Science.gov

Sample records for 3p 5q 17p

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

    NASA Astrophysics Data System (ADS)

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

    1993-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-11-01

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

  4. Genetics Home Reference: 5q minus syndrome

    MedlinePlus

    ... in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes. Ann Hematol. 2014 Jan;93( ... Celebrates Its 15th Anniversary Genetic Information Non-Discrimination Act (GINA) Turns 10 All ... is newborn screening? New Pages Lyme disease ...

  5. Cryptorchidism due to chromosome 5q inversion duplication.

    PubMed

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

    2013-12-01

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

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

    PubMed Central

    2012-01-01

    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. PMID:22390313

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

    NASA Astrophysics Data System (ADS)

    Lacerda, Pedro; Jewitt, D.

    2012-10-01

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

  8. 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).

    PubMed

    Poiré, Xavier; Labopin, Myriam; Maertens, Johan; Yakoub-Agha, Ibrahim; Blaise, Didier; Ifrah, Norbert; Socié, Gérard; Gedde-Dhal, Tobias; Schaap, Nicolaas; Cornelissen, Jan J; Vigouroux, Stéphane; Sanz, Jaime; Michaux, Lucienne; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon

    2017-01-18

    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. 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. 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. 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.

  9. Molecular cytogenetic analysis of de novo dup(5)(q35.2q35.3) and review of the literature of pure partial trisomy 5q.

    PubMed

    Chen, Chih-Ping; Lin, Shuan-Pei; Lin, Chyi-Chyang; Chen, Yann-Jang; Chern, Schu-Rern; Li, Yueh-Chun; Hsieh, Lie-Jiau; Lee, Chen-Chi; Pan, Chen-Wen; Wang, Wayseen

    2006-07-15

    An 11-year-old girl presented with the phenotype of microcephaly, moderate mental retardation, motor retardation, short stature, strabismus, brachydactyly, and facial dysmorphism. She had undergone surgery for inguinal hernias. Detailed examinations of the heart and other internal organs revealed normal findings. Her karyotype was 46,XX,dup(5)(q35.2q35.3) de novo. Molecular cytogenetic analysis showed a paternally derived 5q35.2 --> q35.3 direct duplication and led to a correlation between the particular genotype and phenotype. This is the first description of a direct duplication of 5q35.2 --> q35.3. Our case represents the smallest distal duplication of chromosome 5q that is not associated with congenital heart defects. Our case also represents the smallest distal duplication of chromosome 5q that is associated with short stature and microcephaly. Mutations or deletions of the NSD1 gene, mapped to 5q35.2 --> q35.3, has been known to cause Sotos syndrome with cerebral gigantism, macrocephaly, advanced bone age and overgrowth. Our case provides evidence that the gene dosage effect of the NSD1 gene causes a reversed phenotype of microcephaly and short stature. Copyright 2006 Wiley-Liss, Inc.

  10. De novo acute leukemia with a sole 5q-: morphological, immunological, and clinical correlations.

    PubMed

    Duchayne, E; Dastugue, N; Kuhlein, E; Huguet, F; Pris, J

    1993-11-01

    The 5 q deletion is frequently found in myelodysplastic syndromes and acute non lymphoid leukemia, but this anomaly is usually found in secondary diseases and associated with many other chromosomal aberrations. This report describes four cases of "de novo" acute leukemia with a sole 5q- anomaly. They had no cytological, genetic or clinical characteristics of secondary disorders. It is important to note that of the four patients studied, three had proliferation of immature blast cells. One case was classified as a MO AML and two as "undifferentiated" acute leukemia. Furthermore, these four cases of acute leukemia showed a deletion of the same portion of the long arm of chromosome 5: q22q33. On the same part of this chromosome many hematopoietic growth factor genes have been located, like IL3 and GM-CSF which have early undifferentiated hematopoietic stem cells as a their target.

  11. Association of the Philadelphia chromosome and 5q- in secondary blood disorder

    SciTech Connect

    Dastugue, N.; Demur, C.; Pris, F.

    1988-02-01

    A patient developed a secondary blood disorder 7 years after radiotherapy for a gastric lymphoma. The initial myelodysplastic syndrome evolved to a myeloproliferative phase with transient polycythemia, progressive thrombocythemia, and hyperleukocytosis. Chromosome analysis performed in the terminal phase showed del(5)(q13q31),t(9;22)(q34;q11), and a complex rearrangement involving chromosomes number2 and number3. A correlation between chromosomal abnormalities and hematologic findings could be established. In this case, we have assumed that the Philadelphia translocation is a late event, due to prior mutagen exposure, and its association with a common secondary abnormality (5q-), followed by a progressively developing myeloproliferative phase. Furthermore, the association of Phmore » and 5q- in a single clone seems to indicate that the same stem cell is affected by these two abnormalities.« less

  12. Water outburst activity in Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    SciTech Connect

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

    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 hairmore » 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.« less

  14. Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q.

    PubMed

    Pieke-Dahl, S; Möller, C G; Kelley, P M; Astuto, L M; Cremers, C W; Gorin, M B; Kimberling, W J

    2000-04-01

    Usher syndrome is a group of autosomal recessive disorders that includes retinitis pigmentosa (RP) with hearing loss. Usher syndrome type II is defined as moderate to severe hearing loss with RP. The USH2A gene at 1q41 has been isolated and characterised. In 1993, a large Usher II family affected with a mild form of RP was found to be unlinked to 1q41 markers. Subsequent linkage studies of families in our Usher series identified several type II families unlinked to USH2A and USH3 on 3q25. After a second unlinked family with many affected members and a mild retinal phenotype was discovered, a genome search using these two large families showed another Usher II locus on 5q (two point lod = 3.1 at D5S484). To date, we have identified nine unrelated 5q linked families (maximum combined multipoint lod = 5.86) as well as three Usher II families that show no significant linkage to any known Usher loci. Haplotype analysis of 5q markers indicates that the new locus is flanked by D5S428 and D5S433. Review of ophthalmological data suggests that RP symptoms are milder in 5q linked families; the RP is often not diagnosed until patients near their third decade. Enamel hypoplasia and severe, very early onset RP were observed in two of the three unlinked families; dental anomalies have not been previously described as a feature of Usher type II.

  15. Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31.

    PubMed

    Bodea, Corneliu A; Middleton, Frank A; Melhem, Nadine M; Klei, Lambertus; Song, Youeun; Tiobech, Josepha; Marumoto, Pearl; Yano, Victor; Faraone, Stephen V; Roeder, Kathryn; Myles-Worsley, Marina; Devlin, Bernie; Byerley, William

    2017-02-01

    To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotypes, ≥10 Mb, identifying clusters of affected individuals who share such haplotypes. This extensive sharing, typically identical by descent, was significantly greater in cases than population controls, even after controlling for relatedness. Several regions of the genome exhibited substantial excess of shared haplotypes for affected individuals, including 3p21, 3p12, 4q28, and 5q23-q31. Two of these regions, 4q28 and 5q23-q31, showed significant linkage by traditional LOD score analysis and could harbor variants of more sizeable risk for psychosis or a multiplicity of risk variants. The pattern of haplotype sharing in 4q28 highlights PCDH10 , encoding a cadherin-related neuronal receptor, as possibly involved in risk.

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

    PubMed

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

    2013-07-01

    Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide. © 2013 John Wiley & Sons Ltd.

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different training...

  18. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  19. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  20. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  2. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q.

    PubMed Central

    Ryan, S G; Dixon, M J; Nigro, M A; Kelts, K A; Markand, O N; Terry, J C; Shiang, R; Wasmuth, J J; O'Connell, P

    1992-01-01

    Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. We performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. PMID:1334371

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

    PubMed

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

    2012-04-01

    Patients with chronic lymphocytic leukaemia (CLL) whose tumour cells harbour a 17p deletion (17p-) are universally considered to have a poor prognosis. The deletion can be detected at diagnosis or during the evolution of the disease, particularly in patients who have received chemotherapy. We sought to evaluate the natural history of patients with 17p- CLL, identify predictive factors within this prognostic subgroup, and evaluate the results of different therapeutic approaches. Data from 294 patients with 17p- CLL followed up at 20 different institutions was retrospectively collected and analysed. Median age was 68 (range 27-98) years at the time of fluorescence in situ hybridization analysis. After 17p- documentation, 52% received treatment, achieving an overall response rate of 50%. Median overall survival was 41 months, and was significantly shorter in patients with elevated beta(2)-microglobulin concentration (P < 0·001), B symptoms (P = 0·016), higher percentage of cells with deletion (P < 0·001), and acquired deletions (P = 0·012). These findings suggest that patients with 17p- CLL have a variable prognosis that can be refined using simple clinical and laboratory features, including 17p- clone size, beta2-microglobulin concentration, presence of B symptoms and type of deletion (de novo versus acquired). © 2012 Blackwell Publishing Ltd.

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

    SciTech Connect

    Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng

    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 eachmore » 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.« less

  5. Chromosome 17p Homodisomy Is Associated With Better Outcome in 1p19q Non-Codeleted and IDH-Mutated Gliomas

    PubMed Central

    Labussière, Marianne; Rahimian, Amithys; Giry, Marine; Boisselier, Blandine; Schmitt, Yohann; Polivka, Marc; Mokhtari, Karima; Delattre, Jean-Yves; Idbaih, Ahmed; Alentorn, Agusti

    2016-01-01

    Background. The 1p19q non-codeleted gliomas with IDH mutation, defined as “molecular astrocytomas,” display frequent TP53 mutations and have an intermediate prognosis. We investigated the prognostic impact of copy number-neutral loss of heterozygosity (CNLOH) in 17p in this population. Methods. We analyzed 793 gliomas (206 grade II, 377 grade III, and 210 grade IV) by single nucleotide polymorphism array and for TP53 mutations. Results. Homodisomy revealed by CNLOH was observed in 156 cases (19.7%). It was more frequent in astrocytomas and oligoastrocytomas (98/256, 38%) than oligodendrogliomas (28/327, 8.6%; p < .0001) or glioblastoma multiforme (30/210, 14.3%; p < .0001), tightly associated with TP53 mutation (69/71 vs. 20/79; p = 2 × 10−16), and mutually exclusive with 1p19q codeletion (1/156 vs. 249/556; p < .0001). In the group of IDH-mutated 1p19q non-codeleted gliomas, CNLOH 17p was associated with longer survival (86.3 vs. 46.2 months; p = .004), particularly in grade III gliomas (overall survival >100 vs. 37.9 months; p = .007). These data were confirmed in an independent dataset from the Cancer Genome Atlas. Conclusion. CNLOH 17p is a prognostic marker and further refines the molecular classification of gliomas. Implications for Practice: Homodisomy of chromosome 17p (CNLOH 17p) is a frequent feature in IDH-mutated 1p19q non-codeleted gliomas (group 2). It is constantly associated with TP53 mutation. It was found, within this specific molecular group of gliomas (corresponding to molecular astrocytomas), that CNLOH 17p is associated with a much better outcome and may therefore represent an additional prognostic marker to refine the prognostic classification of gliomas. PMID:27401888

  6. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS

    PubMed Central

    Schneider, Rebekka K.; Ademà, Vera; Heckl, Dirk; Järås, Marcus; Mallo, Mar; Lord, Allegra M.; Chu, Lisa P.; McConkey, Marie E.; Kramann, Rafael; Mullally, Ann; Bejar, Rafael; Solé, Francesc; Ebert, Benjamin L.

    2014-01-01

    Summary The Casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the non-deleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target. PMID:25242043

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

    SciTech Connect

    Richard, I.; Devaud, C.; Cherif, D.

    1993-10-01

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

  8. The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes

    DTIC Science & Technology

    2017-10-01

    especially in cells with sensitized innate immune signaling8,9,20. To analyze whether treatment of DAMPs could induce the over-production of pro...AWARD NUMBER: W81XWH-15-1-0335 TITLE: The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes...TITLE AND SUBTITLE 5a. CONTRACT NUMBER WThe Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes 5b. GRANT

  9. Localization of a new autosomal dominant retinitis pigmentosa gene on chromosome 17p screeningof candidate genes

    SciTech Connect

    Greenberg, J.; Goliath, R.; Shugart, Y.Y.

    1994-09-01

    A new gene locus for autosomal dominant retinitis pigmentosa (ADRP) on 17p has been identified in a large South African (SA) family consisting of 28 living affected individuals in 4 successive generations. This is the first ADRP gene to be reported from SA. The human recoverin (RCVN) gene, which codes for a retinal-specific protein important in recovery to the dark state after visual excitation, has been mapped to 17p13.1 and was considered as a prime candidate gene for the disorder in this family. Mutation screening (using 8 different electrophoretic conditions to resolve heteroduplexes and SSCPs) did not produce any evidencemore » of RCVN being involved in the pathogenesis of ADRP in this SA family. In addition, a mobility shift detected within exon 1 of the RCVN gene did not track with the ADRP phenotype. RP patients from 77 SA families and 30 normal individuals are being examined to establish the frequency of this polymorphism in the SA population. Highly polymorphic markers from 17p13 are now being sought in order to establish the minimum region containing this novel ADRP-SA gene. Two additional recently described retinal-expressed cDNAs, guanylyl cyclase and pigment epithelium-derived factor, which map to 17p13.1, will be tested for tight linkage to ADRP-SA.« less

  10. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false pH Effluent limitations under... (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 a...

  11. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  12. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true pH Effluent limitations under... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PROVISIONS § 401.17 pH Effluent limitations under continuous monitoring. (a) Where a permittee continuously measures the pH of wastewater pursuant to a...

  13. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true pH Effluent limitations under... (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 a...

  14. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true pH Effluent limitations under... (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 a...

  15. Unimpaired terminal erythroid differentiation and preserved enucleation capacity in myelodysplastic 5q(del) clones: a single cell study

    PubMed Central

    Garderet, Laurent; Kobari, Ladan; Mazurier, Christelle; De Witte, Caroline; Giarratana, Marie-Catherine; Pérot, Christine; Gorin, Norbert Claude; Lapillonne, Hélène; Douay, Luc

    2010-01-01

    Background Anemia is a characteristic of myelodysplastic syndromes, such as the rare 5q- syndrome, but its mechanism remains unclear. In particular, data are lacking on the terminal phase of differentiation of erythroid cells (enucleation) in myelodysplastic syndromes. Design and Methods We used a previously published culture model to generate mature red blood cells in vitro from human hematopoietic progenitor cells in order to study the pathophysiology of the 5q- syndrome. Our model enables analysis of cell proliferation and differentiation at a single cell level and determination of the enucleation capacity of erythroid precursors. Results The erythroid commitment of 5q(del) clones was not altered and their terminal differentiation capacity was preserved since they achieved final erythroid maturation (enucleation stage). The drop in red blood cell production was secondary to the decrease in the erythroid progenitor cell pool and to impaired proliferative capacity. RPS14 gene haploinsufficiency was related to defective erythroid proliferation but not to differentiation capacity. Conclusions The 5q- syndrome should be considered a quantitative rather than qualitative bone marrow defect. This observation might open the way to new therapeutic concepts. PMID:19815832

  16. Translocation (10;17)(p15;q21) is a recurrent anomaly in acute myeloblastic leukemia.

    PubMed

    Tempescul, Adrian; Guillerm, Gaëlle; Douet-Guilbert, Nathalie; Morel, Frédéric; Le Bris, Marie-Josée; De Braekeleer, Marc

    2007-01-01

    We report here two cases of patients with acute myeloblastic leukemia, type M1 (FAB classification), associated with a t(10;17)(p15;q21). Fluorescence in situ hybridization with the LSI PML/RARA dual-color probe showed the breakpoint to be distal to the RARA locus. Four other patients with this translocation have been reported, three of them having acute undifferentiated or poorly differentiated leukemia.

  17. Pharmacokinetics of venetoclax in patients with 17p deletion chronic lymphocytic leukemia.

    PubMed

    Salem, Ahmed Hamed; Dunbar, Martin; Agarwal, Suresh K

    2017-09-01

    Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal. Blood samples for venetoclax assay were collected during the ramp-up period and on day 1 of weeks 8, 12, 16, 24, and every 12 weeks thereafter. The mean postdose (8 h) plasma venetoclax concentrations increased with increasing weekly venetoclax dose during the ramp-up period to reach 1.89 µg/ml on week 5 day 1 at the 400 mg dose. The mean predose concentration at the 400 mg dose ranged between 0.69 and 0.99 µg/ml across visits between weeks 8 and 120. Repeated-measures analysis detected no statistical significance (P≥0.05) for the mean predose concentrations at any of the times tested from weeks 8 to 24. The study shows that the pharmacokinetic profile of venetoclax in CLL patients with the 17p deletion is comparable to the overall CLL as well as non-Hodgkin's lymphoma patient populations. Furthermore, no specific recommendation in terms of fat content in the meal is needed for the intake of venetoclax in patients with CLL.

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

    SciTech Connect

    Juyal, R.C.; Figuera, L.E.; Hauge, X.

    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 chromosomemore » 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.« less

  19. What is the best frontline therapy for patients with CLL and 17p deletion?

    PubMed

    Badoux, Xavier C; Keating, Michael J; Wierda, William G

    2011-03-01

    Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with significant variation in disease progression, response to therapy, and survival outcome. Deletions of 17p or mutations of TP53 have been identified as one of the poorest prognostic factors, being predictive of short time for disease progression, lack of response to therapy, short response duration, and short overall survival. The treatment of patients with CLL has improved significantly with the development of chemoimmunotherapy, but this benefit was not pronounced in patients with 17p deletion. We compare various treatment strategies used in these patients, including FCR-like chemoimmunotherapy, alemtuzumab, other antibody combinations, or novel targeted therapies with promising results. Allogeneic stem cell transplantation offers the possibility for long-term disease control in these patients and should be considered early in younger, transplant-eligible patients. The current state of therapy is far from optimal and resources should be applied to studying therapeutic options for patients who have CLL with loss of p53 function.

  20. Translocation (3;5)(q21;q34) in erythroleukemia: a molecular and in situ hybridization study.

    PubMed

    Kwong, Y L

    1998-05-01

    Translocation (3;5) is an uncommon karyotypic aberration in acute myeloid leukemia (AML). With the exception of M3, t(3;5) has been reported in every other subtype of AML, being most frequently associated with AML M6. Although a variety of breakpoints have been described, it has been suggested that the breakpoints in t(3;5) of all the reported cases should be assigned to 3q25.1 and 5q34. Recently, the breakpoints in three pediatric cases of AML M2 with t(3;5) were cloned and shown to involve the myelodysplasia/myeloid leukemia factor I (MLF1) gene on 3q25.1 and the nucleophosmin (NPM) gene on 5q34, generating a chimeric NPM/MLF1 transcript. An adult case of indolent erythroleukemia was found on karyotypic analysis to have t(3;5)(q21;q34). In about 60% of cells, the translocation was unbalanced, resulting in loss of the der(3) chromosome, implying that the critical leukemogenic sequence might reside on the der(5) chromosome. Molecular analysis of this case, however, failed to show rearrangement of the NPM gene and an MLF1/NPM transcript. A review of other reported cases of AML M6 with t(3;5) showed that the commonest breakpoint on chromosome 3 was also assigned to 3q21, as in our case. The considerable clinical, pathologic, cytogenetic and molecular differences observed in AML with t(3;5) suggest that these cases might be heterogeneous.

  1. Polymorphism in and localization of the gene LCP2 (SLP-76) to chromosome 5q33.1-qter

    SciTech Connect

    Sunden, S.L.F.; Carr, L.L.; Clements, J.L.

    This report describes the localization of the human LCP2 gene to human chromosome 5q33.1-qter using single-stranded conformation polymorphisms analysis. This gene encodes an SH2 domain containing leukocyte protein of 76 kDa (SLP-76), which plays a functional role in T-cell activation. It remains to be determined whether mutations in this gene or translocations at this chromosome location are the genetic basis for various diseases, including lymphoblastic leukemia. 12 refs., 1 fig.

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

    SciTech Connect

    Ishiguro, Masateru; Kim, Yoonyoung; Warjurkar, Dhanraj S.

    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 conventionalmore » 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.« less

  3. "Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.

    PubMed

    Chapiro, Elise; Lesty, Claude; Gabillaud, Clémentine; Durot, Eric; Bouzy, Simon; Armand, Marine; Le Garff-Tavernier, Magali; Bougacha, Nadia; Struski, Stéphanie; Bidet, Audrey; Laharanne, Elodie; Barin, Carole; Veronese, Lauren; Prié, Nolwen; Eclache, Virginie; Gaillard, Baptiste; Michaux, Lucienne; Lefebvre, Christine; Gaillard, Jean-Baptiste; Terré, Christine; Penther, Dominique; Bastard, Christian; Nadal, Nathalie; Fert-Ferrer, Sandra; Auger, Nathalie; Godon, Catherine; Sutton, Laurent; Tournilhac, Olivier; Susin, Santos A; Nguyen-Khac, Florence

    2018-03-01

    Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL. © 2017 Wiley Periodicals, Inc.

  4. Localization of the Netherton Syndrome Gene to Chromosome 5q32, by Linkage Analysis and Homozygosity Mapping

    PubMed Central

    Chavanas, Stéphane; Garner, Chad; Bodemer, Christine; Ali, Mohsin; Teillac, Dominique Hamel-; Wilkinson, John; Bonafé, Jean-Louis; Paradisi, Mauro; Kelsell, David P.; Ansai, Shin-ichi; Mitsuhashi, Yoshihiko; Larrègue, Marc; Leigh, Irene M.; Harper, John I.; Taïeb, Alain; Prost, Yves de; Cardon, Lon R.; Hovnanian, Alain

    2000-01-01

    Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Iα, the α subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor β2, and the diastrophic dysplasia sulfate–transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity. PMID:10712206

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1995-10-01

    The term {open_quotes}retintis pigmentosa{close_quotes} (RP) refers to a group of inherited retinal degenerative disorders. Clinical manifestations include night-blindness, with variable age of onset, followed by constriction of the visual field that may progress to total loss of sight in later life. Previous studies have shown that RP is caused by mutations within different genes and may be inherited as an X-linked recessive (XLRRP), autosomal recessive (ARRP), or autosomal dominant (ADRP) trait. The AD form of this group of conditions has been found to be caused by mutations within the rhodopsin gene in some families and the peripherin/RDS gene in others.more » 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.« less

  7. Allelic imbalance on chromosome 17p13 in borderline (low malignant potential) epithelial ovarian tumors.

    PubMed

    Zanotti, K M; Hart, W R; Kennedy, A W; Belinson, J L; Casey, G

    1999-07-01

    Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalance [AI] when identified by polymerase chain reaction) on chromosome 17p13, one of which includes the p53 gene, have been implicated in the development of ovarian and breast cancers. To provide evidence that genes in these regions also may be involved in the development of BEOTs, we undertook a detailed analysis of AI at all three loci in BEOTs from 21 patients. Seventeen of the BEOTs were serous and four were mucinous. Five of 21 tumors (24%) had AI at one or more loci. Four tumors had AI using the D17S695 marker, two of which showed AI only at this locus. In addition, three tumors exhibited AI at the D17S654 locus, one of which showed AI only at this locus. These data suggest that there may be two tumor suppressor genes distal to p53 involved in the development of at least a subset of BEOTs. Peritoneal implants from a subset of serous BEOTs also were evaluated for AI and were found to be concordant with the primary tumor in all cases. Their genetic similarity is consistent with the implantation theory of peritoneal spread of serous BEOTs in these cases.

  8. New developments in Smith-Magenis syndrome (del 17p11.2).

    PubMed

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

    2007-04-01

    Recent clinical, neuroimaging, sleep, and molecular cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review. Cross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith-Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype. Findings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder.

  9. Mineral abundances of comet 17P/Holmes derived from the mid-infrared spectrum

    NASA Astrophysics Data System (ADS)

    Shinnaka, Yoshiharu; Yamaguchi, MItsuru; Ootsubo, Takafumi; Kawakita, Hideyo; Sakon, Itsuki; Honda, Mitsuhiko; Watanabe, Jun-ichi

    2017-10-01

    Dust grains of crystalline silicate, which is rarely presented in an interstellar space, were found in cometary nuclei (Messenger et al. 1996, LPI, 27, 867; Wooden et al. 1999, ApJ, 517, 1058, references therein). It is thought that these crystalline silicates had formed by annealing or condensations of amorphous grains near the Sun in the solar nebula, and incorporated into a cometary nucleus in a cold region (farther than formation regions of the crystalline silicates) by radial transportation in the solar nebula. It is considered that transportation mechanisms to outside of the solar nebula were turbulent and/or X-wind. An abundance of the crystalline dust grains was therefore expected to be smaller as far from the Sun (Gail, 2001, A&A, 378, 192; Bockelée-Morvan et al. 2002, A&A, 384, 1107). Namely, the abundance ratio of the crystalline silicate in cometary dust grains relates a degree of mass transportation and a distance from the Sun when cometary nucleus formed in the Solar nebula. The mass ratio of crystalline silicates of dust grains is determined from by Si-O stretching vibrational bands of silicate grains around 10 μm using difference of spectral band features between crystalline and amorphous grains. We present the crystalline-to-amorphous mass ratio of silicate grains in the comet 17P/Holmes by using the thermal emission mode of the dust grains (Ootsubo et al. 2007, P&SS, 55, 1044) applied to the mid-infrared spectra of the comet. These spectra were taken by the COMICS mounted on the Subaru Telescope on 2007 October 25, 26, 27 and 28 immediately after the great outburst of the comet (started on October 23). We discuss about formation conditions of the nucleus of the comet based on the derived mass ratio of silicate grains of the comet.

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

    PubMed

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

    2006-05-01

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

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

    SciTech Connect

    Ishiguro, Masateru; Kim, Yoonyoung; Kwon, Yuna G.

    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 themore » 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.« less

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

    SciTech Connect

    Qi, Chunhua; Gurwell, Mark A.; Wilner, David J.

    2015-01-20

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

  13. Early recurrence in standard-risk medulloblastoma patients with the common idic(17)(p11.2) rearrangement

    PubMed Central

    Bien-Willner, Gabriel A.; López-Terrada, Dolores; Bhattacharjee, Meena B.; Patel, Kayuri U.; Stankiewicz, Paweł; Lupski, James R.; Pfeifer, John D.; Perry, Arie

    2012-01-01

    Medulloblastoma is diagnosed histologically; treatment depends on staging and age of onset. Whereas clinical factors identify a standard- and a high-risk population, these findings cannot differentiate which standard-risk patients will relapse and die. Outcome is thought to be influenced by tumor subtype and molecular alterations. Poor prognosis has been associated with isochromosome (i)17q in some but not all studies. In most instances, molecular investigations document that i17q is not a true isochromosome but rather an isodicentric chromosome, idic(17)(p11.2), with rearrangement breakpoints mapping within the REPA/REPB region on 17p11.2. This study explores the clinical utility of testing for idic(17)(p11.2) rearrangements using an assay based on fluorescent in situ hybridization (FISH). This test was applied to 58 consecutive standard- and high-risk medulloblastomas with a 5-year minimum of clinical follow-up. The presence of i17q (ie, including cases not involving the common breakpoint), idic(17)(p11.2), and histologic subtype was correlated with clinical outcome. Overall survival (OS) and disease-free survival (DFS) were consistent with literature reports. Fourteen patients (25%) had i17q, with 10 (18%) involving the common isodicentric rearrangement. The presence of i17q was associated with a poor prognosis. OS and DFS were poor in all cases with anaplasia (4), unresectable disease (7), and metastases at presentation (10); however, patients with standard-risk tumors fared better. Of these 44 cases, tumors with idic(17)(p11.2) were associated with significantly worse patient outcomes and shorter mean DFS. FISH detection of idic(17)(p11.2) may be useful for risk stratification in standard-risk patients. The presence of this abnormal chromosome is associated with early recurrence of medulloblastoma. PMID:22573308

  14. Utility of a Fluorescence Microscopy Imaging System for Analyzing the DNA Ploidy of Pathological Megakaryocytes Including 5q- Syndrome.

    PubMed

    Nakahara, Takako; Suemori, Shinichiro; Tsujioka, Takayuki; Kataoka, Mikio; Kataoka, Hiromi; Shibakura, Misako; Tohyama, Kaoru

    2018-06-01

    To investigate megakaryocyte (MK) DNA ploidy in various hematological diseases, fluorescence microscopy imaging system (FMI) can be used to analyze DNA ploidy with cell morphology at the single-cell level by using specialized image-processing software. Here we compared DNA ploidy obtained by FMI measured with that obtained flow cytometry (FCM). With FMI, we could evaluate the DNA ploidy in long-term preserved bone marrow smear samples after staining. We next analyzed the MK DNA ploidy in 42 bone marrow smear samples including 26 myeloid neoplasm cases, and we compared the DNA ploidy and platelet counts in the patients' peripheral blood; the production of platelets was significantly high compared to DNA ploidy in the myeloproliferative neoplasms group. The FMI method revealed that the patients with 5q- syndrome exhibited relatively low DNA ploidy despite high platelet counts, and this result suggested that increased DNA ploidy is not indispensable to abundant platelet production. The FMI method for DNA ploidy will be a useful tool to clarify the relationship between DNA ploidy and platelet production by MKs.

  15. Analysis of complex repeat sequences within the spinal muscular atrophy (SMA) candidate region in 5q13

    SciTech Connect

    Davies, K.E.; Morrison, K.E.; Daniels, R.I.

    1994-09-01

    We previously reported that the 400 kb interval flanked the polymorphic loci D5S435 and D5S557 contains blocks of a chromosome 5 specific repeat. This interval also defines the SMA candidate region by genetic analysis of recombinant families. A YAC contig of 2-3 Mb encompassing this area has been constructed and a 5.5 kb conserved fragment, isolated from a YAC end clone within the above interval, was used to obtain cDNAs from both fetal and adult brain libraries. We describe the identification of cDNAs with stretches of high DNA sequence homology to exons of {beta} glucuronidase on human chromosome 7. Themore » cDNAs map both to the candidate region and to an area of 5p using FISH and deletion hybrid analysis. Hybridization to bacteriophage and cosmid clones from the YACs localizes the {beta} glucuronidase related sequences within the 400 kb region of the YAC contig. The cDNAs show a polymorphic pattern on hybridization to genomic BamH1 fragments in the size range of 10-250 kb. Further analysis using YAC fragmentation vectors is being used to determine how these {beta} glucuronidase related cDNAs are distributed within 5q13. Dinucleotide repeats within the region are being investigated to determine linkage disequilibrium with the disease locus.« less

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

    PubMed Central

    Weckbaugh, Brandon; Sirridge, Christopher; Woodroof, Janet; Persons, Diane

    2016-01-01

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

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

    PubMed Central

    Virgilio, Maria; Narla, Anupama; Sun, Hong; Levine, Michelle; Paw, Barry H.; Berliner, Nancy; Look, A. Thomas; Ebert, Benjamin L.

    2012-01-01

    Haploinsufficiency of ribosomal proteins (RPs) has been proposed to be the common basis for the anemia observed in Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome with loss of chromosome 5q [del(5q) MDS]. We have modeled DBA and del(5q) MDS in zebrafish using antisense morpholinos to rps19 and rps14, respectively, and have demonstrated that, as in humans, haploinsufficient levels of these proteins lead to a profound anemia. To address the hypothesis that RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation. This resulted in a striking improvement of the anemia associated with RP loss. We confirmed our findings in primary human CD34+ cells, after shRNA knockdown of RPS19 and RPS14. Furthermore, we showed that loss of Rps19 or Rps14 activates the mTOR pathway, and this is accentuated by L-leucine in both Rps19 and Rps14 morphants. This effect could be abrogated by rapamycin suggesting that mTOR signaling may be responsible for the improvement in anemia associated with L-leucine. Our studies support the rationale for ongoing clinical trials of L-leucine as a therapeutic agent for DBA, and potentially for patients with del(5q) MDS. PMID:22734070

  18. 31 CFR 30.5 - Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Q-5: How does a TARP recipient comply... recipient? 30.5 Section 30.5 Money and Finance: Treasury Office of the Secretary of the Treasury TARP STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.5 Q-5: How does a TARP recipient comply with the...

  19. 31 CFR 30.5 - Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that the compensation committee discuss... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.5 Q-5: How does a TARP recipient comply with the...

  20. 31 CFR 30.5 - Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that the compensation committee discuss... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.5 Q-5: How does a TARP recipient comply with the...

  1. 31 CFR 30.5 - Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that the compensation committee discuss... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.5 Q-5: How does a TARP recipient comply with the...

  2. Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome.

    PubMed

    Volkert, Sarah; Kohlmann, Alexander; Schnittger, Susanne; Kern, Wolfgang; Haferlach, Torsten; Haferlach, Claudia

    2014-05-01

    We analyzed 1,200 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) harboring a 5q deletion in order to clarify whether the type of 5q loss is associated with other biological markers and prognosis. We investigated all patients by chromosome banding analysis, FISH with a probe for EGR1 (5q31) and, if necessary, to resolve complex karyotypes with 24-color-FISH. Moreover, 420 patients were analyzed for mutations in the TP53 gene. The patient cohort was subdivided based on type of 5q loss: Patients with interstitial deletions and patients with 5q loss due to unbalanced rearrangements or monosomy 5. Loss of the long arm of chromosome 5 due to an unbalanced rearrangement occurred more often in AML (286/627; 45.6%) than MDS (188/573; 32.8%; P < 0.001). In both entities, patients with 5q loss due to unbalanced translocations showed complex karyotypes more frequently (MDS: 179/188; 95.2% vs. 124/385; 32.2%; P < 0.001; AML: 274/286; 95.8% vs. 256/341; 75.1%; P < 0.001). Moreover, in MDS unbalanced 5q translocations were associated with clonal evolution (109/188; 58.0% vs. 124/385; 32.2%; P < 0.001), mutation of TP53 (64/67; 95.5% vs. 40/120; 40.0%; P < 0.001), and shorter survival (15.3 months vs. not reached; P < 0.001). In MDS, complex karyotype was an independent adverse prognostic factor (HR = 5.34; P = 0.032), whereas in AML presence of TP53 mutations was the strongest adverse prognostic factor (HR = 2.21; P = 0.026). In conclusion, in AML and MDS, loss of the long arm of chromosome 5 due to unbalanced translocations is associated with complex karyotype and in MDS, moreover, with clonal evolution, mutations in the TP53 gene and adverse prognosis. Copyright © 2014 Wiley Periodicals, Inc.

  3. 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.

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

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

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

    SciTech Connect

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

    1996-02-02

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

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

    SciTech Connect

    Brown, A.; Phelan, M.C.; Rogers, R.C.

    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/more » 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.« less

  7. Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11p and 17p in medulloblastomas.

    PubMed

    Albrecht, S; von Deimling, A; Pietsch, T; Giangaspero, F; Brandner, S; Kleihues, P; Wiestler, O D

    1994-02-01

    Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas, epithelial jaw cysts, and skeletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53, and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS. Both these cases were informative at D9S55 without LOH.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study.

    PubMed

    Stilgenbauer, Stephan; Eichhorst, Barbara; Schetelig, Johannes; Coutre, Steven; Seymour, John F; Munir, Talha; Puvvada, Soham D; Wendtner, Clemens-Martin; Roberts, Andrew W; Jurczak, Wojciech; Mulligan, Stephen P; Böttcher, Sebastian; Mobasher, Mehrdad; Zhu, Ming; Desai, Monali; Chyla, Brenda; Verdugo, Maria; Enschede, Sari Heitner; Cerri, Elisa; Humerickhouse, Rod; Gordon, Gary; Hallek, Michael; Wierda, William G

    2016-06-01

    Deletion of chromosome 17p (del[17p]) in patients with chronic lymphocytic leukaemia confers very poor prognosis when treated with standard chemo-immunotherapy. Venetoclax is an oral small-molecule BCL2 inhibitor that induces chronic lymphocytic leukaemia cell apoptosis. In a previous first-in-human study of venetoclax, 77% of patients with relapsed or refractory chronic lymphocytic leukaemia achieved an overall response. Here we aimed to assess the activity and safety of venetoclax monotherapy in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia. In this phase 2, single-arm, multicentre study, we recruited patients aged 18 years and older with del(17p) relapsed or refractory chronic lymphocytic leukaemia (as defined by 2008 Modified International Workshop on Chronic Lymphocytic Leukemia guidelines) from 31 centres in the USA, Canada, UK, Germany, Poland, and Australia. Patients started once daily venetoclax with a weekly dose ramp-up schedule (20, 50, 100, 200, 400 mg) over 4-5 weeks. Patients were then given daily 400 mg continuous dosing until disease progression or discontinuation for another reason. The primary endpoint was the proportion of patients achieving an overall response, assessed by an independent review committee. Activity and safety analyses included all patients who received at least one dose of study drug (per protocol). This study is registered with ClinicalTrials.gov, number NCT01889186. Follow-up is ongoing, and patients are still receiving treatment. Between May 27, 2013, and June 27, 2014, 107 patients were enrolled into the study. At a median follow-up of 12·1 months (IQR 10·1-14·2), an overall response by independent review was achieved in 85 (79·4%; 95% CI 70·5-86·6) of 107 patients. The most common grade 3-4 adverse events were neutropenia (43 [40%]), infection (21 [20%]), anaemia (19 [18%]), and thrombocytopenia (16 [15%]). Serious adverse events occurred in 59 (55%) patients, irrespective of their

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

    PubMed

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

    2008-07-01

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

  10. Clinical characteristics and outcomes according to age in lenalidomide-treated patients with RBC transfusion-dependent lower-risk MDS and del(5q).

    PubMed

    Fenaux, Pierre; Giagounidis, Aristoteles; Selleslag, Dominik; Beyne-Rauzy, Odile; Mittelman, Moshe; Muus, Petra; Nimer, Stephen D; Hellström-Lindberg, Eva; Powell, Bayard L; Guerci-Bresler, Agnes; Sekeres, Mikkael A; Deeg, H Joachim; Del Cañizo, Consuelo; Greenberg, Peter L; Shammo, Jamile M; Skikne, Barry; Yu, Xujie; List, Alan F

    2017-06-26

    Particularly since the advent of lenalidomide, lower-risk myelodysplastic syndromes (MDS) patients with del(5q) have been the focus of many studies; however, the impact of age on disease characteristics and response to lenalidomide has not been analyzed. We assessed the effect of age on clinical characteristics and outcomes in 286 lenalidomide-treated MDS patients with del(5q) from two multicenter trials. A total of 33.9, 34.3, and 31.8% patients were aged <65 years, ≥65 to <75 years, and ≥75 years, respectively. Age <65 years was associated with less favorable International Prognostic Scoring System (IPSS) risk and additional cytopenias at baseline versus older age groups, significantly lower cytogenetic response rates (p = 0.022 vs. ≥65 to <75 years; p = 0.047 vs. ≥75 years), and higher rates of acute myeloid leukemia (AML) progression (Gray's test, p = 0.013). Lenalidomide was equally well tolerated across age groups, producing consistently high rates of red blood cell transfusion independence ≥26 weeks. Baseline disease characteristics and AML progression appear to be more severe in younger lower-risk MDS patients with del(5q), whereas older age does not seem to compromise the response to lenalidomide. ClinicalTrials.gov NCT00065156 and NCT00179621.

  11. 7 CFR 1942.9 - Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... §§ 1942.17(p) and 1942.18] 1942.9 Section 1942.9 Agriculture Regulations of the Department of...) ASSOCIATIONS Community Facility Loans § 1942.9 Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18] (a) Review of construction plans and specifications. All plans and specifications...

  12. 7 CFR 1942.9 - Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18] 1942.9 Section 1942.9 Agriculture Regulations of the Department of....17(p) and 1942.18] (a) Review of construction plans and specifications. All plans and specifications...

  13. 7 CFR 1942.9 - Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18] 1942.9 Section 1942.9 Agriculture Regulations of the Department of....17(p) and 1942.18] (a) Review of construction plans and specifications. All plans and specifications...

  14. Obtaining P3P privacy policies for composite services.

    PubMed

    Sun, Yi; Huang, Zhiqiu; Ke, Changbo

    2014-01-01

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

  15. Obtaining P3P Privacy Policies for Composite Services

    PubMed Central

    Sun, Yi; Huang, Zhiqiu; Ke, Changbo

    2014-01-01

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

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

    PubMed

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

    2014-08-01

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

  17. Where are χ _{cJ}(3P)?

    NASA Astrophysics Data System (ADS)

    Chen, Dian-Yong

    2016-12-01

    In the present work, we propose Y(4140) as the χ _{c1}(3P) state by studying the χ _{c1} π ^+ π ^- invariant mass spectrum of the B→ K χ _{c1} π ^+ π ^- process. In the Dbar{D} invariant mass spectrum of the B→ K Dbar{D} process, we find a new resonance with the mass and width to be ( 4083.0 ± 5.0) and (24.1 ± 15.4) MeV, respectively, which could be a good candidate of the χ _{c0}(3P) state. The theoretical investigations on the decay behaviors of the χ _{cJ}(3P) in the present work support the assignments of the Y(4140) and Y(4080) as the χ _{c1}(3P) and χ _{c0}(3P) states, respectively. In addition, the χ _{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.

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

    SciTech Connect

    Dixon, M.J.; Dixon, J.; Houseal, T.

    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 tomore » 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.« less

  19. Convergent linkage evidence from two Latin-American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34.

    PubMed

    Herzberg, Ibi; Jasinska, Anna; García, Jenny; Jawaheer, Damini; Service, Susan; Kremeyer, Barbara; Duque, Constanza; Parra, María V; Vega, Jorge; Ortiz, Daniel; Carvajal, Luis; Polanco, Guadalupe; Restrepo, Gabriel J; López, Carlos; Palacio, Carlos; Levinson, Matthew; Aldana, Ileana; Mathews, Carol; Davanzo, Pablo; Molina, Julio; Fournier, Eduardo; Bejarano, Julio; Ramírez, Magui; Ortiz, Carmen Araya; Araya, Xinia; Sabatti, Chiara; Reus, Victor; Macaya, Gabriel; Bedoya, Gabriel; Ospina, Jorge; Freimer, Nelson; Ruiz-Linares, Andrés

    2006-11-01

    We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by the previous studies of BP in Costa Rica. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided a genome-wide significant evidence of linkage of BPI to a candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric linkage score=4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.

  20. A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.

    PubMed

    Amundsen, Silja Svanstrøm; Adamovic, Svetlana; Hellqvist, Asa; Nilsson, Staffan; Gudjónsdóttir, Audur H; Ascher, Henry; Ek, Johan; Larsson, Kristina; Wahlström, Jan; Lie, Benedicte A; Sollid, Ludvig M; Naluai, Asa Torinsson

    2007-09-01

    Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31-33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31-33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1,404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.

  1. Reaction kinetics of O( 3P) with acrylonitrile and crotononitrile

    NASA Astrophysics Data System (ADS)

    Upadhyaya, Hari P.; Naik, Prakash D.; Pavanaja, Ubaradka B.; Kumar, Awadhesh; Vatsa, Rajesh K.; Sapre, Avinash V.; Mittal, Jai P.

    1997-08-01

    The reaction of oxygen atoms O( 3P) with unsaturated nitriles (RCN), viz. acrylonitrile (CH 2=CHCN), and crotononitrile (CH 3CH=CHCN), was studied in a flow discharge tube in the pressure range 1.2-1.7 Torr using the O( 3P) chemiluminescence titration method. The rate constants for the reaction O( 3P) + RCN → products was determined at room temperature to be (4.9 ± 1.0) × 10 -13 and (5.4 ± 0.8) × 10 -13 cm 3 molecule -1 s -1 for acrylonitrile and crotononitrile respectively. The activation energies for the above reactions were estimated using the MNDO method. The formation of a biradical involving the addition of an oxygen atom to the double bond is proposed as the major channel for the reaction.

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

    SciTech Connect

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

    1994-09-01

    We assessed the usefulness of in situ hybridization with a DNA probe to the area of chromosome 17 at p11.2 as a diagnostic tool for screening for Charcot Marte Tooth 1A (CMT 1A). In situ hybridization with a probe to 17p11.2 was performed on fixed lymphocytes from the following groups of individuals: (1) normal controls; (2) patients evoking a strong clinical suspicion of CMT 1A; and (3) 3 families with an apparent autosomal dominant peripheral neuropathy of unknown diagnoses. Group 2 patients had evidence of demyelination as defined by nerve conduction of less that 50% of the normal mean ormore » 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.« less

  3. Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis.

    PubMed

    Schetelig, Johannes; van Biezen, Anja; Brand, Ronald; Caballero, Dolores; Martino, Rodrigo; Itala, Maija; García-Marco, José A; Volin, Liisa; Schmitz, Norbert; Schwerdtfeger, Rainer; Ganser, Arnold; Onida, Francesco; Mohr, Brigitte; Stilgenbauer, Stephan; Bornhäuser, Martin; de Witte, Theo; Dreger, Peter

    2008-11-01

    Patients with chronic lymphocytic leukemia (CLL) and 17p deletion (17p-) have a poor prognosis. Although allogeneic hematopoietic stem-cell transplantation (HCT) has the potential to cure patients with advanced CLL, it is not known whether this holds true for patients with 17p-CLL. Baseline data from patients, for whom information on the presence of 17p-CLL was available, were downloaded from the European Group for Blood and Marrow Transplantation database. Additional information on the course of CLL and follow-up was collected with a questionnaire. A total of 44 patients with 17p-CLL received allogeneic HCT between March 1995 and July 2006 from a matched sibling (n = 24) or an alternative donor (n = 20). 17p-CLL had been diagnosed by fluorescent in situ hybridization in 82% of patients and by conventional banding in 18% of patients. The median age was 54 years. Before HCT, a median of three lines of chemotherapy had been administered. At HCT, 53% of patients were in remission. Reduced-intensity conditioning was applied in 89% of patients. Acute, grade 2 to 4 graft-versus-host disease (GVHD) occurred in 43% of patients, and extensive chronic GVHD occurred in 53% of patients. At last follow-up, 19 patients were alive, with a median observation time of 39 months (range, 18 to 101 months). Three-year overall survival and progression-free survival rates were 44% and 37%, respectively. The cumulative incidence of progressive disease at 4 years was 34%. No late relapse occurred in nine patients with a follow-up longer than 4 years. Allogeneic HCT has the potential to induce long-term disease-free survival in patients with 17p-CLL.

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

    SciTech Connect

    Jabs, E.W.; Li, Xiang; Coss, C.

    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.more » 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.« less

  5. Energetic band structure of Zn3P2 crystals

    NASA Astrophysics Data System (ADS)

    Stamov, I. G.; Syrbu, N. N.; Dorogan, A. V.

    2013-01-01

    Optical functions n, k, ε1, ε2 and d2ε2/dE2 have been determined from experimental reflection spectra in the region of 1-10 eV. The revealed electronic transitions are localized in the Brillouin zone. The magnitude of valence band splitting caused by the spin-orbital interaction ΔSO is lower than the splitting caused by the crystal field ΔCR in the center of Brillouin zone and L and X points. The switching effects are investigated in Zn3P2 crystals. The characteristics of experimental samples with electric switching, adjustable resistors, and time relays based on Zn3P2 are presented.

  6. Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials.

    PubMed

    Jones, Jeffrey; Mato, Anthony; Coutre, Steven; Byrd, John C; Furman, Richard R; Hillmen, Peter; Osterborg, Anders; Tam, Constantine; Stilgenbauer, Stephan; Wierda, William G; Heerema, Nyla A; Eckert, Karl; Clow, Fong; Zhou, Cathy; Chu, Alvina D; James, Danelle F; O'Brien, Susan M

    2018-06-05

    Patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) with deletion 17p [del(17p)] have poor outcomes with chemoimmunotherapy. Ibrutinib is indicated for the treatment of CLL/SLL, including del(17p) CLL/SLL, and allows for treatment without chemotherapy. This integrated analysis was performed to evaluate outcomes in 230 patients with relapsed/refractory del(17p) CLL/SLL from three ibrutinib studies. With a median of 2 prior therapies (range, 1-12), 18% and 79% of evaluable patients had del(11q) or unmutated IGHV, respectively. With a median follow-up of 28 months, overall response rate was 85% and estimated 30-month progression-free and overall survival rates were 57% [95% confidence interval (CI) 50-64] and 69% (95% CI 61-75), respectively. Patients with normal lactate dehydrogenase or no bulky disease had the most favourable survival outcomes. Sustained haematological improvements in haemoglobin, platelet count and absolute neutrophil count occurred in 61%, 67% and 70% of patients with baseline cytopenias, respectively. New onset severe cytopenias and infections decreased in frequency over time. Progression-free and overall survival with ibrutinib surpass those of other therapies for patients with del(17p) CLL/SLL. These results provide further evidence of the robust clinical activity of ibrutinib in difficult-to-treat CLL/SLL populations. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

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

    PubMed

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

    2015-03-01

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

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

    PubMed

    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. © 2014 Wiley Periodicals, Inc.

  9. Structural Evolution of Schreibersite, Fe3P, at High Pressure

    NASA Astrophysics Data System (ADS)

    Howard, J.; Sinogeikin, S.; Nicol, M.; Tschauner, O.

    2007-12-01

    Fe3P schreibersite is an abundant mineral in iron meteorites. Previous work [Scott et. al., Geophys. Res. Lett. (2007) 34, L06302/1-5] reported a phase transition occurred in a powder sample of Fe3P schreibersite above 17 GPa at ambient temperature, but did not identify the structure of this high pressure phase. This high pressure phase is not quenchable to ambient pressure, however, the transition and its reversion may induce characteristic twinning in schreibersite crystals, which may be identified in meteoritic material and, thus, help to constrain shock pressures for iron meteorites. By using a diamond anvil cell with a methanol/ethanol pressure medium to generate pressure, the structure of single crystal Fe3P was studied by X-ray diffraction up to 30 GPa (at room temperature) at end station 16 ID-B of the Advanced Photon Source. Our experiment indicates that the phase transition occurs around 10 GPa and appears to suggest that the material twins during compression. Acknowledgement: The authors thank the HPCAT team for their help, and U.S. DOE Cooperative Agreement No. FC08-06NA27684 with UNLV for supporting the work. Portions of this work were performed at HPCAT (Sector 16), APS, ANL. HPCAT facility is supported by DOE-BES, DOE-NNSA, NSF, and the W.M. Keck Foundation. The APS is supported by the U. S. DOE-BES under Contract No. W-31-109-Eng-38.

  10. Analysis of spectra of 3s-3p and 3p-3d transitions of highly-charged copper ions

    NASA Astrophysics Data System (ADS)

    Su, M. G.; Min, Q.; He, S. Q.; Wu, L.; Sun, R.; Ding, X. B.; Sun, D. X.

    2017-08-01

    Beam-foil excited spectra in the range of 160-360 Å from highly charged copper ions were identified with the aid of the National Institute of Standards and Technology Atomic Spectra Database and theoretical calculations with Cowan and Flexible Atomic Code (FAC) calculations. Spectra arising from 3s-3p and 3p-3d transitions of Cu13+-Cu22+ ions were considered. The ion fraction at an ion beam energy of 110 MeV was estimated from the equilibrium charge distribution of the fast ion beams after passing through the solid. The corresponding simulated spectra were in good agreement with the experimental result. Our Cowan and FAC calculation results should be useful for further spectral identification and lifetime measurements of highly charged copper ions.

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

    PubMed

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

    2015-01-08

    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. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All

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

    PubMed Central

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

    2015-01-01

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

  13. Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.

    PubMed

    Sawyer, Jeffrey R; Tian, Erming; Heuck, Christoph J; Epstein, Joshua; Johann, Donald J; Swanson, Charles M; Lukacs, Janet L; Johnson, Marian; Binz, Regina; Boast, Angela; Sammartino, Gael; Usmani, Saad; Zangari, Maurizio; Waheed, Sarah; van Rhee, Frits; Barlogie, Bart

    2014-04-17

    Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease.

  14. WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations.

    PubMed

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-07-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.

  15. Linkage Analysis of a Model Quantitative Trait in Humans: Finger Ridge Count Shows Significant Multivariate Linkage to 5q14.1

    PubMed Central

    Medland, Sarah E; Loesch, Danuta Z; Mdzewski, Bogdan; Zhu, Gu; Montgomery, Grant W; Martin, Nicholas G

    2007-01-01

    The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds [LOD] = 3.34, pointwise-empirical p-value = 0.00025) that was predominantly driven by linkage to the ring, index, and middle fingers. The strongest univariate linkage was to 1q42.2 (LOD = 2.04, point-wise p-value = 0.002, genome-wide p-value = 0.29). In summary, the combination of univariate and multivariate results was more informative than simple univariate analyses alone. Patterns of quantitative trait loci factor loadings consistent with developmental fields were observed, and the simple pleiotropic model underlying the absolute ridge count was not sufficient to characterize the interrelationships between the ridge counts of individual fingers. PMID:17907812

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

    PubMed

    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.

  17. Clinical and cytogenetic features of a Potocki-Lupski syndrome with the shortest 0.25Mb microduplication in 17p11.2 including RAI1.

    PubMed

    Lee, Cha Gon; Park, Sang-Jin; Yim, Shin-Young; Sohn, Young Bae

    2013-08-01

    Potocki-Lupski syndrome (PTLS [MIM 610883]) is a recently recognized microduplication syndrome associated with 17p11.2. It is characterized by mild facial dysmorphic features, hypermetropia, infantile hypotonia, failure to thrive, mental retardation, autistic spectrum disorders, behavioral abnormalities, sleep apnea, and cardiovascular anomalies. In several studies, the critical PTLS region was deduced to be 1.3Mb in length, and included RAI1 and 17 other genes. We report a 3-year-old Korean boy with the smallest duplication in 17p11.2 and a milder phenotype. He had no family history of neurologic disease or developmental delay and no history of seizure, autistic features, or behavior problems. He showed subtle facial dysmorphic features (dolichocephaly and a mildly asymmetric smile) and flat feet. All laboratory tests were normal and he had no evidence of internal organ anomalies. He was found to have mild intellectual disabilities (full scale IQ 65 on K-WPPSI) and language developmental delay (age of 2.2year-old on PRESS). Array comparative genomic hybridization (CGH) showed about a 0.25Mb microduplication on chromosome 17p11.2 containing four Refseq (NCBI reference sequence) genes, including RAI1 [arr 17p11.2(17,575,978-17,824,623)×3]. When compared with previously reported cases, the milder phenotype of our patient may be associated with the smallest duplication in 17p11.2, 0.25Mb in length. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed

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

    1996-01-18

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

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

    SciTech Connect

    Clines, G.; Lovett, M.

    1994-09-01

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

  3. Intrachromosomal 3p insertion as a cause of reciprocal pure interstitial deletion and duplication in two siblings: further delineation of the emerging proximal 3p deletion syndrome.

    PubMed

    Lloveras, Elisabet; Vendrell, Teresa; Fernández, Asunción; Castells, Neus; Cueto, Ana; del Campo, Miguel; Hernando, Cristina; Villa, Olaya; Plaja, Alberto

    2014-01-01

    Very few cases of constitutional interstitial deletions of the proximal short arm of chromosome 3 have been reported; however, the proximal 3p deletion is emerging as a clinically recognizable syndrome. We present an intrachromosomal insertion of 3p12.3p14.1 in a phenotypic normal man (46,XY,ins(3)(p25p12.3p14.1)) which is responsible for the unbalanced karyotype in 2 affected offspring, one with a 3p12.3p14.1 interstitial deletion and the other with a reciprocal duplication. The exceptionality of these 2 reciprocal recombinants contributes to a better definition of the proximal 3p deletion syndrome and its duplication counterpart.

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

    SciTech Connect

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji

    1997-03-31

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

  5. Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Kojis, T.L.; Heinzmann, C.; Ngo, J.T.

    1996-02-01

    In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yieldedmore » a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families. 39 refs., 4 figs., 3 tabs.« less

  6. Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.

    PubMed

    Nakamine, Alisa; Ouchanov, Leonid; Jiménez, Patricia; Manghi, Elina R; Esquivel, Marcela; Monge, Silvia; Fallas, Marietha; Burton, Barbara K; Szomju, Barbara; Elsea, Sarah H; Marshall, Christian R; Scherer, Stephen W; McInnes, L Alison

    2008-03-01

    Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3.3 Mb on chromosome 17p11.2 in a male child with autism and severe expressive language delay. The duplication was confirmed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Gene expression analyses revealed increased expression of three candidate genes for the Smith-Magenis neurobehavioral phenotype, RAI1, DRG2, and RASD1, in transformed lymphocytes from Case 81A, suggesting gene dosage effects. Our results add to a growing body of evidence suggesting that duplications of 17(p11.2p11.2) result in language delay as well as autism and related phenotypes. As Smith-Magenis syndrome is also associated with language delay, a gene involved in acquisition of language may lie within this interval. Whether a parent of origin effect, gender of the case, the presence of allelic variation, or changes in expression of genes outside the breakpoints influence the resultant phenotype remains to be determined. (c) 2007 Wiley-Liss, Inc.

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

    PubMed

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

    2014-11-06

    The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed

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

    2015-11-01

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

  10. Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis

    PubMed Central

    Philippi, Anne; Tores, Frédéric; Carayol, Jérome; Rousseau, Francis; Letexier, Mélanie; Roschmann, Elke; Lindenbaum, Pierre; Benajjou, Abdel; Fontaine, Karine; Vazart, Céline; Gesnouin, Philippe; Brooks, Peter; Hager, Jörg

    2007-01-01

    Background Autism is a complex, heterogeneous, behaviorally-defined disorder characterized by disruptions of the nervous system and of other systems such as the pituitary-hypothalamic axis. In a previous genome wide screen, we reported linkage of autism with a 1.2 Megabase interval on chromosome 5q31. For the current study, we hypothesized that 3 of the genes in this region could be involved in the development of autism: 1) paired-like homeodomain transcription factor 1 (PITX1), which is a key regulator of hormones within the pituitary-hypothalamic axis, 2) neurogenin 1, a transcription factor involved in neurogenesis, and 3) histone family member Y (H2AFY), which is involved in X-chromosome inactivation in females and could explain the 4:1 male:female gender distortion present in autism. Methods A total of 276 families from the Autism Genetic Resource Exchange (AGRE) repository composed of 1086 individuals including 530 affected children were included in the study. Single nucleotide polymorphisms tagging the three candidate genes were genotyped on the initial linkage sample of 116 families. A second step of analysis was performed using tightly linked SNPs covering the PITX1 gene. Association was evaluated using the FBAT software version 1.7.3 for single SNP analysis and the HBAT command from the same package for haplotype analysis respectively. Results Association between SNPs and autism was only detected for PITX1. Haplotype analysis within PITX1 showed evidence for overtransmission of the A-C haplotype of markers rs11959298 – rs6596189 (p = 0.0004). Individuals homozygous or heterozygous for the A-C haplotype risk allele were 2.54 and 1.59 fold more likely to be autistic than individuals who were not carrying the allele, respectively. Conclusion Strong and consistent association was observed between a 2 SNPs within PITX1 and autism. Our data suggest that PITX1, a key regulator of hormones within the pituitary-hypothalamic axis, may be implicated in the

  11. Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis.

    PubMed

    Philippi, Anne; Tores, Frédéric; Carayol, Jérome; Rousseau, Francis; Letexier, Mélanie; Roschmann, Elke; Lindenbaum, Pierre; Benajjou, Abdel; Fontaine, Karine; Vazart, Céline; Gesnouin, Philippe; Brooks, Peter; Hager, Jörg

    2007-12-06

    Autism is a complex, heterogeneous, behaviorally-defined disorder characterized by disruptions of the nervous system and of other systems such as the pituitary-hypothalamic axis. In a previous genome wide screen, we reported linkage of autism with a 1.2 Megabase interval on chromosome 5q31. For the current study, we hypothesized that 3 of the genes in this region could be involved in the development of autism: 1) paired-like homeodomain transcription factor 1 (PITX1), which is a key regulator of hormones within the pituitary-hypothalamic axis, 2) neurogenin 1, a transcription factor involved in neurogenesis, and 3) histone family member Y (H2AFY), which is involved in X-chromosome inactivation in females and could explain the 4:1 male:female gender distortion present in autism. A total of 276 families from the Autism Genetic Resource Exchange (AGRE) repository composed of 1086 individuals including 530 affected children were included in the study. Single nucleotide polymorphisms tagging the three candidate genes were genotyped on the initial linkage sample of 116 families. A second step of analysis was performed using tightly linked SNPs covering the PITX1 gene. Association was evaluated using the FBAT software version 1.7.3 for single SNP analysis and the HBAT command from the same package for haplotype analysis respectively. Association between SNPs and autism was only detected for PITX1. Haplotype analysis within PITX1 showed evidence for overtransmission of the A-C haplotype of markers rs11959298 - rs6596189 (p = 0.0004). Individuals homozygous or heterozygous for the A-C haplotype risk allele were 2.54 and 1.59 fold more likely to be autistic than individuals who were not carrying the allele, respectively. Strong and consistent association was observed between a 2 SNPs within PITX1 and autism. Our data suggest that PITX1, a key regulator of hormones within the pituitary-hypothalamic axis, may be implicated in the etiology of autism.

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

    PubMed Central

    Muñoz, Sofía; Manjón, Elvira; Sánchez, Yolanda

    2014-01-01

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

  13. Precision microwave measurement of the 2(3)P(1)-2(3)P(0) interval in atomic helium: a determination of the fine-structure constant.

    PubMed

    George, M C; Lombardi, L D; Hessels, E A

    2001-10-22

    The 2(3)P(1)-to- 2(3)P(0) interval in atomic helium is measured using a thermal beam of metastable helium atoms excited to the 2(3)P state using a 1.08-microm diode laser. The 2(3)P(1)-to- 2(3)P(0) transition is driven by 29.6-GHz microwaves in a rectangular waveguide cavity. Our result of 29,616,950.9+/-0.9 kHz is the most precise measurement of helium 2(3)P fine structure. When compared to precise theory for this interval, this measurement leads to a determination of the fine-structure constant of 1/137.0359864(31).

  14. Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2)

    PubMed Central

    Walz, Katherina; Paylor, Richard; Yan, Jiong; Bi, Weimin; Lupski, James R.

    2006-01-01

    Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is important for the elucidation of genes responsible for complex neurobehavioral phenotypes. Smith-Magenis syndrome is associated with a 3.7-Mb deletion in 17p11.2, and its clinical presentation is caused by retinoic acid inducible 1 (RAI1) haploinsufficiency. The reciprocal microduplication syndrome, dup(17)(p11.2p11.2), manifests several neurobehavioral abnormalities, but the responsible dosage-sensitive gene(s) remain undefined. We previously generated a mouse model for dup(17)(p11.2p11.2), Dp(11)17/+, that recapitulated most of the phenotypes observed in human patients. We have now analyzed compound heterozygous mice carrying a duplication [Dp(11)17] in one chromosome 11 along with a null allele of Rai1 in the other chromosome 11 homologue [Dp(11)17/Rai1– mice] in order to study the relationship between Rai1 gene copy number and the Dp(11)17/+ phenotypes. Normal disomic Rai1 gene dosage was sufficient to rescue the complex physical and behavioral phenotypes observed in Dp(11)17/+ mice, despite altered trisomic copy number of the other 18 genes present in the rearranged genomic interval. These data provide a model for variation in copy number of single genes that could influence common traits such as obesity and behavior. PMID:17024248

  15. Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13.3: Assessment of Their Roles in Breast and Ovarian Carcinogenesis

    DTIC Science & Technology

    1997-07-01

    minimum region of allelic loss on chromosome 17p 13.3, between polymorphic markers D17S5 and D17S28, in genomic DNA from breast and ovarian tumors (Figure 1...encode proteins of 443 and 227 amino acids, with no known functional motifs. Comparison of genomic and cDNA sequences showed that the genes overlap...is tissue specific (Figure 4). When zoo blots comprised of EcoRI fragments of genomic DNA from various species were probed with the unique exon 1 of

  16. Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial.

    PubMed

    Stilgenbauer, Stephan; Eichhorst, Barbara; Schetelig, Johannes; Hillmen, Peter; Seymour, John F; Coutre, Steven; Jurczak, Wojciech; Mulligan, Stephen P; Schuh, Anna; Assouline, Sarit; Wendtner, Clemens-Martin; Roberts, Andrew W; Davids, Matthew S; Bloehdorn, Johannes; Munir, Talha; Böttcher, Sebastian; Zhou, Lang; Salem, Ahmed Hamed; Desai, Monali; Chyla, Brenda; Arzt, Jennifer; Kim, Su Young; Verdugo, Maria; Gordon, Gary; Hallek, Michael; Wierda, William G

    2018-07-01

    Purpose Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported. Patients and Methods Overall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up. Responses were based on 2008 International Workshop on Chronic Lymphocytic Leukemia criteria, with monthly physical exams and blood counts. Computed tomography scan was mandatory at week 36, after which assessment made was by clinical evaluation. Marrow biopsy was performed when complete remission was suspected. MRD was assessed by flow cytometry. Results Patients had a median of two prior therapies (range, zero to 10 therapies), 71% had TP53 mutation, and 48% had nodes that were ≥ 5 cm. Median time on venetoclax was 23.1 months (range, 0 to 44.2 months) and median time on study was 26.6 months (range, 0 to 44.2 months). For all patients, investigator-assessed objective response rate was 77% (122 of 158 patients; 20% complete remission) and estimated progression-free survival at 24 months was 54% (95% CI, 45% to 62%). For 16 patients who received prior kinase inhibitors, objective response rate was 63% (10 of 16 patients) and 24-month progression-free survival estimate was 50% (95% CI, 25% to 71%). By intent-to-treat analysis, 48 (30%) of 158 patients achieved MRD below the cutoff of 10 -4 in blood. Common grade 3 and 4 adverse events were hematologic and managed with supportive care and/or dose adjustments. Conclusion Venetoclax achieves durable responses and was well tolerated in patients with del(17p) CLL

  17. 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.

    PubMed

    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

  18. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations

    PubMed Central

    Le Meur, Nathalie; Holder-Espinasse, Muriel; Jaillard, Sylvie; Goldenberg, Alice; Joriot, Sylvie; Amati-Bonneau, Patrizia; Guichet, Agnès; Barth, Magalie; Charollais, Aude; Journel, Hubert; Auvin, Stéphane; Boucher, Cécile; Kerckaert, Jean-Pierre; David, Véronique; Manouvrier-Hanu, Sylvie; Saugier-Veber, Pascale; Frébourg, Thierry; Dubourg, Christèle; Andrieux, Joris; Bonneau, Dominique

    2010-01-01

    Over the last few years, array-CGH has remarkably improved the ability to detect cryptic unbalanced rearrangements in patients presenting with syndromic mental retardation. Using whole genome oligonucleotide array-CGH, we detected 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb in 5 unrelated patients showing phenotypic similarities, namely severe mental retardation with absent speech, hypotonia and stereotypic movements. Most of the patients presented also with facial dysmorphic features, epilepsy and/or cerebral malformations. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, known to act in brain as a neurogenesis effector which regulates excitatory synapse number. In a patient presenting a similar phenotype, we subsequently identified a MEF2C nonsense mutation. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations. PMID:19592390

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

    SciTech Connect

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

    1995-11-01

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

  20. Common regions of deletion in chromosome regions 3p12 and 3p14.2 in primary clear cell renal carcinomas.

    PubMed

    Lubinski, J; Hadaczek, P; Podolski, J; Toloczko, A; Sikorski, A; McCue, P; Druck, T; Huebner, K

    1994-07-15

    Nearly all clear cell renal cell carcinomas (RCCs) exhibit loss of alleles on the short arm of chromosome 3. Loss and mutation at the von Hippel-Lindau (VHL) gene at 3p25 probably occurs in most RCCs and, since the VHL gene was recently cloned, data on VHL involvement in RCCs is accumulating. However, the region 3p14-p12, a region that contains the familial RCC-associated t(3;8)(p14.2;q24) chromosome translocation and the small cell lung carcinoma-associated homozygous deletion at 3p13-12, has also been reported to exhibit allele loss in a large fraction of RCCs. In order to focus future studies on potential suppressor genes in the 3p14-p12 region, we have studied allele loss in 30 RCCs with 9 polymorphic simple sequence repeat markers spanning 3p21.1-p12. Partial losses in the 3p21-p12 region were observed, allowing determination of common regions of loss of heterozygosity overlap in 15 RCCs. Results suggested that most RCCs exhibit loss in a region which brackets the t(3;8) familial chromosome translocation at 3p14.2, and some show additional deletions within the U2020 small cell lung carcinoma deletion at 3p12.

  1. Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1–q35.3 susceptibility locus identified by whole-exome sequencing

    PubMed Central

    Karolak, Justyna A; Gambin, Tomasz; Pitarque, Jose A; Molinari, Andrea; Jhangiani, Shalini; Stankiewicz, Pawel; Lupski, James R; Gajecka, Marzena

    2017-01-01

    Keratoconus (KTCN) is a protrusion and thinning of the cornea, resulting in impairment of visual function. The extreme genetic heterogeneity makes it difficult to discover factors unambiguously influencing the KTCN phenotype. In this study, we used whole-exome sequencing (WES) and Sanger sequencing to reduce the number of candidate genes at the 5q31.1–q35.3 locus and to prioritize other potentially relevant variants in an Ecuadorian family with KTCN. We applied WES in two affected KTCN individuals from the Ecuadorian family that showed a suggestive linkage between the KTCN phenotype and the 5q31.1–q35.3 locus. Putative variants identified by WES were further evaluated in this family using Sanger sequencing. Exome capture discovered a total of 173 rare (minor allele frequency <0.001 in control population) nonsynonymous variants in both affected individuals. Among them, 16 SNVs were selected for further evaluation. Segregation analysis revealed that variants c.475T>G in SKP1, c.671G>A in PROB1, and c.527G>A in IL17B in the 5q31.1–q35.3 linkage region, and c.850G>A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied KTCN family. We demonstrate that a combination of various techniques significantly narrowed the studied genomic region and reduced the list of the putative exonic variants. Moreover, since this locus overlapped two other chromosomal regions previously recognized in distinct KTCN studies, our findings suggest that this 5q31.1–q35.3 locus might be linked with KTCN. PMID:27703147

  2. Serum expression levels of microRNA-382-3p, -598-3p, -1246 and -184 in breast cancer patients.

    PubMed

    Fu, Lun; Li, Zhaoyun; Zhu, Jie; Wang, Pan; Fan, Guangmin; Dai, Yuechu; Zheng, Zhibao; Liu, Yang

    2016-07-01

    The purpose of the present study was to investigate the serum levels of microRNA (miRNA/miR)-382-3p, -598-3p, -1246 and -184 in breast cancer patients and to assess their feasibility as biomarkers for breast cancer screening. Serum samples were obtained from 100 breast cancer patients and 40 age-matched healthy control subjects in Taizhou Central Hospital (Taizhou, Zhejiang, China) between January 2013 and September 2014. The serum expression levels of miR-382-3p, -598-3p, -1246 and -184 were determined by stem-loop reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curves were drawn to evaluate the sensitivity and specificity of the serum miRNA expression levels for the screening of breast cancer. miR-382-3p and -1246 were significantly upregulated in the serum of the breast cancer patients, while miR-598-3p and -184 were significantly downregulated. The sensitivity and specificity to detect breast cancer were as follows: miR-382-3p, 52.0 and 92.5%; miR-598-3p, 95.0 and 85.0%; miR-1246, 93.0 and 75.0%; and miR-184, 87.5 and 71.0%, respectively. The expression levels of the four serum miRNAs were not correlated with the patients' clinical stage. In summary, miR-382-3p, -598-3p, -1246 and -184 are all involved in the development of breast cancer, and are promising biomarkers for breast cancer detection.

  3. Serum expression levels of microRNA-382-3p, −598-3p, −1246 and −184 in breast cancer patients

    PubMed Central

    FU, LUN; LI, ZHAOYUN; ZHU, JIE; WANG, PAN; FAN, GUANGMIN; DAI, YUECHU; ZHENG, ZHIBAO; LIU, YANG

    2016-01-01

    The purpose of the present study was to investigate the serum levels of microRNA (miRNA/miR)-382-3p, −598-3p, −1246 and −184 in breast cancer patients and to assess their feasibility as biomarkers for breast cancer screening. Serum samples were obtained from 100 breast cancer patients and 40 age-matched healthy control subjects in Taizhou Central Hospital (Taizhou, Zhejiang, China) between January 2013 and September 2014. The serum expression levels of miR-382-3p, −598-3p, −1246 and −184 were determined by stem-loop reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curves were drawn to evaluate the sensitivity and specificity of the serum miRNA expression levels for the screening of breast cancer. miR-382-3p and −1246 were significantly upregulated in the serum of the breast cancer patients, while miR-598-3p and −184 were significantly downregulated. The sensitivity and specificity to detect breast cancer were as follows: miR-382-3p, 52.0 and 92.5%; miR-598-3p, 95.0 and 85.0%; miR-1246, 93.0 and 75.0%; and miR-184, 87.5 and 71.0%, respectively. The expression levels of the four serum miRNAs were not correlated with the patients' clinical stage. In summary, miR-382-3p, −598-3p, −1246 and −184 are all involved in the development of breast cancer, and are promising biomarkers for breast cancer detection. PMID:27347136

  4. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study.

    PubMed

    O'Brien, Susan; Jones, Jeffrey A; Coutre, Steven E; Mato, Anthony R; Hillmen, Peter; Tam, Constantine; Österborg, Anders; Siddiqi, Tanya; Thirman, Michael J; Furman, Richard R; Ilhan, Osman; Keating, Michael J; Call, Timothy G; Brown, Jennifer R; Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F; Chu, Alvina D; Hallek, Michael; Stilgenbauer, Stephan

    2016-10-01

    The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall

  5. Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration.

    PubMed

    Engdahl, Elin; Dunn, Nicky; Niehusmann, Pitt; Wideman, Sarah; Wipfler, Peter; Becker, Albert J; Ekström, Tomas J; Almgren, Malin; Fogdell-Hahn, Anna

    2017-06-01

    Human herpesvirus 6B (HHV-6B) is a neurotropic betaherpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with an Illumina 450K array, comparing HHV-6B-infected and uninfected Molt-3 T cells 3 days postinfection. Bisulfite pyrosequencing was used to validate the Illumina results and to investigate methylation over time in vitro Expression of genes was investigated using quantitative PCR (qPCR), and virus integration was investigated with PCR. A total of 406 CpG sites showed a significant HHV-6B-induced change in methylation in vitro Remarkably, 86% (351/406) of these CpGs were located <1 Mb from chromosomal ends and were all hypomethylated in virus-infected cells. This was most evident at chromosome 17p13.3, where HHV-6B had induced CpG hypomethylation after 2 days of infection, possibly through TET2, which was found to be upregulated by the virus. In addition, virus-induced cytosine hydroxymethylation was observed. Genes located in the hypomethylated region at 17p13.3 showed significantly upregulated expression in HHV-6B-infected cells. A temporal experiment revealed HHV-6B integration in Molt-3 cell DNA 3 days after infection. The telomere at 17p has repeatedly been described as an integration site for HHV-6B, and we show for the first time that HHV-6B induces hypomethylation in this region during acute infection, which may play a role in the integration process, possibly by making the DNA more accessible. IMPORTANCE The ability to establish latency in the host is a hallmark of herpesviruses, but the mechanisms differ. Human herpesvirus 6B (HHV-6B) is known to establish latency through integration of its genome into the telomeric regions of host cells, with the ability to reactivate. Our study is the first to show that HHV-6B specifically induces

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

    SciTech Connect

    Lorenzetti, D.; Pandolfo, M.; Pareyson, D.

    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 onmore » 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.« less

  7. BPDE induced lymphocytic chromosome 3p deletions may predict renal cell carcinoma risk.

    PubMed

    Zhu, Yimin; Horikawa, Yohei; Yang, Hushan; Wood, Christopher G; Habuchi, Tomonori; Wu, Xifeng

    2008-06-01

    Cigarette smoking is a risk factor for renal cell carcinoma. BPDE (benzo[alpha]pyrene diol epoxide) (Midwest Research Institute, Kansas City, Missouri), which is a major constituent of cigarette smoke, induces 3p aberrations that are associated with susceptibility to other smoking associated cancers. Because chromosome 3p deletions are known to be the most frequent genetic alterations in renal cell carcinoma, we tested whether 3p sensitivity to BPDE predicts susceptibility to renal cell carcinoma. Cultured peripheral blood lymphocytic cells from 170 cases and 135 controls were treated with 2 microM BPDE for 24 hours and assessed for 3p deletions by fluorescence in situ hybridization using probes directed to 3p25.2, 3p21.3, 3p14.2 and 3p12.2. A probe for 3q13 served as a control. One thousand lymphocyte interphases were scored per sample. At each locus BPDE induced 3p deletions were significantly more common in cases than in controls. No significant differences between cases and controls were observed for deletions in 3q13. Using the median value in controls as the cutoff point for BPDE sensitivity we found that the OR in subjects with high BPDE sensitivity at 3p25.2, 3p21.3, 3p14.2 and 3p12.2 was 2.02 (95% CI 1.18-3.46), 2.28 (95% CI 1.33-3.92), 1.84 (95% CI 1.07-3.16) and 1.97 (95% CI 1.15-3.37), respectively. There were dose dependent relationships between the number of deletions at each locus and the risk of renal cell carcinoma. This study demonstrates that chromosome 3p may be a specific molecular target of cigarette carcinogens and BPDE sensitivity in chromosome 3p may reflect the genetic susceptibility of an individual to renal cell carcinoma.

  8. Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma.

    PubMed

    Riquelme, Erick; Tang, Moying; Baez, Sergio; Diaz, Alfonso; Pruyas, Martha; Wistuba, Ignacio I; Corvalan, Alejandro

    2007-05-18

    Gallbladder carcinoma (GBC) is a highly malignant neoplasm that represents the leading cause of death for cancer in Chilean females. There is limited information about the molecular abnormalities involved in its pathogenesis. We have identified a number of molecular changes in GBC, including frequent allelic losses at chromosome 3p regions. Four distinct 3p sites (3p12, 3p14.2, 3p21.3 and 3p22-24) with frequent and early allelic losses in the sequential pathogenesis of this neoplasm have been detected. We investigated epigenetic and genetic abnormalities in GBC affecting 6 candidate tumor suppressor genes (TSG) located in chromosome 3p, including DUTT1 (3p12), FHIT (3p14.2), BLU, RASSF1A, SEMA3B and hMLH1 (3p21.3). DNA extracted from frozen tissue obtained from 50 surgical resected GBCs was examined for gene promoter methylation using MSP (methylation-specific PCR) technique after bisulfite treatment in all 6 genes. In addition, we performed PCR-based mutation examination using SSCP in FHIT and RASSF1A genes and loss of heterozygosity (LOH) analysis using microdissected tissue in a subset of tumors for the 3p21.3 region with 8 microsatellite markers. A very high frequency of GBC methylation was detected in SEMA3B (46/50, 92%) and FHIT (33/50, 66%), intermediate incidences in BLU (13/50, 26%) and DUTT1 (11/50, 22%) and very low frequencies in RASSF1A (4/50, 8%) and hMLH1 (2/50, 4%). Allelic loss at 3p21.3 was found in nearly half of the GBCs examined. We conclude that epigenetic inactivation by abnormal promoter methylation is a frequent event in chromosome 3p candidate TSGs in GBC pathogenesis, especially affecting genes SEMA3B (3p21.3) and FHIT (3p14.2).

  9. The Aftermath of the Largest Cometary Outburst in Recorded History - An In-Depth Study of Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Stevenson, Rachel Ann

    On UT 2007 Oct. 23, Jupiter Family comet 17P/Holmes underwent the largest cometary outburst in recorded history when it brightened by a factor of nearly a million in less than 2 days. This unprecedented event prompted a four-month observing campaign to observe the aftermath of the outburst. The wide field imager, MegaCam mounted on the Canada-France-Hawaii telescope was used to obtain r' images of the nucleus and the rapidly expanding dust coma. These images are unequaled in their quality and scope, and form a unique dataset with which to study the outburst aftermath. This original work examines the morphology of the outburst, and constrains the characteristics of the ejected material. Spatial filtering of images obtained in 2007 Nov. revealed numerous fragments moving away from the nucleus. The fragments were too bright to have been inactive, monolithic blocks and must have been acting as mini-comets with their own sources of sublimating volatiles and dust comae. They represented a significant (~ 10%) of the total ejected mass. The fragments had unusually high velocities relative to the nucleus, suggesting that they were accelerated by high gas pressure inside the nucleus prior to ejection. This work presents the first detection of such large, rapidly moving cometary fragments. The scarcity of similar ejecta around other fragmenting comets may be due to observational biases, rather than being unique to 17P/Holmes. Aperture photometry was used to study the evolution of the inner coma, which faded rapidly in the weeks and months following the initial outburst. Despite the observed fading, the nucleus must have remained active, continuing to supply fresh material to the inner coma. A second, much smaller outburst was detected on UT 2007 Nov. 12, which released an estimated 106 kg of dust into the inner coma. The secondary outburst showed that the nucleus remained unstable for several weeks after the initial event. Surface brightness profiles of the inner coma were

  10. Noble-gas-induced collisional broadening of the 3P12-3P32 transition of sodium measured by the trilevel-echo technique

    NASA Astrophysics Data System (ADS)

    Mossberg, T. W.; Whittaker, E.; Kachru, R.; Hartmann, S. R.

    1980-11-01

    A variant of the trilevel-echo effect is observed and utilized to measure the effective cross section for broadening of the 3P12-3P32 transition of sodium by the noble gases. The cross section measured here should be the same as the broadening cross section obtained from a direct measurement of the collisionally broadened 3P12-3P32 transition linewidth (if such a measurement were possible). The new echo, the "inverted-difference-frequency" (IDF) trilevel echo, is well suited to the study of transitions between excited states of the same parity. At 400 K the measured broadening cross sections are He 115(12) Å2, Ne 120(12) Å2, Ar 234(23) Å2, Kr 266(27) Å2, and Xe 311(31) Å2. With He as the perturber, the cross section for broadening of the 3P12-3P32 transition can be calculated from measured depolarization and fine-structure-changing collision cross sections. With the other perturbers, however, collisional phase changes appear to be important. An intuitive diagrammatic technique for the analysis of echoes is applied to the IDF trilevel echo.

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

    PubMed Central

    Horváth, Emese; Sikovanyecz, János; Pál, Attila; Kaiser, László; Bálint, Bálint L.; Szilárd, Póliska; Kozinszky, Zoltán; Szabó, János

    2010-01-01

    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. PMID:21274281

  12. Development of an NPM1/MLF1 D-FISH probe set for the detection of t(3;5)(q25;q35) identified in patients with acute myeloid leukemia.

    PubMed

    Aypar, Umut; Knudson, Ryan A; Pearce, Kathryn E; Wiktor, Anne E; Ketterling, Rhett P

    2014-09-01

    The t(3;5)(q25;q35) NPM1/MLF1 fusion has an incidence of approximately 0.5% in acute myeloid leukemia (AML) and has an intermediate prognosis at diagnosis. We have developed a dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) assay to detect fusion of the MLF1 and NPM1 genes. A blinded investigation was performed using 25 normal bone marrow specimens and 26 bone marrow samples from patients with one or more metaphases with a t(3;5)(q21-q25;q31-q35) or a der(5)t(3;5)(q21-q25;q31-q35) previously identified by chromosome analysis. Once unblinded, the results indicate our D-FISH method identified NPM1/MLF1 fusion in 15 of the 26 fully evaluated patient samples. Excluding three samples with a single abnormal t(3;5) metaphase, 15 of 17 (88%) patient samples with a balanced t(3;5) demonstrated NPM1/MLF1 fusion, and 0 of 6 patient samples with a der(5)t(3;5) demonstrated NPM1/MLF1 fusion, suggesting only the balanced form of this 3;5 translocation as observed by karyotype is associated with NPM1/MLF1 fusion. Overall, the FISH results demonstrated five different outcomes (NPM1/MLF1 fusion, MLF1 disruption, MLF1 duplication, NPM1 deletion, and normal), indicating significant molecular heterogeneity when the 3;5 translocation is identified. The development of this sensitive D-FISH strategy for the detection of NPM1/MLF1 fusion adds to the AML FISH testing repertoire and is effective in the detection of this translocation at diagnosis as well as monitoring residual disease in AML patients. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

    2009-01-01

    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 originate from a distinct

  14. Loss in 3p and 4p and gain of 3q are concomitant aberrations in squamous cell carcinoma of the vulva.

    PubMed

    Jee, K J; Kim, Y T; Kim, K R; Kim, H S; Yan, A; Knuutila, S

    2001-05-01

    Neoplasm of the vulva is a rare malignancy accounting for <5% of all female genital-tract cancer. However, in recent years the incidence of vulva intraepithelial neoplasia, known to serve as a precursor to carcinoma, has increased in young women generating considerable interest in its pathogenesis. Genetic changes at the molecular level in precursor or invasive vulvar tumors are not well investigated, and DNA copy number changes have not been reported until now. We used comparative genomic hybridization (CGH) to analyze genetic alterations in 10 primary invasive squamous cell carcinomas of the vulva. Chromosomal aberrations were identified in 8/10 cases. The most frequent chromosomal losses were 4p13-pter (five cases), 3p (four cases), and 5q (two cases), and less frequent losses were detected at 6q, 11q, and 13q (one case each). The most frequent chromosomal gains were 3q (four cases) and 8p (three cases), and less frequent gains were found in 9p, 14, 17, and 20q (one case each). The pattern of chromosomal imbalance in vulvar cancer detected by CGH was revealed to be very similar to that in cervical cancers, despite regional differences in their prevalence. These results suggest that the pathogenic pathways in vulvar and cervical carcinomas may be similar and that the genetic background may be common to these two squamous cell carcinomas.

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

    PubMed Central

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

    2016-01-01

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

  16. Subaru/COMICS Mid-Infrared Observation of the Near-Nucleus Region of Comet 17P/Holmes at the Early Phase of an Outburst

    NASA Astrophysics Data System (ADS)

    Watanabe, Jun-Ichi; Honda, Mitsuhiko; Ishiguro, Masateru; Ootsubo, Takafumi; Sarugaku, Yuki; Kadono, Toshihiko; Sakon, Itsuki; Fuse, Tetsuharu; Takato, Naruhisa; Furusho, Reiko

    2009-08-01

    Mid-infrared 8--25μm imaging and spectroscopic observations of the comet 17P/Holmes in the early phase of its outburst in brightness were performed on 2007 October 25--28UT using the Cooled Mid-Infrared Camera and Spectrometer (COMICS) on the 8.2-m Subaru Telescope. We detected an isolated dust cloud that moved toward the south-west direction from the nucleus. The 11.2μm peak of a crystalline silicate feature onto a broad amorphous silicate feature was also detected both in the central condensation of the nucleus and an isolated dust cloud. The color temperature of the isolated dust cloud was estimated to be ˜200K, which is slightly higher than the black-body temperature. Our analysis of the motion indicates that the isolated cloud moved anti-sunward. We propose several possibilities for the motion of the cloud: fluffy dust particles in the isolated cloud started to depart from the nucleus due to radiation pressure almost as soon as the main outburst occurred, or dust particles moved by some other anti-sunward forces, such as a rocket effect and photophoresis when the surrounding dust coma became optically thin. The origin and the nature of the isolated dust cloud are discussed in this paper.

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

    SciTech Connect

    Murakami, Tatsufumi; Lupski, J.R.

    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 cosmidmore » 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.« less

  18. BPDE-Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk

    PubMed Central

    Zhu, Yimin; Horikawa, Yohei; Yang, Hushan; Wood, Christopher G.; Habuchi, Tomonori; Wu, Xifeng

    2009-01-01

    Purpose Cigarette smoking is a risk factor for renal cell carcinoma (RCC). Benzo[α]pyrene diol expoxide (BPDE), a major constituent of cigarette smoke, induces 3p aberrations that are associated with susceptibility to other smoking-associated cancers. Because chromosome 3p deletions are known to the most frequent genetic alterations in RCC, we tested whether 3p sensitivity to BPDE predicted susceptibility to RCC. Material and Methods Cultured peripheral blood lymphocytic cells from 170 cases and 135 control subjects were treated with 2 μM BPDE for 24 hours and assessed for 3p deletions by flourescenence in situ hybridization using probes directed to 3p25.2, 3p21.3, 3p14.2, and 3p12.2; a probe for 3q13 was used as a control. One thousand lymphocyte interphases were scored for each sample. Results At each locus, BPDE-induced 3p deletions were significantly more frequent in cases than in controls. No significant differences between cases and controls were observed for deletions in 3q13. Using the median value in the controls as the cutoff point for BPDE sensitivity, we found the odds ratios for subjects with high BPDE sensitivity at 3p25.2, 3p21.3, 3p14.2, and 3p12.2 were 2.02 (95% confidence interval [CI], 1.15–3.37), 2.28 (95% CI, 1.07–3.16), 1.84 (95% CI, 1.33–3.92), and 1.97 (95% CI, 1.18–3.46), respectively. There were dose-dependent relationships between the number of deletions at each locus and risk for RCC. Conclusions This study demonstrated that chromosome 3p may be a specific molecular target of cigarette carcinogens and that BPDE sensitivity in chromosome 3p may reflect an individual’s genetic susceptibility to RCC. PMID:18433782

  19. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations.

    PubMed

    Le Meur, N; Holder-Espinasse, M; Jaillard, S; Goldenberg, A; Joriot, S; Amati-Bonneau, P; Guichet, A; Barth, M; Charollais, A; Journel, H; Auvin, S; Boucher, C; Kerckaert, J-P; David, V; Manouvrier-Hanu, S; Saugier-Veber, P; Frébourg, T; Dubourg, C; Andrieux, J; Bonneau, D

    2010-01-01

    Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.

  20. Bone-related Circulating MicroRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their Association to Bone Microstructure and Histomorphometry.

    PubMed

    Feichtinger, Xaver; Muschitz, Christian; Heimel, Patrick; Baierl, Andreas; Fahrleitner-Pammer, Astrid; Redl, Heinz; Resch, Heinrich; Geiger, Elisabeth; Skalicky, Susanna; Dormann, Rainer; Plachel, Fabian; Pietschmann, Peter; Grillari, Johannes; Hackl, Matthias; Kocijan, Roland

    2018-03-20

    The assessment of bone quality and the prediction of fracture risk in idiopathic osteoporosis (IOP) are complex prospects as bone mineral density (BMD) and bone turnover markers (BTM) do not indicate fracture-risk. MicroRNAs (miRNAs) are promising new biomarkers for bone diseases, but the current understanding of the biological information contained in the variability of miRNAs is limited. Here, we investigated the association between serum-levels of 19 miRNA biomarkers of idiopathic osteoporosis to bone microstructure and bone histomorphometry based upon bone biopsies and µCT (9.3 μm) scans from 36 patients. Four miRNAs were found to be correlated to bone microarchitecture and seven miRNAs to dynamic histomorphometry (p < 0.05). Three miRNAs, namely, miR-29b-3p, miR-324-3p, and miR-550a-3p showed significant correlations to histomorphometric parameters of bone formation as well as microstructure parameters. miR-29b-3p and miR-324-p were found to be reduced in patients undergoing anti-resorptive therapy. This is the first study to report that serum levels of bone-related miRNAs might be surrogates of dynamic histomorphometry and potentially reveal changes in bone microstructure. Although these findings enhance the potential value of circulating miRNAs as bone biomarkers, further experimental studies are required to qualify the clinical utility of miRNAs to reflect dynamic changes in bone formation and microstructure.

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

    SciTech Connect

    Liu, Shuling, E-mail: liusl8888@yahoo.com.cn; Li, Shu; Wang, Jingping

    2012-11-15

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

  2. MiR-590-3p suppresses hepatocellular carcinoma growth by targeting TEAD1.

    PubMed

    Ge, Xin; Gong, Liansheng

    2017-03-01

    MicroRNA signature is altered in different disease states including cancer, and some microRNAs act as oncogenes or tumor suppressors. MiR-590-3p has been shown to be involved in human cancer progression. However, its role in hepatocellular carcinoma remains unknown. In this study, miR-590-3p level was measured, and clinicopathological features were determined in hepatocellular carcinoma tissues. The function of miR-590-3p was examined in vitro and in vivo. Real-time reverse transcription polymerase chain reaction analysis demonstrated downregulation of miR-590-3p in hepatocellular carcinoma tissues, and its downregulation was associated with a poor overall survival of hepatocellular carcinoma patients. Ectopic expression of miR-590-3p promoted growth of hepatocellular carcinoma cells, whereas its depletion inhibited cell growth. Transcriptional enhancer activator domain 1 was identified as a validated miR-590-3p target. Upregulation of transcriptional enhancer activator domain 1 was found in hepatocellular carcinoma tissues and inversely correlated with miR-590-3p. Our results indicate a tumor suppressor role of miR-590-3p in hepatocellular carcinoma through targeting transcriptional enhancer activator domain 1 and suggest its use in the diagnosis and prognosis of liver cancer.

  3. Ge 3P 6Si 2O 25: A cage structure closely related to the intersecting tunnel structure KMo 3P 6Si 2O 25

    NASA Astrophysics Data System (ADS)

    Leclaire, A.; Raveau, B.

    1988-08-01

    A germanosilicophosphate Ge 3P 6Si 2O 25 has been isolated. Its structure was solved from a single-crystal study in the space group P overline31c . Its cell parameters are a = b = 7.994(1) Å, c = 16.513(2) Å, Z = 2. The refinement by full-matrix least-squares calculations leads to R = 0.043 with 686 independent reflections. The structure of this oxide is built up from corner-sharing PO 4 and SiO 4 tetrahedra and GeO 6 octahedra. One observes a feature common to several silicophosphates: the presence of the structural unit P 6Si 2O 25 built up from a disilicate group sharing its corners with six PO 4 tetrahedra. The structural relationships between this oxide and the silicophosphates AMo 3P 6Si 2O 25 and Si 3P 6Si 2O 25 (or Ge 3P 6 Ge 2O 25) are described.

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

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  5. Orientation of Zn3P2 films via phosphidation of Zn precursors

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    Fortenberry, Ryan C.; Lukemire, Joseph A.

    2015-11-01

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

  7. Molecular and cytogenetic characterization of a de novo partial trisomy 3p case with review

    SciTech Connect

    Conte, R.A.; Pitter, J.; Verma, R.S.

    A one-year-old male infant was found to have a de novo unbalanced translocation resulting in partial trisomy for 3p, i.e. 46,XY,der(7)t(3;7)(p24.2;p22). Major clinical features included: dysmorphic ears, decreased muscle tone and episodes of seizures associated with fever. GTG- and QFQ-banding revealed additional material suggestive of chromosome 3p that was translocated to the terminal 7p. The FISH technique with two-color specific DNA probes for whole chromosomes 3 and 7 verified this finding. Other probands with the same amount of trisomic 3p2 segments as the present case had additional clinical abnormalities. Previously, identification of this so-called trisomy 3p2 syndrome was invariably basedmore » on the analysis of GTG-banded metaphase chromosomes. A review of 37 earlier cases revealed that the clinical manifestations varied with the amount of 3p2 material in the trisomic state, demonstrating increased anomalies with increased 3p2 sub-band trisomy. Phenotype to genotype correlation is best understood under conditions that can achieve respective characterization with a high degree of certainty. Presently, the FISH technique fulfills this requirement and the employment of loci probes that span 3p, when available, will ultimately increase the characterization resolution to the gene level.« less

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

    SciTech Connect

    Kononenko, Oleksiy

    2015-03-26

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

  9. Observation of the $$\\chi_\\mathrm{b1}$$(3P) and $$\\chi_\\mathrm{b2}$$(3P) and measurement of their masses

    SciTech Connect

    Sirunyan, Albert M; et al.

    Themore » $$\\chi_\\mathrm{b1}$$(3P) and $$\\chi_\\mathrm{b3}$$(3P) states are observed through their $$\\Upsilon$$(3S) $$\\gamma$$ decays, using an event sample of proton-proton collisions collected by the CMS experiment at the CERN LHC. data were collected at a center-of-mass energy of 13 TeV and correspond to an integrated luminosity of 80.0 fb$$^{-1}$$. $$\\Upsilon$$(3S) mesons are identified through their dimuon decay channel, while the low-energy photons are detected after converting to e$^+$e$^-$ pairs in the silicon tracker, leading to a $$\\chi_\\mathrm{b}$$(3P) mass resolution of 2.2 MeV. This is the first time that the $J =$ 1 and 2 states are well resolved and their masses individually measured: 10$$\\,$$513.42 $$\\pm$$ 0.41 (stat) $$\\pm$$ 0.18 (syst) MeV and 10$$\\,$$524.02 $$\\pm$$ 0.57 (stat) $$\\pm$$ 0.18 (syst) MeV; they are determined with respect to the world-average value of the $$\\Upsilon$$(3S) mass, which has an uncertainty of 0.5 MeV. mass splitting is measured to be 10.60 $$\\pm$$ 0.64 (stat) $$\\pm$$ 0.17 (syst) MeV.« less

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  11. Synthesis and characterization of hollow spherical copper phosphide (Cu 3P) nanopowders

    NASA Astrophysics Data System (ADS)

    Liu, Shuling; Qian, Yitai; Xu, Liqiang

    2009-03-01

    In this paper, hollow spherical Cu 3P nanopowders were synthesized by using copper sulfate pentahydrate (CuSO 4ṡ5H 2O) and yellow phosphorus in a mixed solvent of glycol, ethanol and water at 140-180 ∘C for 12 h. X-ray powder diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), electron diffraction pattern (ED) and transmission electronic microscopy (TEM) studies show that the as-synthesized nanocrystal is pure hexagonal phase Cu 3P with a hollow spherical morphology. Based on the TEM observations, a possible aggregation growth mechanism was proposed for the formation of Cu 3P hollow structures. Meanwhile, the effects of some key factors such as solvents, reaction temperature and reaction time on the final formation of the Cu 3P hollow structure were also discussed.

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  13. Study of radially excited Ds(21 S 0) and Ds(3P)

    NASA Astrophysics Data System (ADS)

    Tian, Yu; Zhao, Ze; Zhang, Ai-Lin

    2017-08-01

    The unobserved JP = 0- radial excitation Ds(21 S 0) is anticipated to have mass 2650 MeV (denoted as Ds(2650)). Study of hadronic production is an important way to identify highly excited states. We study hadronic production of Ds(2650) from higher excited resonances in a 3 P 0 model. Relevant hadronic partial decay widths are found to be very small, which implies it is difficult to observe Ds(2650) in hadronic decays of higher excited resonances. Hadronic decay widths of radially excited Ds(3P) have also been estimated. The total decay widths of four Ds(3P) are large, but the branching ratios in the Ds(2650)η channel are very small, which implies that it seems impossible to observe Ds(2650) in hadronic decays of Ds(3P). The dominant decay channels of the four Ds(3P) have been pointed out, and D1(2420), D1(2430), , D(2550), D(2600), (11D2)D(2750) and are possible to observe in hadronic production from Ds(3P). Supported by National Natural Science Foundation of China (11475111)

  14. Increased miR-132-3p expression is associated with chronic neuropathic pain

    PubMed Central

    Leinders, M.; Üçeyler, N.; Pritchard, R.A.; Sommer, C.; Sorkin, L.S.

    2016-01-01

    Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or painless inflammatory or non-inflammatory neuropathies based on clinical diagnosis. We found a 2.6 fold increase in miR-132-3p expression in WBC of neuropathy patients compared to healthy controls (p<0.001). MiR-132-3p expression was also slightly up-regulated in sural nerve biopsies from neuropathy patients suffering from neuropathic pain compared to those without pain (1.2 fold; p<0.001). These promising findings were investigated further in an animal model of neuropathic pain, the spared nerve injury model (SNI). For this purpose miR-132-3p expression levels were measured in dorsal root ganglia and spinal cord of rats. Subsequently, miR-132-3p expression was pharmacologically modulated with miRNA antagonists or mimetics, and evoked pain and pain aversion were assessed. Spinal miR-132-3p levels were highest 10 days after SNI, a time when persistent allodynia was established (p<0.05). Spinal administration of miR-132-3p antagonists via intrathecal (i.t.) catheters dose dependently reversed mechanical allodyina (p<0.001) and eliminated pain behavior in the place escape avoidance paradigm (p<0.001). Intrathecal administration of miR-132-3p mimetic dose-dependently induced pain behavior in naïve rats (p<0.001). Taken together these results indicate a pro-nociceptive effect of miR-132-3p in chronic neuropathic pain. PMID:27349406

  15. Cellular microRNA-miR-548g-3p modulates the replication of dengue virus.

    PubMed

    Wen, Weitao; He, Zhenjian; Jing, Qinlong; Hu, Yiwen; Lin, Cuiji; Zhou, Rui; Wang, Xiaoqun; Su, Yangfan; Yuan, Jiehao; Chen, Zhenxin; Yuan, Jie; Wu, Jueheng; Li, Jun; Zhu, Xun; Li, Mengfeng

    2015-06-01

    It has been well recognized that microRNA plays a role in the host-pathogen interaction network. The significance of microRNA in the regulation of dengue virus (DENV) replication, however, remains unknown. The objective of our study was to determine the biological function of miR-548g-3p in modulating the replication of dengue virus. Here we report that employment of a microRNA target search algorithm to analyze the 5' untranslated region (5'UTR) consensus sequences of DENV (DENV serotypes 1-4) led to a discovery that miR-548g-3p directly targets the stem loop A promoter element within the 5'UTR, a region essential for DENV replication. Real-time PCR was used to measure the expression levels of miR-548g-3p under DENV infection. We performed overexpression and inhibition assays to test the role of miR-548g-3p on DENV replication. The protein and mRNA levels of interferon were measured by ELISA and real-time PCR respectively. We found that overexpression of miR-548g-3p suppressed multiplication of DENV 1, 2, 3 and 4, and that miR-548g-3p was also found to interfere with DENV translation, thereby suppressing the expression of viral proteins. Our results suggest that miR-548g-3p directly regulates DENV replication and warrant further study to investigate the feasibility of microRNA-based anti-DENV approaches. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  17. Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma.

    PubMed

    Smol, Thomas; Dufour, Annika; Tricot, Sabine; Wemeau, Mathieu; Stalnikiewicz, Laure; Bernardi, Franck; Terré, Christine; Ducourneau, Benoît; Bisiau, Hervé; Daudignon, Agnès

    2017-01-01

    Our aim was to set the FISH combination of del(17p13), t(4;14), 1q21 gain and del(1p32), four adverse cytogenetic factors rarely evaluated together, and compare our technical thresholds with those defined in the literature. Two hundred thirty-three patients with MM at diagnosis were studied using FISH to target 4 unfavorable cytogenetic abnormalities: 17p13 deletion, t(4;14) translocation, 1p32 deletion and 1q21 gain. Technical thresholds were determined for each probe using isolated CD138-expressing PC from patients without MM. The FISH analysis identified abnormalities in 79.0% of patients. Del(17p13) was detected in 15.0% of cases, t(4;14) in 11.5%, 1q21 gain in 37.8% and del(1p32) in 8.7%. Adding 1p32/1q21 FISH probes has enabled us to identify adverse cytogenetic profiles in 39.0% of patients without del(17p13) or t(4;14). Clonal heterogeneity was observed in 51.1% of patients as well as an increase in the number of adverse abnormalities when related clones were greater than or equal to 2 (85.1% against 45.6%). FISH allowed detecting accumulation of adverse abnormalities and clonal heterogeneity in MM with a combination of 4 probes. The impacts of these two parameters need to be evaluated, and could be included in future cytogenetic classifications.

  18. UCS protein Rng3p activates actin filament gliding by fission yeast myosin-II

    PubMed Central

    Lord, Matthew; Pollard, Thomas D.

    2004-01-01

    We purified native Myo2p/Cdc4p/Rlc1p (Myo2), the myosin-II motor required for cytokinesis by Schizosaccharomyces pombe. The Myo2p heavy chain associates with two light chains, Cdc4p and Rlc1p. Although crude Myo2 supported gliding motility of actin filaments in vitro, purified Myo2 lacked this activity in spite of retaining full Ca-ATPase activity and partial actin-activated Mg-ATPase activity. Unc45-/Cro1p-/She4p-related (UCS) protein Rng3p restored the full motility and actin-activated Mg-ATPase activity of purified Myo2. The COOH-terminal UCS domain of Rng3p alone restored motility to pure Myo2. Thus, Rng3p contributes directly to the motility activity of native Myo2. Consistent with a role in Myo2 activation, Rng3p colocalizes with Myo2p in the cytokinetic contractile ring. The absence of Rlc1p or mutations in the Myo2p head or Rng3p compromise the in vitro motility of Myo2 and explain the defects in cytokinesis associated with some of these mutations. In contrast, Myo2 with certain temperature-sensitive forms of Cdc4p has normal motility, so these mutations compromise other functions of Cdc4p required for cytokinesis. PMID:15504913

  19. Identification of Yju3p as functional orthologue of mammalian monoglyceride lipase in the yeast Saccharomycescerevisiae.

    PubMed

    Heier, Christoph; Taschler, Ulrike; Rengachari, Srinivasan; Oberer, Monika; Wolinski, Heimo; Natter, Klaus; Kohlwein, Sepp D; Leber, Regina; Zimmermann, Robert

    2010-09-01

    Monoacylglycerols (MAGs) are short-lived intermediates of glycerolipid metabolism. Specific molecular species, such as 2-arachidonoylglycerol, which is a potent activator of cannabinoid receptors, may also function as lipid signaling molecules. In mammals, enzymes hydrolyzing MAG to glycerol and fatty acids, resembling the final step in lipolysis, or esterifying MAG to diacylglycerol, are well known; however, despite the high level of conservation of lipolysis, the corresponding activities in yeast have not been characterized yet. Here we provide evidence that the protein Yju3p functions as a potent MAG hydrolase in yeast. Cellular MAG hydrolase activity was decreased by more than 90% in extracts of Yju3p-deficient cells, indicating that Yju3p accounts for the vast majority of this activity in yeast. Loss of this activity was restored by heterologous expression of murine monoglyceride lipase (MGL). Since yju3Delta mutants accumulated MAG in vivo only at very low concentrations, we considered the possibility that MAGs are re-esterified into DAG by acyltransferases. Indeed, cellular MAG levels were further increased in mutant cells lacking Yju3p and Dga1p or Lro1p acyltransferase activities. In conclusion, our studies suggest that catabolic and anabolic reactions affect cellular MAG levels. Yju3p is the functional orthologue of mammalian MGL and is required for efficient degradation of MAG in yeast. 2010 Elsevier B.V. All rights reserved.

  20. Identification of Yju3p as functional orthologue of mammalian monoglyceride lipase in the yeast Saccharomycescerevisiae

    PubMed Central

    Heier, Christoph; Taschler, Ulrike; Rengachari, Srinivasan; Oberer, Monika; Wolinski, Heimo; Natter, Klaus; Kohlwein, Sepp D.; Leber, Regina; Zimmermann, Robert

    2010-01-01

    Monoacylglycerols (MAGs) are short-lived intermediates of glycerolipid metabolism. Specific molecular species, such as 2-arachidonoylglycerol, which is a potent activator of cannabinoid receptors, may also function as lipid signaling molecules. In mammals, enzymes hydrolyzing MAG to glycerol and fatty acids, resembling the final step in lipolysis, or esterifying MAG to diacylglycerol, are well known; however, despite the high level of conservation of lipolysis, the corresponding activities in yeast have not been characterized yet. Here we provide evidence that the protein Yju3p functions as a potent MAG hydrolase in yeast. Cellular MAG hydrolase activity was decreased by more than 90% in extracts of Yju3p-deficient cells, indicating that Yju3p accounts for the vast majority of this activity in yeast. Loss of this activity was restored by heterologous expression of murine monoglyceride lipase (MGL). Since yju3Δ mutants accumulated MAG in vivo only at very low concentrations, we considered the possibility that MAGs are re-esterified into DAG by acyltransferases. Indeed, cellular MAG levels were further increased in mutant cells lacking Yju3p and Dga1p or Lro1p acyltransferase activities. In conclusion, our studies suggest that catabolic and anabolic reactions affect cellular MAG levels. Yju3p is the functional orthologue of mammalian MGL and is required for efficient degradation of MAG in yeast. PMID:20554061

  1. Self-broadening of the sodium resonance lines and excitation transfer between the 3P32 and 3P12 levels

    NASA Astrophysics Data System (ADS)

    Huennekens, J.; Gallagher, A.

    1983-04-01

    Sodium vapor, in the density range 1013 to 5 × 1014 cm-3, was excited by a cw dye laser, tuned 20-150 GHz from either the D1 or D2 resonance line. We observed a three-peak scattered spectrum, consisting of the Rayleigh component at the laser frequency, and the two fluorescence components (direct and sensitized) at the atomic resonance-line frequencies. Corrections to the Rayleigh signals for anisotropy and polarization effects, and to the fluorescence signals for radiation trapping, were made in order to obtain the ratio of the sum of the total intensities of the two fluorescence components to that of the Rayleigh component. This ratio combined with a measurement of the line-wing absorption coefficient yields the sodium density and the D-line self-broadening rate coefficients [kbr=4.67×10-7 cm3s-1 (+/-15%) for the D2 line and kbr=3.07×10-7 cm3s-1 (+/-15%) for the D1 line]. Asymmetry in the self-broadened line wings due to fine-structure recoupling was observed. The measured intensity ratio of the D lines, combined with pulsed measurements of the effective radiative decay rates in the presence of radiation trapping, yields the fine-structure collisional-mixing cross section [σ(3P32-->3P12)=172Å2(+/-18%)] at T≅300° C. Our results are compared to other experiments and to theory.

  2. Tune-out wavelength for the 1 s 2 s3 S - 1 s 3 p 3 P transition of helium: relativistic effects

    NASA Astrophysics Data System (ADS)

    Drake, Gordon W. F.; Manalo, Jacob

    2017-04-01

    The tune-out wavelength is the wavelength at which the frequency dependent polarizability of an atom vanishes. It can be measured to very high precision by means of an interferometric comparison between two beams. This paper is part of a joint theoretical/ experimental project with K. Baldwin et al. (Australian National University) and L.-Y. Tang et al. (Wuhan Institute of Physics and Mathematics) to perform a high precision comparison between theory and experiment as a probe of atomic structure, including relativistic and quantum electrodynamic effects. We will report the results of calculations for the tune-out wavelength that is closest to the 1 s 2 s3 S - 1 s 3 p3 P transition of 4He. Our result for the M = 0 magnetic substate, obtained with a fully correlated Hylleraas basis set, is 413 . 079 958 51 (12) nm. This includes a leading relativistic contribution of - 0 . 059 218 5 (16) nm from the Breit interaction as a perturbation, and a relativistic recoil contribution of - 0 . 000 044 47 (17) nm. The results will be compared with recent relativistic CI calculations. Research supported by tha Natural Sciences and Engineering Research Council of Canada.

  3. Characterization of Potocki-Lupski Syndrome (dup(17)(p11.2p11.2)) and Delineation of a Dosage-Sensitive Critical Interval That Can Convey an Autism Phenotype

    PubMed Central

    Potocki, Lorraine; Bi, Weimin; Treadwell-Deering, Diane; Carvalho, Claudia M. B.; Eifert, Anna; Friedman, Ellen M.; Glaze, Daniel; Krull, Kevin; Lee, Jennifer A.; Lewis, Richard Alan; Mendoza-Londono, Roberto; Robbins-Furman, Patricia; Shaw, Chad; Shi, Xin; Weissenberger, George; Withers, Marjorie; Yatsenko, Svetlana A.; Zackai, Elaine H.; Stankiewicz, Pawel; Lupski, James R.

    2007-01-01

    The duplication 17p11.2 syndrome, associated with dup(17)(p11.2p11.2), is a recently recognized syndrome of multiple congenital anomalies and mental retardation and is the first predicted reciprocal microduplication syndrome described—the homologous recombination reciprocal of the Smith-Magenis syndrome (SMS) microdeletion (del(17)(p11.2p11.2)). We previously described seven subjects with dup(17)(p11.2p11.2) and noted their relatively mild phenotype compared with that of individuals with SMS. Here, we molecularly analyzed 28 additional patients, using multiple independent assays, and also report the phenotypic characteristics obtained from extensive multidisciplinary clinical study of a subset of these patients. Whereas the majority of subjects (22 of 35) harbor the homologous recombination reciprocal product of the common SMS microdeletion (∼3.7 Mb), 13 subjects (∼37%) have nonrecurrent duplications ranging in size from 1.3 to 15.2 Mb. Molecular studies suggest potential mechanistic differences between nonrecurrent duplications and nonrecurrent genomic deletions. Clinical features observed in patients with the common dup(17)(p11.2p11.2) are distinct from those seen with SMS and include infantile hypotonia, failure to thrive, mental retardation, autistic features, sleep apnea, and structural cardiovascular anomalies. We narrow the critical region to a 1.3-Mb genomic interval that contains the dosage-sensitive RAI1 gene. Our results refine the critical region for Potocki-Lupski syndrome, provide information to assist in clinical diagnosis and management, and lend further support for the concept that genomic architecture incites genomic instability. PMID:17357070

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  5. Effects of Magnetic Field and Rotation on 3P2 Superfluidity in Neutron Stars

    NASA Astrophysics Data System (ADS)

    Masuda, Kota; Nitta, Muneto

    2014-09-01

    It is believed that an anisotropic 3P2 superfluid state is realized in the core of neutron stars. Historically, a lot of works (Anderson et al. (1961), Hoffberg et al. (1970) and Tamagaki (1970)) discussed the properties of 3P2 superfluid state. Ginzburg-Landau (GL) equation was derived by Fujita, Tsuneto (1972) and Richardson (1972). After that, Mermin (1974) solved the problem of minimizing GL free energy density for d-wave pairing and showed what ground states are realized. By using these results, Sauls and Serene (1978) concluded that the unitary phase is realized in BCS limit, and Sauls et al. (1982) showed 3P2 vortices have a spontaneous magnetization. In this presentation, we firstly introduce GL equation and show some analogy to that of spin2-BEC. In BCS limit, degenerate ground states are parameterized by one parameter. We show effects of gradient terms, magnetic field and rotation on ground states and half-quantized 3P2 vortices are the most stable states under certain conditions. Next, by using an anisotropic GL equation, we discuss a spontaneous magnetization caused by half-quantized 3P2 vortices and compare results with that of integer vortices. Finally, we comment on possible effects of 3P2 superfluid state on neutron star observables. It is believed that an anisotropic 3P2 superfluid state is realized in the core of neutron stars. Historically, a lot of works (Anderson et al. (1961), Hoffberg et al. (1970) and Tamagaki (1970)) discussed the properties of 3P2 superfluid state. Ginzburg-Landau (GL) equation was derived by Fujita, Tsuneto (1972) and Richardson (1972). After that, Mermin (1974) solved the problem of minimizing GL free energy density for d-wave pairing and showed what ground states are realized. By using these results, Sauls and Serene (1978) concluded that the unitary phase is realized in BCS limit, and Sauls et al. (1982) showed 3P2 vortices have a spontaneous magnetization. In this presentation, we firstly introduce GL equation and

  6. Genetic instability of 3p12-p21-specific microsatellite sequences in renal cell carcinoma.

    PubMed

    Willers, C P; Siebert, R; Bardenheuer, W; Lux, A; Michaelis, S; Seeber, S; Luboldt, H J; Opalka, B; Schütte, J

    1996-04-01

    To determine the role of structural alterations of human chromosome region 3p12-p21 in the possible inactivation of one or more tumour-suppressor genes in the pathogenesis of renal cell carcinoma (RCC), lung cancer and other neoplasms. As microsatellite instability (MI), in particular MI with loss of heterozygosity (LOH), may indicate putative tumour-suppressor gene loci, 20 kidney tumours, including 14 clear cell carcinomas and six non-clear cell neoplasms, were investigated with 10 polymorphic simple sequence-repeat markers spanning 3p12-p21. Six of these markers map to the region of deletion flanked by markers D3S1285 and D3S1295 bracketing the t(3;8) translocation break-point in 3p14.2 of hereditary RCC. Twelve of 14 clear cell RCCs displayed MI for at least one locus, as opposed to none of the non-clear cell tumours (P = 0.001). Locus D3S1274 in 3p13 located in the region deleted in lung cancer line U2020 and loci D3S1313 and D3S1300 in 3p14.3 characterized common regions of instability and LOH. Two patients with RCC who also had lung cancer and colon cancer, respectively, showed LOH at D3S1313 or D3S1300 as the only alterations of their kidney tumours. These results suggest that human chromosome region 3p14.3 distal to the hereditary t(3;8) translocation breakpoint and the region deleted in the U2020 lung cancer cell line might be involved in the tumorigenesis or progression of clear cell RCC.

  7. Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.

    PubMed

    Pezzolo, Annalisa; Sementa, Angela Rita; Lerone, Margherita; Morini, Martina; Ognibene, Marzia; Defferrari, Raffaella; Mazzocco, Katia; Conte, Massimo; Gigliotti, Anna Rita; Garaventa, Alberto; Pistoia, Vito; Varesio, Luigi

    2017-05-04

    Neuroblastoma (NB) is a common and often lethal cancer of early childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents ≥ 10 y. There is increasing evidence that NB has unique biology and an chronic disease course in older children and adolescents, but ultimately dismal survival. We describe a rare constitutional 3p26.3 terminal microdeletion which occurred in an adolescent with NB, with apparently normal phenotype without neurocognitive defects. We evaluated the association of expression of genes involved in the microdeletion with NB patient outcomes using R2 platform. We screened NB patient's tumor cells for CHL1 protein expression using immunofluorescence. Constitutional and tumor DNA were tested by array-comparative genomic hybridization and single nucleotide-polymorphism-array analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb sub-microscopic constitutional terminal 3p deletion that extended to band p26.3. The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1 genes were hemizygously deleted, each of these genes encode neuronal cell adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB patients, whereas low CHL1 expression characterized 417 NB patients having worse overall survival. CHL1 protein expression on tumor cells from the patient was weaker than positive control. This is the first report of a constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p, indicative of the presence of one or more tumor suppressor genes in this region, occur frequently in neuroblastoma, our results pave the way to the identification of one putative NB suppressor genes mapping in 3p26.3.

  8. Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma

    PubMed Central

    Gawrych, Katarzyna; Casjens, Swaantje; Brik, Alexander; Lehnert, Martin; Taeger, Dirk; Pesch, Beate; Kollmeier, Jens; Bauer, Torsten T.; Johnen, Georg; Brüning, Thomas

    2017-01-01

    The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance. PMID:28321148

  9. High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis.

    PubMed

    de Ronde, Maurice W J; Kok, Maayke G M; Moerland, Perry D; Van den Bossche, Jan; Neele, Annette E; Halliani, Amalia; van der Made, Ingeborg; de Winther, Menno P J; Meijers, Joost C M; Creemers, Esther E; Pinto-Sietsma, Sara-Joan

    2017-08-01

    The risk of developing cardiovascular disease (CVD) is twice as high among smoking individuals compared to non-smokers. Monocytes are involved in smoking-related atherosclerotic plaque formation. In this study, we investigated whether smokers with an increased risk of developing CVD can be identified on the basis of monocyte-derived miRNA expression levels. We performed a miRNA microarray experiment on isolated monocytes from smoking, former smoking and non-smoking individuals in a cohort of patients with premature CVD and healthy controls (Cohort I, n = 76). We found miR-124-3p to be heterogeneously expressed among all smoking individuals, whereas expression was low in non-smokers. Subsequently, RT-qPCR measurements on whole blood showed that among smoking individuals an increase in miR-124-3p is associated with an increased risk for advanced atherosclerotic disease (cohort II, n = 24) (OR 11.72 95% CI 1.09-126.53) and subclinical atherosclerosis (coronary artery calcium score ≥ 80 th percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05-7.01). This was not observed among former smokers or non-smoking individuals. Flow cytometric analysis demonstrated that high miR-124-3p expression was associated with upregulation of the monocyte surface markers CD45RA, CD29 and CD206, indicating an altered monocyte phenotype. Finally, overexpression of miR-124-3p resulted in an upregulation of CD206 surface expression on monocytes. High miR-124-3p expression is associated with an increased risk of subclinical atherosclerosis in smoking individuals and with an altered monocyte phenotype. This may suggest that miR-124-3p identifies which smoking individuals are susceptible to the atherogenic effects of smoking. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Circulating miR-323-3p as a Biomarker of Ectopic Pregnancy

    PubMed Central

    Zhao, Zhen; Zhao, Qiuhong; Warrick, Joshua; Lockwood, Christina M.; Woodworth, Alison; Moley, Kelle H.; Gronowski, Ann M.

    2013-01-01

    BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping, and were diagnosed with viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were determined by immunoassays. Serum miR-323-3p, miR-517a, miR-519d, and miR-525-3p concentrations were measured using TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA than in VIP. In contrast, the concentration of miR-323-3p was significantly elevated in EP as compared to SA and VIP. As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed-specificity of 90%). Comparatively, combined hCG, progesterone, and miR-323-3p panel yielded the highest sensitivity of 77.8% (at a fixed-specificity of 90%). A stepwise analysis using hCG, then progesterone, and then miR-323-3p resulted in 96.3% sensitivity and 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added significant diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP. PMID:22395025

  11. Electronic structure and magnetism of titanium substituted Cd3P2: An ab-initio study

    NASA Astrophysics Data System (ADS)

    Jaiganesh, G.; Jaya, S. Mathi

    2018-05-01

    Using the ab-initio computations that are based on the density functional theory, we have investigated the magnetism and electronic properties of one and two Ti atom substituted Cd3P2 compound. The magnetic stability of the substituted compounds was obtained by analyzing the minimum total energies in nonmagnetic, ferromagnetic and antiferromagnetic phases. Our results indicated the formation of magnetic order in one and two Ti atom substituted Cd3P2 as well as metallic characteristics in these systems. A significant value of the magnetic moment of Ti atom is observed from our calculations. We further find that the neighboring Cd and P atoms too acquire a small magnetic moment.

  12. Systematization of experimental data on the spectra of 3s--3p and 3p--3d transitions of Ar IX (436--861 A)

    SciTech Connect

    Kramida, A.E.

    1985-04-01

    The article correlates and systematizes published data on the wavelengths of lines in the spectra of argon obtained by various authors by the so-called beam-foil method. The energies of the levels are compared with the results of an extrapolation along an isoelectronic sequence, and the lifetimes of the levels are compared with theoretical calculations. The energies of all 26 energy levels of the 2p/sup 5/3s, 3p and 3d configurations of Ar IX are determined and refined. Forty-five transitions between these configurations in the 436--861 A region are identified. The identifications are supported by combinations according to the Ritz principle andmore » by a semiempirical calculation of the energies of the levels.« less

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  14. Understanding the quantum nature of low-energy C(3P j ) + He inelastic collisions.

    PubMed

    Bergeat, Astrid; Chefdeville, Simon; Costes, Michel; Morales, Sébastien B; Naulin, Christian; Even, Uzi; Kłos, Jacek; Lique, François

    2018-05-01

    Inelastic collisions that occur between open-shell atoms and other atoms or molecules, and that promote a spin-orbit transition, involve multiple interaction potentials. They are non-adiabatic by nature and cannot be described within the Born-Oppenheimer approximation; in particular, their theoretical modelling becomes very challenging when the collision energies have values comparable to the spin-orbit splitting. Here we study inelastic collisions between carbon in its ground state C( 3 P j=0 ) and helium atoms-at collision energies in the vicinity of spin-orbit excitation thresholds (~0.2 and 0.5 kJ mol -1 )-that result in spin-orbit excitation to C( 3 P j=1 ) and C( 3 P j=2 ). State-to-state integral cross-sections are obtained from crossed-beam experiments with a beam source that provides an almost pure beam of C( 3 P j=0 ) . We observe very good agreement between experimental and theoretical results (acquired using newly calculated potential energy curves), which validates our characterization of the quantum dynamical resonances that are observed. Rate coefficients at very low temperatures suitable for chemical modelling of the interstellar medium are also calculated.

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

    ERIC Educational Resources Information Center

    Tynjala, Paivi

    2013-01-01

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

  16. Muenke Syndrome Mutation, FgfR3P244R, Causes TMJ Defects

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2007-10-15

    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 Saccharomyces cerevisiae. Scm3p is conserved across fungi, and displays a remarkable variation in protein size, ranging from approximately 200 amino acids in S. cerevisiae to approximately 1300 amino acids in Neurospora crassa. This is primarily due a variable C-terminal segment that is linked to a conserved N-terminal, CenH3-interacting domain. We have discovered that the extended C-terminal region of Scm3p is strikingly characterized by lineage-specific fusions of single or multiple predicted DNA-binding domains different versions of the MYB and C2H2 zinc finger domains, AT-hooks, and a novel cysteine-rich metal-chelating cluster that are absent from the small versions of Scm3. Instead, S. cerevisiae point centromeres are recognized by components of the CBF3 DNA binding complex, which are conserved amongst close relatives of budding yeast, but are correspondingly absent from more distant fungi that possess regional centromeres. Hence, the C-terminal DNA binding motifs found in large Scm3p proteins may, along with CenH3, serve as a key epigenetic signal by recognizing and accommodating the lineage-specific diversity of centromere DNA in course of evolution.

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. WHO-defined ‘myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations

    PubMed Central

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-01-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with ‘myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age ⩾70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or ⩾2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations. PMID:20485371

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

    DOE PAGES

    Savee, John D.; Borkar, Sampada; Welz, Oliver; ...

    2015-05-18

    Here, the reaction of O( 3P) + propyne (C 3H 4) was investigated at 298 K and 4 Torr using time-resolved multiplexed photoionization mass spectrometry and a synchrotron-generated tunable vacuum ultraviolet light source. The time-resolved mass spectra of the observed products suggest five major channels under our conditions: C 2H 3 + HCO, CH 3 + HCCO, H + CH 3CCO, C 2H 4 + CO, and C 2H 2 + H 2 + CO. The relative branching ratios for these channels were found to be 1.00, (0.35 ± 0.11), (0.18 ± 0.10), (0.73 ± 0.27), and (1.31 ± 0.62).more » In addition, we observed signals consistent with minor production of C 3H 3 + OH and H 2 + CH 2CCO, although we cannot conclusively assign them as direct product channels from O( 3P) + propyne. The direct abstraction mechanism plays only a minor role (≤1%), and we estimate that O( 3P) addition to the central carbon of propyne accounts for 10% of products, with addition to the terminal carbon accounting for the remaining 89%. The isotopologues observed in experiments using d1-propyne (CH 3CCD) and analysis of product branching in light of previously computed stationary points on the singlet and triplet potential energy surfaces (PESs) relevant to O( 3P) + propyne suggest that, under our conditions, (84 ± 14)% of the observed product channels from O( 3P) + propyne result from intersystem crossing from the initial triplet PES to the lower-lying singlet PES.« less

  2. MiR-3613-3p affects cell proliferation and cell cycle in hepatocellular carcinoma

    PubMed Central

    Zhang, Donghui; Liu, Enqin; Kang, Jian; Yang, Xin; Liu, Hong

    2017-01-01

    Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with poor sensitivity to chemotherapy drugs and poor prognosis among patients. In the present study, we downloaded the original data from the Gene Expression Omnibus and compared gene expression profiles of liver cancer cells in patients with HCC with those of colon epithelial cells of healthy controls to identify differentially expressed genes (DEGs). After filtering target microRNAs (miRNA) from core DEGs, we cultured HepG2 cells in vitro, knocked down the miRNA and core mRNAs, and analyzed the effects. We found 228 differentially expressed genes between liver cancer tissue and healthy control tissue. We also integrated the protein-proteininteraction network and module analysis to screen 13 core genes, consisting of 12 up-regulated genes and 1 down-regulated gene. Five core genes were regulated hsa-miR-3613-3p, therefor we hypothesized that hsa-miR-3613-3p was a critical miRNA. After the transfection procedure, we found that changes in hsa-miR-3613-3p were the most obvious. Therefore, we speculated that hsa-miR-3613-3p was a main target miRNA. In addition, we transfected with si (BIRC5, CDK1, NUF2, ZWINT and SPC24), to target genes that can be targeted by miR-3613-3p. Our data shows that BIRC5, NUF2, and SPC24 may be promising liver cancer biomarkers that may not only predict disease occurrence but also potential personalized treatment options. PMID:29190974

  3. Circulating miR-142-3p levels in patients with systemic sclerosis.

    PubMed

    Makino, K; Jinnin, M; Kajihara, I; Honda, N; Sakai, K; Masuguchi, S; Fukushima, S; Inoue, Y; Ihn, H

    2012-01-01

    Recently, increased evidence has shown that serum micro (mi)RNA levels are a useful biomarker for the diagnosis, prognosis and therapeutic value of various diseases. However, serum miRNA has not been investigated in patients with systemic sclerosis (SSc), to our knowledge. To investigate the possibility that serum levels of Homo sapiens miR-142 stem-loop (hsa-miR-142-3p), one of the miRNAs regulating the expression of integrin αV, could be a specific disease marker for SSc. Serum samples were obtained from 61 patients with SSc and 20 healthy controls. Patients with systemic lupus erythematosus (SLE), dermatomyositis (DM) and scleroderma spectrum disorder (SSD), who did not fulfil American College of Rheumatology criteria for SSc but might develop SSc in the future, were included as disease controls in this study. miRNAs were purified from serum, and miR-142-3p levels were measured with a quantitative real-time PCR assay. Serum miR-142-3p levels in patients with SSc were significantly higher than in patients with SSD, SLE or DM, and healthy control groups. Patients with increased miR-142-3p levels tended to have a short sublingual frenulum. Our data indicate that serum levels of miR-142-3p may be elevated specifically in patients with SSc, correlating with the severity of this disease, and may be useful diagnostic markers for the presence of SSc and for the differentiation of SSc from SSD. © The Author(s). CED © 2011 British Association of Dermatologists.

  4. Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14

    PubMed Central

    Etain, Bruno; Mathieu, Flavie; Rietschel, Marcella; Maier, Wolfgang; Albus, Margot; Mckeon, Patrick; Roche, S.; Kealey, Carmel; Blackwood, Douglas; Muir, Walter; Bellivier, Franc; Henry, C.; Dina, Christian; Gallina, Sophie; Gurling, H.; Malafosse, Alain; Preisig, Martin; Ferrero, François; Cichon, Sven; Schumacher, J.; Ohlraun, Stéphanie; Borrmann-Hassenbach, M.; Propping, Peter; Abou Jamra, Rami; Schulze, Thomas G.; Marusic, Andrej; Dernovsek, Mojca Z.; Giros, Bruno; Bourgeron, Thomas; Lemainque, Arnaud; Bacq, Delphine; Betard, Christine; Charon, Céline; Nöthen, Markus M.; Lathrop, Mark; Leboyer, Marion

    2006-01-01

    Summary Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (age at onset of 21 years or below). Non parametric multi-point analysis suggested eight regions of linkage with p-values <0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide p-value estimated over 10.000 simulated replicates of 0.015 [0.01–0.02]). After genome-wide search analysis, we performed additional linkage analyses with increase marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non parametric linkage score increased from 3.51 to 3.83. This study is the first to use early onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families. PMID:16534504

  5. Comparison of plateletpheresis on the Fresenius AS.TEC 204 and Haemonetics MCS 3p.

    PubMed

    Ranganathan, Sudha

    2007-02-01

    This is an attempt at comparing two cell separators for plateletpheresis, namely the Fresenius AS.TEC 204 and Haemonetics MCS 3p, at a tertiary care center in India. Donors who weighed between 55-75 kg, who had a hematocrit of 41-43%, and platelet counts of 250x10(3)-400x10(3)/microl were selected for the study. The comparability of the donors who donated on the two cell separators were analysed by t-test independent samples and no significant differences were found (P>0.05). The features compared were time taken for the procedure, volume processed on the separators, adverse reactions of the donors, quality control of the product, separation efficiency of the separators, platelet loss in the donors after the procedure, and the predictor versus the actual yield of platelets given by the cell separator. The volume processed to get a target yield of >3x10(11) was equal to 2.8-3.2 l and equal in both the cell separators. Symptoms of citrate toxicity were seen in 4 and 2.5% of donors who donated on the MCS 3p and the AS.TEC 204, respectively, and 3 and 1% of donors, respectively, had vasovagal reactions. All the platelet products collected had a platelet count of >3x10(11); 90% of the platelet products collected on the AS.TEC 204 attained the predicted yield that was set on the cell separator where as 75% of the platelet products collected on the MCS 3p attained the target yield. Quality control of the platelets collected on both the cell separators complied with the standards except that 3% of the platelets collected on the MCS 3p had a visible red cell contamination. The separation efficiency of the MCS 3p was higher, 50-52% as compared to the 40-45% on the AS.TEC 204. A provision of double venous access, less adverse reactions, negligible RBC contamination with a better predictor yield of platelets makes the AS.TEC 204 a safer and more reliable alternative than the widely used Haemonetics MCS 3p. Copyright (c) 2006 Wiley-Liss, Inc.

  6. Photoelectric characteristics of CH3NH3PbI3/p-Si heterojunction

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

  8. The carcinogenicity of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU).

    PubMed

    Warzok, R; Martin, J; Mendel, J; Thust, R; Schwarz, H

    1983-01-01

    In long-term experiments with Hooded rats the carcinogenic potential of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU) could be demonstrated for the first time. Br-MPNU is formed also endogenously after combined administration of 1-methyl-3(p-bromophenyl)-urea (Br-MPU) and sodium nitrite. After repeated intragastric administration of 0.33 mmol Br-MPU and 0.73 mmol NaNO2 per kg b.w. papillomas and carcinomas of the forestomach developed in 83%. After repeated administration of 0.28 mmol Br-MPNU per kg b.w. these neoplasms were observed in 88%. The comparison of results obtained in similar experiments with 1-methyl-3-phenyl-1-nitrosourea shows that bromine substitution led to a reduction of the carcinogenic activity. The present paper is part of a complex program studying the interrelationships between structure, physico-chemical properties, mutagenicity and carcinogenicity of nitrosoureas.

  9. Operationalising the Lean principles in maternity service design using 3P methodology

    PubMed Central

    Smith, Iain

    2016-01-01

    The last half century has seen significant changes to Maternity services in England. Though rates of maternal and infant mortality have fallen to very low levels, this has been achieved largely through hospital admission. It has been argued that maternity services may have become over-medicalised and service users have expressed a preference for more personalised care. NHS England's national strategy sets out a vision for a modern maternity service that continues to deliver safe care whilst also adopting the principles of personalisation. Therefore, there is a need to develop maternity services that balance safety with personal choice. To address this challenge, a maternity unit in North East England considered improving their service through refurbishment or building new facilities. Using a design process known as the production preparation process (or 3P), the Lean principles of understanding user value, mapping value-streams, creating flow, developing pull processes and continuous improvement were applied to the design of a new maternity department. Multiple stakeholders were engaged in the design through participation in a time-out (3P) workshop in which an innovative pathway and facility for maternity services were co-designed. The team created a hybrid model that they described as “wrap around care” in which the Lean concept of pull was applied to create a service and facility design in which expectant mothers were put at the centre of care with clinicians, skills, equipment and supplies drawn towards them in line with acuity changes as needed. Applying the Lean principles using the 3P method helped stakeholders to create an innovative design in line with the aspirations and objectives of the National Maternity Review. The case provides a practical example of stakeholders applying the Lean principles to maternity services and demonstrates the potential applicability of the Lean 3P approach to design healthcare services in line with policy requirements

  10. Collision Dynamics of O(3P) + DMMP Using a Specific Reaction Parameters Potential Form

    DTIC Science & Technology

    2012-01-27

    CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18 . NUMBER OF PAGES 14 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified...b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39- 18 Collision Dynamics of O(3P...SRP POTENTIAL Although there have been great strides in developing accurate, multidimensional, global potential energy surfaces, 18 −24 mole- cules with

  11. Operationalising the Lean principles in maternity service design using 3P methodology.

    PubMed

    Smith, Iain

    2016-01-01

    The last half century has seen significant changes to Maternity services in England. Though rates of maternal and infant mortality have fallen to very low levels, this has been achieved largely through hospital admission. It has been argued that maternity services may have become over-medicalised and service users have expressed a preference for more personalised care. NHS England's national strategy sets out a vision for a modern maternity service that continues to deliver safe care whilst also adopting the principles of personalisation. Therefore, there is a need to develop maternity services that balance safety with personal choice. To address this challenge, a maternity unit in North East England considered improving their service through refurbishment or building new facilities. Using a design process known as the production preparation process (or 3P), the Lean principles of understanding user value, mapping value-streams, creating flow, developing pull processes and continuous improvement were applied to the design of a new maternity department. Multiple stakeholders were engaged in the design through participation in a time-out (3P) workshop in which an innovative pathway and facility for maternity services were co-designed. The team created a hybrid model that they described as "wrap around care" in which the Lean concept of pull was applied to create a service and facility design in which expectant mothers were put at the centre of care with clinicians, skills, equipment and supplies drawn towards them in line with acuity changes as needed. Applying the Lean principles using the 3P method helped stakeholders to create an innovative design in line with the aspirations and objectives of the National Maternity Review. The case provides a practical example of stakeholders applying the Lean principles to maternity services and demonstrates the potential applicability of the Lean 3P approach to design healthcare services in line with policy requirements.

  12. [Chronic insomnia: treatment methods based on the current "3P" model of insomnia].

    PubMed

    Poluektov, M G; Pchelina, P V

    2015-01-01

    Authors consider one of the popular models of the pathogenesis of chronic insomnia--"3P" model. It explains the origin and course of insomnia on the basis of interaction of three factors: predisposing, precipitating and perpetuating. The role of each group of factors and its connection to the cerebral hyperarousal state is discussed. Different variants of cognitive-behavioral therapy and pharmacological treatment of chronic insomnia are described.

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

    PubMed Central

    Smith, Iain

    2016-01-01

    In the UK, bowel cancer is the second largest cancer killer. Diagnosing people earlier can save lives but demand for endoscopies is increasing and this can put pressure on waiting times. To address this challenge, an endoscopy unit in North East England decided to improve their facilities to increase capacity and create environments that improve the experience of users. This presented a significant opportunity for step change improvement but also a problem in terms of creating designs that meet user requirements whilst addressing structural or space constraints. The Lean design process known as ‘3P' (standing for the production preparation process) was utilised as a participative design strategy to engage stakeholders in the design of the new department. This involved a time-out workshop (or 3P event) in which Lean and participative design tools were utilised to create an innovative design based on ‘point of delivery' (POD) principles. The team created a design that demonstrated an increase in treatment room capacity by 25% and bed capacity by 70% whilst reducing travel distance for patients by 25.8% and staff by 27.1%. This was achieved with an increase in available space of only 13%. The Lean 3P method provided a structured approach for corporate and clinical staff to work together with patient representatives as cross-functional teams. This participative approach facilitated communication and learning between stakeholders about care processes and personal preferences. Lean 3P therefore appears to be a promising approach to improving the healthcare facilities design process to meet user requirements. PMID:27493744

  14. Hydrogen atom migration in the oxidation of aldehydes - O(3P) + H2CO

    NASA Technical Reports Server (NTRS)

    Dupuis, M.; Lester, W. A., Jr.

    1984-01-01

    An ab initio study of hydrogen atom migration in methylenebis(oxy)H2CO2(3B2) to form triplet formic acid HCOOH (3A1) is reported. From HF, MCHF, and CI calculated energy barriers, the activation energy is estimated to be no less than 30 kcal/mol. It is concluded that the hydrogen migration channel is not accessible in recent room temperature experiments on the O(3P) + H2CO reaction.

  15. Fine mapping of the NRC-1 tumor suppressor locus within chromosome 3p12.

    PubMed

    Zhang, Kun; Lott, Steven T; Jin, Li; Killary, Ann McNeill

    2007-08-31

    Identification of tumor suppressor genes based on physical mapping exercises has proven to be a challenging endeavor, due to the difficulty of narrowing regions of loss of heterozygosity (LOH), infrequency of homozygous deletions, and the labor-intensive characterization process for screening candidates in a given genomic interval. We previously defined a chromosome 3p12 tumor suppressor locus NRC-1 (Nonpapillary Renal Carcinoma-1) by functional complementation experiments in which renal cell carcinoma microcell hybrids containing introduced normal chromosome 3p fragments were either suppressed or unsuppressed for tumorigenicity following injection into athymic nude mice. We now present the fine-scale physical mapping of NRC-1 using a QPCR-based approach for measuring copy number at sequence tagged sites (STS) which allowed a sub-exon mapping resolution. Using STS-QPCR and a novel statistical algorithm, the NRC-1 locus was narrowed to 4.615-Mb with the distal boundary mapping within a 38-Kb interval between exon 3 and exon 4 of the DUTT1/Robo1 gene, currently the only candidate tumor suppressor gene in the interval. Further mutational screening and gene expression analyses indicate that DUTT1/ROBO1 is not involved in the tumor suppressor activity of NRC-1, suggesting that there are at least two important tumor suppressor genes within the chromosome 3p12 interval.

  16. Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma.

    PubMed

    Carroll, P R; Murty, V V; Reuter, V; Jhanwar, S; Fair, W R; Whitmore, W F; Chaganti, R S

    1987-06-01

    In an effort to determine whether or not any characteristic chromosomal abnormalities exist in renal cancer, cytogenetic findings were correlated with tumor histology in nine cases of renal adenocarcinoma. Metaphase preparations adequate for analysis were obtained from cultures harvested between day 3 and day 21. Model chromosome number was diploid in three cases, hypodiploid in three, and hyperdiploid in the remaining three. One clear cell adenocarcinoma failed to reveal any chromosomal abnormality. Two tumors, a tubular/papillary carcinoma and an acinar/papillary carcinoma, showed the clonal abnormalities del(1)(p2l),+2,+7,+8,+12,+13,+16,+17,-21 and t(2;10)(q14-21;q26),+7q,+11q,-18, respectively. Interestingly, five of six clear cell tumors studied had clonal abnormalities affecting the short arm of chromosome #3 in the 3p12-21 region, and in the remaining case, of 15 karyotyped metaphases suitable for interpretation, one showed a deletion in 3p. These data indicate that clear cell carcinoma of the kidney may be associated with a nonrandom chromosomal abnormality involving the 3p12-14 region.

  17. Characterization of a microdissection library from human chromosome region 3p14

    SciTech Connect

    Bardenheuer, W.; Szymanski, S.; Lux, A.

    1994-01-15

    Structural alterations in human chromosome region 3p14-p23 resulting in the inactivation of one or more tumor suppressor genes are thought to play a pathogenic role in small cell lung cancer, renal cell carcinoma, and other human neoplasms. To identify putative tumor suppressor genes, 428 recombinant clones from a microdissection library specific for human chromosome region 3p14 were isolated and characterized. Ninety-six of these (22.5%) were human single-copy DNA sequences, 57 of which were unique sequence clones. Forty-four of these were mapped to the microdissected region using a cell hybrid mapping panel. Within this mapping panel, four probes detected two newmore » chromosome breakpoints that were previously indistinguishable from the translocation breakpoint t(3;8) in 3p14.2 in hereditary renal cell carcinoma. One probe maps to the homozygously deleted region of the small cell lung cancer cell line U2020. In addition, microdissection clones have been shown to be suitable for isolation of yeast artificial chromosomes. 52 refs., 3 figs., 2 tabs.« less

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

    PubMed

    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.

  19. Pulsed laser photolysis study of the reaction between O(3P) and HO2

    NASA Technical Reports Server (NTRS)

    Ravishankara, A. R.; Wine, P. H.; Nicovich, J. M.

    1983-01-01

    It is pointed out that bimolecular reactions involving two free radicals are of great interest because both reactants have unpaired electrons and hence could interact at distances longer than those typical of radical-molecule encounters. A method based on laser photolysis is being developed to produce selectively free radicals in the homogeneous gas phase. This is to be done in such a way as to isolate the reaction of interest and subsequently follow the course of the reaction using spectroscopic techniques. The present investigation is concerned with a study in which the rate coefficient for the reaction of O(3P) with HO2, has been measured at N2 pressures ranging from 10 to 500 torr, taking into account the reaction O(3P)+HO2 yields OH-O2. In the described study, O(3P) and HO2 were produced by cophotolysis of O3 and H2O2 in N2 at 248.5 nm using a KrF excimer laser.

  20. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p.

    PubMed

    Peters, Brian M; Ovchinnikova, Ekaterina S; Krom, Bastiaan P; Schlecht, Lisa Marie; Zhou, Han; Hoyer, Lois L; Busscher, Henk J; van der Mei, Henny C; Jabra-Rizk, Mary Ann; Shirtliff, Mark E

    2012-12-01

    The bacterium Staphylococcus (St.) aureus and the opportunistic fungus Candida albicans are currently among the leading nosocomial pathogens, often co-infecting critically ill patients, with high morbidity and mortality. Previous investigations have demonstrated preferential adherence of St. aureus to C. albicans hyphae during mixed biofilm growth. In this study, we aimed to characterize the mechanism behind this observed interaction. C. albicans adhesin-deficient mutant strains were screened by microscopy to identify the specific receptor on C. albicans hyphae recognized by St. aureus. Furthermore, an immunoassay was developed to validate and quantify staphylococcal binding to fungal biofilms. The findings from these experiments implicated the C. albicans adhesin agglutinin-like sequence 3 (Als3p) in playing a major role in the adherence process. This association was quantitatively established using atomic force microscopy, in which the adhesion force between single cells of the two species was significantly reduced for a C. albicans mutant strain lacking als3. Confocal microscopy further confirmed these observations, as St. aureus overlaid with a purified recombinant Als3 N-terminal domain fragment (rAls3p) exhibited robust binding. Importantly, a strain of Saccharomyces cerevisiae heterologously expressing Als3p was utilized to further confirm this adhesin as a receptor for St. aureus. Although the parental strain does not bind bacteria, expression of Als3p on the cell surface conferred upon the yeast the ability to strongly bind St. aureus. To elucidate the implications of these in vitro findings in a clinically relevant setting, an ex vivo murine model of co-infection was designed using murine tongue explants. Fluorescent microscopic images revealed extensive hyphal penetration of the epithelium typical of C. albicans mucosal infection. Interestingly, St. aureus bacterial cells were only seen within the epithelial tissue when associated with the invasive

  1. Separated oscillatory field microwave measurement of the n=2 3P1 to n=2 3P2 fine-structure interval of helium

    NASA Astrophysics Data System (ADS)

    Borbely, Joseph S.

    2009-11-01

    The fine-structure constant is a fundamental constant of nature that represents the strength of the coupling interaction between charged particles. Comparison of high-precision theory and high-precision experiment of the n=2 3PJ fine-structure intervals of helium will allow for a determination of the fine-structure constant. The 23P1(mJ=0)-to-23P 2(mJ=0) magnetic-dipole transition in helium is measured to be 2 291 177.53(35) kHz using Ramsey separated oscillatory fields. A thermal beam of 23S1 metastable helium atoms is produced in a DC discharge source and enters a chamber where a vertical DC magnetic field lifts the degeneracy of the mJ states. Initially, the 2 3S1(mJ=-1, 0, 1) states are equally populated. A linearly polarized 1083-nm diode laser drives the 23S 1(mJ=0) atoms up to the 23P0(m J=0) state, emptying the 23S1(mJ=0) state. A 15-ns laser pulse drives the 23S1(m J=+1)-to-23P1(mJ=0) transitions and this laser pulse is followed by two microwave pulses that drive the 2.29-GHz 23P1(mJ=0)-to-23P 2(mJ=0) transition. The atoms which undergo this microwave transition can spontaneously decay to the previously-emptied 23S 1(mJ=0) state. The 23P1(m J=0) state is forbidden to decay to the 23S1(m J=0) state since the transition has a zero electric-dipole matrix element. Therefore, any re-population of the 23S1(m J=0) state is a direct indication that the 2.29-GHz microwave transition has been driven. A linearly polarized 1083-nm diode laser detects the 2 3S1(mJ=0) atoms by exciting them up to the 2 3P0(mJ=0) state and the radiation from the resulting spontaneous decay is observed by focusing it onto a liquid-nitrogen-cooled InGaAs photodiode. The two microwave pulses are alternatively in phase or 180°out of phase and the difference of these signals versus microwave frequency leads to a Ramsey separated oscillatory field interference pattern.

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

    SciTech Connect

    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 ofmore » 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.« less

  3. Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer cell line monoallelic for chromosome 3p.

    PubMed

    Cody, N A L; Ouellet, V; Manderson, E N; Quinn, M C J; Filali-Mouhim, A; Tellis, P; Zietarska, M; Provencher, D M; Mes-Masson, A-M; Chevrette, M; Tonin, P N

    2007-01-25

    Multiple chromosome 3p tumor suppressor genes (TSG) have been proposed in the pathogenesis of ovarian cancer based on complex patterns of 3p loss. To attain functional evidence in support of TSGs and identify candidate regions, we applied a chromosome transfer method involving cell fusions of the tumorigenic OV90 human ovarian cancer cell line, monoallelic for 3p and an irradiated mouse cell line containing a human chromosome 3 in order to derive OV90 hybrids containing normal 3p fragments. The resulting hybrids showed complete or incomplete suppression of tumorigenicity in nude mouse xenograft assays, and varied in their ability to form colonies in soft agarose and three-dimensional spheroids in a manner consistent with alteration of their in vivo tumorigenic phenotypes. Expression microarray analysis identified a set of common differentially expressed genes, such as SPARC, DAB2 and VEGF, some of which have been shown implicated in ovarian cancer. Genotyping assays revealed that they harbored normal 3p fragments, some of which overlapped candidate TSG regions (3p25-p26, 3p24 and 3p14-pcen) identified previously in loss of heterozygosity analyses of ovarian cancers. However, only the 3p12-pcen region was acquired in common by all hybrids where expression microarray analysis identified differentially expressed genes. The correlation of 3p12-pcen transfer and tumor suppression with a concerted re-programming of the cellular transcriptome suggest that the putative TSG may have affected key underlying events in ovarian cancer.

  4. Precision measurement of the three 2(3)P(J) helium fine structure intervals.

    PubMed

    Zelevinsky, T; Farkas, D; Gabrielse, G

    2005-11-11

    The three 2(3)P fine structure intervals of 4H are measured at an improved accuracy that is sufficient to test two-electron QED theory and to determine the fine structure constant alpha to 14 parts in 10(9). The more accurate determination of alpha, to a precision higher than attained with the quantum Hall and Josephson effects, awaits the reconciliation of two inconsistent theoretical calculations now being compared term by term. A low pressure helium discharge presents experimental uncertainties quite different than for earlier measurements and allows direct measurements of light pressure shifts.

  5. Homozygous deletions at 3p12 in breast and lung cancer.

    PubMed

    Sundaresan, V; Chung, G; Heppell-Parton, A; Xiong, J; Grundy, C; Roberts, I; James, L; Cahn, A; Bench, A; Douglas, J; Minna, J; Sekido, Y; Lerman, M; Latif, F; Bergh, J; Li, H; Lowe, N; Ogilvie, D; Rabbitts, P

    1998-10-01

    We have constructed a physical map of the region homozygously deleted in the U2020 cell line at 3p12, including the location of putative CpG islands. Adjacent to one of these islands, we have identified and cloned a new gene (DUTT1) and used probes from this gene to detect two other homozygous deletions occurring in lung and breast carcinomas: the smallest deletion is within the gene itself and would result in a truncated protein. The DUTT1 gene is a member of the neural cell adhesion molecule family, although its widespread expression suggests it plays a less specialized role compared to other members of the family.

  6. Microduplication of 3p26.3 Implicated in Cognitive Development

    PubMed Central

    Te Weehi, Leah; Maikoo, Raj; Mc Cormack, Adrian; Mazzaschi, Roberto; Ashton, Fern; Zhang, Liangtao; George, Alice M.; Love, Donald R.

    2014-01-01

    We report here a 34-month-old boy with global developmental delay referred for molecular karyotyping and fragile X studies. Molecular karyotype analysis revealed a microduplication in the 3p26.3 region involving part of the CHL1 and CNTN6 genes. Several deletions, one translocation, and one duplication have previously been described in this region of chromosome 3. The CHL1 gene has been proposed as a dosage-sensitive gene with a central role in cognitive development, and so the microduplication reported here appears to be implicated in our patient's phenotype. PMID:24778888

  7. Facilitating ADLs by Caregivers of Persons with Dementia: The C3P Model

    PubMed Central

    Amella, Elaine J.; Batchelor-Aselage, Melissa B.

    2015-01-01

    The purpose of this paper is to explicate a change model for caregivers of persons with dementia to assist them in facilitating meals in the home, at community-based programs and in institutional settings. Building on a Social Ecological Model, the C3P Model—Change the Person, Change the People, Change the Place offers a clear method to adapt care strategies to foster independence while providing appropriate support as the person with dementia cognitively and functionally declines. Meals are highly embedded within a culture and are ritualized events within a family requiring an individualized approach when modifications are needed. PMID:24354332

  8. MicroRNA-127-3p inhibits proliferation and invasion by targeting SETD8 in human osteosarcoma cells

    SciTech Connect

    Zhang, Jun; Hou, Wengen; Chai, Mingxiang

    2016-01-22

    MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as, inflammation, proliferation, apoptosis and invasion. In the present study, we focused on the influence of the miR-127-3p on the proliferation, migration and invasion of osteosarcoma (OS). MiR-127-3p was found at reduced levels in OS tissues and cell lines. Overexpression of miR-127-3p in the OS cell lines significantly inhibited the cell proliferation, migration and invasion; however, inhibition of miR-127-3p increased the proliferation, migration and invasion of OS in vitro. SETD8 was identified as a direct target of miR-127-3p, and SETD8 expression decreasedmore » post miR-127-3p overexpression, while SETD8 overexpression could reverse the potential influence of miR-127-3p on the migration and invasion of OS cells. MiR-127-3p is suggested to act mainly via the suppression of SETD8 expression. Overall, the results revealed that miR-127-3p acts as a tumor suppressor and that its down-regulation in cancer may contribute to OS progression and metastasis, suggesting that miR-127-3p could be a potential therapeutic target in the treatment of OS. - Highlights: • MiR-127-3p is decreased in osteosarcoma tissues and cell lines. • MiR-127-3p overexpression suppresses cell migration and invasion in MG63 and U2OS. • SETD8 overexpression abolishes the roles of miR-127-3p in osteosarcoma.« less

  9. Chromosome 3p allele loss in early invasive breast cancer: detailed mapping and association with clinicopathological features

    PubMed Central

    Martinez, A; Walker, R A; Shaw, J A; Dearing, S J; Maher, E R; Latif, F

    2001-01-01

    Aims—Chromosome 3p allele loss is a frequent event in many common sporadic cancers including lung, breast, kidney, ovarian, and head and neck cancer. To analyse the extent and frequency of 3p allelic losses in T1N0 and T1N1 invasive sporadic breast cancer, 19 microsatellite markers spread along 3p were analysed in 40 such breast carcinomas with known clinicopathological parameters. Methods—Loss of heterozygosity analysis was carried out using 3p microsatellite markers that were non-randomly distributed and chosen to represent regions that show hemizygous and/or homozygous losses in lung cancer (lung cancer tumour suppressor gene region 1 ( LCTSGR1) at 3p21.3 and LCTSGR2 at 3p12), and regions demonstrating suppression of tumorigenicity in breast, kidney, lung, and ovarian cancer. Results—Allelic loss was seen at one or more loci in 22 of these clinically early stage sporadic breast tumours, but none had complete 3p allele loss. Several regions with non-overlapping deletions were defined, namely: (1) 18 tumours showed loss at 3p21–22, a physical distance of 12 Mb; (2) 11 tumours showed loss at 3p12 within a physical distance of 1 Mb, this region is contained within LCTSGR2; (3) six tumours showed loss at 3p25–24, including the von Hippel-Lindau (VHL) locus; (4) five tumours showed loss at 3p14.2, including the fragile histidine triad (FHIT) locus. Conclusions—This is the largest study to date defining the extent and range of 3p allelic losses in early stage invasive breast cancer and the results indicate that region 3p21–22 containing LCTSGR1 and a region at 3p12 within LCTSGR2 are the most frequent sites of 3p allelic loss in these breast carcinomas. This suggests that tumour suppressor genes located in these regions may play important roles in the development of breast cancer. There was an association between increasing 3p allelic loss and increasing tumour grade and loss of progesterone (p = 0.0098) and oestrogen (p = 0.0472) receptor expression

  10. Chromosome 3p allele loss in early invasive breast cancer: detailed mapping and association with clinicopathological features.

    PubMed

    Martinez, A; Walker, R A; Shaw, J A; Dearing, S J; Maher, E R; Latif, F

    2001-10-01

    Chromosome 3p allele loss is a frequent event in many common sporadic cancers including lung, breast, kidney, ovarian, and head and neck cancer. To analyse the extent and frequency of 3p allelic losses in T1N0 and T1N1 invasive sporadic breast cancer, 19 microsatellite markers spread along 3p were analysed in 40 such breast carcinomas with known clinicopathological parameters. Loss of heterozygosity analysis was carried out using 3p microsatellite markers that were non-randomly distributed and chosen to represent regions that show hemizygous and/or homozygous losses in lung cancer (lung cancer tumour suppressor gene region 1 ( LCTSGR1) at 3p21.3 and LCTSGR2 at 3p12), and regions demonstrating suppression of tumorigenicity in breast, kidney, lung, and ovarian cancer. Allelic loss was seen at one or more loci in 22 of these clinically early stage sporadic breast tumours, but none had complete 3p allele loss. Several regions with non-overlapping deletions were defined, namely: (1) 18 tumours showed loss at 3p21-22, a physical distance of 12 Mb; (2) 11 tumours showed loss at 3p12 within a physical distance of 1 Mb, this region is contained within LCTSGR2; (3) six tumours showed loss at 3p25-24, including the von Hippel-Lindau (VHL) locus; (4) five tumours showed loss at 3p14.2, including the fragile histidine triad (FHIT) locus. This is the largest study to date defining the extent and range of 3p allelic losses in early stage invasive breast cancer and the results indicate that region 3p21-22 containing LCTSGR1 and a region at 3p12 within LCTSGR2 are the most frequent sites of 3p allelic loss in these breast carcinomas. This suggests that tumour suppressor genes located in these regions may play important roles in the development of breast cancer. There was an association between increasing 3p allelic loss and increasing tumour grade and loss of progesterone (p = 0.0098) and oestrogen (p = 0.0472) receptor expression, indicating a link between 3p allelic loss and the

  11. RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency.

    PubMed

    Meier, Jochen C; Henneberger, Christian; Melnick, Igor; Racca, Claudia; Harvey, Robert J; Heinemann, Uwe; Schmieden, Volker; Grantyn, Rosemarie

    2005-06-01

    The function of supramedullary glycine receptors (GlyRs) is still unclear. Using Wistar rat collicular slices, we demonstrate GlyR-mediated inhibition of spike discharge elicited by low glycine (10 microM). Searching for the molecular basis of this phenomenon, we identified a new GlyR isoform. GlyR alpha3(P185L), a result of cytidine 554 deamination, confers high glycine sensitivity (EC50 approximately 5 microM) to neurons and thereby promotes the generation of sustained chloride conductances associated with tonic inhibition. The level of GlyR alpha3-C554U RNA editing is sensitive to experimentally induced brain lesion, inhibition of cytidine deamination by zebularine and inhibition of mRNA transcription by actinomycin D, but not to blockade of protein synthesis by cycloheximide. Conditional regulation of GlyR alpha3(P185L) is thus likely to be part of a post-transcriptional adaptive mechanism in neurons with enhanced excitability.

  12. A Mixed-Valent Molybdenum Monophosphate with a Layer Structure: KMo 3P 2O 14

    NASA Astrophysics Data System (ADS)

    Guesdon, A.; Borel, M. M.; Leclaire, A.; Grandin, A.; Raveau, B.

    1994-03-01

    A new mixed-valent molybdenum monophosphate with a layer structure KMo 3P 2O 14 has been isolated. It crystallizes in the space group P2 1/ m with a = 8.599(2) Å, b = 6.392(2) Å, c = 10.602(1) Å, and β = 111.65(2)°. The layers [Mo 3P 2O 14] ∞ are parallel to (100) and consist of [MoPO 8] ∞ chains running along limitb→ , in which one MoO 6 octahedron alternates with one PO 4 tetrahedron. In fact, four [MoPO 8] ∞ chains share the corners of their polyhedra and the edges of their octahedra, forming [Mo 4P 4O 24] ∞ columns which are linked through MoO 5 bipyramids along limitc→. The K + ions interleaved between these layers are surrounded by eight oxygens, forming bicapped trigonal prisms KO 8. Besides the unusual trigonal bipyramids MoO 5, this structure is also characterized by a tendency to the localization of the electrons, since one octahedral site is occupied by Mo(V), whereas the other octahedral site and the trigonal bipyramid are occupied by Mo(VI). The similarity of this structure with pure octahedral layer structures suggests the possibility of generating various derivatives, and of ion exchange properties.

  13. Stereodynamics of Ne(3P2) reacting with Ar, Kr, Xe, and N2

    NASA Astrophysics Data System (ADS)

    Zou, Junwen; Gordon, Sean D. S.; Tanteri, Silvia; Osterwalder, Andreas

    2018-04-01

    Stereodynamics experiments of Ne(3P2) reacting with Ar, Kr, Xe, and N2 leading to Penning and associative ionization have been performed in a crossed molecular beam apparatus. A curved magnetic hexapole was used to state-select and polarize Ne(3P2) atoms which were then oriented in a rotatable magnetic field and crossed with a beam of Ar, Kr, Xe, or N2. The ratio of associative to Penning ionization was recorded as a function of the magnetic field direction for collision energies between 320 cm-1 and 500 cm-1. Reactivities are obtained for individual states that differ only in Ω, the projection of the neon total angular momentum vector on the inter-particle axis. The results are rationalized on the basis of a model involving a long-range and a short-range reaction mechanism. Substantially lower probability for associative ionization was observed for N2, suggesting that predissociation plays a critical role in the overall reaction pathway.

  14. Quenching of I(2P 1/2) by O 3 and O( 3P)

    NASA Astrophysics Data System (ADS)

    Azyazov, V. N.; Antonov, I. O.; Ruffner, S.; Heaven, M. C.

    2006-02-01

    Oxygen-iodine lasers that utilize electrical or microwave discharges to produce singlet oxygen are currently being developed. The discharge generators differ from conventional chemical singlet oxygen generators in that they produce significant amounts of atomic oxygen. Post-discharge chemistry includes channels that lead to the formation of ozone. Consequently, removal of I(2P 1/2) by O atoms and O 3 may impact the efficiency of discharge driven iodine lasers. In the present study we have measured the rate constants for quenching of I(2P 1/2) by O( 3P) atoms and O 3 using pulsed laser photolysis techniques. The rate constant for quenching by O 3, 1.8x10 -12 cm 3 s -1, was found to be a factor of five smaller than the literature value. The rate constant for quenching by O( 3P) was 1.2x10 -11 cm 3 s -1. This was six times larger than a previously reported upper bound, but consistent with estimates obtained by modeling the kinetics of discharge-driven laser systems.

  15. Quenching of I(2P1/2) by O3 and O(3P).

    PubMed

    Azyazov, Valeriy N; Antonov, Ivan O; Heaven, Michael C

    2007-04-26

    Oxygen-iodine lasers that utilize electrical or microwave discharges to produce singlet oxygen are currently being developed. The discharge generators differ from conventional chemical singlet oxygen generators in that they produce significant amounts of atomic oxygen. Post-discharge chemistry includes channels that lead to the formation of ozone. Consequently, removal of I(2P1/2) by O atoms and O3 may impact the efficiency of discharge driven iodine lasers. In the present study, we have measured the rate constants for quenching of I(2P1/2) by O(3P) atoms and O3 using pulsed laser photolysis techniques. The rate constant for quenching by O3, (1.8 +/- 0.4) x 10(-12) cm3 s-1, was found to be a factor of 5 smaller than the literature value. The rate constant for quenching by O(3P) was (1.2 +/- 0.2) x 10(-11) cm3 s-1.

  16. Measurement of the 3 s 1 / 2 - 3 p 3 / 2 resonance line of sodiumlike Eu 52 +

    SciTech Connect

    Träbert, E.; Beiersdorfer, P.; Hell, N.

    2015-08-01

    We have measured the 3 s 1 / 2 - 3 p 3 / 2 transition in sodiumlike Eu 52 + situated at 41.232 Å with an uncertainty of 73 ppm. Our measurement extends previous high-precision measurements into the 56 < Z < 78 range of atomic numbers. We also present measurements of 3 s 1 / 2 - 3 p 3 / 2 and 3 p 1 / 2 - 3 d 3 / 2 transitions in the neighboring magnesiumlike, aluminumlike, and siliconlike europium ions.

  17. MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor.

    PubMed

    Qin, Bing; Shu, Yaqing; Long, Ling; Li, Haiyan; Men, Xuejiao; Feng, Li; Yang, Huan; Lu, Zhengqi

    2018-06-27

    Atherosclerosis, a multifactorial chronic disease, is the main cause of death and impairment in the world. Endothelial cells (ECs) apoptosis plays a crucial role in the onset and development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a well-defined tumor suppressor in several types of cancer, while the role of miR-142-3p in ECs apoptosis and the development of atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-142-3p in ECs apoptosis during atherosclerosis and the underlying mechanism. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT-PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay. Prediction of the binding between miR-142-3p and 3'-UTR of Rictor mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis were further analyzed in an in vivo model using ApoE-/- mice fed with high-fat diet (HFD). MiR-142-3p expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti-apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway was found to mediate the beneficial effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded the progression of atherosclerosis in the aorta of ApoE-/- mice. Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic

  18. Nmd3p Is a Crm1p-Dependent Adapter Protein for Nuclear Export of the Large Ribosomal Subunit

    PubMed Central

    Ho, Jennifer Hei-Ngam; Kallstrom, George; Johnson, Arlen W.

    2000-01-01

    In eukaryotic cells, nuclear export of nascent ribosomal subunits through the nuclear pore complex depends on the small GTPase Ran. However, neither the nuclear export signals (NESs) for the ribosomal subunits nor the receptor proteins, which recognize the NESs and mediate export of the subunits, have been identified. We showed previously that Nmd3p is an essential protein from yeast that is required for a late step in biogenesis of the large (60S) ribosomal subunit. Here, we show that Nmd3p shuttles and that deletion of the NES from Nmd3p leads to nuclear accumulation of the mutant protein, inhibition of the 60S subunit biogenesis, and inhibition of the nuclear export of 60S subunits. Moreover, the 60S subunits that accumulate in the nucleus can be coimmunoprecipitated with the NES-deficient Nmd3p. 60S subunit biogenesis and export of truncated Nmd3p were restored by the addition of an exogenous NES. To identify the export receptor for Nmd3p we show that Nmd3p shuttling and 60S export is blocked by the Crm1p-specific inhibitor leptomycin B. These results identify Crm1p as the receptor for Nmd3p export. Thus, export of the 60S subunit is mediated by the adapter protein Nmd3p in a Crm1p-dependent pathway. PMID:11086007

  19. MiR-27b-3p Regulation in Browning of Human Visceral Adipose Related to Central Obesity.

    PubMed

    Yu, Jing; Lv, Yifan; Di, Wenjuan; Liu, Juan; Kong, Xiaocen; Sheng, Yunlu; Huang, Min; Lv, Shan; Qi, Hanmei; Gao, Mei; Liang, Hui; Kim, Sarah; Fu, Zan; Zhou, Hong; Ding, Guoxian

    2018-02-01

    Given the rising prevalence of central obesity and the discovery that beige cells appear within white adipose tissue, strategies to enhance these energy-expending adipocytes or "browning" within white adipose depots have become of therapeutic interest to combat obesity and its associated disorders. This study focused on, the role of microRNA (miRNA)-27b-3p in human visceral adipose tissue (VAT) browning. Expression of miR-27b-3p and UCP1 in VAT and serum of humans was measured. MiR-27b-3p was overexpressed or suppressed in human visceral stromal fraction cells to analyze the potential role of miR-27b-3p. UCP1 expression in human VAT decreased with elevated BMI and waist-hip ratio, whereas expression of miR-27b-3p was found to correlate positively with BMI and waist-hip ratio. High expression of miR-27b-3p was associated with reduced browning ability of human visceral adipocytes. Antagonism of miR-27b-3p led to the enhancement of browning ability in human visceral adipocytes. These findings highlight the decreased browning ability of VAT from humans with obesity and the role of miR-27b-3p in regulating browning of human visceral adipocytes. They suggest that miR-27b-3p should be further explored as a potential target for the treatment of central obesity. © 2017 The Obesity Society.

  20. MicroRNA-141-3p/200a-3p target and may be involved in post-transcriptional repression of RNA decapping enzyme Dcp2 during renal development.

    PubMed

    Zhang, Ming-Nan; Tang, Qun-Ye; Li, Rui-Min; Song, Man-Gen

    2018-06-18

    The RNA decapping enzyme Dcp2 is a crucial enzyme involved in the process of RNA turnover, which can post-transcriptionally regulate gene expression. Dcp2 has been found to be highly expressed in embryonic, but not adult, kidneys. Here we showed that Dcp2 mRNA was expressed, but Dcp2 proteins were absent, in mouse kidneys after postnatal day 10 (P10). In kidneys of adult Dcp2-IRES-EGFP knock-in mice, Dcp2 was undetectable but EGFP was expressed, indicating that Dcp2 mRNA was not completely silenced in adult kidneys. Using luciferase reporter assays, we found that miR-141-3p/200a-3p directly targeted the 3' UTR of Dcp2 mRNA. Overexpression of miR-141-3p and miR-200a-3p downregulated endogenous Dcp2 protein expression. Furthermore, miR-141-3p and miR-200a-3p expression was low in embryonic kidneys but increased dramatically after P10 and was negatively correlated with Dcp2 protein expression during renal development. These results suggest miR-141-3p/200a-3p may be involved in post-transcriptional repression of Dcp2 expression during renal development. IRES: internal ribosome entry site; EGFP: enhanced green fluorescent protein; UTR: untranslated region.

  1. Assignment of xeroderma pigmentosum group C(XPC) gene to chromosome 3p25

    SciTech Connect

    Legerski, R.J.; Liu, P.; Li, L.

    1994-05-01

    The human gene XPC (formerly designated XPCC), which corrects the repair deficiency of xeroderma pigmentosum (XP) group C cells, was mapped to 3p25. A cDNA probe for Southern blot hybridization and diagnostic PCR analyses of hybrid clone panels informative for human chromosomes in general and portions of chromosome 3 in particular produced the initial results. Fluorescence in situ hybridization utilizing both a yeast artificial chromosome DNA containing the gene and XPC cDNA as probes provided verification and specific regional assignment. A conflicting assignment of XPC to chromosome 5 is discussed in light of inadequacies in the exclusive use of microcell-mediatedmore » chromosome transfer for gene mapping. 12 refs., 3 figs.« less

  2. Ar 3p photoelectron sideband spectra in two-color XUV + NIR laser fields

    NASA Astrophysics Data System (ADS)

    Minemoto, Shinichirou; Shimada, Hiroyuki; Komatsu, Kazma; Komatsubara, Wataru; Majima, Takuya; Mizuno, Tomoya; Owada, Shigeki; Sakai, Hirofumi; Togashi, Tadashi; Yoshida, Shintaro; Yabashi, Makina; Yagishita, Akira

    2018-04-01

    We performed photoelectron spectroscopy using femtosecond XUV pulses from a free-electron laser and femtosecond near-infrared pulses from a synchronized laser, and succeeded in measuring Ar 3p photoelectron sideband spectra due to the two-color above-threshold ionization. In our calculations of the first-order time-dependent perturbation theoretical model based on the strong field approximation, the photoelectron sideband spectra and their angular distributions are well reproduced by considering the timing jitter between the XUV and the NIR pulses, showing that the timing jitter in our experiments was distributed over the width of {1.0}+0.4-0.2 ps. The present approach can be used as a method to evaluate the timing jitter inevitable in FEL experiments.

  3. Reactions of N(+) (3P) ions with normal, para, and deuterated hydrogens at low temperatures

    NASA Astrophysics Data System (ADS)

    Marquette, J. B.; Rebrion, C.; Rowe, B. R.

    1988-08-01

    The method of reaction kinetics in uniform supersonic flow (French designation CRESU; Dupeyrat et al., 1985) is used to study the reactions of N(+) (3P) with n-H2, p-H2, HD, and D2 at temperatures 8, 20, 27, 45, 68, 163, and 300 K. Results obtained using either He or N2 as the buffer gas are presented in tables and graphs and discussed in detail. The reaction with p-H2 is shown to be significantly slower than that with n-H2, a finding attributed to rotational-energy and spin-orbit-energy driving of these processes. It is pointed out that these results are in agreement with those of Barlow et al. (1986) and Herbst et al. (1987), apparently ruling out these reactions as the source of the NH3 observed in dense interstellar cloud cores.

  4. Reactions of Atomic Oxygen (O(3P)) with Polybutadienes and Related Polymers

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

    Thin films of the following polymers were exposed at ambient temperature to ground-state oxygen atoms (O(3P)), generated by a radio-frequency glow discharge in O2: cis- and trans-1,4-polybutadienes (CB and TB), amorphous 1,2-polybutadiene (VB), polybutadienes with different 1,4/1,2 contents, trans polypentenamer (TP), cis and trans polyoctenamers (CO and TO), and ethylene-propylene rubber (EPM). Transmission infrared spectra of CB and TB films revealed extensive surface recession, or etching, unaccompanied by any microstructural changes within the films, demonstrating that the reactions were confined to the surface layers. Contrary to the report by Rabek, Lucki, and Ranby (1979), there was no O(3P)-induced cis-trans isomerization in CB or TB. From weight-loss measurements, etch rates for polybutadienes were found to be markedly dependent on vinyl content, decreasing by two orders of magnitude from CB (2% 1,2) to structures with 30 to 40% 1,2 double bonds, thereafter increasing by half an order of magnitude to VB (97% 1,2). Relative etch rates for EMP and the polyalkenamers were in the order: EMP is greater than CO (or TO) is greater than TP is greater than CB. The sole non-elastomer examined, TB, had an etch rate about six times that of CB, ascribable to a morphology difference. Cis/trans content had a negligible effect on the etch rate of the polyalkenamers. Mechanisms involving crosslinking through units are proposed for the unexpected protection imparted to polybutadienes by the 1,2 double bonds.

  5. Laser Spectroscopy of the Fine-Structure Splitting in the 2^{3}P_{J} Levels of ^{4}He.

    PubMed

    Zheng, X; Sun, Y R; Chen, J-J; Jiang, W; Pachucki, K; Hu, S-M

    2017-02-10

    The fine-structure splitting in the 2^{3}P_{J} (J=0, 1, 2) levels of ^{4}He is of great interest for tests of quantum electrodynamics and for the determination of the fine-structure constant α. The 2^{3}P_{0}-2^{3}P_{2} and 2^{3}P_{1}-2^{3}P_{2} intervals are measured by laser spectroscopy of the ^{3}P_{J}-2^{3}S_{1} transitions at 1083 nm in an atomic beam, and are determined to be 31 908 130.98±0.13  kHz and 2 291 177.56±0.19  kHz, respectively. Compared with calculations, which include terms up to α^{5}Ry, the deviation for the α-sensitive interval 2^{3}P_{0}-2^{3}P_{2} is only 0.22 kHz. It opens the window for further improvement of theoretical predictions and an independent determination of the fine-structure constant α with a precision of 2×10^{-9}.

  6. MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7.

    PubMed

    Deng, Boya; Zhang, Yi; Zhang, Siyang; Wen, Fang; Miao, Yuan; Guo, Kejun

    2015-09-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles in tumorigenesis and tumor progression through regulation of gene expression. Earlier, miR-142-3p was shown to decreased in cervical cancer cells; here; we explore the biological functional role of miR-142-3p and underlying mechanism in cervical cancer cells. We first detected the expression of miR-142-3p in six human cervical cancer cell lines and chose HeLa and SiHa cells for functional studies. By gain and loss of function experiments, we showed that overexpression of miR142-3p resulted in downregulation of Frizzled7 receptor (FZD7) and inhibited proliferation and invasion in HeLa and SiHa cells, whereas miR142-3p inhibitor-transfected cells showed reduced FZD7 expression and increased invasion capacity. In addition, we demonstrated that FZD7 was a direct target of miR-142-3p by dual luciferase assay and Western blot analysis. Overexpression of FZD7 expression was able to reverse the inhibitory effects induced by miR-142-3p. Taken together, miR-142-3p functions tumor suppressive effects in cell proliferation and invasion in cervical cancer cells, suggesting a potential therapeutic approach for cervical cancer.

  7. Role of microRNA508-3p in melanogenesis by targeting microphthalmia transcription factor in melanocytes of alpaca.

    PubMed

    Zhang, J; Liu, Y; Zhu, Z; Yang, S; Ji, K; Hu, S; Liu, X; Yao, J; Fan, R; Dong, C

    2017-02-01

    It has been demonstrated that microRNAs (miRNAs) play important roles in the control of melanogenesis and hair color in mammals. By comparing miRNA expression profiles between brown and white alpaca skin, we previously identified miR508-3p as a differentially expressed miRNA suggesting its potential role in melanogenesis and hair color formation. The present study was conducted to determine the role of miR508-3p in melanogenesis in alpaca melanocytes. In situ hybridization showed that miR508-3p is abundantly present in the cytoplasma of alpaca melanocytes. miR508-3p was predicted to target the gene encoding microphthalmia transcription factor (MITF) and a luciferase reporter assay indicated that miR508-3p regulates MITF expression by directly targeting its 3'UTR. Overexpression of miR508-3p in alpaca melanocytes down-regulated MITF expression both at the messenger RNA and protein level and resulted in decreased expression of key melanogenic genes including tyrosinase and tyrosinase-related protein 2. Overexpression of miR508-3p in melanocytes also resulted in decreased melanin production including total alkali-soluble melanogenesis, eumelanogenesis and pheomelanogenesis. Results support a functional role of miR508-3p in regulating melanogenesis in alpaca melanocytes by directly targeting MITF.

  8. 78 FR 12130 - Social Security Ruling, SSR 13-3p; Appeal of an Initial Medical Disability Cessation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... SOCIAL SECURITY ADMINISTRATION [Docket No. SSA-2011-0106] Social Security Ruling, SSR 13-3p; Appeal of an Initial Medical Disability Cessation Determination or Decision AGENCY: Social Security Administration. ACTION: Notice of Social Security Ruling (SSR). SUMMARY: We are giving notice of SSR 13-3p. This...

  9. MiR-590-3p suppresses epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma by inhibiting SIP1 expression

    PubMed Central

    Zu, Chao; Liu, Shizhang; Cao, Wei; Liu, Zongzhi; Qiang, Hui; Li, Yong; Cheng, Chong; Ji, Le; Li, Jianhui; Li, Jingyuan

    2017-01-01

    The functional roles and clinical significances of miR-590-3p in ICC remain unclear. In the current study, we investigated the expression of miR-590-3p in tissues and sera of ICC by real-time quantitative polymerase chain reaction. We found miR-590-3p was significantly down-regulated in the sera and tissues of ICC patients, especially in those patients with lymph node metastasis or distant metastasis. AUC curves and Cox proportional hazards mode revealed serum miR-590-3p could be novel diagnostic and prognostic biomarker for ICC patients. MiR-590-3p dramatically suppressed epithelial-mesenchymal transition, cell migration, and invasion of ICC cells. SIP1 was identified as direct and functional target of miR-590-3p in ICC cells by luciferase assays. Finally, we found SIP1 expression was inversely correlated with miR-590-3p and closely related to diminished survival in ICC patients. These findings reveal functional and mechanistic roles of miR-590-3p and EMT activator SIP1 in the pathogenesis of ICC. PMID:28423728

  10. MicroRNA-409-3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression.

    PubMed

    Bai, Rongpan; Weng, Chunhua; Dong, Haojie; Li, Siqi; Chen, Guangdi; Xu, Zhengping

    2015-11-15

    Colorectal cancer (CRC) is one of the most common cancers worldwide and its metastasis accounts for the majority of deaths. However, the molecular mechanisms underlying CRC progression are not well characterized. In this study, we identified miR-409-3p as a tumor suppressor of CRC. MiR-409-3p expression was significantly downregulated in CRC tissue compared to adjacent non-tumor tissue, and reduced miR-409-3p expression was correlated with CRC metastasis. In vitro and in vivo studies revealed that miR-409-3p negatively regulated CRC metastatic capacities, including suppressing cancer cell migration, invasion and metastasis. To explore the mechanism of action of miR-409-3p, we adopted a pathway and pathophysiological event-based target screening and validation approach, and found nine known metastasis-related genes as potential targets. The 3'-UTR binding assays between the candidates and miR-409-3p suggested that only GAB1, NR4A2 and LMO4 were directly regulated by the miRNA. However, endogenous expression analysis revealed that only GAB1 was modulated by miR-409-3p in CRC cells at both the mRNA and protein levels. Furthermore, we provided evidence to conclude that GAB1 was partially responsible for miR-409-3p-mediated metastasis. Taken together, our data demonstrate that miR-409-3p is a metastatic suppressor, and post-transcriptional inhibition of the oncoprotein GAB1 is one of the mechanisms of action of this miRNA. Our finding suggests miR-409-3p might be a novel target for CRC metastasis treatment. © 2015 UICC.

  11. Delimitation of duplicated segments and identification of their parental origin in two partial chromosome 3p duplications.

    PubMed

    Antonini, Sylvie; Kim, Chong A; Sugayama, Sofia M; Vianna-Morgante, Angela M

    2002-11-22

    Two chromosome 3 short arm duplications identified through G-banding were further investigated using fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) of microsatellite markers, aiming at mapping breakpoints and disclosing mechanisms of origin of these chromosome aberrations. Patient 1 was found to be a mosaic: a 3p12 --> 3p21 duplication was observed in most of his cells, and a normal cell line occurred with a frequency of about 3% in blood. In situ hybridization of chromosome 3 short- and long-arm libraries confirmed the short-arm duplication. Using FISH of short-arm sequences, the YAC 961_h_3 was shown to contain the proximal breakpoint (3p12.1 or 3p12.2), and the distal breakpoint was located between the YACs 729_c_3 and 806_h_2, which are adjacent in the WC 3.10 contig (3p21.1). In Patient 2, G-banding indicated a 3p21 --> 3p24 duplication, without mosaicism. In situ hybridization of chromosome 3 short- and long-arm libraries confirmed the duplication of short-arm sequences. FISH of chromosome 3 sequences showed that the YAC 749_a_7 spanned the proximal breakpoint (3p21.33). The distal breakpoint mapped to the interval between YACs 932_b_6 (3p24.3) and 909_b_6 (3p25). In both cases, microsatellite genotyping pointed to a rearrangement between paternal sister chromatids. Copyright 2002 Wiley-Liss, Inc.

  12. Functional Expression and Characterization of Schizosaccharomyces pombe Avt3p as a Vacuolar Amino Acid Exporter in Saccharomyces cerevisiae.

    PubMed

    Chardwiriyapreecha, Soracom; Manabe, Kunio; Iwaki, Tomoko; Kawano-Kawada, Miyuki; Sekito, Takayuki; Lunprom, Siriporn; Akiyama, Koichi; Takegawa, Kaoru; Kakinuma, Yoshimi

    2015-01-01

    In Saccharomyces cerevisiae, Avt3p and Avt4p mediate the extrusion of several amino acids from the vacuolar lumen into the cytosol. SpAvt3p of Schizosaccharomyces pombe, a homologue of these vacuolar amino acid transporters, has been indicated to be involved in spore formation. In this study, we confirmed that GFP-SpAvt3p localized to the vacuolar membrane in S. pombe. The amounts of various amino acids increased significantly in the vacuolar pool of avt3Δ cells, but decreased in that of avt3+-overexpressing avt3Δ cells. These results suggest that SpAvt3p participates in the vacuolar compartmentalization of amino acids in S. pombe. To examine the export activity of SpAvt3p, we expressed the avt3+ gene in S. cerevisiae cells. We found that the heterologously overproduced GFP-SpAvt3p localized to the vacuolar membrane in S. cerevisiae. Using the vacuolar membrane vesicles isolated from avt3+-overexpressing S. cerevisiae cells, we detected the export activities of alanine and tyrosine in an ATP-dependent manner. These activities were inhibited by the addition of a V-ATPase inhibitor, concanamycin A, thereby suggesting that the activity of SpAvt3p is dependent on a proton electrochemical gradient generated by the action of V-ATPase. In addition, the amounts of various amino acids in the vacuolar pools of S. cerevisiae cells were decreased by the overproduction of SpAvt3p, which indicated that SpAvt3p was functional in S. cerevisiae cells. Thus, SpAvt3p is a vacuolar transporter that is involved in the export of amino acids from S. pombe vacuoles.

  13. MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4

    PubMed Central

    Zhang, Kundong; Cen, Gang; Jiang, Tao; Cao, Jun; Huang, Kejian; Zhao, Qian; Qiu, Zhengjun

    2015-01-01

    Background Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. Methods By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. Results Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues. Conclusion MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4. PMID:26019136

  14. microRNA-124-3p inhibits the progression of congenital hypothyroidism via targeting programmed cell death protein 6.

    PubMed

    Li, Wenjie; Song, Dongpo; Sun, Yingmei; Lv, Yanan; Lv, Jinfeng

    2018-06-01

    The incidence of congenital hypothyroidism (CH) in newborn infants ranges from 1 in 3,000 to 1 in 4,000. Previous studies have indicated the neuroprotective role of microRNA (miR)-124-3p, however the expression and role of miR-124-3p in CH remain unclear. Therefore, the present study was performed to investigate the role and precise molecular mechanism of miR-124-3p in CH. Propylthiouracil (50 mg/day) was injected into the stomach of pregnant rats from gestational day 15 until parturition in order to establish a thyroid hypofunction model. Newborn rats were divided into the following four groups: The control group; the thyroid hypofunction group; the miR-124-3p mimic group; and the miR-124-3p negative control group. Reverse transcription-quantitative polymerase chain reaction indicated that miR-124-3p was significantly decreased in the hippocampus of the thyroid hypofunction group compared with the control group. Bioinformatics software was used to predict mRNA targets recognized by miR-124-3p and the programmed cell death protein 6 (PDCD6) 3' untranslated region (UTR) was demonstrated to exhibit the seed sequence of miR-124-3p. The interaction between miRNA-124-3p and PDCD6 was then verified using a dual-luciferase reporter assay system. PDCD6 expression was significantly increased in the hippocampus of rats with CH compared with the control group. Flow cytometry was performed to investigate the effects of miR-124-3p on neuronal cell apoptosis and the results indicated that the apoptosis rate in the thyroid hypofunction group was significantly increased compared with the control group; this increase was reversed by transfection with miR-124-3p mimics. Western blot analysis was used to detect the levels of cleaved poly [ADP-ribose] polymerase (PARP), full-length PARP, caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) proteins. The results indicated that the expression of cleaved PARP, caspase-3 and Bax protein were significantly increased

  15. The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B.

    PubMed

    Jiang, Y-C; Ma, J-X

    2018-06-01

    To investigate the expression of microRNA-324-3p (miR-324-3p) in polycystic ovary syndrome (PCOS) and its effects on the proliferation and apoptosis of ovarian granulosa cells. A total of 60 Sprague-Dawley (SD) rats were randomly divided into normal group (n=30) and experimental group (n=30). Rats in the experimental group were intramuscularly injected with dehydroepiandrosterone (DHEA) (6 mg/100 g of body weight) and 0.2 mL oil for injection, while those in normal group were intramuscularly injected with 0.2 mL oil for injection. The ovarian tissues of PCOS model rats were removed to extract the total ribose nucleic acid (RNA). The expression of miR-324-3p was detected via reverse transcription-polymerase chain reaction (RT-PCR). Primary ovarian granulosa cells were isolated and cultured, and NC-miRNA and miR-324-3p mimic were transfected into cells. After 48 h, cell proliferation and apoptosis were detected via cell counting kit 8 (CCK-8) and flow cytometry assay, respectively. The targeted molecule of miR-324-3p was explored using bioinformatics, and dual-luciferase assay was performed to verify the effect of miR-324-3p on WNT2B expression. Granulosa cells were co-transfected with WNT2B-small-interfering RNA (siRNA) and miR-324-3p mimic, and then cell proliferation and apoptosis were detected via CCK-8 and flow cytometry assay, respectively. The expression of miR-324-3p in ovarian tissues of PCOS group was significantly lower than that of normal group (p < 0.01). After transfection with miR-324-3p mimic into granulosa cells, cell proliferation was significantly inhibited and cell apoptosis was promoted (p < 0.01). MiR-324-3p exerted its effect on granulosa cells by directly targeting WNT2B. Silencing WNT2B expression could reverse the effects of miR-324-3p on proliferation and apoptosis of granulosa cells (p < 0.05). The expression of miR-324-3p in the ovary of PCOS rats is decreased significantly. Overexpression of miR-324-3p can reduce the proliferation and

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

    SciTech Connect

    Lei, Dian; Wang, Wei; Gong, Xiao, E-mail: elegong@nus.edu.sg, E-mail: yeo@ieee.org

    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 trapmore » 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.« less

  17. Edge profiles in K shell photoabsorption spectra of gaseous hydrides of 3p elements and homologues

    NASA Astrophysics Data System (ADS)

    Hauko, R.; Gomilšek, J. Padežnik; Kodre, A.; Arčon, I.; Aquilanti, G.

    2017-10-01

    Photoabsorption spectra of gaseous hydrides of 3p elements (PH3, H2S, HCl) are measured in the energy region of photoexcitations pertaining to K edge. The analysis of the edge profile is extended to hydrides of 4p series (GeH4, AsH3, H2Se, HBr) from an earlier experiment, and to published spectra of 2p hydrides (CH4, NH3, H2O, HF) and noble gases Ar, Kr and Ne and SiH4. The edge profiles are modelled with a linear combination of lorentzian components, describing excitations to individual bound states and to continuum. Transition energies and probabilities are also calculated in the non-relativistic molecular model of the ORCA code, in good agreement with the experiment. Edge profiles in the heavier homologues are closely similar, the symmetry of the molecule governs the transitions to the lowest unoccupied orbitals. In 2p series the effect of the strong nuclear potential prevails. Transitions to higher, atomic-like levels remain very much the same as in free atoms.

  18. Semiconducting cubic titanium nitride in the Th 3 P 4 structure

    SciTech Connect

    Bhadram, Venkata S.; Liu, Hanyu; Xu, Enshi

    We report the discovery of a long-sought-after phase of titanium nitride with stoichiometry Ti 3 N 4 using diamond anvil cell experiments combined with in situ high-resolution x-ray diffraction and Raman spectroscopy techniques, supported by ab initio calculations. Ti 3 N 4 crystallizes in the cubic Th 3 P 4 structure [space group I ¯ 4 3 d (220)] from a mixture of TiN and N 2 above ≈ 75 GPa and ≈ 2400 K. The density ( ≈ 5.22 g/cc) and bulk modulus ( K 0 = 290 GPa) of cubic- Ti 3 N 4 ( c - Timore » 3 N 4 ) at 1 atm, estimated from the pressure-volume equation of state, are comparable to rocksalt TiN. Ab initio calculations based on the GW approximation and using hybrid functionals indicate that c - Ti 3 N 4 is a semiconductor with a direct band gap between 0.8 and 0.9 eV, which is larger than the previously predicted values. The c - Ti 3 N 4 phase is not recoverable to ambient pressure due to dynamic instabilities, but recovery of Ti 3 N 4 in the defect rocksalt (or related) structure may be feasible.« less

  19. Two-colored fluorescence correlation spectroscopy screening for LC3-P62 interaction inhibitors.

    PubMed

    Tsuganezawa, Keiko; Shinohara, Yoshiyasu; Ogawa, Naoko; Tsuboi, Shun; Okada, Norihisa; Mori, Masumi; Yokoyama, Shigeyuki; Noda, Nobuo N; Inagaki, Fuyuhiko; Ohsumi, Yoshinori; Tanaka, Akiko

    2013-10-01

    The fluorescence correlation spectroscopy (FCS)-based competitive binding assay to screen for protein-protein interaction inhibitors is a highly sensitive method as compared with the fluorescent polarization assay used conventionally. However, the FCS assay identifies many false-positive compounds, which requires specifically designed orthogonal screenings. A two-colored application of the FCS-based screening was newly developed, and inhibitors of a protein-protein interaction, involving selective autophagy, were selected. We focused on the interaction of LC3 with the adaptor protein p62, because the interaction is crucial to degrade the specific target proteins recruited by p62. First, about 10,000 compounds were subjected to the FCS-based competitive assay using a TAMRA-labeled p62-derived probe, and 29 hit compounds were selected. Next, the obtained hits were evaluated by the second FCS assay, using an Alexa647-labeled p62-derived probe to remove the false-positive compounds, and six hit compounds inhibited the interaction. Finally, we tested all 29 compounds by surface plasmon resonance-based competitive binding assay to evaluate their inhibition of the LC3-p62 interaction and selected two inhibitors with IC50 values less than 2 µM. The two-colored FCS-based screening was shown to be effective to screen for protein-protein interaction inhibitors.

  20. Characterization of rtSH3p13 gene encoding a development protein involved in vesicular traffic in spermiogenesis.

    PubMed

    Qiao, Yuan; Yang, Ju Xiang; Zhang, Xiao Dong L; Liu, Yu; Zhang, Jian Chao; Zong, Shu Dong; Miao, Shi Ying; Wang, Lin Fang; Koide, Samuel S

    2004-06-01

    A cDNA, designated as rtSH3p13, was isolated from a rat testis cDNA library. It consists of 1463 bp nuclear acids, which encodes a protein of 312 amino acids and was assigned the GenBank accession number AF227439. The deduced rtSH3p13 protein is a truncated isoform of SH3p13 as a result of mRNA alternative splicing. It is mainly expressed in the rat testis, detected in spermatids at the steps 8-19 of spermiogenesis, and found around the acrosome. During postnatal development, rtSH3p13 appears on day 18 and reaches maximum on day 60. Further experimental results suggested that rtSH3p13 forms a complex with activated epidermal growth factor receptor (EGFR) and interacts with synaptojanin I. Surprisingly, similar to SH3 domain, the V region of rtSH3p13 also inhibits endocytosis in CHO cells. Our results reveal a link between an rtSH3p13-synaptojanin-clathrin complex-mediated formation of pits and the process of spermiogenesis.

  1. MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by targeting MDM2

    PubMed Central

    Wang, Lei; Zheng, Mengliang; Wu, Shuishui; Niu, Zhiqiang

    2018-01-01

    Sevoflurane is a commonly used inhalation anesthetic. Sevoflurane-induced neuroapoptosis and cognitive impairments in animals are widely reported, however, the underlying molecular mechanisms remain largely unknown. The results of the present study demonstrated that sevoflurane anesthesia induced spatial memory impairments in rats, as determined by the Morris water maze test. Mechanistically, the current study demonstrated that sevoflurane administration significantly enhanced the expression of microRNA (miR)-188-3p. Furthermore, inhibition of miR-188-3p using lentiviral miR-188-3p inhibitors attenuated sevoflurane-induced cognitive impairments in rats. The present study also demonstrated that miR-188-3p targeted MDM2 proto-oncogene (MDM2) and negatively regulated the expression of MDM2, as determined by luciferase assays, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Furthermore, decreased abundance of MDM2 following transfection with miR-188-3p mimics was associated with increased stability of p53 protein. Suppression of p53 activity using the specific p53 inhibitor pifithrin-α alleviated sevoflurane-induced neuroapoptosis. These results indicate that the miR-188-3p-MDM2-p53 axis may have a critical role in sevoflurane-induced cognitive dysfunction. Therefore, miR-188-3p may be a potential target for the treatment of sevoflurane-induced cognitive impairment. PMID:29344658

  2. Transcriptome profiling reveals miR-9-3p as a novel tumor suppressor in gastric cancer.

    PubMed

    Meng, Qingshun; Xiang, Longquan; Fu, Jingwei; Chu, Xianqun; Wang, Chunlin; Yan, Bingzheng

    2017-06-06

    It has been well established that microRNAs (miRNAs) play important roles in biological processes. To comprehensively measure the altered miRNA expression, we presented the miRNA expression profile of gastric cancer using microarray. We identified 33 miRNAs that were significantly differentially regulated in gastric specimens compared to adjacent normal tissues, among which miR-9-3p expression are significantly down-regulated in gastric cancers. Next, a cohort of 100 gastric cancer tissues and matched normal tissues were enrolled. Kaplan-Meier and multivariate Cox survival analyses were applied to evaluate the prognostic value of miR-9-3p expression, and the result showed that patients with lower miR-9-3p expression level have significantly poorer overall survival. The expression level of miR-9-3p has been proved to be an independent prognostic factor for 5-year overall survival. Furthermore, the result indicated that over-expression of miR-9-3p can inhibit gastric cancer cell invasion. Taken together, our results suggested that miR-9-3p plays important role in tumor invasion, and these findings implicated the potential effects of miR-9-3p on prognosis of gastric cancer.

  3. UCS Protein Rng3p Is Essential for Myosin-II Motor Activity during Cytokinesis in Fission Yeast

    PubMed Central

    Stark, Benjamin C.; James, Michael L.; Pollard, Luther W.; Sirotkin, Vladimir; Lord, Matthew

    2013-01-01

    UCS proteins have been proposed to operate as co-chaperones that work with Hsp90 in the de novo folding of myosin motors. The fission yeast UCS protein Rng3p is essential for actomyosin ring assembly and cytokinesis. Here we investigated the role of Rng3p in fission yeast myosin-II (Myo2p) motor activity. Myo2p isolated from an arrested rng3-65 mutant was capable of binding actin, yet lacked stability and activity based on its expression levels and inactivity in ATPase and actin filament gliding assays. Myo2p isolated from a myo2-E1 mutant (a mutant hyper-sensitive to perturbation of Rng3p function) showed similar behavior in the same assays and exhibited an altered motor conformation based on limited proteolysis experiments. We propose that Rng3p is not required for the folding of motors per se, but instead works to ensure the activity of intrinsically unstable myosin-II motors. Rng3p is specific to conventional myosin-II and the actomyosin ring, and is not required for unconventional myosin motor function at other actin structures. However, artificial destabilization of myosin-I motors at endocytic actin patches (using a myo1-E1 mutant) led to recruitment of Rng3p to patches. Thus, while Rng3p is specific to myosin-II, UCS proteins are adaptable and can respond to changes in the stability of other myosin motors. PMID:24244528

  4. Reduced microRNA-188-3p expression contributes to apoptosis of spermatogenic cells in patients with azoospermia.

    PubMed

    Song, Wen-Yan; Meng, Hui; Wang, Xue-Gai; Jin, Hai-Xia; Yao, Gui-Dong; Shi, Sen-Lin; Wu, Liang; Zhang, Xiang-Yang; Sun, Ying-Pu

    2017-02-01

    Human mutL homologl (MLH1) works coordinately in sequential steps to initiate repair of DNA mismatches, and aberrant MLH1 expression is related to spermatogenetic malfunction. In the present study, MLH1 expression in patients with azoospermia was investigated, and moderating effects of miR-188-3p on MLH1 expression and spermatogenesis were identified. Testicular tissues from 16 patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), and tissues of eight healthy patients were collected. Real-time PCR, Western blotting and immunohistochemical staining were used to detect MLH1 expression. Chromatin immunoprecipitation assay and luciferase reporter assay were performed to evaluate histone acetylation level of miR-188-3p and relationships between miR-188-3p and MLH1. Testicular MLH1 expression at mRNA and protein levels was significantly increased, while miR-188-3p expression was lower in patients with OA and NOA than that in controls. Reduced histone acetylation level of miR-188-3p promoter was observed in patients with azoospermia. Overexpression/inhibition of HDAC1, but not HDAC2, contributed to the significant reduction/increase of miR-188-3p expression. miR-188-3p targeted 3' UTR of MLH1 and regulated MLH1 expression. miR-188-3p inhibitor led to elevation of apoptotic level of spermatogenic cells in mice, while this effect was reversed by si-MLH1. Down-regulation of miR-188-3p by reducing histone acetylation up-regulated MLH1 expression and contributed to promotion of apoptosis in spermatogenic cells, in patients with azoospermia. © 2016 John Wiley & Sons Ltd.

  5. Acute myeloid leukemia associated with t(10;17)(p13-15;q12-21) and phagocytic activity by leukemic blasts: a clinical study and review of the literature.

    PubMed

    Oh, Seung Hwan; Park, Tae Sung; Cho, Sun Young; Kim, Min Jin; Huh, Jungwon; Kim, Bomi; Song, Sae Am; Lee, Ja Young; Jun, Kyung Ran; Shin, Jeong Hwan; Kim, Hye Ran; Lee, Jeong Nyeo

    2010-10-01

    Translocation (10;17)(p13-15;q12-21) in acute leukemia is rarely reported in the literature. Here, we present both a novel t(10;17) case study and a review of relevant literature on t(10;17) in acute leukemia (10 cases). In summary, we came to the following preliminary conclusions: t(10;17) is associated with poorly differentiated acute leukemia subtype [90%; eight cases of acute myeloid leukemia (AML M0, M1) and one case of acute undifferentiated leukemia], phagocytic activity by blasts occurs (30%), and the survival time was short in three of the seven t(10;17) cases for whom follow-up data were available (median, 8 months). More clinical studies concerning the prognosis, treatment response, and survival of patients with t(10;17) are necessary. 2010 Elsevier Inc. All rights reserved.

  6. microRNA-199a-3p functions as tumor suppressor by regulating glucose metabolism in testicular germ cell tumors.

    PubMed

    Liu, Xiaowen; Duan, Hongyan; Zhou, Shihua; Liu, Zhiyong; Wu, Daobing; Zhao, Ting; Xu, Shan; Yang, Lifang; Li, Dan

    2016-09-01

    microRNA (miR)-199a-3p serves critical roles in cancer development and progression. In order to improve knowledge of the functional mechanism of miR‑199a‑3p in testicular tumors, the present study characterized the regulation of aerobic glycolysis by miR‑199a‑3p and its impact on metabolism. Using 3‑4,5‑dimethylthiazol‑2‑yl‑2,5 diphenyl tetrazolium bromide, wound healing and flow cytometry assays, it was determined that overexpression of miR‑199a‑3p in Ntera‑2 cells caused suppression of cell growth and migration. Further biochemical methods and high‑throughput quantitative polymerase chain reaction array of metabolic genes showed that inhibition of miR‑199a‑3p markedly elevated lactate production and 12 differentially expressed genes, including 2 upregulated and 10 downregulated genes, were identified following treatment with miR‑199a‑3p in Ntera‑2 cells. In clinical samples, four selected genes, lactate dehydrogenase A, monocarboxylate transporter 1, phosphoglycerate kinase 1 and TP53‑inducible glycolysis and apoptosis regulator, were significantly overexpressed in malignant testicular germ cell tumor, and their expression inversely correlated with the expression of miR‑199a‑3p, suggesting that these four genes may be affected by miR‑199a‑3p. Using bioinformatics analysis, the transcription factor Sp1 binding site was identified in the promoter region of the four selected genes. In addition, miR‑199a‑3p was predicted to bind to conservative target sequences in the 3'‑untranslated region of Sp1 mRNA, suggesting that miR-199a-3p may downregulate these four metabolic genes through Sp1. It was demonstrated the dysregulated expression and activation of miR‑199a‑3p may serve important roles in aerobic glycolysis and tumorigenesis in patients with testicular cancer. Therefore, miR-199a-3p may be a potential biomarker in the prognosis and treatment of testicular tumors.

  7. Measurement of the 3 s 1 / 2 - 3 p 3 / 2 resonance line of sodiumlike Eu 52 +

    SciTech Connect

    Träbert, E.; Beiersdorfer, P.; Hell, N.

    2015-08-20

    We have measured the 3s 1/2-3p 3/2 transition in sodiumlike Eu 52+ situated at 41.232 Å with an uncertainty of 73 ppm. Our measurement extends previous high-precision measurements into the 56< Z< 78 range of atomic numbers. We also present measurements of 3s 1/2-3p 3/2 and 3p 1/2-3d 3/2 transitions in the neighboring magnesiumlike, aluminumlike, and siliconlike europium ions.

  8. Wakefield Computations for the CLIC PETS using the Parallel Finite Element Time-Domain Code T3P

    SciTech Connect

    Candel, A; Kabel, A.; Lee, L.

    In recent years, SLAC's Advanced Computations Department (ACD) has developed the high-performance parallel 3D electromagnetic time-domain code, T3P, for simulations of wakefields and transients in complex accelerator structures. T3P is based on advanced higher-order Finite Element methods on unstructured grids with quadratic surface approximation. Optimized for large-scale parallel processing on leadership supercomputing facilities, T3P allows simulations of realistic 3D structures with unprecedented accuracy, aiding the design of the next generation of accelerator facilities. Applications to the Compact Linear Collider (CLIC) Power Extraction and Transfer Structure (PETS) are presented.

  9. Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma.

    PubMed

    Sheu, Jim Jinn-Chyuan; Lee, Chia-Huei; Ko, Jenq-Yuh; Tsao, George S W; Wu, Chung-Chun; Fang, Chih-Yeu; Tsai, Fuu-Jen; Hua, Chun-Hung; Chen, Chi-Long; Chen, Jen-Yang

    2009-10-01

    Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed. A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors. A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25% of cases) and SKIL (33%); and deletion of ADAMTS9 (30%), LRIG1 (35%), MPDZ (15%), and ADFP (15%). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114). The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.

  10. FAST TRACK COMMUNICATION: Generalized geometrical model for photoionization of polarized atoms: II. Magnetic dichroism in the 3p photoemission from the K 3p64s 2S1/2 ground state

    NASA Astrophysics Data System (ADS)

    Grum-Grzhimailo, A. N.; Cubaynes, D.; Heinecke, E.; Hoffmann, P.; Zimmermann, P.; Meyer, M.

    2010-10-01

    The generalized geometrical model for photoionization from polarized atoms is extended to include mixing of configurations in the initial atomic and/or the final photoion states. The theoretical results for angle-resolved linear and circular magnetic dichroism are in good agreement with new high-resolution photoelectron data for 3p-1 photoionization of potassium atoms polarized in the K 3p64s 2S1/2 ground state by laser optical pumping.

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

    SciTech Connect

    Lorenzetti, D.; Roa, B.B.; Abbas, N.E.

    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 amore » 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.« less

  12. Selective cyclopalladation of R3P=NCH2Aryl iminophosphoranes. Experimental and computational study.

    PubMed

    Bielsa, Raquel; Navarro, Rafael; Urriolabeitia, Esteban P; Lledós, Agustí

    2007-11-26

    The orientation of the orthopalladation of iminophosphoranes R3P=NCH2Aryl (R=Ph, Aryl=Ph (1a), C6H(4)-2-Br (1b), C6H4-Me-2 (1e), C6H3-(Me)(2)-2,5 (1f); R=p-tolyl, Aryl=Ph (1c); R=m-tolyl, Aryl=Ph (1d); R3P=MePh2P, and Aryl=Ph (1g)) has been studied. 1a reacts with Pd(OAc)2 (OAc=acetate) giving endo-[Pd(micro-Cl){C,N-C6H4(PPh2=NCH2Ph)-2}]2 (3a), while exo-[Pd(micro-Br){C,N-C6H4(CH2N=PPh3)-2}]2 (3b) could only be obtained by the oxidative addition of 1b to Pd2(dba)3. The endo form of the metalated ligand is favored kinetically and thermodynamically, as shown by the conversion of exo-[Pd(micro-OAc){C,N-C6H4(CH2N=PPh3)-2}]2 (2b) into endo-[Pd(micro-OAc){C,N-C6H4(PPh2=NCH2Ph)-2}]2 (2a) in refluxing toluene. The orientation of the reaction is not affected by the introduction of electron-releasing substituents at the Ph rings of the PR3 (1c and 1d) or the benzyl units (1e and 1f), and endo complexes (3c-3f) were obtained in all cases. The palladation of MePh2P=NCH2Ph (1g) can be regioselectively oriented as a function of the solvent. The exo isomer [Pd(micro-Cl){C6H4(CH2N=PPh2Me)-2}]2 (exo-3g) is obtained in refluxing CH2Cl2, while endo-[Pd(micro-Cl){C,N-C6H4(PPh(Me)=NCH2Ph)-2}]2 (endo-3g) can be isolated as a single isomer in refluxing toluene. In this case, the exo metalation is kinetically favored while an endo process occurs under thermodynamic control, as shown through the rearrangement of [Pd(micro-OAc){C6H4(CH2N=PPh2Me)-2}]2 (exo-2g) into [Pd(micro-OAc){C,N-C6H4(P(Ph)Me=NCH2Ph)-2}]2 (endo-2g) in refluxing toluene. The preference for the endo palladation of 1a and the kinetic versus thermodynamic control in 1g has been explained through DFT studies of the reaction mechanism.

  13. Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

    DOE PAGES

    Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; ...

    2015-02-05

    The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

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

    PubMed

    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. Copyright 2010 Elsevier Inc. All rights reserved.

  15. PKC-alpha modulation by miR-483-3p in platinum-resistant ovarian carcinoma cells

    SciTech Connect

    Arrighetti, Noemi, E-mail: Noemi.Arrighetti@istitu

    The occurrence of drug resistance limits the efficacy of platinum compounds in the cure of ovarian carcinoma. Since microRNAs (miRNAs) may contribute to this phenomenon by regulating different aspects of tumor cell response, the aim of this study was to exploit the analysis of expression of miRNAs in platinum sensitive/resistant cells in an attempt to identify potential regulators of drug response. MiR-483-3p, which may participate in apoptosis and cell proliferation regulation, was found up-regulated in 4 platinum resistant variants, particularly in the IGROV-1/Pt1 subline, versus parental cells. Transfection of a synthetic precursor of miR-483-3p in IGROV-1 parental cells elicited amore » marked up-regulation of the miRNA levels. Growth-inhibition and colony-forming assays indicated that miR-483-3p over-expression reduced cell growth and conferred mild levels of cisplatin resistance in IGROV-1 cells, by interference with their proliferative potential. Predicted targets of miR-483-3p included PRKCA (encoding PKC-alpha), previously reported to be associated to platinum-resistance in ovarian carcinoma. We found that miR-483-3p directly targeted PRKCA in IGROV-1 cells. In keeping with this finding, cisplatin sensitivity of IGROV-1 cells decreased upon molecular/pharmacological inhibition of PKC-alpha. Overall, our results suggest that overexpression of miR-483-3p by ovarian carcinoma platinum-resistant cells may interfere with their proliferation, thus protecting them from DNA damage induced by platinum compounds and ultimately representing a drug-resistance mechanism. The impairment of cell growth may account for low levels of drug resistance that could be relevant in the clinical setting. - Highlights: • miR-483-3p is up-regulated in ovarian carcinoma cells resistant to platinum drugs. • Ectopic expression of miR-483-3p in IGROV-1 confers mild levels of Pt-resistance. • Overexpression of miR-483-3p down-regulates PRKCA levels in ovarian carcinoma cells.

  16. let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer.

    PubMed

    García-Vázquez, Raúl; Gallardo Rincón, Dolores; Ruiz-García, Erika; Meneses García, Abelardo; Hernández De La Cruz, Olga N; Astudillo-De La Vega, Horacio; Isla-Ortiz, David; Marchat, Laurence A; Salinas-Vera, Yarely M; Carlos-Reyes, Ángeles; López-González, Sullivan; Ramos-Payan, Rosalio; López-Camarillo, César

    2018-06-01

    Altered expression of microRNAs contributes to the heterogeneous biological behavior of human malignancies and it may correlate with the clinical pathological features of patients. The let-7 microRNA family is frequently downregulated in human cancers and its aberrant expression may be a useful marker for prediction of the clinical response to therapy in patients. In the present study, we analyzed the expression of three members of the let-7 family (let-7a-3p, let-7d-3p and let-7f), which remains largely uncharacterized in ovarian cancer tissues. We also investigated the function of let-7d-3p in the apoptosis and sensitization to chemotherapy in ovarian cancer cells. Our data from stem-loop quantitative RT-PCR showed that expression of let-7a-3p and let-7d-3p, but not let-7f, was significantly (P<0.04) upregulated in ovarian tumors relative to that noted in normal ovarian tissues. Markedly, an increased expression of let‑7d-3p (also known as let-7d-3*) was associated with positive response to carboplatin/paclitaxel treatment in ovarian cancer patients. To investigate the biological relevance of let‑7d-3p, we knocked down its expression in SKOV-3 ovarian cancer cell line using antagomiRs. Loss of function analysis showed that inhibition of let-7d-3p significantly (P<0.05) impaired cell proliferation and activated apoptosis. In contrast, scratch/wound healing and Transwell chamber assays showed that migration and invasion abilities were not affected in the let-7d-3p-deficient SKOV-3 cancer cells. Notably, Annexin V assays showed a significant (P<0.05) increase in cell death of cancer cells treated with the let-7d-3p inhibitor plus carboplatin indicating a synergistic effect of the drug with antagomiR therapy. Gene ontology classification of predicted targets of let-7d-3p identified a number of genes involved in cellular pathways associated with therapy resistance such as ABC transporters, HIF-1, RAS and ErbB signaling. In summary, our findings showed that

  17. Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis.

    PubMed

    Mesci, Aruz; Huang, Xiaoyong; Taeb, Samira; Jahangiri, Sahar; Kim, Yohan; Fokas, Emmanouil; Bruce, Jeff; Leong, Hon S; Liu, Stanley K

    2017-05-09

    MicroRNAs (miRs) are involved in the regulation of many processes that contribute to malignancy, including cell proliferation, radiation resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated in breast cancer, remains unclear. We examine the association of miR-330-3p with distant relapse-free survival in the Oxford cohort of breast cancer patients. We also study miR-330-3p function using in vitro invasion and ex ovo metastasis assays. Using in vitro luciferase assays, we validate a novel target gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1). We assess functional consequences of CCBE1 loss by using siRNA-mediated knockdown followed by in vitro invasion assays. Lastly, we examine the expression profile of CCBE1 in breast carcinomas in the Curtis and TCGA Breast Cancer data sets using Oncomine Platform as well as distant relapse-free and overall survival of patients in the Helsinki University breast cancer data set according to CCBE1 expression status. miR-330-3p is enriched in breast cancer, and higher levels of miR-330-3p expression are associated with lower distant relapse-free survival in a cohort of breast cancer patients. Consistent with these observations, overexpression of miR-330-3p in breast cancer cell lines results in greater invasiveness in vitro, and miR-330-3p-overexpressing cells also metastasise more aggressively ex ovo. We identify CCBE1 as a direct target of miR-330-3p, and show that knockdown of CCBE1 results in a greater invasive capacity. Accordingly, in breast cancer patients CCBE1 is frequently downregulated, and its loss is associated with reduced distant relapse-free and overall survival. We show for the first time that miR-330-3p targets CCBE1 to promote invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers in breast cancer.

  18. Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

    NASA Astrophysics Data System (ADS)

    Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

    2015-01-01

    In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations.

  19. Are HO radicals produced in the reaction of O(3P) with 1-C4H8 ?

    NASA Technical Reports Server (NTRS)

    Luria, M.; Simonaitis, R.; Heicklen, J.

    1972-01-01

    The reaction of O(3P) with 1-C4H8 was examined in the presence of CO which scavenges HO radicals to produce CO2. From the CO2 quantum yield, an upper limit to the efficiency of HO production in the reaction of O(3P) with 1-C4H8 was found to be 0.020 at both 298 and 473 K.

  20. Computational Study of Collisions Between O(3P) and NO(2Pi) at Temperatures Relevant to the Hypersonic Flight Regime

    DTIC Science & Technology

    2014-10-29

    hypersonic flight regime. For this reason, the thermal rate coefficients for reactive processes involving O(3P) and NO(2_) are relevant over a wide...hypersonic flight regime. For this reason, the thermal rate coefficients for reactive processes involving O(3P) and NO(2) are relevant over a wide...N) is of particular interest since the thermal dissociation threshold for O2 is lower than that for N2 in air. A central question is how

  1. MiR-141-3p promotes prostate cancer cell proliferation through inhibiting kruppel-like factor-9 expression

    SciTech Connect

    Li, Jiu-zhi; Department of Urology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001; Li, Jia

    Evidence has revealed that some microRNAs play a critical role in tumor proliferation. We demonstrated that miR-141-3p appears to be a novel oncogene miRNA, which promotes prostate tumorigenesis and facilitates the stemness of prostate cancer cells via suppressing a key transcription factor kruppel-like factor-9 (KLF9). KLF9 is the core effector protein that might suppress tumor growth. MiR-141-3p is upregulated in prostate cancer cells and tissues compared to non-tumorigenic prostate epithelial cells and prostate tissues. MiR-141-3p positively regulated proliferation, spheroid formation, and expression of the stemness factors OCT-4, Nanog, SOX-9, Bmil, CCND1, and CD44 in PC-3 cells. Restoration of miR-141-3p suppresses themore » expression of the transcription factor KLF9 in PC-3 and accelerates prostate tumorigenesis via targeted binding with its 3′-UTR. Downregulation of KLF9 enhances spheres formation of prostate cancer cells. Our results suggest that miR-141-3p/KLF9 may play an important role in regulating the growth of prostate cancer and is a potential target of prevention and therapy. - Highlights: • MiR-141-3p is upregulated in human prostate cancer. • MiR-141-3p induces cell proliferation and apoptosis resistance. • KLF9 is a direct and functional target of miR-141-3p.« less

  2. miR-141-3p functions as a tumor suppressor modulating activating transcription factor 5 in glioma.

    PubMed

    Wang, Mengyuan; Hu, Ming; Li, Zhaohua; Qian, Dongmeng; Wang, Bin; Liu, David X

    2017-09-02

    Glioma is the most common malignant primary brain tumor which arises from the central nervous system. Our studies reported that an anti-apoptotic factor, activating transcription factor 5 (ATF5), is highly expressed in malignant glioma specimens and cell lines. Downregulation by dominant-negetive ATF5 could repress glioma cell proliferation and accelerate apoptosis. Here, we further investigate the upstream factor which regulates ATF5 expression. Bioinformatic analysis showed that ATF5 was a potential target of miR-141-3p. Luciferase reporter assay verified that miR-141-3p specifically targeted the ATF5 3'-UTR in glioma cells. Functional studied suggested that miR-141-3p overexpression inhibited proliferation and promoted apoptosis of glioma cells (U87MG and U251). Xenograft experiments proved the inhibition of miR-141-3p on glioma growth in vivo. Moreover, exogenous ATF5 without 3'-UTR restored the cell proliferation inhibition triggered by miR-141-3p. Taken together, we put forward that miR-141-3p is a new upstream target towards ATF5. It can serve as a crucial tumor suppressor in regulating the ATF5-regulated growth of malignant glioma. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

    PubMed Central

    Pang, Fei; Zha, Ruopeng; Zhao, Yingjun; Wang, Qifeng; Chen, Di; Zhang, Zhenfeng; Chen, Taoyang; Yao, Ming; Gu, Jianren; He, Xianghuo

    2014-01-01

    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. PMID:24599008

  4. Novel Mad2-targeting miR-493-3p controls mitotic fidelity and cancer cells' sensitivity to paclitaxel.

    PubMed

    Tambe, Mahesh; Pruikkonen, Sofia; Mäki-Jouppila, Jenni; Chen, Ping; Elgaaen, Bente Vilming; Straume, Anne Hege; Huhtinen, Kaisa; Cárpen, Olli; Lønning, Per Eystein; Davidson, Ben; Hautaniemi, Sampsa; Kallio, Marko J

    2016-03-15

    The molecular pathways that contribute to the proliferation and drug response of cancer cells are highly complex and currently insufficiently characterized. We have identified a previously unknown microRNA-based mechanism that provides cancer cells means to stimulate tumorigenesis via increased genomic instability and, at the same time, evade the action of clinically utilized microtubule drugs. We demonstrate miR-493-3p to be a novel negative regulator of mitotic arrest deficient-2 (MAD2), an essential component of the spindle assembly checkpoint that monitors the fidelity of chromosome segregation. The microRNA targets the 3' UTR of Mad2 mRNA thereby preventing translation of the Mad2 protein. In cancer cells, overexpression of miR-493-3p induced a premature mitotic exit that led to increased frequency of aneuploidy and cellular senescence in the progeny cells. Importantly, excess of the miR-493-3p conferred resistance of cancer cells to microtubule drugs. In human neoplasms, miR-493-3p and Mad2 expression alterations correlated with advanced ovarian cancer forms and high miR-493-3p levels were associated with reduced survival of ovarian and breast cancer patients with aggressive tumors, especially in the paclitaxel therapy arm. Our results suggest that intratumoral profiling of miR-493-3p and Mad2 levels can have diagnostic value in predicting the efficacy of taxane chemotherapy.

  5. Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1.

    PubMed

    Chang, Hong; Li, Lingyi; Peng, Tao; Grigoroiu-Serbanescu, Maria; Bergen, Sarah E; Landén, Mikael; Hultman, Christina M; Forstner, Andreas J; Strohmaier, Jana; Hecker, Julian; Schulze, Thomas G; Müller-Myhsok, Bertram; Reif, Andreas; Mitchell, Philip B; Martin, Nicholas G; Cichon, Sven; Nöthen, Markus M; Jamain, Stéphane; Leboyer, Marion; Bellivier, Frank; Etain, Bruno; Kahn, Jean-Pierre; Henry, Chantal; Rietschel, Marcella; Xiao, Xiao; Li, Ming

    2017-09-01

    Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta  = 5.72 × 10 -4 ), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10 -16 ). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a "proxy phenotype" of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2 Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis.

  6. Differential deletions in 3p are associated with the development of head and neck squamous cell carcinoma in Indian patients.

    PubMed

    Chakraborty, Suman Bhusan; Dasgupta, Santanu; Roy, Anup; Sengupta, Arunava; Ray, Bidyut; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2003-10-15

    In this study we performed detailed deletion mapping of two broad regions in the short arm (p) of chromosome 3 (i.e., 3p21.2 approximately p22 and 3p12 approximately p13), which were shown to have a high rate of deletions in head and neck lesions in our previous study. Using 18 highly polymorphic microsatellite markers, the deletion mapping was done in 35 dysplastic lesions and 46 primary head and neck squamous cell carcinoma (HNSCC) samples from Indian patients. Within the 21.6-megabase (Mb) region of 3p21.1 approximately p21.33, we have identified four areas (D1, 3p21.33; D2, 3p21.32; D3, 3p21.31; D4, 3p21.1) that showed a high frequency (46%-69%) of deletions in our samples. In the 3p12 approximately p13 region, we narrowed down the deletion within the 0.7-Mb region (D5, 3p12.1). Among these five regions (D1-D5), deletion in D3 is suggested to be necessary for the development of early dysplastic lesions, whereas the deletion in D2 may be necessary for dysplastic lesions and tumor progression. On the other hand, the deletion in D5 is significantly associated with progression of the lesions from mild/moderate to severe dysplasia. The deletions in D1 and D4, however, are required for tumor progression. As in our previous study, microsatellite size alterations (MA) were observed to be high in and around the highly deleted regions and gradually increased during the progression of the tumor. Loss of normal copy/interstitial alterations of chromosome 3 in the late stages of the tumor as well as rare biallelic alterations around the highly deleted regions also were seen in our samples. Human papilloma virus infection has been found to be associated with the deletion in the D5 region and MA in the D1 region, whereas nodal involvement of the tumor correlated only with the MA in D1 and D5. Thus, this study indicates that multiple tumor suppressor genes whose differential deletions are associated with the development of HNSCC may be present in 3p.

  7. MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer.

    PubMed

    Shen, Peng-fei; Chen, Xue-qin; Liao, Yong-chuan; Chen, Ni; Zhou, Qiao; Wei, Qiang; Li, Xiang; Wang, Jia; Zeng, Hao

    2014-05-01

    Although SDF-1/CXCR4 pathway is a potential mechanism of tumor proliferation and progression, the mechanism of controlling CXCR4 expression is not fully understood. This study was to confirm that miR-494-3p might be a potentially post-transcriptional regulator of CXCR4 and over-expression of miR-494 might suppress prostate cancer progression and metastasis. We firstly postulated the post-transcriptional regulation of CXCR4 by miR-494-3p through bioinformatics analysis, and then it was demonstrated that miR-494-3p could regulate the CXCR4 mRNA post-transcriptionally by binding to the predicted site by dual reporter gene assays. The biological effect of miR-494-3p on prostate cancer cells proliferation, apoptosis, migration, and invasion was measured by MTT, TUNEL, flow cytometry, migration, and invasion assays. It was shown that the mRNA and protein expression levels of CXCR4 were significantly up-regulated in PC-3 and DU145, whereas barely detected in LNCaP and RWPE-1. However, the CXCR4 protein levels were inversely related to the mature miR-494-3p expression levels in RWPE-1 and prostate cancer cells. The constitutive over-expression of miR-494-3p could down-regulate the protein level of CXCR4 in PC-3 and DU145. MiR-494-3p also could bind to the seed sequences in the 3'-UTR of the CXCR4 gene. Artificial over-expression of miR-494-3p could inhibit the growth, promote the apoptosis, and inhibit the migration and invasion of PC-3 and DU145 cells in vivo. Our results suggested that miR-494-3p might play crucial role in prostate cancer by post-transcriptional regulation to CXCR4 mRNA. MiR-494-3p/CXCR4 pathway may be a potential therapeutic target to prevent prostate cancer progression and metastasis. © 2014 Wiley Periodicals, Inc.

  8. MicroRNA-495-3p functions as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis.

    PubMed

    Eun, Jung Woo; Kim, Hyung Seok; Shen, Qingyu; Yang, Hee Doo; Kim, Sang Yean; Yoon, Jung Hwan; Park, Won Sang; Lee, Jung Young; Nam, Suk Woo

    2018-01-01

    MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here, we demonstrate that microRNA-495-3p (miR-495-3p) functions as a potent tumor suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate 15 EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression. Computational target prediction yielded miR-495-3p, which targets as many as ten of the 15 candidate oncogenic EMs. Ectopic expression of miRNA mimics in GC cells caused miR-495-3p to suppress ten EMs, and inhibited tumor cell growth and proliferation via caspase-dependent and caspase-independent cell death processing. In addition, in vitro metastasis assays showed that miR-495-3p plays a role in the metastatic behavior of GC cells by regulating SLUG, vimentin, and N-cadherin. Furthermore, treatment of GC cells with 5-aza-2'-deoxcytidine restored miR-495-3p expression; sequence analysis revealed hypermethylation of the miR-495-3p promoter region in GC cells. A negative regulatory loop is proposed, whereby DNMT1, among ten oncogenic EMs, regulates miR-495-3p expression via hypermethylation of the miR-495-3p promoter. Our findings suggest that the functional loss or suppression of miR-495-3p triggers overexpression of multiple oncogenic EMs, and thereby contributes to malignant transformation and growth of gastric epithelial cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. The putative RNA helicase Dbp6p functionally interacts with Rpl3p, Nop8p and the novel trans-acting Factor Rsa3p during biogenesis of 60S ribosomal subunits in Saccharomyces cerevisiae.

    PubMed Central

    de la Cruz, Jesús; Lacombe, Thierry; Deloche, Olivier; Linder, Patrick; Kressler, Dieter

    2004-01-01

    Ribosome biogenesis requires at least 18 putative ATP-dependent RNA helicases in Saccharomyces cerevisiae. To explore the functional environment of one of these putative RNA helicases, Dbp6p, we have performed a synthetic lethal screen with dbp6 alleles. We have previously characterized the nonessential Rsa1p, whose null allele is synthetically lethal with dbp6 alleles. Here, we report on the characterization of the four remaining synthetic lethal mutants, which reveals that Dbp6p also functionally interacts with Rpl3p, Nop8p, and the so-far-uncharacterized Rsa3p (ribosome assembly 3). The nonessential Rsa3p is a predominantly nucleolar protein required for optimal biogenesis of 60S ribosomal subunits. Both Dbp6p and Rsa3p are associated with complexes that most likely correspond to early pre-60S ribosomal particles. Moreover, Rsa3p is co-immunoprecipitated with protA-tagged Dbp6p under low salt conditions. In addition, we have established a synthetic interaction network among factors involved in different aspects of 60S-ribosomal-subunit biogenesis. This extensive genetic analysis reveals that the rsa3 null mutant displays some specificity by being synthetically lethal with dbp6 alleles and by showing some synthetic enhancement with the nop8-101 and the rsa1 null allele. PMID:15126390

  10. MicroRNA-130a-3p suppresses cell viability, proliferation and invasion in nasopharyngeal carcinoma by inhibiting CXCL12.

    PubMed

    Qu, Rongfeng; Sun, Yan; Li, Yarong; Hu, Chunmei; Shi, Guang; Tang, Yan; Guo, Dongrui

    2017-01-01

    Incidence of nasopharyngeal carcinoma (NPC) has remained high worldwide, posing a serious health problem. MicroRNAs (miRNAs) are a family of about 20-23 nucleotides small non-coding molecules, which play a significant role in NPC. In this study, we explored the molecular mechanisms of miR-130a-3p in inhibiting viability, proliferation, migration and invasion of NPC cells by suppressing CXCL12 . The relative expression of miR-130a-3p and CXCL12 mRNA expression in tissues and cells was measured by qRT-PCR. NPC cell line CNE-2Z was transfected with miR-130a-3p mimics, CXCL12 siRNA, cDNA- CXCL12 and negative control. Western Blot was performed to detect CXCL12 expression. The MTT assay was performed to study cell viability. The colony formation assay was done to test cell growth. Flow cytometry was conducted to analyze cell cycle and apoptosis. The Transwell assay was used to investigate cell migration and invasion. The results found that the up-regulation of miR-130a-3p or down-regulation of CXCL12 could inhibit viability, proliferation, migration and invasion of CNE-2Z cells. Luciferase-reporting system assay was performed to investigate miR-130a-3p could bind to the 3'UTR region of CXCL12 and the overexpression of miR-130a-3p could suppress CXCL12 expression. Collectively, our finding suggested demonstrated that miR-130a-3p could prohibit the progression of NPC by suppressing CXCL12 , which might serve as potential therapeutic targets for NPC.

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

    PubMed

    Pan, Chao-Yu; Kuo, Wei-Ting; Chiu, Chien-Yuan; Lin, Wen-Chang

    2017-01-01

    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.

  12. miR-130b-3p Modulates Epithelial-Mesenchymal Crosstalk in Lung Fibrosis by Targeting IGF-1.

    PubMed

    Li, Shuhong; Geng, Jing; Xu, Xuefeng; Huang, Xiaoxi; Leng, Dong; Jiang, Dingyuan; Liang, Jiurong; Wang, Chen; Jiang, Dianhua; Dai, Huaping

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal fibrotic lung disease with largely unknown etiology and pathogenesis. Evidence suggests microRNAs (miRNA) contribute to pathogenesis of IPF. In this study, we sought to identify miRNA expression signatures and determine the role of miR-130b-3p in lung fibrosis. The miRNA expression profile of the lungs from patients with IPF and normal donors was determined by Affymetrix microarray, and transcriptome with Affymetrix array. The functions and signal pathways as well as miRNA-mRNA networks were established by bioinformatics analysis. Luciferase assays and ELISA were used to confirm the miRNA target gene. The effect of miRNA-transfected epithelium on fibroblast activities was assessed using a co-culture system. The fibroblast activities were determined by qRT-PCR, western blotting, Transwell and BrdU assays. Seven miRNAs were significantly decreased in IPF lungs, with miR-130b-3p being the highest in the miRNA-mRNA network. Insulin-like growth factor (IGF-1) was a target gene of miR-130b-3p in the epithelium. miR-130b-3p inhibition in the epithelium induced collagen I expression and enhanced the proliferation and migration ability of fibroblast in co-culture systems, which mimicked the functions of exogenous IGF-1 on fibroblasts. Neutralizing IGF-1 with an antibody significantly reduced the modulatory effects of miR-130b-3p inhibitor-transfected epithelium on the activation of fibroblasts. Our results show that miR-130b-3p was downregulated in IPF lungs. miR-130b-3p downregulation contributed to the activation of fibroblasts and the dysregulated epithelial-mesenchymal crosstalk by promoting IGF-1 secretion from lung epithelium, suggesting a key regulatory role for this miRNA in preventing lung fibrosis.

  13. Can germ cell neoplasia in situ be diagnosed by measuring serum levels of microRNA371a-3p?

    PubMed

    Radtke, A; Cremers, J-F; Kliesch, S; Riek, S; Junker, K; Mohamed, S A; Anheuser, P; Belge, G; Dieckmann, K-P

    2017-11-01

    Diagnosing germ cell neoplasia in situ (GCNis) can detect germ cell tumours (GCTs) at the pre-invasive stage. To date, testicular biopsy with the potential of surgical complications is the only way of safely diagnosing GCNis. Recently, microRNAs (miRs) 371-3, and miR 367 were shown to be valuable serum biomarkers of GCTs. We explored the usefulness of these candidate miRs as a marker for GCNis. 27 patients with GCNis and no concomitant GCT were enrolled. All patients underwent measuring serum levels of miR-371a-3p and miR-367-3p before treatment, 11 had repeat measurement after treatment, 2 also had testicular vein blood examinations. Serum levels were measured by quantitative PCR. In addition, four orchiectomy specimens of patients with GCT were examined immunohistochemically and by in situ hybridization (ISH) with a probe specific for miR-371a-3p to look for the presence of this miR in GCNis cells. The median serum level of miR-371a-3p was significantly higher in patients with GCNis than in controls, miR-367 levels were not elevated. Overall, 14 patients (51.9%) had elevated serum levels of miR-371a-3p. The highest levels were found in patients with bilateral GCNis. Levels in testicular vein serum were elevated in both of the cases. After treatment, all elevated levels dropped to normal. In two orchiectomy specimens, miR-371a-3p was detected by ISH in GCNis cells. Measuring miR-371a-3p serum levels can replace control biopsies after treatment of GCNis. In addition, the test can guide clinical decision making regarding the need of testicular biopsy in cases suspicious of GCNis.

  14. A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis.

    PubMed

    Xiao, Fei; Yu, Junjie; Liu, Bin; Guo, Yajie; Li, Kai; Deng, Jiali; Zhang, Jin; Wang, Chunxia; Chen, Shanghai; Du, Ying; Lu, Yingli; Xiao, Yuzhong; Zhang, Zhou; Guo, Feifan

    2014-08-01

    MicroRNAs (miRNAs) are endogenous, noncoding, short, single-stranded RNAs that are evolutionarily conserved and believed to play a role in controlling a variety of biological processes. The roles of miRNAs in insulin resistance and liver steatosis, however, are largely unknown. The objective of this study was to evaluate the roles of miR-130a in the regulation of insulin sensitivity and liver steatosis. In our current study, we observed that overexpression of miR-130a-3p increases insulin signaling in both HepG2 cells and primary mouse hepatocytes, and silencing of miR-130a-3p has the opposite effects. However, miR-130a-5p has no effect in the regulation of insulin signaling. Consistently, whole-body and hepatic insulin sensitivity are improved in mice injected with adenoviruses that overexpress miR-130a-3p. Furthermore, we provided evidence showing that growth factor receptor-bound protein 10 is required for miR-130a-3p-regulated insulin sensitivity. On the other hand, we observed that expression of miR-130a-3p is decreased in the livers of db/db mice and that adenovirus-mediated overexpression of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of which is achieved via suppressing fatty acid synthase expression in these mice. This study identifies a novel function for hepatic miR-130a-3p in the regulation of insulin sensitivity and liver steatosis. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Evolutionary conservation and expression of miR-10a-3p in olive flounder and rock bream.

    PubMed

    Jo, Ara; Im, Jennifer; Lee, Hee-Eun; Jang, Dongmin; Nam, Gyu-Hwi; Mishra, Anshuman; Kim, Woo-Jin; Kim, Won; Cha, Hee-Jae; Kim, Heui-Soo

    2017-09-10

    MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the seed sequences located within the 3' untranslated region (3' UTR) of target genes. They perform an important biological function as regulators of gene expression. Different genes can be regulated by the same miRNA, whilst different miRNAs can be regulated by the same genes. Here, the evolutionary conservation and expression pattern of miR-10a-3p in olive flounder and rock bream was examined. Binding sites (AAAUUC) to seed region of the 3' UTR of target genes were highly conserved in various species. The expression pattern of miR-10a-3p was ubiquitous in the examined tissues, whilst its expression level was decreased in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to the normal control. In the case of rock bream, the spleen, kidney, and liver tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues in the rock bream samples infected by the iridovirus indicated a dominant miR-10a-3p expression. The gene ontology (GO) analysis of predicted target genes for miR-10a-3p revealed that multiple genes are related to binding activity, catalytic activity, cell components as well as cellular and metabolic process. Overall the results imply that the miR-10a-3p could be used as a biomarker to detect VHSV infection in olive flounder and iridovirus infection in rock bream. In addition, the data provides fundamental information for further study of the complex interaction between miR-10a-3p and gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Identification of Four Oxidative Stress-Responsive MicroRNAs, miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p, in Hepatocellular Carcinoma.

    PubMed

    Wan, Yong; Cui, Ruixia; Gu, Jingxian; Zhang, Xing; Xiang, Xiaohong; Liu, Chang; Qu, Kai; Lin, Ting

    2017-01-01

    Increasing evidence suggests that oxidative stress plays an essential role during carcinogenesis. However, the underlying mechanism between oxidative stress and carcinogenesis remains unknown. Recently, microRNAs (miRNAs) are revealed to be involved in oxidative stress response and carcinogenesis. This study aims to identify miRNAs in hepatocellular carcinoma (HCC) cells which might involve in oxidative stress response. An integrated analysis of miRNA expression signature was performed by employing robust rank aggregation (RRA) method, and four miRNAs (miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p) were identified as the oxidative stress-responsive miRNAs. Pathway enrichment analysis suggested that these four miRNAs played an important role in antiapoptosis process. Our data also revealed miR-34a-5p and miR-1915-3p, but not miR-150-3p and miR-638, were regulated by p53 in HCC cell lines under oxidative stress. In addition, clinical investigation revealed that these four miRNAs might be involved in oxidative stress response by targeting oxidative stress-related genes in HCC tissues. Kaplan-Meier analysis showed that these four miRNAs were associated with patients' overall survival. In conclusion, we identified four oxidative stress-responsive miRNAs, which were regulated by p53-dependent (miR-34a-5p and miR-1915-3p) and p53-independent pathway (miR-150-3p and miR-638). These four miRNAs may offer new strategy for HCC diagnosis and prognosis.

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

    PubMed

    Bian, Chen; Xu, Tongda; Zhu, Hong; Pan, Defeng; Liu, Yang; Luo, Yuanyuan; Wu, Pei; Li, Dongye

    2015-01-01

    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.

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

    PubMed Central

    Zhu, Hong; Pan, Defeng; Liu, Yang; Luo, Yuanyuan; Wu, Pei; Li, Dongye

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression

  19. Dysregulation of serum microRNA-574-3p and its clinical significance in hepatocellular carcinoma.

    PubMed

    Shen, Xianjuan; Xue, Yajing; Cong, Hui; Wang, Xudong; Ju, Shaoqing

    2018-07-01

    Objectives To explore microRNA-574-3p expression in serum of patients with hepatocellular carcinoma and investigate correlations between serum microRNA-574-3p expression and the development and prognosis of hepatocellular carcinoma. Design and methods Serum samples were collected from 70 patients with primary hepatocellular carcinoma, 40 patients with cirrhosis and 45 healthy controls. Serum microRNA-574-3p expression levels were detected by real-time quantitative polymerase chain reaction. The linearity, specificity and reproducibility were evaluated. In addition, the diagnostic value of microRNA-574-3p and its correlations with clinicopathologic features were assessed. Results The relative expression of microRNA-574-3p in hepatocellular carcinoma patients, cirrhosis patients and healthy controls was 2.306 (1.801-3.130), 1.362 (0.994-1.665) and 1.263 (0.765-1.723), respectively, indicating that it was significantly higher in hepatocellular carcinoma patients than that in the other two groups ( U = 439.5, 514.5, both P < 0.0001) and was significantly correlated with hepatitis B virus DNA copies ( U = 383.0, P = 0.018). In hepatitis B virus-positive hepatocellular carcinoma patients, the relative expression of microRNA-574-3p was significantly correlated with hepatitis B virus DNA concentration ( r = 0.348, P = 0.022). Compared with healthy control group, AUC ROC of serum microRNA-574-3p in hepatocellular carcinoma group was 0.837 with 95% CI: 0.763-0.910. Combining microRNA-574-3p, AFU and alpha-fetoprotein together, the sensitivity was highest compared with other markers alone or combined. Conclusions The relative expression of serum microRNA-574-3p in hepatocellular carcinoma patients was significantly higher than that in cirrhosis patients and healthy controls, and it may be an important biomarker in the auxiliary diagnosis of hepatocellular carcinoma.

  20. Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p.

    PubMed

    Meng, Qiang; Yang, Bao-Ying; Liu, Bei; Yang, Ji-Xue; Sun, Yang

    2018-05-01

    Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

  1. A tumor suppressor locus within 3p14-p12 mediates rapid cell death of renal cell carcinoma in vivo.

    PubMed Central

    Sanchez, Y; el-Naggar, A; Pathak, S; Killary, A M

    1994-01-01

    High frequency loss of alleles and cytogenetic aberrations on the short arm of chromosome 3 have been documented in renal cell carcinoma (RCC). Potentially, three distinct regions on 3p could encode tumor suppressor genes involved in the genesis of this cancer. We report that the introduction of a centric fragment of 3p, encompassing 3p14-q11, into a highly malignant RCC cell line resulted in a dramatic suppression of tumor growth in athymic nude mice. Another defined deletion hybrid contained the region 3p12-q24 of the introduced human chromosome and failed to suppress tumorigenicity. These data functionally define a tumor suppressor locus, nonpapillary renal carcinoma-1 (NRC-1), within 3p14-p12, the most proximal region of high frequency allele loss in sporadic RCC as well as the region containing the translocation breakpoint in familial RCC. Furthermore, we provide functional evidence that NRC-1 controls the growth of RCC cells by inducing rapid cell death in vivo. Images PMID:8159756

  2. Regulation of Cell Diameter, For3p Localization, and Cell Symmetry by Fission Yeast Rho-GAP Rga4p

    PubMed Central

    Das, Maitreyi; Wiley, David J.; Medina, Saskia; Vincent, Helen A.; Larrea, Michelle; Oriolo, Andrea

    2007-01-01

    Control of cellular dimensions and cell symmetry are critical for development and differentiation. Here we provide evidence that the putative Rho-GAP Rga4p of Schizosaccharomyces pombe controls cellular dimensions. rga4Δ cells are wider in diameter and shorter in length, whereas Rga4p overexpression leads to reduced diameter of the growing cell tip. Consistent with a negative role in cell growth control, Rga4p protein localizes to the cell sides in a “corset” pattern, and to the nongrowing cell tips. Additionally, rga4Δ cells show an altered growth pattern similar to that observed in mutants of the formin homology protein For3p. Consistent with these observations, Rga4p is required for normal localization of For3p and for normal distribution of the actin cytoskeleton. We show that different domains of the Rga4p protein mediate diverse morphological functions. The C-terminal GAP domain mediates For3p localization to the cell tips and maintains cell diameter. Conversely, overexpression of the N-terminal LIM homology domain of Rga4p promotes actin cable formation in a For3p-dependent manner. Our studies indicate that Rga4p functionally interacts with For3p and has a novel function in the control of cell diameter and cell growth. PMID:17377067

  3. Fine-structure relaxation of O(3P) induced by collisions with He, H and H2

    NASA Astrophysics Data System (ADS)

    Lique, F.; Kłos, J.; Alexander, M. H.; Le Picard, S. D.; Dagdigian, P. J.

    2018-02-01

    The excitation of fine-structure levels of O(3P) by collisions is an important cooling process in the interstellar medium (ISM). We investigate here spin-orbit (de-)excitation of O(3Pj, j = 0, 1, 2) induced by collisions with He, H and H2 based on quantum scattering calculations of the relevant rate coefficients in the 10-1000 K temperature range. The underlying potential energy surfaces are derived from highly correlated abinitio calculations. Significant differences were found with the rate coefficients currently used in astrophysical applications. In particular, our new rate coefficients for collisions with H are up to a factor of 5 lower. Radiative transfer computations allow the assessment of the astrophysical impact of these new rate coefficients. In the case of molecular clouds, the new data are found to increase slightly the flux of the 3P1 → 3P2, while decreasing the flux of the 3P0 → 3P1 line. In the case of atomic clouds, the flux of both lines is predicted to decrease. The new rate coefficients are expected to impact significantly the modelling of cooling in astrophysical environments while also allowing new insights into oxygen chemistry in the ISM.

  4. miR-8-3p regulates mitoferrin in the testes of Bactrocera dorsalis to ensure normal spermatogenesis

    PubMed Central

    Tariq, Kaleem; Metzendorf, Christoph; Peng, Wei; Sohail, Summar; Zhang, Hongyu

    2016-01-01

    Genetics-enhanced sterile insect techniques (SIT) are promising novel approaches to control Bactrocera dorsalis, the most destructive horticultural pest in East Asia and the Pacific region. To identify novel genetic agents to alter male fertility of B. dorsalis, previous studies investigated miRNA expression in testes of B. dorsalis. One miRNA, miR-8-3p was predicted to bind the 3′UTR of putative B. dorsalis mitoferrin (bmfrn). The ortholog of bmfrn in D. melanogaster is essential for male fertility. Here we show that bmfrn has all conserved amino acid residues of known mitoferrins and is most abundantly expressed in B. dorsalis testes, making miR-8-3p and mitoferrin candidates for genetics-enhanced SIT. Furthermore, using a dual-luciferase reporter system, we show in HeLa cells that miR-8-3p interacts with the 3′UTR of bmfrn. Dietary treatments of adult male flies with miR-8-3p mimic, antagomiR, or bmfrn dsRNA, altered mitoferrin expression in the testes and resulted in reduced male reproductive capacity due to reduced numbers and viability of spermatozoa. We show for the first time that a mitoferrin is regulated by a miRNA and we demonstrate miR-8-3p as well as bmfrn dsRNA to be promising novel agents that could be used for genetics-enhanced SIT. PMID:26932747

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

    PubMed

    Shen, Shu; Tobery, Cynthia E; Rose, Mark D

    2009-05-01

    Nuclear membrane fusion is the last step in the mating pathway of the yeast Saccharomyces cerevisiae. We adapted a bioinformatics approach to identify putative pheromone-induced membrane proteins potentially required for nuclear membrane fusion. One protein, Prm3p, was found to be required for nuclear membrane fusion; disruption of PRM3 caused a strong bilateral defect, in which nuclear congression was completed but fusion did not occur. Prm3p was localized to the nuclear envelope in pheromone-responding cells, with significant colocalization with the spindle pole body in zygotes. A previous report, using a truncated protein, claimed that Prm3p is localized to the inner nuclear envelope. Based on biochemistry, immunoelectron microscopy and live cell microscopy, we find that functional Prm3p is a peripheral membrane protein exposed on the cytoplasmic face of the outer nuclear envelope. In support of this, mutations in a putative nuclear localization sequence had no effect on full-length protein function or localization. In contrast, point mutations and deletions in the highly conserved hydrophobic carboxy-terminal domain disrupted both protein function and localization. Genetic analysis, colocalization, and biochemical experiments indicate that Prm3p interacts directly with Kar5p, suggesting that nuclear membrane fusion is mediated by a protein complex.

  6. The Sin3p PAH Domains Provide Separate Functions Repressing Meiotic Gene Transcription in Saccharomyces cerevisiae ▿

    PubMed Central

    Mallory, Michael J.; Law, Michael J.; Buckingham, Lela E.; Strich, Randy

    2010-01-01

    Meiotic genes in budding yeast are repressed during vegetative growth but are transiently induced during specific stages of meiosis. Sin3p represses the early meiotic gene (EMG) by bridging the DNA binding protein Ume6p to the histone deacetylase Rpd3p. Sin3p contains four paired amphipathic helix (PAH) domains, one of which (PAH3) is required for repressing several genes expressed during mitotic cell division. This report examines the roles of the PAH domains in mediating EMG repression during mitotic cell division and following meiotic induction. PAH2 and PAH3 are required for mitotic EMG repression, while electrophoretic mobility shift assays indicate that only PAH2 is required for stable Ume6p-promoter interaction. Unlike mitotic repression, reestablishing EMG repression following transient meiotic induction requires PAH3 and PAH4. In addition, the role of Sin3p in reestablishing repression is expanded to include additional loci that it does not control during vegetative growth. These findings indicate that mitotic and postinduction EMG repressions are mediated by two separate systems that utilize different Sin3p domains. PMID:20971827

  7. Double-stranded DNA-dependent ATPase Irc3p is directly involved in mitochondrial genome maintenance

    PubMed Central

    Sedman, Tiina; Gaidutšik, Ilja; Villemson, Karin; Hou, YingJian; Sedman, Juhan

    2014-01-01

    Nucleic acid-dependent ATPases are involved in nearly all aspects of DNA and RNA metabolism. Previous studies have described a number of mitochondrial helicases. However, double-stranded DNA-dependent ATPases, including translocases or enzymes remodeling DNA-protein complexes, have not been identified in mitochondria of the yeast Saccharomyces cerevisae. Here, we demonstrate that Irc3p is a mitochondrial double-stranded DNA-dependent ATPase of the Superfamily II. In contrast to the other mitochondrial Superfamily II enzymes Mss116p, Suv3p and Mrh4p, which are RNA helicases, Irc3p has a direct role in mitochondrial DNA (mtDNA) maintenance. Specific Irc3p-dependent mtDNA metabolic intermediates can be detected, including high levels of double-stranded DNA breaks that accumulate in irc3Δ mutants. irc3Δ-related topology changes in rho- mtDNA can be reversed by the deletion of mitochondrial RNA polymerase RPO41, suggesting that Irc3p counterbalances adverse effects of transcription on mitochondrial genome stability. PMID:25389272

  8. miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B.

    PubMed

    Sun, Feng; Yu, Mengchao; Yu, Jing; Liu, Zhijian; Zhou, Xinyan; Liu, Yanqing; Ge, Xiaolong; Gao, Haidong; Li, Mei; Jiang, Xiaohong; Liu, Song; Chen, Xi; Guan, Wenxian

    2018-05-09

    Gastric cancer (GC) is one of the most common malignant tumors and peritoneal metastasis is the primary cause for advanced GC's mortality. Protein-tyrosine phosphatase 1B (PTP1B) functions as an oncogene and involves in carcinogenesis and cancer dissemination. However, the function and regulation of PTP1B in GC remain poorly understood. In this study, we found that PTP1B was upregulated in GC tissues and overexpression of PTP1B in vitro promoted cell migration and prevented apoptosis. Then, we predicted that PTP1B was a target of miR-338-3p and we revealed an inverse correlation between miR-338-3p levels and PTP1B protein levels in GC tissues. Next, we verified that PTP1B was inhibited by miR-338-3p via direct targeting to its 3'-untranslated regions. Moreover, overexpression of miR-338-3p in vitro attenuated GC cell migration and promoted apoptosis, and these effects could be partially reversed by reintroduction of PTP1B. Finally, we established an orthotopic xenograft model and a peritoneal dissemination model of GC to demonstrate that miR-338-3p restrained tumor growth and dissemination in vivo by targeting PTP1B. Taken together, our results highlight that PTP1B is an oncogene and is negatively regulated by miR-338-3p in GC, which may provide new insights into novel molecular therapeutic targets for GC.

  9. Spectroscopic characterization and O2 reactivity of the trinuclear Cu cluster of mutants of the multicopper oxidase Fet3p.

    PubMed

    Palmer, Amy E; Quintanar, Liliana; Severance, Scott; Wang, Tzu-Pin; Kosman, Daniel J; Solomon, Edward I

    2002-05-21

    Fet3p is a multicopper oxidase that uses four copper ions (one type 1, one type 2, and one type 3 binuclear site) to couple substrate oxidation to the reduction of O(2) to H(2)O. The type 1 Cu site shuttles electrons between the substrate and the type 2/type 3 Cu sites which form a trinuclear Cu cluster that is the active site for O(2) reduction. This study extends the spectroscopic and reactivity studies that have been conducted with type 1-substituted Hg (T1Hg) laccase to Fet3p and a mutant of Fet3p in which the trinuclear Cu cluster is perturbed. To examine the reaction between the trinuclear Cu cluster and O(2), the type 1 Cu Cys(484) was mutated to Ser, resulting in a type 1-depleted (T1D) form of the enzyme. Additional His to Gln mutations were made at the trinuclear cluster to further probe specific contributions to reactivity. One of these mutants (His(126)Gln) produces the first stable but perturbed trinuclear Cu cluster (T1DT3' Fet3p). Spectroscopic characterization (absorption, circular dichroism, magnetic circular dichroism, and electron paramagnetic resonance) of the resting trinuclear sites in T1D and T1DT3' Fet3p reveal that the His(126)Gln mutation changes the electronic structure of both the type 3 and type 2 Cu sites. The trinuclear clusters in T1D and T1DT3' Fet3p react with O(2) to produce peroxide intermediates analogous to that observed in T1Hg laccase. Spectroscopic data on the peroxide intermediates in the three forms provide further insight into the structure of this intermediate. In T1D Fet3p, the decay of this peroxide intermediate is pH-dependent, and the rate of decay is 10-fold higher at low pH. In T1DT3' Fet3p, the decay of the peroxide intermediate is pH-independent and is slow at all pH's. This change in the pH dependence provides new insight into the mechanism of intermediate decay involving reductive cleavage of the O-O bond.

  10. Dimensionality of superconductivity in the layered organic material EtMe3P [Pd(dmit)2] 2 under pressure

    NASA Astrophysics Data System (ADS)

    Yamamoto, R.; Yanagita, Y.; Namaizawa, T.; Komuro, S.; Furukawa, T.; Itou, T.; Kato, R.

    2018-06-01

    We measured the ac magnetic susceptibility for the layered organic superconductor EtMe3P [Pd(dmit)2] 2 under pressure with a dc magnetic field applied perpendicular to the ac field. We investigated the dc field dependence of the ac susceptibility in detail and concluded that the superconductivity in EtMe3P [Pd(dmit)2] 2 is an anisotropic three-dimensional superconductivity even at low temperatures, which contrasts with the large majority of other correlated electron layered superconductors such as high-Tc cuprate and κ -(ET) 2X systems.

  11. miR-199a-3p regulates brown adipocyte differentiation through mTOR signaling pathway.

    PubMed

    Gao, Yao; Cao, Yan; Cui, Xianwei; Wang, Xingyun; Zhou, Yahui; Huang, Fangyan; Wang, Xing; Wen, Juan; Xie, Kaipeng; Xu, Pengfei; Guo, Xirong; You, Lianghui; Ji, Chenbo

    2018-05-10

    Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans. Conversely, its level was induced during the differentiation course of human white pre-adipocytes derived from visceral fat. miR-199a-3p expression was relatively abundant in interscapular BAT (iBAT) and differentially regulated in the activated and aging BAT in mice. Additionally, miR-199a-3p expression level in human brown adipocytes was observed decreased upon thermogenic activation and increased by aging-related stimuli. Using primary pre-adipocytes, miR-199a-3p over-expression was capable of attenuating lipid accumulation and adipogenic gene expression as well as impairing brown adipocytes' metabolic characteristics as revealed by decreased mitochondrial DNA content and respiration. Suppression of miR-199a-3p by a locked nucleic acid (LNA) modified-anti-miR led to increased differentiation and thermogenesis in human brown adipocytes. By combining target prediction and examination, we identified mechanistic target of rapamycin kinase (mTOR) as a direct target of miR-199a-3p that affected brown adipogenesis and thermogenesis. Our results point to a novel role for miR-199a-3p and its downstream effector mTOR in human brown adipocyte differentiation and maintenance of thermogenic characteristics, which can be manipulated as therapeutic targets against obesity and its related metabolic disorders. Copyright © 2018. Published by Elsevier B.V.

  12. High-resolution spectrum of the second member in the ( πu3 p) 4 ( πg3 p) ( πunp) Rydberg series of 32S 2

    NASA Astrophysics Data System (ADS)

    Ramanamma Chaudhri, Y. V.; Mahajan, C. G.

    1991-02-01

    High-resolution spectra of S 2 in the region of the E and F- X progressions have been used to carry out the rotational analyses of the bands at 65 869, 66 666, 65 978, 66 380, and 67 094 cm -1. The first two bands form a single progression and have been attributed to the transition E1 u( {1}/{2}, {1}/{2}) ← X0 g+. The bands at 65 978 and 66 380 cm -1 are shown to belong to the electronic transitions E'0 u+( {1}/{2}, {1}/{2}) ← X0 g+ and F1 u( {3}/{2}, {1}/{2}) ← X0 g+, respectively. The group of states E, E', and F constitutes the second member ( n = 5) of the Rydberg series ( πu3 p) 4 ( πu3 p) ( πunp) whose first member ( n = 4) is the state 3Σ u-. The band at 67 094 cm -1 has been assigned to the transition D'1 u ← X0 g+ which, when considered in the light of the state D3Π u, seems to form a second member of the Rydberg series ( πu3 p) 4 ( πg3 p) ( σunp). The vibrational and rotational constants of these electronic states have also been derived.

  13. Etude des mécanismes d'ionisation de H{2}O par interaction He^{*}(2 ^1S, 2 ^3S)/Ne^{*}(^3P{0}, ^3P{2})+H{2}O

    NASA Astrophysics Data System (ADS)

    Le Nadan, André; Sinou, Guillaume; Tuffin, Firmin

    1993-06-01

    Experimental observations of Penning ionisation of H{2}O by the helium metastables 21S and 23S and by the neon metastables ^3P{0} and ^3P{2} are reported. The kinetic energies of the ions created during the collision process (both parent and fragment) are analysed. Certain particularities of the experimental results are explained by involving the hypothesis of transfers of vibrational energy to kinetic energy. Furthermore, the forms of the energy distributions of the fragment ions are explained by th predissociation of the ^2B{2} state of H{2}O+. Nous avons étudié l'ionisation Penning de H{2}O par des métastables 21S et 23S de l'hélium, ainsi que ^3P{0} et ^3P{2} du néon. Nous avons analysé l'énergie cinétique des ions créés au cours de la collision (parents et fragments). Afin d'interpréter certaines particularités expérimentales, l'hypothèse de transferts d'énergie de vibration en énergie cinétique est proposées. Par ailleurs, les caractéristiques des distributions en énergie des ions fragments sont expliquées par la prédissociation de l'état ^2B{2} de H{2}O+.

  14. Physical and functional mapping of a tumor suppressor locus for renal cell carcinoma within chromosome 3p12.

    PubMed

    Lott, S T; Lovell, M; Naylor, S L; Killary, A M

    1998-08-15

    Using a functional genetic approach, we previously identified a novel genetic locus, NRC-1 (Nonpapillary Renal Cell Carcinoma 1), that mediated tumor suppression and rapid cell death of renal cell carcinoma (RCC) cells in vivo. For these experiments, a defined subchromosomal fragment of human chromosome 3p was transferred into a sporadic RCC cell line via microcell fusion, and microcell hybrid clones were tested for tumorigenicity in vivo. The results indicated functional evidence for a novel tumor suppressor locus within the 3p14-p12 interval known to contain the most common fragile site of the human genome (FRA3B), the FHIT gene, and the breakpoint region associated with the familial form of RCC. We now report the physical mapping of the NRC-1 critical region by detailed microsatellite analyses of novel microcell hybrid clones containing transferred fragments of chromosome 3p in the RCC cell background that were phenotypically suppressed or unsuppressed for tumorigenicity in vivo. The results limit the region containing the tumor suppressor locus within chromosome 3p12. The FHIT gene, FRA3B, and the familial RCC breakpoint region were excluded from the NRC-1 critical region. Furthermore, the NRC-1 locus falls within a well-characterized homozygous deletion region of 5-7 Mb associated with a small cell lung carcinoma cell line, U2020, suggesting that a more general tumor suppressor gene may reside in this region.

  15. Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression.

    PubMed

    Chen, Yan; Huang, Shai; Wu, Bo; Fang, Jiankai; Zhu, Minsheng; Sun, Li; Zhang, Lifeng; Zhang, Yongsheng; Sun, Maomin; Guo, Lingling; Wang, Shouli

    2017-07-25

    Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

  16. Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive Disorder

    PubMed Central

    Roy, Bhaskar; Dunbar, Michael; Shelton, Richard C; Dwivedi, Yogesh

    2017-01-01

    Major depressive disorder (MDD) is predicted to be the second leading cause of global disease burden by 2030. A large number of MDD patients do not respond to the currently available medication because of its poorly understood etiology. Recently, studies of microRNAs (miRNAs), which act as a molecular switch of gene expression, have shown promise in identifying a molecular network that could provide significant clues to various psychiatric illnesses. Using an in vitro system, a rodent depression model, and a human postmortem brain, we investigated the role of a brain-enriched, neuron-specific miRNA, miR-124-3p, whose expression is highly dysregulated in stressed rodents, and identified a set of target genes involved in stress response and neural plasticity. We also found that miR-124-3p is epigenetically regulated and its interaction with the RNA-induced silencing complex (RISC) is compromised in MDD. Using blood serum, we found similar dysregulation of miR-124-3p in antidepressant-free MDD subjects. Altogether, our study demonstrates potential contribution of miR-124-3p in the pathophysiology of MDD and suggests that this miRNA may serve as a novel target for drug development and a biomarker for MDD pathogenesis. PMID:27577603

  17. APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p.

    PubMed

    Wang, Kun; Liu, Cui-Yun; Zhou, Lu-Yu; Wang, Jian-Xun; Wang, Man; Zhao, Bing; Zhao, Wen-Ke; Xu, Shi-Jun; Fan, Li-Hua; Zhang, Xiao-Jie; Feng, Chang; Wang, Chao-Qun; Zhao, Yan-Fang; Li, Pei-Feng

    2015-04-10

    The abnormal autophagy is associated with a variety of cardiovascular diseases. Long noncoding RNAs (lncRNAs) are emerging as new factors in gene regulation, but how lncRNAs operate in the regulation of autophagy in the heart is unclear. Here we report that a long noncoding RNA, named autophagy promoting factor (APF), can regulate autophagic cell death by targeting miR-188-3p and ATG7. The results show that miR-188-3p suppresses autophagy and myocardial infarction by targeting ATG7. Further, we find that APF lncRNA regulates miR-188-3p, and thus affects ATG7 expression, autophagic cell death and myocardial infarction. Our present study reveals a novel regulating model of autophagic programme, which comprises APF, miR-188-3p and ATG7 in the heart. Modulation of their levels may serve as potential targets and diagnostic tools for novel therapeutic strategies of myocardial infarction and heart failure.

  18. STX--Fortran-4 program for estimates of tree populations from 3P sample-tree-measurements

    Treesearch

    L. R. Grosenbaugh

    1967-01-01

    Describes how to use an improved and greatly expanded version of an earlier computer program (1964) that converts dendrometer measurements of 3P-sample trees to population values in terms of whatever units user desires. Many new options are available, including that of obtaining a product-yield and appraisal report based on regression coefficients supplied by user....

  19. MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway

    PubMed Central

    Xu, Hong; Wu, Yuting; Li, Li; Yuan, Weifeng; Zhang, Deming; Yan, Qitao; Guo, Zhenhui; Huang, Wenjie

    2017-01-01

    Objectives COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA). MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders. Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD. Materials and methods miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats. The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay. Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene. Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells. Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed. Results COPD rat model was successfully induced by smoke inhalation. Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene. In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2. In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition. Conclusion Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients. PMID:28243080

  20. Simultaneous retrieval of daytime O(3P) and O3 concentrations in the altitude interval 80 - 100 km.

    NASA Astrophysics Data System (ADS)

    Yankovsky, Valentine; Manuilova, Rada; Koval, Andrey

    2017-04-01

    We propose methods of simultaneously independent retrievals of the key components of Mesosphere and Lower Thermosphere (MLT) [O3] and [O(3P)]. The altitude profile of ozone concentration, [O3], can be measured by direct method of the measurement of absorbing radiation from the Sun or the stars in the UV range of the spectrum. However, this method is most often realized in twilight. Retrieval of daytime [O3] depends on a prior information about the O(3P) altitude profile. Vice versa, atomic oxygen concentration, [O(3P)], is usually retrieved from the measured values of [O3]. The problem of independent and simultaneous retrieval of [O3] and [O(3P)] can be solved by using individual proxy for each of the target component. Using a sensitivity study and uncertainty analysis of the contemporary model of O3 and O2 photolysis in the MLT, YM2011, we determined that populations of three excited electronic-vibrational levels O2(b1, v = 0, 1, 2) and of metastable O(1D) atom depend on [O(3P)] and [O3] concentrations. For [O(3P)] retrieval the following transitions should be used: O2(b1, v') -> O2(X3, v") which produce emissions: (a) at 780.4 nm in the band (v' = 2, v" = 2) and at 697.0 nm in the band (2, 1) with the uncertainty of retrieval smaller than 30% for the whole altitude range 80 - 100 km; (b) at 771.0 nm in the band (1, 1), 688.4 nm in the band (1, 0) and at 874.4 nm in the band (1, 2) with the uncertainty of retrieval about 30% above 90 km. For [O3] retrieval the following transitions should be used: O2(b1, v') -> O2(X3, v") which produce emissions: (c) at 762.1 nm in the band (0, 0) and at 864.7 nm in the band (0, 1) with the uncertainty of retrieval 20 - 25% for the altitude range 80 - 85 km and smaller than 20% in the interval 85 - 95 km; (d) in the line of O(1D) 630.0 nm with the uncertainty of retrieval 10 - 15% in the interval 80 - 95 km. Above 95 km the uncertainty of [O3] retrieval grows and reaches up to 80% at 100 km for all suggested proxies. For

  1. Perfluorooctane Sulfonate Disturbs Nanog Expression through miR-490-3p in Mouse Embryonic Stem Cells

    PubMed Central

    Chen, Minjian; Han, Xiumei; Du, Guizhen; Ji, Xiaoli; Chang, Chunxin; Rehan, Virender K.; Wang, Xinru; Xia, Yankai

    2013-01-01

    Perfluorooctane sulfonate (PFOS) poses potential risks to reproduction and development. Mouse embryonic stem cells (mESCs) are ideal models for developmental toxicity testing of environmental contaminants in vitro. However, the mechanism by which PFOS affects early embryonic development is still unclear. In this study, mESCs were exposed to PFOS for 24 h, and then general cytotoxicity and pluripotency were evaluated. MTT assay showed that neither PFOS (0.2 µM, 2 µM, 20 µM, and 200 µM) nor control medium (0.1% DMSO) treatments affected cell viability. Furthermore, there were no significant differences in cell cycle and apoptosis between the PFOS treatment and control groups. However, we found that the mRNA and protein levels of pluripotency markers (Sox2, Nanog) in mESCs were significantly decreased following exposure to PFOS for 24 h, while there were no significant changes in the mRNA and protein levels of Oct4. Accordingly, the expression levels of miR-145 and miR-490-3p, which can regulate Sox2 and Nanog expressions were significantly increased. Chrm2, the host gene of miR-490-3p, was positively associated with miR-490-3p expression after PFOS exposure. Dual luciferase reporter assay suggests that miR-490-3p directly targets Nanog. These results suggest that PFOS can disturb the expression of pluripotency factors in mESCs, while miR-145 and miR-490-3p play key roles in modulating this effect. PMID:24098361

  2. MiR-30a-3p Negatively Regulates BAFF Synthesis in Systemic Sclerosis and Rheumatoid Arthritis Fibroblasts

    PubMed Central

    Philippe, Lucas; Gong, Ya-Zhuo; Bahram, Seiamak; Cetin, Semih; Pfeffer, Sébastien; Gottenberg, Jacques-Eric; Wachsmann, Dominique; Georgel, Philippe; Sibilia, Jean

    2014-01-01

    We evaluated micro (mi) RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i) synovial fibroblasts (FLS) isolated from healthy controls (N) or Rheumatoid Arthritis (RA) patients; (ii) human dermal fibroblasts (HDF) isolated from healthy controls (N) or Systemic Sclerosis (SSc) patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C) or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C) or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C)- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C)- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc. PMID:25360821

  3. MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ.

    PubMed

    Wang, Dan; He, Sirong; Liu, Bicui; Liu, Chuntao

    2018-05-16

    Activation of alveolar macrophages (AMs) and the release of cytokines play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms of AM activation. miRNAs have recently emerged as key regulators of inflammation and as mediators of macrophage activation and polarization. We identified potential miRNAs related to AM activation using miRNA microarray analysis, which showed that miR-27-3p expression was up-regulated in AMs and the lung tissues of mice exposed to cigarette smoke (CS)/lipopolysaccharide (LPS), and found that miR-27-3p regulated proinflammatory cytokine production and AM polarization depending on TLR2/4 intracellular signaling in AMs. We also found that miR-27-3p controlled TLR2/4 signaling in AMs via targetting the 3'-UTR sequences of peroxisome proliferator-activated receptor γ (PPARγ) and inhibiting PPARγ activation. Moreover, we found that PPARγ activation not only inhibited CS/LPS-induced TLR2/4 expression and miR-27-3p -mediated TLR2/4 signaling cascades involving the nuclear factor-κB (NF-κB), c-Jun NH 2 -terminal kinase (JNK)/p38, and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways in AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation. Our study revealed that miR-27-3p mediated AM activation by the inhibition of PPARγ activation and sensitization of TLR signaling. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  4. Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients.

    PubMed

    Ghanbari, Reza; Rezasoltani, Sama; Hashemi, Javad; Mohamadkhani, Ashraf; Tahmasebifar, Arash; Arefian, Ehsan; Mobarra, Naser; Asadi, Jahanbakhsh; Nazemalhosseini Mojarad, Ehsan; Yazdani, Yaghoub; Knuutila, Sakari; Malekzadeh, Reza

    2017-02-01

    Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Early diagnosis of this neoplasm is critical and may reduce patients' mortality. MicroRNAs are small non-coding RNA molecules whose expression pattern can be altered in various diseases such as CRC. In this study, we evaluated the expression levels of miR-142-3p, miR-26a-5p (their reduced expression in plasma samples of CRC patients was previously confirmed), miR-4478 and miR-1295-3p (their reduced expression in stool samples of CRC patients was previously confirmed) in tissue samples of CRC patients in comparison to healthy subjects. To achieve this purpose, total RNA including small RNA was extracted from 53 CRC and 35 normal subjects' Formalin-fixed, Paraffin-embedded (FFPE) tissue samples using the miRNeasy FFPE Mini Kit. The expression levels of these four selected miRNAs were measured using quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). We found that the expression levels of miR-4478 and miR-1295b-3p (two previously down-regulated fecal miRNAs) were significantly decreased in FFPE samples of CRC patients compared to healthy controls. On the other hand, no significant differences were seen in expression levels of miR-142-3p and miR-26a-5p (two previously down-regulated circulating miRNAs) in FFPE samples between these two groups. Regarding current findings, it may be concluded that to diagnose CRC patients based on the miRNAs approach, stool samples are more likely preferable to plasma samples; nevertheless, additional studies with more samples are needed to confirm the results.

  5. Inhibition of miR-141-3p Ameliorates the Negative Effects of Poststroke Social Isolation in Aged Mice.

    PubMed

    Verma, Rajkumar; Ritzel, Rodney M; Harris, Nia M; Lee, Juneyoung; Kim, TaeHee; Pandi, Gopal; Vemuganti, Raghu; McCullough, Louise D

    2018-06-04

    Social isolation increases mortality and impairs recovery after stroke in clinical populations. These detrimental effects have been recapitulated in animal models, although the exact mechanism mediating these effects remains unclear. Dysregulation of microRNAs (miRNAs) occurs in both strokes as well as after social isolation, which trigger changes in many downstream genes. We hypothesized that miRNA regulation is involved in the detrimental effects of poststroke social isolation in aged animals. We pair-housed 18-month-old C57BL/6 male mice for 2 weeks before a 60-minute right middle cerebral artery occlusion or sham surgery and then randomly assigned mice to isolation or continued pair housing immediately after surgery. We euthanized mice either at 3, 7, or 15 days after surgery and isolated the perilesional frontal cortex for whole microRNAome analysis. In an additional cohort, we treated mice 1 day after stroke onset with an in vivo-ready antagomiR-141 for 3 days. Using whole microRNAome analysis of 752 miRNAs, we identified miR-141-3p as a unique miRNA that was significantly upregulated in isolated mice in a time-dependent manner up to 2 weeks after stroke. Posttreatment with an antagomiR-141-3p reduced the postisolation-induced increase in miR-141-3p to levels almost equal to those of pair-housed stroke controls. This treatment significantly reduced mortality (by 21%) and normalized infarct volume and neurological scores in poststroke-isolated mice. Quantitative PCR analysis revealed a significant upregulation of Tgfβr1 (transforming growth factor beta receptor 1, a direct target of miR-141-3p) and Igf-1 (insulin-like growth factor 1) mRNA after treatment with antagomiR. Treatment also increased the expression of other pleiotropic cytokines such as Il-6 (interleukin 6) and Tnf-α (tumor necrosis factor-α), an indirect or secondary target) in brain tissue. miR-141-3p is increased with poststroke isolation. Inhibition of miR-141-3p improved mortality

  6. Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma.

    PubMed

    Dong, Zhen; Lei, Qian; Yang, Rui; Zhu, Shunqin; Ke, Xiao-Xue; Yang, Liqun; Cui, Hongjuan; Yi, Liang

    2017-06-06

    Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored. Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry. Cytochrome c release was detected by using immunofluorescence. Mitochondrial membrane potential (MMP, ΔΨm) loss was stained by JC-1 and detected by immunofluorescence or flow cytometry. Apoptosis antibody array and microRNA microarray were performed to seek the potential regulators of NTSR1 inhibition-induced apoptosis. Interaction between let-7a-3p and Bcl-w 3'UTR was evaluated by using luciferase assay. SR48692 induced massive apoptosis, which was related to mitochondrial cytochrome c release and MMP loss. Knockdown of NTSR1 induced slight apoptosis and significant MMP loss. In addition, NTSR1 inhibition sensitised glioblastoma cells to actinomycin D or doxorubicin-induced apoptosis. Consistently, NTSR1 inhibition-induced mitochondrial apoptosis was accompanied by downregulation of Bcl-w and Bcl-2. Restoration of Bcl-w partly rescued NTSR1 deficiency-induced apoptosis. In addition, NTSR1 deficiency promoted higher let-7a-3p expression and inhibition let-7a-3p partly rescued NTSR1 inhibition-induced apoptosis. In addition, let-7a-3p inhibition promoted 3'UTR activities of Bcl-w and the expression of c-Myc and LIN28, which were the upstream of let-7a-3p, decreased after NTSR1 inhibition. NTSR1 had an important role in protecting glioblastoma from intrinsic apoptosis via c-Myc/LIN28/let-7a-3p/Bcl-w axis.

  7. miR-148b-3p functions as a tumor suppressor in GISTs by directly targeting KIT.

    PubMed

    Wang, Yu; Li, Jun; Kuang, Dong; Wang, Xiaoyan; Zhu, Yuanli; Xu, Sanpeng; Chen, Yaobing; Cheng, Henghui; Zhao, Qiu; Duan, Yaqi; Wang, Guoping

    2018-04-16

    Gain-of-function mutations and overexpression of KIT are characteristic features of gastrointestinal stromal tumor (GIST). Dysregulation in miRNA expression may lead to KIT overexpression and tumorigenesis. miRNA microarray analysis and real-time PCR were used to determine the miRNA expression profiles in a cohort of 69 clinical samples including 50 CD117 IHC+ /KIT mutation GISTs and 19 CD117 IHC- /wild-type GISTs. GO enrichment and KEGG pathway analyses were performed to reveal the predicted targets of the dysregulated miRNAs. Of the dysregulated miRNAs whose expression was inversely correlated with that of KIT miRNAs were predicted by bioinformatics analysis and confirmed by luciferase reporter assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to measure the cell proliferation, cycle arrest and apoptosis. Wound healing and transwell assays were used to evaluate migration and invasion. A xenograft BALB/c nude mouse model was applied to investigate the tumorigenesis in vivo. Western blot and qRT-PCR were used to investigate the protein and mRNA levels of KIT and its downstream effectors including ERK, AKT and STAT3. Of the six miRNAs whose expression was inversely correlated with that of KIT, we found that miR-148b-3p was significantly downregulated in the CD117 IHC+ /KIT mutation GIST cohort. This miRNA was subsequently found to inhibit proliferation, migration and invasion of GIST882 cells. Mechanistically, miR-148b-3p was shown to regulate KIT expression through directly binding to the 3'-UTR of the KIT mRNA. Restoration of miR-148b-3p expression in GIST882 cells led to reduced expression of KIT and the downstream effectors proteins ERK, AKT and STAT3. However, overexpression of KIT reversed the inhibitory effect of miR-148b-3p on cell proliferation, migration and invasion. Furthermore, we found that reduced miR-148b-3p expression correlated with poor overall survival (OS) and disease-free survival (DFS) in GIST patients. miR-148b-3p functions as

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

    PubMed

    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.

  9. Differential cross sections for the electron impact ionization of Ar (3 p) atoms for equal energy final state electrons

    NASA Astrophysics Data System (ADS)

    Purohit, Ghanshyam; Singh, Prithvi

    2017-06-01

    The electron-impact ionization of inert gases for asymmetric final state energy sharing conditions has been studied in detail. However, there have been relatively few studies examining equal energy final state electrons. We report in this communication the results of triple differential cross sections (TDCSs) for electron impact ionization of Ar (3 p) for equal energy sharing of the outgoing electrons. We calculate TDCS in the modified distorted wave Born approximation (DWBA) formalism including post collision interaction (PCI) and polarization potential. We compare the results of our calculation with available measurements [Phys. Rev. A 87, 022712 (2013)]. We study the effect of PCI, target polarization on the trends of TDCS for the single ionization of Ar (3 p) targets.

  10. 174Yb 3P1 level relaxation found via weak magnetic field dependence of collision-induced stimulated photon echo

    NASA Astrophysics Data System (ADS)

    Rubtsova, N. N.; Gol’dort, V. G.; Khvorostov, E. B.; Kochubei, S. A.; Reshetov, V. A.

    2018-06-01

    Collision-induced stimulated photon echo generated at transition was analyzed theoretically and investigated experimentally in the gaseous mixture of ytterbium vapour diluted with a large amount of buffer gas xenon in the presence of a weak longitudinal magnetic field. The inter-combination transition of 174Yb (6s2) 1S(6s6p) 3P1 was used; all experimental parameters were carefully controlled for their correspondence to the broad spectral line conditions. The curve representing the collision-induced stimulated photon echo variations versus a weak magnetic field strength showed very good agreement with the corresponding theoretical curve; this agreement permitted getting the decay rates for 174Yb level 3P1 orientation and alignment in collisions with Xe.

  11. Recombination reactions of 5-eV O(3P) atoms on a MgF2 surface

    NASA Technical Reports Server (NTRS)

    Orient, O. J.; Chutjian, A.; Murad, E.

    1990-01-01

    A source of hyperthermal, ground-state, impurity-free, atomic oxygen of an energy variable in the range 2-100 eV has been developed. Experimental results are presented of emission spectra in the wavelength range 250-850 nm produced by collisions of 5-eV O(3P) atoms with adsorbed NO and CO molecules on a MgF2 surface.

  12. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.

    PubMed

    Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

    2017-05-16

    Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

  13. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma

    PubMed Central

    Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

    2017-01-01

    Background Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients. PMID:28380419

  14. High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma

    PubMed Central

    Wistuba, I I; Maitra, A; Carrasco, R; Tang, M; Troncoso, P; Minna, J D; Gazdar, A F

    2002-01-01

    Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified 3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity. The present study was undertaken to more precisely identify the presence and location of regions of frequent allele loss involving those chromosomes in gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were analysed for PCR-based loss of heterozygosity using 81 microsatellite markers spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We also studied the role of those allele losses in gallbladder carcinoma pathogenesis by examining 45 microdissected normal and dysplastic gallbladder epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers. Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%), and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13 distinct regions undergoing frequent loss of heterozygosity in tumours. Allele losses were frequently detected in normal and dysplastic gallbladder epithelia. There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes. Allele losses were not random and followed a sequence. This study refines several distinct chromosome 3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder carcinoma that will aid in the positional identification of tumour suppressor genes involved in gallbladder carcinoma pathogenesis. British Journal of Cancer (2002) 87, 432–440. doi:10.1038/sj.bjc.6600490 www.bjcancer.com © 2002 Cancer Research UK PMID:12177780

  15. Lifetimes of 3s3p2 J=12,52 levels in Au66+ and Br22+

    NASA Astrophysics Data System (ADS)

    Beck, Donald R.; Norquist, Peggy L.

    2000-04-01

    Relativistic configuration-interaction length and velocity lifetimes have been obtained for 3s3p2 J=1/2, 5/2 levels in Au66+ and Br22+. Results from the two gauges agree well, and we have moderately improved earlier multiconfigurational Dirac-Fock results, as compared to experiment. However, there remains a discrepancy for the Au66+ J=5/2 lifetime, which may be due to satellite spectra associated with 5g and other spectator electrons.

  16. The quenching rate of O(1D) by O(3P). [with data from Visible Airglow experiment on AE satellites

    NASA Technical Reports Server (NTRS)

    Abreu, V. J.; Yee, J. H.; Solomon, S. C.; Dalgarno, A.

    1986-01-01

    The rate coefficient for the quenching of O(1D) by O(3P) has recently been calculated by Yee et al. (1985). Their results indicate that quenching by atomic oxygen should not be ignored in the analysis of the 6300 A emission airglow. Data obtained by the Visible Airglow Experiment on board the AE satellites have been reanalyzed to determine the quenching rate of O(1D) by atomic oxygen. The results of this analysis are presented.

  17. An Evaluation of Law Enforcement Application of the Trafficking Victims Protection Act 3P Strategy from 2003 to 2014

    DTIC Science & Technology

    2016-06-10

    Approved for Public Release; Distribution is Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Human Trafficking ( HT ) is the modern day form of...slavery. In 2000, the United States joined the worldwide efforts and made to the commitment to combat HT with passing of the Trafficking Victims...Protection Act (TVPA). In 2003, they adopted the world approach to combating HT through the 3P paradigm of prevention, protection, and prosecution. Since

  18. miR-4725-3p targeting Stim1 signaling is involved in xanthohumol inhibition of glioma cell invasion.

    PubMed

    Ho, Kuo-Hao; Chang, Cheng-Kuei; Chen, Peng-Hsu; Wang, Yu-Jia; Chang, Wei-Chiao; Chen, Ku-Chung

    2018-05-10

    Glioblastoma multiforme (GBM) is the most common brain tumor in adults. Due to its highly invasive nature, it is not easy to treat, resulting in high mortality rates. Stromal interacting molecule 1 (Stim1) plays important roles in regulating store-operated Ca 2+ entry (SOCE), and controls invasion by cancer cells. However, the mechanisms and functions of Stim1 in glioma progression are still unclear. In this study, we investigated the effects of targeting Stim1 expression on glioma cell invasion. By analyzing profiles of GBM patients from RNA-sequencing data in The Cancer Genome Atlas (TCGA), higher expression levels of STIM1 were correlated with the poor survival. Furthermore, signaling pathways associated with tumor malignancy, including the epithelial-to-mesenchymal transition (EMT), were activated in patients with high STIM1 expression according to gene set enrichment analyses. Higher Stim1 levels were found in glioma cells compared to human astrocytes, and these higher levels enhanced glioma cell invasion. Xanthohumol (XN), a prenylated flavonoid extracted from the hop plant Humulus lupulus L. (Cannabaceae), significantly reduced cell invasion through inhibiting Stim1 expression. From an micro(mi)RNA array analysis, miR-4725-3p was upregulated by XN treatment. Overexpression of miR-4725-3p inhibited glioma cell invasion via directly targeting the 3'-untranslated region of STIM1. The extracellular signal-regulated kinase/c-Fos pathway was also validated to participate in XN-upregulated miR-4725-3p expression according to promoter and chromatin immunoprecipitation assays. These results emphasize that miR-4725-3p-inhibited STIM1 signaling is involved in XN-attenuated glioma cell invasion. These findings may provide insights into novel therapeutic strategies for future glioblastoma therapy and drug development. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Wakefield Simulation of CLIC PETS Structure Using Parallel 3D Finite Element Time-Domain Solver T3P

    SciTech Connect

    Candel, A.; Kabel, A.; Lee, L.

    In recent years, SLAC's Advanced Computations Department (ACD) has developed the parallel 3D Finite Element electromagnetic time-domain code T3P. Higher-order Finite Element methods on conformal unstructured meshes and massively parallel processing allow unprecedented simulation accuracy for wakefield computations and simulations of transient effects in realistic accelerator structures. Applications include simulation of wakefield damping in the Compact Linear Collider (CLIC) power extraction and transfer structure (PETS).

  20. A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth.

    PubMed

    Li, H; Li, J; Su, Y; Fan, Y; Guo, X; Li, L; Su, X; Rong, R; Ying, J; Mo, X; Liu, K; Zhang, Z; Yang, F; Jiang, G; Wang, J; Zhang, Y; Ma, D; Tao, Q; Han, W

    2014-06-12

    Deletion of 3p12-22 is frequent in multiple cancer types, indicating the presence of critical tumor-suppressor genes (TSGs) at this region. We studied a novel candidate TSG, CMTM7, located at the 3p22.3 CMTM-gene cluster, for its tumor-suppressive functions and related mechanisms. The three CMTM genes, CMTM6, 7 and 8, are broadly expressed in human normal adult tissues and normal epithelial cell lines. Only CMTM7 is frequently silenced or downregulated in esophageal and nasopharyngeal cell lines, but uncommon in other carcinoma cell lines. Immunostaining of tissue microarrays for CMTM7 protein showed its downregulation or absence in esophageal, gastric, pancreatic, liver, lung and cervix tumor tissues. Promoter CpG methylation and loss of heterozygosity were both found contributing to CMTM7 downregulation. Ectopic expression of CMTM7 in carcinoma cells inhibits cell proliferation, motility and tumor formation in nude mice, but not in immortalized normal cells, suggesting a tumor inhibitory role of CMTM7. The tumor-suppressive function of CMTM7 is associated with its role in G1/S cell cycle arrest, through upregulating p27 and downregulating cyclin-dependent kinase 2 (CDK2) and 6 (CDK6). Moreover, CMTM7 could promote epidermal growth factor receptor (EGFR) internalization, and further suppress AKT signaling pathway. Thus, our findings suggest that CMTM7 is a novel 3p22 tumor suppressor regulating G1/S transition and EGFR/AKT signaling during tumor pathogenesis.

  1. Nuclear and magnetic supercells in the multiferroic candidate: Pb 3TeMn 3P 2O 14

    DOE PAGES

    Silverstein, Harlyn J.; Huq, Ashfia; Lee, Minseong; ...

    2014-10-18

    Here we report that the dugganites, Te 6+-containing members of the langasite series, have attracted recent interest due to their complex low-temperature magnetic unit cells, magnetodielectric, and potentially multiferroic properties. For Pb 2+-containing dugganites, a large monoclinic supercell was reported and was found to have a profound effect on the low temperature magnetism and spin excitation spectra. Pb 3TeMn 3P 2O 14 is another dugganite previously shown to distort away from the canonical P321 langasite unit cell, although this supercell was never fully solved. We report the full crystal and magnetic structure solution of Pb 3TeMn 3P 2O 14 usingmore » synchrotron x-ray and neutron diffraction data: a large trigonal supercell is observed in this material, which is believed to be the first supercell of its kind in the langasite family. Here, the magnetic structure, high-magnetic field behavior, and dielectric properties of Pb 3TeMn 3P 2O 14 are presented. In addition to showing weak magnetoelectric behavior similar to other langasites, it was found that a phase transition occurs at 3 T near the antiferromagnetic transition temperature.« less

  2. Investigation of the 6 p 2(3 P 0) n p Rydberg series of bismuth by multiphoton excitation

    NASA Astrophysics Data System (ADS)

    Bühler, B.; Cremer, C.; Gerber, G.

    1985-03-01

    Rydberg states of the odd-parity series 6 p 2(3 p 0) n p of BiI are excited by a three-photon process. A two-photon dissociation of Bi2 into excited atomic states followed by a one-photon absorption leads to highly excited atomic Rydberg states up to n = 32. States of the even-parity Rydberg series 6 p 2(3 p 0) nsJ=1/2, ndJ=3/2 and ndJ=5/2 are also observed. In order to avoid the background caused by ionization of the bismuth molecules we performed a two-color excitation with pulsed dye lasers. With this experiment the 6 p 2(3 p 0) npJ=3/2 Rydberg series could be resolved up to n=75. The increasing quantum defect of this series is due to a perturbing state close to the first ionization limit. By a MQDT analysis we obtain the energy of the perturbing state and a value of 58,761.68±0.1 cm-1 for the first ionization limit of atomic bismuth.

  3. Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.

    PubMed

    Degueurce, Gwendoline; D'Errico, Ilenia; Pich, Christine; Ibberson, Mark; Schütz, Frédéric; Montagner, Alexandra; Sgandurra, Marie; Mury, Lionel; Jafari, Paris; Boda, Akash; Meunier, Julien; Rezzonico, Roger; Brembilla, Nicolò Costantino; Hohl, Daniel; Kolios, Antonios; Hofbauer, Günther; Xenarios, Ioannis; Michalik, Liliane

    2016-08-01

    Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  4. Drosophila Mtm and class II PI3K coregulate a PI(3)P pool with cortical and endolysosomal functions.

    PubMed

    Velichkova, Michaella; Juan, Joe; Kadandale, Pavan; Jean, Steve; Ribeiro, Inês; Raman, Vignesh; Stefan, Chris; Kiger, Amy A

    2010-08-09

    Reversible phosphoinositide phosphorylation provides a dynamic membrane code that balances opposing cell functions. However, in vivo regulatory relationships between specific kinases, phosphatases, and phosphoinositide subpools are not clear. We identified myotubularin (mtm), a Drosophila melanogaster MTM1/MTMR2 phosphoinositide phosphatase, as necessary and sufficient for immune cell protrusion formation and recruitment to wounds. Mtm-mediated turnover of endosomal phosphatidylinositol 3-phosphate (PI(3)P) pools generated by both class II and III phosphatidylinositol 3-kinases (Pi3K68D and Vps34, respectively) is needed to down-regulate membrane influx, promote efflux, and maintain endolysosomal homeostasis. Endocytosis, but not endolysosomal size, contributes to cortical remodeling by mtm function. We propose that Mtm-dependent regulation of an endosomal PI(3)P pool has separable consequences for endolysosomal homeostasis and cortical remodeling. Pi3K68D depletion (but not Vps34) rescues protrusion and distribution defects in mtm-deficient immune cells and restores functions in other tissues essential for viability. The broad interactions between mtm and class II Pi3K68D suggest a novel strategy for rebalancing PI(3)P-mediated cell functions in MTM-related human disease.

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

    PubMed

    Lin, Abraham; Jimenez, Jose; Derr, Julien; Vera, Pedro; Manapat, Michael L; Esvelt, Kevin M; Villanueva, Laura; Liu, David R; Chen, Irene A

    2011-01-01

    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. Inhibition of Bacterial Conjugation by Phage M13 and Its Protein g3p: Quantitative Analysis and Model

    PubMed Central

    Lin, Abraham; Jimenez, Jose; Derr, Julien; Vera, Pedro; Manapat, Michael L.; Esvelt, Kevin M.; Villanueva, Laura; Liu, David R.; Chen, Irene A.

    2011-01-01

    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. PMID:21637841

  7. Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis.

    PubMed

    Martinez, A; Fullwood, P; Kondo, K; Kishida, T; Yao, M; Maher, E R; Latif, F

    2000-06-01

    Chromosome 3p deletions and loss of heterozygosity (LOH) for 3p markers are features of clear cell renal cell carcinoma but are rare in non-clear cell renal cell carcinoma. The VHL tumour suppressor gene, which maps to 3p25, is a major gatekeeper gene for clear cell renal cell carcinoma and is inactivated in most sporadic cases of this disease. However, it has been suggested that inactivation of other 3p tumour suppressor genes might be crucial for clear cell renal cell carcinoma tumorigenesis, with inactivation (VHL negative) and without inactivation (VHL positive) of the VHL tumour suppressor gene. This study set out to investigate the role of non-VHL tumour suppressor genes in VHL negative and VHL positive clear cell renal cell carcinoma. Eighty two clear cell renal cell carcinomas of known VHL inactivation status were analysed for LOH at polymorphic loci within the candidate crucial regions for chromosome 3p tumour suppressor genes (3p25, LCTSGR1 at 3p21.3, LCTSGR2 at 3p12 and at 3p14.2). Chromosome 3p12-p21 LOH was frequent both in VHL negative and VHL positive clear cell renal cell carcinoma. However, although the frequency of 3p25 LOH in VHL negative clear cell renal cell carcinoma was similar to that at 3p12-p21, VHL positive tumours demonstrated significantly less LOH at 3p25 than at 3p12-p21. Although there was evidence of LOH for clear cell renal cell carcinoma tumour suppressor genes at 3p21, 3p14.2, and 3p12, both in VHL negative and VHL positive tumours, the major clear cell renal cell carcinoma LOH region mapped to 3p21.3, close to the lung cancer tumour suppressor gene region 1 (LCTSGR1). There was no association between tumour VHL status and tumour grade and stage. These findings further indicate that VHL inactivation is not sufficient to initiate clear cell renal cell carcinoma and that loss of a gatekeeper 3p21 tumour suppressor gene is a crucial event for renal cell carcinoma development in both VHL negative and VHL positive clear cell renal

  8. Pediatric peripheral blood progenitor cell collection: haemonetics MCS 3P versus COBE Spectra versus Fresenius AS104.

    PubMed

    Bambi, F; Faulkner, L B; Azzari, C; Gelli, A M; Tamburini, A; Tintori, V; Lippi, A A; Tucci, F; Bernini, G; Genovese, F

    1998-01-01

    An increasing number of apheresis machines are becoming available for peripheral blood progenitor cell (PBPC) collection in children. At the Children's Hospital of Florence (Italy), three apheresis machines were evaluated: MCS 3P (Haemonetics) (10 procedures in 4 patients, aged 10-12 years, weight 23.5-64 kg), Spectra, (COBE) (8 procedures in 3 patients, aged 4-17 years, weight 19-59 kg), and AS104 (Fresenius) (24 procedures in 9 patients, aged 2-16 years, weight 13.6-60 kg). For PBPC quantitative analysis, CD34 cytofluorimetry was employed. Relevant variables analyzed included efficiency of CD34+ cell extraction and enrichment, mononuclear cell purity and red cell contamination of the apheresis components, and platelet count decreases after leukapheresis. No significant differences in CD34+ cell-extraction abilities were found. However, the AS104 provided consistently purer leukapheresis components in terms of mononuclear cell and CD34+ cell enrichment (441 +/- 59%, vs. 240 +/- 35% and 290 +/- 42% for MCS 3P and Spectra, respectively). Postapheresis platelet counts dropped the least with the AS104. The smallest patient who underwent apheresis with MCS 3P (the only machine working on discontinuous flow and hence with greater volume shifts) weighed 23.5 kg and tolerated the procedure well, with no signs of hemodynamic instability. No significant complications were observed. All machines seem to have comparable PBPC extraction efficiency, but the AS104 seems to give the component with the greatest PBPC enrichment. This feature might be relevant for further ex vivo cell processing (CD34+ cell selection, expansion, and so on).

  9. Synthesis and characterization study of n-Bi2O3/p-Si heterojunction dependence on thickness

    NASA Astrophysics Data System (ADS)

    Al-Maiyaly, Bushra K. H.; Hussein, Bushra H.; Salih, Ayad A.; Shaban, Auday H.; Mahdi, Shatha H.; Khudayer, Iman H.

    2018-05-01

    In this work, Bi2O3 was deposited as a thin film of different thickness (400, 500, and 600 ±20 nm) by using thermal oxidation at 573 K with ambient oxygen of evaporated bismuth (Bi) thin films in a vacuum on glass substrate and on Si wafer to produce n-Bi2O3/p-Si heterojunction. The effect of thickness on the structural, electrical, surface and optical properties of Bi2O3 thin films was studied. XRD analysis reveals that all the as deposited Bi2O3 films show polycrystalline tetragonal structure, with preferential orientation in the (201) direction, without any change in structure due to increase of film thickness. AFM and SEM images are used to investigate the influences of film thickness on surface properties. The optical measurement were taken for the wave length range (400-1100) nm showed that the nature of the optical transition has been direct allowed with average band gap energies varies in the range of (2.9-2.25) eV with change thickness parameter. The extent and nature of transmittance, absorbance, reflectance and optimized band gap of the material assure to utilize it for photovoltaic applications. Hall measurements showed that all the films are n-type. The electrical properties of n-Bi2O3/p-Si heterojunction (HJ) were obtained by I-V (dark and illuminated) and C-V measurement at frequency (10 MHz) at different thickness. The ideality factor saturation current density, depletion width, built-in potential and carrier concentration are characterized under different thickness. The results show these HJ were of abrupt type. The photovoltaic measurements short-circuit current density, open-circuit voltage, fill factor and efficiencies are determined for all samples. Finally thermal oxidation allowed fabrication n-Bi2O3/p-Si heterojunction with different thickness for solar cell application.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins.

    PubMed

    Kawada, Daiki; Kobayashi, Hiromu; Tomita, Tsuyoshi; Nakata, Eisuke; Nagano, Makoto; Siekhaus, Daria Elisabeth; Toshima, Junko Y; Toshima, Jiro

    2015-01-01

    Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6

    SciTech Connect

    Sun, Chengcao; Li, Shujun; Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan

    2016-02-26

    Hsa-microRNA-187-3p (miR-187-3p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-187-3p on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-187-3p on the development of NSCLC. The results indicated that miR-187-3p was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-187-3p in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of BCL6. In addition, miR-187-3p induced apoptosis, as indicated by concomitantly with up-regulation ofmore » the activities of caspase-3 and caspase-7, and inhibited cellular migration and invasiveness through inhibition of BCL6. Further, oncogene BCL6 was revealed to be a putative target of miR-187-3p, which was inversely correlated with miR-187-3p expression in NSCLC. Taken together, our results demonstrated that miR-187-3p played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic BCL6.« less

  13. Carcinogenicity of 1-methyl-3(p-chlorophenyl)-1-nitrosourea and its 1-methyl trideuterated derivative in rats.

    PubMed

    Schreiber, D; Martin, J; Mendel, J

    1986-01-01

    The carcinogenic activity of 1-methyl-3(p-chlorophenyl)-1-nitrosourea (Cl-MPNU) and its 1-methyl trideuterated analog (Cl-MPNU-d3) was compared by intragastric administration to hooded rats of equimolar doses of both compounds. A 100% frequency of forestomach tumors was observed in both groups. However, the mean latency period of the animals treated with Cl-MPNU-d3 was significantly longer (P less than 0.01). The results suggest the occurrence of a deuterium isotope effect in nitrosoureas but not as distinct as in nitrosamines.

  14. Gln3p and Nil1p regulation of invertase activity and SUC2 expression in Saccharomyces cerevisiae.

    PubMed

    Oliveira, Edna Maria Morais; Mansure, José João; Bon, Elba Pinto da Silva

    2005-04-01

    In Saccharomyces cerevisiae, sensing and signalling pathways regulate gene expression in response to quality of carbon and nitrogen sources. One such system, the target of rapamycin (Tor) proteins, senses nutrients and uses the GATA activators Gln3p and Nil1p to regulate translation in response to low-quality carbon and nitrogen. The signal transduction, triggered in response to nitrogen nutrition that is sensed by the Tor proteins, operates via a regulatory pathway involving the cytoplasmic factor Ure2p. When carbon and nitrogen are abundant, the phosphorylated Ure2p anchors the also phosphorylated Gln3p and Nil1p in the cytoplasm. Upon a shift from high- to low-quality nitrogen or treatment with rapamycin all three proteins are dephosphorylated, causing Gln3p and Nil1p to enter the nucleus and promote transcription. The genes that code for yeast periplasmic enzymes with nutritional roles would be obvious targets for regulation by the sensing and signalling pathways that respond to quality of carbon and nitrogen sources. Indeed, previous results from our laboratory had shown that the GATA factors Gln3p, Nil1p, Dal80p, Nil2p and also the protein Ure2 regulate the expression of asparaginase II, coded by ASP3. We also had observed that the activity levels of the also periplasmic invertase, coded by SUC2, were 6-fold lower in ure2 mutant cells in comparison to wild-type cells collected at stationary phase. These results suggested similarities between the signalling pathways regulating the expression of ASP3 and SUC2. In the present work we showed that invertase levels displayed by the single nil1 and gln3 and by the double gln3nil1 mutant cells, cultivated in a sucrose-ammonium medium and collected at the exponential phase, were 6-, 10- and 60-fold higher, respectively, in comparison to their wild-type counterparts. RT-PCR data of SUC2 expression in the double-mutant cells indicated a 10-fold increase in the mRNA(SUC2) levels.

  15. A coincidence study of electron and positron impact ionization of Ar (3p) at 1 keV

    NASA Astrophysics Data System (ADS)

    Campeanu, Radu I.; Walters, James H. R.; Whelan, Colm T.

    2015-10-01

    Distorted-wave calculations of the triple differential cross section (TDCS) are presented for electron and positron impact ionization of Ar(3p) in coplanar asymmetric geometry at an impact energy of 1 keV and are compared with a recent experiment. The experiment indicates that the positron TDCS is generally larger than the equivalent electron TDCS. It is shown that the magnitude of the TDCS is extremely sensitive to the energy of the ejected electron and that only when the cross section is averaged over energy do we get a reasonable agreement with experiment.

  16. Fabrication of IrSi(3)/p-Si Schottky diodes by a molecular beam epitaxy technique

    NASA Technical Reports Server (NTRS)

    Lin, T. L.; Iannelli, J. M.

    1990-01-01

    IrSi(3)/p-Si Schottky diodes have been fabricated by a molecular beam epitaxy technique at 630 C. Good surface morphology was observed for IrSi(3) layers grown at temperatures below 680 C, and an increasing tendency to form islands is observed in samples grown at higher temperatures. Good diode current-voltage characteristics were observed and Schottky barrier heights of 0.14-0.18 eV were determined by activation energy analysis and spectral response measurement.

  17. Genetics Home Reference: 5q31.3 microdeletion syndrome

    MedlinePlus

    ... of the characteristic features of the condition. The protein produced from the PURA gene, called Pur-alpha ( ... aiding in the copying (replication) of DNA. This protein is especially important for normal brain development; it ...

  18. Manganese toxicity and Saccharomyces cerevisiae Mam3p, a member of the ACDP (ancient conserved domain protein) family

    PubMed Central

    2004-01-01

    Manganese is an essential, but potentially toxic, trace metal in biological systems. Overexposure to manganese is known to cause neurological deficits in humans, but the pathways that lead to manganese toxicity are largely unknown. We have employed the bakers' yeast Saccharomyces cerevisiae as a model system to identify genes that contribute to manganese-related damage. In a genetic screen for yeast manganese-resistance mutants, we identified S. cerevisiae MAM3 as a gene which, when deleted, would increase cellular tolerance to toxic levels of manganese and also increased the cell's resistance towards cobalt and zinc. By sequence analysis, Mam3p shares strong similarity with the mammalian ACDP (ancient conserved domain protein) family of polypeptides. Mutations in human ACDP1 have been associated with urofacial (Ochoa) syndrome. However, the functions of eukaryotic ACDPs remain unknown. We show here that S. cerevisiae MAM3 encodes an integral membrane protein of the yeast vacuole whose expression levels directly correlate with the degree of manganese toxicity. Surprisingly, Mam3p contributes to manganese toxicity without any obvious changes in vacuolar accumulation of metals. Furthermore, through genetic epistasis studies, we demonstrate that MAM3 operates independently of the well-established manganese-trafficking pathways in yeast, involving the manganese transporters Pmr1p, Smf2p and Pho84p. This is the first report of a eukaryotic ACDP family protein involved in metal homoeostasis. PMID:15498024

  19. ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis.

    PubMed

    Nascimbeni, Anna Chiara; Giordano, Francesca; Dupont, Nicolas; Grasso, Daniel; Vaccaro, Maria I; Codogno, Patrice; Morel, Etienne

    2017-07-14

    The double-membrane-bound autophagosome is formed by the closure of a structure called the phagophore, origin of which is still unclear. The endoplasmic reticulum (ER) is clearly implicated in autophagosome biogenesis due to the presence of the omegasome subdomain positive for DFCP1, a phosphatidyl-inositol-3-phosphate (PI3P) binding protein. Contribution of other membrane sources, like the plasma membrane (PM), is still difficult to integrate in a global picture. Here we show that ER-plasma membrane contact sites are mobilized for autophagosome biogenesis, by direct implication of the tethering extended synaptotagmins (E-Syts) proteins. Imaging data revealed that early autophagic markers are recruited to E-Syt-containing domains during autophagy and that inhibition of E-Syts expression leads to a reduction in autophagosome biogenesis. Furthermore, we demonstrate that E-Syts are essential for autophagy-associated PI3P synthesis at the cortical ER membrane via the recruitment of VMP1, the stabilizing ER partner of the PI3KC3 complex. These results highlight the contribution of ER-plasma membrane tethers to autophagosome biogenesis regulation and support the importance of membrane contact sites in autophagy. © 2017 The Authors.

  20. O({sup 3}P{sub J}) formation and desorption by 157-nm photoirradiation of amorphous solid water

    SciTech Connect

    DeSimone, Alice J.; Orlando, Thomas M., E-mail: thomas.orlando@chemistry.gatech.edu; School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332–0400

    2014-03-07

    Photodissociation of amorphous solid water (ASW) deposited on a thinly oxidized copper substrate at 82 K was studied by measuring O({sup 3}P{sub J=2,1,0}) photoproducts detected with resonance-enhanced multiphoton ionization. For each spin-orbit state, the oxygen atom time-of-flight spectrum was measured as a function of H{sub 2}O exposure, which is related to ice thickness, and 157-nm irradiation time. Four Maxwell-Boltzmann distributions with translational temperatures of 10 000 K, 1800 K, 400 K, and 82 K were found to fit the data. The most likely formation mechanisms are molecular elimination following ionization of water and ion-electron recombination, secondary recombination of hydroxyl radicals, andmore » photodissociation of adsorbed hydroxyl radicals. Evidence for O-atom diffusion through bulk ASW was found for H{sub 2}O exposures of at least 5 Langmuir (1 L = 10{sup −6} Torr s). The cross sections for O({sup 3}P{sub 2}) depletion were 1.3 × 10{sup −19} and 6.5 × 10{sup −20} cm{sup 2} for 1 and 5 L, respectively.« less

  1. Modeling microbiological and chemical processes in municipal solid waste bioreactor, Part II: Application of numerical model BIOKEMOD-3P.

    PubMed

    Gawande, Nitin A; Reinhart, Debra R; Yeh, Gour-Tsyh

    2010-02-01

    Biodegradation process modeling of municipal solid waste (MSW) bioreactor landfills requires the knowledge of various process reactions and corresponding kinetic parameters. Mechanistic models available to date are able to simulate biodegradation processes with the help of pre-defined species and reactions. Some of these models consider the effect of critical parameters such as moisture content, pH, and temperature. Biomass concentration is a vital parameter for any biomass growth model and often not compared with field and laboratory results. A more complex biodegradation model includes a large number of chemical and microbiological species. Increasing the number of species and user defined process reactions in the simulation requires a robust numerical tool. A generalized microbiological and chemical model, BIOKEMOD-3P, was developed to simulate biodegradation processes in three-phases (Gawande et al. 2009). This paper presents the application of this model to simulate laboratory-scale MSW bioreactors under anaerobic conditions. BIOKEMOD-3P was able to closely simulate the experimental data. The results from this study may help in application of this model to full-scale landfill operation.

  2. MicroRNAs-1614-3p gene seed region polymorphisms and association analysis with chicken production traits.

    PubMed

    Li, Hong; Sun, Gui-Rong; Tian, Ya-Dong; Han, Rui-Li; Li, Guo-Xi; Kang, Xiang-Tao

    2013-05-01

    In the present study, a total of 860 chickens from a Gushi-Anka F2 resource population were used to evaluate the genetic effect of the gga-miR-1614-3p gene. A novel, silent, single nucleotide polymorphism (SNP, +5 C>T) was detected in the gga-miR-1614-3p gene seed region through AvaII polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR products sequencing methods. Associations between the SNP and chicken growth, meat quality and carcass traits were performed by association analysis. The results showed that the SNP was significantly associated with breast muscle shear force and leg muscle water loss rate, wing weight, liver weight and heart weight (p<0.05), and highly significantly associated with the weight of the abdominal fat (p<0.01). The secondary structure of gga-miR-1614 and the free energy were altered due to the variation predicted by the M-fold program.

  3. DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme

    PubMed Central

    Yang, Jian-kai; Song, Jian; Huo, Hao-ran; Zhao, Yin-long; Zhang, Guang-yu; Zhao, Zong-mao; Sun, Guo-zhu; Jiao, Bao-hua

    2017-01-01

    Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM. PMID:29449895

  4. Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

    PubMed

    Bensefa-Colas, L; Telle-Lamberton, M; Faye, S; Bourrain, J-L; Crépy, M-N; Lasfargues, G; Choudat, D; Momas, I

    2015-12-01

    Occupational contact urticaria (OCU) is an occupational contact dermatitis that can cause serious health consequences and disability at work. To describe OCU and its temporal trends by the main causal agents and activity sectors in a nationwide scheme in France. Using data from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P), we described OCU reported during the period 2001-10 and analysed the temporal trends of OCU and OCU attributed to the most frequent agents over the study period. Trends analyses were supported by reporting odds ratios using a logistic regression model with reference to 2001, or with time as a continuous variable. During the study period, 251 cases of OCU were reported in RNV3P, half of which were due to natural rubber latex, in particular in the health and social work activity sector (HSW). The number of these cases declined significantly over the study period (19% per year), and particularly after 2006. Conversely, the other causes of OCU did not decrease. Using surveillance data from a French national network, this study has found that there was a significant decline in OCU due to natural rubber latex, particularly in the HSW, when powdered latex gloves were banned from French hospitals. Our results show the effectiveness of this preventive measure, and suggest that this practice should be extended to other sectors. © 2015 British Association of Dermatologists.

  5. Age-related changes in miR-143-3p:Igfbp5 interactions affect muscle regeneration.

    PubMed

    Soriano-Arroquia, Ana; McCormick, Rachel; Molloy, Andrew P; McArdle, Anne; Goljanek-Whysall, Katarzyna

    2016-04-01

    A common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age-related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA-143-3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR-143 as a regulator of the insulin growth factor-binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR-143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR-143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR-143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR-143-3p:Igfbp5 interactions in satellite cells with age may be responsible for age-related changes in satellite cell function. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  6. MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1.

    PubMed

    Li, Qiang; Xia, Xuefeng; Ji, Jie; Ma, Jianghui; Tao, Liang; Mo, Linjun; Chen, Wei

    2017-05-16

    Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different human malignancies, however, little is known about miR-199a-3p in cholangiocarcinoma cells. In this study, we demonstrate the essential role and mechanism of miR-199a-3p in regulating cisplatin sensitivity in cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that expression of miR-199a-3p was positively correlated with cisplatin sensitivity in cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the proliferation rate and increase apoptosis of cholangiocarcinoma cells in the presence of cisplatin, while miR-199a-3p inhibition had the opposite effect. Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue experiments proved that miR-199a-3p could increase the cisplatin sensitivity of cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also found that miR-199a-3p overexpression could reduce cisplatin induced MDR1 expression by decreasing the synthesis and increasing the degradation of MDR1, thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In conclusion, miR-199a-3p could increase cisplatin sensitivity of cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling pathway and decreasing the expression of MDR1.

  7. [Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate cancer cells by reducing TRAF4].

    PubMed

    Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

    2018-01-01

    Objective To observe the effect of microRNA-519d-3p (miR-519d-3p) on the proliferation of prostate cancer cells and explore the possible molecular mechanism. Methods The expression level of miR-519d-3p in PC-3, DU-145, 22RV1, PC-3M, LNCaP human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time quantitative PCR. miR-519d-3p mimics or negative control microRNAs (miR-NC) was transfected into the prostate cancer cells with the lowest level of miR-519d-3p expression. Transfection efficiency was examined. The effect of miR-519d-3p on the cell cycle of prostate cancer was detected by flow cytometry. MTT assay and plate clone formation assay were used to detect its effect on the proliferation of prostate cancer cells. Bioinformatics software was used to predict and dual luciferase reporter assay was used to validate the target gene of miR-519d-3p. Real-time quantitative PCR was used to detect the expression of miR-519d-3p target gene. Western blot analysis was used to detect the expression of target gene protein and downstream protein. Results The expression of miR-519d-3p in normal prostate epithelial cells was significantly higher than that in prostate cancer cells, and the lowest was found in DU-145 cells. After transfected with miR-519d-3p mimics, the expression level of miR-519d-3p in DU-145 cells increased significantly. Bioinformatics prediction and dual luciferase reporter gene confirmed that tumor necrosis factor receptor associated factor 4 (TRAF4) was the target gene of miR-519d-3p. Overexpression of miR-519d-3p significantly reduced the expression of TRAF4 gene and its downstream TGF-β signaling pathway proteins in the prostate cancer cells. Conclusion The expression of miR-519d-3p is down-regulated in prostate cancer cells. Overexpression of miR-519d-3p can inhibit the proliferation of prostate cancer cells. The possible mechanism is that miR-519d-3p inhibits the expression of TRAF4.

  8. Decreased expression of miR‑490‑3p in colorectal cancer predicts poor prognosis and promotes cell proliferation and invasion by targeting RAB14.

    PubMed

    Wang, Bo; Yin, Mujun; Cheng, Cheng; Jiang, Hongpeng; Jiang, Kewei; Shen, Zhanlong; Ye, Yingjiang; Wang, Shan

    2018-06-19

    Growing evidence indicates a potential role for miR‑490‑3p in tumorigenesis. However, its function in colorectal carcinoma (CRC) remains undefined. In this study, miR‑490‑3p was markedly downregulated in fifty colorectal cancer tissue samples compared with the corresponding adjacent non‑cancerous specimens, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of miR‑490‑3p were closely associated with tumor differentiation and distant metastasis. In addition, both Kaplan-Meier and multivariate analyses indicated CRC patients with elevated miR‑490‑3p amounts had prolonged overall survival. Overexpression of miR‑490‑3p markedly reduced proliferation, colony formation and invasion in CRC cells by enhancing apoptosis and promoting G2/M phase arrest. Furthermore, ectopic expression of miR‑490‑3p resulted in decreased expression of RAB14, which was directly targeted by miR‑490‑3p, as shown by the dual-luciferase reporter gene assay. Finally, in a nude mouse model, miR‑490‑3p overexpression significantly suppressed the growth of CRC cells. The above results indicated that miR‑490‑3p might constitute a prognostic indicator and a novel molecular target for miRNA-based CRC therapy.

  9. PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery.

    PubMed

    Krawczyk, Marcin; Jiménez-Agüero, Raúl; Alustiza, José M; Emparanza, José I; Perugorria, María J; Bujanda, Luis; Lammert, Frank; Banales, Jesús M

    2016-12-01

    Obesity is the major trigger of nonalcoholic fatty liver disease (NAFLD). NAFLD is further favored by the patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M, transmembrane 6 superfamily member 2 (TM6SF2) p.E167K, and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 variants. To investigate the relationship between the PNPLA3, TM6SF2, and MBOAT7 genotypes and the outcomes of bariatric surgery. University hospital. Prospectively we monitored 84 obese individuals (body mass index 35-64 kg/m 2 ) scheduled for bariatric surgery. The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants were genotyped using restriction fragment length polymorphism analysis and TaqMan assays. Hepatic steatosis was determined before surgery using analysis of liver biopsy samples and a novel magnetic resonance imaging-based equation. One year later, steatosis was reevaluated by magnetic resonance imaging. The presence of the PNPLA3 allle [M] was associated with increased hepatic triglyceride content (P = .03), steatosis detected by magnetic resonance imaging (P = 0.04), and decreased serum glucose concentrations (P = .04). Neither variant TM6SF2 nor MBOAT7 increased hepatic steatosis (all P>.05); however, the MBOAT7 polymorphism was associated with increased triglyceride, total cholesterol, low density lipoprotein, and serum glucose levels (all P<.05). Patients carrying the prosteatotic PNPLA3 allele [M] lost more weight (P<.01) and liver fat (P = .04) one year after surgery, as compared to individuals having the common genotype. The PNPLA3 genotype and initial grade of steatosis, but not the TM6SF2 or MBOAT7 variants, were independent predictors of NAFLD improvement (P = .03 and P<.01, respectively). In obese patients, the presence of the PNPLA3 p.I148M allele might be associated with greater improvement of hepatic steatosis after bariatric surgery in comparison to carriers of PNPLA3 wild-type alleles. Copyright © 2016 American Society for

  10. Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes

    SciTech Connect

    Lu, Yin; Wang, Jianshe

    Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5 mg/kg/d of PFOA for 28 d (> 1.5-fold and P < 0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins aftermore » PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. - Highlights: • Endocytosis and blood-testis barrier proteins were changed after PFOA exposure. • Seventeen miRNAs were differentially expressed in testes after PFOA exposure. • MiRNAs might play a role in gene regulation in testes after PFOA exposure.CLTA is a potential target of

  11. Investigation of trapping levels in p-type Zn3P2 nanowires using transport and optical properties

    NASA Astrophysics Data System (ADS)

    Lombardi, G. A.; de Oliveira, F. M.; Teodoro, M. D.; Chiquito, A. J.

    2018-05-01

    Here, we report the synthesis and structural characterization of high-quality Zn3P2 nanowires via chemical vapour deposition. Structural and morphological characterization studies revealed a reliable growth process of long, uniform, and single-crystalline nanowires. From temperature dependent transport and photoluminescence measurements, we have observed the contribution of different acceptor levels (15, 50, 70, 90, and 197 meV) to the conduction mechanisms. These levels were associated with zinc vacancies and phosphorous interstitial atoms which assigned a p-type character to this semiconductor. From time resolved photoluminescence experiments, a 91 ps lifetime decay was found. Such a fast lifetime decay is in agreement with the exciton transition along the bulk emission from high quality crystalline nanowires.

  12. Optical emission generated by collisions of 5 eV O(3P) atoms with surface-absorbed hydrazine

    NASA Technical Reports Server (NTRS)

    Orient, O. J.; Martus, K. E.; Chutjian, A.; Murad, E.

    1992-01-01

    Optical emission has been observed corresponding to vibrational bands in the NH (A 3Pi - X 3Sigma(-)) electronic transition during collisions of 5 eV, ground-state oxygen O(3P) atoms with MgF2 and Ni surfaces continuously exposed to a beam of hydrazine (N2H4). The NH emission intensity is observed to be about five times greater for MgF2 than for Ni. No dependence on temperature was observed for either surface in the range 240 - 340 K, implying that the NH-producing intermediate species is tightly bound. The half-lifetime for desorption of hydrazine from each surface was measured. This was found to be 120 min for the MgF2 surface at 240 K, and less than 20 min for Ni. After exposure, the surface composition was measured using X-ray photoelectron spectroscopy on the exposed and unexposed areas of both targets.

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

    SciTech Connect

    Kraus, C.; Liehr, T.; Ballhausen, G.

    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 themore » CTNNB1 locus close to the marker D3S2 in 3p21. 22 refs., 3 figs.« less

  14. Ab initio thermal rate calculations of HO + HO = O(3P) + H2O reaction and isotopologues.

    PubMed

    Nguyen, Thanh Lam; Stanton, John F

    2013-04-04

    The forward and reverse reactions, HO + HO ⇌ O((3)P) + H2O, which play roles in both combustion and laboratory studies, were theoretically characterized with a master equation approach to compute thermal reaction rate constants at both the low and high pressure limits. Our ab initio k(T) results for the title reaction and two isotopic variants agree very well with experiments (within 15%) over a wide temperature range. The calculated reaction rate shows a distinctly non-Arrhenius behavior and a strong curvature consistent with the experiment. This characteristic behavior is due to effects of positive barrier height and quantum mechanical tunneling. Tunneling is very important and contributes more than 70% of total reaction rate at room temperature. A prereactive complex is also important in the overall reaction scheme.

  15. Electron-impact ionization of Ne (2 p ) and Ar (3 p ) at intermediate energies: Role of the postcollision interaction

    NASA Astrophysics Data System (ADS)

    Hu, Xiaoqing; Gao, Cong-Zhang; Chen, Zhanbin; Wang, Jianguo; Wu, Yong; Wang, Yang

    2017-11-01

    We present the absolute triple differential cross section (TDCS) for single ionization of Ne (2 p ) at an impact energy of 599.6 eV and Ar (3 p ) at 195 eV. The role of the postcollision interaction (PCI) is studied using a high-order distorted-wave Born approximation model with a continuum distorted-waves expansion. Both the second- and third-order effects are considered in the present calculations, and the third-order distorted wave Born approximation model is reported in the (e ,2 e ) reaction. The calculated results show satisfactory agreement with experimental data. The magnitude of the absolute TDCS is enhanced by a factor 2-3 when the strength factor γ of the PCI amplitude is summarized just from 0 to 2. This proves that the PCI plays an important role in the absolute TDCS of the (e ,2 e ) reaction in the intermediate-energy region.

  16. Residual stress analysis on AA6061+22% Al2O3p simple shape demonstrators of a wheel hub

    NASA Astrophysics Data System (ADS)

    Giuliani, Alessandra; Albertini, Gianni; Fiori, Fabrizio; Girardin, Emmanuelle

    2004-07-01

    The effects of thermal treatments in a component for automotive industry are considered: the induced residual stresses in wheel hubs were investigated. Measurements have been carried out on two identical simple shape demonstrators made of AA6061+22% Al2O3p in order to evaluate the stress conditions after forging and T6 treatment and without taking into account the final design of the wheel hub. One sample was analysed in as-forged conditions while the second after forging and T6 treatment (560°C for 2h, 20°C water quenching, artificial aging at 177°C for 10h). Particular attention was given to the stresses in the radial and hoop directions, as the main consequences of the in-service fatigue are expected to be related to stresses along these two directions.

  17. Interactions of solute (3p, 4p, 5p and 6p) with solute, vacancy and divacancy in bcc Fe

    NASA Astrophysics Data System (ADS)

    You, Yu-Wei; Kong, Xiang-Shan; Wu, Xue-Bang; Liu, Wei; Liu, C. S.; Fang, Q. F.; Chen, J. L.; Luo, G.-N.; Wang, Zhiguang

    2014-12-01

    Solute-vacancy binding energy is a key quantity in understanding solute diffusion kinetics and phase segregation, and may help choice of alloy compositions for future material design. However, the binding energy of solute with vacancy is notoriously difficult to measure and largely unknown in bcc Fe. With first-principles method, we systemically calculate the binding energies of solute (3p, 4p, 5p and 6p alloying solutes are included) with vacancy, divacancy and solute in bcc Fe. The binding energy of Si with vacancy in the present work is in good consistent with experimental value available. All the solutes considered are able to form stable solute-vacancy, solute-divacancy complexes, and the binding strength of solute-divacancy is about two times larger than that of solute-vacancy. Most solutes could not form stable solute-solute complexes except S, Se, In and Tl. The factors controlling the binding energies are analyzed at last.

  18. [Over-expression of miR-151a-3p inhibits proliferation and migration of PC-3 prostate cancer cells].

    PubMed

    Zhang, Yi; Hao, Tongtong; Zhang, Han; Wei, Pengtao; Li, Xiaohui

    2018-03-01

    Objective To observe the effect of microRNA-151a-3p (miR-151a-3p) up-regulation on the proliferation and migration of prostate cancer cells and explore the possible molecular mechanism. Methods The expression of miR-151a-3p in PC-3M, C4-2B, 22RV1, DU-145, PC-3, LNCap human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time fluorescence quantitative PCR. PC-3 cells with the lowest expression of miR-151a-3p were used for subsequent experiments. Bioinformatics and dual-luciferase reporter assay were performed to predict and test potential target genes of miR-151a-3p. The miR-151a-3p mimics or negative control microRNAs (miR-NCs) were transfected into PC-3 cells. Real-time fluorescence quantitative PCR was used to detect the expression of miR-151a-3p and potential target gene mRNA. The protein expressions of target genes and downstream signaling pathway proteins were analyzed by Western blotting. The proliferation of PC-3 cells was examined by MTT assay, and the migration of PC-3 cells was detected by Transwell TM assay. Results The expression level of miR-151a-3p in the prostate cancer cells was significantly lower than that in RWPE-1 normal human prostate epithelial cells. PC-3 cells had the lowest expression level of miR-151a-3p. The bioinformatics and dual-luciferase reporter assay showed that NEK2 was the potential target gene for miR-151a-3p. After transfection with miR-151a-3p mimics, the expression of miR-151a-3p in PC-3 cells significantly increased and the expression of NEK2 mRNA significantly decreased. The protein expressions of PI3K-AKT-mTOR signaling pathway were also reduced. Up-regulation of miR-151a-3p significantly inhibited the proliferation and migration of PC-3 cells. Conclusion The expression of miR-151a-3p is reduced in prostate cancer cells. Up-regulation of miR-151a-3p can inhibit the proliferation and migration of P-3 in prostate cancer by decreasing the expression of NEK2 and PI3K

  19. A novel electrochemical sensor based on Cu3P@NH2-MIL-125(Ti) nanocomposite for efficient electrocatalytic oxidation and sensitive detection of hydrazine

    NASA Astrophysics Data System (ADS)

    Wang, Minghua; Yang, Longyu; Hu, Bin; Liu, Yongkang; Song, Yingpan; He, Linghao; Zhang, Zhihong; Fang, Shaoming

    2018-07-01

    A novel electrocatalyst based on amine-functionalized Ti-based metal-organic framework (NH2-MIL-125(Ti)) embedded with Cu3P nanocrystals (denoted by Cu3P@NH2-MIL-125(Ti)) was synthesized and used for electrocatalytic oxidation and detection of hydrazine in aqueous solution. A series of Cu3P@NH2-MIL-125(Ti) nanocomposites were obtained by adding Cu3P nanoparticles into the preparation system of NH2-MIL-125(Ti), with the Cu3P nanocrystals derived from the phospatization of Cu(OH)2 at high temperature. Based on the detailed characterizations and analysis of the chemical and physical performances of the series of Cu3P@NH2-MIL-125(Ti) nanocomposites at dosages of Cu3P nanocrystals at 5, 20, 50, and 100 mg, the good synergic effect between the Cu3P (50 mg) and the NH2-MIL-125(Ti) endows the as-prepared Cu3P50@NH2-MIL-125(Ti) nanocomposite with the excellent electrocatalytic activity toward the electrocatalytic oxidation of hydrazine. The Cu3P50@NH2-MIL-125(Ti)-based electrochemical sensor exhibited a detection limit of 79 nM (S/N = 3) within a wider linear range from 5 μM to 7.5 mM. Moreover, the developed sensor exhibited high selectivity toward the detection of hydrazine with the addition of certain common interferents and good applicability in real samples. All of these results imply that the Cu3P50@NH2-MIL-125(Ti) nanocomposite could be promising for detecting hydrazine and offer potential applications in the field of electroanalytical chemistry.

  20. MiR-520d-3p antitumor activity in human breast cancer via post-transcriptional regulation of spindle and kinetochore associated 2 expression.

    PubMed

    Ren, Zhouhui; Yang, Tong; Ding, Jie; Liu, Weihong; Meng, Xiangyu; Zhang, Pingping; Liu, Kaitai; Wang, Ping

    2018-01-01

    MicroRNAs (miRNAs) play an important role in human tumorigenesis as oncogenes or tumor suppressors by directly binding to the 3'-untranslated region of their target mRNAs. MiR-520d-3p has been reported as a tumor suppressor gene in ovarian cancer and gastric cancer, while the function of miR-520d-3p in human breast cancers is still uninvolved. In this study, we initially identified that the expression of miR-520d-3p was significantly reduced in breast cancer specimens and cell lines. The restoration of miR-520d-3p expression not only reduced breast cancer cell viability by causing the accumulation of G2 phase and cell apoptosis, but also inhibited tumorigenicity in vivo . In addition, as a critical target of miR-520d-3p, the activity of spindle and kinetochore associated 2 (SKA2) was greatly inhibited by miR-520d-3p, and overexpression of miR-520d-3p decreased the expression of SKA2. SKA2 downregulation suppressed cell viability, whereas restoration of SKA2 expression significantly reversed the inhibitory effects of miR-520d-3p antitumor activity. Furthermore, SKA2 was frequently overexpressed in clinical specimens and cell lines, and the expression levels were statistically inversely correlated with miR-520d-3p expression. In conclusion, our data demonstrated that miR-520d-3p antitumor activity is achieved by targeting the SKA2 in human breast cancer cells, suggesting that miR-520d-3p may be a potential target molecule for the therapy.

  1. Modulated magnetic structure of F e3P O7 as seen by 57Fe Mössbauer spectroscopy

    NASA Astrophysics Data System (ADS)

    Sobolev, A. V.; Akulenko, A. A.; Glazkova, I. S.; Pankratov, D. A.; Presniakov, I. A.

    2018-03-01

    The paper reports results of the 57Fe Mössbauer measurements on an F e3P O4O3 powder sample recorded at various temperatures, including the point of magnetic phase transition TN≈163 K . The spectra measured above TN consist of a quadrupole doublet with high quadrupole splitting of Δ300 K≈1.10 mm /s , emphasizing that F e3 + ions are located in crystal positions with a strong electric-field gradient (EFG). To predict the sign and orientation of the main components of the EFG tensor, we calculated the EFG using the density-functional-theory approach. In the temperature range T 3P O4O3 .

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

    NASA Technical Reports Server (NTRS)

    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.

  3. Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome.

    PubMed

    Salo-Mullen, Erin E; Lynn, Patricio B; Wang, Lu; Walsh, Michael; Gopalan, Anuradha; Shia, Jinru; Tran, Christina; Man, Fung Ying; McBride, Sean; Schattner, Mark; Zhang, Liying; Weiser, Martin R; Stadler, Zsofia K

    2018-01-01

    Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity.

  4. Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes.

    PubMed

    Lu, Yin; Wang, Jianshe; Guo, Xuejiang; Yan, Shengmin; Dai, Jiayin

    2017-03-01

    Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. 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)].

    PubMed

    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)].

  6. 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

    SciTech Connect

    Andreotti, M.; Bagnasco, S.; Baldini, W.

    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}{submore » 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.« less

  7. A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations.

    PubMed

    Iype, Thomas; Alakbarzade, Vafa; Iype, Mary; Singh, Royana; Sreekantan-Nair, Ajith; Chioza, Barry A; Mohapatra, Tribhuvan M; Baple, Emma L; Patton, Michael A; Warner, Thomas T; Proukakis, Christos; Kulkarni, Abhi; Crosby, Andrew H

    2015-11-10

    The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.

  8. Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export.

    PubMed

    Krebber, H; Taura, T; Lee, M S; Silver, P A

    1999-08-01

    Npl3p, the major mRNA-binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear.

  9. High-Resolution Chromosome 3p Allelotyping of Breast Carcinomas and Precursor Lesions Demonstrates Frequent Loss of Heterozygosity and a Discontinuous Pattern of Allele Loss

    PubMed Central

    Maitra, Anirban; Wistuba, Ignacio I.; Washington, Constance; Virmani, Arvind K.; Ashfaq, Raheela; Milchgrub, Sara; Gazdar, Adi F.; Minna, John D.

    2001-01-01

    We performed high-resolution allelotyping for loss of heterozygosity (LOH) analysis on microdissected samples from 45 primary breast cancers, 47 mammary preneoplastic epithelial foci, and 18 breast cancer cell lines, using a panel of 27 polymorphic chromosome 3p markers. Allele loss in some regions of chromosome 3p was detected in 39 of 45 (87%) primary breast tumors. The 3p21.3 region had the highest frequency of LOH (69%), followed by 3p22-24 (61%), 3p21.2-21.3 (58%), 3p25 (48%), 3p14.2 (45%), 3p14.3 (41%), and 3p12 (35%). Analysis of all of the data revealed at least nine discrete intervals showing frequent allele loss: D3S1511-D3S1284 (U2020/DUTT1 region centered on D3S1274 with a homozygous deletion), D3S1300-D3S1234 [fragile histidine triad (FHIT)/FRA3B region centered on D3S1300 with a homozygous deletion], D3S1076-D3S1573, D3S4624/Luca2.1-D3S4597/P1.5, D3S1478-D3S1029, D3S1029 (with a homozygous deletion), D3S1612-D3S1537, D3S1293-D3S1597, and D3S1597-telomere; it is more than likely that additional localized regions of LOH not examined in this study also exist on chromosome 3p. In multiple cases, there was discontinuous allele loss at several 3p sites in the same tumor. Twenty-one of 47 (45%) preneoplastic lesions demonstrated 3p LOH, including 12 of 13 (92%) ductal carcinoma in situ, 2 of 7 (29%) apocrine metaplasia, and 7 of 25 (28%) usual epithelial hyperplasia. The 3p21.3 region had the highest frequency of LOH in preneoplastic breast epithelium (36%), followed by 3p21.2-21.3 (20%), 3p14.2/FHIT region (11%), 3p25 (10%), and 3p22-24 (5%). In 39 3p loci showing LOH in both the tumor and accompanying preneoplasia, 34 (87%) showed loss of the same parental allele (P = 1.2 × 10−6, cumulative binomial test). In addition, when 21 preneoplastic samples showing LOH were compared to their accompanying cancers, 67% were clonally related, 20% were potentially clonally related but were divergent, and 13% were clonally unrelated. Overall this demonstrated the

  10. Kinetics of the benzyl + O(3P) reaction: a quantum chemical/statistical reaction rate theory study.

    PubMed

    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

  11. miR-324-3p promotes gastric cancer development by activating Smad4-mediated Wnt/beta-catenin signaling pathway.

    PubMed

    Sun, Guang-Li; Li, Zheng; Wang, Wei-Zhi; Chen, Zheng; Zhang, Lei; Li, Qing; Wei, Song; Li, Bo-Wen; Xu, Jiang-Hao; Chen, Liang; He, Zhong-Yuan; Ying, Kai; Zhang, Xuan; Xu, Hao; Zhang, Dian-Cai; Xu, Ze-Kuan

    2018-06-01

    Emerging evidence suggested that miRNAs can function as oncogenes or tumor suppressors by regulating downstream target genes. miR-324-3p has been reported to function in several carcinomas, but its role in gastric cancer (GC) is still unknown. This study aims to explore the effects of miR-324-3p on the development of GC. Expression of miR-324-3p was examined in GC cells and tissues by qRT-PCR. Effects of miR-324-3p on GC cells were evaluated by cell vitality assay, colony formation assay, cell migration assay, and flow cytometric assay. The dual luciferase assay was used to verify whether miR-324-3p could interact with the potential target genes. Western blot was used to assess the expression level of Smad4 and beta-catenin. Intracellular ATP level was also examined. The tumor xenografts were established using nude mice. A gastric organoid model was made from fresh stomach tissue. miR-324-3p was expressed at higher levels in the tumor tissues compared with adjacent normal tissues. Overexpression of miR-324-3p promoted cell growth, migration, and decreased apoptosis. miR-324-3p repressed the expression of Smad4, and loss of Smad4 activated the Wnt/beta-catenin signaling pathway. Overexpression of Smad4 rescued the effects of miR-324-3p on GC cells. The intracellular ATP level was upregulated with overexpression of miR-324-3p. miR-324-3p facilitated tumor cell colonization and growth in vivo and contributed to the growth of gastric organoids. The results suggested that miR-324-3p promoted GC through activating the Smad4-mediated Wnt/beta-catenin signaling pathway. The miR-324-3p/Smad4/Wnt signaling axis may be a potential therapeutic target to prevent GC progression.

  12. Mir-338-3p Mediates Tnf-A-Induced Hepatic Insulin Resistance by Targeting PP4r1 to Regulate PP4 Expression.

    PubMed

    Dou, Lin; Wang, Shuyue; Sun, Libo; Huang, Xiuqing; Zhang, Yang; Shen, Tao; Guo, Jun; Man, Yong; Tang, Weiqing; Li, Jian

    2017-01-01

    Insulin resistance is a critical factor contributing to the pathogenesis of type 2 diabetes and other metabolic diseases. Recent studies have indicated that miR-338-3p plays an important role in cancer. Here, we investigated whether miR-338-3p mediates tumour necrosis factor-α (TNF-α)-induced hepatic insulin resistance. The activation of the insulin signalling pathway and the level of glycogenesis were examined in the livers of the db/db and high fat diet (HFD)-fed mice and in HEP1-6 cells transfected with miR-338-3p mimic or inhibitor. Computational prediction of microRNA target, luciferase assay and Western blot were used to assess the miR-338-3p target. Chromatin immunoprecipitation (ChIP) assay was used to determine the transcriptional regulator of miR-338-3p. miR-338-3p was down-regulated in the livers of the db/db, HFD-fed and TNF-α-treated C57BL/6J mice, as well as in mouse HEP1-6 hepatocytes treated with TNF-α. Importantly the down-regulation of miR-338-3p induced insulin resistance, as indicated by impaired glucose tolerance and insulin tolerance. Further research showed that the down-regulated miR-338-3p resulted in the impaired AKT/ glycogen synthase kinase 3 beta (GSl·Gβ) signalling pathway and glycogen synthesis. In contrast, hepatic over-expression of miR-338-3p rescued the TNF-α-induced insulin resistance. Moreover, protein phosphatase 4 regulator subunit 1 (PP4R1) was identified as a direct target of miR-338-3p that mediated hepatic insulin signalling by regulating protein phosphatase 4 (PP4). Finally we identified hepatic nuclear factor 4 alpha (HNF-4α) as the transcriptional regulator of miRNA-338-3p. Our studies provide novel insight into the critical role and molecular mechanism by which miR-338-3p is involved in TNF-α-induced hepatic insulin resistance. miR-338-3p might mediate TNF-α-induced hepatic insulin resistance by targeting PP4R1 to regulate PP4 expression. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Bragg gravity-gradiometer using the 1S0–3P1 intercombination transition of 88Sr

    NASA Astrophysics Data System (ADS)

    del Aguila, R. P.; Mazzoni, T.; Hu, L.; Salvi, L.; Tino, G. M.; Poli, N.

    2018-04-01

    We present a gradiometer based on matter-wave interference of alkaline-earth-metal atoms, namely 88Sr. The coherent manipulation of the atomic external degrees of freedom is obtained by large-momentum-transfer Bragg diffraction, driven by laser fields detuned away from the narrow 1S0–3P1 intercombination transition. We use a well-controlled artificial gradient, realized by changing the relative frequencies of the Bragg pulses during the interferometer sequence, in order to characterize the sensitivity of the gradiometer. The sensitivity reaches 1.5 × 10‑5 s‑2 for an interferometer time of 20 ms, limited only by geometrical constraints. We observed extremely low sensitivity of the gradiometric phase to magnetic field gradients, approaching a value 104 times lower than the sensitivity of alkali-atom based gradiometers, limited by the interferometer sensitivity. An efficient double-launch technique employing accelerated red vertical lattices from a single magneto-optical trap cloud is also demonstrated. These results highlight strontium as an ideal candidate for precision measurements of gravity gradients, with potential application in future precision tests of fundamental physics.

  14. Functions of the Magnaporthe oryzae Flb3p and Flb4p transcription factors in the regulation of conidiation.

    PubMed

    Matheis, S; Yemelin, A; Scheps, D; Andresen, K; Jacob, S; Thines, E; Foster, A J

    2017-03-01

    The Magnaporthe oryzae genes FLB3 and FLB4, orthologues of the Aspergillus nidulans regulators of conidiation FlbC and FlbD, were inactivated. These genes encode C2H2 zinc finger and Myb-like transcription factors, respectively, in A. nidulans. Analysis of the resultant mutants demonstrated that FLB4 is essential for spore formation and that strains lacking this gene are fluffy in their colony morphology due to an inability to complete conidiophore formation. Meanwhile, FLB3 is required for normal levels of aerial mycelium formation. We identified genes dependent on both transcription factors using microarray analysis. This analysis revealed that the transcription of several genes encoding proteins implicated in sporulation in Magnaporthe oryzae and other filamentous fungi are affected by FLB3 or FLB4 inactivation. Furthermore, the microarray analysis indicates that Flb3p may effectively reprogramme the cell metabolically by repressing transcription of genes encoding biosynthetic enzymes and inducing transcription of genes encoding catabolic enzymes. Additionally, qRT-PCR was employed and showed that FLB3 and FLB4 transcripts are enriched in synchronously sporulating cultures, as were the transcripts of other genes that are necessary for normal conidiation, consistent with a role for their gene products in this process. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  15. Dual-level direct dynamics studies for the hydrogen abstraction reaction of 1,1-difluoroethane with O( 3P)

    NASA Astrophysics Data System (ADS)

    Liu, Jing-yao; Li, Ze-sheng; Dai, Zhen-wen; Zhang, Gang; Sun, Chia-chung

    2004-01-01

    We present dual-level direct dynamics calculations for the CH 3CHF 2 + O( 3P) hydrogen abstraction reaction in a wide temperature range, based on canonical variational transition-state theory including small curvature tunneling corrections. For this reaction, three distinct transition states, one for α-abstraction and two for β-abstraction, have been located. The potential energy surface information is obtained at the MP2(full)/6-311G(d,p) level of theory, and higher-level single-point calculations for the stationary points are preformed at several levels, namely QCISD(T)/6-311+G(3df,3pd), G2, and G3 using the MP2 geometries, as well as at the G3//MP4SDQ/6-311G(d,p) level. The energy profiles are further refined with the interpolated single-point energies method at the G3//MP2(full)/6-311G(d,p) level. The total rate constants match the experimental data reasonable well in the measured temperature range 1110-1340 K. It is shown that at low temperature α-abstraction may be the major reaction channel, while β-abstraction will have more contribution to the whole reaction rate as the temperature increases.

  16. Electrical Investigation of Nanostructured Fe2O3/p-Si Heterojunction Diode Fabricated Using the Sol-Gel Technique

    NASA Astrophysics Data System (ADS)

    Mansour, Shehab A.; Ibrahim, Mervat M.

    2017-11-01

    Iron oxide (α-Fe2O3) nanocrystals have been synthesized via the sol-gel technique. The structural and morphological features of these nanocrystals were studied using x-ray diffraction, Fourier transform-infrared spectroscopy and transmission electron microscopy. Colloidal solution of synthesized α-Fe2O3 (hematite) was spin-coated onto a single-crystal p-type silicon (p-Si) wafer to fabricate a heterojunction diode with Mansourconfiguration Ag/Fe2O3/p-Si/Al. This diode was electrically characterized at room temperature using current-voltage (I-V) characteristics in the voltage range from -9 V to +9 V. The fabricated diode showed a good rectification behavior with a rectification factor 1.115 × 102 at 6 V. The junction parameters such as ideality factor, barrier height, series resistance and shunt resistance are determined using conventional I-V characteristics. For low forward voltage, the conduction mechanism is dominated by the defect-assisted tunneling process with conventional electron-hole recombination. However, at higher voltage, I-V ohmic and space charge-limited current conduction was became less effective with the contribution of the trapped-charge-limited current at the highest voltage range.

  17. Simultaneous ionization-excitation of helium to the 3s, 3p, and 3d states of He+

    NASA Astrophysics Data System (ADS)

    Zatsarinny, Oleg; Bartschat, Klaus

    2015-05-01

    We extended our work on ionization of helium with simultaneous excitation to the n = 2 states to include the n = 3 manifold of the residual ion. This requires the inclusion of pseudo-states constructed on the 3s, 3p, and 3d ionic core. We used a parallelized version of the B-spline R-matrix (BSR) package to perform a calculation with 1,254 target states, resulting in up to 3,027 coupled channels and matrices of rank up to 200,000 to be diagonalized. The triple-differential cross section (TDCS) was extracted by the projection method. We obtain excellent agreement with experiment regarding the angular dependence of the TDCS for all kinematical situations available for comparison. Some discrepancies remain for the absolute magnitude. Results for the n = 2 states are stable and closely agree with previous predictions. Work supported by the United States National Science Foundation under grants No. PHY-1212450, PHY-1430245 and the XSEDE allocation PHY-090031.

  18. Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-repressive Loop

    PubMed Central

    Chen, Jun-An; Huang, Yuan-Ping; Mazzoni, Esteban O.; Tan, G. Christopher; Zavadil, Jiri; Wichterle, Hynek

    2011-01-01

    SUMMARY Neural patterning relies on transcriptional cross-repressive interactions that ensure unequivocal assignment of neural progenitor identity to proliferating cells. Progenitors of spinal motor neurons (pMN) and V2 interneurons (p2) are specified by a pair of cross-repressive transcription factors Olig2 and Irx3. Lineage tracing revealed that many p2 progenitors transiently express the pMN marker Olig2 during spinal cord development. Here we demonstrate that the repression of Olig2 in p2 domain is controlled by mir-17-3p microRNA-mediated silencing of Olig2 mRNA. Mice lacking all microRNAs or just the mir-17~92 cluster manifest a dorsal shift in pMN/p2 boundary and impairment in the production of V2 interneurons. Our findings suggest that microRNA-mediated repression of Olig2 mRNA plays a critical role during the patterning of ventral spinal progenitor domains by shifting the balance of cross-repressive interactions between Olig2 and Irx3 transcription factors. PMID:21338882

  19. Computational and spectral studies of 6-phenylazo-3-(p-tolyl)-2H-chromen-2-one

    NASA Astrophysics Data System (ADS)

    Manimekalai, A.; Vijayalakshmi, N.

    2015-02-01

    6-Phenylazo-3-(p-tolyl)-2H-chromen-2-one 4 was prepared and characterized by IR, 1H, and 13C NMR spectral studies. The optimized structure of the chromen-2-one 4 was investigated by the Gaussian 03 B3LYP density functional method calculations at 6-31G(d,p) basis set. The gauge-independent atomic orbital (GIAO) 13C and 1H chemical shift calculations for the synthesized chromen-2-one in CDCl3 were also made by the same method. The computed IR frequencies of the chromen-2-one and the corresponding vibrational assignments were analyzed by means of potential energy distribution (PED%) calculation using vibrational energy distribution analysis (VEDA) program. The first order hyperpolarizability (βtot), polarizability (α) and dipole moment (μ) were calculated using 6-311G(d,p) basis set and the nonlinear optical (NLO) properties are also addressed theoretically. Stability of the chromen-2-one 4 molecule has been analyzed by calculating the intramolecular charge transfer using natural bond order (NBO) analysis. The molecular electrostatic potentials, HOMO-LUMO energy gap and geometrical parameters were also computed. Topological properties of the electronic charge density in chromen-2-one 4 were analyzed employing the Bader's Atoms in Molecule (AIM) theory which indicated the presence of intramolecular hydrogen bond in the molecule.

  20. Computational and spectral studies of 6-phenylazo-3-(p-tolyl)-2H-chromen-2-one.

    PubMed

    Manimekalai, A; Vijayalakshmi, N

    2015-02-05

    6-Phenylazo-3-(p-tolyl)-2H-chromen-2-one 4 was prepared and characterized by IR, (1)H, and (13)C NMR spectral studies. The optimized structure of the chromen-2-one 4 was investigated by the Gaussian 03 B3LYP density functional method calculations at 6-31G(d,p) basis set. The gauge-independent atomic orbital (GIAO) (13)C and (1)H chemical shift calculations for the synthesized chromen-2-one in CDCl3 were also made by the same method. The computed IR frequencies of the chromen-2-one and the corresponding vibrational assignments were analyzed by means of potential energy distribution (PED%) calculation using vibrational energy distribution analysis (VEDA) program. The first order hyperpolarizability (βtot), polarizability (α) and dipole moment (μ) were calculated using 6-311G(d,p) basis set and the nonlinear optical (NLO) properties are also addressed theoretically. Stability of the chromen-2-one 4 molecule has been analyzed by calculating the intramolecular charge transfer using natural bond order (NBO) analysis. The molecular electrostatic potentials, HOMO-LUMO energy gap and geometrical parameters were also computed. Topological properties of the electronic charge density in chromen-2-one 4 were analyzed employing the Bader's Atoms in Molecule (AIM) theory which indicated the presence of intramolecular hydrogen bond in the molecule. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Design and Comparative Study of O3/P2 Hybrid Structures for Room Temperature Sodium-Ion Batteries.

    PubMed

    Qi, Xingguo; Liu, Lilu; Song, Ningning; Gao, Fei; Yang, Kai; Lu, Yaxiang; Yang, Haitao; Hu, Yong-Sheng; Cheng, Zhao-Hua; Chen, Liquan

    2017-11-22

    Rechargeable sodium-ion batteries have drawn increasing attention as candidates for the post lithium-ion batteries in large-scale energy storage systems. Layered oxides are the most promising cathode materials and their pure phases (e.g., P2, O3) have been widely investigated. Here we report a series of cathode materials with O3/P2 hybrid phase for sodium-ion batteries, which possesses advantages of both P2 and O3 structures. The designed material, Na 0.78 Ni 0.2 Fe 0.38 Mn 0.42 O 2 , can deliver a capacity of 86 mAh g -1 with great rate capability and cycling performance. 66% capacity is still maintained when the current rate reaches as high as 10C, and the capacity retention is 90% after 1500 cycles. Moreover, in situ XRD was performed to examine the structure change during electrochemical testing in different voltage ranges, and the results demonstrate 4 V as the optimized upper voltage limit, with which smaller polarization, better structural stability, and better cycling performance are achieved. The results obtained here provide new insights in designing cathode materials with optimal structure and improved performance for sodium-ion batteries.

  2. Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry.

    PubMed

    Pugsley, Haley R

    2017-07-21

    Autophagy is a catabolic pathway in which normal or dysfunctional cellular components that accumulate during growth and differentiation are degraded via the lysosome and are recycled. During autophagy, cytoplasmic LC3 protein is lipidated and recruited to the autophagosomal membranes. The autophagosome then fuses with the lysosome to form the autolysosome, where the breakdown of the autophagosome vesicle and its contents occurs. The ubiquitin-associated protein p62, which binds to LC3, is also used to monitor autophagic flux. Cells undergoing autophagy should demonstrate the co-localization of p62, LC3, and lysosomal markers. Immunofluorescence microscopy has been used to visually identify LC3 puncta, p62, and/or lysosomes on a per-cell basis. However, an objective and statistically rigorous assessment can be difficult to obtain. To overcome these problems, multispectral imaging flow cytometry was used along with an analytical feature that compares the bright detail images from three autophagy markers (LC3, p62 and lysosomal LAMP1) and quantifies their co-localization, in combination with LC3 spot counting to measure autophagy in an objective, quantitative, and statistically robust manner.

  3. Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

    PubMed Central

    Pugsley, Haley R.

    2017-01-01

    Autophagy is a catabolic pathway in which normal or dysfunctional cellular components that accumulate during growth and differentiation are degraded via the lysosome and are recycled. During autophagy, cytoplasmic LC3 protein is lipidated and recruited to the autophagosomal membranes. The autophagosome then fuses with the lysosome to form the autolysosome, where the breakdown of the autophagosome vesicle and its contents occurs. The ubiquitin-associated protein p62, which binds to LC3, is also used to monitor autophagic flux. Cells undergoing autophagy should demonstrate the co-localization of p62, LC3, and lysosomal markers. Immunofluorescence microscopy has been used to visually identify LC3 puncta, p62, and/or lysosomes on a per-cell basis. However, an objective and statistically rigorous assessment can be difficult to obtain. To overcome these problems, multispectral imaging flow cytometry was used along with an analytical feature that compares the bright detail images from three autophagy markers (LC3, p62 and lysosomal LAMP1) and quantifies their co-localization, in combination with LC3 spot counting to measure autophagy in an objective, quantitative, and statistically robust manner. PMID:28784946

  4. Performance Parameters Analysis of an XD3P Peugeot Engine Using Artificial Neural Networks (ANN) Concept in MATLAB

    NASA Astrophysics Data System (ADS)

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

    DOE PAGES

    Bourgalais, Jeremy; Capron, Michael; Kailasanathan, Ranjith Kumar Abhinavam; ...

    2015-10-13

    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 + NH 3 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 themore » 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 + H 2CN production channel represents 100% of the product yield for this reaction. As a result, 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.« less

  6. Cloning and expression of antibacterial goat lactoferricin from Escherichia coli AD494(DE3)pLysS expression system.

    PubMed

    Chen, Gen-Hung; Yin, Li-Jung; Chiang, I-Hua; Jiang, Shann-Tzong

    2008-12-01

    Goat lactoferricin (GLfcin), an antibacterial peptide, is released from the N terminus of goat lactoferrin by pepsin digestion. Two GLfcin-related cDNAs, GLfcin L and GLfcin S, encoding Ala20-Ser60 and Ser36-Ser60 of goat lactoferrin, respectively, were cloned into the pET-23a(+) expression vector upstream from (His)6-Tag gene and transformed into Escherichia coli AD494(DE3)pLysS expression host. After being induced by isopropyl-beta-D-thiogalactopyranoside (IPTG), two (His)6-Tag fused recombinant lactoferricins, GLfcin L-His*Tag and GLfcin S-His*Tag, were expressed in soluble form within the E. coli cytoplasm. The GLfcin L-His*Tag and GLfcin S-His*Tag were purified using HisTrap affinity chromatography. According to an antibacterial activity assay using the agar diffusion method, GLfcin L-His*Tag had antibacterial activity against E. coli BCRC 11549, Staphylococcus aureus BCRC 25923, and Propionibacterium acnes BCRC 10723, while GLfcin S-His*Tag was able to inhibit the growth of E. coli BCRC 11549 and P. acnes BCRC 10723. These two recombinant lactoferricins behaved as thermostable peptides, which could retain their activity for up to 30 min of exposure at 100 degrees C.

  7. MiR224-3p inhibits hypoxia-induced autophagy by targeting autophagy-related genes in human glioblastoma cells.

    PubMed

    Guo, Xing; Xue, Hao; Guo, Xiaofan; Gao, Xiao; Xu, Shugang; Yan, Shaofeng; Han, Xiao; Li, Tong; Shen, Jie; Li, Gang

    2015-12-08

    Human glioblastoma multiforme (GBM) is a malignant solid tumor characterized by severe hypoxia. Autophagy plays a protective role in cancer cells under hypoxia. However, the microRNA (miRNA)-related molecular mechanisms underlying hypoxia-reduced autophagy remain poorly understood in GBM. In this study, we performed a miRNA microarray analysis on GBM cells and found that numerous miRNAs were differentially expressed under hypoxic conditions. Further research showed that miR224-3p, one of the significantly down-regulated miRNAs, was involved in regulating hypoxia-induced autophagy in GBM cells. Overexpression of miR224-3p abolished hypoxia-induced autophagy, whereas knocking down endogenous miR224-3p increased autophagic activity under normoxia. In addition, we demonstrated that miR224-3p inhibited autophagy by directly suppressing the expression of two autophagy-related genes (ATGs), ATG5 and FAK family-interacting protein of 200 kDa (FIP200). Furthermore, in vitro, miR224-3p attenuated cell proliferation and promoted hypoxia-induced apoptosis, and in vivo, overexpression of miR224-3p inhibited tumorigenesis of GBM cells. Collectively, our study identified a novel hypoxia-down-regulated miRNA, miR224-3p, as a key modulator of autophagy by inhibiting ATGs in GBM cells.

  8. MiR-144-3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4.

    PubMed

    Huang, Cong; Geng, Junnan; Wei, Xiajie; Zhang, Ruirui; Jiang, Siwen

    2016-03-01

    Despite extensive research on osteoblast differentiation and proliferation in mesenchymal stem cells (MSCs), the accurate mechanism remains to be further elucidated. MicroRNAs have been reported to be key regulators of osteoblast differentiation and proliferation. Here, we found that miR-144-3p is down-regulated during osteoblast differentiation of C3H10T1/2 cells. Overexpression of miR-144-3p inhibited osteogenic differentiation, whereas inhibition of miR-144-3p reversed this process. Furthermore, miR-144-3p inhibited the proliferation of C3H10T1/2 cells by arresting cells at the G0/G1 phase. Results from bioinformatics analysis, luciferase assay and western blotting demonstrated that miR-144-3p directly targeted Smad4. Additionally, Smad4 knockdown blocks the effects of miR-144-3p inhibitor. Therefore, we conclude that miR-144-3p negatively regulates osteogenic differentiation and proliferation of C3H10T1/2 cells by targeting Smad4. © 2016 Federation of European Biochemical Societies.

  9. MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.

    PubMed

    Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

    2015-01-01

    MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.

  10. MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2

    PubMed Central

    Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

    2015-01-01

    MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer. PMID:26722475

  11. A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity.

    PubMed

    Yu, Keshun; Soares, Juliana Moreira; Mandal, Mihir Kumar; Wang, Caixia; Chanda, Bidisha; Gifford, Andrew N; Fowler, Joanna S; Navarre, Duroy; Kachroo, Aardra; Kachroo, Pradeep

    2013-04-25

    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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Hyperfine quenching of the 2s2 2p5 3 s3P2 state of Ne-like ions

    NASA Astrophysics Data System (ADS)

    Safronova, U. I.; Stafford, A.; Safronova, A. S.

    2017-04-01

    The many-body perturbation theory (RMBPT) is used to calculate energies and multipole matrix elements to evaluate hyperfine quenching of the 2s2 2p5 3 s 3P2 state in Ne-like ions. In particular, the 3P2 excited state decays to the 1S0 ground state by M2 emission, while both 1P1 and 3P1 states decay to the ground-state by E1 emission, which is substantially faster. For odd-A nuclei, the hyperfine interaction induces admixtures of 3P1 and 1P1 states into the 3P2 state, resulting in an increase of the 3P2 transition rate and a corresponding reduction of the 3P2 lifetime. We consider 22 Ne like ions with Z = 14 - 94 and nuclear moment I =1/2. We found that the largess hyperfine quenching contribution by a factor of 2 are for Ne-like 31P and 203Tl. The smallest (less than 1%) induced contribution are the following Ne-like ions: 57Fe, 107Ag, 109Ag, 183W, and 187Os ions. For another 15 Ne-like ions the hyperfine quenching contribution is between 15% and 35%. Applications to x-ray line polarization of Ne-like lines is considered. This work is supported by the Department of Energy, National Nuclear Security Administration, under Award Number DE-NA0002954.

  13. Preparation and structure of Na2Ag5Fe3(P2O7)4 -Ag metal composite: Insights on electrochemistry

    SciTech Connect

    Zhang, Yiman; Marschilok, Amy C.; Takeuchi, Esther S.

    ABSTRACT Ag 7Fe 3(P 2O 7) 4is a 3D structured material which has been recently studied as a possible cathode material for lithium batteries. Notably, Na 7Fe 3(P 2O 7) 4is reported to be a fast-ion conductor, yet poor electrical conductor. Here, partial replacement of Na +for Ag +yielded Na 2Ag 5Fe 3(P 2O 7) 4pyrophosphate framework where the formation of Ag metal is proposed to increase the intrinsic low electrical conductivity of this polyanion electrode. Specifically, the Ag 5Na 2Fe 3(P 2O 7) 4-Ag composite is synthesized via chemical reduction of Ag 7Fe 3(P 2O 7) 4using NaBH 4.more » The occupancy of Ag +and Na +in each site was determined via Rietveld analysis of the diffraction pattern. Electrochemistry of the Ag 5Na 2Fe 3(P 2O 7) 4-Ag metal composite was explored with voltammetry and galvanostatic charge/discharge cycling. The Ag 5Na 2Fe 3(P 2O 7) 4-Ag metal composite electrodes displayed good rate capability assisted by the presence of Ag metal from the chemical reduction and in-situ electrochemical formation of a Ag conductive network.« less

  14. Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases.

    PubMed

    Müller-Deile, Janina; Dannenberg, Jan; Schroder, Patricia; Lin, Meei-Hua; Miner, Jeffrey H; Chen, Rongjun; Bräsen, Jan-Hinrich; Thum, Thomas; Nyström, Jenny; Staggs, Lynne Beverly; Haller, Hermann; Fiedler, Jan; Lorenzen, Johan M; Schiffer, Mario

    2017-10-01

    The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna. Zebrafish vegf-A protein could not rescue this phenotype. However, mouse Npnt constructs containing a mutated 3'UTR region prevented the phenotype caused by miR-378a-3p mimic injection. Overexpression of miR-378a-3p in mice confirmed glomerular dysfunction in a mammalian model. Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT. Thus, miR-378a-3p-mediated suppression of the glomerular matrix protein NPNT is a novel mechanism for proteinuria development in active glomerular diseases. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  15. New nighttime retrievals of O(3P) and OH densities in the mesosphere/lower thermosphere using SABER/TIMED observations

    NASA Astrophysics Data System (ADS)

    Panka, P.; Kutepov, A. A.; Kalogerakis, K. S.; Janches, D.; Feofilov, A.; Rezac, L.; Marsh, D. R.; Yigit, E.

    2017-12-01

    We present first retrievals of O(3P) and OH densities in the mesosphere/lower thermosphere (MLT) using SABER/TIMED OH 2.0 and 1.6 μm limb emission observations. Recently, Kaufmann et al. [2014] reported that current SABER O(3P) densities are on average 30% higher compared to other observations. In this study we applied new detailed non-LTE model [Panka et al. 2017] of nighttime OH(v), which accounts for the new mechanism OH(v≥5)+O(3P)→O(1D)+OH(v-5) of energy transfer recently suggested by Sharma et al. [2015] and confirmed through laboratory studies by Kalogerakis et al. [2016]. Based on this model we developed a new self-consistent two channel retrieval approach for O(3P) and OH density. Using this approach, we retrieved O(3P) densities that are 10-40% lower than current SABER O(3P), as well as total OH density which is retrieved for the first time using SABER observations. We compare our retrieveals with the results of other observations and models. As it was recently shown by Panka et al. [2017], the new mechanism of OH quenching produces a significant pumping of CO2 4.3 µm emission. We discuss the effects these new O(3P) and OH retrievals have on the nighttime CO2 density retrievals from the SABER 4.3 µm channel.

  16. Stress and developmental regulation of the yeast C-type cyclin Ume3p (Srb11p/Ssn8p).

    PubMed Central

    Cooper, K F; Mallory, M J; Smith, J B; Strich, R

    1997-01-01

    The ume3-1 allele was identified as a mutation that allowed the aberrant expression of several meiotic genes (e.g. SPO11, SPO13) during mitotic cell division in Saccharomyces cerevisiae. Here we report that UME3 is also required for the full repression of the HSP70 family member SSA1. UME3 encodes a non-essential C-type cyclin (Ume3p) whose levels do not vary through the mitotic cell cycle. However, Ume3p is destroyed during meiosis or when cultures are subjected to heat shock. Ume3p mutants resistant to degradation resulted in a 2-fold reduction in SPO13 mRNA levels during meiosis, indicating that the down-regulation of this cyclin is important for normal meiotic gene expression. Mutational analysis identified two regions (PEST-rich and RXXL) that mediate Ume3p degradation. A third destruction signal lies within the highly conserved cyclin box, a region that mediates cyclin-cyclin-dependent kinase (Cdk) interactions. However, the Cdk activated by Ume3p (Ume5p) is not required for the rapid destruction of this cyclin. Finally, Ume3p destruction was not affected in mutants defective for ubiquitin-dependent proteolysis. These results support a model in which Ume3p, when exposed to heat shock or sporulation conditions, is targeted for destruction to allow the expression of genes necessary for the cell to respond correctly to these environmental cues. PMID:9303311

  17. Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression

    PubMed Central

    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

  18. MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2.

    PubMed

    Werner, Tamara V; Hart, Martin; Nickels, Ruth; Kim, Yoo-Jin; Menger, Michael D; Bohle, Rainer M; Keller, Andreas; Ludwig, Nicole; Meese, Eckart

    2017-03-23

    Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype.Following in silico prediction of potential targets of miR-34a-3p, SMAD4 , FRAT1 , and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3'UTRs. Disruption of the miR-34a-3p binding sites in the 3'UTRs resulted in loss of responsiveness to miR-34a-3p overexpression. In meningioma cells, overexpression of miR-34a-3p resulted in decreased protein levels of SMAD4, FRAT1 and BCL2, while inhibition of miR-34a-3p led to increased levels of these proteins as confirmed by Western blotting. Furthermore, deregulation of miR-34a-3p altered cell proliferation and apoptosis of meningioma cells in vitro .We show that SMAD4 , FRAT1 and BCL2 are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro . As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation of SMAD4 , FRAT1 and BCL2 might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas.

  19. MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

    PubMed Central

    Werner, Tamara V.; Hart, Martin; Nickels, Ruth; Kim, Yoo-Jin; Menger, Michael D.; Bohle, Rainer M.; Keller, Andreas; Ludwig, Nicole; Meese, Eckart

    2017-01-01

    Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype. Following in silico prediction of potential targets of miR-34a-3p, SMAD4, FRAT1, and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3'UTRs. Disruption of the miR-34a-3p binding sites in the 3'UTRs resulted in loss of responsiveness to miR-34a-3p overexpression. In meningioma cells, overexpression of miR-34a-3p resulted in decreased protein levels of SMAD4, FRAT1 and BCL2, while inhibition of miR-34a-3p led to increased levels of these proteins as confirmed by Western blotting. Furthermore, deregulation of miR-34a-3p altered cell proliferation and apoptosis of meningioma cells in vitro. We show that SMAD4, FRAT1 and BCL2 are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro. As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation of SMAD4, FRAT1 and BCL2 might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas. PMID:28340489

  20. MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway.

    PubMed

    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.

  1. Methylation-associated silencing of microRNA-129-3p promotes epithelial-mesenchymal transition, invasion and metastasis of hepatocelluar cancer by targeting Aurora-A.

    PubMed

    Cui, Shiyun; Zhang, Kai; Li, Chen; Chen, Jing; Pan, Yan; Feng, Bing; Lu, Lei; Zhu, Ziman; Wang, Rui; Chen, Longbang

    2016-11-22

    Metastasis and recurrence has become one major obstacle for further improving the survival of hepatocelluar cancer (HCC) patients. Therefore, it is critical to elucidate the mechanisms involved in HCC metastasis. This study aimed to investigate the roles of microRNA (miR)-129-3p in HCC metastasis and its possible molecular mechanisms. By using microarray analysis to compare levels of different miRNAs in HCC tissues with or without lymph node metastasis (LNM), we showed that HCC tissues with LNM had reduced levels of miR-129-3p, which was related to its promoter hypermethylation and correlated with tumor metastasis, recurrence and poor prognosis. Gain - and loss - of - function assays indicated that re-expression of miR-129-3p could reverse epithelial-mesenchymal transition (EMT), and reduce in vitro invasion and in vivo metastasis of HCC cells. Aurora-A, a serine/threonine protein kinase, was identified as a direct target of miR-129-3p. Knockdown of Aurora-A phenocopied the effect of miR-129-3p overexpression on HCC metastasis. In addition, Aurora-A upregulation could partially rescue the effect of miR-129-3p. We further demonstrated that activation of PI3K/Akt and p38-MAPK signalings were involved in miR-129-3p-mediated HCC metastasis. These findings suggest that methylation-mediated miR-129-3p downregulation promotes EMT, in vitro invasion and in vivo metastasis of HCC cells via activation of PI3K/Akt and p38-MAPK signalings partially by targeting Aurora-A. Therefore, miR-129-3p may be a novel prognostic biomarker and potential therapeutic target for HCC.

  2. Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver.

    PubMed

    Zhang, Wenxiang; Wang, Peng; Chen, Siyu; Zhang, Zhao; Liang, Tingming; Liu, Chang

    2016-06-01

    Circadian clocks orchestrate daily oscillations in mammalian behaviors, physiology, and gene expression. MicroRNAs (miRNAs) play a crucial role in fine-tuning of the circadian system. However, little is known about the direct regulation of the clock genes by specific miRNAs. In this study, we found that miR-27b-3p exhibits rhythmic expression in the metabolic tissues of the mice subjected to constant darkness. MiR-27b-3p's expression is induced in livers of unfed and ob/ob mice. In addition, the oscillation phases of miR-27b-3p can be reversed by restricted feeding, suggesting a role of peripheral clock in regulating its rhythmicity. Bioinformatics analysis indicated that aryl hydrocarbon receptor nuclear translocator-like (also known as Bmal1) may be a direct target of miR-27b-3p. Luciferase reporter assay showed that miR-27b-3p suppressed Bmal1 3' UTR activity in a dose-dependent manner, and mutagenesis of their binding site abolished this suppression. Furthermore, overexpression of miR-27b-3p dose-dependently reduced the protein expression levels of BMAL1 and impaired the endogenous BMAL1 and gluconeogenic protein rhythmicity. Collectively, our results suggest that miR-27b-3p plays an important role in the posttranscriptional regulation of BMAL1 protein in the liver. MiR-27b-3p may serve as a novel node to integrate the circadian clock and energy metabolism.-Zhang, W., Wang, P., Chen, S., Zhang, Z., Liang, T., Liu, C. Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver. © FASEB.

  3. MicroRNA-124-3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study.

    PubMed

    He, Rong-Quan; Yang, Xia; Liang, Liang; Chen, Gang; Ma, Jie

    2018-04-01

    The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed. Differentially expressed genes identified following miR-124-3p transfection, the prospective target genes predicted in silico and the key genes of HCC obtained from Natural Language Processing (NLP) were integrated to obtain potential target genes of miR-124-3p in HCC. Relevant signaling pathways were assessed with protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Annotation Through Evolutionary Relationships (PANTHER) pathway enrichment analysis. miR-124-3p expression was significantly reduced in HCC tissues compared with expression in adjacent non-cancerous liver tissues. In HCC, miR-124-3p was demonstrated to be associated with clinical stage. The mean survival time of the low miR-124-3p expression group was reduced compared with that of the high expression group. A total of 132 genes overlapped from differentially expressed genes, miR-124-3p predicted target genes and NLP identified genes. PPI network construction revealed a total of 109 nodes and 386 edges, and 20 key genes were identified. The major enriched terms of three GO categories included regulation of cell proliferation, positive regulation of cellular biosynthetic processes, cell leading edge, cytosol and cell projection, protein kinase activity, transcription activator activity and enzyme binding. KEGG analysis revealed pancreatic cancer, prostate cancer and non-small cell lung cancer as the

  4. Computational study of collisions between O(3P) and NO(2Π) at temperatures relevant to the hypersonic flight regime.

    PubMed

    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.

  5. 6-[3-(p-Tolyl­sulfonyl­amino)­prop­yl]diquino­thia­zine1

    PubMed Central

    Jeleń, Małgorzata; Shkurenko, Aleksander; Suwińska, Kinga; Pluta, Krystian; Morak-Młodawska, Beata

    2013-01-01

    In the title mol­ecule {systematic name: N-[3-(diquino[3,2-b;2′,3′-e][1,4]thia­zin-6-yl)prop­yl]-4-methyl­benzene­sulfon­amide}, C28H24N4O2S2, the penta­cyclic system is relatively planar [maximum deviation from the mean plane = 0.242 (1) Å]. The dihedral angle between two quinoline ring systems is 8.23 (2)° and that between the two halves of the 1,4-thia­zine ring is 5.68 (3)°. The conformation adopted by the 3-(p-tolyl­sulfonyl­amino)­propyl substituent allows for the formation of an intra­molecular N—H⋯N hydrogen bond and places the benzene ring of this substituent above one of the quinoline fragments of the penta­cyclic system. In the crystal, mol­ecules are arranged via π–π stacking inter­actions into (0-11) layers [centroid–centroid distances = 3.981 (1)–4.320 (1) Å for the rings in the penta­cyclic system and 3.645 (1) Å for the tolyl benzene rings]. In addition, mol­ecules are involved in weak C—H⋯O, which connect the layers, and C—H⋯S hydrogen bonds. The title compound shows promising anti­cancer activity against renal cancer cell line UO-31. PMID:23795128

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

    SciTech Connect

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

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

  7. Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis

    PubMed Central

    Jackson, Joseph W.; Singh, Meera V.; Singh, Vir B.; Jones, Letitia D.; Davidson, Gregory A.; Ture, Sara; Morrell, Craig N.; Schifitto, Giovanni; Maggirwar, Sanjay B.

    2016-01-01

    Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies. PMID:27270236

  8. Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis.

    PubMed

    Jackson, Joseph W; Singh, Meera V; Singh, Vir B; Jones, Letitia D; Davidson, Gregory A; Ture, Sara; Morrell, Craig N; Schifitto, Giovanni; Maggirwar, Sanjay B

    2016-01-01

    Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies.

  9. Investigation of tumor suppressor genes apart from VHL on 3p by deletion mapping in sporadic clear cell renal cell carcinoma (cRCC).

    PubMed

    Singh, Rashmi Bhat; Amare Kadam, Pratibha S

    2013-10-01

    To investigate the most recurrent deletion loci on 3p12-p26 by deletion mapping studies by PCR-LOH and BAC array-FISH in sporadic conventional renal cell carcinoma (cRCC) and further, to evaluate the their clinicopathologic significance in cRCC. Comparative allelotyping studies in cRCC and major epithelial carcinomas (MEC) such as lung, breast, and bladder tumors were also carried out to investigate the specificity of the targeted loci in cRCC. A total of 40 c-RCC patients were enrolled in this study, categorized in to 2 groups: group I comprises of patients of stages I and II and group II includes patients at stages III and IV. Loss of heterozygosity (LOH) studies were performed by PCR using 15 microsatellite markers of region 3p12-p26 on paired normal-tumor tissues. The recurrent LOH loci found in 27 cRCC tumors were further validated by BAC array-FISH using 23 serially mapped BAC clones. Simultaneously, the allelic deletion status of fragile histidine triad (FHIT) gene was studied by FISH in cRCC and major epithelial carcinoma (MEC) tumors. The numerical aberrations of chromosome 3 were also studied using the centromere enumeration probe (CEP) probe for chromosome 3 to validate the observed allelic losses by BAC array-FISH in cRCC as well as MECs. Our study revealed 3 affected regions of LOH on 3p in cRCC: 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 in both group I (stages I and II) and group II (stage III and IV). Comparative allelotyping studies revealed that except for LOH loci D3S2406 (20%), D3S1766 (14%), and D3S1560 (20%), remaining affected loci revealed retention of heterozygosity (ROH) in breast carcinomas. Lung and bladder tumors revealed ROH at all affected LOH loci. FISH with FHIT gene probe revealed deletions in cRCC (88%), breast (30%), and lung tumors (10%). FHIT gene deletions frequency was almost equal in both groups I and II (>70%), whereas a locus 3p13 (D3S2454) revealed the highest LOH in group II (83%) patients in comparison to group I (16

  10. An in-situ phosphorus source for the synthesis of Cu 3P and the subsequent conversion to Cu 3PS 4 nanoparticle clusters

    SciTech Connect

    Sheets, Erik J.; Stach, Eric A.; Yang, Wei -Chang

    2015-09-20

    The search for alternative earth abundant semiconducting nanocrystals for sustainable energy applications has brought forth the need for nanoscale syntheses beyond bulk synthesis routes. Of particular interest are metal phosphides and derivative I-V-VI chalcogenides including copper phosphide (Cu 3P) and copper thiophosphate (Cu 3PS 4). Herein, we report a one-pot, solution-based synthesis of Cu 3P nanocrystals utilizing an in-situ phosphorus source: phosphorus pentasulfide (P 2S 5) in trioctylphosphine (TOP). By injecting this phosphorus source into a copper solution in oleylamine (OLA), uniform and size controlled Cu 3P nanocrystals with a phosphorous-rich surface are synthesized. The subsequent reaction of the Cumore » 3P nanocrystals with decomposing thiourea forms nanoscale Cu 3PS 4 particles having p-type conductivity and an effective optical band gap of 2.36 eV.« less

  11. Downregulation of miR-221-3p contributes to IL-1β-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway.

    PubMed

    Zheng, Xin; Zhao, Feng-Chao; Pang, Yong; Li, Dong-Ya; Yao, Sheng-Cheng; Sun, Shao-Song; Guo, Kai-Jin

    2017-06-01

    Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4

  12. Purification, crystallization and preliminary X-ray diffraction analysis of a soluble variant of the monoglyceride lipase Yju3p from the yeast Saccharomyces cerevisiae

    SciTech Connect

    Rengachari, Srinivasan; Aschauer, Philipp; Sturm, Christian

    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 =more » 167.7 Å. The asymmetric unit contained four molecules with a solvent content of 46.4%.« less

  13. MicroRNA-19a/b-3p protect the heart from hypertension-induced pathological cardiac hypertrophy through PDE5A.

    PubMed

    Liu, Kun; Hao, Qiongyu; Wei, Jie; Li, Gong-Hao; Wu, Yong; Zhao, Yun-Feng

    2018-04-16

    PDE5A is a leading factor contributing to cGMP signaling and cardiac hypertrophy. However, microRNA-mediated posttranscriptional regulation of PDE5A has not been reported. The aim of this study is to screen the microRNAs that are able to regulate PDE5A and explore the function of the microRNAs in cardiac hypertrophy and remodeling. Although miR-19a/b-3p (microRNA-19a-3p and microRNA-19b-3p) have been reported to be differentially expressed during cardiac hypertrophy, the direct targets and the functions of this microRNA family for regulation of cardiac hypertrophy have not yet been investigated. The present study identified some direct targets and the underlying functions of miR-19a/b-3p by using bioinformatics tools and gene manipulations within mouse neonatal cardiomyocytes. Transfection of miR-19a/b-3p down-regulated endogenous expressions of PDE5A at both mRNA and protein levels with real-time PCR and western blot. Luciferase reporter assays showed that PDE5A was a direct target of miR-19a/b-3p. In mouse models of cardiac hypertrophy, we found that miR-19a/b-3p was expressed in cardiomyocytes and that its expression was reduced in pressure overload-induced hypertrophic hearts. miR-19a/b-3p transgenic mice prevented the progress of cardiac hypertrophy and cardiac remodeling in response to angiotensin II infusion with echocardiographic assessment and pressure-volume relation analysis. Our study elucidates that PDE5A is a novel direct target of miR-19a/b-3p, and demonstrates that antihypertrophic roles of the miR-19a/b-3p family in Ang II-induced hypertrophy and cardiac remodeling, suggests that endogenous miR-19a/b-3p might have clinical potential to suppress cardiac hypertrophy and heart failure.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any

  14. MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3

    SciTech Connect

    Li, Butian; Zhang, Shengping; Shen, Hao

    MicroRNAs are aberrantly expressed in a wide variety of human cancers. The present study aims to elucidate the effects and molecular mechanisms of miR-144-3p that underlie gastric cancer (GC) development. It was observed that miR-144-3p expression was significantly decreased in GC tissues compared to that in paired non-tumor tissues; moreover, its expression was lower in tissues of advanced stage and larger tumor size, as well as in lymph node metastasis tissues compared to that in control groups. miR-144-3p expression was associated with depth of invasion (P = 0.030), tumor size (P = 0.047), lymph node metastasis (P = 0.047), and TNM stage (P = 0.048). Additionally, miR-144-3p significantlymore » inhibited proliferation, migration, and invasion in GC cells. It also reduced F-actin expression and suppressed epithelial-to-mesenchymal transition (EMT) in GC cells. Furthermore, pre-leukemia transcription factor 3 (PBX3) was a direct target gene of miR-144-3p. PBX3 was overexpressed in GC tissues and promoted EMT in GC cells. The effects of miR-144-3p mimics or inhibitors on cell migration, invasion, and proliferation were reversed by PBX3 overexpression or downregulation respectively. These results suggest that miR-144-3p suppresses GC progression by inhibiting EMT through targeting PBX3. - Highlights: • miR-144-3p is downregulated in gastric cancer tissues and associated with malignant clinical factors. • miR-144-3p inhibits proliferation, migration, and invasion in gastric cancer cells. • PBX3 is a direct target of miR-144-3p and promotes EMT in gastric cancer. • miR-144-3p suppresses EMT in gastric cancer by regulating PBX3.« less

  15. Overexpression of long intergenic noncoding RNA LINC00312 inhibits the invasion and migration of thyroid cancer cells by down-regulating microRNA-197-3p.

    PubMed

    Liu, Kai; Huang, Wen; Yan, Dan-Qing; Luo, Qing; Min, Xiang

    2017-08-31

    The study evaluated the ability of long intergenic noncoding RNA LINC00312 (LINC00312) to influence the proliferation, invasion, and migration of thyroid cancer (TC) cells by regulating miRNA-197-3p. TC tissues and adjacent normal tissues were collected from 211 TC patients. K1 (papillary TC), SW579 (squamous TC), and 8505C (anaplastic TC) cell lines were assigned into a blank, negative control (NC), LINC00312 overexpression, miR-197-3p inhibitors, and LINC00312 overexpression + miR-197-3p mimics group. The expression of LINC00312, miR-197-3p , and p120 were measured using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation was assessed via CCK8 assay, cell invasion through the scratch test, and cell migration via Transwell assay. In comparison with adjacent normal tissues, the expression of LINC00312 is down-regulated and the expression of miR-197-3p is up-regulated in TC tissues. The dual luciferase reporter gene assay confirmed that P120 is a target of miR-197-3p The expression of LINC00312 and p120 was higher in the LINC00312 overexpression group than in the blank and NV groups. However, the expression of miR-197-3p was lower in the LINC00312 overexpression group than in the blank and NC groups. The miR-197-3p inhibitors group had a higher expression of miR-197-3p , but a lower expression of p120 than the blank and NC groups. The LINC00312 overexpression and miR-197-3p inhibitor groups had reduced cell proliferation, invasion and migration than the blank and NC groups. These results indicate that a LINC00312 overexpression inhibits the proliferation, invasion, and migration of TC cells and that this can be achieved by down-regulating miR-197-3p . © 2017 The Author(s).

  16. Long noncoding RNA FTX is upregulated in gliomas and promotes proliferation and invasion of glioma cells by negatively regulating miR-342-3p.

    PubMed

    Zhang, Weiguang; Bi, Yunke; Li, Jianhua; Peng, Fei; Li, Hui; Li, Chenguang; Wang, Laizang; Ren, Fubin; Xie, Chen; Wang, Pengwei; Liang, Weiwei; Wang, Zhi; Zhu, Dan

    2017-04-01

    Gliomas remain a major public health challenge, posing a high risk for brain tumor-related morbidity and mortality. However, the mechanisms that drive the development of gliomas remain largely unknown. Emerging evidence has shown that long noncoding RNAs are key factors in glioma pathogenesis. qRT-PCR analysis was used to assess the expression of FTX and miR-342-3p in the different stages of gliomas in tissues. Bioinformatics tool DIANA and TargetSCan were used to predict the targets of FTX and miR-342-3p, respectively. Pearson's correlation analysis was performed to test the correlation between the expression levels of FTX, miR-342-3p, and astrocyte-elevated gene-1 (AEG-1). To examine the role of FTX in regulating proliferation and invasion of glioma cells, specific siRNA was used to knockdown FTX, and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell assays were performed. Furthermore, rescue experiments were performed to further confirm the regulation of miR-342-3p by FTX. We then found that the expression of FTX and miR-342-3p was associated with progression of gliomas. FTX directly inhibited the expression of miR-342-3p, which subsequently regulates the expression of AEG-1. Collectively, FTX is critical for proliferation and invasion of glioma cells by regulating miR-342-3p and AEG-1. Our findings indicate that FTX and miR-342-3p may serve as a biomarker of glioma diagnosis, and offer potential novel therapeutic targets of treatment of gliomas.

  17. The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis.

    PubMed

    Ren, Lin-Lin; Yan, Ting-Ting; Shen, Chao-Qin; Tang, Jia-Yin; Kong, Xuan; Wang, Ying-Chao; Chen, Jinxian; Liu, Qiang; He, Jie; Zhong, Ming; Chen, Hao-Yan; Hong, Jie; Fang, Jing-Yuan

    2018-06-07

    The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.

  18. LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p.

    PubMed

    Wang, Qiujun; Li, Ying; Zhang, Yuanxia; Ma, Lan; Lin, Lin; Meng, Jia; Jiang, Lihong; Wang, Liping; Zhou, Ping; Zhang, Yina

    2017-05-01

    Long non-coding RNA (lncRNA) MEG3 has proven to be an important regulator involved in the pathogenesis and development of various human diseases. However, the functional involvement of MEG3 in postmenopausal osteoporosis (PMOP) and its mechanism is still unclear. Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured from mouse pathologic models and patients with PMOP, respectively. The expression of MEG3 and miR-133a-3p in BMSCs was detected using qRT-PCR. The recombinant expression vector was constructed and transfected into BMSCs to regulate the endogenous expression of MEG3 and miR-133a-3p. The mineralized nodules formation, alkaline phosphatase (ALP) activity and Runx2, OCN, OPN expressions were used as specific markers for the differentiation of osteoblasts. The expressions of MEG3 and miR-133a-3p in BMSCs from PMOP were increased, and there was a positive correlation between MEG3 and miR-133a-3p expression in BMSCs. In the differentiation process from BMSCs to osteoblasts, the expressions of MEG3 and miR-133a-3p were markedly decreased, and MEG3 overexpression reversed the osteogenic induction-mediated downregulation of miR-133a-3p, which was accompanied by significant decline in SLC39A1 expression. Furthermore, miR-133a-3p silencing or upregulation eliminated the effects of MEG3 on the osteogenic differentiation of BMSCs through direct binding. The research indicated that MEG3 regulated the expression of miR-133a-3p, and inhibited the osteogenic differentiation of BMSCs induced PMOP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. MicroRNA-101-3p suppresses cell proliferation, invasion and enhances chemotherapeutic sensitivity in salivary gland adenoid cystic carcinoma by targeting Pim-1

    PubMed Central

    Liu, Xiao-Yu; Liu, Zhi-Jian; He, Hong; Zhang, Chen; Wang, Yun-Long

    2015-01-01

    MicroRNAs (miRNAs) play critical roles in carcinogenesis and tumor progression. Recent research has revealed miR-101-3p as an important regulator in several cancers. Nevertheless, its function in salivary gland Adenoid cystic carcinoma (ACC), a relatively rare malignance with poor long-term survival rate arisen in head and neck region, remain unknown. In this study, down-regulated miR-101-3p expression was detected in ACC tissues and ACC cell lines with high potential for metastasis. Ectopic expression of miR-101-3p significantly repressed the invasion, proliferation, colony formation, and formation of nude mice xenografts and induced potent apoptosis in ACC cell lines. The provirus integration site for Moloney murine leukemia virus 1 (Pim-1) oncogene was subsequently confirmed as a direct target gene of miR-101-3p in ACC. Functional restoration assays revealed that miR-101-3p inhibits cell growth and invasion by directly decreasing Pim-1 expression. Protein levels of Survivin, Cyclin D1 and β-catenin were also down-regulated by miR-101-3p. miR-101-3p enhanced the sensitivity of cisplatin in ACC cell lines. Taken together, our results demonstrate that the novel miR-101-3p/Pim-1 axis provides excellent insights into the carcinogenesis and tumor progression of ACC and may be a promising therapeutic target for this type of cancer. PMID:26693056

  20. Radiation induces premature chromatid separation via the miR-142-3p/Bod1 pathway in carcinoma cells.

    PubMed

    Pan, Dong; Du, Yarong; Ren, Zhenxin; Chen, Yaxiong; Li, Xiaoman; Wang, Jufang; Hu, Burong

    2016-09-13

    Radiation-induced genomic instability plays a vital role in carcinogenesis. Bod1 is required for proper chromosome biorientation, and Bod1 depletion increases premature chromatid separation. MiR-142-3p influences cell cycle progression and inhibits proliferation and invasion in cervical carcinoma cells. We found that radiation induced premature chromatid separation and altered miR-142-3p and Bod1 expression in 786-O and A549 cells. Overexpression of miR-142-3p increased premature chromatid separation and G2/M cell cycle arrest in 786-O cells by suppressing Bod1 expression. We also found that either overexpression of miR-142-3p or knockdown of Bod1 sensitized 786-O and A549 cells to X-ray radiation. Overexpression of Bod1 inhibited radiation- and miR-142-3p-induced premature chromatid separation and increased resistance to radiation in 786-O and A549 cells. Taken together, these results suggest that radiation alters miR-142-3p and Bod1 expression in carcinoma cells, and thus contributes to early stages of radiation-induced genomic instability. Combining ionizing radiation with epigenetic regulation may help improve cancer therapies.

  1. 18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling.

    PubMed

    Cao, Donghui; Jia, Zhifang; You, Lili; Wu, Yanhua; Hou, Zhen; Suo, Yueer; Zhang, Houjun; Wen, Simin; Tsukamoto, Tetsuya; Oshima, Masanobu; Jiang, Jing; Cao, Xueyuan

    2016-11-01

    18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer.

  2. Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis.

    PubMed

    Lapointe, Christopher P; Stefely, Jonathan A; Jochem, Adam; Hutchins, Paul D; Wilson, Gary M; Kwiecien, Nicholas W; Coon, Joshua J; Wickens, Marvin; Pagliarini, David J

    2018-01-24

    Coenzyme Q (CoQ) is a redox-active lipid required for mitochondrial oxidative phosphorylation (OxPhos). How CoQ biosynthesis is coordinated with the biogenesis of OxPhos protein complexes is unclear. Here, we show that the Saccharomyces cerevisiae RNA-binding protein (RBP) Puf3p regulates CoQ biosynthesis. To establish the mechanism for this regulation, we employed a multi-omic strategy to identify mRNAs that not only bind Puf3p but also are regulated by Puf3p in vivo. The CoQ biosynthesis enzyme Coq5p is a critical Puf3p target: Puf3p regulates the abundance of Coq5p and prevents its detrimental hyperaccumulation, thereby enabling efficient CoQ production. More broadly, Puf3p represses a specific set of proteins involved in mitochondrial protein import, translation, and OxPhos complex assembly (pathways essential to prime mitochondrial biogenesis). Our data reveal a mechanism for post-transcriptionally coordinating CoQ production with OxPhos biogenesis, and they demonstrate the power of multi-omics for defining genuine targets of RBPs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia.

    PubMed

    Li, Qinghua; Pan, Zhifang; Wang, Xuejian; Gao, Zhiqin; Ren, Chune; Yang, Weiwei

    2014-10-10

    Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. miR-659-3p is involved in the regulation of the chemotherapy response of colorectal cancer via modulating the expression of SPHK1

    PubMed Central

    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

  5. miR-24-3p Suppresses Malignant Behavior of Lacrimal Adenoid Cystic Carcinoma by Targeting PRKCH to Regulate p53/p21 Pathway.

    PubMed

    Zhang, Ming-Xue; Zhang, Jie; Zhang, Hong; Tang, Hua

    2016-01-01

    MicroRNA (miRNA) may function as an oncogene or a tumor suppressor in tumorigenesis. However, the mechanism of miRNAs in adenoid cystic carcinoma (ACC) is unclear. Here, we provide evidence that miR-24-3p was downreglated and functions as a tumor suppressor in human lacrimal adenoid cystic carcinoma by suppressing proliferation and migration/invasion while promoting apoptosis. miR-24-3p down-regulated protein kinase C eta (PRKCH) by binding to its untranslated region (3'UTR). PRKCH increased the of the cell growth and migration/invasion in ACC cells and suppressed the expression of p53 and p21 in both mRNA and protein level. The overexpression of miR-24-3p decreased its malignant phenotype. Ectopic expression of PRKCH counteracted the suppression of malignancy induced by miR-24-3p, as well as ectopic expression of miR-24-3p rescued the suppression of PRKCH in the p53/p21 pathway. These results suggest that miR-24-3p promotes the p53/p21 pathway by down-regulating PRKCH expression in lacrimal adenoid cystic carcinoma cells.

  6. 18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling

    PubMed Central

    Cao, Donghui; Jia, Zhifang; You, Lili; Wu, Yanhua; Hou, Zhen; Suo, Yueer; Zhang, Houjun; Wen, Simin; Tsukamoto, Tetsuya; Oshima, Masanobu; Jiang, Jing; Cao, Xueyuan

    2016-01-01

    18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer. PMID:27713126

  7. Utility of miR‑133a‑3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta‑analysis and bioinformatics.

    PubMed

    Liang, Hai-Wei; Yang, Xia; Wen, Dong-Yue; Gao, Li; Zhang, Xiang-Yu; Ye, Zhi-Hua; Luo, Jie; Li, Zu-Yun; He, Yun; Pang, Yu-Yan; Chen, Gang

    2018-01-01

    Increasing evidence has demonstrated that microRNA (miR)‑133a‑3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR‑133a‑3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR‑133a‑3p expression and clinicopathological features of HCC. Eventually, putative targets of miR‑133a‑3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR‑133a‑3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=‑0.54; 95% confidence interval (CI), ‑0.74 to ‑0.35; P<0.001]. Consistently, the level of miR‑133a‑1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR‑133a‑1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR‑133a‑3p expression in HCC group was noted (SMD=‑0.69; 95% CI, ‑1.10 to ‑0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR‑133a‑3p in HCC. The study reveals that miR‑133a‑3p

  8. MicroRNA-22-3p is down-regulated in the plasma of Han Chinese patients with premature ovarian failure.

    PubMed

    Dang, Yujie; Zhao, Shidou; Qin, Yingying; Han, Ting; Li, Weiping; Chen, Zi-Jiang

    2015-03-01

    To determine whether plasma microRNAs (miRNAs) are differentially expressed between women with and without premature ovarian failure (POF), and to uncover the association of miRNAs with risk of POF. Microarray with real-time polymerase chain reaction validation. University hospital. A total of 140 individuals with premature ovarian failure (POF) and 140 age- and body mass index-matched control subjects of Han Chinese ancestry. None. Relative miRNA expression levels in plasma of POF and control group. Fifty-one differentially expressed miRNAs were identified by chip-based discovery stage between ten patients with POF and ten control subjects, among which nine miRNAs (let-7b-5p, let-7c, miR-15b-5p, miR-22-3p, miR-23a-3p, miR-23b-3p, miR-24-3p, miR-151a-5p, and miR-151b) were selected and validated. The relative expression level of miR-22-3p was significantly down-regulated in POF compared with control subjects. MiR-22-3p yielded a receiver operating characteristic (ROC) curve area of 0.668 (95% confidence interval 0.602-0.733) in discriminating POF from controls. In addition, logistic binary regression analysis and linear regression analysis showed the miR-22-3p to be a protective factor for POF (odds ratio 0.766, 95% CI 0.643-0.912) and negatively associated with serum FSH. Furthermore, bioinformatics analysis indicated that the target function of miR-22-3p was involved in apoptosis, endocytosis, and tumorigenesis. Mir-22-3p showed a lower expression level in POF and was modestly effective in distinguishing POF from control subjects. The decreased expression of miR-22-3p in plasma of POF may reflect the diminished ovarian reserve and be a consequence of the pathologic process of POF. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Aberrant Expression of miR-142-3p and its Target Gene HMGA1 and FZD7 in Breast Cancer and its Clinical Significance.

    PubMed

    Jia, Xiu-Peng; Meng, Ling-Li; Fang, Jian-Chen; Wang, Hong-Wei; Chen, Jie; Zhou, Jue; Wang, Chun-Nian; Jiang, Wei-Feng

    2018-06-01

    Breast cancer is the second leading cause of cancer-related death among women worldwide. The aim of this study is to investigate the role of miR-142-3p in breast cancer cells and the related mechanism. Sixty paired breast cancer tissues were collected and 60 breast tissues from patients with mammary hyperplasia served as the control group. The expression of miR-142-3p was examined using RT-qPCR methods; moreover, we also performed receiver operating characteristic (ROC) curve analysis to determine whether miR142-3p can distinguish breast cancer patients from the controls. Next, HMGA1 and FZD7 have been predicted as target genes of miR-142-3p, and the expressions of HMGA1 and FZD7 in breast cancer tissue and the control group were examined using RT-qPCR and western blot methods. miR-142-3p was significantly down-regulated in breast cancer tissue compared with the controls, and the levels of miR-142-3p was negatively correlated with the tumor size, degree of differentiation, and metastasis (p < 0.01). Moreover, results of ROC curve analysis indicated that the expression of miR-142-3p can distinguish between patients with breast cancer and the control group (AUC = 0.819, 95% CI, 0.756 - 0.881). Furthermore, the expressions of HMGA1 and FZD7 were significantly up-regulated in patients with breast cancer compared with the controls. The level of miR-142-3p was negatively correlated with expressions of HMGA1 (r = -0.3507, p = 0.006) and FZD7 (r = -0.3410, p = 0.0077) in patients with breast cancer. Our results proved that miR-142-3p may serve as a tumor suppressor in breast cancer by suppressing the expression of oncogene HMGA1 and FZD7, suggesting that miR-142-3p has the potential to become a diagnostic marker and therapeutic target for the early diagnosis and treatment of breast cancer.

  10. miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA.

    PubMed

    Xia, Yu-Fang; Pei, Gui-Hua; Wang, Ning; Che, Yan-Ci; Yu, Feng-Sheng; Yin, Fu-Fen; Liu, Hai-Xia; Luo, Bing; Wang, Yan-Kui

    2017-02-04

    Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Herein, the purposes of this study were to identify the relationship between HPV infection and aberrantly expressed miRNAs and to investigate their pathogenic roles in CC. miRNA expression was assessed using a microRNAs microarray in HPV16 E6- and E7-integrated HPV-negative HT-3 cell lines and mock vector-transfected HT-3 cells. The microarray results were validated, and the expression of miR-3156-3p was identified in HPV-positive and -negative CC cell lines as well as primary CC and normal cervical epithelium tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), flow cytometry, transwell analysis, tube formation, and Western blotting were used to identify the functional role of miR-3156-3p in CaSki, SiHa, and HeLa cell lines. Six underexpressed microRNAs (miR-3156-3p, 6779-3p, 4779-3p, 6841-3p, 454-5p and 656-5p) were consistently identified in HPV16 E6- and E7-integrated HT-3 cells. Further investigation confirmed a significant decrease of miR-3156-3p in HPV16/18 positive CC lesions. CCK8, flow cytometry, transwell analysis, tube formation assays, and Western blotting of the CC cell lines with miR-3156-3p over/under-expression in vitro showed that miR-3156-3p was involved in cell proliferation, apoptosis, migration, neovascularization, and SLC6A6 regulation. Our findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection.

  11. A qRT-PCR and Gene Functional Enrichment Study Focused on Downregulation of miR-141-3p in Hepatocellular Carcinoma and Its Clinicopathological Significance.

    PubMed

    Liu, Cui-Zhen; Ye, Zhi-Hua; Ma, Jie; He, Rong-Quan; Liang, Hai-Wei; Peng, Zhi-Gang; Chen, Gang

    2017-01-01

    The clinical significance of miR-141-3p in hepatocellular carcinoma has not been verified. Therefore, we conducted this study to examine miR-141-3p expression and its clinical significance in hepatocellular carcinoma and to investigate the functions of its potential targets. The Cancer Genome Atlas database and the Gene Expression Omnibus database were used to explore the aberrant expression of miR-141-3p in hepatocellular carcinoma. Furthermore, we assessed the miR-141-3p levels in 95 hepatocellular carcinoma tissues with 95 matched adjacent tissues using real-time quantitative polymerase chain reaction. Moreover, a target gene prediction analysis of miR-141-3p, a natural language processing analysis for hepatocellular carcinoma using PubMed, and a gene functional enrichment analysis were conducted to search the potential function of miR-141-3p in the pathogenesis of hepatocellular carcinoma. Regarding The Cancer Genome Atlas data, miR-141-3p levels were markedly downregulated in hepatocellular carcinoma tissue compared to para- or nontumor tissue (4.6112 [1.7096] vs 5.3053 [1.4254], P = .045). MiR-141-3p expression was reduced in patients with hepatocellular carcinoma with a low pathologic T stage ( P = .006), a low grade ( P = .01), elderly hepatocellular carcinoma patients ( P = .001), and male patients with hepatocellular carcinoma ( P = .01) compared with that in patients with hepatocellular carcinoma with high pathologic T stages, high grades, young patients with hepatocellular carcinoma, and female patients with hepatocellular carcinoma. However, according to the Gene Expression Omnibus database, no significant differences in the expression of miR-141-3p were observed between hepatocellular carcinoma tissue and normal liver tissue ( P = .984). Real-time quantitative polymerase chain reaction confirmed a similar trend of decreased miR-141-3p in hepatocellular carcinoma tissue (1.7542 [0.8663] vs 2.5562 [1.7913], P = .001) as observed in The Cancer Genome

  12. The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis

    PubMed Central

    Dreijerink, Koen; Braga, Eleonora; Kuzmin, Igor; Geil, Laura; Duh, Fuh-Mei; Angeloni, Debora; Zbar, Berton; Lerman, Michael I.; Stanbridge, Eric J.; Minna, John D.; Protopopov, Alexei; Li, Jingfeng; Kashuba, Vladimir; Klein, George; Zabarovsky, Eugene R.

    2001-01-01

    Clear cell-type renal cell carcinomas (clear RCC) are characterized almost universally by loss of heterozygosity on chromosome 3p, which usually involves any combination of three regions: 3p25-p26 (harboring the VHL gene), 3p12-p14.2 (containing the FHIT gene), and 3p21-p22, implying inactivation of the resident tumor-suppressor genes (TSGs). For the 3p21-p22 region, the affected TSGs remain, at present, unknown. Recently, the RAS association family 1 gene (isoform RASSF1A), located at 3p21.3, has been identified as a candidate lung and breast TSG. In this report, we demonstrate aberrant silencing by hypermethylation of RASSF1A in both VHL-caused clear RCC tumors and clear RCC without VHL inactivation. We found hypermethylation of RASSF1A's GC-rich putative promoter region in most of analyzed samples, including 39 of 43 primary tumors (91%). The promoter was methylated partially or completely in all 18 RCC cell lines analyzed. Methylation of the GC-rich putative RASSF1A promoter region and loss of transcription of the corresponding mRNA were related causally. RASSF1A expression was reactivated after treatment with 5-aza-2′-deoxycytidine. Forced expression of RASSF1A transcripts in KRC/Y, a renal carcinoma cell line containing a normal and expressed VHL gene, suppressed growth on plastic dishes and anchorage-independent colony formation in soft agar. Mutant RASSF1A had reduced growth suppression activity significantly. These data suggest that RASSF1A is the candidate renal TSG gene for the 3p21.3 region. PMID:11390984

  13. YAC contigs covering an 8-megabase region of 3p deleted in the small-cell lung cancer cell line U2020

    SciTech Connect

    Todd, S.; Bolin, R.; Drabkin, H.A.

    1995-01-01

    Somatic deletions of chromosome 3p occur at high frequencies in cancers of kidney, breast, cervix, head and neck, nasopharynx, and lung. The frequency of 3p deletion in lung cancer approaches 100% among small cell lesions and 70 to 80% in non-small cell lesions. This evidence strongly implies that one or more tumor suppressor genes of potentially widespread significance reside within the deleted region(s). Precise definition of the deleted target region(s) has been difficult due to the extensive area(s) lost and use of markers with low informativeness. However, improved definition remains essential to permit isolation of putative tumor suppressor genes frommore » 3p. The identification of several small, homozygous 3p deletions in lung cancer cell lines has provided a critical resource that will assist this search. The U2020 cell line contains a small homozygous deletion that maps to a very proximal region of 3p and includes the marker D3S3. We previously identified a subset of DNA markers located within the deleted region and determined their relative order by pulsed-field gel mapping studies. In the present report, we describe the development of YAC contigs that span the majority of the deleted region and link up to flanking markers on both sides. The centromere proximal portion of the contig crosses the breakpoint from an X;3 translocation located within 3p12 providing both location and orientation to the map. PCR-based (CA){sub n} microsatellite polymorphisms have been localized within and flanking the deletion region. These markers should greatly facilitate loss-of-heterozygosity studies of this region in human cancer. The contig provides a direct means for isolation of putative tumor suppressor genes from this segment of 3p. 51 refs., 3 figs., 3 tabs.« less

  14. miR-338-3p confers 5-fluorouracil resistance in p53 mutant colon cancer cells by targeting the mammalian target of rapamycin.

    PubMed

    Han, Jia; Li, Jie; Tang, Kaijie; Zhang, Huahua; Guo, Bo; Hou, Ni; Huang, Chen

    2017-11-15

    Evidence demonstrate that p53 mutations and microRNAs (miRs) are important components of 5-FU resistance in colorectal cancer (CRC). miR-338-3p has been reported associated with cancer prognosis. However whether or not it influences chemotherapy sensitivity and the underlying mechanisms have not been elucidated. Here, three types of human colon cancer cell lines, HT29 (mutant p53), HCT116 (wild-type p53), and HCT116 p53 -/- (deficient p53), were treated with 5-FU. We showed that expres