased in human atherosclerosis plaque while H2S levels decreased in plasma of atherosclerosis patients. Our data suggest that the stability of eNOS protein and the NO production could be regulated by H2S through miR-455-3p. PMID:28322298

  16. miR-409-3p sensitizes colon cancer cells to oxaliplatin by inhibiting Beclin-1-mediated autophagy.

    Science.gov (United States)

    Tan, Shifan; Shi, Huijuan; Ba, Mingchen; Lin, Shengqv; Tang, Hongsheng; Zeng, Xiaoqi; Zhang, Xiangliang

    2016-04-01

    The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR‑409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR‑409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR‑409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR‑409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR‑409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR‑409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR‑409-3p. In a xenograft model using nude mice, we examined the effects of miR‑409-3p on tumor growth during chemotherapy. miR‑409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.

  17. Multifunctional g3p-peptide tag for current phage display systems.

    Science.gov (United States)

    Beckmann, C; Haase, B; Timmis, K N; Tesar, M

    1998-03-15

    We have previously described a monoclonal antibody (mAb), 10C3, directed against the gene-3 protein (g3p) of filamentous phage M13, which was produced to study g3p fusion protein expression in Escherichia coli and its incorporation in the phage capsid [Tesar, M., Beckmann, C., Röttgen, P., Haase, B., Faude, U., Timmis, K., 1995. Monoclonal antibody against pIII of filamentous phage: an immunological tool to study pIII fusion protein expression in phage display systems. Immunology 1, 53-54]. In this study we report mapping of the antigenic epitope of the mAb 10C3, by means of short overlapping peptide-sequences [Frank, R., Overwin, H., 1996. Spot synthesis. In: Morris, G.E. (Ed.), Methods in Molecular Biology, Vol. 66: Epitope Mapping Protocols. Humana Press, Totowa, NJ, pp. 149-169.] comprising the C-terminal half of the g3-protein. A minimal recognizable peptide was found which is represented in the 11 amino acid sequence from positions 292 to 302 of g3p [Wezenbeek van, P.M.G.P., Hulsebos, T.J.M., Schoenmakers, J.G.G., 1980. Nucleotide sequence of the filamentous bacteriophage M13 DNA genome: comparison with phage fd. Gene 11, 129-148]. In order to use the antibody also for detection and purification of recombinant proteins, such as single chain antibodies, the epitope was introduced as a tag sequence into the phagemid pHEN1 [Hoogenboom, H.R., Griffith, A.D., Johnson, K., Chiswell, D.J., Hudson, P., Winter, G., 1991. Multi-subunit proteins on the surface of the filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acid Res. 19, 4133-4137; Nissim, A., Hoogenboom, H.R., Tomlinson, I.M., Flynn, G., Midgley, C., Lane, D., Winter, G., 1994. Antibody fragments from a single pot phage display library as immunochemical reagents. EMBO J. 13 (3) 692-698]. Purified single chain antibodies containing this tag were detectable down to a concentration of 2 ng ml(-1) under non-denaturing conditions (ELISA) or 4 ng per lane on immunoblots

  18. miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200

    Science.gov (United States)

    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

  19. MicroRNA-338-3p suppresses tumor growth of esophageal squamous cell carcinoma in vitro and in vivo.

    Science.gov (United States)

    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 (PESCC, 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.

  20. miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Peng; Wu, Dingguo; You, Yu; Sun, Jing; Lu, Lele; Tan, Jiaxing; Bie, Ping, E-mail: bieping2010@163.com

    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.

  1. Measurement of Integrated Stokes Parameters for He 3 3p State Excited by Spin-Polarized Electrons

    Institute of Scientific and Technical Information of China (English)

    DING Hai-Bing; PANG Wen-Ning; LIU Yi-Bao; SHANG Ren-Cheng

    2005-01-01

    @@ Integrated Stokes parameters Pi (i = 1, 2, 3) for the He 3 3p → 2 3S1 (388.9nm) transition after excitation from the ground state to the 3 3 P state by a transversely spin-polarized electron beam are measured in near threshold energy region. The experimental results are presented. The linear-polarization P2 are consistent with zero over the incident energy range, providing evidence for the LS coupling mechanism of the 3 3P state. The measured circular polarization P3 are non-zero, indicating strong electron-electron exchange effects in the spin-polarized electron-atom collision process.

  2. Functional expression of pig renal organic anion transporter 3 (pOAT3).

    Science.gov (United States)

    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.

  3. Precision frequency measurement of 1S0-3P1 intercombination lines of Sr isotopes

    Science.gov (United States)

    Liu, Hui; Gao, Feng; Ye-Bing, Wang; Xiao, Tian; Jie, Ren; Ben-Quan, Lu; Qin-Fang, Xu; Yu-Lin, Xie; Hong, Chang

    2015-01-01

    We report on frequency measurement of the intercombination (5s2)1S0-(5s5p)3P1 transition of the four natural isotopes of strontium, including 88Sr (82.58%), 87Sr (7.0%), 86Sr (9.86%), and 84Sr (0.56%). A narrow-linewidth laser that is locked to an ultra-low expansion (ULE) optical cavity with a finesse of 12000 is evaluated at a linewidth of 200 Hz with a fractional frequency drift of 2.8×10-13 at an integration time of 1 s. The fluorescence collector and detector are specially designed, based on a thermal atomic beam. Using a double-pass acousto-optic modulator (AOM) combined with a fiber and laser power stabilization configuration to detune the laser frequency enables high signal-to-noise ratios and precision saturated spectra to be obtained for the six transition lines, which allows us to determine the transition frequency precisely. The optical frequency is measured using an optical frequency synthesizer referenced to an H maser. Both the statistical values and the final values, including the corrections and uncertainties, are derived for a comparison with the values given in other works. Project supported by the National Natural Science Foundation of China (Grant No. 61127901) and the Key Project of the Chinese Academy of Sciences (Grant No. KJZD-EW-W02).

  4. Join the CERN ISEF special award winners | 16 June - 3 p.m.

    CERN Multimedia

    2016-01-01

    Come and join the CERN ISEF special award winners at their lightning talks session on 16 June at 3.00 p.m. in the main auditorium.   The 2016 Intel ISEF CERN special award winners on stage with the selection committee on 17 May 2016 in Phoenix, Arizona, USA. (Picture: Society for Science and the Public) Between 11 and 17 June 2016, the ten finalists of the Intel International Science and Engineering Fair (ISEF) who won the CERN Special Award, will visit CERN to partake in various educational lectures. ISEF is the world's largest international pre-college science competition, with approximately 1,700 high school students from more than 75 countries taking part. They will present their projects in short 5 minutes lightning talks' sessions at the main auditorium on Thursday 16 June at 3 p.m. The award winners would be also very happy to have a chance to interact and discuss with you af...

  5. Dynamics of the gas-liquid interfacial reaction of O(3P) atoms with hydrocarbons

    Science.gov (United States)

    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.

  6. Theoretical investigation of hyperthermal reactions at the gas-liquid interface: O (3P) and squalane.

    Science.gov (United States)

    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).

  7. Dynamics of interfacial reactions between O(3 P) atoms and long-chain liquid hydrocarbons

    Science.gov (United States)

    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.

  8. Excitons into one-axis crystals of zinc phosphide (Zn3P2

    Directory of Open Access Journals (Sweden)

    D.M. Stepanchikov

    2009-01-01

    Full Text Available Theoretical study of excitons spectra is offered in this report as for Zn3P2 crystals. Spectra are got in the zero approach of the theory of perturbations with consideration of both the anisotropy of the dispersion law and the selection rules. The existence of two exciton series was found, which corresponds to two valence bands (hh, lh and the conductivity band (c. It is noteworthy that anisotropy of the dispersion law plus the existence of crystalline packets (layers normal to the main optical axis, both will permit the consideration of two-dimensional excitons too. The high temperature displaying of these 2D-exciton effects is not eliminated even into bulk crystals. The calculated values of the binding energies as well as the oscillator's strength for the optical transitions are given for a volume (3D and for two-dimensional (2D excitons. The model of energy exciton transitions and four-level scheme of stimulated exciton radiation for receiving laser effect are offered.

  9. 共沉默miR-221-3p/222-3p表达抑制骨髓间充质干细胞增殖及促成软骨分化%Down-regulation of miR-221-3p/222-3p inhibits cell proliferation and promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    闫继红; 周德山; 杨姝; 孙海梅; 曹丹丹; 张秀英; 季凤清; 郭多; 吴波; 孙婷怡

    2015-01-01

    BACKGROUND:The use of mesenchymal stem cels in the field of tissue engineering for osteoarticular injury repair is a very promising tool since these cels are readily expandable and able to differentiate into chondrocytes. Abundant evidence suggests that microRNAs play critical roles in chondrogenic differentiation of mesenchymal stem cels. OBJECTIVE:To observe the chondrogenic effect of human bone marrow mesenchymal stem cels transfected with lentiviral vectors bearing miR-221-3p/222-3p inhibition, thereby provding new strategies for cartilage injury. METHODS: miRNA microarray technology was applied to detect microRNAs expression profiles at three different stages of chondrogenic differentiation induction after transforming growth factor-β3 treatment and verified by real-time fluorescence quantitative PCR (RT-qPCR). Human bone marrow mesenchymal stem cels were infected with lentivirus bearing miR-221-3p/222-3p inhibition. After co-suppressing the expression of miR-221/222-3p, cel counting kit-8 was used to determine the cel proliferation, the differentiation of bone marrow mesenchymal stem cels towards chondrocytes was verified by type II colagen protein expression through immunohistochemistry and glycosaminoglycan accumulation was also elevated by sarranine O staining. RT-PCR was used to detect type II colagen and aggrecan mRNA expression at 21 days of chondrogenic induction. RESULTS AND CONCLUSION: The expression of miR-221-3p/222-3p was inhibited after Lv-miR221-3p/222-3p inhibition co-transfected into bone marrow mesenchymal stem cels. microRNA microarray and RT-qPCR results showed that the expression of miR-221-3p/222-3p was declined significantly at the anaphase of chondrogenic differentiation. The expression levels of chondrogenic markers, Aggrecan and type II colagen were significantly increased in the miR-221-3p/222-3p inhibition group and cel proliferation was also inhibited significantly compared with non-transduced cels or transduced with the empty

  10. External lipid PI3P mediates entry of eukaryotic pathogen effectors into plant and animal host cells.

    Science.gov (United States)

    Kale, Shiv D; Gu, Biao; Capelluto, Daniel G S; Dou, Daolong; Feldman, Emily; Rumore, Amanda; Arredondo, Felipe D; Hanlon, Regina; Fudal, Isabelle; Rouxel, Thierry; Lawrence, Christopher B; Shan, Weixing; Tyler, Brett M

    2010-07-23

    Pathogens of plants and animals produce effector proteins that are transferred into the cytoplasm of host cells to suppress host defenses. One type of plant pathogens, oomycetes, produces effector proteins with N-terminal RXLR and dEER motifs that enable entry into host cells. We show here that effectors of another pathogen type, fungi, contain functional variants of the RXLR motif, and that the oomycete and fungal RXLR motifs enable binding to the phospholipid, phosphatidylinositol-3-phosphate (PI3P). We find that PI3P is abundant on the outer surface of plant cell plasma membranes and, furthermore, on some animal cells. All effectors could also enter human cells, suggesting that PI3P-mediated effector entry may be very widespread in plant, animal and human pathogenesis. Entry into both plant and animal cells involves lipid raft-mediated endocytosis. Blocking PI3P binding inhibited effector entry, suggesting new therapeutic avenues.

  11. Theoretical study on the two-band degenerate-gaps superconductors: Application to SrPt3P

    Science.gov (United States)

    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. The Involvement of miR-29b-3p in Arterial Calcification by Targeting Matrix Metalloproteinase-2

    Science.gov (United States)

    Jiang, Wenhong; Zhang, Zhanman; Yang, Han; Lin, Qiuning; Han, Chuangye

    2017-01-01

    Vascular calcification is a risk predictor and common pathological change in cardiovascular diseases that are associated with elastin degradation and phenotypic transformation of vascular smooth muscle cells via gelatinase matrix metalloproteinase-2 (MMP2). However, the mechanisms involved in this process remain unclear. In this study, we investigated the relationships between miR-29b-3p and MMP2, to confirm miR-29b-3p-mediated MMP2 expression at the posttranscriptional level in arterial calcification. In male Sprague Dawley rats, arterial calcification was induced by subcutaneous injection of a toxic dose of cholecalciferol. In vivo, the quantitative real-time polymerase chain reaction (qRT-PCR) showed that MMP2 expression was upregulated in calcified arterial tissues, and miR-29b-3p expression was downregulated. There was a negative correlation between MMP2 mRNA expression and miR-29b-3p levels (P = 0.0014, R2 = 0.481). Western blotting showed that MMP2 expression was significantly increased in rats treated with cholecalciferol. In vitro, overexpression of miR-29b-3p led to decreased MMP2 expression in rat vascular smooth muscle cells, while downregulation of miR-29b-3p expression led to increased MMP2 expression. Moreover, the luciferase reporter assay confirmed that MMP2 is the direct target of miR-29b-3p. Together, our results demonstrated that a role of miR-29b-3p in vascular calcification involves targeting MMP2. PMID:28164126

  13. The Involvement of miR-29b-3p in Arterial Calcification by Targeting Matrix Metalloproteinase-2

    Directory of Open Access Journals (Sweden)

    Wenhong Jiang

    2017-01-01

    Full Text Available Vascular calcification is a risk predictor and common pathological change in cardiovascular diseases that are associated with elastin degradation and phenotypic transformation of vascular smooth muscle cells via gelatinase matrix metalloproteinase-2 (MMP2. However, the mechanisms involved in this process remain unclear. In this study, we investigated the relationships between miR-29b-3p and MMP2, to confirm miR-29b-3p-mediated MMP2 expression at the posttranscriptional level in arterial calcification. In male Sprague Dawley rats, arterial calcification was induced by subcutaneous injection of a toxic dose of cholecalciferol. In vivo, the quantitative real-time polymerase chain reaction (qRT-PCR showed that MMP2 expression was upregulated in calcified arterial tissues, and miR-29b-3p expression was downregulated. There was a negative correlation between MMP2 mRNA expression and miR-29b-3p levels (P=0.0014, R2=0.481. Western blotting showed that MMP2 expression was significantly increased in rats treated with cholecalciferol. In vitro, overexpression of miR-29b-3p led to decreased MMP2 expression in rat vascular smooth muscle cells, while downregulation of miR-29b-3p expression led to increased MMP2 expression. Moreover, the luciferase reporter assay confirmed that MMP2 is the direct target of miR-29b-3p. Together, our results demonstrated that a role of miR-29b-3p in vascular calcification involves targeting MMP2.

  14. Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p

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    Yi Zhi

    2016-10-01

    Full Text Available Background/Aims: Ginkgolide B (GB is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. Methods: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. Conclusion: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

  15. MiR-525-3p enhances the migration and invasion of liver cancer cells by downregulating ZNF395.

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    Fei Pang

    Full Text Available Liver cancer is one of leading causes of cancer-related deaths. A deeper mechanistic understanding of liver cancer could lead to the development of more effective therapeutic strategies. In our previous work, we screened 646 miRNAs and identified 11 that regulate liver cancer cell migration. The current study shows that miR-525-3p is frequently up-regulated in liver cancer tissues, and enhanced expression of miR-525-3p can promote liver cancer cell migration and invasion. Zinc finger protein 395 (ZNF395 is the direct functional target gene for miR-525-3p, and it is frequently down-regulated in liver cancer tissues. High expression of ZNF395 can significantly inhibit while knockdown of ZNF395 expression can markedly enhance the migration and invasion of liver cancer cells, suggesting that ZNF395 suppresses metastasis in liver cancer. Down-regulation of ZNF395 can mediate miR-525-3p induced liver cancer cell migration and invasion. In conclusion, miR-525-3p promotes liver cancer cell migration and invasion by directly targeting ZNF395, and the fact that miR-525-3p and ZNF395 both play important roles in liver cancer progression makes them potential therapeutic targets.

  16. Structure and Function of the PLAA/Ufd3-p97/Cdc48 Complex

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Liyan; Pashkova, Natasha; Walker, John R.; Winistorfer, Stanley; Allali-Hassani, Abdellah; Akutsu, Masato; Piper, Robert; Dhe-Paganon, Sirano (Iowa); (Toronto)

    2010-02-11

    PLAA (ortholog of yeast Doa1/Ufd3, also know as human PLAP or phospholipase A2-activating protein) has been implicated in a variety of disparate biological processes that involve the ubiquitin system. It is linked to the maintenance of ubiquitin levels, but the mechanism by which it accomplishes this is unclear. The C-terminal PUL (PLAP, Ufd3p, and Lub1p) domain of PLAA binds p97, an AAA ATPase, which among other functions helps transfer ubiquitinated proteins to the proteasome for degradation. In yeast, loss of Doa1 is suppressed by altering p97/Cdc48 function indicating that physical interaction between PLAA and p97 is functionally important. Although the overall regions of interaction between these proteins are known, the structural basis has been unavailable. We solved the high resolution crystal structure of the p97-PLAA complex showing that the PUL domain forms a 6-mer Armadillo-containing domain. Its N-terminal extension folds back onto the inner curvature forming a deep ridge that is positively charged with residues that are phylogenetically conserved. The C terminus of p97 binds in this ridge, where the side chain of p97-Tyr805, implicated in phosphorylation-dependent regulation, is buried. Expressed in doa1{Delta} null cells, point mutants of the yeast ortholog Doa1 that disrupt this interaction display slightly reduced ubiquitin levels, but unlike doa1{Delta} null cells, showed only some of the growth phenotypes. These data suggest that the p97-PLAA interaction is important for a subset of PLAA-dependent biological processes and provides a framework to better understand the role of these complex molecules in the ubiquitin system.

  17. Chemical preparation, kinetics of thermal behavior and infrared studies of Pb3(P3O92.3H2O and Cd3(P3O92.14H2O

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    Said Belaaouad

    2013-05-01

    Full Text Available Chemical preparation, thermal behavior, kinetic and IR studies are given for the cyclotriphosphates Pb3(P3O92.3H2O and Cd3(P3O92.14H2O. The later cyclotriphosphates have never been studied except their crystallographic characterization and are stable in the conditions of temperature and pressure of our laboratory until 343K. The final products of the dehydration and calcination of Pb3(P3O92.3H2O and Cd3(P3O92.14H2O, under atmospheric pressure, are respectively their long chain polyphosphates, [Pb(PO32]∞ and β[Cd(PO32]∞. The intermediate product of the dehydration of Cd3(P3O92.14H2O, under atmospheric pressure, is its long chain polyphosphate form α, α[Cd(PO32]. [Pb(PO32]∞ and β[Cd(PO32]∞ are stable until their melting points at respectively 946K and 1153K. Two different methods, Ozawa and KAS have been selected in order to study the kinetics of thermal behavior of the cyclotriphosphates Pb3(P3O92.3H2O and Cd3(P3O92.14H2O for the first time. The kinetic and thermodynamic features of the dehydration, of the cited cyclotriphosphates, were determined and discussed on the basis of their crystalline structure. [Pb(PO32]∞, α[Cd(PO32] and β[Cd(PO32] have many applications in industry such as corrosion inhibitors.

  18. Relationship between miRNA-338-3p expression and progression and prognosis of human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sun Kai; Su Guiyuan; Deng Haijun; Dong Jingqing; Lei Shangtong; Li Guoxin

    2014-01-01

    Background miR-338-3p is a recently discovered miRNA and is involved in cell differentiation.However,few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma (CRC).This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms.Methods The 40 CRC,adjacent nontumorous tissues and 2 human CRC-derived cell lines (SW-480 and SW-620) were collected,respectively,and the total RNA and protein were isolated routinely.The miR-338-3p expression pattern was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting.Smoothened (SMO,possible target of miR-338-3p) mRNA and corresponding protein expression pattern were detected by semiquantitative RT-PCR and Western blotting.miR-338-3p expression patterns were compared between nontumor mucosa and CRC samples,graded by progression-related factors.Disease outcome was calculated by Kaplan-Meier survival analysis to determine whether miR-338-3p was related to disease-free survival (DFS) and overall survival (OS) of patients.Moreover,SMO 3'-UTR fragment was PCR amplified from genome DNA of human colon and inserted into a luciferase reporter plasmid.The luciferase reporter plasmid construct was then transfected into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase activity in the transfected cells was detected.Results The expression of miR-338-3p was significantly downregulated in CRCs than those in the adjacent nontumorous tissues,and the value was negatively related to advanced TNM stage and local invasion (P <0.01).Furthermore,miR338-3p value was decreased markedly in SW-620 cell line relative to SW-480 (P <0.01).Low expression of miR-338-3p was associated with unfavorable outcome in DFS but not in OS independent of clinical covariates.Moreover,RT-PCR and Western blotting analysis demonstrated that there was no

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-01-01

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

  20. miR-4782-3p Inhibited Non-Small Cell Lung Cancer growth via USP14

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    Ning Wu

    2014-02-01

    Full Text Available Background: Lung cancer is the leading cause of cancer-related mortality worldwide, with near 1.4 million deaths each year. NSCLC accounts for nearly 85% of all case of lung cancer. MiRNAs play important roles in regulation of gene expression at the post-transcriptional level. MiRNAs profiles may predict prognosis and disease recurrence in early-stage NSCLC. Our previous study proved that over-expression of ubiquitin specific peptidase 14 (USP14, a deubiquitinating enzyme, was associated with favorable prognosis in NSCLC patients and promoted tumor cells proliferation. Here, we tried to identify which miRNAs targeted USP14, and the roles of these miRNAs in NSCLC. Methods: MiR-4782-3p and its potential targeted genes were identified by bioinformatics algorithm. Dual luciferase reporter assay system was used to analyze the interaction between miR-4782-3p and targeted genes. Cell proliferation was assayed by MTT and BdU assay. MiRNAs and mRNA expression were assayed by qRT-PCR. USP14 protein level was assayed by Western blot. The role of miR-4782-3p in patients survival was revealed by Kaplan-Meier plot of overall survival. Results: Up-expression of miR-4782-3p in NSCLC cells decreased the USP14 expression. Down-expression of miR-4782-3p increased USP14 expression. In NSCLC specimen, Negative correlation between USP14 mRNA level and miR-4782-3p level was identified. Higher miR-4782-3p expression is associated with longer survival. USP14, ZEB2, XIAP overexpression reversed the inhibitory effect of miR-4782-3p. Conclusions: High expression of miR-4782-3p was associated with favorable prognosis in NSCLC patients. MiR-4782-3p inhibited cell proliferation in NSCLC by targeting USP14, ZEB2 and XIAP.

  1. Reactions of N+ (3P) ions with H2 and HD molecules at low temperatures

    Science.gov (United States)

    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.

  2. Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

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    Chao-Yu Pan

    2017-01-01

    Full Text Available MicroRNAs (miRNAs play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

  3. Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.

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    Chen Bian

    Full Text Available Luteolin (LUT, a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R. However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs. The purpose of this study was to determine which miRs and target genes LUT exerted such function through.Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets oncogene homolog 1. MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1.LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.

  4. Development of a chromosomally integrated metabolite-inducible Leu3p-alpha-IPM "off-on" gene switch.

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    Maria Poulou

    Full Text Available BACKGROUND: Present technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that a chromosomally integrated yeast 'Leu3p-alpha-IotaRhoMu' system constitutes a ligand-inducible regulatory "off-on" genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of alpha-isopropylmalate (alpha-IotaRhoMu in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable alpha-IPM presents an EC(50 equal to 0.8837 mM and fast "OFF-ON" kinetics (t(50ON = 43 min, t(50OFF = 2.18 h, it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the 'Leu3p-alpha-IotaRhoMu' constitutes a simpler and safer system for inducible gene expression in biomedical applications.

  5. Prm3p is a pheromone-induced peripheral nuclear envelope protein required for yeast nuclear fusion.

    Science.gov (United States)

    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.

  6. Propofol Inhibits Neurogenesis of Rat Neural Stem Cells by Upregulating MicroRNA-141-3p.

    Science.gov (United States)

    Jiang, Qiliang; Wang, Yingwei; Shi, Xueyin

    2017-02-01

    Prolonged or high-dose exposure to anesthetics, such as propofol, can cause brain cell degeneration and subsequent long-term learning or memory deficits, particularly in the developing brain. However, the cellular and molecular mechanisms underlying the deleterious effects of propofol at certain stages of development remain unclear. In this study we found that propofol inhibited the proliferation, neuronal differentiation, and migration of neural stem cells (NSCs) while upregulating miR-141-3p. Silencing of miR-141-3p abrogated the effects of propofol on NSC neurogenesis. Propofol treatment downregulated IGF2BP2, a direct target of miR-141-3p, whereas overexpression of IGF2BP2 attenuated the effects of propofol and miR-141-3p on NSC neurogenesis. In short, propofol inhibits NSC neurogenesis through a mechanism involving the miR-141-3p/IGF2BP2 axis. Our results may provide a potential approach for preventing the neurodegenerative effects of propofol in the developing brain.

  7. Combination of MiR-103a-3p and Mesothelin Improves the Biomarker Performance of Malignant Mesothelioma Diagnosis

    Science.gov (United States)

    Bryk, Oleksandr; Raiko, Irina; Pesch, Beate; Kollmeier, Jens; Bauer, Torsten T.; Brüning, Thomas

    2014-01-01

    Background For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma. Methods/Principal Findings Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated. Conclusions/Significance The results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel. PMID:25469901

  8. Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis.

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    Daniel G Weber

    Full Text Available For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma.Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated.The results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel.

  9. miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110.

    Science.gov (United States)

    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.

  10. The ATF/CREB site is the key element for transcription of the human RNA methyltransferase like 1 (RNMTL1) gene, a newly discovered 17p13.3 gene

    Institute of Scientific and Technical Information of China (English)

    JIAN; XU; JING; DE; ZHU; MIN; NI; DA; FANG; WAN; JIAN; REN; GU

    2002-01-01

    The human RNA methyltransferase like i gene (RNMTL1) is one of thirteen newly discovered geneswithin a 116 Kb segment of the chromosome 17p13.3 that suffers from a high frequent loss of heterozygosityin human hepatocellular carcinoma in China[1-5]. To understand the molecular mechanisms underlyingtranscription control of the RNMTL1 gene in human cancers, we decline using of the conventional approachwhere the cis-elements bound by the known transcription factors are primary targets, and carried out thesystematic analyses to dissect the promoter structure and identify/characterize the key cis-elements thatare responsible for its strong expression in cell. The molecular approaches applied included 1, the primerextension for mapping of the transcription starts; 2, the transient transfection/reporter assays on a largenumber of deletion and site-specific mutants of the promoter segment for defining the minimal promoterand the crucial elements within; and 3, the electrophoresis mobility shift assay with specific antibodies forreconfirming the nature of the transcription factors and their cognate cis-elements. We have shown that theinteraction of an ATF/CREB element (-38 to -31) and its cognate transcription factors play a predominantrole in the promoter activity of the RNMTL1 gene. The secondary DNA structures of the ATF/CREBelement play a more vital role in the protein-DNA interaction. Finally, we reported a novel mechanismunderlying the YY1 mediated transcription repression, namely, the ATF/CREB dependent transcription-repression by YY1 is executed in absence of its own sequence-specific binding.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  12. Regulatory role of the sequences downstream from nodD3 P1 promoter of Rhizobium meliloti

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The 660 bp region between nodD3 P1 promoter and the following coding region of Rhizobium meliloti has been studied.This region is designated "downstream sequences".It consists of two potential open reading frames,ORF1 and ORF2.Studies on the role of the downstream sequences on the activity of nodD3 P1 with nod D3(P1)-lacZ fusion show that deletion of the sequences containing ORF2 causes the increase of the activity of the fusion; on the contrary,addition of extra copies of ORF2 markedly decreases the activity of the fusion.These results indicate that the product of ORF2 plays a negative role in the expression of nod D3.

  13. Biomimetic-Inspired Infrared Sensors from Zn3P2 Microwires: Study of Their Photoconductivity and Infrared Spectrum Properties

    Directory of Open Access Journals (Sweden)

    M. Israelowitz

    2014-01-01

    Full Text Available The fire beetle, Melanophila acuminata (Coleoptera: Buprestidae, senses infrared radiation at wavelengths of 3 and 10–25 microns via specialized protein-containing sensilla. Although the protein denatures outside of a biological system, this detection mechanism has inspired our bottom-up approach to produce single zinc phosphide microwires via vapour transport for IR sensing. The Zn3P2 microwires were immobilized and electrical contact was made by dielectrophoresis. Photoconductivity measurements have been extended to the near IR range, spanning the Zn3P2 band gaps. Purity and integrity of the Zn3P2 microwires including infrared light scattering properties were confirmed by infrared transmission microscopy. This biomimetic microwire shows promise for infrared chip development.

  14. Energetics, transition states, and intrinsic reaction coordinates for reactions associated with O(3P) processing of hydrocarbon materials

    Science.gov (United States)

    Yan, Tianying; Hase, William L.; Doubleday, Charles

    2004-05-01

    Electronic structure calculations based on multiconfiguration wave functions are used to investigate a set of archetypal reactions relevant to O(3P) processing of hydrocarbon molecules and surfaces. These include O(3P) reactions with methane and ethane to give OH plus methyl or ethyl radicals, O(3P)+ethane to give CH3O+CH3, and secondary reactions of the OH product radical with ethane and the ethyl radical. Geometry optimization is carried out with CASSCF/cc-pVTZ for all reactions, and with CASPT2/cc-pVTZ for O(3P)+methane/ethane. Single-point energy corrections are applied with CASPT2, CASPT3, and MRCI+Q with the cc-pVTZ and cc-pVQZ basis sets, and the energies extrapolated to the complete basis set limit (CBL). Where comparison of computed barriers and energies of reaction with experiment is possible, the agreement is good to excellent. The best agreement (within experimental error) is found for MRCI+Q/CBL applied to O(3P)+methane. For the other reactions, CASPT2/CBL and MRCI+Q/CBL predictions differ from experiment by 1-5 kcal/mol for 0 K enthalpies of reaction, and are within 1 kcal/mol of the best-estimate experimental range of 0 K barriers for O(3P)+ethane and OH+ethane. The accuracy of MRCI+Q/CBL is limited mainly by the quality of the active space. CASPT2/CBL barriers are consistently lower than MRCI+Q/CBL barriers with identical reference spaces.

  15. Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts.

    Science.gov (United States)

    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.

  16. Lifetime measurement of the metastable 2{sup 3}P{sub 0} state in He-like uranium

    Energy Technology Data Exchange (ETDEWEB)

    Toleikis, S. [Lawrence Berkeley National Laboratory, 1 Cyclotron Rd., MS 88R0192, Berkeley, CA 94720-8101 (United States) and Texas A and M University, College Station, TX (United States)]. E-mail: stoleikis@lbl.gov; Manil, B. [GANIL, Caen (France); Bednarz, G. [IFUJ, Cracow (Poland); Berdermann, E. [GSI, Darmstadt (Germany); Beyer, H.F. [GSI, Darmstadt (Germany); Bosch, F. [GSI, Darmstadt (Germany); Braeuning-Demian, A. [GSI, Darmstadt (Germany); Gumberidze, A. [GSI, Darmstadt (Germany); Indelicato, P. [Universite P. et M. Curie, Paris (France); Kozhuharov, C. [GSI, Darmstadt (Germany); Liesen, D. [GSI, Darmstadt (Germany); Marrus, R. [University of California, Berkeley, CA (United States); Mokler, P.H. [GSI, Darmstadt (Germany); Stachura, Z. [INP, Cracow (Poland); Stoehlker, T. [GSI, Darmstadt (Germany); Warczak, A. [IFUJ, Cracow (Poland)

    2005-07-01

    The lifetime of the 2{sup 3}P{sub 0} state in He-like uranium has been measured in a beam-foil time-of-flight experiment at the Gesellschaft fur Schwerionenforschung accelerator facility with the result {tau}(2{sup 3}P{sub 0})=58.2(9.5)ps. With the measured lifetime it is possible to derive a value of {delta}E{sub 2s}{sup Lamb}=76.3+/-20.6eV for the n=2 Lamb shift in uranium.

  17. A proof of the linearity conjecture for k-blocking sets in PG(n, p3), p prime

    CERN Document Server

    Lavrauw, Michel; Van de Voorde, Geertrui

    2012-01-01

    In this paper, we show that a small minimal k-blocking set in PG(n, q3), q = p^h, h >= 1, p prime, p >=7, intersecting every (n-k)-space in 1 (mod q) points, is linear. As a corollary, this result shows that all small minimal k-blocking sets in PG(n, p^3), p prime, p >=7, are Fp-linear, proving the linearity conjecture (see [7]) in the case PG(n, p3), p prime, p >= 7.

  18. SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

    DEFF Research Database (Denmark)

    Wainwright, Elanor N; Jorgensen, Joan S; Kim, Youngha;

    2013-01-01

    . Expression of the primary transcript of miR-202-5p/3p remained low in XY gonads in a conditional Sox9-null mouse model, suggesting that pri-miR-202 transcription is downstream of SOX9, a transcription factor that is both necessary and sufficient for male sex determination. We identified the pri-miR-202...... findings indicate that expression of the conserved gonad microRNA, miR-202-5p/3p, is downstream of the testis-determining factor SOX9, suggesting an early role in testis development....

  19. Measurement of the Hyperfine Structure and Isotope Shifts of the 3s23p2 3P2 to 3s3p3 3Do3 Transition in Silicon

    CERN Document Server

    Lee, Siu Au

    2010-01-01

    The hyperfine structure and isotope shifts of the 3s23p2 3P2 to 3s3p3 3Do3 transition in silicon have been measured. The transition at 221.7 nm was studied by laser induced fluorescence in an atomic Si beam. For 29Si, the hyperfine A constant for the 3s23p2 3P2 level was determined to be -160.1+-1.3 MHz (1 sigma error), and the A constant for the 3s3p3 3Do3 level is -532.9+-0.6 MHz. This is the first time that these constants were measured. The isotope shifts (relative to the abundant isotope 28Si) of the transition were determined to be 1753.3+-1.1 MHz for 29Si and 3359.9+-0.6 MHz for 30Si. This is an improvement by about two orders of magnitude over a previous measurement. From these results we are able to predict the hyperfine structure and isotope shift of the radioactive 31Si atom, which is of interest in building a scalable quantum computer.

  20. High lying energy positions of doubly (2pns) {sup 1,3}P{sup o} and (2pnd) {sup 1,3}P{sup o} excited states of the beryllium atom

    Energy Technology Data Exchange (ETDEWEB)

    Sakho, I., E-mail: aminafatima_sakho@yahoo.fr [UFR Sciences and Technologies, Department of physics, University of Ziguinchor, Ziguinchor (Senegal)

    2011-12-15

    The Screening Constant by Unit Nuclear Charge (SCUNC) method is used to study (2pns) {sup 1,3}P{sup o} and (2pnd) {sup 1,3}P{sup o} autoionizing states of the beryllium atom. Energy positions are reported up to n=20. In addition, resonance widths of the (2pns) {sup 1}P{sup o} states also presented. The current results compared very well to available theoretical and experimental literature values up to n=15. The accurate data presented in this work may be of interest for future experimental and theoretical studies in the photoabsorption spectrum of Be. - Highlights: > Accurate energy positions of (2pns) {sup 1,3}P{sup o} and (2pnd) {sup 1,3}P{sup o} (n=3-20) autoionizing states of Be atoms. > Currently results compared very well to theoretical and experimental literature values up to n=15. > Presently data may be of interest for future experimental and theoretical studies in the photoabsorption spectrum of Be.

  1. miR-199a-3p 靶基因预测及生物信息学分析%Prediction of miR-199a-3p targets gene and its bioinformatics analysis

    Institute of Scientific and Technical Information of China (English)

    谢小娟; 潘晶晶; 魏力强; 陈葳

    2016-01-01

    Objective To provide theoretical guidance for further research on the role of miR-1 99a-3p in formation and development of bladder cancer.Methods Mature sequence of miR-1 99a-3p was analyzed;target genes and transcription factors of miRNA-1 99a-3p were predicted,and the target genes were analyzed for gene ontology (GO)enrichment and Kyoto Encyclopedia of Genes and Genome (KEGG)pathway.Then TF-miRNA-mRNA network diagram was constructed.Results Sequences of miR-1 99a-3p were highly conserved in various species.In GO analysis,the target genes of miR-1 99a-3p were enriched in many biological processes,such as regulation of cellular process,regulation of macromolecule metabolic process,and regulation of biological process (P <0.01 ).In KEGG pathway,the target genes were mainly located in bacterial invasion pathway of epithelial cells,ECM-receptor interaction pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,small cell lung cancer pathway,and proteoglycans pathway in the cancer (P <0.05).According to the TF-miRNA-mRNA network diagram,the important genes that might be regulated by miR-1 99a-3p were MYC,SP1,mTOR,NFκB,and NFκB1.Conclusion miR-1 99a-3p may directly target mTOR and participate in the formation and development of bladder cancer through regulating PI3K-Akt-mTOR signaling pathway.%目的:为深入研究 miR-199a-3p 在膀胱癌形成和发展中的作用提供理论依据。方法分析 miR-199a-3p 序列,预测其靶基因和转录因子,并对靶基因进行 GO 富集和 KEGG Pathway 分析;构建 TF-miR-199a-3p-靶基因网络调控图。结果miR-199a-3p 序列在多物种间具有高度保守性;GO 分析发现 miR-199a-3p 的靶基因参与细胞调节、代谢调节、细胞大分子生物合成等生物过程(P <0.01);KEGG Pathway 分析发现 miR-199a-3p 的靶基因显著富集在上皮细胞的细菌入侵通路、ECM 受体的相互作用通路、PI3K-Akt 信号通路、MAPK 信号通路、小细胞肺癌通路、癌症中的蛋白

  2. Microstructure and Wear Behaviors of In-situ Al2O3p/7075 Composites%原位Al2O3P/7075复合材料微观组织与磨损行为

    Institute of Scientific and Technical Information of China (English)

    刘慧敏; 杨树青; 许萍; 李进福

    2012-01-01

    采用原位反应近液相线铸造法制备具有不同质量分数的Al2O3P/7075复合材料,并对其进行干滑动磨损实验研究,通过OM,SEM,TEM等材料分析方法测试了材料的微观组织和磨损表面形貌.结果表明,原位Al2O3颗粒对7075铝合金的晶粒组织有明显细化效果,Al2O3P/7075复合材料的耐磨性比基体7075铝合金有明显的提高.原因是原位合成的复合材料界面结合良好,原位Al2O3颗粒在摩擦过程中起着抑制金属流动和支撑的双重作用.磨损表面形貌显示,原位Al2O3颗粒的加入,使磨损机制由黏着磨损变为磨粒磨损,从而改善了材料的耐磨性.%The Al2O3P/7075 Al composites were synthesized by in-situ reaction near-liquidus casting. The microstructure and dry sliding wear behavior of the prepared composites were analyzed using OM, SEM and TEM as well as wear friction testing. The results reveal that in-situ Al2O3 particle with average size of approximately <1μm is uniformly distributed in the matrix, which exhibits desirable refining effects on microstructure of 7075 Al alloy. The wear behavior of the composites is greatly superior to that of the matrix, which is attributed to the grain refining and formation of a compact interface of Al2O3P/7075 Al composites. In addition, in-situ Al2O3 particles exhibit coupling effects of inhibiting metal flow and bearing some load in process of friction. The wear mechanism of the matrix 7075A1 alloy is adhesive wear, while the wear surface of Al2O3p/7075 Al composites is superior to that of the matrix 7075 Al alloy. The wear mechanism of Al2O3P/7075 Al composites is abrasive wear, and wear resistance of Al2O3P/7075 Al is improved.

  3. Phospholipid flippases Lem3p-Dnf1p and Lem3p-Dnf2p are involved in the sorting of the tryptophan permease Tat2p in yeast.

    Science.gov (United States)

    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.

  4. Relativistic calculations of 3s2 1S0-3s3p 1P1 and 3s2 1S0-3s3p 3P1,2 transition probabilities in the Mg isoelectronic sequence

    Institute of Scientific and Technical Information of China (English)

    Cheng Cheng; Gao Xiang; Qing Bo; Zhang Xiao-Le; Li Jia-Ming

    2011-01-01

    Using the multi-configuration Dirac-Fock self-consistent field method and the relativistic configuration-interaction method, calculations of transition energies, oscillator strengths and rates are performed for the 3s2 1S0-3s3p 1P1 spinallowed transition, 3s2 1S0-3s3p 3P1,2 intercombination and magnetic quadrupole transition in the Mg isoelectronic sequence (Mg Ⅰ, Al Ⅱ, Si ⅢⅢ, P Ⅳ and S Ⅴ). Electron correlations are treated adequately, including intravalence electron correlations. The influence of the Breit interaction on oscillator strengths and transition energies are investigated. Quantum electrodynamics corrections are added as corrections. The calculation results are found to be in good agreement with the experimental data and other theoretical calculations.

  5. Radiative rates for E1, E2, M1, and M2 transitions among the 3s$^2$3p$^5$, 3s3p$^6$, and 3s$^2$3p$^4$3d configurations of Cl-like W LVIII

    CERN Document Server

    Aggarwal, K M

    2014-01-01

    We report calculations of energy levels, radiative decay rates, and lifetimes for transitions among the 3s$^2$3p$^5$, 3s3p$^6$, and 3s$^2$3p$^4$3d configurations of Cl-like W LVIII. The general-purpose relativistic atomic structure package (GRASP) has been adopted for our calculations. Comparisons are made with the most recent results of Mohan et al. [Can. J. Phys. {\\bf 92} (2014) xxx] and discrepancies in lifetimes are noted, up to four orders of magnitude in some instances. Our energy levels are estimated to be accurate to better than 0.5\\%, whereas results for radiative rates and lifetimes should be accurate to better than 20\\%.

  6. Absence of mutations in the coding sequence of the potential tumor suppressor 3pK in metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Houben Roland

    2005-12-01

    Full Text Available Abstract Background Activation of Ras or Raf contributes to tumorigenesis of melanoma. However, constitutive Raf activation is also a characteristic of the majority of benign melanocytic nevi and high intensity signaling of either Ras or Raf was found to induce growth inhibition and senescence rather than transformation. Since the chromosome 3p kinase (3pK is a target of the Ras/Raf/Mek/Erk signaling pathway which antagonizes the function of the oncogene and anti-differentiation factor Bmi-1, 3pK may function as a tumor suppressor in tumors with constitutive Ras/Raf activation. Consequently, we tested whether inactivating 3pK mutations are present in melanoma. Methods 30 metastatic melanoma samples, which were positive for activating mutations of either BRaf or NRas, were analyzed for possible mutations in the 3pk gene. The 10 coding exons and their flanking intron sequences were amplified by PCR and direct sequencing of the PCR products was performed. Results This analysis revealed that besides the presence of some single nucleotide polymorphisms in the 3pk gene, we could not detect any possible loss of function mutation in any of these 30 metastatic melanoma samples selected for the presence of activating mutations within the Ras/Raf/Mek/Erk signaling pathway. Conclusion Hence, in melanoma with constitutively active Ras/Raf inactivating mutations within the 3pk gene do not contribute to the oncogenic phenotype of this highly malignant tumor.

  7. $\\beta$3$p$-spectroscopy and proton-$\\gamma$ width determination in the decay of $^{31}$Ar

    CERN Multimedia

    We propose to perform a detailed study of the $\\beta$-decay of the dripline nucleus $^{31}$Ar. This will allow a detailed study of the $\\beta$-delayed 3$p$-decay as well as provide important information on the resonances of $^{30}$S and $^{29}$P, in particular the ratio between the $p$- and $\\gamma$- partial widths relevant for astrophysics.

  8. Reduced miR-659-3p levels correlate with progranulin increase in hypoxic conditions: implications for frontotemporal dementia.

    Directory of Open Access Journals (Sweden)

    Paola ePiscopo

    2016-05-01

    Full Text Available Progranulin (PGRN is a secreted protein expressed ubiquitously throughout the body, including the brain, where it localizes in neurons and 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 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 24h 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.

  9. Evidence that intramolecular interactions are involved in masking the activation domain of transcriptional activator Leu3p.

    Science.gov (United States)

    Wang, D; Hu, Y; Zheng, F; Zhou, K; Kohlhaw, G B

    1997-08-01

    The Leu3 protein of Saccharomyces cerevisiae regulates the expression of genes involved in branched chain amino acid biosynthesis and in ammonia assimilation. It is modulated by alpha-isopropylmalate, an intermediate in leucine biosynthesis. In the presence of alpha-isopropylmalate, Leu3p is a transcriptional activator. In the absence of the signal molecule, the activation domain is masked, and Leu3p acts as a repressor. The recent discovery that Leu3p retains its regulatory properties when expressed in mammalian cells (Guo, H., and Kohlhaw, G. B. (1996) FEBS Lett. 390, 191-195) suggests that masking and unmasking of the activation domain occur without the participation of auxiliary proteins. Here we present experimental support for this notion and address the mechanism of masking. We show that modulation of Leu3p is exceedingly sensitive to mutations in the activation domain. An activation domain double mutant (D872N/D874N; designated Leu3-dd) was constructed that has the characteristics of a permanently masked activator. Using separately expressed segments containing either the DNA binding domain-middle region or the activation domain of wild type Leu3p (or Leu3-dd) in a modified yeast two-hybrid system, we provide direct evidence for alpha-isopropylmalate-dependent interaction between these segments. Finally, we use the phenotype of Leu3-dd-containing cells (slow growth in the absence of added leucine) to select for suppressor mutations that map to the middle region of Leu3-dd. The properties of nine such suppressors further support the idea that masking is an intramolecular process and suggest a means for mapping the surface involved in masking.

  10. MiR-466b-1-3p regulates P-glycoprotein expression in rat cerebral microvascular endothelial cells.

    Science.gov (United States)

    Yang, Xiaobo; Ren, Weimin; Shao, Yiye; Chen, Yinghui

    2017-04-03

    Epilepsy is one of the most common neurological disorders, and approximately one-third of epilepsy cases are resistant to treatment with anti-epileptic drug (AED). P-glycoprotein (P-gp) is a multi-drug transporter that is thought to play a pivotal role in multiple drug resistance (MDR) in epilepsy. The regulatory mechanism of P-gp remains largely unknown; however, recent studies have demonstrated that microRNAs (miRNAs) may regulate the chemo-resistance mediated by P-gp. This study investigated the effect of specific miRNAs that regulate P-gp expression in rat cerebral microvascular endothelial cells (RCMECs). Primary cultures of RCMECs were treated with phenobarbital (PB) at various concentrations to induce P-gp overexpression. MiRNA microarrays were used to investigate the expression profiles of miRNAs in the resistant RCMECs induced by PB and corresponding non-resistant cells. Our data demonstrated decreased miR-466b-1-3p expression in the resistant cells compared with the non-resistant cells. Moreover, the recombinant RNA of 466b-1-3p (mimic) and the artificial antisense RNA of miR-466b-1-3p (inhibitor) were constructed and transfected into resistant RCMECs. The expression and function of P-gp were measured by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry using rhodamine efflux. The mRNA and protein levels of P-gp increased as the concentration of PB increased, whereas miR-466b-1-3p levels decreased with increasing PB concentrations (Pp mimic down-regulated P-gp expression, whereas the miR-466b-1-3p inhibitor up-regulated P-gp expression (Pp may regulate PB-induced P-gp expression in RCMECs.

  11. Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shinya Takigawa

    2016-02-01

    Full Text Available 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.

  12. MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice

    Science.gov (United States)

    Lee, Benjamin P.; Burić, Ivana; George-Pandeth, Anupriya; Flurkey, Kevin; Harrison, David E.; Yuan, Rong; Peters, Luanne L.; Kuchel, George A.; Melzer, David; Harries, Lorna W.

    2017-01-01

    MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3’ untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = −0.6447, p = 4.8 × 10−11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10−8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10−6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals. PMID:28304372

  13. Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells

    Directory of Open Access Journals (Sweden)

    Zhang L

    2015-04-01

    Full Text Available Linlin Zhang,1,2,* Arun K lyer,3,4,* Xiaoqian Yang,1 Eisuke Kobayashi,1 Yuqi Guo,1,2 Henry Mankin,1 Francis J Hornicek,1 Mansoor M Amiji,3 Zhenfeng Duan1 1Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA; 2Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, USA; 4Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA *These authors contributed equally to this work Abstract: 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

  14. Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures

    DEFF Research Database (Denmark)

    Thevenon, Julien; Monnier, Nicole; Callier, Patrick

    2014-01-01

    Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis......, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low......-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1...

  15. Photoassociation spectroscopy of long-range molecular states below the 2s + 3p 6Li2 asymptote

    Science.gov (United States)

    Gross, Christian; Chaudhuri, Saptarishi; Gan, Jaren; Dieckmann, Kai

    2015-05-01

    We present photoassociation spectra of high-lying vibrational states of the interatomic potentials correlating to the 2s + 3p asymptote of 6Li2 . Starting from an atomic cloud in a magneto-optical trap we first drive a free-to-bound transition into a molecular bound state using a tunable ultra-violet laser. Thereafter we ionize these long-range molecules using a 532 nm laser and detect the resulting ions with a channeltron. We determine the absolute positions of the transitions with MHz precision utilizing a frequency comb based calibration. Lithium dimers are extensively studied theoretically using various models and methods. Spectroscopic measurements are crucial to test and benchmark these methods and are available for various electronic states and inter-nuclear distances of 6Li2 molecule. Our study provides the first experimental observation of long-range states of the 2s + 3p asymptote of 6Li2 .

  16. A software platform to analyse the ethical issues of electronic patient privacy policy: the S3P example.

    Science.gov (United States)

    Mizani, M A; Baykal, N

    2007-12-01

    Paper-based privacy policies fail to resolve the new changes posed by electronic healthcare. Protecting patient privacy through electronic systems has become a serious concern and is the subject of several recent studies. The shift towards an electronic privacy policy introduces new ethical challenges that cannot be solved merely by technical measures. Structured Patient Privacy Policy (S3P) is a software tool assuming an automated electronic privacy policy in an electronic healthcare setting. It is designed to simulate different access levels and rights of various professionals involved in healthcare in order to assess the emerging ethical problems. The authors discuss ethical issues concerning electronic patient privacy policies that have become apparent during the development and application of S3P.

  17. Efficient transfer hydrogenation reaction Catalyzed by a dearomatized PN 3P ruthenium pincer complex under base-free Conditions

    KAUST Repository

    He, Lipeng

    2012-03-01

    A dearomatized complex [RuH(PN 3P)(CO)] (PN 3PN, N′-bis(di-tert-butylphosphino)-2,6-diaminopyridine) (3) was prepared by reaction of the aromatic complex [RuH(Cl)(PN 3P)(CO)] (2) with t-BuOK in THF. Further treatment of 3 with formic acid led to the formation of a rearomatized complex (4). These new complexes were fully characterized and the molecular structure of complex 4 was further confirmed by X-ray crystallography. In complex 4, a distorted square-pyramidal geometry around the ruthenium center was observed, with the CO ligand trans to the pyridinic nitrogen atom and the hydride located in the apical position. The dearomatized complex 3 displays efficient catalytic activity for hydrogen transfer of ketones in isopropanol. © 2011 Elsevier B.V. All rights reserved.

  18. Stationary and dispersive features in resonant inelastic soft X-ray scattering at the Ge 3p resonances

    Energy Technology Data Exchange (ETDEWEB)

    Glover, C.J. [Department of Electronic Materials Engineering, Australian National University, Canberra, ACT 0200 (Australia); Schmitt, T. [SLS, Paul Scherrer Institut, PSI West, CH-5232 Villigen PSI (Switzerland); Mattesini, M. [Departamento de Fisica de la Tierra, Astronomia y Astrofisica I, Universidad Complutense de Madrid, E-28040 (Spain); Adell, M.; Ilver, L.; Kanski, J. [Chalmers University of Technology, SE-412 96 Goeteborg (Sweden); Kjeldgaard, L. [MAX-lab, Lund University, P.O. Box 118, SE-22100 Lund (Sweden); Agaker, M. [Department of Physics and Materials Science, Uppsala University, PO Box 530, SE-751 21 Uppsala (Sweden); Martensson, N. [MAX-lab, Lund University, P.O. Box 118, SE-22100 Lund (Sweden); Department of Physics and Materials Science, Uppsala University, PO Box 530, SE-751 21 Uppsala (Sweden); Ahuja, R.; Nordgren, J. [Department of Physics and Materials Science, Uppsala University, PO Box 530, SE-751 21 Uppsala (Sweden); Rubensson, J.-E. [Department of Physics and Materials Science, Uppsala University, PO Box 530, SE-751 21 Uppsala (Sweden)], E-mail: jan-erik.rubensson@fysik.uu.se

    2009-07-15

    Resonant inelastic soft X-ray scattering at the 3p resonances in crystalline Ge is presented. Both stationary and dispersive features are observed in a wide energy range above as well as below the ionization limits. These observations are in agreement with theoretical predictions based on a two-step model where the initially excited electron has no influence on the emission step. Excess population of states in the conduction band is found, and discussed in terms of attosecond electron dynamics.

  19. Nonlinear Zeeman effect in photoassociation spectra of $^{40}$Ca near the $^3$P$_1$+$^1$S$_0$ asymptote

    CERN Document Server

    Tiemann, Eberhard; Pachomow, Evgenij; Riehle, Fritz; Sterr, Uwe

    2015-01-01

    We present calculations of the Zeeman effect of narrow photoassociation lines of $^{40}$Ca near the $^3$P$_1$ + $^1$S$_0$ asymptote. Using a coupled-channel model we find a nonlinear Zeeman effect that even at low fields of a few mT amounts to several kHz. With this model we analyze previous measurements and give corrected long range dispersion coefficients of the $^3\\Pi_{u}$ and $^3\\Sigma^+ _{u}$ states.

  20. A software platform to analyse the ethical issues of electronic patient privacy policy: the S3P example

    OpenAIRE

    Mizani, M A; Baykal, N

    2007-01-01

    Paper‐based privacy policies fail to resolve the new changes posed by electronic healthcare. Protecting patient privacy through electronic systems has become a serious concern and is the subject of several recent studies. The shift towards an electronic privacy policy introduces new ethical challenges that cannot be solved merely by technical measures. Structured Patient Privacy Policy (S3P) is a software tool assuming an automated electronic privacy policy in an electronic healthcare setting...

  1. miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting CCDC6 Gene

    Science.gov (United States)

    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

  2. Phase transformation and disorder effect on optical and electrical properties of Zn3P2 thin films.

    Science.gov (United States)

    El Zawawi, I K; Abdel Moez, A; Hammad, T R; Ibrahim, R S

    2012-08-01

    The phase transformation of zinc phosphide (Zn(3)P(2)) thin films was detected through isochronal annealing process. The effects on isochronal annealing on the internal structural, optical and electrical properties of deposited Zn(3)P(2) thin films have been discussed. The films were prepared by thermal evaporation under constant preparation conditions of vacuum 1.3×10(-5)Torr, substrate temperature (300K), rate of deposition (∼1nm/s) and film thickness (480nm). The annealing process was carried out under vacuum for 2h at different temperatures ranging from 373 to 623K. X-ray diffraction patterns showed that the as-deposited films and those annealed at temperatures less than 623K exhibit amorphous structure, while the films annealed at 623K showed tetragonal polycrystalline structure. The optical transmission and reflection spectra were measured at the wavelength range of 190-2500nm. The absorption coefficient spectra and the degree of disorder as measured from the absorption edge were determined. The indirect and direct optical energy band gaps were evaluated for indirect allowed and direct allowed transitions for amorphous and polycrystalline films, respectively. The refractive index n(o) increases with raising the annealing temperature which refers to more condensation in the material. The electrical resistivity for Zn(3)P(2) films decreases exponentially with raising the annealing temperature up to 623K as influenced by structure transformation and decreasing the degree of disorder in the films.

  3. The fast C(3P) + CH3OH reaction as an efficient loss process for gas-phase interstellar methanol

    CERN Document Server

    Shannon, Robin J; Loison, Jean-Christophe; Caubet, Philippe; Balucani, Nadia; Seakins, Paul W; Wakelam, Valentine; Hickson, Kevin M

    2014-01-01

    Rate constants for the C(3P) + CH3OH reaction have been measured in a continuous supersonic flow reactor over the range 50 K to 296 K. C(3P) was created by the in-situ pulsed laser photolysis of CBr4, a multiphoton process which also produced some C(1D), allowing us to investigate simultaneously the low temperature kinetics of the C(1D) + CH3OH reaction. C(1D) atoms were followed by an indirect chemiluminescent tracer method in the presence of excess CH3OH. C(3P) atoms were detected by the same chemiluminescence technique and also by direct vacuum ultra-violet laser induced fluorescence (VUV LIF). Secondary measurements of product H(2S) atom formation have been undertaken allowing absolute H atom yields to be obtained by comparison with a suitable reference reaction. In parallel, statistical calculations have been performed based on ab-initio calculations of the complexes, adducts and transition states (TSs) relevant to the title reaction. By comparison with the experimental H atom yields, the preferred react...

  4. MicroRNA 874-3p Exerts Skeletal Anabolic Effects Epigenetically during Weaning by Suppressing Hdac1 Expression*

    Science.gov (United States)

    Kushwaha, Priyanka; Khedgikar, Vikram; Sharma, Deepika; Yuen, Tony; Gautam, Jyoti; Ahmad, Naseer; Karvande, Anirudha; Mishra, Prabhat R.; Trivedi, Prabodh K.; Sun, Li; Bhadada, Sanjay K.; Zaidi, Mone; Trivedi, Ritu

    2016-01-01

    Embryonic skeletogenesis and postnatal bone development require the transfer of calcium from the mother to the offspring during pregnancy and lactation. Therefore, bone resorption in the mother becomes elevated during these periods, resulting in significant maternal skeletal loss. There follows an anabolic phase around weaning during which there is a remarkable recovery of the maternal skeleton. However, the mechanism(s) of this anabolic response remain(s) largely unknown. We identified eight differentially expressed miRNAs by array profiling, of which miR-874-3p was highly expressed at weaning, a time when bone loss was noted to recover. We report that this weaning-associated miRNA is an anabolic target. Therefore, an agomir of miR-874-3p induced osteoblast differentiation and mineralization. These actions were mediated through the inhibition of Hdac1 expression and enhanced Runx2 transcriptional activation. When injected in vivo, the agomir significantly increased osteoblastogenesis and mineralization, reversed bone loss caused by ovariectomy, and increased bone strength. We speculate that elevated miR-874-3p expression during weaning enhances bone formation and that this miRNA may become a therapeutic target for conditions of bone loss. PMID:26663087

  5. Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.

    Directory of Open Access Journals (Sweden)

    Abraham Lin

    Full Text Available Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage, these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.

  6. New high-pressure polymorph of In2S3 with defect Th3P4-type structure

    Science.gov (United States)

    Lai, Xiaojing; Zhu, Feng; Wu, Ye; Huang, Rong; Wu, Xiang; Zhang, Qian; Yang, Ke; Qin, Shan

    2014-02-01

    The high pressure behavior of β-In2S3 (I41/amd and Z=16) has been studied by in situ synchrotron radiation X-ray diffraction combined with diamond anvil cell up to 71.7 GPa. Three pressure-induced phase transitions are evidenced at ~6.6 GPa, ~11.1 GPa at room temperature and 35.6 GPa after the high-temperature annealing using a portable laser heating system. The new polymorph of In2S3 at 35.6 GPa is assigned to the denser cubic defect Th3P4 structure (I4bar3d and Z=5.333), whose unit-cell parameters are a=7.557(1) Å and V=431.6(2) Å3. The Th3P4-type phase can be stable at least up to 71.7 GPa and cannot be preserved at ambient pressure. The pressure-volume relationship is well described by the second-order Birch-Murnaghan Equation of State, which yields B0=63(3) GPa and B0‧=4 (fixed) for the β-In2S3 phase and B0=87(3) GPa and B0‧=4 (fixed) for the defect Th3P4-type phase respectively.

  7. A new form of Ca{sub 3}P{sub 2} with a ring of Dirac nodes

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Lilia S.; Schoop, Leslie M.; Seibel, Elizabeth M.; Gibson, Quinn D.; Xie, Weiwei; Cava, Robert J., E-mail: rcava@princeton.edu [Department of Chemistry, Princeton University, Princeton, New Jersey 08544 (United States)

    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.

  8. miR-142-3p as a biomarker of blastocyst implantation failure - A pilot study

    Science.gov (United States)

    Borges Jr., Edson; Setti, Amanda Souza; Braga, Daniela P.A.F.; Geraldo, Murilo V; Figueira, Rita de Cássia S; Iaconelli Jr, Assumpto

    2016-01-01

    Objective This study aims to find whether microRNAs (miRNAs) detected in the culture medium of embryos produced in vitro could be potential biomarkers of embryo implantation. Methods Culture media samples from 36 embryos, derived from patients undergoing intracytoplasmic sperm injection (ICSI) in a private university-affiliated IVF center, were collected between January/2015 and November/2015. Samples were collected on day three and embryo transfers were performed on day five and all embryos reached the blastocyst stage. Samples were split into groups according to the embryo implantation result: Positive-Implantation-Group (n=18) or Negative-Implantation-Group (n=18). For the first analysis, samples were pooled in three sets for each group (6-7 spent media per pool). MicroRNAs were extracted from spent media and cDNA was synthesized. C. elegans miR-39 was used as RNA spike-in to normalize the gene expression analysis. The expression of microRNAs into the spent media from the Positive-Implantation-Group was compared with those from the Negative-Implantation-Group. A set of seven miRNAs (miR-21, miR-142-3p, miR-19b, miR-92a, miR-20b, miR-125a and miR148a) selected according with the literature, was tested. To check whether miRNAs could be detected in individual samples of culture media, in a second analysis, ten more samples were tested for miR-21 and miR-142-3p. Results From the sevens tested miRNAs, a significant increased expression of miR-142-3p could be noted in the Negative-Implantation-Group (P<0.001). For other three miRNAs (miR-21, miR-19b and miR-92a) a difference in expression was observed, however it did not reach a statistical significance. In addition, when ten non-redundant samples were tested to check if miRNAs could be detected in individual samples of culture media, the highly specific amplification of mature miRNAs, including miR-142-3p, could be noted. Conclusion Our findings suggest that miR-142-3p, previously described as a tumor suppressor and

  9. Yeast mitochondrial biogenesis: a role for the PUF RNA-binding protein Puf3p in mRNA localization.

    Directory of Open Access Journals (Sweden)

    Yann Saint-Georges

    Full Text Available The asymmetric localization of mRNA plays an important role in coordinating posttranscriptional events in eukaryotic cells. We investigated the peripheral mitochondrial localization of nuclear-encoded mRNAs (MLR in various conditions in which the mRNA binding protein context and the translation efficiency were altered. We identified Puf3p, a Pumilio family RNA-binding protein, as the first trans-acting factor controlling the MLR phenomenon. This allowed the characterization of two classes of genes whose mRNAs are translated to the vicinity of mitochondria. Class I mRNAs (256 genes have a Puf3p binding motif in their 3'UTR region and many of them have their MLR properties deeply affected by PUF3 deletion. Conversely, mutations in the Puf3p binding motif alter the mitochondrial localization of BCS1 mRNA. Class II mRNAs (224 genes have no Puf3p binding site and their asymmetric localization is not affected by the absence of PUF3. In agreement with a co-translational import process, we observed that the presence of puromycin loosens the interactions between most of the MLR-mRNAs and mitochondria. Unexpectedly, cycloheximide, supposed to solidify translational complexes, turned out to destabilize a class of mRNA-mitochondria interactions. Classes I and II mRNAs, which are therefore transported to the mitochondria through different pathways, correlated with different functional modules. Indeed, Class I genes code principally for the assembly factors of respiratory chain complexes and the mitochondrial translation machinery (ribosomes and translation regulators. Class II genes encode proteins of the respiratory chain or proteins involved in metabolic pathways. Thus, MLR, which is intimately linked to translation control, and the activity of mRNA-binding proteins like Puf3p, may provide the conditions for a fine spatiotemporal control of mitochondrial protein import and mitochondrial protein complex assembly. This work therefore provides new openings

  10. 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.

    Science.gov (United States)

    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.

  11. Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis.

    Science.gov (United States)

    Budak, Ferah; Bal, Salih Haldun; Tezcan, Gulcin; Akalın, Halis; Goral, Guher; Oral, Haluk Barbaros

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10-30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.

  12. 99Tcm-3P4-RGD2 SPECT显像对孤立性肺结节的诊断价值%Diagnostic value of solitary pulmonary nodules using 99Tcm-3P4-RGD2 scintigraphy

    Institute of Scientific and Technical Information of China (English)

    孙昱; 王任婕; 高识; 纪铁凤; 纪滨; 贾兵; 戚良晨; 马庆杰

    2013-01-01

    Objective To investigate the value of 99Tcm-HYNIC-(poly-(ethylene glycol),PEG) 4-E (PEG4-c(RGDfK))2 (99Tcm-3P4-RGD2) SPECT imaging in the diagnosis of SPN by visual and semiquantitative analysis.Methods Twenty-one patients (13 men,8 women; age range 37-77 (58±11) years)with SPN observed on CT were analyzed prospectively.All patients underwent SPECT imaging after administration of 99Tcm-3P4-RGD2 with a dose of (939 ± 118) MBq.The gold standard was based on the histopathological diagnosis of the surgical samples from all recruited patients.The diagnostic performance of CT,SPECT visual and semiquantitative analysis was compared and analyzed with ROC curves.Immunohistochemistry was performed in part of the samples to obtain the information of integrin αvβ3 expression.Informed consent was obtained from all patients.Application of a new radiopharmaceutical was permitted and approved by the local independent Ethics Committee and the Institutional Review Board of the China-Japan Union Hospital.One-way analysis of variance,two-sample t test were used with SPSS 13.0.Results Among the 21 SPN patients,15 cases (71%) were diagnosed as malignant,and the other 6 (29%) were benign.T/NT ratio in malignant SPN was higher than that in benign SPN (1.87 ± 0.39 vs 1.41 ± 0.65),but with no statistical significance (t =2.01,P > 0.05).The sensitivities for CT,SPECT visual and semiquantitative analysis were 80% (12/15),100% (15/15) and 100% (15/15) respectively,and the specificity were all 4/6.The AUC was 0.811 (95% CI 58%-95%) for CT,0.833 (95% CI 61%-96%) for SPECT and 0.844 (95% CI 62%-96%) for T/NT ratios,which showed no statistical significance (F =0.83,P >0.05).Immunohistochemistry confirmed αvβ3 expression in both the malignant and benign nodules which had uptake of 99Tcm-3P4-RGD2 in SPECT imaging.Conclusion SPECT visual and semiquantitative analysis with 99Tcm-3P4-RGD2 appears to have high sensitivity and consistency in diagnosis of SPN

  13. O(3P)+HBr(DBr)反应的含时量子散射计算%Time-dependent Quantum Scattering Calculation of the O(3P)+HBr(DBr) Reaction

    Institute of Scientific and Technical Information of China (English)

    左国平; 唐壁玉; 韩克利

    2005-01-01

    An exact three-dimensional time-dependent quantum wave packet was employed to calculate the O(3P) +HBr(DBr) reaction using a generalized London-Ering-Polanyi-Sato(LEPS) potential energy surface. The results showed that vibrational excitation is effective for the reaction, and rotational excitation has an orientational effect in definite energy range. The rate constants and the reaction cross sections for the title reactions have been computed, the calculated rate constants ko+HBr agreed well with experimental data. By comparing with relevant results, it can be found that the kinetic isotopic effects of the reaction are relatively obvious.%基于LEPS势能面,用三维含时量子波包法对O(3P)+HBr(DBr)反应进行了准确的动力学计算.计算的结果表明,振动激发对这个反应是有效的,而转动激发在某一能量范围内具有方位效应.计算得到了该反应的速率常数和反应截面,速率常数kO+HBr的计算值同实验值符合得很好.通过对相应结果的对比,可以发现这个反应具有比较明显的同位素效应.

  14. Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis

    Science.gov (United States)

    Budak, Ferah; Bal, Salih Haldun; Tezcan, Gulcin; Akalın, Halis; Goral, Guher

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis. PMID:27722176

  15. Dynamics of carbon-hydrogen and carbon-methyl exchanges in the collision of 3P atomic carbon with propene

    Science.gov (United States)

    Lee, Shih-Huang; Chen, Wei-Kan; Chin, Chih-Hao; Huang, Wen-Jian

    2013-11-01

    We investigated the dynamics of the reaction of 3P atomic carbon with propene (C3H6) at reactant collision energy 3.8 kcal mol-1 in a crossed molecular-beam apparatus using synchrotron vacuum-ultraviolet ionization. Products C4H5, C4H4, C3H3, and CH3 were observed and attributed to exit channels C4H5 + H, C4H4 + 2H, and C3H3 + CH3; their translational-energy distributions and angular distributions were derived from the measurements of product time-of-flight spectra. Following the addition of a 3P carbon atom to the C=C bond of propene, cyclic complex c-H2C(C)CHCH3 undergoes two separate stereoisomerization mechanisms to form intermediates E- and Z-H2CCCHCH3. Both the isomers of H2CCCHCH3 in turns decompose to C4H5 + H and C3H3 + CH3. A portion of C4H5 that has enough internal energy further decomposes to C4H4 + H. The three exit channels C4H5 + H, C4H4 + 2H, and C3H3 + CH3 have average translational energy releases 13.5, 3.2, and 15.2 kcal mol-1, respectively, corresponding to fractions 0.26, 0.41, and 0.26 of available energy deposited to the translational degrees of freedom. The H-loss and 2H-loss channels have nearly isotropic angular distributions with a slight preference at the forward direction particularly for the 2H-loss channel. In contrast, the CH3-loss channel has a forward and backward peaked angular distribution with an enhancement at the forward direction. Comparisons with reactions of 3P carbon atoms with ethene, vinyl fluoride, and vinyl chloride are stated.

  16. The effects of surface temperature on the gas-liquid interfacial reaction dynamics of O(3P)+squalane

    Science.gov (United States)

    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.

  17. Intrinsic product polarization and branch ratio in the S(1D, 3P)+HD reaction on three electronic states

    Science.gov (United States)

    Li, Lin; Dong, Shunle

    2016-09-01

    The intrinsic product polarization and intramolecular isotope effect of the S(1D, 3P)+HD reaction have been investigated on both the lowest singlet state (1A‧) and the triplet state (3A‧ and 3A″) potential energy surfaces by using quasi-classical trajectory and quantum mechanical methods. The calculations indicate that intramolecular isotope effects are different on the three electronic states. The stereodynamics study shows that the P(θr) distributions, P(ϕr) distributions, and polarization-dependent differential cross sections (PDDCSs) (00) are sensitive to mass factor and the product angular momentum vectors are not only aligned but also oriented.

  18. The yeast antiviral proteins Ski2p, Ski3p, and Ski8p exist as a complex in vivo.

    OpenAIRE

    Brown, J. T.; Bai, X.; Johnson, A. W.

    2000-01-01

    The yeast superkiller (SKI) genes were originally identified from mutations allowing increased production of killer toxin encoded by M "killer" virus, a satellite of the dsRNA virus L-A. XRN1 (SKI1) encodes a cytoplasmic 5'-exoribonuclease responsible for the majority of cytoplasmic RNA turnover, whereas SKI2, SKI3, and SKI8 are required for normal 3'-degradation of mRNA and for repression of translation of poly(A) minus RNA. Ski2p is a putative RNA helicase, Ski3p is a tetratricopeptide repe...

  19. Attosecond time delay in the photoionization of Mn in the $3p \\rightarrow 3d$ giant resonance region

    CERN Document Server

    Dolmatov, V K; Deshmukh, P C; Manson, S T

    2014-01-01

    The dramatic effect of the $3p \\rightarrow 3d$ giant autoionization resonance on time delay of photoemission from the $3d$ and $4s$ valence subshells of the Mn atom is unraveled. Strong sensitivity of the time delay of the $4s$ photoemission to the final-state term of the ion-remainder [${\\rm Mn^{+}}(4s^{1},$$^{5}S)$ vs. ${\\rm Mn^{+}}(4s^{1},$$^{7}S)$] is discovered. The features of time delay uncovered in Mn photoionization are expected to be general properties of transition-metal atoms and ions. The "spin-polarized" random phase approximation with exchange was employed in the study.

  20. miR-187-3p inhibits the metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting S100A4.

    Science.gov (United States)

    Dou, Changwei; Liu, Zhikui; Xu, Meng; Jia, Yuli; Wang, Yufeng; Li, Qing; Yang, Wei; Zheng, Xin; Tu, Kangsheng; Liu, Qingguang

    2016-10-28

    miR-187-3p, a novel cancer-related microRNA, was previously reported to play promoting or suppressive roles in different malignancies. However, the expression level, biological function, and underlying mechanisms of miR-187-3p in hepatocellular carcinoma (HCC) remain unknown. This study demonstrated that miR-187-3p was significantly down-regulated in HCC tissues and cell lines, and was associated with advanced TNM stage and metastasis in HCC. Functional studies confirmed that miR-187-3p could inhibit the metastasis of HCC both in vitro and in vivo. Moreover, we proved that miR-187-3p could prevent the epithelial-mesenchymal transition (EMT) of HCC cells. Mechanically, S100A4 was a direct downstream target of miR-187-3p, and mediated the functional influence of miR-187-3p in HCC. Furthermore, miR-187-3p and S100A4 expression was evidently correlated with adverse clinical features and poor prognosis of HCC. Lastly, we showed that hypoxia was responsible for the significantly decreased level of miR-187-3p in HCC, and miR-187-3p was involved in the promoting effects of hypoxia on the metastasis and EMT of HCC cells. Taken together, miR-187-3p inhibits the metastasis and EMT in HCC by targeting S100A4. miR-187-3p can serve as a prognostic indicator and a promising therapeutic target for HCC patients.

  1. Identification of an amphipathic helix important for the formation of ectopic septin spirals and axial budding in yeast axial landmark protein Bud3p.

    Science.gov (United States)

    Guo, Jia; Gong, Ting; Gao, Xiang-Dong

    2011-03-08

    Correct positioning of polarity axis in response to internal or external cues is central to cellular morphogenesis and cell fate determination. In the budding yeast Saccharomyces cerevisiae, Bud3p plays a key role in the axial bud-site selection (axial budding) process in which cells assemble the new bud next to the preceding cell division site. Bud3p is thought to act as a component of a spatial landmark. However, it is not clear how Bud3p interacts with other components of the landmark, such as the septins, to control axial budding. Here, we report that overexpression of Bud3p causes the formation of small septin rings (∼1 µm in diameter) and arcs aside from previously reported spiral-like septin structures. Bud3p closely associates with the septins in vivo as Bud3p colocalizes with these aberrant septin structures and forms a complex with two septins, Cdc10p and Cdc11p. The interaction of Bud3p with the septins may involve multiple regions of Bud3p including 1-858, 850-1220, and 1221-1636 a.a. since they all target to the bud neck but exhibit different effects on septin organization when overexpressed. In addition, our study reveals that the axial budding function of Bud3p is mediated by the N-terminal region 1-858. This region shares an amphipathic helix (850-858) crucial for bud neck targeting with the middle portion 850-1103 involved in the formation of ectopic septin spirals and rings. Interestingly, the Dbl-homology domain located in 1-858 is dispensable for axial bud-site selection. Our findings suggest that multiple regions of Bud3p ensure efficient targeting of Bud3p to the bud neck in the assembly of the axial landmark and distinct domains of Bud3p are involved in axial bud-site selection and other cellular processes.

  2. MiR-338-3p targets pyruvate kinase M2 and affects cell proliferation and metabolism of ovarian cancer

    OpenAIRE

    Zhang, Yuting; Shi, Bing; Chen, Jiang; Hu, Lina; Zhao, Chunquan

    2016-01-01

    MiR-338-3p is down-regulated in cancer, which inhibits cancer cell proliferation, metastasis, and increases chemosensitivity, but its functions in ovarian cancer remains unknown. The present study aims to identify the miR-338-3p targeted genes and to investigate the associated regulatory mechanisms in ovarian cancer cell proliferation and metabolism. Our results demonstrated miR-338-3p expression was down-regulated in most of ovarian cancer tissues and cell lines. Restoration of miR-338-3p ex...

  3. miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells

    DEFF Research Database (Denmark)

    Rasmussen, Mads Heilskov; Lyskjær, Iben; Jersie-Christensen, Rosa Rakownikow;

    2016-01-01

    Oxaliplatin resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Herein, we show that miR-625-3p functionally induces oxaliplatin resistance in CRC cells, and identify the...... as one likely mechanism of oxaliplatin resistance. Our study shows that miR-625-3p induces oxaliplatin resistance by abrogating MAP2K6-p38-regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p....

  4. White light generation from Dy3+-doped ZnO-B2O3-P2O5 glasses

    Science.gov (United States)

    Jayasimhadri, M.; Jang, Kiwan; Lee, Ho Sueb; Chen, Baojiu; Yi, Soung-Soo; Jeong, Jung-Hyun

    2009-07-01

    Dysprosium doped ZnO-B2O3-P2O5 (ZBP) glasses were prepared by a conventional melt quenching technique in order to study the luminescent properties and their utility for white light emitting diodes (LEDs). X-ray diffraction spectra revealed the amorphous nature of the glass sample. The present glasses were characterized by infrared and Raman spectra to evaluate the vibrational features of the samples. The emission and excitation spectra were reported for the ZBP glasses. Strong blue (484 nm) and yellow (574 nm) emission bands were observed upon various excitations. These two emissions correspond to the F49/2→H615/2 and F49/2→H613/2 transitions of Dy3+ ions, respectively. Combination of these blue and yellow bands gives white light to the naked eye. First time, it was found that ZnO-B2O3-P2O5 glasses efficiently emit white light under 400 and 454 nm excitations, which are nearly match with the emissions of commercial GaN blue LEDs and InGaN LED, respectively. CIE chromaticity coordinates also calculated for Dy3+: ZBP glasses to evaluate the white light emission.

  5. Yeast Agp2p and Agp3p function as amino acid permeases in poor nutrient conditions.

    Science.gov (United States)

    Schreve, James L; Garrett, Jinnie M

    2004-01-16

    The gene AGP2 and the ORF YFL055w (here named AGP3) are classified as members of the yeast amino acid permease gene family. Analysis of the growth of multiply-mutant strains in which these genes are disrupted shows that both encode permeases capable of supplying branched chain, and other, amino acids as nitrogen source. Both Agp2p and Agp3p are low affinity permeases for leucine (Kmapp 0.2-0.5 mM) and are expressed at lower levels than other permeases on all media tested. Thus, it appears that these two permeases can function as low affinity, relatively non-specific, permeases with redundant functions in the cell. Transcription of AGP2 and AGP3 is very low but is increased in cells lacking other functional general amino acid permeases (Gap1p or Agp1p). These results suggest Agp2p and Agp3p function in amino acid transport when nitrogen sources are limiting and/or other permeases are inactive.

  6. PI3P 和 NO 在 UV-B 诱导蚕豆气孔关闭中的关系%The interactions of PI3P and NO in UV-B-induced stomatal closure of broad bean

    Institute of Scientific and Technical Information of China (English)

    樊彩明; 王静; 胡洁; 贺军民

    2015-01-01

    By stomatal bioassay and measurement of endogenous nitric oxide (NO)level in guard cells,the interactions of NO and phosphatidylinositol 3-phosphate (PI3P)[the product of phos-phatidylinositol 3-kinase (PI3K)]in UV-B-induced stomatal closure were studied in the epidermal strips of abaxial surface of broad bean(Vicia faba L.)leaves.The results showed that both the NO production in guard cells and stomatal closure induced by UV-B were significantly inhibited by PI3K inhibitors wortmannin (WM)and LY294002 (LY).Meanwhile,exogenous NO-relea-sing compound sodium nitroprusside (SNP)could completely reverse the inhibitory effect of LY and WM on the UV-B-induced stomatal closure,and WM and LY could not inhibit exogenous SNP-induced stomatal closure of broad bean.These results indicate that PI3P acts upstream of NO in the signal transduction pathway of UV-B-induced stomatal closure of broad bean.%以蚕豆(Vicia faba L.)叶片下表皮为材料,结合气孔开度分析和保卫细胞内源一氧化氮(NO)水平的测定,研究了 NO 和磷脂酰肌醇3-激酶(PI3K)的催化产物磷脂酰肌醇3-磷酸(PI3P)在紫外线 B(UV-B)诱导气孔关闭中的关系。结果显示:UV-B 辐射诱导蚕豆保卫细胞 NO 产生和气孔关闭的效应能被 PI3K 抑制剂沃曼青霉素(WM)和 LY294002(LY)显著抑制。同时,外源 NO释放剂硝普钠(SNP)处理能完全逆转 WM 和 LY 对 UV-B 诱导气孔关闭的抑制效应,而 WM 和LY 却不能抑制外源 SNP 诱导蚕豆气孔关闭的效应。结果说明,在 UV-B 诱导蚕豆气孔关闭的信号转导途径中 PI3P 的作用在 NO 上游。

  7. A study of angle-resolved photoemission extended fine structure as applied to the Ni 3p, Cu 3s, and Cu 3p core levels of the respective clean (111) surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Huff, W.R.A.; Moler, E.J.; Kellar, S.A. [Lawrence Berkeley National Lab., CA (United States)] [and others

    1997-04-01

    The first non-s initial state angle-resolved photoemission extended fine structure (ARPEFS) study of clean surfaces for the purpose of further understanding the technique is reported. 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 in the same plane as the emitters and double-scattering events. Using a newly 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 known contraction of the first two Cu(111) layers is confirmed. The best-fit calculation for clean Ni(111) indicates an expansion of the first two layers. To better understand the ARPEFS technique, the authors studied s and non-s initial state photoemission from clean metal surfaces.

  8. THE FUNGAL HYDROPHOBIN SC3P SELF-ASSEMBLES AT THE SURFACE OF AERIAL HYPHAE AS A PROTEIN MEMBRANE CONSTITUTING THE HYDROPHOBIC RODLET LAYER

    NARCIS (Netherlands)

    WOSTEN, HAB; ASGEIRSDOTTIR, SA; KROOK, JH; DRENTH, JHH; WESSELS, JGH

    1994-01-01

    The Schizophyllum commune hydrophobin Sc3p is a small, hydrophobic, cysteine-rich protein involved in the formation of aerial hyphae. Using an antibody against purified Sc3p we found that the hydrophobin is secreted into the medium at the spices of growing submerged hyphae but in emerging aerial hyp

  9. Reactions of R(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)]. A general and efficient entry to phosphanylphosphinidene complexes of platinum. Syntheses and structures of [(eta(2)-P=(i)Pr(2))Pt(p-Tol(3)P)(2)], [(eta(2)-P=(t)Bu(2))Pt(p-Tol(3)P)(2)], [{eta(2)-P=(N(i)Pr(2))(2)}Pt(p-Tol(3)P)(2)] and [{(Et(2)PhP)(2)Pt}(2)P(2)].

    Science.gov (United States)

    Domańska-Babul, Wioleta; Chojnacki, Jaroslaw; Matern, Eberhard; Pikies, Jerzy

    2009-01-07

    The reactions of lithium derivatives of diphosphanes R(2)P-P(SiMe(3))Li (R = (t)Bu, (i)Pr, Et(2)N and (i)Pr(2)N) with [(R'(3)P)(2)PtCl(2)] (R'(3)P = Et(3)P, Et(2)PhP, EtPh(2)P and p-Tol(3)P) proceed in a facile manner to afford side-on bonded phosphanylphosphinidene complexes of platinum [(eta(2)-P=R(2))Pt(PR'(3))(2)]. The related reactions of Ph(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)] did not yield [(eta(2)-P=PPh(2))Pt(PR'(3))(2)] and resulted mainly in the formation of [{(R'(3)P)(2)Pt}(2)P(2)], Ph(2)P-PLi-PPh(2), (Me(3)Si)(2)PLi and (Me(3)Si)(3)P. Crystallographic data are reported for the compounds [(eta(2)-P=R(2))Pt(p-Tol(3)P)(2)] (R = (t)Bu, (i)Pr, ((i)Pr(2)N)(2)P) and for [{(Et(2)PhP)(2)Pt}(2)P(2)].

  10. Neanderthal introgression at chromosome 3p21.31 was under positive natural selection in East Asians.

    Science.gov (United States)

    Ding, Qiliang; Hu, Ya; Xu, Shuhua; Wang, Jiucun; Jin, Li

    2014-03-01

    Studies of the Neanderthal and Denisovan genomes demonstrate archaic hominin introgression in Eurasians. Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans. We also detected a signal of strong positive selection in this region only in East Asians. Our data indicate that likely candidate targets of selection include rs12488302-T and its associated alleles--among which four are nonsynonymous, including rs35455589-G in HYAL2, a gene related to the cellular response to ultraviolet-B irradiation. Furthermore, suggestive evidence supports latitude-dependent selection, implicating a role of ultraviolet-B. Interestingly, the distribution of rs35455589-G suggests that this allele was lost during the exodus of ancestors of modern Eurasians from Africa and reintroduced to Eurasians from Neanderthals.

  11. Kinetics and thermodynamic behavior of WO{sub 3} and WO{sub 3}:P thin films

    Energy Technology Data Exchange (ETDEWEB)

    Avellaneda, Cesar O.; Bulhoes, Luis O.S. [Laboratorio Interdisciplinar de Eletroquimica e Ceramica-LIEC, Departamento de Quimica, Universidade Federal de Sao Carlos, C.P. 676, CEP 13565-905, Sao Carlos-SP (Brazil)

    2006-03-06

    There is a considerable interest in the research and development of materials and devices, that can be used for optical switching of large-scale glazings. Several potential switching technologies are available for glazings, including those based on electrochromic, thermochromic and photochromic phenomena. One of the most promising technologies for optical switching devices is electrochromism (EC). In order to improve the electrochromic properties of tungsten oxide, we have investigated the effect of phosphorous insertion on the electrochromic behavior of oxide films prepared by the sol-gel process. The kinetics and thermodynamics of electrochemical intercalation of lithium into Li{sub x}WO{sub 3} and Li{sub x}WO{sub 3}:P films prepared by the sol-gel process were investigated. The standard Gibbs energy for lithium intercalation was calculated. The chemical diffusion coefficients, D, of lithium intercalation into oxide, were measured by galvanostatic intermittent titration technique (GITT), as functions of the depth of lithium intercalation. (author)

  12. Magnetic control of ultra-cold $^6$Li and $^{174}$Yb($^3P_2$) atom mixtures with Feshbach resonances

    CERN Document Server

    Petrov, Alexander; Kotochigova, Svetlana

    2015-01-01

    We theoretically evaluate the feasibility to form magnetically-tunable Feshbach molecules in collisions between fermionic $^6$Li atoms and bosonic metastable $^{174}$Yb($^3$P$_2$) atoms. In contrast to the well-studied alkali-metal atom collisions, collisions with meta-stable atoms are highly anisotropic. Our first-principle coupled-channel calculation of these collisions reveals the existence of broad Feshbach resonances due to the combined effect of anisotropic-molecular and atomic-hyperfine interactions. In order to fit our predictions to the specific positions of experimentally-observed broad resonance structures \\cite{Deep2015} we optimized the shape of the short-range potentials by direct least-square fitting. This allowed us to identify the dominant resonance by its leading angular momentum quantum numbers and describe the role of collisional anisotropy in the creation and broadening of this and other resonances.

  13. Photoconductivity of novel poly(N-vinyl)-3-[p-nitrophenylazo]carbazole/CdS-nanoparticle polymer composite

    Institute of Scientific and Technical Information of China (English)

    DING Li-yun; JIANG De-sheng; HUANG Jun; DAI Lei; LIU Cheng; WANG Jun-tao; LI Bin

    2006-01-01

    The photoconductive characteristic of the inorganic/organic hybridized polymer system is reported,in which a novel bi-functional photorefractive (PR) poly(N-vinyl)-3-[p-nitrophenylazo]carbazole (PVNPAK) serves as a polymeric charge-transporting and second-order nonliner optical matrix and quantum dots composed of surface passivated cadmium sulfide serve as a charge-generation sensitizer. The hybrid PVNPAK/CdS-nanoparticles polymer composites with different mass ratio of CdS to PVNPAK were prepared. The generation of photocurrent on illumination and photoconductive properties of the PVNPAK/CdS-nanoparticles polymer composites were studied. The results show that the addition of CdS nanoparticle as a photosensitizer can enhance the photoconductivity of the PVNPAK significantly because of the properties of the high quantum efficiency of photosensitization and high charge transport to conducting polymer.

  14. Spin-orbit and rotational couplings in radiative association of C(3P) and N(4S) atoms.

    Science.gov (United States)

    Antipov, Sergey V; Gustafsson, Magnus; Nyman, Gunnar

    2011-11-14

    The role of spin-orbit and rotational couplings in radiative association of C((3)P) and N((4)S) atoms is investigated. Couplings among doublet electronic states of the CN radical are considered, giving rise to a 6-state model of the process. The solution of the dynamical problem is based on the L(2) method, where a complex absorbing potential is added to the Hamiltonian operator in order to treat continuum and bound levels in the same manner. Comparison of the energy-dependent rate coefficients calculated with and without spin-orbit and rotational couplings shows that the couplings have a strong effect on the resonance structure and low-energy baseline of the rate coefficient.

  15. Localization of the human {beta}-catenin gene (CTNNB1) to 3p21: A region implicated in tumor development

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, C.; Liehr, T.; Ballhausen, G. [Institut fuer Humangenetik der Universitaet, Erlangen (Germany)] [and others

    1994-09-01

    The human {beta}-catenin locus (CTNNB1) was mapped by in situ fluorescence analysis to band p21 on the short arm of chromosome 3, a region frequently affected by somatic alterations in a variety of tumors. PCR primers for the genomic amplification of {beta}-catenin sequences were selected on the basis of homology to exon 4 of the Drosophila armadillo gene. Analysis of a panel of somatic cell hybrids confirmed the localization of {beta}-catenin on human chromosome 3. Furthermore, exclusion mapping of three hybrids carrying defined fragments of the short arm of human chromosome 3 allowed us to determine the position of the CTNNB1 locus close to the marker D3S2 in 3p21. 22 refs., 3 figs.

  16. Atomic scattering in the diffraction limit: electron transfer in keV Li+-Na(3s, 3p) collisions

    DEFF Research Database (Denmark)

    Poel, Mike van der; Nielsen, C.V.; Rybaltover, M.;

    2002-01-01

    . This setup yields a momentum resolution of 0.12 an, an order of magnitude better angular resolution than previous measurements on this system. This enables us to clearly resolve Fraunhofer-type diffraction patterns in the angle DCS. In particular, the angular width of the ring structure is given by the ratio...... of the de Broglie wavelength lambda(dB) = 150 fm at a velocity v = 0.20 au and the effective atomic diameter for electron capture 2R = 20 au. Parallel AO and MO semiclassical coupled-channel calculations of the Na(3s, 3p) --> Li(2s, 2p) state-to-state collision amplitudes have been performed, and quantum...

  17. The C(3P) + NH3 reaction in interstellar chemistry: I. Investigation of the product formation channels

    CERN Document Server

    Bourgalais, Jeremy; Kailasanathan, Ranjith Kumar Abhinavam; Osborn, David L; Hickson, Kevin M; Loison, Jean-Christophe; Wakelam, Valentine; Goulay, Fabien; Picard, Sébastien D Le

    2016-01-01

    The product formation channels of ground state carbon atoms, C(3P), reacting with ammonia, NH3, have been investigated using two complementary experiments and electronic structure calculations. Reaction products are detected in a gas flow tube experiment (330 K, 4 Torr) using tunable VUV photoionization coupled with time of flight mass spectrometry. Temporal profiles of the species formed and photoionization spectra are used to identify primary products of the C + NH3 reaction. In addition, H-atom formation is monitored by VUV laser induced fluorescence from room temperature to 50 K in a supersonic gas flow generated by the Laval nozzle technique. Electronic structure calculations are performed to derive intermediates, transition states and complexes formed along the reaction coordinate. The combination of photoionization and laser induced fluorescence experiments supported by theoretical calculations indicate that in the temperature and pressure range investigated, the H + H2CN production channel represents ...

  18. Detection of S1-P1 and S3-P3 interactions between papain and four synthetic substrates

    Directory of Open Access Journals (Sweden)

    Emmanuel M Papamichael

    1999-01-01

    Full Text Available In this study, the S1 - P1 and S3 - P3 interactions between papain and four synthetic peptide substrates were found as to be important. The values of Km were estimated as to be practically identical between these substrates; this latter is supporting the conclusions obtained by considering the estimated values of other kinetic parameters. Nevertheless, based on the estimated kcat and/or k cat/Km parameters of the used substrates, we concluded that an aromatic ring at the P3 position, and a positively charged side chain of the residue at the P1 position of the synthetic substrates were favored considerably their interaction with papain.Neste estudo, o S1 - P1 e S3 - P3, interações entre papaina e quatro substratos sintéticos de pepetídios foram considerados importantes. Os valores de Km foram estimados e são praticamente idênticos entre esses substratos; Isso dá suporte as conclusões obtidas, considerando os valores parâmetros cinéticos estimados. No obstante, baseou na estimação parâmetros kcat e/ou k cat /Km dos substratos utilizados. Se pode concluir que um anel aromático na posição P3, e uma corrente carregada positivamente da cadeia do resíduo na posição P1 dos substratos sintéticos favoreceram interação com a papaina.

  19. Bonding and Site Preferences in the New Quasi-Binary Zr 2.7Hf 11.3P 9

    Science.gov (United States)

    Kleinke, Holger; Franzen, Hugo F.

    1998-03-01

    The new quasi-binary Zr 2.7Hf 11.3P 9was synthesized by arc-melting of Zr, Hf, Co, and HfP in a ratio corresponding to the initial composition "Zr 2.25Hf 6.75Co 2P 4". Zr 2.7Hf 11.3P 9crystallizes in the Zr 14P 9structure type, which is unknown in the binary Hf/P system. The ideal orthorhombic lattice dimensions (space group Pnnm(No. 58), Z=4) were refined to a=16.640(7) Å, b=27.40(2) Å, c=3.619(1) Å, V=1650(2) Å 3. The structure consists of three-dimensional condensed one-, two-, and three-capped trigonal (Zr, Hf) 6P prisms, occurring with numerous short M- Mbonds ( M=Zr, Hf). Each of the 15 metal sites is statistically occupied by a mixture of Zr and Hf, which varies significantly from site to site. The Hf/Zr ratio in a given site depends on the M- Mand M-P interactions. The systematic increase of this ratio with increasing total bond order, as evaluated via Mulliken overlap populations and Pauling bond orders, can be understood based on the trend that Hf forms stronger M- Mand M-P bonds than Zr. As expected for a metal-rich phosphide, band structure calculations for the hypothetical "Hf 14P 9" carried out with the extended Hückel approximation result in a significant density of states at the Fermi level.

  20. Major weapon system environmental life-cycle cost estimating for Conservation, Cleanup, Compliance and Pollution Prevention (C3P2)

    Science.gov (United States)

    Hammond, Wesley; Thurston, Marland; Hood, Christopher

    1995-01-01

    The Titan 4 Space Launch Vehicle Program is one of many major weapon system programs that have modified acquisition plans and operational procedures to meet new, stringent environmental rules and regulations. The Environmental Protection Agency (EPA) and the Department of Defense (DOD) mandate to reduce the use of ozone depleting chemicals (ODC's) is just one of the regulatory changes that has affected the program. In the last few years, public environmental awareness, coupled with stricter environmental regulations, has created the need for DOD to produce environmental life-cycle cost estimates (ELCCE) for every major weapon system acquisition program. The environmental impact of the weapon system must be assessed and budgeted, considering all costs, from cradle to grave. The Office of the Secretary of Defense (OSD) has proposed that organizations consider Conservation, Cleanup, Compliance and Pollution Prevention (C(sup 3)P(sup 2)) issues associated with each acquisition program to assess life-cycle impacts and costs. The Air Force selected the Titan 4 system as the pilot program for estimating life-cycle environmental costs. The estimating task required participants to develop an ELCCE methodology, collect data to test the methodology and produce a credible cost estimate within the DOD C(sup 3)P(sup 2) definition. The estimating methodology included using the Program Office weapon system description and work breakdown structure together with operational site and manufacturing plant visits to identify environmental cost drivers. The results of the Titan IV ELCCE process are discussed and expanded to demonstrate how they can be applied to satisfy any life-cycle environmental cost estimating requirement.

  1. MiR-291b-3p Induces Apoptosis in Liver Cell Line NCTC1469 by Reducing the Level of RNA-binding Protein HuR

    Directory of Open Access Journals (Sweden)

    Jun Guo

    2014-03-01

    Full Text Available Background: There is increasing evidence that miRNAs are involved in cellular apoptosis. However, the specific role of miR-291b-3p in apoptosis has not been elucidated. In the present study, we investigated the effect of miR-291b-3p on NCTC1469 cell growth and apoptosis. Methods: Cell viability and apoptosis were examined in NCTC1469 cells transfected with miR-291b-3p mimics, inhibitor miRNA or negative control. Using computational miRNA target prediction databases, HuR was predicted as a target of miR-291b-3p. Luciferase assay, immunofluorescence and western blot were used to further explore the effects of miR-291b-3p on HuR expression. In addition, the effect of HuR on cell apoptosis was evaluated using a HuR-specific siRNA. Results: TNF-α-induced hepatocyte apoptosis was accompanied by enhanced expression of miR-291b-3p, suggesting that miR-291b-3p might contribute to the apoptotic process. Follow-up experiments showed that upregulation of miR-291b-3p decreased cell viability and induced NCTC1469 cell apoptosis. Additionally, similar to the activity of miR-519, which is another member of the same miRNA family, miR-291b-3p suppressed HuR translation through binding to the HuR coding region (CR. We further showed that the downregulation of HuR expression by miR-291b-3p was accompanied by reduced Bcl-2 expression. Moreover, knockdown of HuR also impaired Bcl-2 expression and increased the ratio of Bax/Bcl-2. More significantly, downregulation of miR-291b-3p failed to increase Bcl2 expression in NCTC1469 cells that were co-transfected with siRNA-HuR. Finally, inhibition of miR-291b-3p led to reduced apoptosis, while knockdown of HuR by siRNA promoted apoptosis, even in NCTC1469 cells that were co-transfected with the miR-291b-3p inhibitor. Conclusion: The current data suggested that miR-291b-3p contributed to NCTC1469 cell apoptosis by regulating the expression of HuR, which in turn increased Bcl-2 stability.

  2. Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3P critical for the degradation of apoptotic cells.

    Directory of Open Access Journals (Sweden)

    Nan Lu

    2012-01-01

    Full Text Available Phosphatidylinositol 3-phosphate (PtdIns(3P is a signaling molecule important for many membrane trafficking events, including phagosome maturation. The level of PtdIns(3P on phagosomes oscillates in two waves during phagosome maturation. However, the physiological significance of such oscillation remains unknown. Currently, the Class III PI 3-kinase (PI3K Vps34 is regarded as the only kinase that produces PtdIns(3P in phagosomal membranes. We report here that, in the nematode C. elegans, the Class II PI3K PIKI-1 plays a novel and crucial role in producing phagosomal PtdIns(3P. PIKI-1 is recruited to extending pseudopods and nascent phagosomes prior to the appearance of PtdIns(3P in a manner dependent on the large GTPase dynamin (DYN-1. PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3P on phagosomes. Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3P and disables phagosomes from recruiting multiple essential maturation factors, resulting in a complete arrest of apoptotic-cell degradation. We have further identified MTM-1, a PI 3-phosphatase that antagonizes the activities of PIKI-1 and VPS-34 by down-regulating PtdIns(3P on phagosomes. Remarkably, persistent appearance of phagosomal PtdIns(3P, as a result of inactivating mtm-1, blocks phagosome maturation. Our findings demonstrate that the proper oscillation pattern of PtdIns(3P on phagosomes, programmed by the coordinated activities of two PI3Ks and one PI 3-phosphatase, is critical for phagosome maturation. They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.

  3. miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma

    Science.gov (United States)

    Zhang, Hui; Wang, Cheng; Liang, Jianfeng; Chen, Guanhui; Li, Wenqing; Tang, Haikuo

    2017-01-01

    MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.

  4. A novel acquired cryptic three-way translocation t(2;11;5)(p21.3;q13.5;q23.2) with a submicroscopic deletion at 11p14.3 in an adult with hypereosinophilic syndrome.

    Science.gov (United States)

    Kjeldsen, Eigil

    2015-08-01

    Hypereosinophilic syndrome (HES) is a clinically and pathologically heterogeneous disease entity. It is characterized by persistent eosinophilia and organ damage after excluding other causes. Clonal eosinophilia is distinguished from idiopathic eosinophilia by the presence of histologic, cytogenetic, or molecular evidence of an underlying malignancy. There are two distinct subcategories of clonal eosinophilia: chronic eosinophilic leukemia, not otherwise specified and myeloid/lymphoid neoplasms with eosinophilia and mutations involving platelet-derived growth factor receptor α/β or fibroblast growth factor receptor 1. More than 50% of HES are without knowledge of underlying pathogenic molecular pathways. Here we examined a HES patient by oligo-based aCGH analysis and molecular cytogenetic methods. Examination for the common eosinophilia-related cytogenetic abnormalities involving the genes PDGFRA, PDGFRB, and FGFR1 together with BCR-ABL fusion gene was negative. Cytogenetic analysis and multi-color FISH analysis revealed a novel cryptic three-way translocation t(2;11;5)(p21.3;q13.5;q23.2). By oaCGH analysis we could not find any copy number changes related to the cytogenetic breakpoints but instead detected a 0.9Mb submicroscopic deletion at 11p14.3. The deleted region involved the 5'-upstream sequences and exons 1-4 of the LUZP2 gene, which encodes a leucine zipper protein. Analysis of surrogate germ-line cells revealed a normal result showing that the detected chromosomal aberrations were acquired. This is the first report on a HES patient associated with a novel complex three-way translocation t(2;11;5)(p21.3;q13.5;q23.2) and a submicroscopic deletion in chromosome band 11p14.3. The study also demonstrates the benefits of oligo-based aCGH analysis in detecting hidden disease related chromosomal abnormalities. The present findings provide additional clues to unravel important molecular pathways in HES to obtain the full spectrum of acquired chromosomal and

  5. miR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Henry, Jon C. [Department of Surgery, Ohio State University Medical Center, Columbus, OH (United States); Park, Jong-Kook; Jiang, Jinmai; Kim, Ji Hye [College of Pharmacy, Ohio State University, Columbus, OH (United States); Nagorney, David M.; Roberts, Lewis R. [Divisions of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN (United States); Banerjee, Soma [Center for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata (India); Schmittgen, Thomas D., E-mail: Schmittgen.2@osu.edu [College of Pharmacy, Ohio State University, Columbus, OH (United States)

    2010-12-03

    Research highlights: {yields} miR-199a-3p targets CD44 in HCC. {yields} Proliferation and invasion are reduced by miR-199a-3p in CD44+ HCC. {yields} miR-199a-3p is reduced and CD44 protein is increased in HCC tissues. {yields} The duplex form of miR-199a-3p mimetic is required for activity. -- Abstract: Previous work by us and others reported decreased expression of miR-199a-3p in hepatocellular carcinoma (HCC) tissues compared to adjacent benign tissue. We report here a significant reduction of miR-199a-3p expression in 7 HCC cell lines. To determine if miR-199a-3p has a tumor suppressive role, pre-miR-199a-3p oligonucleotides were transfected into the HCC cell lines. Pre-miR-199a-3p oligonucleotide reduced cell proliferation by approximately 60% compared to control oligonucleotide in only two cell lines (SNU449 and SNU423); the proliferation of the other 5 treated cell lines was similar to control oligonucleotide. A pre-miR-199a-3p oligonucleotide formulated with chemical modifications to enhance stability while preserving processing, reduced cell proliferation in SNU449 and SNU423 to the same extent as the commercially available pre-miR-199a-3p oligonucleotide. Furthermore, only the duplex miR-199a-3p oligonucleotide, and not the guide strand alone, was effective at reducing cell viability. Since a CD44 variant was essential for c-Met signaling [V. Orian-Rousseau, L. Chen, J.P. Sleeman, P. Herrlich, H. Ponta, CD44 is required for two consecutive steps in HGF/c-Met signaling, Genes Dev. 16 (2002) 3074-3086] and c-Met is a known miR-199a-3p target, we hypothesized that miR-199a-3p may also target CD44. Immunoblotting confirmed that only the two HCC lines that were sensitive to the effects of pre-miR-199a-3p were CD44+. Direct targeting of CD44 by miR-199a-3p was confirmed using luciferase reporter assays and immunoblotting. Transfection of miR-199a-3p into SNU449 cells reduced in vitro invasion and sensitized the cells to doxorubicin; both effects were enhanced

  6. MicroRNA-219-2-3p functions as a tumor suppressor in gastric cancer and is regulated by DNA methylation.

    Directory of Open Access Journals (Sweden)

    Huizi Lei

    Full Text Available BACKGROUND AIMS: Gastric cancer is the most frequent gastrointestinal tumor in adults and is the most lethal form of human cancer. Despite of the improvements in treatments, the underlying mechanism of gastric carcinogenesis is not well known. To define novel modulators that regulate susceptibility to tumorgenesis, we focused on miR-219-2-3p. METHODS: Quantitative RT-PCR was employed to investigate the level of miR-219-2-3p in gastric cancer (GC tissues (n = 113 and their matched adjacent normal tissues (n = 113. In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate biological effects of miR-219-2-3p. Since silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorgenesis, GC cells were treated with 5-aza-2'-deoxycytidine and trichostatin A, and expression changes of miR-219-2-3p were subsequently examined by quantitative RT-PCR. Finally, the methylation status of CpG island upstream of miR-219-2-3p was analyzed by methylation-specific PCR in GC tissues (n = 22. RESULTS: miR-219-2-3p was down-regulated in GC and cell lines. In addition, the experiments documented the lower expression of miR-219-2-3p in GC specimens with higher grade and later stage tumors. Meanwhile, miR-219-2-3p exerted antiproliferative, proapoptotic, and antimetastatic roles and reduced levels of p-ERK1/2 in GC cells. Furthermore, 5-aza-2'-deoxycytidine and trichostatin A increased the expression (~2 fold of miR-219-2-3p in GC cells. By methylation-specific PCR, DNA methylation in the upstream region of miR-219-2-3p was detected in both adjacent normal tissues and cancer tissues. As expected, the methylation level was considerably higher in the miR-219-2-3p down-regulated group than up-regulated group. CONCLUSIONS: miR-219-2-3p is potentially involved in gastric cancer progression and metastasis by regulating ERK1/2-related signal pathways, which may provide a novel therapeutic strategy

  7. Measurement of the resonance parameters of the chi(1)(1**3P(1)) and chi(2)(1**3P(2)) states of charmonium formed in antiproton-proton annihilations

    Energy Technology Data Exchange (ETDEWEB)

    Andreotti, M.; Bagnasco, S.; Baldini, W.; Bettoni, D.; Borreani, G.; Buzzo, A.; Calabrese, R.; Cester, R.; Cibinetto, G.; Dalpiaz, P.; Garzoglio, G.; Gollwitzer, K.E.; Graham, M.; Hu, M.; Joffe, D.; Kasper, J.; Lasio, G.; Lo Vetere, M.; Luppi, E.; Macri, M.; Mandelkern, M.; /Fermilab /INFN, Ferrara /Ferrara U. /INFN, Genoa /Genoa U. /UC, Irvine

    2005-03-01

    The authors have studied the {sup 3}P{sub J} ({chi}{sub e}) states of charmonium in formation by antiproton-proton annihilations in experiment E835 at the Fermilab Antiproton Source. The authors report new measurements of the mass, width, and B({chi}{sub cJ} {yields} {bar p}p) x {Lambda}({chi}{sub eJ} {yields} J/{psi} + anything) for the {chi}{sub c1} and {chi}{sub c2} by means of the inclusive reaction {bar p}p {yields} {chi}{sub cJ} {yields} J/{psi} + anything {yields} (e{sup +}e{sup -}) + anything. Using the subsample of events where {chi}{sub cJ} {yields} {gamma} + J/{psi} {yields} {gamma} + (e{sup +}e{sup -}) is fully reconstructed, we derive B({chi}{sub cJ} {yields} {bar p}p) x {Lambda}({chi}{sub cJ} {yields} J/{psi} + {gamma}). They summarize the results of the E760 (updated) and E835 measurements of mass, width and B({chi}{sub cJ} {yields} {bar p}p){Lambda}({chi}{sub cJ} {yields} J/{psi} + {gamma}) (J = 0,1,2) and discuss the significance of these measurements.

  8. Diffusion welding process of submicron aluminium matrix composite Al2O3p/6061 Al%亚微米级Al2O3p/6061Al铝基复合材料扩散焊接工艺

    Institute of Scientific and Technical Information of China (English)

    刘黎明; 高振坤; 董长富; 韩文波

    2004-01-01

    以亚微米级Al2O3p/6061 Al铝基复合材料为对象,研究了直接扩散焊与采用中间层扩散焊两种工艺焊接铝基复合材料的特点、机理,分析了中间层对接头强度的影响规律.结果表明,在铝基复合材料液、固温度区间,存在"临界温度区域",在此温度区域进行直接扩散焊接时,通过液相基体金属的浸润,使得在扩散接合面中增强相-增强相接触转化为增强相-基体-增强相的有机结合,获得高质量焊接接头;进一步研究发现,在扩散接合面上采用合适的基体中间层同样可以将增强相-增强相接触转化为增强相-基体-增强相的有机结合,同时增大"临界温度区域"范围,接头性能更加稳定,接头变形量进一步减小(<2%).

  9. miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells

    DEFF Research Database (Denmark)

    Rasmussen, Mads Heilskov; Lyskjær, Iben; Jersie-Christensen, Rosa Rakownikow

    2016-01-01

    the signalling networks affected by miR-625-3p. We show that the p38 MAPK activator MAP2K6 is a direct target of miR-625-3p, and, accordingly, is downregulated in non-responder patients of oxaliplatin therapy. miR-625-3p-mediated resistance is reversed by anti-miR-625-3p treatment and ectopic expression of a mi......R-625-3p insensitive MAP2K6 variant. In addition, reduction of p38 signalling by using siRNAs, chemical inhibitors or expression of a dominant-negative MAP2K6 protein induces resistance to oxaliplatin. Transcriptome, proteome and phosphoproteome profiles confirm inactivation of MAP2K6-p38 signalling...... as one likely mechanism of oxaliplatin resistance. Our study shows that miR-625-3p induces oxaliplatin resistance by abrogating MAP2K6-p38-regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p....

  10. A Feedback Regulatory Loop between G3P and Lipid Transfer Proteins DIR1 and AZI1 Mediates Azelaic-Acid-Induced Systemic Immunity

    Directory of Open Access Journals (Sweden)

    Keshun Yu

    2013-04-01

    Full Text Available Systemic acquired resistance (SAR, a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P. Pathogen inoculation induced the release of free unsaturated fatty acids (FAs and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway.

  11. The miR-24-3p/p130Cas: a novel axis regulating the migration and invasion of cancer cells.

    Science.gov (United States)

    Kang, Hoin; Rho, Jun Gi; Kim, Chongtae; Tak, Hyosun; Lee, Heejin; Ji, Eunbyul; Ahn, Sojin; Shin, A-Ri; Cho, Hyun-Il; Huh, Yun Hyun; Song, Woo Keun; Kim, Wook; Lee, Eun Kyung

    2017-03-24

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. Differential expression of miRNAs is involved in the pathogenesis of several diseases including cancer. Here, we investigated the role of-miR-24-3p as a downregulated miRNA in metastatic cancer. miR-24-3p was decreased in metastatic cancer and lower expression of miR-24-3p was related to poor survival of cancer patients. Consistently, ectopic expression of miR-24-3p suppressed the cell migration, invasion, and proliferation of MCF7, Hep3B, B16F10, SK-Hep1, and PC-3 cells by directly targeting p130Cas. Stable expression of p130Cas restored miR-24-3p-mediated inhibition of cell migration and invasion. These results suggest that miR-24-3p functions as a tumor suppressor and the miR-24-3p/p130Cas axis is a novel factor of cancer progression by regulating cell migration and invasion.

  12. Emergence of a novel equine-like G3P[8] inter-genogroup reassortant rotavirus strain associated with gastroenteritis in Australian children.

    Science.gov (United States)

    Cowley, Daniel; Donato, Celeste M; Roczo-Farkas, Susie; Kirkwood, Carl D

    2016-02-01

    During 2013, a novel equine-like G3P[8] rotavirus emerged as the dominant strain in Australian children with severe rotavirus gastroenteritis. Full genome analysis demonstrated that the strain was an inter-genogroup reassortant, containing an equine-like G3 VP7, a P[8] VP4 and a genogroup 2 backbone I2-R2-C2-M2-A2-N2-T2-E2-H2. The genome constellation of the equine-like G3P[8] was distinct to Australian and global G3P[8] strains. Phylogenetic analysis demonstrated a genetic relationship to multiple gene segments of Japanese strains RVA/JPN/S13-30/2013/G3P[4] and RVA/Human-wt/JPN/HC12016/2012/G1P[8]. The Australian equine-like G3P[8] strain displayed a distinct VP7 antigenic profile when compared with the previously circulating Australian G3P[8] strains. Identification of similar genes in strains from several geographical regions suggested the equine-like G3P[8] strain was derived by multiple reassortment events between globally co-circulating strains from both human and animal sources. This study reinforces the dynamic nature of rotavirus strains and illustrates the potential for novel human/animal reassortant strains to emerge within the human population.

  13. Kinetics of the benzyl + O(3P) reaction: a quantum chemical/statistical reaction rate theory study.

    Science.gov (United States)

    da Silva, Gabriel; Bozzelli, Joseph W

    2012-12-14

    The resonance stabilized benzyl radical is an important intermediate in the combustion of aromatic hydrocarbons and in polycyclic aromatic hydrocarbon (PAH) formation in flames. Despite being a free radical, benzyl is relatively stable in thermal, oxidizing environments, and is predominantly removed through bimolecular reactions with open-shell species other than O(2). In this study the reaction of benzyl with ground-state atomic oxygen, O((3)P), is examined using quantum chemistry and statistical reaction rate theory. C(7)H(7)O energy surfaces are generated at the G3SX level, and include several novel pathways. Transition state theory is used to describe elementary reaction kinetics, with canonical variational transition state theory applied for barrierless O atom association with benzyl. Apparent rate constants and branching ratios to different product sets are obtained as a function of temperature and pressure from solving the time-dependent master equation, with RRKM theory for microcanonical k(E). These simulations indicate that the benzyl + O reaction predominantly forms the phenyl radical (C(6)H(5)) plus formaldehyde (HCHO), with lesser quantities of the C(7)H(6)O products benzaldehyde, ortho-quinone methide, and para-quinone methide (+H), along with minor amounts of the formyl radical (HCO) + benzene. Addition of O((3)P) to the methylene site in benzyl produces a highly vibrationally excited C(7)H(7)O* adduct, the benzoxyl radical, which can β-scission to benzaldehyde + H and phenyl + HCHO. In order to account for the experimental observation of benzene as the major reaction product, a roaming radical mechanism is proposed that converts the nascent products phenyl and HCHO to benzene + HCO. Oxygen atom addition at the ortho and para ring sites in benzyl, which has not been previously considered, is shown to lead to the quinone methides + H; these species are less-stable isomers of benzaldehyde that are proposed as important combustion intermediates, but

  14. MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway.

    Science.gov (United States)

    Mu, Shengzhi; Kang, Bei; Zeng, Weihui; Sun, Yaowen; Yang, Fan

    2016-05-01

    Post-traumatic hypertrophic scar (HS) is a fibrotic disease with excessive extracellular matrix (ECM) production, which is a response to tissue injury by fibroblasts. Although emerging evidence has indicated that miRNA contributes to hypertrophic scarring, the role of miRNA in HS formation remains unclear. In this study, we found that miR-143-3p was markedly downregulated in HS tissues and fibroblasts (HSFs) using qRT-PCR. The expression of connective tissue growth factor (CTGF/CCN2) was upregulated both in HS tissues and HSFs, which is proposed to play a key role in ECM deposition in HS. The protein expression of collagen I (Col I), collagen III (Col III), and α-smooth muscle actin (α-SMA) was obviously inhibited after treatment with miR-143-3p in HSFs. The CCK-8 assay showed that miR-143-3p transfection reduced the proliferation ability of HSFs, and flow cytometry showed that either early or late apoptosis of HSFs was upregulated by miR-143-3p. In addition, the activity of caspase 3 and caspase 9 was increased after miR-143-3p transfection. On the contrary, the miR-143-3p inhibitor was demonstrated to increase cell proliferation and inhibit apoptosis of HSFs. Moreover, miR-143-3p targeted the 3'-UTR of CTGF and caused a significant decrease of CTGF. Western blot demonstrated that Akt/mTOR phosphorylation and the expression of CTGF, Col I, Col III, and α-SMA were inhibited by miR-143-3p, but increased by CTGF overexpression. In conclusion, we found that miR-143-3p inhibits hypertrophic scarring by regulating the proliferation and apoptosis of human HSFs, inhibiting ECM production-associated protein expression by targeting CTGF, and restraining the Akt/mTOR pathway.

  15. Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression

    Science.gov (United States)

    Ye, Jian; Yao, Yufeng; Song, Qixue; Li, Sisi; Hu, Zhenkun; Yu, Yubing; Hu, Changqing; Da, Xingwen; Li, Hui; Chen, Qiuyun; Wang, Qing K.

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant cancers. To elucidate new regulatory mechanisms for heptocarcinogenesis, we investigated the regulation of p21, a cyclin-dependent kinase (CDK) inhibitor encoded by CDKN1A, in HCC. The expression level of p21 is decreased with the progression of HCC. Luciferase assays with a luciferase-p21-3′ UTR reporter and its serial deletions identified a 15-bp repressor element at the 3′-UTR of CDKN1A, which contains a binding site for miR-95-3p. Mutation of the binding site eliminated the regulatory effect of miR-95-3p on p21 expression. Posttranscriptional regulation of p21 expression by miR-95-3p is mainly on the protein level (suppression of translation). Overexpression of miR-95-3p in two different HCC cell lines, HepG2 and SMMC7721, significantly promoted cell proliferation, cell cycle progression and cell migration, whereas a miR-95-3p specific inhibitor decreased cell proliferation, cell cycle progression and cell migration. The effects of miR-95-3p on cellular functions were rescued by overexpression of p21. Overexpression of miR-95-3p promoted cell proliferation and tumor growth in HCC xenograft mouse models. Expression of miR-95-3p was significantly higher in HCC samples than in adjacent non-cancerous samples. These results demonstrate that miR-95-3p is a potential new marker for HCC and regulates hepatocarcinogenesis by directly targeting CDKN1A/p21 expression. PMID:27698442

  16. MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α.

    Directory of Open Access Journals (Sweden)

    Haitao Xu

    Full Text Available Hypoxia is a common feature of solid tumors and an important contributor to anti-tumor drug resistance. Hypoxia inducible factor-1 (HIF-1 is one of the key mediators of the hypoxia signaling pathway, and was recently proven to be required for sorafenib resistance in hepatocarcinoma (HCC. MicroRNAs have emerged as important posttranslational regulators in HCC. It was reported that miR-338-3p levels are associated with clinical aggressiveness of HCC. However, the roles of miR-338-3p in HCC disease and resistance to its therapeutic drugs are unknown. In this study, we found that miR-338-3p was frequently down-regulated in 14 HCC clinical samples and five cell lines. Overexpression of miR-338-3p inhibited HIF-1α 3'-UTR luciferase activity and HIF-1α protein levels in HepG2, SMMC-7721, and Huh7 cells. miR-338-3p significantly reduced cell viability and induced cell apoptosis of HCC cells. Additionally, HIF-1α overexpression rescued and HIF-1α knock-down abrogated the anti-HCC activity of miR-338-3p. Furthermore, miR-338-3p sensitized HCC cells to sorafenib in vitro and in a HCC subcutaneous nude mice tumor model by inhibiting HIF-1α. Collectively, miR-338-3p inhibits HCC tumor growth and sensitizes HCC cells to sorafenib by down-regulating HIF-1α. Our data indicate that miR-338-3p could be a potential candidate for HCC therapeutics.

  17. miRNA-556-3p promotes tumorigenesis and metastasis by negatively regulating DAB2IP expression in human bladder cancer

    Institute of Scientific and Technical Information of China (English)

    CHEN Feng; SUN Ping; LI Mingqiu; LIU Yueguang; FENG Yukuan; FENG Kejian

    2015-01-01

    Objective:MicroRNAs ( miRNAs) function as key regulator of gene expression and their dereg-ulation play critical roles in tumorigenesis and metastasis of various cancers. The purpose of this study is to identify miRNAs targeting DAB2IP and to determine their expression and function in bladder cancer (BC). Methods and Results:We first predicted candidate miRNAs targeting Disabled homolog 2- interaction protein ( DAB2IP) and then determine their expression and biological function in BC. We showed that miRNA-556-3p directly regulated DAB2 IP expression by binding to DAB2 IP 3 '-UTR and endogenous miRNA-556-3 p expression was significantly up-regulated in clinical samples of BC patients and BC cell lines in comparison to the controls. Conversely, simul-taneous DAB2IP expression in BC tissues and BC cell lines was remarkably down-regulated. Gain or loss function showed that enhanced miRNA-556-3p expression by Lv-miRNA-556-3p transfection promoted proliferation,in-vasion, migration, and colony formation of BC cells, whereas repressed miRNA-556-3p expression by Lv-sh-miRNA-556-3p transfection resulted inan opposite results. Importantly,restored DAB2IP expression by "rescue"assay could attenuate the promotion effect induced by miRNA-556-3p. Further investigation verified that overex-pressed miRNA-556-3p in BC cells not only decreased DAB2IP expression, but also dramatically increased Ras-and pERK1/2 protein expression. In conclusion, our results suggested that DAB2IP was a direct target of miRNA-556-3p, and endogenous miRNA-556-3p expression was reversely correlated with simultaneous DAB2IP expres-sion in BC tissues and cells. Conclusions: MiRNA-556-3p, as a tumor promoter, functioned in tumorigenesis and metastasis of BC via targeting DAB2IP. Moreover, miRNA-556-3p mediated DAB2IP suppression played an oncogenic role by activation of Ras-ERK pathway partially.

  18. The C(3P) + NH3 Reaction in Interstellar Chemistry. I. Investigation of the Product Formation Channels

    Science.gov (United States)

    Bourgalais, Jérémy; Capron, Michael; Abhinavam Kailasanathan, Ranjith Kumar; Osborn, David L.; Hickson, Kevin M.; Loison, Jean-Christophe; Wakelam, Valentine; Goulay, Fabien; Le Picard, Sébastien D.

    2015-10-01

    The product formation channels of ground state carbon atoms, C(3P), reacting with ammonia, NH3, have been investigated using two complementary experiments and electronic structure calculations. Reaction products are detected in a gas flow tube experiment (330 K, 4 Torr) using tunable vacuum-ultraviolet (VUV) photoionization coupled with time of flight mass spectrometry. Temporal profiles of the species formed and photoionization spectra are used to identify primary products of the C + NH3 reaction. In addition, H-atom formation is monitored by VUV laser induced fluorescence (LIF) from room temperature to 50 K in a supersonic gas flow generated by the Laval nozzle technique. Electronic structure calculations are performed to derive intermediates, transition states, and complexes formed along the reaction coordinate. The combination of photoionization and LIF experiments supported by theoretical calculations indicate that in the temperature and pressure range investigated, the H + H2CN production channel represents 100% of the product yield for this reaction. Kinetics measurements of the title reaction down to 50 K and the effect of the new rate constants on interstellar nitrogen hydride abundances using a model of dense interstellar clouds are reported in Paper II.

  19. Theoretical investigations of α,α,α-trifluoro-3, -p and o-nitrotoluene by means of density functional theory.

    Science.gov (United States)

    Yildirim, G; Senol, S D; Dogruer, M; Ozturk, O; Senol, A; Tasci, A T; Terzioglu, C

    2012-01-01

    This study reports the optimized molecular structures, vibrational frequencies including Infrared intensities and Raman activities, corresponding vibrational assignments, (1)H and (13)C NMR chemical shifts, the magnitudes of the JCH and JCC coupling constants, Ultraviolet-visible (UV-vis) spectra, thermodynamic properties and atomic charges of the title compounds, α,α,α-trifluoro-3, -p and o-nitrotoluene, in the ground state by means of the density functional theory (DFT) with the standard B3LYP/6-311++G(d,p) method and basis set combination for the first time. Theoretical vibrational spectra were interpreted by normal coordinate analysis based on scaled density functional force field. The results show that the vibrational frequencies and chemical shifts calculated were obtained to be in good agreement with the experimental data. Based on the comparison between experimental results and theoretical data, the calculation level chosen is powerful approach for understanding the identification of all the molecules studied. In addition, not only were frontier molecular orbitals (HOMO and LUMO), molecular electrostatic potential (MEP) and electrostatic potential (ESP) simulated but also the dipole moment, softness, electronegativity, chemical hardness, electrophilicity index, transition state and energy band gap values were predicted. According to the investigations, all compounds were found to be useful to bond metallically and interact intermolecularly; however, the thermodynamic properties confirm that the α,α,α-trifluoro-p-nitrotoluene was more reactive and more polar than the others.

  20. Semirigid vibrating rotor target calculation for reaction O(3p)+CH4 →CH3+OH

    Institute of Scientific and Technical Information of China (English)

    LIU; Xinguo; BAI; Lihua; ZHANG; Qinggang

    2004-01-01

    The time-dependent quantum dynamics calculation for reaction O(3p)+CH4→ CH3+OH is made, using of the semirigid vibrating rotor target (SVRT) model and the time-dependent wave packet (TDWP) method. The corresponding reaction probabilities of different initial states are provided. From the calculation of initial rovibrational state j= 0,v= 0, 1, we can see that the excitation of the H-CH3 stretching vibration gives significant enhancement of reaction probability and the reaction threshold decreases dramatically with the enhancement of the vibrating excitation, which indicates that the vibrating energy of reagent molecules contributes a lot to the molecular collision. As for the calculation of reaction probability of state v= 0, j= 0,1,2,3, the results show that the reaction probability rises significantly with the enhancement of rotational quantum number j while the reaction threshold has no changes. The spatial steric effect of the title reaction is studied and analyzed too after the calculation of reaction probability of states j= 5, k= 0-2, n= 0 and j=5, k=2, n=0-2 is made.

  1. Electronic nonadiabatic effects in low temperature radical-radical reactions. I. C(3P) + OH(2Π).

    Science.gov (United States)

    Maergoiz, A I; Nikitin, E E; Troe, J

    2014-07-28

    The formation of collision complexes, as a first step towards reaction, in collisions between two open-electronic shell radicals is treated within an adiabatic channel approach. Adiabatic channel potentials are constructed on the basis of asymptotic electrostatic, induction, dispersion, and exchange interactions, accounting for spin-orbit coupling within the multitude of electronic states arising from the separated reactants. Suitable coupling schemes (such as rotational + electronic) are designed to secure maximum adiabaticity of the channels. The reaction between C((3)P) and OH((2)Π) is treated as a representative example. The results show that the low temperature association rate coefficients in general cannot be represented by results obtained with a single (generally the lowest) potential energy surface of the adduct, asymptotically reaching the lowest fine-structure states of the reactants, and a factor accounting for the thermal population of the latter states. Instead, the influence of non-Born-Oppenheimer couplings within the multitude of electronic states arising during the encounter markedly increases the capture rates. This effect extends up to temperatures of several hundred K.

  2. Remote frequency measurement of the 1S0-3P1 transition in laser cooled 24Mg

    CERN Document Server

    Friebe, J; Wübbena, T; Pape, A; Kelkar, H; Ertmer, W; Terra, O; Sterr, U; Weyers, S; Grosche, G; Schnatz, H; Rasel, E M

    2011-01-01

    We perform Ramsey-Borde spectroscopy on laser cooled magnesium atoms in free fall to measure the 1S0-3P1 intercombination transition frequency. The measured value of 655 659 923 839 730 (48) Hz is consistent with our former atomic beam measurement. We improve upon the fractional accuracy of the previous measurement by more than an order of magnitude to 7 x 10^-14. The magnesium frequency standard was referenced to a fountain clock of the Physikalisch Technische Bundesanstalt (PTB) via a phase-stabilized telecom fiber link and its stability characterized for interrogation times up to 8000 s. Our measurement revealed a new systematic effect due to the movement of atoms across the spectroscopy beams. A remarkable property of this effect is the counterintuitive reduction of residual Doppler shift with increasing resolution. Our theoretical model of the atom-light interaction is in agreement with the observed effect and allows us to quantify its contribution in the uncertainty budget.

  3. Dynamics of interfacial reactions between O({sup 3} P) atoms and long-chain liquid hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Allan, Mhairi [School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); Bagot, Paul A J [School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); Koehler, Sven P K [School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); Reed, Stewart K [Department of Physics and Astronomy, University of Edinburgh, The King' s Buildings, Edinburgh EH9 3JZ (United Kingdom); Westacott, Robin E [School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); Costen, Matthew L [School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); McKendrick, Kenneth G [School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom)

    2007-09-15

    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({sup 3}P) 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.

  4. Performance Parameters Analysis of an XD3P Peugeot Engine Using Artificial Neural Networks (ANN) Concept in MATLAB

    Science.gov (United States)

    Rangaswamy, T.; Vidhyashankar, S.; Madhusudan, M.; Bharath Shekar, H. R.

    2015-04-01

    The current trends of engineering follow the basic rule of innovation in mechanical engineering aspects. For the engineers to be efficient, problem solving aspects need to be viewed in a multidimensional perspective. One such methodology implemented is the fusion of technologies from other disciplines in order to solve the problems. This paper mainly deals with the application of Neural Networks in order to analyze the performance parameters of an XD3P Peugeot engine (used in Ministry of Defence). The basic propaganda of the work is divided into two main working stages. In the former stage, experimentation of an IC engine is carried out in order to obtain the primary data. In the latter stage the primary database formed is used to design and implement a predictive neural network in order to analyze the output parameters variation with respect to each other. A mathematical governing equation for the neural network is obtained. The obtained polynomial equation describes the characteristic behavior of the built neural network system. Finally, a comparative study of the results is carried out.

  5. 多通道反应O(3P)+CH2F的理论研究%Vibrational Mode Analysis for the Multi-channel Reactions of O(3P) with CH2F

    Institute of Scientific and Technical Information of China (English)

    曹小龙; 郭丽

    2004-01-01

    用密度泛函理论研究了氧原子与氟代甲基自由基的反应.反应中出现的所有物种的平衡构型用B3LYP方法在6-311++G(2 d,2p)基组水平上进行了优化,同时对各物种进行了频率分析;在同一理论水平上计算了各反应通道的势能面变化,分析了反应物、中间体、过渡态、产物的振动模式随反应途径的变化关系,阐明了该多通道反应的反应机理.%All species involved in the multi-channel reaction of an oxygen atom with a fluorinated methyl radical have been investigated using density functional theory (DFT) . The geometries of the reactants, intermediates, transition states and products are optimized at the B3LYP/6-311 + + G(2 d, 2p) level. The potential energy surface for this reaction is calculated at the same level of theory. Various possible production channels involved in the reaction of O(3 P) +CH2F are examined. The vibrational mode analysis is used to elucidate the relationship between the transition states, intermediates and the products. The extensive investigation shows that the reaction mechanism is reliable.

  6. Experimental Determination of the 24Mg I (3s3p)3P2 Lifetime

    DEFF Research Database (Denmark)

    Jensen, Brian Bak; He, Ming; Westergaard, Philip Grabow;

    2011-01-01

    We present the first experimental determination of the electric-dipole forbidden (3s3p)3P2¿(3s2)1S0 (M2) transition rate in 24Mg and compare to state-of-the-art theoretical predictions. Our measurement exploits a magnetic trap isolating the sample from perturbations and a magneto-optical trap...... as an amplifier converting each 3P2¿1S0 decay event into millions of photons readily detected. The transition rate is determined to be (4.87±0.3)×10-4¿¿s-1 corresponding to a 3P2 lifetime of 2050-110+140 sec. This value is in agreement with recent theoretical predictions, and to our knowledge the longest lifetime...

  7. T3P as an efficient cyclodehydration reagent for the one-pot synthesis of 2-amino-1,3,4-oxadiazoles

    Indian Academy of Sciences (India)

    Andivelu Ilangovan; Shanmugasundar Saravanakumar; Siddappa Umesh

    2015-05-01

    A scalable and environmentally friendly one-pot method for the synthesis of 2-amino-1,3,4-oxadiazoles from acylhydrazides and isocyanates has been achieved with propane phosponic anhydride (T3P) acting as cyclodehydrating reagent.

  8. Purification, crystallization and preliminary X-ray diffraction analysis of a soluble variant of the monoglyceride lipase Yju3p from the yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Rengachari, Srinivasan; Aschauer, Philipp; Sturm, Christian; Oberer, Monika, E-mail: m.oberer@uni-graz.at [University of Graz, Humboldtstrasse 50/3, 8010 Graz (Austria)

    2015-01-28

    A soluble variant of the monoglyceride lipase Yju3p was successfully expressed, purified and crystallized. Diffraction data were collected to 2.4 Å resolution. The protein Yju3p is the orthologue of monoglyceride lipases in the yeast Saccharomyces cerevisiae. A soluble variant of this lipase termed s-Yju3p (38.3 kDa) was generated and purified to homogeneity by affinity and size-exclusion chromatography. s-Yju3p was crystallized in a vapour-diffusion setup at 293 K and a complete data set was collected to 2.4 Å resolution. The crystal form was orthorhombic (space group P2{sub 1}2{sub 1}2{sub 1}), with unit-cell parameters a = 77.2, b = 108.6, c = 167.7 Å. The asymmetric unit contained four molecules with a solvent content of 46.4%.

  9. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

    DEFF Research Database (Denmark)

    Ferland-McCollough, D; Fernandez-Twinn, D S; Cannell, I G

    2012-01-01

    Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA...... expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro...... substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early...

  10. Synthesis and Characterization of Organophosphazene Polyoxotungstate [(N3P3)(SiW11O39H2)3]12-

    Institute of Scientific and Technical Information of China (English)

    Jian GONG; Chang Lu SHAO; Lun Yu QU

    2004-01-01

    A new organophosphazene polyoxotungstate, [(N3P3)(SiW11O39H2)3]12-, has been prepared by reaction of hexachlorocyclotriphosphazene with undecatungstosilicate, and characterized by elemental analysis, infrared spectroscopy, and multinuclear 31P NMR.

  11. Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Zheng, Kehong; Zhou, Xinying; Yu, Jinlong; Li, Qiang; Wang, Hui; Li, Mingyi; Shao, Ziyun; Zhang, Feifei; Luo, Yuhao; Shen, Zetao; Chen, Fei; Shi, Fujun; Cui, Chunhui; Zhao, Dachuan; Lin, Zhiqun; Zheng, Wei; Zou, Zhaowei; Huang, Zonghai; Zhao, Liang

    2016-06-28

    The Wnt/β-catenin pathway is known to contribute to colorectal cancer (CRC) progression, although little is known about the contribution of β-catenin on this process. We investigated the role of miR-490-3p, which was recently reported to suppress tumorigenesis through its effect on Wnt/β-catenin signaling. We found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis and inhibits cell invasiveness by repressing the initiation of epithelial-to-mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1) protein was identified as a direct target of miR-490-3p and contributes to its tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on β-catenin expression in nuclear fractions of CRC cells, whereas FRAT1 expression is associated with the accumulation of β-catenin in the nucleus of cells, which could be weakened by transfection with miR-490-3p. Our findings suggest that the miR-490-3p/FRAT1/β-catenin axis is important in CRC progression and provides new insight into the molecular mechanisms underlying CRC. They may help to confirm the pathway driving CRC aggressiveness and serve for the development of a novel miRNA-targeting anticancer therapy.

  12. miR-181b-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization by directly targeting YWHAG.

    Science.gov (United States)

    Yoo, Je-Ok; Kwak, Seo-Young; An, Hyun-Ju; Bae, In-Hwa; Park, Myung-Jin; Han, Young-Hoon

    2016-07-01

    Epithelial-mesenchymal transition (EMT) is essential for increased invasion and metastasis during cancer progression. Among the candidate EMT-regulating microRNAs that we previously identified, miR-181b-3p was found to induce EMT in MCF7 breast cancer cells, as indicated by an EMT-characteristic morphological change, increased invasiveness, and altered expression of an EMT marker. Transfection with a miR-181b-3p inhibitor reduced the expression of mesenchymal markers and the migration and invasion of highly invasive breast cancer cells. miR-181b-3p induced the upregulation of Snail, a master EMT inducer and transcriptional repressor of E-cadherin, through protein stabilization. YWHAG was identified as a direct target of miR-181b-3p, downregulation of which induced Snail stabilization and EMT phenotypes. Ectopic expression of YWHAG abrogated the effect of miR-181b-3p, including Snail stabilization and the promotion of invasion. In situ hybridization and immunohistochemical analyses indicated that YWHAG expression was inversely correlated with the expression of miR-181b-3p and Snail in human breast cancer tissues. Furthermore, transfection with miR-181b-3p increased the frequency of metastatic nodule formation in the lungs of mice in experimental metastasis assays using MDA-MB-231 cells. Taken together, our data suggest that miR-181b-3p functions as a metastasis activator by promoting Snail-induced EMT, and may therefore be a therapeutic target in metastatic cancers.

  13. p53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO

    Science.gov (United States)

    Yang, Ruhao; Xu, Xuan; Li, Huiling; Chen, Jinwen; Xiang, Xudong; Dong, Zheng; Zhang, Dongshan

    2017-01-01

    The role of p53 in renal fibrosis has recently been suggested, however, its function remains controversial and the underlying mechanism is unclear. Here, we show that pharmacological and genetic blockade of p53 attenuated renal interstitial fibrosis, apoptosis, and inflammation in mice with unilateral urethral obstruction (UUO). Interestingly, p53 blockade was associated with the suppression of miR-215-5p, miR-199a-5p&3p, and STAT3. In cultured human kidney tubular epithelial cells (HK-2), TGF-β1 treatment induced fibrotic changes, including collagen I and vimentin expression, being associated with p53 accumulation, p53 Ser15 phosphorylation, and miR-199a-3p expression. Inhibition of p53 by pifithrin-α blocked STAT3 activation and the expression of miR-199a-3p, collagen I, and vimentin during TGF-β1 treatment. Over-expression of miR-199a-3p increased TGFβ1-induced collagen I and vimentin expression and restored SOCS7 expression. Furthermore, SOCS7 was identified as a target gene of miR-199a-3p, and silencing of SOCS7 promoted STAT3 activation. ChIp analyses indicated the binding of p53 to the promoter region of miR-199a-3p. Consistently, kidney biopsies from patients with IgA nephropathy and diabetic nephropathy exhibited substantial activation of p53 and STAT3, decreased expression of SOCS7, and increase in profibrotic proteins and miR-199a-3p. Together, these results demonstrate the novel p53/miR-199a-3p/SOCS7/STAT3 pathway in renal interstitial fibrosis. PMID:28240316

  14. miR-659-3p is involved in the regulation of the chemotherapy response of colorectal cancer via modulating the expression of SPHK1

    Science.gov (United States)

    Li, Shuyuan; Fang, Ying; Qin, Hai; Fu, Wenzheng; Zhang, Xipeng

    2016-01-01

    Colorectal cancer (CRC) is one of most prevalent malignant diseases worldwide. Metastasis and chemo-resistance are the two prominent death-related factors of CRCs. Thus, it is urgent to understand the mechanism responsible for the chemo-resistant properties of CRC and develop new therapeutic methods. Here, we found that the expression of miR-659-3p was significantly reduced in cisplatin (CDDP)-resistant HT29 and LOVO colorectal cancer cells and in CDDP-resistant clinical colorectal cancer samples compared with respective CDDP-sensitive counterparts. Sphingosine kinase 1 (SPHK1) is a direct target of miR-659-3p in colorectal cancer cells, and it is negatively regulated by miR-659-3p. We found that anti-miR-659-3p could increase the IC50 of CDDP in parental HT29 and LOVO colorectal cancer cells; additionally, miR-659-3p mimics decreased the IC50 of CDDP in HT29/CDDP and LOVO/CDDP colorectal cancer cells. Furthermore, we showed that the miR-659-3p/SPHK1 pathway was involved in the regulation of chemotherapy responses of colorectal cancer cells in vivo. In all, our findings suggest a new mechanism involved in the regulation of the chemotherapy response of CRC and might provide new targets for CRC prevention and treatment. PMID:27725903

  15. Experimental and theoretical studies of rate coefficients for the reaction O(3P)+CH3OH at high temperatures.

    Science.gov (United States)

    Lu, Chih-Wei; Chou, Shen-Long; Lee, Yuan-Pern; Xu, Shucheng; Xu, Z F; Lin, M C

    2005-06-22

    Rate coefficients of the reaction O((3)P) + CH(3)OH in the temperature range of 835-1777 K were determined using a diaphragmless shock tube. O atoms were generated by photolysis of SO(2) with a KrF excimer laser at 248 nm or an ArF excimer laser at 193 nm; their concentrations were monitored via atomic resonance absorption excited by emission from a microwave-discharged mixture of O(2) and He. The rate coefficients determined for the temperature range can be represented by the Arrhenius equation, k(T) = (2.29 +/- 0.18) x 10(-10) exp[-(4210 +/- 100)T] cm(3) molecule(-1) s(-1); unless otherwise noted, all the listed errors represent one standard deviation in fitting. Combination of these and previous data at lower temperature shows a non-Arrhenius behavior described as the three-parameter equation, k(T) = (2.74 +/- 0.07) x 10(-18)T(2.25 +/- 0.13) exp[-(1500 +/- 90)T] cm(3)molecule(-1) s(-1). Theoretical calculations at the Becke-3-Lee-Yang-Parr (B3LYP)6-311 + G(3df,2p) level locate three transition states. Based on the energies computed with coupled clusters singles, doubles (triples) [CCSD(T)]/6-311 + G(3df,2p)B3LYP6-311 + G(3df,2p), the rate coefficients predicted with canonical variational transition state theory with small curvature tunneling corrections agree satisfactorily with the experimental observations. The branching ratios of two accessible reaction channels forming OH + CH(2)OH (1a) and OH + CH(3)O (1b) are predicted to vary strongly with temperature. At 300 K, reaction (1a) dominates, whereas reaction (1b) becomes more important than reaction (1a) above 1700 K.

  16. Design of a Robust, Computation-Efficient and Secure 3P-EKE Protocol using Analogous Message Transmission

    Directory of Open Access Journals (Sweden)

    Archana Raghuvamshi

    2016-05-01

    Full Text Available In this modern era of digital communication even a trivial task needs to be performed over internet which is not secure. Many cryptographic algorithms existed to provide security which facilitates secure communication through internet. As these algorithms need a secret session key, it is required to interchange this key in a secure way. In two-party communication, two clients initially share a low random (entropy password through a secure channel to establish a secret session key. But this paradigm necessitates high maintenance of passwords, since each communicating pair requires separate passwords to establish a secure session key. In three-party communication network, each communication party shares a password with the trusted third-party (server to exchange a secret session key. The beauty of this setting is that, even a server does not know the session key. The Password Authenticated Encrypted Key Exchange (PA-EKE protocols have attracted a lot of curiosity to authors to propose various two-party and three-party PA-EKE protocols. Security flaws in various protocols proposed by Chang-Chang, Yoon-Yoo, PSRJ and Raj et al. inspired to design a robust, computationally efficient and highly secure protocol. This paper is an attempt to propose a secure and novel Password Authenticated 3P-EKE protocol using XOR operations and analogous (parallel message transmission. The proposed protocol is easy to design and more secured against all types of attacks like password guessing, replay, pre-play, server spoofing etc. which made this protocol special.

  17. Intersystem crossing and dynamics in O(3P) + C2H4 multichannel reaction: experiment validates theory.

    Science.gov (United States)

    Fu, Bina; Han, Yong-Chang; Bowman, Joel M; Angelucci, Luca; Balucani, Nadia; Leonori, Francesca; Casavecchia, Piergiorgio

    2012-06-19

    The O((3)P) + C(2)H(4) reaction, of importance in combustion and atmospheric chemistry, stands out as a paradigm reaction involving triplet- and singlet-state potential energy surfaces (PESs) interconnected by intersystem crossing (ISC). This reaction poses challenges for theory and experiments owing to the ruggedness and high dimensionality of these potentials, as well as the long lifetimes of the collision complexes. Primary products from five competing channels (H + CH(2)CHO, H + CH(3)CO, H(2) + CH(2)CO, CH(3) + HCO, CH(2) + CH(2)O) and branching ratios (BRs) are determined in crossed molecular beam experiments with soft electron-ionization mass-spectrometric detection at a collision energy of 8.4 kcal/mol. As some of the observed products can only be formed via ISC from triplet to singlet PESs, from the product BRs the extent of ISC is inferred. A new full-dimensional PES for the triplet state as well as spin-orbit coupling to the singlet PES are reported, and roughly half a million surface hopping trajectories are run on the coupled singlet-triplet PESs to compare with the experimental BRs and differential cross-sections. Both theory and experiment find almost equal contributions from the two PESs to the reaction, posing the question of how important is it to consider the ISC as one of the nonadiabatic effects for this and similar systems involved in combustion chemistry. Detailed comparisons at the level of angular and translational energy distributions between theory and experiment are presented for the two primary channel products, CH(3) + HCO and H + CH(2)CHO. The agreement between experimental and theoretical functions is excellent, implying that theory has reached the capability of describing complex multichannel nonadiabatic reactions.

  18. Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3pNoMo

    Energy Technology Data Exchange (ETDEWEB)

    Tilly, W.; Gellermann, J.; Graf, R.; Felix, R.; Wust, P. [Dept. of Radiation Medicine, Charite Medical School, Berlin (Germany); Hildebrandt, B. [Dept. of Internal Medicine - Hematology and Oncology, Charite Medical School, Berlin (Germany); Weissbach, L. [Dept. of Urology, Urban Hospital, Berlin (Germany); Budach, V. [Dept. of Radiation Oncology, Charite Medical School, Berlin (Germany)

    2005-01-01

    Background and purpose: since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. Patients and methods: from 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pNO MO and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate-specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. Results: mean maximum temperatures along the urethra of 41.4 C (41.0 C for the recurrences), and mean T{sub 90} values of 40.7 C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. Conclusion: regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile. (orig.)

  19. Computational study of collisions between O(3P) and NO(2Π) at temperatures relevant to the hypersonic flight regime.

    Science.gov (United States)

    Castro-Palacio, Juan Carlos; Nagy, Tibor; Bemish, Raymond J; Meuwly, Markus

    2014-10-28

    Reactions involving N and O atoms dominate the energetics of the reactive air flow around spacecraft when reentering the atmosphere in the hypersonic flight regime. For this reason, the thermal rate coefficients for reactive processes involving O((3)P) and NO((2)Π) are relevant over a wide range of temperatures. For this purpose, a potential energy surface (PES) for the ground state of the NO2 molecule is constructed based on high-level ab initio calculations. These ab initio energies are represented using the reproducible kernel Hilbert space method and Legendre polynomials. The global PES of NO2 in the ground state is constructed by smoothly connecting the surfaces of the grids of various channels around the equilibrium NO2 geometry by a distance-dependent weighting function. The rate coefficients were calculated using Monte Carlo integration. The results indicate that at high temperatures only the lowest A-symmetry PES is relevant. At the highest temperatures investigated (20,000 K), the rate coefficient for the "O1O2+N" channel becomes comparable (to within a factor of around three) to the rate coefficient of the oxygen exchange reaction. A state resolved analysis shows that the smaller the vibrational quantum number of NO in the reactants, the higher the relative translational energy required to open it and conversely with higher vibrational quantum number, less translational energy is required. This is in accordance with Polanyi's rules. However, the oxygen exchange channel (NO2+O1) is accessible at any collision energy. Finally, this work introduces an efficient computational protocol for the investigation of three-atom collisions in general.

  20. Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Igor Landais

    2015-05-01

    Full Text Available Human Cytomegalovirus (HCMV encodes multiple microRNAs (miRNAs whose functions are just beginning to be uncovered. Using in silico approaches, we identified the Toll-Like Receptor (TLR innate immunity pathway as a possible target of HCMV miRNAs. Luciferase reporter assay screens further identified TLR2 as a target of HCMV miR-UL112-3p. TLR2 plays a major role in innate immune response by detecting both bacterial and viral ligands, including HCMV envelope proteins gB and gH. TLR2 activates a variety of signal transduction routes including the NFκB pathway. Furthermore, TLR2 plays an important role in controlling CMV infection both in humans and in mice. Immunoblot analysis of cells transfected with a miR-UL112-3p mimic revealed that endogenous TLR2 is down-regulated by miR-UL112-3p with similar efficiency as a TLR2-targeting siRNA (siTLR2. We next found that TLR2 protein level decreases at late times during HCMV infection and correlates with miR-UL112-3p accumulation in fibroblasts and monocytic THP1 cells. Confirming direct miR-UL112-3p targeting, down-regulation of endogenous TLR2 was not observed in cells infected with HCMV mutants deficient in miR-UL112-3p expression, but transfection of miR-UL112-3p in these cells restored TLR2 down-regulation. Using a NFκB reporter cell line, we found that miR-UL112-3p transfection significantly inhibited NFκB-dependent luciferase activity with similar efficiency as siTLR2. Consistent with this observation, miR-UL112-3p transfection significantly reduced the expression of multiple cytokines (IL-1β, IL-6 and IL-8 upon stimulation with a TLR2 agonist. Finally, miR-UL112-3p transfection significantly inhibited the TLR2-induced post-translational activation of IRAK1, a kinase located in the upstream section of the TLR2/NFκB signaling axis. To our knowledge, this is the first identified mechanism of TLR2 modulation by HCMV and is the first report of functional targeting of TLR2 by a viral miRNA. These

  1. miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer.

    Science.gov (United States)

    Pan, Yinghong; Robertson, Gordon; Pedersen, Lykke; Lim, Emilia; Hernandez-Herrera, Anadulce; Rowat, Amy C; Patil, Sagar L; Chan, Clara K; Wen, Yunfei; Zhang, Xinna; Basu-Roy, Upal; Mansukhani, Alka; Chu, Andy; Sipahimalani, Payal; Bowlby, Reanne; Brooks, Denise; Thiessen, Nina; Coarfa, Cristian; Ma, Yussanne; Moore, Richard A; Schein, Jacquie E; Mungall, Andrew J; Liu, Jinsong; Pecot, Chad V; Sood, Anil K; Jones, Steven J M; Marra, Marco A; Gunaratne, Preethi H

    2016-05-03

    Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E-3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P < 1.0E-3). We found that miR-509-3p attenuated migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers.

  2. Class III PI 3-kinase is the main source of PtdIns3P substrate and membrane recruitment signal for PIKfyve constitutive function in podocyte endomembrane homeostasis.

    Science.gov (United States)

    Ikonomov, Ognian C; Sbrissa, Diego; Venkatareddy, Madhusudan; Tisdale, Ellen; Garg, Puneet; Shisheva, Assia

    2015-05-01

    The evolutionarily conserved PIKfyve, which synthesizes PtdIns5P from PtdIns, and PtdIns(3,5)P2 from PtdIns3P, requires PtdIns3P as both an enzyme substrate and a membrane recruitment signal. Whereas the PtdIns3P source is undetermined, class III PI3K (Vps34), the only evolutionarily conserved of the eight mammalian PI3Ks, is presumed as a main candidate. A hallmark of PIKfyve deficiency is formation of multiple translucent cytoplasmic vacuoles seen by light microscopy in cells cultured in complete media. Such an aberrant phenotype is often observed in cells from conditional Vps34 knockout (KO) mice. To clarify the mechanism of Vps34 KO-triggered vacuolation and the PtdIns3P source for PIKfyve functionality, here we have characterized a podocyte cell type derived from Vps34fl/fl mice, which, upon Cre-mediated gene KO, robustly formed cytoplasmic vacuoles resembling those in PikfyveKO MEFs. Vps34wt, expressed in Vps34KO podocytes restored the normal morphology, but only if the endogenous PIKfyve activity was intact. Conversely, expressed PIKfyvewt rescued completely the vacuolation only in PikfyveKO MEFs but not in Vps34KO podocytes. Analyses of phosphoinositide profiles by HPLC and localization patterns by a PtdIns3P biosensor revealed that Vps34 is the main supplier of localized PtdIns3P not only for PIKfyve activity but also for membrane recruitment. Concordantly, Vps34KO podocytes had severely reduced steady-state levels of both PtdIns(3,5)P2 and PtdIns5P, along with PtdIns3P. We further revealed a plausible physiologically-relevant Vps34-independent PtdIns3P supply for PIKfyve, operating through activated class I PI3Ks. Our data provide the first evidence that the vacuolation phenotype in Vps34KO podocytes is due to PIKfyve dysfunction and that Vps34 is a main PtdIns3P source for constitutive PIKfyve functionality.

  3. Repression of microRNA-768-3p by MEK/ERK signalling contributes to enhanced mRNA translation in human melanoma.

    Science.gov (United States)

    Jiang, C C; Croft, A; Tseng, H-Y; Guo, S T; Jin, L; Hersey, P; Zhang, X D

    2014-05-15

    Increased global protein synthesis and selective translation of mRNAs encoding proteins contributing to malignancy is common in cancer cells. This is often associated with elevated expression of eukaryotic translation initiation factor 4 (eIF4E), the rate-limiting factor of cap-dependent translation initiation. We report here that in human melanoma downregulation of miR-768-3p as a result of activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway has an important role in the upregulation of eIF4E and enhancement in protein synthesis. Melanoma cells displayed increased nascent protein production and elevated eIF4E expression, which was associated with the downregulation of miR-768-3p that was predicted to target the 3'-untranslated region of the eIF4E mRNA. Overexpression of miR-768-3p led to the downregulation of the endogenous eIF4E protein, reduction in nascent protein synthesis and inhibition of cell survival and proliferation. These effects were efficiently reversed when eIF4E was co-overexpressed in melanoma cells. On the other hand, introduction of anti-miR-768-3p into melanocytes upregulated endogenous eIF4E protein expression and increased global protein synthesis. Downregulation of miR-768-3p appeared to be mediated by activation of the MEK/ERK pathway, in that treatment of BRAF(V600E) melanoma cells with the mutant BRAF inhibitor PLX4720 or exposure of either BRAF(V600E) or wild-type BRAF melanoma cells to the MEK inhibitor U0126 resulted in the upregulation of miR-768-3p and inhibition of nascent protein synthesis. This inhibition was partially blocked in cells cointroduced with anti-miR-768-3p. Significantly, miR-768-3p was similarly downregulated, which was inversely associated with the expression levels of eIF4E in fresh melanoma isolates. Taken together, these results identify downregulation of miR-768-3p and subsequent upregulation of eIF4E as an important mechanism in addition to

  4. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Jesus Adrian [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico); Alvarez-Salas, Luis Marat, E-mail: lalvarez@cinvestav.mx [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico)

    2011-06-10

    Highlights: {yields} In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. {yields} We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. {yields} We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. {yields} miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. {yields} In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  5. Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma

    Science.gov (United States)

    Wang, Jianguo; Lyu, Xiaoming; Chen, Yuxiang; Liu, Jinkun; Cai, Hongbing; Wang, Ying; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-Jun. Knockdown of PTEN mimicked EBV-miR-BART7-3p-induced tumorigenic phenotype. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p. Silencing of EBV-miR-BART7-3p reduced tumor growth in animal model. We conclude that EBV-miR-BART7-3p favors carcinogenesis, representing a potential target for miRNA-based therapy. PMID:25691053

  6. Mitochondria-related miR-141-3p contributes to mitochondrial dysfunction in HFD-induced obesity by inhibiting PTEN.

    Science.gov (United States)

    Ji, Juan; Qin, Yufeng; Ren, Jing; Lu, Chuncheng; Wang, Rong; Dai, Xiuliang; Zhou, Ran; Huang, Zhenyao; Xu, Miaofei; Chen, Minjian; Wu, Wei; Song, Ling; Shen, Hongbing; Hu, Zhibin; Miao, Dengshun; Xia, Yankai; Wang, Xinru

    2015-11-09

    Mitochondria-related microRNAs (miRNAs) have recently emerged as key regulators of cell metabolism and can modulate mitochondrial fusion and division. In order to investigate the roles of mitochondria-related miRNAs played in obesity, we conducted comprehensive molecular analysis in vitro and in vivo. Based on high-fat-diet (HFD) induced obese mice, we found that hepatic mitochondrial function was markedly altered. Subsequently, we evaluated the expression levels of selected mitochondria-related miRNAs and found that miR-141-3p was up-regulated strikingly in HFD mice. To further verify the role of miR-141-3p in obesity, we carried out gain-and-loss-of-function study in human HepG2 cells. We found that miR-141-3p could modulate ATP production and induce oxidative stress. Through luciferase report gene assay, we identified that phosphatase and tensin homolog (PTEN) was a target of miR-141-3p. Inhibiting PTEN could alter the mitochondrial function, too. Our study suggested that mitochondria-related miR-141-3p induced mitochondrial dysfunction by inhibiting PTEN.

  7. MiRNA-199a-3p Regulates C2C12 Myoblast Differentiation through IGF-1/AKT/mTOR Signal Pathway

    Directory of Open Access Journals (Sweden)

    Long Jia

    2013-12-01

    Full Text Available MicroRNAs constitute a class of ~22-nucleotide non-coding RNAs. They modulate gene expression by associating with the 3' untranslated regions (3' UTRs of messenger RNAs (mRNAs. Although multiple miRNAs are known to be regulated during myoblast differentiation, their individual roles in muscle development are still not fully understood. In this study, we showed that miR-199a-3p was highly expressed in skeletal muscle and was induced during C2C12 myoblasts differentiation. We also identified and confirmed several genes of the IGF-1/AKT/mTOR signal pathway, including IGF-1, mTOR, and RPS6KA6, as important cellular targets of miR-199a-3p in myoblasts. Overexpression of miR-199a-3p partially blocked C2C12 myoblast differentiation and the activation of AKT/mTOR signal pathway, while interference of miR-199a-3p by antisense oligonucleotides promoted C2C12 differentiation and myotube hypertrophy. Thus, our studies have established miR-199a-3p as a potential regulator of myogenesis through the suppression of IGF-1/AKT/mTOR signal pathway.

  8. Phosphatidic acid and phosphoinositides facilitate liposome association of Yas3p and potentiate derepression of ARE1 (alkane-responsive element one)-mediated transcription control.

    Science.gov (United States)

    Kobayashi, Satoshi; Hirakawa, Kiyoshi; Horiuchi, Hiroyuki; Fukuda, Ryouichi; Ohta, Akinori

    2013-12-01

    In the n-alkane assimilating yeast Yarrowia lipolytica, the expression of ALK1, encoding a cytochrome P450 that catalyzes terminal mono-oxygenation of n-alkanes, is induced by n-alkanes. The transcription of ALK1 is regulated by a heterocomplex that comprises the basic helix-loop-helix transcription activators, Yas1p and Yas2p, and binds to alkane-responsive element 1 (ARE1) in the ALK1 promoter. An Opi1 family transcription repressor, Yas3p, represses transcription by binding to Yas2p. Yas3p localizes in the nucleus when Y. lipolytica is grown on glucose but localizes to the endoplasmic reticulum (ER) upon the addition of n-alkanes. In this study, we showed that recombinant Yas3p binds to the acidic phospholipids, phosphatidic acid (PA) and phosphoinositides (PIPs), in vitro. The ARE1-mediated transcription was enhanced in vivo in mutants defective in an ortholog of the Saccharomyces cerevisiae gene PAH1, encoding PA phosphatase, and in an ortholog of SAC1, encoding PIP phosphatase in the ER. Truncation mutation analyses for Yas3p revealed two regions that bound to PA and PIPs. These results suggest that the interaction with acidic phospholipids is important for the n-alkane-induced association of Yas3p with the ER membrane.

  9. 3p14.1 de novo microdeletion involving the FOXP1 gene in an adult patient with autism, severe speech delay and deficit of motor coordination.

    Science.gov (United States)

    Palumbo, Orazio; D'Agruma, Leonardo; Minenna, Adelaide Franca; Palumbo, Pietro; Stallone, Raffaella; Palladino, Teresa; Zelante, Leopoldo; Carella, Massimo

    2013-03-01

    Interstitial deletion of chromosome region 3p14.1, including FOXP1 gene, is relatively rare and, until recently, there were no strong evidences to support the hypothesis that this microdeletion could play a role in the etiology of genomic disorders. Here, we report on an adult patient with a recognizable phenotype of autism, severe speech delay, deficit of motor coordination and typical dysmorphic features. Analysis of a dense whole genome single-nucleotide polymorphism (SNP) array showed a 1Mb interstitial deletion of chromosome region 3p14.1 including the entire coding region of FOXP1 (MIM 605515) gene. In order to study the parental origin of the deletion, we analyzed selected SNPs in the deleted area in the proband and his parents showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of paternal origin. Despite the frequency of this genomic alteration has not been estimated, our patient confirm the hypothesis that microdeletion of 3p14.1 seems to be a rare cause of cognitive disorders and that haploinsufficiency of FOXP1 may play a role in neurological and language deficits in patients carrying a 3p14.1 deletion. Finally, our patient is also important because useful to further delineate the clinical spectrum secondary to the 3p14.1 microdeletions.

  10. Novel RNA-binding properties of Pop3p support a role for eukaryotic RNase P protein subunits in substrate recognition.

    Science.gov (United States)

    Brusca, E M; True, H L; Celander, D W

    2001-11-09

    Ribonuclease P (RNase P) catalyzes the 5'-end maturation of transfer RNA molecules. Recent evidence suggests that the eukaryotic protein subunits may provide substrate-binding functions (True, H. L., and Celander, D. W. (1998) J. Biol. Chem. 273, 7193-7196). We now report that Pop3p, an essential protein subunit of the holoenzyme in Saccharomyces cerevisiae, displays novel RNA-binding properties. A recombinant form of Pop3p (H6Pop3p) displays a 3-fold greater affinity for binding pre-tRNA substrates relative to tRNA products. The recognition sequence for the H6Pop3p-substrate interaction in vitro was mapped to a 39-nucleotide long sequence that extends from position -21 to +18 surrounding the natural processing site in pre-tRNA substrates. H6Pop3p binds a variety of RNA molecules with high affinity (K(d) = 16-25 nm) and displays a preference for single-stranded RNAs. Removal or modification of basic C-terminal residues attenuates the RNA-binding properties displayed by the protein specifically for a pre-tRNA substrate. These studies support the model that eukaryotic RNase P proteins bind simultaneously to the RNA subunit and RNA substrate.

  11. The duplication 17p13.3 phenotype

    DEFF Research Database (Denmark)

    Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica

    2013-01-01

    additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large....... Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype...... was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome....

  12. Repumping and spectroscopy of laser-cooled Sr atoms using the (5s5p)3P2 - (5s4d)3D2 transition

    CERN Document Server

    Mickelson, P G; Anzel, P; DeSalvo, B J; Nagel, S B; Traverso, A J; Yan, M; Killian, T C

    2009-01-01

    We describe repumping and spectroscopy of laser-cooled strontium (Sr) atoms using the (5s5p)3P2 - (5s4d)3D2 transition. Atom number in a magneto-optical trap is enhanced by driving this transition because Sr atoms that have decayed into the (5s5p)3P2 dark state are repumped back into the (5s2)1S0 ground state. Spectroscopy of 84Sr, 86Sr, 87Sr, and 88Sr improves the value of the (5s5p)3P2 - (5s4d)3D2 transition frequency for 88Sr and determines the isotope shifts for the transition.

  13. Repumping and spectroscopy of laser-cooled Sr atoms using the (5s5p)3P2-(5s4d)3D2 transition

    Science.gov (United States)

    Mickelson, P. G.; Martinez de Escobar, Y. N.; Anzel, P.; De Salvo, B. J.; Nagel, S. B.; Traverso, A. J.; Yan, M.; Killian, T. C.

    2009-12-01

    We describe repumping and spectroscopy of laser-cooled strontium (Sr) atoms using the (5s5p)3P2-(5s4d)3D2 transition. Atom number in a magneto-optical trap is enhanced by driving this transition because Sr atoms that have decayed into the (5s5p)3P2 dark state are repumped back into the (5s2)1S0 ground state. Spectroscopy of 84Sr, 86Sr, 87Sr and 88Sr improves the value of the (5s5p)3P2-(5s4d)3D2 transition frequency and determines the isotope shifts for the transition accurately enough to guide laser-cooling experiments with less abundant isotopes.

  14. Valence-band electronic structure of Zn3P2 as a function of annealing as studied by synchrotron radiation photoemission

    Science.gov (United States)

    Nelson, Art J.; Kazmerski, L. L.; Engelhardt, Mike; Hochst, Hartmut

    1990-02-01

    Ultraviolet photoemission (UPS) utilizing synchrotron radiation has been used to characterize changes in the valence-band electronic structure of crystalline Zn3P2 as a function of annealing temperature. The Zn3P2 crystal was etched in bromine-methanol prior to analysis and annealing was performed in vacuum at 300 and 350 °C after sputter cleaning. The UPS spectra for the virgin material are qualitatively similar to the photoemission results for various II-VI Zn compound semiconductors and a comparison of the Zn 3d binding energies with respect to the valence band maximum is presented. The results for the virgin material and the 300 °C anneal are further compared with the theoretically predicted band structure of Zn3P2 as determined by a pseudopotential energy band calculation. Loss of phosphorus from the surface and the presence of elemental zinc on the surface after the 350 °C anneal is evident.

  15. miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Si-Yi; Lu, Zhong-Ming; Lin, Ye-Feng; Chen, Liang-Si; Luo, Xiao-Ning; Song, Xin-Han; Chen, Shao-Hua; Wu, Yi-Long

    2016-03-08

    Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR-144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and α-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis.

  16. Up-regulation of Serum MiR-130b-3p Level is Associated with Renal Damage in Early Lupus Nephritis

    Science.gov (United States)

    Wang, Wanpeng; Mou, Shan; Wang, Ling; Zhang, Minfang; Shao, Xinghua; Fang, Wei; Lu, Renhua; Qi, Chaojun; Fan, Zhuping; Cao, Qin; Wang, Qin; Fang, Yan; Ni, Zhaohui

    2015-08-01

    Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic inflammatory disease. Lupus nephritis (LN) is a serious complication of SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are emerging as biomarkers for pathological conditions and play significant roles in intercellular communication. In present research, serum samples from healthy control, early and late stage LN patients were used to analyze the expression profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p in serum of patients with early stage LN were significantly up-regulated when compared with healthy controls. In addition,we have also observed that the expression of a large amount of circulating microRNAs significantly decreased in patients with late stage LN. The further analysis found that the expression of serum miR-130b-3p was positively correlated with 24-hour proteinuria and renal chronicity index in patients with early stage LN.Transfection of renal tubular cellline(HK-2)with miR-130b-3p mimics can promote epithelial-mesenchymal transition (EMT). The opposite effects were observed when transfected with miR-130b-3p inhibitors. MiR-130b-3p negatively regulated ERBB2IP expression by directly targeting the 3‧-UTR of ERBB2IP The circulating miR-130b-3p might serve as a biomarker and play an important role in renal damage in early stage LN patients.

  17. miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer

    Science.gov (United States)

    Pedersen, Lykke; Lim, Emilia; Hernandez-Herrera, Anadulce; Rowat, Amy C.; Patil, Sagar L.; Chan, Clara K.; Wen, Yunfei; Zhang, Xinna; Basu-Roy, Upal; Mansukhani, Alka; Chu, Andy; Sipahimalani, Payal; Bowlby, Reanne; Brooks, Denise; Thiessen, Nina; Coarfa, Cristian; Ma, Yussanne; Moore, Richard A.; Schein, Jacquie E.; Mungall, Andrew J.; Liu, Jinsong; Pecot, Chad V.; Sood, Anil K.; Jones, Steven J.M.; Marra, Marco A.; Gunaratne, Preethi H.

    2016-01-01

    Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E–3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers. PMID:27036018

  18. Structural, elastic, electronic and optical properties of platinum-based superconductor SrPt3P under pressure: a first-principles study

    Science.gov (United States)

    Zhang, Xiu-Qing; Li, Guo-Jun; Cheng, Yan; Ji, Guang-Fu

    2016-02-01

    The structural, elastic, electronic and optical properties of the platinum-based superconductor SrPt3P under pressure are investigated by the generalized gradient approximation with the Perdew-Burke-Ernzerhof exchange-correlation functional in the framework of density-functional theory. The calculated structural parameters (a, c) and the primitive cell volume V of SrPt3P at the ground state are in good agreement with the available experimental data and seem to be better than other calculated results. The pressure dependences of the elastic constants Cnolimitsij, bulk modulus B, shear modulus G, Young's modulus E and Poisson's ratio σ of SrPt3P are also obtained successfully. The computed elastic constants indicate that SrPt3P is mechanically stable up to 100 GPa. The obtained B/G is 2.56 at the ground state, indicating that SrPt3P behaves in a ductile manner. The ratio B/G also increases with growing pressures, indicating that the structure becomes more and more ductile. Even though SrPt3P is an ionic-covalent crystal, the obtained density of states shows that it has metallic characteristic. These conclusions can be further demonstrated by analysing the charge and Mulliken population. In addition, we have investigated the dielectric function and the loss function. It is found that the dielectric function in (E||x, E||y) is isotropic, whereas the directions (E||x, E||z) are anisotropic; the effect of pressure on the loss function of the deep ultraviolet region gradually increases as the pressure increases.

  19. High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Rasmussen, Mads H; Jensen, Niels F; Tarpgaard, Line S; Qvortrup, Camilla; Rømer, Maria U; Stenvang, Jan; Hansen, Tine P; Christensen, Lise L; Lindebjerg, Jan; Hansen, Flemming; Jensen, Benny V; Hansen, Torben F; Pfeiffer, Per; Brünner, Nils; Ørntoft, Torben F; Andersen, Claus L

    2013-06-01

    The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major unsolved problem is that no predictors of response to these treatments are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among others, high expression of miR-625-3p, miR-181b and miR-27b to be associated with poor clinical response. In a validation cohort of 94 mCRC patients treated first-line with XELOX, high expression of miR-625-3p was confirmed to be associated with poor response (OR = 6.25, 95%CI [1.8; 21.0]). Independent analyses showed that miR-625-3p was not dysregulated between normal and cancer samples, nor was its expression associated with recurrence of stage II or III disease, indicating that miR-625-3p solely is a response marker. Finally, we also found that these miRNAs were up-regulated in oxaliplatin resistant HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) colon cancer cell lines as compared with their isogenic parental cells. Altogether, our results suggest an association between miR-625-3p and response to first-line oxaliplatin based chemotherapy of mCRC.

  20. miR-483-3p plays an oncogenic role in esophageal squamous cell carcinoma by targeting tumor suppressor EI24.

    Science.gov (United States)

    Ma, Jiaojiao; Hong, Liu; Xu, Guanghui; Hao, Junfeng; Wang, Rui; Guo, Hao; Liu, Jinqiang; Zhang, Yujie; Nie, Yongzhan; Fan, Daiming

    2016-04-01

    microRNAs (miRNAs), through negatively regulating their target genes, influence the development and progression of many cancers. Previously, we found miR-483 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues, and its overexpression was negatively correlated with the prognosis and positively correlated with multidrug resistance of ESCC, but whether it could affect the biological role of proliferation and migration in ESCC cell lines is unknown. In the present study, we found miR-483-3p was overexpressed in ESCC cell lines as compared with the normal esophageal squamous epithelial cell line. Functional experiments in vitro showed that miR-483-3p could promote the proliferation, migration, transformation of cell cycle from G1 phase to G2 phase of ESCC cells and could inhibit cells' sensitivity to chemotherapy drugs. Nude mouse tumorigenicity assay indicated that miR-483-3p could promote the growth of ESCC cells in vivo. Western blot assay showed that ectopic expression of miR-483-3p in ESCC cells could downregulate the protein level of etoposide induced 2.4 (EI24), which is a tumor suppressor and has not been reported in ESCC. Luciferase reporter assay demonstrated that EI24 was a direct target of miR-483-3p. Collectively, our study demonstrated that miR-483-3p could promote ESCC progression at least in part through directly targeting EI24, supplying a potential strategy for miRNA-based ESCC therapy.

  1. microRNA miR-142-3p Inhibits Breast Cancer Cell Invasiveness by Synchronous Targeting of WASL, Integrin Alpha V, and Additional Cytoskeletal Elements.

    Directory of Open Access Journals (Sweden)

    Alexander Schwickert

    Full Text Available MicroRNAs (miRNAs, micro ribonucleic acids are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrich syndrome-like, protein: N-WASP, Integrin-αV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility. ROCK2, IL6ST, KLF4, PGRMC2 and ADCY9 were identified as additional targets in a subset of cell lines. Decreased Matrigel invasiveness was associated with the miR-142-3p-induced expression changes. Confocal immunofluorescence microscopy, nanoscale atomic force microscopy and digital holographic microscopy revealed a change in cell morphology as well as a reduced cell volume and size. A more cortical actin distribution and a loss of membrane protrusions were observed in cells overexpressing miR-142-3p. Luciferase activation assays confirmed direct miR-142-3p-dependent regulation of the 3'-untranslated region of ITGAV and WASL. siRNA-mediated depletion of ITGAV and WASL resulted in a significant reduction of cellular invasiveness, highlighting the contribution of these factors to the miRNA-dependent invasion phenotype. While knockdown of WASL significantly reduced the number of membrane protrusions compared to controls, knockdown of ITGAV resulted in a decreased cell volume, indicating differential contributions of these factors to the miR-142-3p-induced phenotype. Our data identify WASL, ITGAV and several additional cytoskeleton-associated molecules as novel invasion-promoting targets of miR-142-3

  2. Mutation in the splicing factor Hprp3p linked to retinitis pigmentosa impairs interactions within the U4/U6 snRNP complex.

    Science.gov (United States)

    Gonzalez-Santos, Juana Maria; Cao, Huibi; Duan, Rongqi Cathleen; Hu, Jim

    2008-01-15

    Mutations in PRPF3, a gene encoding the essential pre-mRNA splicing factor Hprp3p, have been identified in patients with autosomal dominant retinitis pigmentosa type 18 (RP18). Patients with RP18 have one of two single amino acid substitutions, Pro493Ser or Thr494Met, at the highly conserved Hprp3p C-terminal region. Pro493Ser occurs sporadically, whereas Thr494Met is observed in several unlinked RP families worldwide. The latter mutation also alters a potential recognition motif for phosphorylation by casein kinase II (CKII). To understand the molecular basis of RP18, we examined the consequences of Thr494Met mutation on Hprp3p molecular interactions with components of the U4/U6.U5 small nuclear ribonucleoprotein particles (snRNPs) complex. Since numerous mutations causing human diseases change pre-mRNA splice sites, we investigated whether Thr494Met substitution affects the processing of PRPF3 mRNA. We found that Thr494Met does not affect PRPF3 mRNA processing, indicating that the mutation may exert its effect primarily at the protein level. We used small hairpin RNAs to specifically silence the endogenous PRPF3 while simultaneously expressing HA-tagged Thr494Met. We demonstrated that the C- but not N-terminal region of Hprp3p is indeed phosphorylated by CKII in vitro and in cells. CKII-mediated Hprp3p phosphorylation was significantly reduced by Thr494Met mutation. Consequently, the Hprp3p C-terminal region is rendered partially defective in its association with itself, Hprp4p, and U4/U6 snRNA. Our findings provide new insights into the biology of Hprp3p and suggest that the loss of Hprp3p phosphorylation at Thr494 is a key step for initiating Thr494Met aberrant interactions within U4/U6 snRNP complex and that these are likely linked to the RP18 phenotype.

  3. The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death.

    Science.gov (United States)

    Chen, Peng-Hsu; Chang, Cheng-Kuei; Shih, Chwen-Ming; Cheng, Chia-Hsiung; Lin, Cheng-Wei; Lee, Chin-Cheng; Liu, Ann-Jeng; Ho, Kuo-Hao; Chen, Ku-Chung

    2016-11-01

    Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.

  4. C-H and H-H Bond Activation via Ligand Dearomatization/Rearomatization of a PN3P-Rhodium(I) Complex

    KAUST Repository

    Huang, Kuo-Wei

    2015-04-13

    A neutral complex PN3P-Rh(I)Cl (2) was prepared from a reaction of the PN3P pincer ligand (1) with [Rh(COD)Cl]2 (COD = 1,5-cyclooctadiene). Upon treatment with a suitable base, H–H and Csp2–H activation reactions can be achieved through the deprotonation/reprotonation of one of the N–H arms and dearomatization/rearomatization of the central pyridine ring with the oxidation state of Rh remaining I.

  5. Communication: Direct measurements of nascent O({sup 3}P{sub 0,1,2}) fine-structure distributions and branching ratios of correlated spin-orbit resolved product channels CO(ã{sup 3}Π; v) + O({sup 3}P{sub 0,1,2}) and CO(Χ{sup ~1}Σ{sup +}; v) + O({sup 3}P{sub 0,1,2}) in VUV photodissociation of CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Zhou; Chang, Yih Chung; Gao, Hong; Benitez, Yanice; Song, Yu; Ng, C. Y., E-mail: cyng@chem.ucdavis.edu, E-mail: wmjackson@ucdavis.edu; Jackson, W. M., E-mail: cyng@chem.ucdavis.edu, E-mail: wmjackson@ucdavis.edu [Department of Chemistry, University of California, Davis, Davis, California 95616 (United States)

    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{sup 3}Π; v) + O({sup 3}P{sub 0,1,2}) and CO(Χ{sup ~1}Σ{sup +}; v) + O({sup 3}P{sub 0,1,2}), formed by VUV photoexcitation of CO{sub 2} to the 4s(1{sub 0}{sup 1}) Rydberg state at 97,955.7 cm{sup −1}. The total kinetic energy release (TKER) spectra obtained from the O{sup +} VMI-PI images of O({sup 3}P{sub 0,1,2}) reveal the formation of correlated CO(ã{sup 3}Π; v = 0–2) with well-resolved v = 0–2 vibrational bands. This observation shows that the dissociation of CO{sub 2} to form the spin-allowed CO(ã{sup 3}Π; v = 0–2) + O({sup 3}P{sub 0,1,2}) channel has no potential energy barrier. The TKER spectra for the spin-forbidden CO(Χ{sup ~1}Σ{sup +}; v) + O({sup 3}P{sub 0,1,2}) channel were found to exhibit broad profiles, indicative of the formation of a broad range of rovibrational states of CO(Χ{sup ~1}Σ{sup +})  with significant vibrational populations for v = 18–26. While the VMI-PI images for the CO(ã{sup 3}Π; v = 0–2) + O({sup 3}P{sub 0,1,2}) channel are anisotropic, indicating that the predissociation of CO{sub 2} 4s(1{sub 0}{sup 1}) occurs via a near linear configuration in a time scale shorter than the rotational period, the angular distributions for the CO(Χ{sup ~1}Σ{sup +}; v) + O({sup 3}P{sub 0,1,2}) channel are close to isotropic, revealing a slower predissociation process, which possibly occurs on a triplet surface via an intersystem crossing mechanism.

  6. A Poll about Children and Weight: Crunch Time during the American Work and School Week--3 P.M. to Bed. Summary

    Science.gov (United States)

    Robert Wood Johnson Foundation, 2013

    2013-01-01

    Childhood obesity is a major public health challenge today, with complex roots interwoven into nearly every facet of American life. This poll addresses one narrow slice of this web: the challenges that families face during the "crunch time" of the work and school week, between 3 p.m. and the time children go to bed. Compared to the school day,…

  7. Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase.

    Science.gov (United States)

    Wu, Xiaobin; Kim, Heejeong; Seravalli, Javier; Barycki, Joseph J; Hart, P John; Gohara, David W; Di Cera, Enrico; Jung, Won Hee; Kosman, Daniel J; Lee, Jaekwon

    2016-04-29

    Acquisition and distribution of metal ions support a number of biological processes. Here we show that respiratory growth of and iron acquisition by the yeast Saccharomyces cerevisiae relies on potassium (K(+)) compartmentalization to the trans-Golgi network via Kha1p, a K(+)/H(+) exchanger. K(+) in the trans-Golgi network facilitates binding of copper to the Fet3p multi-copper ferroxidase. The effect of K(+) is not dependent on stable binding with Fet3p or alteration of the characteristics of the secretory pathway. The data suggest that K(+) acts as a chemical factor in Fet3p maturation, a role similar to that of cations in folding of nucleic acids. Up-regulation of KHA1 gene in response to iron limitation via iron-specific transcription factors indicates that K(+) compartmentalization is linked to cellular iron homeostasis. Our study reveals a novel functional role of K(+) in the binding of copper to apoFet3p and identifies a K(+)/H(+) exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast.

  8. Microarray based analysis of an inherited terminal 3p26.3 deletion, containing only the CHL1 gene, from a normal father to his two affected children

    Directory of Open Access Journals (Sweden)

    Lerone Margherita

    2011-04-01

    Full Text Available Abstract Background terminal deletions of the distal portion of the short arm of chromosome 3 cause a rare contiguous gene disorder characterized by growth retardation, developmental delay, mental retardation, dysmorphisms, microcephaly and ptosis. The phenotype of individuals with deletions varies from normal to severe. It was suggested that a 1,5 Mb minimal terminal deletion including the two genes CRBN and CNTN4 is sufficient to cause the syndrome. In addition the CHL1 gene, mapping at 3p26.3 distally to CRBN and CNTN4, was proposed as candidate gene for a non specific mental retardation because of its high level of expression in the brain. Methods and Results we describe two affected siblings in which array-CGH analysis disclosed an identical discontinuous terminal 3p26.3 deletion spanning less than 1 Mb. The deletion was transmitted from their normal father and included only the CHL1 gene. The two brothers present microcephaly, light mental retardation, learning and language difficulties but not the typical phenotype manifestations described in 3p- syndrome. Conclusion a terminal 3p26.3 deletion including only the CHL1 gene is a very rare finding previously reported only in one family. The phenotype of the affected individuals in the two families is very similar and the deletion has been inherited from an apparently normal parent. As already described for others recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.

  9. MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drags as judged by interference with nucleotide trapping

    NARCIS (Netherlands)

    Smith, A.J.; van Helvoort, A.; van Meer, G.; Szabó, K.; Welker, E.; Szakács, G.; Váradi, A.; Sarkadi, B.; Borst, P.

    2000-01-01

    The human MDR3 gene is a member of the multidrug resistance (MDR) gene family. The MDR3 P-glycoprotein is a transmembrane protein that translocates phosphatidylcholine. The MDR1 P-glycoprotein related transports cytotoxic drugs. Its overexpression can make cells resistant to a variety of drugs. Atte

  10. Follow-up of an intelligent odd-mannered teenager with del(3)(p26). Remarks on authorship and ethical commitment.

    Science.gov (United States)

    Rivera, H; Domínguez, M G; Matute, E

    2006-01-01

    A male teenager formerly found to have a 46,XY,del(3)(p26)de novo karyotype was restudied. At the age of 14(8/12) yr, he attends the last grade of middle school and was a cooperating teenager with slender habitus, severe myopia, prominent nose, sacral dimples, pubertal stage Tanner III, and multiple surgical scars. Neuropsychological studies revealed a full scale IQ of 95 with slow performance (WISC-IV Spanish test) as well as an internalizing behavioral profile, poor social skills, a mild attention deficit, somatic complaints, and a feminized gender role. FISH with the 3p subtelomeric probe revealed that the deleted chromosome actually lacked the specific signal (n=10 cells). The patient's average intelligence confirms that euchromatic imbalances do not necessarily cause mental retardation and suggests that his deletion actually included the CALL gene, the Contactin 4 gene and other 3p26 genes related to intellectual capabilities; yet, the resulting hemizygosity either did not lead to haploinsufficiency or was minimally expressed. Moreover, the patient's peculiar cognitive and behavioral profile suggests that the 3p26 deletion is associated with a distinctive neuropsychological phenotype. Incidentally we comment on authorship and publication ethics in order to urge our institutional ethics committee to arbitrate authorship conflicts and thereby be consistent with its ethical commitment.

  11. Lnc-ATB contributes to gastric cancer growth through a MiR-141-3p/TGFβ2 feedback loop.

    Science.gov (United States)

    Lei, Kecheng; Liang, Xin; Gao, Yuwei; Xu, Baixue; Xu, Yichun; Li, Yueqi; Tao, Yiwen; Shi, Weibin; Liu, Jianwen

    2017-03-11

    The long noncoding RNA (lncRNA) ATB is an important regulator in human tumors. Here, we aimed to investigate the potential molecular mechanisms of lnc-ATB in gastric cancer (GC) tumorigenesis. RT-qPCR analysis was used to detect lnc-ATB expression level in 20 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANTs). Moreover, the biological role of lnc-ATB was determined in vitro. We found that lnc-ATB was significantly upregulated in GC tissues compared to lnc-ATB expression in ANTs. These high lnc-ATB expression levels predicted poor prognosis in GC patients. Low levels of lnc-ATB inhibited GC cell proliferation and cell cycle arrest in vitro. Lnc-ATB was found to directly bind miR-141-3p. Moreover, TGF-β actives lnc-ATB and TGF-β2 directly binds mir-141-3p. Finally, we demonstrated that lnc-ATB fulfilled its oncogenic roles in a ceRNA-mediated manner. Our study suggests that lnc-ATB promotes tumor progression by interacting with miR-141-3p and that Lnc-ATB may be a valuable prognostic predictor for GC. In conclusion, the positive feedback loop of lnc-ATB/miR-141-3p/TGF-β2 may be a potential therapeutic target for the treatment of GC.

  12. Allelic variants of hexose transporter Hxt3p and hexokinases Hxk1p/Hxk2p in strains of Saccharomyces cerevisiae and interspecies hybrids.

    Science.gov (United States)

    Zuchowska, Magdalena; Jaenicke, Elmar; König, Helmut; Claus, Harald

    2015-11-01

    The transport of sugars across the plasma membrane is a critical step in the utilization of glucose and fructose by Saccharomyces cerevisiae during must fermentations. Variations in the molecular structure of hexose transporters and kinases may affect the ability of wine yeast strains to finish sugar fermentation, even under stressful wine conditions. In this context, we sequenced and compared genes encoding the hexose transporter Hxt3p and the kinases Hxk1p/Hxk2p of Saccharomyces strains and interspecies hybrids with different industrial usages and regional backgrounds. The Hxt3p primary structure varied in a small set of amino acids, which characterized robust yeast strains used for the production of sparkling wine or to restart stuck fermentations. In addition, interspecies hybrid strains, previously isolated at the end of spontaneous fermentations, revealed a common amino acid signature. The location and potential influence of the amino acids exchanges is discussed by means of a first modelled Hxt3p structure. In comparison, hexokinase genes were more conserved in different Saccharomyces strains and hybrids. Thus, molecular variants of the hexose carrier Hxt3p, but not of kinases, correlate with different fermentation performances of yeast.

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

    Science.gov (United States)

    Kellogg, Gregory; Sum, John; Wallerstein, Robert

    2013-06-01

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

  14. The influence of SiO2 Addition on 2MgO-Al2O3-3.3P2O5 Glass

    DEFF Research Database (Denmark)

    Larsen, P.H.; Poulsen, F.W.; Berg, Rolf W.

    1999-01-01

    2MgO-Al2O3-3.3P2O5 glasses with increasing amounts of SiO2 are considered for sealing applications in Solid Oxide Fuel Cells (SOFC). The change in chemical durability under SOFC anode conditions and the linear thermal expansion is measured as functions of the SiO2 concentration. Raman spectroscopy...

  15. Analysis of a new homozygous deletion in the tumor suppressor region at 3p12.3 reveals two novel intronic noncoding RNA genes

    NARCIS (Netherlands)

    Angeloni, Debora; ter Elst, Arja; Wei, Ming Hui; van der Veen, Anneke Y.; Braga, Eleonora A.; Klimov, Eugene A.; Timmer, Tineke; Korobeinikova, Luba; Lerman, Michael I.; Buys, Charles H. C. M.

    2006-01-01

    Homozygous deletions or loss of heterozygosity (LOH) at human chromosome band 3p12 are consistent features of lung and other malignancies, suggesting the presence of a tumor suppressor gene(s) (TSG) at this location. Only one gene has been cloned thus far from the overlapping region deleted in lung

  16. Correlation Between the Expression of MicroRNA-301a-3p and the Proportion of Th17 Cells in Patients with Rheumatoid Arthritis.

    Science.gov (United States)

    Tang, Xinyi; Yin, Kai; Zhu, Hongsheng; Tian, Jie; Shen, Dong; Yi, Lixian; Rui, Ke; Ma, Jie; Xu, Huaxi; Wang, Shengjun

    2016-04-01

    Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and subsequent joint destruction. Previous studies have confirmed that Th17 cells play a critical role in the pathogenesis of RA. MicroRNA (miR)-301a-3p is a regulatory factor for Th17 cells differentiation that contributes to the pathogenesis of autoimmune diseases. The purposes of this study were to identify the alteration of Th17 cells and analyze the correlation between the expression of the miR-301a-3p and the proportion of Th17 cells in RA patients. The results showed that the frequency of Th17 cells and the expression of transcription factors (RORγt and STAT3) significantly increased in the peripheral blood mononuclear cells (PBMCs) from RA patients, and the associated proinflammatory cytokines were also upregulated. We also observed that the expression of protein inhibitor of activated STAT3 (PIAS3), the main cellular inhibitor of STAT3, was attenuated in RA patients and negatively correlated with the percentage of Th17 cells in RA. Interestingly, miR-301a-3p, an inhibitor of PIAS3 expression, was overexpressed in the PBMCs from RA patients and positively correlated with the frequency of Th17 cells in patients with RA. Taken together, these data indicated that miR-301a-3p and Th17 cells were augmented in peripheral blood, which may play an important role in the process of RA.

  17. Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal Electroporation Device.

    Science.gov (United States)

    Amante, Dinah H; Smith, Trevor R F; Mendoza, Janess M; Schultheis, Katherine; McCoy, Jay R; Khan, Amir S; Sardesai, Niranjan Y; Broderick, Kate E

    2015-08-01

    The CELLECTRA-3P dermal electroporation device (Inovio Pharmaceuticals, Plymouth Meeting, PA) has been evaluated in the clinic and shown to enhance the delivery of an influenza DNA vaccine. To understand the mechanism by which this device aids in enhancing the host immune response to DNA vaccines we investigated the expression kinetics and localization of a reporter plasmid (pGFP) delivered via the CELLECTRA-3P. Histological analysis revealed green fluorescent protein (GFP) expression as early as 1 hr posttreatment in the epidermal and dermal layers, and as early as 2 hr posttreatment in the subdermal layers. Immunofluorescence techniques identified keratinocytes, fibrocytes, dendritic-like cells, adipocytes, and myocytes as the principal cell populations transfected. We proceeded to demonstrate elicitation of robust host immune responses after plasmid DNA (pDNA) vaccination. In guinea pigs equivalent humoral (antibody binding titers) immune responses were observed between protocols using either CELLECTRA-3P or intramuscular electroporation to deliver the DNA vaccine. In nonhuman primates, robust interferon-γ enzyme-linked immunospot and protective levels of hemagglutination inhibition titers after pDNA vaccination were observed in groups treated with the CELLECTRA-3P. In conclusion, these findings may assist in the future to design efficient, tolerable DNA vaccination strategies for the clinic.

  18. MicroRNA-450a-3p represses cell proliferation and regulates embryo development by regulating Bub1 expression in mouse.

    Directory of Open Access Journals (Sweden)

    Min Luo

    Full Text Available Bub1 is a critical component of the spindle assembly checkpoint (SAC and closely linked to cell proliferation and differentiation. We previously found that spontaneous abortion embryos contained a low level of Bub1 protein but normal mRNA level, while the knockdown of Bub1 leads to abnormal numerical chromosomes in embryonic cells. Here, we investigated the mechanism through which governs the post-transcriptional regulation of Bub1 protein expression level. We first conducted bioinformatics analysis and identified eight putative miRNAs that may target Bub1. Luciferase reporter assay confirmed that miR-450a-3p can directly regulate Bub1 by binding to the 3'-untranslated region of Bub1 mRNA. We found that the overexpression of miR-450a-3p in mouse embryonic fibroblast (MEF cells down-regulated Bub1 protein level, repressed cell proliferation, increased apoptosis and restricted most cells in G1 phase of the cell cycle. Furthermore, when the fertilized eggs were microinjected with miR-450a-3p mimics, the cleavage of zygotes was effectively suppressed. Our results strongly suggest that an abnormally decreased Bub1 level regulated by miRNAs may be implicated in the pathogenesis of spontaneous miscarriage. Therefore, the blockade of miR-450a-3p may be explored as a novel therapeutic strategy for preventing spontaneous miscarriages.

  19. Synthesis of group 10 metal complexes with a new unsymmetrical PN3P-pincer ligand through ligand post-modification: Structure and reactivity

    KAUST Repository

    Wang, Xiufang

    2017-01-01

    A post-modification strategy are used to synthesize a new class of diimine-amido PN3P-pincer group-10 transition metal complexes. The coordination chemistry and the thermal stabilities of their organometallic derivatives are characterized and investigated.

  20. Molecular epidemiology and genetic evolution of the whole genome of G3P[8] human rotavirus in Wuhan, China, from 2000 through 2013.

    Directory of Open Access Journals (Sweden)

    Yuan-Hong Wang

    Full Text Available Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses referred to as "new variant G3" have emerged and spread in China, being a dominant genotype until 2010, although their genomic evolution has not yet been well investigated.The complete genomes of 33 G3P[8] human rotavirus strains detected in Wuhan, China, from 2000 through 2013 were analyzed. Phylogenetic trees of concatenated sequences of all the RNA segments and individual genes were constructed together with published rotavirus sequences.Genotypes of 11 gene segments of all the 33 strains were assigned to G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis of the concatenated full genome sequences indicated that all the modern G3P[8] strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P[8] strains. While main lineages of all the 11 gene segments persisted during the study period, different lineages appeared occasionally in RNA segments encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations. In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes. Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007 and became dominant in 2008-2009 epidemic season, while lineage A1-1 persisted throughout the study period.Chinese G3P[8] rotavirus strains have evolved since 2000 by intra-genogroup reassortment with co-circulating strains, accumulating more reassorted genes over the years. This is the first large-scale whole genome-based study to assess the long-term evolution of common human rotaviruses (G3P[8] in an Asian country.

  1. Pressure-induced Pr{sup 3+} {sup 3}P{sub 0} luminescence in cubic Y{sub 2}O{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Alok M. [GE Global Research, One Research Circle, Niskayuna 12309, NY (United States); Renero-Lecuna, Carlos [MALTA CONSOLIDER Team – Dpto. Física Aplicada, Facultad de Ciencias, Universidad de Cantabria, Santander 39005 (Spain); Santamaría-Pérez, David [MALTA CONSOLIDER Team – Dpto. Químico Física, Facultad de Ciencias Químicas, Universidad Complutense Madrid, E-28040 Madrid (Spain); Rodríguez, Fernando [MALTA CONSOLIDER Team – DCITIMAC, Facultad de Ciencias, Universidad de Cantabria, Santander 39005 (Spain); Valiente, Rafael, E-mail: valientr@unican.es [MALTA CONSOLIDER Team – Dpto. Física Aplicada, Facultad de Ciencias, Universidad de Cantabria, Santander 39005 (Spain)

    2014-02-15

    An explanation for the puzzling absence of luminescence from the Pr{sup 3+} {sup 3}P{sub J[=0,1,2]} states in C-Ln{sub 2}O{sub 3} (cubic; Ln{sup 3+}=Lu{sup 3+}, Y{sup 3+}, Gd{sup 3+}) family of materials is provided by conducting a study of the emission properties of C-Y{sub 2}O{sub 3}:Pr{sup 3+} under applied hydrostatic pressure. Above 7 GPa, electronic transitions from the Pr{sup 3+} {sup 3}P{sub J[=0,1,2]} states are observed in the emission spectrum of C-Y{sub 2}O{sub 3}:Pr{sup 3+} at room temperature and below. The experimental data reveal that the crystal-field split Pr{sup 3+} 4f{sup 1}5d{sup 1} configuration is located entirely within the host lattice conduction band and that the promotion of the electron to the Pr{sup 3+} 4f{sup 1}5d{sup 1} state produces a self-trapped exciton-like state with the configuration, [Pr{sup 4+}+e{sub CB}], where e{sub CB} indicates an electron in the host lattice conduction band. Upon excitation, the exciton-like state bypasses the upper emitting {sup 3}P{sub J[=0,1,2]} states and directly feeds the lower emitting {sup 1}D{sub 2} state. This explains the absence of optical transitions from the Pr{sup 3+} {sup 3}P{sub J[=0,1,2]} states in the emission spectrum of C-Y{sub 2}O{sub 3}:Pr{sup 3+} at ambient pressure. At high pressures, emission transitions from the Pr{sup 3+} {sup 3}P{sub J[=0,1,2]} states are observed because of the localization of the Pr{sup 3+} 4f{sup 1}5d{sup 1} state to below the host lattice conduction band edge. -- Highlights: • Explanation for the complete absence of luminescence from the Pr{sup 3+} {sup 3}P{sub J} state in cubic Ln{sub 2}O{sub 3} sesquioxides. • By high pressure experiments, we have associated the absence of Pr{sup 3+} {sup 3}P{sub J} emission to the presence of an exciton state • The exciton state bypasses the upper emitting {sup 3}P{sub J} states and directly feeds the lower emitting {sup 1}D{sub 2} state. • Apart from the fundamental interest, this finding is relevantly

  2. miR-26b-3p Regulates Human Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation by Targeting Estrogen Receptor.

    Science.gov (United States)

    Wang, Qiaoling; Xu, Chen; Zhao, Yunpeng; Xu, Zhenyu; Zhang, Yan; Jiang, Junfeng; Yan, Binghao; Gu, Daolan; Wu, Minjuan; Wang, Yue; Liu, Houqi

    2016-03-01

    Human umbilical cord-derived mesenchymal stem cells (hUC-MSC) have been considered as promising candidates for cell-based regeneration medicine. However, the application was limited to its poor in vitro proliferation ability against the huge demand of cells. MicroRNA plays important roles in the regulation of cell proliferation, apoptosis, and differentiation. The objective of this study is to explore the roles of miRNAs in regulating the in vitro proliferation of hUC-MSC and unveil their possible mechanism. In this study, we found that miR-26b-3p was significantly upregulated during serial in vitro passage of hUC-MSC and was correlated with cellular senescence and cell cycle genes. The overexpression of miR-26b-3p greatly inhibited the proliferation of hUC-MSC in vitro, which is indicated by 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, cell cycle, and cell growth curve analyses. miR-26b-3p suppression partly rescued this phenotype by maintaining its proliferation ability in vitro. For mechanism studies, we predicted and validated that miR-26b-3p suppresses estrogen receptor 1 (ESR1) expression by directly binding to the coding sequence (CDS) region of its message RNA (mRNA), thus subsequently changing the expression of its downstream effector Cyclin D1. In conclusion, we found that miR-26b-3p played an important role in the regulation of hUC-MSC proliferation in vitro by targeting the ESR-CCND1 pathway.

  3. Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.

    Science.gov (United States)

    Shende, Vikram R; Neuendorff, Nichole; Earnest, David J

    2013-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modulation of core clock genes in the master circadian pacemaker, we examined miR-142-3p for evidence of circadian expression in the suprachiasmatic nuclei (SCN), regulation of its putative clock gene target Bmal1 via specific binding sites in the 3' UTR and overexpression-induced changes in the circadian rhythm of BMAL1 protein levels in SCN cells. In mice exposed to constant darkness (DD), miR-142-3p levels in the SCN were characterized by circadian rhythmicity with peak expression during early subjective day at CT 3. Mutagenesis studies indicate that two independent miRNA recognition elements located at nucleotides 1-7 and 335-357 contribute equally to miR-142-3p-induced repression of luciferase-reported Bmal1 3' UTR activity. Importantly, overexpression of miR-142-3p in immortalized SCN cells abolished circadian variation in endogenous BMAL1 protein levels in vitro. Collectively, our results suggest that miR-142-3p may play a role in the post-transcriptional modulation of Bmal1 and its oscillatory regulation in molecular feedback loops mediating SCN circadian function.

  4. Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.

    Directory of Open Access Journals (Sweden)

    Vikram R Shende

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modulation of core clock genes in the master circadian pacemaker, we examined miR-142-3p for evidence of circadian expression in the suprachiasmatic nuclei (SCN, regulation of its putative clock gene target Bmal1 via specific binding sites in the 3' UTR and overexpression-induced changes in the circadian rhythm of BMAL1 protein levels in SCN cells. In mice exposed to constant darkness (DD, miR-142-3p levels in the SCN were characterized by circadian rhythmicity with peak expression during early subjective day at CT 3. Mutagenesis studies indicate that two independent miRNA recognition elements located at nucleotides 1-7 and 335-357 contribute equally to miR-142-3p-induced repression of luciferase-reported Bmal1 3' UTR activity. Importantly, overexpression of miR-142-3p in immortalized SCN cells abolished circadian variation in endogenous BMAL1 protein levels in vitro. Collectively, our results suggest that miR-142-3p may play a role in the post-transcriptional modulation of Bmal1 and its oscillatory regulation in molecular feedback loops mediating SCN circadian function.

  5. A new family of two-dimensional zeolites prepared from the intermediate layered precursor IPC-3P obtained during the synthesis of TUN zeolite.

    Science.gov (United States)

    Kubů, Martin; Roth, Wieslaw J; Greer, Heather F; Zhou, Wuzong; Morris, Russell E; Přech, Jan; Čejka, Jiří

    2013-10-04

    The crystallization of zeolite TUN with 1,4-bis(N-methylpyrrolidinium)butane as template proceeds through an intermediate, designated IPC-3P, following the Ostwald rule of successive transformations. This apparently layered transient product has been thoroughly investigated and found to consist of MWW monolayers stacked without alignment in register, that is, disordered compared with MCM-22P. The structure was confirmed based on X-ray diffraction and high-resolution (HR)TEM analysis. The layered zeolite precursor IPC-3P can be swollen and pillared affording a combined micro- and mesoporous material with enhanced Brunauer-Emmett-Teller (BET) surface area (685 m(2) g(-1) ) and greater accessibility of Brønsted acid sites for bulky molecules. This mesoporous material was probed with 2,6-di-tert-butylpyridine (DTBP). IPC-3P and its modification create a new layered zeolite sub-family belonging to the MWW family. FTIR data indicate that (Al)MWW materials MCM-22 and IPC-3 with Si/Al ratios greater than 20 exhibit a lower relative ratio of Brønsted to Lewis acid sites than MCM-22 (with Si/Al ratios of around 13), that is, less than 2 versus more than 3, respectively. This is maintained even upon pillaring and warrants further exploration of materials like IPC-3P with a higher Al content. The unique XRD features of IPC-3P indicating misaligned stacking of layers and distinct from MCM-22P, are also seen in other MWW materials such as EMM-10P, hexamethonium-templated (HM)-MCM-22, ITQ-30, and UZM-8 suggesting the need for more detailed study of their identity and properties.

  6. Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression.

    Science.gov (United States)

    Gao, Yong-Tao; Chen, Xiao-Bing; Liu, Hong-Lin

    2016-01-01

    MicroRNAs (miRNA) are believed to play an important role in glioblastoma multiforme (GBM)chemotherapy. Our study aims to investigate potential miRNA biomarkers in GBM. Sixty GBM patients, which were given temozolomide (TMZ) chemotherapy and recurrent radiotherapy, were recruited. miRNA array was performed in cancerous and in paired normal tissues. Microarray results were further validated by a quantitative real-time PCR in selected tissues and GBM cell lines. TMZ resistance cells were developed and cell proliferation along with colony formation assays was determined. Our study employed H2AX formation and flow cytometry to analyse the role of miRNA in DNA damage and apoptosis. Our study illustrated 16 miRNA in which 9 were up-regulated and 7 down-regulated. and their differential expression were demonstrated in a recurrent GBM tissue. Among them, miRNA-370-3p demonstrated the highest level of down- regulation in tissues and in TMZ resistance cells. miRNA-370-3p mimic increased its expression and sensitivity of GBM cells to TMZ by suppressing the self-reparative ability of tumour cell DNA. O(6)-methylguanine-DNA methyltransferase (MGMT) was identified as the direct target gene of miR-370-3p, and it was found to be inversely correlated with miR-370-3p expression in tissue samples obtained. Thus, our study demonstrated a critical clinical role of an up-regulated miR-370-3p expression in glioblastoma multiforme chemotherapy sensitivity.

  7. miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers.

    Directory of Open Access Journals (Sweden)

    Liqin Du

    Full Text Available NSCLC (non-small cell lung cancer often exhibits resistance to paclitaxel treatment. Identifying the elements regulating paclitaxel response will advance efforts to overcome such resistance in NSCLC therapy. Using in vitro approaches, we demonstrated that over-expression of the microRNA miR-337-3p sensitizes NCI-H1155 cells to paclitaxel, and that miR-337-3p mimic has a general effect on paclitaxel response in NSCLC cell lines, which may provide a novel adjuvant strategy to paclitaxel in the treatment of lung cancer. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p on paclitaxel sensitivity. Further investigation showed that miR-337-3p mimic also sensitizes cells to docetaxel, another member of the taxane family, and that STAT3 levels are significantly correlated with taxane resistance in lung cancer cell lines, suggesting that endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer. The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.

  8. Assembly, activation, and trafficking of the Fet3p.Ftr1p high affinity iron permease complex in Saccharomyces cerevisiae.

    Science.gov (United States)

    Singh, Arvinder; Severance, Scott; Kaur, Navjot; Wiltsie, William; Kosman, Daniel J

    2006-05-12

    The high affinity iron uptake complex in the yeast plasma membrane (PM) consists of the ferroxidase, Fet3p, and the ferric iron permease, Ftr1p. We used a combination of yeast two-hybrid analysis, confocal fluorescence microscopy, and fluorescence resonance energy transfer (FRET) quantification to delineate the motifs in the two proteins required for assembly and maturation into an uptake-competent complex. The cytoplasmic, carboxyl-terminal domain of each protein contains a four-residue motif adjacent to the cytoplasm-PM interface that supports an interaction between the proteins. This interaction has been quantified by two-hybrid analysis and is required for assembly and trafficking of the complex to the PM and for the approximately 13% maximum FRET efficiency determined. In contrast, the Fet3p transmembrane domain (TM) can be exchanged with the TM domain from the vacuolar ferroxidase, Fet5p, with no loss of assembly and trafficking. A carboxyl-terminal interaction between the vacuolar proteins, Fet5p and Fth1p, also was quantified. As a measure of the specificity of interaction, no interaction between heterologous ferroxidase permease pairs was observed. Also, whereas FRET was quantified between fluorescent fusions of the copper permease (monomers), Ctr1p, none was observed between Fet3p and Ctr1p. The results are consistent with a (minimal) heterodimer model of the Fet3p.Ftr1p complex that supports the trafficking of iron from Fet3p to Ftr1p for iron permeation across the yeast PM.

  9. miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma.

    Science.gov (United States)

    Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; Di Gennaro, Gianfranco; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-05-10

    The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30-50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs.

  10. Repression of mitochondrial translation, respiration and a metabolic cycle-regulated gene, SLF1, by the yeast Pumilio-family protein Puf3p.

    Directory of Open Access Journals (Sweden)

    Marc Chatenay-Lapointe

    Full Text Available Synthesis and assembly of the mitochondrial oxidative phosphorylation (OXPHOS system requires genes located both in the nuclear and mitochondrial genomes, but how gene expression is coordinated between these two compartments is not fully understood. One level of control is through regulated expression mitochondrial ribosomal proteins and other factors required for mitochondrial translation and OXPHOS assembly, which are all products of nuclear genes that are subsequently imported into mitochondria. Interestingly, this cadre of genes in budding yeast has in common a 3'-UTR element that is bound by the Pumilio family protein, Puf3p, and is coordinately regulated under many conditions, including during the yeast metabolic cycle. Multiple functions have been assigned to Puf3p, including promoting mRNA degradation, localizing nucleus-encoded mitochondrial transcripts to the outer mitochondrial membrane, and facilitating mitochondria-cytoskeletal interactions and motility. Here we show that Puf3p has a general repressive effect on mitochondrial OXPHOS abundance, translation, and respiration that does not involve changes in overall mitochondrial biogenesis and largely independent of TORC1-mitochondrial signaling. We also identified the cytoplasmic translation factor Slf1p as yeast metabolic cycle-regulated gene that is repressed by Puf3p at the post-transcriptional level and promotes respiration and extension of yeast chronological life span when over-expressed. Altogether, these results should facilitate future studies on which of the many functions of Puf3p is most relevant for regulating mitochondrial gene expression and the role of nuclear-mitochondrial communication in aging and longevity.

  11. Photoexcitation and photoionization from the 2p{sup 5}3p[5/2]{sub 2,3} levels in neon

    Energy Technology Data Exchange (ETDEWEB)

    Baig, M. A.; Bokhari, I. A.; Rafiq, M.; Kalyar, M. A.; Hussian, T.; Ali, Raheel; Piracha, N. K. [Atomic and Molecular Physics Laboratory, Department of Physics, Quaid-i-Azam University, 45320 Islamabad (Pakistan); Department of Physics, John Carroll University, 20700 N. Park Boulevard, University Heights, Ohio 44118 (United States)

    2011-07-15

    We present measurements of the excitation spectra from the 2p{sup 5}3p[5/2]{sub 3,2} levels in neon using two-step laser excitation and ionization in conjunction with an optogalvanic detection in dc and rf discharge cells. The 2p{sup 5}3p[5/2]{sub 3,2} intermediate levels have been approached via the collisionally populated 2p{sup 5}3s[3/2]{sub 2} metastable level. The Rydberg series 2p{sup 5}({sup 2}P{sub 3/2})nd[7/2]{sub 4} (12 {<=}n{<=} 44), 2p{sup 5}({sup 2}P{sub 3/2})ns[3/2]{sub 2} (13 {<=}n{<=} 35) and the parity forbidden transitions 2p{sup 5}({sup 2}P{sub 3/2})np[5/2]{sub 3} (13 {<=}n{<=} 19) have been observed from the 2p{sup 5}3p[5/2]{sub 3} level, whereas the 2p{sup 5}({sup 2}P{sub 3/2})nd[7/2]{sub 3} (12 {<=}n{<=} 44), 2p{sup 5}({sup 2}P{sub 3/2})ns[3/2]{sub 2} (13 {<=}n{<=} 35), and 2p{sup 5}({sup 2}P{sub 1/2})nd'[5/2]{sub 3} (9 {<=}n{<=} 12) Rydberg series have been observed from the 2p{sup 5}3p[5/2]{sub 2} level in accordance with the {Delta}J ={Delta}K = {+-} 1 selection rules. The photoionization cross sections from the 2p{sup 5}3p[5/2]{sub 3} intermediate level have been measured at eight ionizing laser wavelengths (399, 395, 390, 385, 380, 370, 364, and 355 nm) and that from the 2p{sup 5}3p[5/2]{sub 2} level at 401.8 nm. These measurements are in excellent agreement with the experimental values reported in the literature, while the experimental data lie much below the theoretically calculated photoionization cross sections curve.

  12. Contribution of Intronic miR-338-3p and Its Hosting Gene AATK to Compensatory β-Cell Mass Expansion.

    Science.gov (United States)

    Jacovetti, Cécile; Jimenez, Veronica; Ayuso, Eduard; Laybutt, Ross; Peyot, Marie-Line; Prentki, Marc; Bosch, Fatima; Regazzi, Romano

    2015-05-01

    The elucidation of the mechanisms directing β-cell mass regeneration and maintenance is of interest, because the deficit of β-cell mass contributes to diabetes onset and progression. We previously found that the level of the microRNA (miRNA) miR-338-3p is decreased in pancreatic islets from rodent models displaying insulin resistance and compensatory β-cell mass expansion, including pregnant rats, diet-induced obese mice, and db/db mice. Transfection of rat islet cells with oligonucleotides that specifically block miR-338-3p activity increased the fraction of proliferating β-cells in vitro and promoted survival under proapoptotic conditions without affecting the capacity of β-cells to release insulin in response to glucose. Here, we evaluated the role of miR-338-3p in vivo by injecting mice with an adeno-associated viral vector permitting specific sequestration of this miRNA in β-cells. We found that the adeno-associated viral construct increased the fraction of proliferating β-cells confirming the data obtained in vitro. miR-338-3p is generated from an intron of the gene coding for apoptosis-associated tyrosine kinase (AATK). Similarly to miR-338-3p, we found that AATK is down-regulated in rat and human islets and INS832/13 β-cells in the presence of the cAMP-raising agents exendin-4, estradiol, and a G-protein-coupled Receptor 30 agonist. Moreover, AATK expression is reduced in islets of insulin resistant animal models and selective silencing of AATK in INS832/13 cells by RNA interference promoted β-cell proliferation. The results point to a coordinated reduction of miR-338-3p and AATK under insulin resistance conditions and provide evidence for a cooperative action of the miRNA and its hosting gene in compensatory β-cell mass expansion.

  13. Towards a Mg lattice clock: Observation of the $^1S_{0}-$$^3P_{0}$ transition and determination of the magic wavelength

    CERN Document Server

    Kulosa, A P; Zipfel, K H; Rühmann, S; Sauer, S; Jha, N; Gibble, K; Ertmer, W; Rasel, E M; Safronova, M S; Safronova, U I; Porsev, S G

    2015-01-01

    We optically excite the electronic state $3s3p~^3P_{0}$ in $^{24}$Mg atoms, laser-cooled and trapped in a magic-wavelength lattice. An applied magnetic field enhances the coupling of the light to the otherwise strictly forbidden transition. We determine the magic wavelength, the quadratic magnetic Zeeman shift and the transition frequency to be 468.463(207)$\\,$nm, -206.6(2.0)$\\,$MHz/T$^2$ and 655 058 646 691(101)$\\,$kHz, respectively. These are compared with theoretical predictions and results from complementary experiments. We also developed a high-precision relativistic structure model for magnesium, give an improved theoretical value for the blackbody radiation shift and discuss a clock based on bosonic magnesium.

  14. Repression of Toll-like receptor-4 by microRNA-149-3p is associated with smoking-related COPD

    Directory of Open Access Journals (Sweden)

    Shen W

    2017-02-01

    Full Text Available Wen Shen,1,* Jia Liu,2,* Guohou Zhao,1 Minjuan Fan,1 Gao Song,3 Yang Zhang,1 Zhiying Weng,3 You Zhang4 1Department of Respiratory Medicine, 2Department of Experimental Zoology, The Second Affiliated Hospital of Kunming Medical University, 3School of Pharmaceutical Science, Kunming Medical University, 4Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China *These authors contributed equally to this work Background: Smoking is the leading cause of COPD. Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease. This study aims to identify specific circulating microRNAs (miRNAs from the blood of COPD patients with a long history of smoking.Methods: Blood samples from four different groups were collected, and miRNA microarray was performed. Differential expression of miRNAs was verified by quantitative polymerase chain reaction. In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE or transfected with miR-149-3p inhibitor/mimics. Protein levels of Toll-like receptor 4 (TLR-4 and nuclear factor κB (NF-κB were detected using Western blot and immunofluorescence. Interleukin (IL-1β and tumor necrosis factor (TNF-α levels were determined by an enzyme-linked immunosorbent assay.Results: miRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups. Expression of miR-149-3p in group C (non-smoker non-COPD was higher than in group S (smoker non-COPD, S-COPD (smoker with stable COPD and AE-COPD (smoker with acute exacerbation COPD. CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-κB levels in THP-1 cells. Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes. Furthermore, overexpression of miR-149-3p inhibited

  15. Trajectory-dependent energy- and charge-transfer in collisions of Br sup + ( sup 3 P sub 2) with Pt(1 1 1)

    CERN Document Server

    Maazouz, P L; Jacobs, D C

    2003-01-01

    Collisions of hyperthermal energy Br sup + ( sup 3 P sub 2) with Pt(1 1 1) produces scattered Br sup - ( sup 1 S sub 0) with a yield approaching 7%. The energy distribution of the scattered product exhibits an unusual dependence on the collision energy. Specifically, as the incident energy increases from 34 to 54 eV, the peak energy of scattered Br sup - ( sup 1 S sub 0) decreases. Furthermore, the anion yield reaches a sharp maximum when Br sup + ( sup 3 P sub 2) approaches the surface with 26 eV of translational energy. The unusual scattering behavior is attributed to a trajectory dependent collision-induced deformation of the lattice. The corresponding electronic perturbation evolves synchronously with the motion of the departing projectile - leading to an enhanced charge-transfer probability.

  16. Half-metallic ferromagnetism in Fe-doped Zn{sub 3}P{sub 2} from first-principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Jaiganesh, G., E-mail: jaiganesh@igcar.gov.in; Jaya, S. Mathi, E-mail: jaiganesh@igcar.gov.in [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam-603102 (India)

    2014-04-24

    Using the first-principles calculations based on the density functional theory, we have studied the magnetism and electronic structure of Fe-doped Zinc Phosphide (Zn{sub 3}P{sub 2}). Our results show that the half-metallic ground state and ferromagnetic stability for the small Fe concentrations considered in our study. The stability of the doped material has been studied by calculating the heat of formation and analyzing the minimum total energies in nonmagnetic and ferromagnetic phases. A large value of the magnetic moment is obtained from our calculations and our calculation suggests that the Fe-doped Zn{sub 3}P{sub 2} may be a useful material in semiconductor spintronics.

  17. Mapping of Microsatellite SW943 to Porcine Chromosome 12p11-(2/3p13) Using Primed in situ Synthesis and Somatic Cell Hybrid Panel

    Institute of Scientific and Technical Information of China (English)

    LIU Bang; WANG Yong-qiang; ZHANG Qing-de; YU Mei; ZHAO Shu-hong; XIONG Tong-an; LI Kui

    2002-01-01

    The porcine microsatellite SW943 was regionally localized on 12p11-(2/3p13) by the two methods: the Primed in situ (PRINS) labelling on the pachytene bivalents of pigs using the Dig-11-dUTP as the report molecule and pig × rodent Somatic Cell Hybrid PaneI(SCHP) which contains 27 cell lines through PCR amplification. Advantages and disadvantages of the two methods for physical mapping of microsatellites were also discussed.

  18. Spectroscopy of the $^{1}S_{0}-\\,^{3}P_{1}$ line in laser cooled Yb with an injection-locked diode laser at 1111.6nm

    CERN Document Server

    Kostylev, Nikita; Tobar, Michael E; McFerran, John J

    2014-01-01

    We generate sub-MHz linewidth 555.8nm radiation through the use of laser injection locking of a semiconductor diode at 1111.6nm followed by frequency doubling in a resonant cavity. The integrity of the injection lock is investigated by studying an offset-beat signal between slave and master lasers, and by performing spectroscopy on the $(6s)^{2}$ $^{1}S_{0}-(6s6p)$$^{3}P_{1}$ transition in magneto-optically trapped ytterbium.

  19. Measurement of the 1s2s 1S0-1s2p 3P1 intercombination interval in helium-like silicon.

    Science.gov (United States)

    Redshaw, M; Myers, E G

    2002-01-14

    Using Doppler-tuned fast-beam laser spectroscopy the 1s2s 1S0-1s2p 3P1 intercombination interval in 28Si12+ has been measured to be 7230.5(2) cm(-1). The experiment made use of a single-frequency Nd:YAG (1.319 microm) laser and a high-finesse optical buildup cavity. The result provides a precision test of modern relativistic and QED atomic theory.

  20. Mild and Efficient Reagents for Oxidation of Alcohols: [MeOCH2(Ph3P]+[CrO3X]ֿ, (X=F, Cl

    Directory of Open Access Journals (Sweden)

    Amir Lashgari

    2015-01-01

    Full Text Available Two fast, mild, and reasonable oxidizing agents, Methoxymethyltriphenylphosphonium Halochromates (VI, [MeOCH2(Ph3P]+ [CrO3X]ֿ (MMTriPPXC are synthesized. The preparations of Methoxymethyltriphenylphosphonium Halochromates are new and efficient reagents for the oxidation of primary and secondary alcohols to their corresponding carbonyl compounds in dichloromethane at ambient temperature. These are obtained with relatively short reaction times. The oxidants/substrates ratios of 1:1 are employed.

  1. A Proteomics Approach to Investigate miR-153-3p and miR-205-5p Targets in Neuroblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Ketan S Patil

    Full Text Available MicroRNAs are key regulators associated with numerous diseases. In HEK293 cells, miR-153-3p and miR-205-5p down-regulate alpha-synuclein (SNCA and Leucine-rich repeat kinase 2 (LRRK2, two key proteins involved in Parkinson's disease (PD. We have used two-dimensional gel electrophoresis (2D-PAGE coupled to mass spectrometry (MS to identify a spectrum of miR-153-3p and miR-205-5p targets in neuronal SH-SY5Y cells. We overexpressed and inhibited both microRNAs in SH-SY5Y cells and through comparative proteomics profiling we quantified ~240 protein spots from each analysis. Combined, thirty-three protein spots were identified showing significant (p-value < 0.05 changes in abundance. Modulation of miR-153-3p resulted in seven up-regulated proteins and eight down-regulated proteins. miR-205 modulation resulted in twelve up-regulated proteins and six down-regulated proteins. Several of the proteins are associated with neuronal processes, including peroxiredoxin-2 and -4, cofilin-1, prefoldin 2, alpha-enolase, human nucleoside diphosphate kinase B (Nm23 and 14-3-3 protein epsilon. Many of the differentially expressed proteins are involved in diverse pathways including metabolism, neurotrophin signaling, actin cytoskeletal regulation, HIF-1 signaling and the proteasome indicating that miR-153-3p and miR-205-5p are involved in the regulation of a wide variety of biological processes in neuroblastoma cells.

  2. Lifetime measurement of some excited states belonging to the 3p4nd ( = 4–6) configurationof ArII

    Indian Academy of Sciences (India)

    S Karmakar; M B Das

    2007-09-01

    The radiative lifetimes of eight levels belonging to the 3p4nd ( = 4–6) configuration of ArII have been measured using high frequency deflection technique together with a delayed coincidence single photon counting arrangement. Lifetimes of some of the levels have been measured for the first time. The results have been compared with other experimental and theoretical values.

  3. Low-dose irradiation promotes Rad51 expression by down-regulating miR-193b-3p in hepatocytes

    Science.gov (United States)

    Lee, Eon-Seok; Won, Yeo Jin; Kim, Byoung-Chul; Park, Daeui; Bae, Jin-Han; Park, Seong-Joon; Noh, Sung Jin; Kang, Yeong-Rok; Choi, Si Ho; Yoon, Je-Hyun; Heo, Kyu; Yang, Kwangmo; Son, Tae Gen

    2016-05-01

    Current evidence indicates that there is a relationship between microRNA (miRNA)-mediated gene silencing and low-dose irradiation (LDIR) responses. Here, alterations of miRNA expression in response to LDIR exposure in male BALB/c mice and three different types of hepatocytes were investigated. The miRNome of the LDIR-exposed mouse spleens (0.01 Gy, 6.5 mGy/h) was analyzed, and the expression of miRNA and mRNA was validated by qRT-PCR. Western blotting, chromatin immunoprecipitation (ChIP), and luciferase assays were also performed to evaluate the interaction between miRNAs and their target genes and to gain insight into the regulation of miRNA expression. The expression of miRNA-193b-3p was down-regulated in the mouse spleen and liver and in various hepatocytes (NCTC, Hepa, and HepG2 cell lines) in response to LDIR. The down-regulation of miR-193b-3p expression was caused by histone deacetylation on the miR-193b-3p promoter in the HepG2 cells irradiated with 0.01 Gy. However, the alteration of histone deacetylation and miR-193b-3p and Rad51 expression in response to LDIR was restored by pretreatment with N-acetyl-cyctein. In conclusion, we provide evidence that miRNA responses to LDIR include the modulation of cellular stress responses and repair mechanisms.

  4. Confirmation of temperature independence in the fluorescence lifetime of the 3P 0 → 3F 2 transition in praseodymium-doped fluoride glass

    Science.gov (United States)

    Nguyen, Thinh B.; Vella, Vince; Baxter, Greg W.; Collins, Stephen F.; Newman, Peter J.; MacFarlane, Douglas R.

    2006-05-01

    The dependence of the fluorescence lifetime from the 3P0 → 3F2 transition in praseodymium-doped fluoride glass as a function of dopant concentration and temperature was investigated. It was found that the fluorescence lifetime at the concentration of 7000 ppm was constant with temperature, confirming the prediction of temperature independence in the lifetime for this transition in Pr3+-doped ZBLAN glass.

  5. Identification of miRNomes in human stomach and gastric carcinoma reveals miR-133b/a-3p as therapeutic target for gastric cancer.

    Science.gov (United States)

    Liu, Yanfang; Zhang, Xin; Zhang, Yujing; Hu, Zunqi; Yang, Dejun; Wang, Changming; Guo, Meng; Cai, Qingping

    2015-12-01

    Gastric cancer (GC) is the fourth most frequent malignant disease and the second leading cause of cancer mortality worldwide, but the molecular mechanisms underlying this clinically heterogeneous disease are complex and remain far from completely understood. Accumulating evidence suggests that abnormal microRNA (miRNA) expression is involved in tumorigenesis. However, their accurate expression pattern, function, and mechanism in GC remain unclear. Here, a heatmap analysis of the miRNomes was performed across TCGA datasets and the expression of miR-133 family was found to be consistently downregulated in GC. This result was confirmed in two GC cell lines and 20 pairs of primary GC tissues, and further study demonstrated that the downregulation of miR-133 was mainly mediated by histone modification within its promoter region. Importantly, restoration of miR-133b/a-3p expression could suppress GC cell proliferation and promote cell apoptosis by targeting anti-apoptotic molecules Mcl-1 and Bcl-xL. Consistent with in vitro results, reintroducing of miR-133b/a-3p expression significantly delayed tumor formation and reduced tumor size of GC cells in xenograft nude mice. And the inverse relationship between miR-133b/a-3p and its targets was verified in xenograft mice. Taken together, our findings suggest that miR-133b/a-3p acts as a tumor suppressor in GC by directly targeting Mcl-1 and Bcl-xL. Revealing novel mechanism for oncogene inhibition by miRNA-mediated pathways offers new avenues for GC treatment.

  6. A novel PtdIns3P and PtdIns(3,5)P-2 phosphatase with an inactivating variant in centronuclear myopathy

    OpenAIRE

    Tosch, Valerie; Rohde, Holger M.; Tronchere, Helene; Zanoteli, Edmar; Monroy, Nancy; Kretz, Christine; Dondaine, Nicolas; Payrastre, Bernard; Mandel, Jean-Louis; Laporte, Jocelyn

    2006-01-01

    In eukaryotic cells, phosphoinositides are lipid second messengers important for many cellular processes and have been found dysregulated in several human diseases. X-linked myotubular (centronuclear) myopathy is a severe congenital myopathy caused by mutations in a phosphatidylinositol 3-phosphate (PtdIns3P) phosphatase called myotubularin, and mutations in dominant centronuclear myopathy (CNM) cases were identified in the dynamin 2 gene. the genes mutated in autosomal recessive cases of CNM...

  7. Synthesis, crystal and electronic structures of the new Zintl phases Ba3Al3Pn5 (Pn = P, As) and Ba3Ga3P5.

    Science.gov (United States)

    He, Hua; Tyson, Chauntae; Saito, Maia; Bobev, Svilen

    2013-01-01

    The new Zintl compounds Ba(3)Al(3)P(5), Ba(3)Al(3)As(5,) and Ba(3)Ga(3)P(5) have been synthesized using molten metal fluxes. They are isoelectronic and isotypic, crystallizing with a novel rhombohedral structure type in the space group R3c with unit cell constants a = 14.5886(9) Å, c = 28.990(3) Å for Ba(3)Al(3)P(5), a = 14.613(3) Å, c = 28.884(8) Å for Ba(3)Ga(3)P(5), and a = 14.9727(13) Å, c = 29.689(4) Å for Ba(3)Al(3)As(5), respectively. The structures are based on TrPn(4) (Tr = Al, Ga; Pn = P, As) tetrahedra that share both edges and corners, leading to intricate arrangements embodied in the [Tr(4)Pn(9)](15-) and [Tr(3)Pn(6)](9-) strands, interconnected by dimeric [Tr(2)Pn(6)](12-) units. The Ba(2+) cations reside within cylindrical channels within the polyanionic framework and provide the valence electrons needed for Tr-Pn covalent bonding. In spite of the large and complex structure, there are no homoatomic Tr-Tr or Pn-Pn interactions, hence, the structures can be readily rationalized in the context of the Zintl-Klemm formalism as follows [Ba(2+)](3)[Tr(3+)](3)[Pn(3-)](5); calculations on their electronic band-structures confirm this reasoning and reveal about 1.4-1.9 eV energy band gaps, that is, semiconducting behavior. Structural parallels with other known Zintl compounds are also presented.

  8. Vibrational quenching of CO2(010) by collisions with O(3P) at thermal energies: a quantum-mechanical study.

    Science.gov (United States)

    de Lara-Castells, M P; Hernández, Marta I; Delgado-Barrio, G; Villarreal, P; López-Puertas, M

    2006-04-28

    The CO(2)(010)-O((3)P) vibrational energy transfer (VET) efficiency is a key input to aeronomical models of the energy budget of the upper atmospheres of Earth, Venus, and Mars. This work addresses the physical mechanisms responsible for the high efficiency of the VET process at the thermal energies existing in the terrestrial upper atmosphere (150 Kmechanical study of the process within a reduced-dimensionality approach. In this model, all the particles remain along a plane and the O((3)P) atom collides along the C(2v) symmetry axis of CO(2), which can present bending oscillations around the linear arrangement, while the stretching C-O coordinates are kept fixed at their equilibrium values. Two kinds of scattering calculations are performed on high-quality ab initio potential energy surfaces (PESs). In the first approach, the calculations are carried out separately for each one of the three PESs correlating to O((3)P). In the second approach, nonadiabatic effects induced by spin-orbit couplings (SOC) are also accounted for. The results presented here provide an explanation to some of the questions raised by the experiments and aeronomical observations. At thermal energies, nonadiabatic transitions induced by SOC play a key role in causing large VET efficiencies, the process being highly sensitive to the initial fine-structure level of oxygen. At higher energies, the two above-mentioned approaches tend to coincide towards an impulsive Landau-Teller mechanism of the vibrational to translational (V-T) energy transfer.

  9. Characteristics of CuO-MoO3-P2O5 catalyst and its catalytic wet oxidation (CWO) of dye wastewater under extremely mild conditions.

    Science.gov (United States)

    Ma, Hongzhu; Zhuo, Qiongfang; Wang, Bo

    2007-11-01

    In order to develop a catalyst with high activity for catalytic wet oxidation (CWO) processing at lower temperatures (35 degrees C) and atmospheric pressure, a new CuO-MoO3-P2O5 catalystwas synthesized by a solid-state reaction method and was characterized by X-ray diffraction (XRD), Fourier transformation infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), selected area electronic diffraction (SAED), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDXS) for elemental mapping. Methylene blue (MB) was adopted to investigate the catalytic activity of CuO-MoO3-P2O5 in CWO processing. The results show that this new catalyst has a high catalytic activity to decolorize MB under mild condition. The color removal of MB (the initial concentration was 0.3 g L(-1) and initial pH was 5) can reach to 99.26% within 10 min at 35 degrees C and atmospheric pressure. Catalyst lifespan and selectivity were also tested, and the results show that after the catalyst was used three times, catalyst activity still remains. Selectivity testing shows that CuO-MoO3-P2O5 has high catalytic activity on degradation of MB, whereas this catalyst has less impact on methyl orange (the color removal was 99.65% for MB and 55% for methyl orange under the same conditions). According to the experimental results, a possible mechanism of catalytic degradation of MB was proposed.

  10. MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis

    Science.gov (United States)

    Lecca, Davide; Marangon, Davide; Coppolino, Giusy T.; Méndez, Aida Menéndez; Finardi, Annamaria; Costa, Gloria Dalla; Martinelli, Vittorio; Furlan, Roberto; Abbracchio, Maria P.

    2016-01-01

    In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here, we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of oligodendroglial maturation, that, in the mammalian CNS regulates the expression of myelin genes by simultaneously acting on several of its already validated targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the cerebrospinal fluid of MS patients bearing active demyelinating lesions, suggesting that its pathological upregulation may contribute to MS development, at least in part by blockade of OPC differentiation leading to impaired repair of demyelinated lesions. PMID:27698367

  11. Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p.

    Science.gov (United States)

    Ding, Guoping; Zhou, Liangjing; Qian, Yingming; Fu, Mingnian; Chen, Jian; Chen, Jionghuang; Xiang, Jianyang; Wu, Zhengrong; Jiang, Guixing; Cao, Liping

    2015-10-06

    It has been reported tumor-derived exosomes can transfer miRNAs to recipient cells in the tumor microenvironment, promoting tumor invasion and metastasis. The present research aimed to explore how pancreatic cancer (PC) derived exosomal miRNAs inhibited mRNA expression of dendritic cells and induced immune tolerance. Our study revealed that 9 PC-related miRNAs were increased and 208 mRNAs were inhibited in exosome-stimulated dendritic cells (exo-iDCs) compared to immature dendritic cells (iDCs). A target prediction between the 9 miRNAs and 208 mRNAs was performed by bioinformatics database analysis. From the target prediction, it was predicted and validated that regulatory factor X-associated protein (RFXAP), an important transcription factor for MHC II, was inhibited by miR-212-3p transferred from PC-secreted exosomes, resulting in decreased MHC II expression. Moreover, a clinical study showed a negative correlation between miR-212-3p and RFXAP in PC tissue. From these data, we concluded that PC-related miRNAs can be transferred to dendritic cells via exosome and inhibit target mRNA expression. More importantly, PC-derived exosomes inhibit RFXAP expression via miR-212-3p, which decrease MHC II expression and induce immune tolerance of dendritic cells. RFXAP deficiency has never been reported in solid tumors. The functions and mechanisms of RFXAP in tumors deserve future explorations.

  12. Effects of Zn doping concentration on resistive switching characteristics in Ag/La$_{1−x}Zn$_x$MnO$_3$/p$^+$-Si devices

    Indian Academy of Sciences (India)

    SHUAISHUAI YAN; HUA WANG; JIWEN XU; LING YANG; WEI QIU; QISONG CHEN; DONG HAN

    2016-12-01

    Ag/La$_{1−x}$Zn$_x$MnO$_3$/p$^+$-Si devices with different Zn doping contents were fabricated through sol–gel method. The effects of Zn doping concentration on the microstructure of La$_{1−x}$Zn$_x$MnO$_3$ films, as well as on the resistance switching behaviour and endurance characteristics of Ag/La$_{1−x}$Zn$_x$MnO$_3$/p$^{+}$-Si were investigated. After annealing at 600$^{\\circ}$C for 1~h, the La$_{1−x}$Zn$_x$MnO$_3$ ($x = 0.1$, 0.2, 0.3, 0.4, 0.5) are amorphous and have bipolar resistance characteristics, with RHRS/RLRS ratios $>$103. However, the endurance characteristics show considerable differences; $x = 0.3$ shows the best endurance characteristics in more than 1000 switching cycles. The conduction mechanism of the Ag/La$_{1−x}$Zn$_x$MnO$_3$/p$^{+}$-Si is the Schottky emission mode at high resistance state. However, the conduction mechanism at low resistance state varies with Zn doping concentration. The dominant mechanism at $x = 0.1$ is filamentary conduction mechanism, whereas that at $x \\ge 0.2$ is space-charge-limited current conduction.

  13. Mps3p is a novel component of the yeast spindle pole body that interacts with the yeast centrin homologue Cdc31p.

    Science.gov (United States)

    Jaspersen, Sue L; Giddings, Thomas H; Winey, Mark

    2002-12-23

    Accurate duplication of the Saccharomyces cerevisiae spindle pole body (SPB) is required for formation of a bipolar mitotic spindle. We identified mutants in SPB assembly by screening a temperature-sensitive collection of yeast for defects in SPB incorporation of a fluorescently marked integral SPB component, Spc42p. One SPB assembly mutant contained a mutation in a previously uncharacterized open reading frame that we call MPS3 (for monopolar spindle). mps3-1 mutants arrest in mitosis with monopolar spindles at the nonpermissive temperature, suggesting a defect in SPB duplication. Execution point experiments revealed that MPS3 function is required for the first step of SPB duplication in G1. Like cells containing mutations in two other genes required for this step of SPB duplication (CDC31 and KAR1), mps3-1 mutants arrest with a single unduplicated SPB that lacks an associated half-bridge. MPS3 encodes an essential integral membrane protein that localizes to the SPB half-bridge. Genetic interactions between MPS3 and CDC31 and binding of Cdc31p to Mps3p in vitro, as well as the fact that Cdc31p localization to the SPB is partially dependent on Mps3p function, suggest that one function for Mps3p during SPB duplication is to recruit Cdc31p, the yeast centrin homologue, to the half-bridge.

  14. Microstructure of interaction interface between Al-Si, Zn-Al alloys and Al2O3p/6061Al composite

    Institute of Scientific and Technical Information of China (English)

    许志武; 闫久春; 吕世雄; 杨士勤

    2004-01-01

    Interaction behaviors between Al-Si, Zn-AI alloys and Al2O3p/6061AI composite at different heating temperatures were investigated. It is found that Al2O3p/6061Al composite can be wetted well by AlSi-1, AlSi-4 and Zn-Al alloys and an interaction layer forms between the alloy and composite during interaction. Little Al-Si alloys remain on the surface when they fully wet the composite and Si element in Al-Si alloy diffuses into composite entirely and assembles in the composite near the interface of Al-Si alloy/composite to form a Si-rich zone. The microstructure in interaction layer with Si penetration is still dense. Much more residual Zn-Al alloy exists on the surface of composite when it wets the composite, and porosities appear at the interface of Zn-Al alloy/composite. The penetration of elements Zn, Cu of Zn-Al alloy into composite leads to the generation of shrinkage cavities in the interaction layer and makes the microstructure of Al2 O3p/6061A1 composite loose.

  15. LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p.

    Science.gov (United States)

    Nie, Wei; Ge, Hui-juan; Yang, Xiao-qun; Sun, Xiangjie; Huang, Hai; Tao, Xia; Chen, Wan-sheng; Li, Bing

    2016-02-01

    Recently, the long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogenic gene in multiple human tumor entitles, and dysregulation of UCA1 was tightly linked to carcinogenesis and cancer progression. However, whether the aberrant expression of UCA1 in non-small cell lung cancer (NSCLC) is associated with malignancy, metastasis or prognosis has not been characterized. In this study, we found that UCA1 was upregulated in NSCLC tissues. Higher expression of UCA1 led to a significantly poorer survival time, and multivariate analysis revealed that UCA1 was an independent risk factor of prognosis. UCA1 overexpression enhanced, whereas UCA1 silencing impaired the proliferation and colony formation of NSCLC cells. Moreover, mechanistic investigations showed that UCA1 upregulated the expression of miR-193a-3p target gene ERBB4 through competitively 'spongeing' miR-193a-3p. Overall, we concluded that UCA1 functions as an oncogene in NSCLC, acting mechanistically by upregulating ERBB4 in part through 'spongeing' miR-193a-3p.

  16. Effects of Mg content on aging behavior of sub-micron Al2O3p/Al-Cu-Mg composites

    Institute of Scientific and Technical Information of China (English)

    JIANG Long-tao; ZHU De-zhi; CHEN Guo-qin; XIU Zi-yang; WU Gao-hui

    2006-01-01

    30%Al2O3p/Al-Cu-2.0Mg composite and Al2O3p/Al-Cu-2.5Mg composite with 0.3 μm-Al2O3 particles were fabricated.Age-hardening behaviors of two composites and the related matrix alloys were studied by means of Brinell-hardness measurement,DSC and TEM. The results show that the hardness of the composite is improved obviously because of the addition of sub-micron Al2O3 particles. But the hardness increment of Al2O3p/Al composite after aging is lower than that of the related matrix alloy.Moreover, the formation of GP region is suppressed by the addition of sub-micron Al2O3 particles, which broadens the exothermic peak of S' phase. The increment of Mg content has a different influence on accelerating the aging processes of aluminum alloys and the composites, and the hardness also increases.

  17. Measurement of photoionization cross section from the 3s3p {sup 1}P{sub 1} excited state of magnesium

    Energy Technology Data Exchange (ETDEWEB)

    Rafiq, M; Hussain, Shahid; Saleem, M; Kalyar, M A; Baig, M A [Department of Physics, Atomic and Molecular Physics Laboratory, Quaid-i-Azam University, Islamabad (Pakistan)

    2007-06-28

    The photoionization cross section from the 3s3p {sup 1}P{sub 1} excited state has been measured in the energy region from the first ionization threshold up to 1.4 eV excess energy using a two-step photoionization and saturated ionization technique in conjunction with an atomic beam source and a time-of-flight mass spectrometer that enables the separation of the three stable isotopes of magnesium on the time axis. The absolute value of the photoionization cross sections from the 3s3p {sup 1}P{sub 1} excited state near the 3s ionization threshold has been measured as 90 {+-} 16 Mb (at 354.5 nm ionizing wavelength) for the dominating isotope ({sup 24}Mg) whereas the value at the peak of the 3p{sup 21}S{sub 0} auto-ionizing resonance has been determined as 785 {+-} 141 Mb. The present experimentally measured photoionization cross sections are compared with the existing experimental and theoretical work, showing excellent agreement.

  18. Absolute photoionization cross section from the 6s6p {sup 1,3}P{sub 1} excited states of barium

    Energy Technology Data Exchange (ETDEWEB)

    Kalyar, M A; Rafiq, M; Sami-ul-Haq; Baig, M A [Atomic and Molecular Physics Laboratory, Department of Physics, Quaid-i-Azam University, Islamabad 45320 (Pakistan)

    2007-06-28

    We present photoionization cross section measurements from the 6s6p {sup 1}P{sub 1} and {sup 3}P{sub 1} excited states of barium at and above the first ionization threshold. The experiments have been performed using a thermionic diode ion detector in a space charge limited mode in conjunction with a Nd:YAG laser system and the saturation technique to determine the photoionization cross sections. The absolute values of the photoionization cross section from the 6s6p {sup 1}P{sub 1} and {sup 3}P{sub 1} excited states at the first ionization threshold have been determined as 90 {+-} 14 Mb and 102 {+-} 15 Mb, respectively. The measured values of the photoionization cross section from the 6s6p {sup 1}P{sub 1} excited state are compared with available experimental and theoretical work, while the absolute photoionization cross sections from the 6s6p {sup 3}P{sub 1} excited state are reported for the first time.

  19. Evidence of multiple reassortment events of feline-to-human rotaviruses based on a rare human G3P[9] rotavirus isolated from a patient with acute gastroenteritis.

    Science.gov (United States)

    Nguyen, Tinh Huu; Than, Van Thai; Thanh, Hien Dang; Kim, Wonyong

    2016-06-01

    A rare human/feline-like rotavirus G3P[9] strain, CAU14-1-262, from a 2-year-old girl with severe gastroenteritis was isolated and sequenced. The 11 gene segments of the CAU14-1-262 strain possessed a novel genotype constellation, G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6, which was identified for the first time. Phylogenetic analysis of this strain identified the following genome origins: VP7, VP4, VP6, VP1-VP3, NSP1, NSP2, and NSP4 genes possessed an AU-1-like genotype 3 constellation with high sequence identity to those of the feline and human/feline-like rotaviruses; NSP5 possessed a H6 lineage, with highest sequence identity to the human/feline-like E2541 strain; and the NSP3 gene possessed a Wa-like genotype 1 constellation with high sequence identity to those of the of human rotaviruses. These results provided evidence of multiple reassortment events in G3P[9] rotavirus CAU14-1-262 and possibility of feline-to-human interspecies transmission.

  20. 3p14 De Novo Interstitial Microdeletion in a Patient with Intellectual Disability and Autistic Features with Language Impairment: A Comparison with Similar Cases

    Directory of Open Access Journals (Sweden)

    Ana Belén de la Hoz

    2015-01-01

    Full Text Available To date, few cases of 3p proximal interstitial deletions have been reported and the phenotype and genotype correlation is not well understood. Here, we report a new case of a 3p proximal interstitial deletion. The patient is an 11-year-old female with speech and social interaction difficulties, learning disability, and slight facial dysmorphism, but no other major malformations. An 8 Mb de novo interstitial deletion at 3p14.2-p14.1, from position 60.461.316 to 68.515.453, was revealed by means of array comparative genomic hybridization and confirmed using quantitative reverse-transcription polymerase chain reaction assays. This region includes six genes: FEZF2, CADPS, SYNPR, ATXN7, PRICKLE, and MAGI1, that are known to have a role in neurodevelopment. These genes are located on the proximal side of the deletion. We compare our case with previously well-defined patients reported in the literature and databases.