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Sample records for 3p 5q 17p

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

    NASA Astrophysics Data System (ADS)

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

    1993-04-01

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

  2. Allelic status of chromosomes 17p, 18q, 22q [corrected] 3p and their clinical usefulness in colorectal cancer.

    PubMed

    Fujita, Shin; Baba, Hideo; Yamamoto, Seiichiro; Akasu, Takayuki; Moriya, Yoshihiro; Sugano, Kokichi; Sugno, Kokichi

    2006-01-01

    To determine whether the allelic status of chromosomes is clinically useful in colorectal cancer, the allelic losses at chromosomes 17p, 18q, 22q and 3p and their relationships with the clinicopathological features in colorectal cancer (CRC) patients, who had undergone curative surgery without adjuvant chemotherapy, were examined. The allelic status at 17p, 18q, 22q and 3p was analyzed by PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) in 139 CRC from patients who had undergone curative surgery between October 1994 and June 1996. The relationships between these allelic losses and the clinicopathological features were investigated. The lymph node status was significantly associated with the allelic status of 17p, 18q and 22q. The tumor site and tumor differentiation were significantly associated with the allelic status of 18q. When patients with more than two allelic losses were defined as the high allelic loss group and those with no, or only one allelic loss were defined as the low allelic loss group, it was found that the lymph node involvement was significantly higher in the high than in the low allelic loss group. Only three out of 25 patients in the low allelic loss group had lymph node metastasis, and 15 patients in this group without lymphatic invasion had no lymph node metastasis. There was no relationship between the allelic status and survival at any stage. The allelic status was significantly associated with lymph node metastasis. A combination of allelic status and lymphatic invasion assessment can predict the lymph node status before radical surgery.

  3. Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomas of the breast.

    PubMed

    Lininger, R A; Zhuang, Z; Man, Y; Park, W S; Emmert-Buck, M; Tavassoli, F A

    1999-12-01

    Apocrine carcinomas of the breast are an unusual special category of predominantly AR+, ER-, and PR- breast cancer, characterized by cells with abundant, eosinophilic cytoplasm and nuclei with often prominent nucleoli. To further investigate these lesions, loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci, including loci frequently mutated in breast cancer. Twenty-five intraductal apocrine carcinomas, 11 invasive apocrine carcinomas, and six apocrine hyperplasias were retrieved from the files of the Armed Forces Institute of Pathology (Washington, DC) and Fairfax Hospital (Fairfax, VA). Cells from lesional as well as normal tissues were microdissected. LOH was performed at a number of chromosomal loci, including loci commonly altered in breast cancer: 1p35-36 (NB), 3p25.5 (VHL), 8p12 (D8S136), 9p21 (p16), 11p13 (D11S904), 11q13 (INT-2 and PYGM), 16p13.3 (TSC2/PKD1 gene region), 17p13 (TP53), 17q13 (NM23), and 22q12 (D22S683). Among informative in situ and invasive apocrine carcinomas, LOH was present in 33% of 15 cases for 17p13 (TP53), as well as 36% of 14 cases for 3p25 (VHL), 30% of 10 cases for 1p35-36 (NB), and 27% of 11 cases for 16p13.3 (TSC2/PKD1). A higher frequency of LOH was noted among invasive apocrine carcinomas (30 to 50%) compared with in situ apocrine carcinomas (23 to 33%) at these loci. LOH was present simultaneously for TP53 and either VHL or NB in five cases. Infrequent (< or =12%) or absent LOH was detected at the remaining loci, including several loci commonly mutated in breast cancer (i.e., INT2, PYGM, and NM23). LOH was not detected in any of the six apocrine hyperplasias. An intermediate frequency of allelic loss was detected at multiple tumor suppressor gene loci, including 17p13 (TP53), as well as 1p35-336 (NB), 3p25 (VHL), and 16p13 (PKD1/ TSC2), in apocrine carcinomas of the breast, with a higher overall frequency of LOH noted among invasive tumors compared with in situ tumors. Aside from LOH at p53, LOH was

  4. Advances in the 5q- syndrome.

    PubMed

    Boultwood, Jacqueline; Pellagatti, Andrea; McKenzie, Andrew N J; Wainscoat, James S

    2010-12-23

    The 5q- syndrome is the most distinct of all the myelodysplastic syndromes with a clear genotype/phenotype relationship. The significant progress made during recent years has been based on the determination of the commonly deleted region and the demonstration of haploinsufficiency for the ribosomal gene RPS14. The functional screening of all the genes in the commonly deleted region determined that RPS14 haploinsufficiency is the probable cause of the erythroid defect in the 5q- syndrome. A mouse model of the human 5q- syndrome has now been created by chromosomal engineering involving a large-scale deletion of the Cd74-Nid67 interval (containing RPS14). A variety of lines of evidence support the model of ribosomal deficiency causing p53 activation and defective erythropoiesis, including most notably the crossing of the "5q- mice" with p53-deficient mice, thereby ameliorating the erythroid progenitor defect. Emerging evidence supports the notion that the p53 activation observed in the mouse model may also apply to the human 5q- syndrome. Other mouse modeling data suggest that haploinsufficiency of the microRNA genes miR-145 and miR-146a may contribute to the thrombocytosis seen in the 5q- syndrome. Lenalidomide has become an established therapy for the 5q- syndrome, although its precise mode of action remains uncertain.

  5. Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited

    PubMed Central

    Jerez, Andres; Gondek, Lukasz P.; Jankowska, Anna M.; Makishima, Hideki; Przychodzen, Bartlomiej; Tiu, Ramon V.; O'Keefe, Christine L.; Mohamedali, Azim M.; Batista, Denise; Sekeres, Mikkael A.; McDevitt, Michael A.; Mufti, Ghulam J.; Maciejewski, Jaroslaw P.

    2012-01-01

    Purpose Interstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations. Patients and Methods We analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders. Results We identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q− syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present. Conclusion Our results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme. PMID:22370328

  6. Deletion 5q35.3

    SciTech Connect

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

    1994-06-01

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

  7. Lenalidomide: Myelodysplastic syndromes with del(5q) and beyond.

    PubMed

    Talati, Chetasi; Sallman, David; List, Alan

    2017-07-01

    Myelodysplastic syndrome (MDS) with deletion 5q (del(5q)) is a distinct clinical and pathological disease subset that is exquisitely sensitive to lenalidomide for the treatment of red blood cell transfusion-dependent anemia. Although lenalidomide has erythropoeitic promoting activity in MDS without del(5q) (non-del(5q) MDS), the frequency of response to treatment is lower and relates to biologically separate drug effects. In del(5q) MDS, lenalidomide suppresses the malignant clone to restore effective erythropoiesis by virtue of synthetic lethality, arising from cereblon-dependent degradation of haplodeficient proteins encoded within the commonly deleted region of the chromosome 5q deletion. In contrast, in non-del(5q) MDS, lenalidomide restores effective erythropoiesis via enhancement of erythropoietin (EPO) receptor-initiated transcriptional response arising from the assembly of signaling-competent receptor complexes within membrane lipid raft domains. Recently, large phase III clinical studies have explored the role of lenalidomide, alone and in combination with, erythropoiesis-stimulating agents showing additive improvement in erythroid responses. Herein, we will describe the mechanisms of lenalidomide action in MDS and pivotal clinical studies testing the benefit of lenalidomide in both del(5q) and non-del(5q) MDS. Furthermore, we discuss evidence-based strategies to incorporate lenalidomide into the treatment algorithm for patients with MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Recurrent genetic defects on chromosome 5q in myeloid neoplasms

    PubMed Central

    Hosono, Naoko; Mahfouz, Reda; Przychodzen, Bartlomiej; Yoshida, Kenichi; Jerez, Andres; LaFramboise, Thomas; Polprasert, Chantana; Clemente, Michael J; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Sanada, Masashi; Cui, Edward; Verma, Amit K; McDevitt, Michael A; List, Alan F; Saunthararajah, Yogen; Sekeres, Mikkael A; Boultwood, Jacqueline; Ogawa, Seishi

    2017-01-01

    Background Deletion of chromosome 5q (del(5q)) is the most common karyotypic abnormality in myeloid neoplasms. Materials and Methods To define the pathogenic molecular features associated with del(5q), next–generation sequencing was applied to 133 patients with myeloid neoplasms (MDS; N = 69, MDS/MPN; N = 5, sAML; N = 29, pAML; N = 30) with del(5q) as a sole abnormally or a part of complex karyotype and results were compared to molecular features of patients diploid for chr5. Findings A number of 5q genes with haploinsufficient expression and/or recurrent somatic mutations were identified; for these genes, CSNK1A1 and G3BP1 within the commonly deleted 5q region and DDX41 within a commonly retained region were most commonly affected by somatic mutations. These genes showed consistent haploinsufficiency in deleted cases; low expression/mutations of G3BP1 or DDX41 were associated with poor survival, likely due to decreased cellular function. The most common mutations on other chromosomes in patients with del(5q) included TP53, and mutations of FLT3 (ITD or TKD), NPM1 or TET2 and were mutually exclusive. Serial sequencing allowed for definition of clonal architecture and dynamics, in patients with exome sequencing allelic imbalance for informative SNPs facilitated simultaneous approximation of clonal size of del(5q) and clonal burden for somatic mutations. Interpretation Our results illuminate the spectrum of molecular defects characteristic of del(5q), their clinical impact and succession of stepwise evolution. PMID:28031539

  9. Genetics Home Reference: 5q31.3 microdeletion syndrome

    MedlinePlus

    ... 4 links) KidsHealth from Nemours: Delayed Speech or Language Development MalaCards: severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion Merck Manual Consumer Version: Seizure ... Association Chromosome Disorder Outreach Resource List from ...

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

    SciTech Connect

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

    1994-09-01

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

  11. Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-.

    PubMed

    Mallo, Mar; Arenillas, Leonor; Espinet, Blanca; Salido, Marta; Hernández, Jesús M; Lumbreras, Eva; del Rey, Mónica; Arranz, Eva; Ramiro, Soraya; Font, Patricia; González, Olga; Renedo, Mónica; Cervera, José; Such, Esperanza; Sanz, Guillermo F; Luño, Elisa; Sanzo, Carmen; González, Miriam; Calasanz, María José; Mayans, José; García-Ballesteros, Carlos; Amigo, Victoria; Collado, Rosa; Oliver, Isabel; Carbonell, Félix; Bureo, Encarna; Insunza, Andrés; Yañez, Lucrecia; Muruzabal, María José; Gómez-Beltrán, Elena; Andreu, Rafael; León, Pilar; Gómez, Valle; Sanz, Angeles; Casasola, Natalia; Moreno, Esperanza; Alegre, Adrián; Martín, María Luisa; Pedro, Carmen; Serrano, Sergi; Florensa, Lourdes; Solé, Francesc

    2008-07-01

    More than 50% of patients with myelodysplastic syndromes present cytogenetic aberrations at diagnosis. Partial or complete deletion of the long arm of chromosome 5 is the most frequent abnormality. The aim of this study was to apply fluorescence in situ hybridization of 5q31 in patients diagnosed with de novo myelodysplastic syndromes in whom conventional banding cytogenetics study had shown a normal karyotype, absence of metaphases or an abnormal karyotype without evidence of del(5q). We performed fluorescence in situ hybridization of 5q31 in 716 patients, divided into two groups: group A patients (n=637) in whom the 5q deletion had not been detected at diagnosis by conventional banding cytogenetics and group B patients (n=79), in whom cytogenetic analysis had revealed the 5q deletion (positive control group). In group A (n=637), the 5q deletion was detected by fluorescence in situ hybridization in 38 cases (5.96%). The majority of positive cases were diagnosed as having the 5q- syndrome. The deletion was mainly observed in cases in which the cytogenetics study had shown no metaphases or an aberrant karyotype with chromosome 5 involved. In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31. Fluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q- syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q- chromosome).

  12. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion.

    PubMed

    List, Alan; Dewald, Gordon; Bennett, John; Giagounidis, Aristotle; Raza, Azra; Feldman, Eric; Powell, Bayard; Greenberg, Peter; Thomas, Deborah; Stone, Richard; Reeder, Craig; Wride, Kenton; Patin, John; Schmidt, Michele; Zeldis, Jerome; Knight, Robert

    2006-10-05

    Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder. One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis. Among the 148 patients, 112 had a reduced need for transfusions (76%; 95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74) no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1 to 49) and sustained; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. The maximum hemoglobin concentration reached a median of 13.4 g per deciliter (range, 9.2 to 18.6), with a corresponding median rise of 5.4 g per deciliter (range, 1.1 to 11.4), as compared with the baseline nadir value before transfusion. Among 85 patients who could be evaluated, 62 had cytogenetic improvement, and 38 of the 62 had a complete cytogenetic remission. There was complete resolution of cytologic abnormalities in 38 of 106 patients whose serial bone marrow samples could be evaluated. Moderate-to-severe neutropenia (in 55% of patients) and thrombocytopenia (in 44%) were the most common reasons for interrupting treatment or adjusting the dose of lenalidomide. Lenalidomide can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients who have the myelodysplastic syndrome with the 5q31 deletion. (ClinicalTrials.gov number, NCT00065156 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

  13. Copy Number Variation at Chromosome 5q21.2 Is Associated With Intraocular Pressure

    PubMed Central

    Nag, Abhishek; Venturini, Cristina; Hysi, Pirro G.; Arno, Matthew; Aldecoa-Otalora Astarloa, Estibaliz; MacGregor, Stuart; Hewitt, Alex W.; Young, Terri L.; Mitchell, Paul; Viswanathan, Ananth C.; Mackey, David A.; Hammond, Christopher J.

    2013-01-01

    Purpose. Glaucoma is a major cause of blindness in the world. Recent genome-wide association studies (GWAS) have identified common genetic variants for glaucoma, but still a significant heritability gap remains. We hypothesized that copy number variants (CNVs) might influence part of the susceptibility to glaucoma or its related quantitative endophenotypes. Methods. This study examined the association between CNVs and intraocular pressure (IOP), the major modifiable risk factor for primary open-angle glaucoma (POAG), in three population panels of European ancestry: the TwinsUK cohort (n = 1047), the Australian Twin Eye Study (n = 561), and the Wellcome Trust Case-Control Consortium 2 (WTCCC2)/Blue Mountains Eye Study (BMES) (n = 1660). We also used PCR-based assays to investigate a locus of interest that we found associated with IOP in a POAG case–control panel of European ancestry from London, United Kingdom. Results. We identified associations between IOP and two CNV regions in the TwinsUK cohort: 5q21.2 (P = 0.003) overlapping the gene RAB9BP1 and 12p13.3 (P = 0.03) overlapping the genes SLC2A14 and SLC2A3. The Australian Twin Eye Study and BMES both replicated the 5q21.2 CNV association and direction of effect (P = 0.001 and P = 0.02, respectively). A meta-analysis across all the cohorts showed that presence of a copy number change at this locus increased IOP by 1.56 mm Hg (P = 1.24 × 10−6). In the case–control study, the 5q21.2 CNV locus did not show association with high-pressure (≥21 mm Hg) POAG cases. Conclusions. The 5q21.2 CNV locus could represent a novel locus controlling IOP. Interestingly, this IOP locus is located in close vicinity to the previously widely replicated GLC1G linkage locus for glaucoma, for which subsequent studies have not reached consensus on the causal gene. PMID:23599335

  14. Copy number variation at chromosome 5q21.2 is associated with intraocular pressure.

    PubMed

    Nag, Abhishek; Venturini, Cristina; Hysi, Pirro G; Arno, Matthew; Aldecoa-Otalora Astarloa, Estibaliz; Macgregor, Stuart; Hewitt, Alex W; Young, Terri L; Mitchell, Paul; Viswanathan, Ananth C; Mackey, David A; Hammond, Christopher J

    2013-05-01

    Glaucoma is a major cause of blindness in the world. Recent genome-wide association studies (GWAS) have identified common genetic variants for glaucoma, but still a significant heritability gap remains. We hypothesized that copy number variants (CNVs) might influence part of the susceptibility to glaucoma or its related quantitative endophenotypes. THIS STUDY EXAMINED THE ASSOCIATION BETWEEN CNVS AND INTRAOCULAR PRESSURE (IOP), THE MAJOR MODIFIABLE RISK FACTOR FOR PRIMARY OPEN-ANGLE GLAUCOMA (POAG), IN THREE POPULATION PANELS OF EUROPEAN ANCESTRY: the TwinsUK cohort (n = 1047), the Australian Twin Eye Study (n = 561), and the Wellcome Trust Case-Control Consortium 2 (WTCCC2)/Blue Mountains Eye Study (BMES) (n = 1660). We also used PCR-based assays to investigate a locus of interest that we found associated with IOP in a POAG case-control panel of European ancestry from London, United Kingdom. WE IDENTIFIED ASSOCIATIONS BETWEEN IOP AND TWO CNV REGIONS IN THE TWINSUK COHORT: 5q21.2 (P = 0.003) overlapping the gene RAB9BP1 and 12p13.3 (P = 0.03) overlapping the genes SLC2A14 and SLC2A3. The Australian Twin Eye Study and BMES both replicated the 5q21.2 CNV association and direction of effect (P = 0.001 and P = 0.02, respectively). A meta-analysis across all the cohorts showed that presence of a copy number change at this locus increased IOP by 1.56 mm Hg (P = 1.24 × 10(-6)). In the case-control study, the 5q21.2 CNV locus did not show association with high-pressure (≥21 mm Hg) POAG cases. The 5q21.2 CNV locus could represent a novel locus controlling IOP. Interestingly, this IOP locus is located in close vicinity to the previously widely replicated GLC1G linkage locus for glaucoma, for which subsequent studies have not reached consensus on the causal gene.

  15. An unusually large 5q duplication in an adult female subject: spreading of inactivation and in vitro instability of the derivative Xp/5q chromosome.

    PubMed

    Rovescalli, A; Ghidoni, A

    1989-01-01

    An unbalanced translocation resulting in an unusually large partial 5q trisomy (5q11-5qter) and partial Xp monosomy (Xp11-Xpter) is reported in a 24 yr old woman with phenotypic abnormalities including gonadal dysgenesis and mental retardation. The karyotypes of the parents and the brother were found normal. Peripheral blood stimulated lymphocytes and cutaneous fibroblasts of the proband exhibited constantly, after BrdU incorporation, selective inactivation of the derivative X;5 chromosome spreading to the 5q duplicate segment. A variety of numerical and structural changes involving the derivative chromosome were observed in about 10% of cells of the cultured lymphoblastoid line established from the subject's lymphocytes. The extended 5q duplication, according to the literature, is generally accompanied by a severe phenotype and by developmental failure; it is therefore believe that genetic inactivation of the 5q duplicated region permitted the proband's development to adult age, despite the profound chromosomal imbalance.

  16. Familial dup(5)(q15q21) associated with normal and abnormal phenotypes.

    PubMed

    Li, S Y; Gibson, L H; Gomez, K; Pober, B R; Yang-Feng, T L

    1998-01-06

    We studied a familial dup(5q) present in a phenotypically normal father and his monozygotic twin daughters with different abnormal phenotypes. High-resolution chromosome analysis suggested that the duplicated segment was of region q15-21, which seems to be the smallest dup(5q) reported thus far. This dup(5q) was confirmed by fluorescence in situ hybridization with a chromosome 5 painting library and 5q cosmid clones. The presence of the dup(5q) in a normal father suggested that the duplication itself may be harmless. The anomalies in the twins may be due to processes other than this chromosome change.

  17. 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.

  18. 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.

  19. 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.

  20. CSNK1A1 mutations and gene expression analysis in myelodysplastic syndromes with del(5q).

    PubMed

    Bello, Erica; Pellagatti, Andrea; Shaw, Jacqueline; Mecucci, Cristina; Kušec, Rajko; Killick, Sally; Giagounidis, Aristoteles; Raynaud, Sophie; Calasanz, María J; Fenaux, Pierre; Boultwood, Jacqueline

    2015-06-18

    Mutations of CSNK1A1, a gene mapping to the commonly deleted region of the 5q- syndrome, have been recently described in patients with del(5q) myelodysplastic syndromes (MDS). Haploinsufficiency of Csnk1a1 in mice has been shown to result in β-catenin activation and expansion of haematopoietic stem cells (HSC). We have screened a large cohort of 104 del(5q) MDS patients and have identified mutations of CSNK1A1 in five cases (approximately 5%). We have shown up-regulation of β-catenin target genes in the HSC of patients with del(5q) MDS. Our data further support a central role of CSNK1A1 in the pathogenesis of MDS with del(5q). © 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  1. Pure partial trisomy 5q33-->5q35 resulting from the adjacent-1 segregation of a paternal (5;14)(q33;p12) translocation.

    PubMed

    Paoloni-Giacobino, A; Bottani, A; Dahoun, S P

    1999-01-01

    A 14-year-old male was referred for evaluation of mental retardation with short stature and dysmorphic features. His karyotype was 46,XY,der(14)t(5;14)(q33;p12)pat, resulting in a pure partial 5q33-q35 trisomy due to the adjacent-1 segregation of a paternal balanced translocation. Paternal blood karyotype revealed a balanced translocation t(5;14)(q33;p12) retaining Ag-Nors. To date, only two cases of pure partial 5q trisomies spanning this region have been reported. Analysis of these cases and the one we report does not allow the delineation of a specific phenotype.

  2. β-Catenin Is a Candidate Therapeutic Target for Myeloid Neoplasms with del(5q).

    PubMed

    Li, Liping; Sheng, Yue; Li, Wenshu; Hu, Chao; Mittal, Nupur; Tohyama, Kaoru; Seba, Amber; Zhao, You-Yang; Ozer, Howard; Zhu, Tongyu; Qian, Zhijian

    2017-08-01

    Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with de novo myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/β-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether β-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here, we report that genetic deletion of a single allele of β-catenin rescues ineffective hematopoiesis in an Apc haploinsufficient mouse model, which recapitulates several characteristic features of the preleukemic stage of myeloid neoplasms with a -5/del(5q). In addition, loss of a single allele of β-catenin reversed the defective self-renewal capacity of Apc-haploinsufficient hematopoietic stem cells and reduced the frequency of apoptosis induced by Apc haploinsufficiency. Suppression of β-catenin by indomethacin or β-catenin shRNA reduced proliferation and survival of human leukemia cell lines with del(5q) but not of control leukemia cell lines in vitro ; β-catenin inactivation also inhibited leukemia progression in vivo in xenograft mice reconstituted with del(5q) leukemia cell lines. Inhibition of β-catenin also stunted growth and colony-forming abilities of primary bone marrow cells from del(5q) AML patients in vitro Overall, our data support the idea that β-catenin could serve as a therapeutic target for the treatment of myeloid neoplasms with del(5q). Cancer Res; 77(15); 4116-26. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Delineation of the dup5q phenotype by molecular cytogenetic analysis in a patient with dup5q/del 5p (cri du chat).

    PubMed

    Levy, Brynn; Dunn, Teresa M; Kern, Jeffrey H; Hirschhorn, Kurt; Kardon, Nataline B

    2002-03-15

    An infant girl presented with multiple congenital abnormalities and a distinctive mewing cry. Her karyotype was 46,XX,add5p. Chromosome analysis on the mother revealed an apparently balanced pericentric inversion of chromosome 5, with the precise position of the breakpoints not clearly discernable by GTG banding, 46,XX,inv(5)(p15.2/3?q35.1?). Fluorescence in situ hybridization (FISH) studies using a commercial cri du chat probe (D5S721,D5S23) revealed signals on both the normal and derivative chromosomes. Telomeric probes specific for 5p and 5q were used to confirm the pericentric inversion in the mother and demonstrated the loss of the terminal 5p region and a duplication of the terminal 5q region in the proband. The imbalance on chromosome 5 in the patient was further defined using comparative genomic hybridization (CGH), which revealed a loss of material from 5p15.3 --> pter and a gain of 5q34 --> qter. The presence of the cat-like cry appears to be the only specific feature that can be linked to the loss of 5p material. The remaining dysmorphic features of this infant appear to be due specifically to the duplication of the 5q sequences. The combination of FISH, CGH, and cytogenetics has confirmed that the characteristic cry of the cri du chat syndrome is due to the deletion of the most distal part of the classic del 5p region. More importantly, our investigation has defined the duplication of 5q34 --> qter as a distinct clinical phenotype.

  4. Extinction in the Coma of Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Lacerda, Pedro; Jewitt, David

    2012-11-01

    On 2007 October 29, the outbursting comet 17P/Holmes passed within 0farcs79 of a background star. We recorded the event using optical, narrowband photometry and detect a 3%-4% dip in stellar brightness bracketing the time of closest approach to the comet nucleus. The detected dimming implies an optical depth τ ≈ 0.04 at 1farcs5 from the nucleus and an optical depth toward the nucleus center τ n < 13.3. At the time of our observations, the coma was optically thick only within ρ <~ 0farcs01 from the nucleus. By combining the measured extinction and the scattered light from the coma, we estimate a dust red albedo pd = 0.006 ± 0.002 at α = 16° phase angle. Our measurements place the most stringent constraints on the extinction optical depth of any cometary coma.

  5. Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide.

    PubMed

    Beier, Fabian; Masouleh, Behzad Kharabi; Buesche, Guntram; Ventura Ferreira, Monica S; Schneider, Rebekka K; Ziegler, Patrick; Wilop, Stefan; Vankann, Lucia; Gattermann, Norbert; Platzbecker, Uwe; Giagounidis, Aristoteles; Götze, Katharina S; Nolte, Florian; Hofmann, Wolf-Karsten; Haase, Detlef; Kreipe, Hans; Panse, Jens; Blasco, Maria A; Germing, Ulrich; Brümmendorf, Tim H

    2015-09-21

    Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug lenalidomide has significantly improved quality of life leading to transfusion independence and complete cytogenetic response rates (CCR) in the majority of patients. Telomeres are located at the end of eukaryotic chromosomes and are linked to replicative history/potential as well as genetic (in) stability of hematopoietic stem cells. Here, we analyzed telomere length (TL) dynamics before and under lenalidomide treatment in the peripheral blood and/or bone marrow of del (5q) patients enrolled in the LEMON-5 study (NCT01081431). Hematopoietic cells from del (5q) MDS patients were characterized by significantly shortened TL compared to age-matched healthy controls. Telomere loss was more accelerated in patients with longer disease duration (>2 years) and more pronounced cytopenias. Sequential analysis under lenalidomide treatment revealed that previously shortened TL in peripheral blood cells was significantly "elongated" towards normal levels within the first six months suggesting a shift from clonal del (5q) cells towards normal hematopoiesis in lenalidomide treated MDS patients. Taken together our findings suggest that the development of the del (5q) clone is associated with accelerated telomere shortening at diagnosis. However, upon induction of CCR and reoccurrence of normal hematopoiesis, the lack of a persistent TL deficit argues against telomere-mediated genetic instability neither as a disease-promoting event of del (5q) MDS nor for lenalidomide mediated development of secondary primary malignancies of the hematopoietic system in responding patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. An unusual combination of trisomy 21 and partial trisomy 5q.

    PubMed Central

    Kim, C. J.; Chi, J. G.; Lee, K. H.; Lee, C. K.; Yoo, M. S.; Paik, Y. K.

    1992-01-01

    The authors describe a male newborn with multiple congenital anomalies; craniofacial dysmorphism, bilateral cleft palate and lip, ambiguous external genitalia with absence of phallus, ventricular septal defect, agenesis of olfactory bulbs, and presence of small round cells simulating migration defect in the cerebellar white matter. Cytogenetic study demonstrated a chromosomal constitution of 47,XY, +21, +5q. Its pathological significance compared with Down's syndrome and hitherto reported partial trisomy 5q is discussed. PMID:1299243

  7. An unusual combination of trisomy 21 and partial trisomy 5q.

    PubMed

    Kim, C J; Chi, J G; Lee, K H; Lee, C K; Yoo, M S; Paik, Y K

    1992-12-01

    The authors describe a male newborn with multiple congenital anomalies; craniofacial dysmorphism, bilateral cleft palate and lip, ambiguous external genitalia with absence of phallus, ventricular septal defect, agenesis of olfactory bulbs, and presence of small round cells simulating migration defect in the cerebellar white matter. Cytogenetic study demonstrated a chromosomal constitution of 47,XY, +21, +5q. Its pathological significance compared with Down's syndrome and hitherto reported partial trisomy 5q is discussed.

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

    SciTech Connect

    Stevenson, R.; Bauer, J. M.; Mainzer, A. K.

    2014-06-01

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

  9. Cytogenetic features of 5q deletion and 5q- syndrome in myelodysplastic syndrome in Korea; marker chromosomes proved to be chromosome 5 with interstitial deletion by fluorescence in situ hybridization.

    PubMed

    Lee, Hye Ryun; Oh, Bora; Hong, Dae Sik; Zang, Dae Young; Yoon, Hwi-Joong; Kim, Hyeoung Joon; Kim, Inho; Ahn, Jae-Sook; Cheong, June-Won; Lee, Kyung-A; Cho, Kyung Sam; Lee, Mark Hong; Bang, Soo-Mee; Kim, Tae Young; Yun, Yeo-Min; Min, Yoo Hong; Lee, You Kyoung; Lee, Dong Soon

    2010-12-01

    We characterized the cytogenetic changes and prognostic characteristics of 133 Korean patients with myelodysplastic syndrome (MDS), focusing on 5q- syndrome and MDS with chromosome abnormalities involving 5q deletion according to World Health Organization 2008 classification. In all patients, G banding and fluorescence in situ hybridization for 5q were performed, and in MDS patients with 5q deletion, the deleted region on chromosome 5 was mapped with fluorescence in situ hybridization for EGR1, CSF1R, and PDGFRB. The frequency of isolated del(5q) syndrome and 5q deletion was 2.2% (3 of 137 patients) and 15.3% (21 of 137 patients), respectively. International Prognostic Scoring System (IPSS) groups were low risk (5.8%), intermediate 1 (51.1%), intermediate 2 (27.8%), and high risk (15.3%). The patients with del(5q) were significantly older (62 years) and showed an unfavorable survival compared to patients without del(5q). Half (53%) of the patients with del(5q) also had complex chromosome abnormalities, including chromosome 7 abnormalities. Of the patients with del(5q), 93.3% were deleted for all three regions on 5q, compared to 66.7% of patients with isolated del(5q). Marker chromosomes proved to be chromosome 5 with interstitial deletion of q arm by fluorescence in situ hybridization in three patients. The biological characteristics of MDS in Korea seem to be markedly different from those of Caucasians, with Koreans having a younger age, lower frequencies of 5q- syndrome, higher frequencies of complex cytogenetic abnormalities including del(5q), and poorer prognosis. We infer that additional chromosome abnormalities contribute to the adverse prognostic impact in patients with del(5q). Copyright © 2010. Published by Elsevier Inc.

  10. Non-DBA Disorders of Ribosome Function: Shwachman-Diamond Syndrome and 5q- Syndrome

    PubMed Central

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

    2011-01-01

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

  11. Duplication of 5q15-q23.2: case report and literature review.

    PubMed

    Douyard, Jaclyn; Hawley, Pamela; Shaham, Meira; Kimonis, Virginia

    2006-04-01

    Pure partial trisomy of chromosome 5q is rare and cases have ranged over the entire region, making it difficult to describe a good phenotypic correlation to the cytogenetic duplication. We present a 4.5-year-old girl with a de novo direct duplication of chromosome 5q15-q23.2. She has moderate developmental delay with lack of speech, microcephaly, and subtle dysmorphic features including prominent forehead, bulbous nose, epicanthic folds, protruding tongue, and slightly posteriorly-rotated ears. A comparison is made with other similar duplication cases reported in the literature and a general description of a proximal 5q duplication phenotype is given, with lack of speech as the principal feature. Copyright 2006 Wiley-Liss, Inc.

  12. Isolated del(5q) in Patients Following Therapies for Various Malignancies May Not All Be Clinically Significant.

    PubMed

    Tang, Guilin; Goswami, Rashmi Shivani; Liang, Cynthia S; Bueso-Ramos, Carlos E; Hu, Shimin; DiNardo, Courtney; Medeiros, L Jeffrey

    2015-07-01

    Deletion 5q is a common chromosomal abnormality in both de novo and therapy-related myeloid neoplasms (t-MNs). The detection of isolated del(5q) in patients following therapies for various malignancies raises serious concern for an emerging t-MN. We identified 25 patients who developed isolated del(5q) following cytotoxic therapy (n = 21) or tyrosine kinase inhibitor (TKI; n = 4) therapy. Twenty-four patients had an interstitial and one had a terminal 5q deletion. The 5q31/EGR1 gene was deleted in 20 patients and intact in five patients. The clone size as assessed by metaphase analysis was minor (10%-30%) in 12 patients and large (45%-100%) in 13 patients. After a median follow-up of 17 months, none of the 12 patients with a minor del(5q) clone developed t-MN; del(5q) disappeared in four patients and persisted in eight patients. By contrast, 12 of 13 patients with a large del(5q) clone developed t-MN, and del(5q) was persistent in all patients who had follow-up cytogenetic testing. Development of del(5q) in patients following cytotoxic therapies or TKI may not always be associated with t-MN. A close follow-up seems an appropriate approach for patients who had a minor del(5q) clone. Copyright© by the American Society for Clinical Pathology.

  13. A family with an inverted tandem duplication 5q22.1q23.2.

    PubMed

    Schmidt, T; Bartels, I; Liehr, T; Burfeind, P; Zoll, B; Shoukier, M

    2013-01-01

    Here, we report a 3-year-old boy with short stature, developmental delay and mild facial dysmorphic signs. Karyotype analysis and array-CGH revealed a pure duplication 5q22.1q23.2 with a length of 14.25 Mb. As demonstrated by multicolor-fluorescence in situ hybridization, the duplicated segment was orientated in an inverted tandem manner. One of the 2 older half-brothers of the index patient was intellectually disabled and showed short stature as well. The mother of the siblings was only 149 cm in height. The affected half-brother as well as the mother of the siblings were tested positive for the same duplication. Duplications of the long arm of chromosome 5 are rare. There are 16 reported cases of different 5q segments with a pure duplication and no additional chromosomal imbalance. In order to refine the 5q-duplication phenotype, reported cases were recently classified in 3 groups on the basis of clinical findings and the involved chromosome segments. However, our case does not fit in any of these groups but is placed in the interjacent chromosomal area between 2 of these groups. Overall, this is the second reported family with a duplication of 5q22.1q23.2 and both families share phenotypic features like short stature, facial dysmorphic signs and speech delay. The reported family provides further information for delineating phenotype-genotype correlations of pure duplications of the 5q region. Copyright © 2012 S. Karger AG, Basel.

  14. Dosage analysis at the CSF1 and CSF1R loci in a new case of partial trisomy 5q.

    PubMed

    Genuardi, M; Flamia, R; Palka, G; Parruti, G; Neri, G

    1992-05-01

    We report on a new case of trisomy for the distal portion of chromosome 5q, arising from a maternal balanced translocation, t(5;22)(q33;q13). The patient presented with mental retardation and peculiar craniofacial anomalies, similar to those already described in trisomy 5q3. Overall, the phenotype bore some resemblance to that of the Brachmann-De Lange syndrome. The extent of the duplicated region was investigated through a combined molecular-cytogenetic approach, using 5q probes for gene dosage analysis by Southern blot, which allowed confirmation of breakpoint assignment to band 5q33. Since most manifestations of trisomy 5q3 are observed in patients with duplications spanning 5q34-qter, it seems that the critical sequences involved in phenotype determination lie within this very distal segment.

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

    SciTech Connect

    Ouafik, L.H.; Giraud, P.; Oliver, C.

    1993-11-01

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

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

    SciTech Connect

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

    1994-09-01

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

  17. Efficacy and safety of lenalidomide in patients with myelodysplastic syndrome with chromosome 5q deletion

    PubMed Central

    Duong, Vu H.; Komrokji, Rami S.

    2012-01-01

    Myelodysplastic syndrome (MDS) with del(5q) is a unique hematopoietic stem cell disease that typically follows an indolent course and demonstrates particular sensitivity to lenalidomide, a second-generation immunomodulatory agent. Early trials demonstrated rapid and durable responses leading to US Food and Drug Administration (FDA) approval in 2005. Definitive confirmatory evidence from a large phase III trial was recently published. Other recent advances include a better understanding of the pathogenesis of disease including haplodeficiency of several candidate genes, and elucidation of the lenalidomide-specific effect on two phosphatases ultimately leading to p53 degradation in the erythroid progenitors and cell cycle arrest in earlier myeloid progenitors. In this review, we describe the pathogenesis of MDS with del(5q), summarize the major clinical studies establishing the activity of lenalidomide in this population, discuss commonly encountered adverse events, and shed light on practical uses of this agent in the clinic. PMID:23556117

  18. Physical mapping, linkage analysis of a putative schizophrenia locus on chromosome 5q.

    PubMed

    Kaufmann, C A; DeLisi, L E; Lehner, T; Gilliam, T C

    1989-01-01

    Two recent studies have suggested that a schizophrenia susceptibility locus may lie on the proximal long arm of chromosome 5. Partial trisomy of a 20-30 centimorgan region of chromosome 5 (5q11.2-13.3) was found to cosegregate with schizophrenia in a Canadian family of Chinese descent. Moreover, DNA markers from proximal 5q (D5S39, D5S76) were found to be linked to schizophrenia and related disorders in seven British and Icelandic families. We now report an initial physical map of DNA markers relative to the partial trisomy chromosome 5, as well as preliminary evidence against linkage of this region to schizophrenia in four American families.

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

    SciTech Connect

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

    1994-09-01

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

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

    SciTech Connect

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

    1994-09-01

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

  1. Experimental determination of the O17(p,α)N14 and O17(p,γ)F18 reaction rates

    NASA Astrophysics Data System (ADS)

    Chafa, A.; Tatischeff, V.; Aguer, P.; Barhoumi, S.; Coc, A.; Garrido, F.; Hernanz, M.; José, J.; Kiener, J.; Lefebvre-Schuhl, A.; Ouichaoui, S.; de Séréville, N.; Thibaud, J.-P.

    2007-03-01

    The O17(p,α)N14 and O17(p,γ)F18 reactions are of major importance to hydrogen-burning nucleosynthesis in a number of different stellar sites. In particular, O17 and F18 nucleosynthesis in classical novae is strongly dependent on the thermonuclear rates of these two reactions. The previously estimated rate for O17(p,α)N14 carries very large uncertainties in the temperature range of classical novae (T=0.01 0.4 GK), whereas a recent measurement has reduced the uncertainty of the O17(p,γ)F18 rate. We report on the observation of a previously undiscovered resonance at Ec.m.=183.3 keV in the O17(p,α)N14 reaction, with a measured resonance strength ωγpα=(1.6±0.2)×10-3 eV. We studied in the same experiment the O17(p,γ)F18 reaction by an activation method, and the resonance strength was found to amount to ωγpγ=(2.2±0.4)×10-6 eV. The excitation energy of the corresponding level in F18 was determined to be 5789.8±0.3 keV in a Doppler shift attenuation method measurement, which yielded a value of τ<2.6 fs for the level lifetime. The O17(p,α)N14 and O17(p,γ)F18 reaction rates were calculated using the measured resonance properties and reconsidering some previous analyses of the contributions of other levels or processes. The O17(p,α)N14 rate is now well established below T=1.5 GK, with uncertainties reduced by orders of magnitude in the temperature range T=0.1 0.4 GK. The uncertainty in the O17(p,γ)F18 rate is somewhat larger because of remaining obscurities in the knowledge of the direct capture process. These new resonance properties have important consequences for O17 nucleosynthesis and γ-ray emission of classical novae.

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

    PubMed

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

    2000-10-23

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

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

    SciTech Connect

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

    2013-02-15

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

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Temporal Chondroblastoma with a Novel Chromosomal Translocation (2;5) (q33;q13)

    PubMed Central

    Carlson, Andrew P.; Yonas, Howard; Olson, Garth T.; Reichard, Kaaren K.; Medina-Flores, Rafael

    2011-01-01

    The case of a 51-year-old man with a large temporal mass is presented. The mass eroded the floor of the middle fossa medially to the sphenoid sinus. A combined approach with neurosurgery and otolaryngology was performed to achieve maximal resection of the mass. Pathology was typical for chondroblastoma: a rare, benign but locally invasive chondroid tumor. Genetic testing revealed a translocation of (2;5) (q33;q13). This is a unique genetic mutation in all chondroid tumors to our knowledge. The diagnostic utility or role of this mutation in the pathobiology of this tumor remains to be determined. PMID:23984205

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Jamsheer, Aleksander; Sowińska, Anna; Simon, Dorota; Jamsheer-Bratkowska, Małgorzata; Trzeciak, Tomasz; Latos-Bieleńska, Anna

    2013-01-24

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

  12. Locus for Familial Migrainous Vertigo Disease Maps to Chromosome 5q35

    PubMed Central

    Bahmad, Fayez; DePalma, Steven R.; Merchant, Saumil N.; Bezerra, Roberta L.; Oliveira, Carlos A.; Seidman, Christine E.; Seidman, Jonathan G.

    2009-01-01

    Objectives Migrainous vertigo (episodic vertigo associated with migraine) is sometimes inherited as an autosomal dominant trait. However, neither disease genes nor loci that might be responsible have been reported. We sought to map the genetic locus for familial migrainous vertigo in a 4-generation family and to define the progression of disease in this family. Methods We studied 23 members in a family in whom migrainous vertigo was inherited as an autosomal dominant trait. Clinical information obtained included case histories and results of otolaryngological, neurologic, audiometric, and imaging evaluations. Genome-wide linkage analysis was performed with Affymetrix Genechip Human Mapping 10K microarrays. Genotyping of family members' DNA with microsatellite markers was used to further assess candidate loci identified from the whole-genome scan. Results Of 23 family members, 10 suffered from migrainous vertigo beginning after 35 years of age. Migraine headaches usually preceded the onset of vertigo by 15 to 20 years. Longitudinal audiometric studies over 12 years showed stable, high-frequency sensorineural hearing loss consistent with presbycusis. Low-frequency or fluctuating hearing loss was not observed. The results of vestibular testing and imaging studies were unremarkable. Genetic analysis defined a 12.0 MB interval on chromosome 5q35 between loci rs244895 and D5S2073 that contained the disease gene (logarithm of odds score, 4.21). Conclusions We report the first locus for familial migrainous vertigo, which mapped to 5q35. PMID:19810609

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

    SciTech Connect

    Melki, J.; Lefebvre, S.; Burglen, L.

    1994-06-03

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

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

    SciTech Connect

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

    1994-06-03

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

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

    SciTech Connect

    Li, Xiang; Wang Jabs, E.; Hawkins, A.L.

    1994-02-01

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

  16. 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

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

    SciTech Connect

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

    1994-02-01

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

  18. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression.

    PubMed

    Jädersten, Martin; Saft, Leonie; Smith, Alexander; Kulasekararaj, Austin; Pomplun, Sabine; Göhring, Gudrun; Hedlund, Anette; Hast, Robert; Schlegelberger, Brigitte; Porwit, Anna; Hellström-Lindberg, Eva; Mufti, Ghulam J

    2011-05-20

    To determine the frequency of TP53 mutations and the level of p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) and to assess their impact on disease progression. Pre- and postprogression bone marrow (BM) samples from 55 consecutive patients with International Prognostic Scoring System low risk (n = 32) or intermediate-1 risk (n = 23) were studied by next-generation sequencing of TP53. IHC for p53 was performed on 148 sequential BM samples. TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Mutations were equally common in low-risk and intermediate-1-risk patients and were associated with evolution to acute myeloid leukemia (5 of 10 v 7 of 45; P = .045). Nine of 10 patients carrying mutations showed more than 2% BM progenitors with strong p53 staining. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients (0 of 7 v 12 of 24; P = .024). By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making.

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2005-09-10

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

  1. Oculocutaneous albinism in a patient with 17p13.2-pter duplication - a review on the molecular syndromology of 17p13 duplication.

    PubMed

    Kucharczyk, Marzena; Jezela-Stanek, Aleksandra; Gieruszczak-Bialek, Dorota; Kugaudo, Monika; Cieslikowska, Agata; Pelc, Magdalena; Krajewska-Walasek, Malgorzata

    2015-06-01

    Chromosomal duplications involving 17p13.3 have recently been defined as a new distinctive syndrome with several diagnosed patients. Some variation is known to occur in the breakpoints of the duplicated region and, consequently, in the phenotype as well. We report on a patient, the fifth to our knowledge, a 4-year-old girl with a pure de novo subtelomeric 17p13.2-pter duplication. She presents all of the facial features described so far for this duplication and in addition, a unilateral palmar transversal crease and oculocutaneous albinism which has not been reported previously. A detailed molecular description of the reported aberration and correlation with the observed phenotypical features based on a literature review. We discuss the possible molecular etiology of albinism in regard to the mode of inheritance. The new data provided here may be useful for further genotype correlations in syndromes with oculocutaneous albinism, especially of autosomal dominant inheritance.

  2. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation.

    PubMed

    Liu, Ting Xi; Becker, Michael W; Jelinek, Jaroslav; Wu, Wen-Shu; Deng, Min; Mikhalkevich, Natallia; Hsu, Karl; Bloomfield, Clara D; Stone, Richard M; DeAngelo, Daniel J; Galinsky, Ilene A; Issa, Jean-Pierre; Clarke, Michael F; Look, A Thomas

    2007-01-01

    Interstitial loss of all or part of the long arm of chromosome 5, or del(5q), is a frequent clonal chromosomal abnormality in human myelodysplastic syndrome (MDS, a preleukemic disorder) and acute myeloid leukemia (AML), and is thought to contribute to the pathogenesis of these diseases by deleting one or more tumor-suppressor genes. Although a major commonly deleted region (CDR) has been delineated on chromosome band 5q31.1 (refs. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions, and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region, showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q).

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

    PubMed

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

    2013-12-01

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

  4. A prognostic impact of separation of refractory cytopenia with multilineage dysplasia and 5q- syndrome from refractory anemia in primary myelodysplastic syndrome.

    PubMed

    Cermák, Jaroslav; Michalová, Kyra; Brezinová, Jana; Zemanová, Zuzana

    2003-03-01

    A prognostic impact of WHO classification of myelodysplastic syndrome (MDS) was studied in a group of 103 primary MDS patients with refractory anemia (RA) according to French-American-British (FAB) classification. Median survival of 37 patients with RA according to WHO criteria of 85.2 months was significantly different from that in both 37 patients with refractory cytopenia with multilineage dysplasia (RCMD) (47.0 months, P=0.002) and 29 patients with 5q- abnormality diagnosed by routine chromosome banding (36.2 months, P=0.0002). A more detailed karyotype analysis with fluorescent in situ hybridization (FISH) techniques confirmed 5q deletion as a sole cytogenetic abnormality in only 12 out of 29 patients, in 4 patients 5q- was associated with complex abnormalities involving 5q region, 13 patients had 5q deletion combined with further karyotype abberations outside 5q. No difference in median survival and estimated 3 years survival was observed between RA patients, patients with 5q- syndrome according to WHO morphology criteria and patients with 5q- as a single abnormality confirmed by FISH in contrast to patients with either additional 5q abberations or further karyotype changes not involving 5q. The same difference was also observed in time to 25% of patients evolving to acute myeloid leukemia (AML). Our study confirmed usefulness of separation of RCMD from RA. RCMD represents a poor prognostic subgroup of MDS clearly distinct from pure RA mainly due to short survival connected with progressive bone marrow failure and increased risk of leukemic transformation. We also suggest to define 5q- syndrome as primary MDS of FAB type RA with 5q deletion as a sole cytogenetic abnormality confirmed by FISH analysis. This definition enabled us to discriminate 5q- patients with favorable prognosis similar as in RA from those with poor outcome associated with 5q- combined with complex abnormalities involving either 5q or regions outside 5q.

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

    SciTech Connect

    Lacy, Dee A.; Wang, Zhi-En; Symula, Derek J.

    1999-12-03

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

  6. Thallium mercury chalcobromides, TlHg6Q4Br5 (Q = S, Se).

    PubMed

    Wibowo, Arief C; Malliakas, Christos D; Chung, Duck Young; Im, Jino; Freeman, Arthur J; Kanatzidis, Mercouri G

    2013-10-21

    The new compounds TlHg6Q4Br5 (Q = S, Se) are reported along with their syntheses, crystal structures, and thermal and optical properties, as well as electronic band structure calculations. Both compounds crystallize in the tetragonal I4/m space group with a = 14.145(1) Å, c = 8.803(1) Å, and dcalc = 7.299 g/cm(3) for TlHg6S4Br5 (compound 1) and a = 14.518(2) Å, c = 8.782(1) Å, and dcalc = 7.619 g/cm(3) for TlHg6Se4Br5 (compound 2). They consist of cuboid Hg12Q8 building units interconnected by trigonal pyramids of BrHg3, forming a three-dimensional structure. The interstitial spaces are filled with thallium and bromide ions. Compounds 1 and 2 melt incongruently and show band gaps of 3.03 and 2.80 eV, respectively, which agree well with the calculated ones. First-principles electronic structure calculations at the density functional theory level reveal that both compounds have indirect band gaps, but there also exist direct transitions at energies similar to the indirect gaps.

  7. 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

  8. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations

    SciTech Connect

    Marsh, D.G.; Neely, J.D.; Ghosh, B.

    1994-05-20

    Sib-pair analysis of 170 individuals from 11 Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum immunoglobulin E (lgE) concentration. No linkage was found between these markers and specific lgE antibody concentrations. Analysis of total lgE within a subset of 128 lgE antibody-negative sib pairs confirmed evidence for linkage to 5q31.1., especially to the interleukin-4 gene (IL4). A combination of segregation and maximum likelihood analyses provided further evidence for this linkage. These analyses suggest that IL4 or a nearby gene in 5q31.1 regulates lgE production in a nonantigen-specific (noncognate) fashion. 37more » refs., 2 figs., 2 tabs.« less

  9. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations

    SciTech Connect

    Marsh, D.G.; Neely, J.D.; Ghosh, B.; Freidhoff, L.R.; Ehrlich-Kautzky, E.; Krishnaswamy, G.; Breazeale, D.R.; Beaty, T.H.; Schou, C.

    1994-05-20

    Sib-pair analysis of 170 individuals from 11 Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum immunoglobulin E (lgE) concentration. No linkage was found between these markers and specific lgE antibody concentrations. Analysis of total lgE within a subset of 128 lgE antibody-negative sib pairs confirmed evidence for linkage to 5q31.1., especially to the interleukin-4 gene (IL4). A combination of segregation and maximum likelihood analyses provided further evidence for this linkage. These analyses suggest that IL4 or a nearby gene in 5q31.1 regulates lgE production in a nonantigen-specific (noncognate) fashion. 37 refs., 2 figs., 2 tabs.

  10. Prenatal diagnosis of monosomy 17p (17p13.3-->pter) associated with polyhydramnios, intrauterine growth restriction, ventriculomegaly, and Miller-Dieker lissencephaly syndrome in a fetus.

    PubMed

    Lin, Chin-Yi; Chen, Chih-Ping; Liau, Chiung-Ling; Su, Pen-Hua; Tsao, Teng-Fu; Chang, Tung-Yao; Wang, Wayseen

    2009-12-01

    To present the prenatal magnetic resonance imaging (MRI) and ultrasound findings of Miller-Dieker lissencephaly syndrome (MDLS) associated with chromosome 17p13.3 deletion in a fetus. A 30-year-old, primigravid woman was referred to the hospital at 31 weeks' gestation because of intrauterine growth restriction (IUGR) and polyhydramnios detected by ultrasound. The pregnancy was uneventful until 31 weeks of gestation when IUGR and polyhydramnios were first noted. Level II ultrasound at 31 weeks' gestation showed fetal biometry equivalent to 27 weeks' gestation, an amniotic fluid index of 33.4 cm, ventriculomegaly, and abnormal sulcal development with absence of gyri and sulci, and a shallow Sylvian fissure. Other organs were unremarkable. Subsequent amniocentesis revealed a 46,XY,del(17)(p13.3) karyotype. Ultrafast fetal MRI performed at 34 weeks of gestation revealed agyria/pachygyria, a figure-eight appearance of the brain, a wide and shallow Sylvian fissure, enlarged subarachnoid space, ventriculomegaly, and polyhydramnios. At 35 weeks' gestation, a 1,346-g male baby was delivered with facial dysmorphism, characteristic of MDLS. Postnatal MRI confirmed the prenatal diagnosis. Polyhydramnios, IUGR and ventriculomegaly are important prenatal ultrasound markers of MDLS. Prenatal diagnosis of these markers should include a detailed investigation of cerebral sulci and fissures, and genetic analysis for MDLS. Fetal MRI is helpful for the diagnosis of lissencephaly.

  11. 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.

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

    PubMed Central

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

    2016-01-01

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

  13. Loss of heterozygosity at 1p, 7q, 17p, and 22q in meningiomas.

    PubMed

    Chang, In Bok; Cho, Byung Moon; Moon, Seung Myung; Park, Se Hyuck; Oh, Sae Moon; Cho, Seong Jin

    2010-07-01

    Allelic losses or loss of heterozygosity (LOH) at many chromosomal loci have been found in the cells of meningiomas. The objective of this study was to evaluate LOH at several loci of different chromosomes (1p32, 17p13, 7q21, 7q31, and 22q13) in different grades of meningiomas. Forty surgical specimens were obtained and classified as benign, atypical, and anaplastic meningiomas. After DNA extraction, ten polymorphic microsatellite markers were used to detect LOH. Medical and surgical records, as well as pathologic findings, were reviewed retrospectively. LOH at 1p32 was detected in 24%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. Whereas LOH at 7q21 was found in only one atypical meningioma. LOH at 7q31 was found in one benign meningioma and one atypical meningioma. LOH at 17p13 was detected in 4%, 40%, and 80% in benign, atypical, and anaplastic meningiomas, respectively. LOH at 22q13 was seen in 48%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. LOH results at 1p32 and 17p13 showed statistically significant differences between benign and non-benign meningiomas. LOH at 1p32 and 17p13 showed a strong correlation with tumor progression. On the other hand, LOH at 7q21 and 7q31 may not contribute to the development of the meningiomas.

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. CSNK1A1 mutations and isolated del(5q) abnormality in myelodysplastic syndrome: a retrospective mutational analysis.

    PubMed

    Smith, Alexander E; Kulasekararaj, Austin G; Jiang, Jie; Mian, Syed; Mohamedali, Azim; Gaken, Joop; Ireland, Robin; Czepulkowski, Barbara; Best, Steven; Mufti, Ghulam J

    2015-05-01

    A mechanism for clonal growth advantage in isolated del(5q) disease remains elusive. CSNK1A1 resides on the critically deleted region, and deletion of this gene has been shown in mouse knockout and transplantation studies to produce some characteristics of bone marrow failure, including a proliferative advantage. We aimed to establish the frequency, nature, and clinical association of CSNK1A1 mutations in patients with myelodysplastic syndrome and associated myeloid neoplasms. Between June 1, 2004, and May 31, 2014, in King's College (London, UK), we did whole-exome sequencing of five patients with isolated del(5q) followed by targeted screening for CSNK1A1 mutations and 20 myelodysplastic syndrome-associated mutations in 245 additional patients with myeloid neoplasms. All patients met present WHO diagnostic criteria for myelodysplastic syndrome and other related myeloid neoplasms. 39 (16%) of 250 patients with myeloid neoplasms had isolated del(5q), of whom seven (18%) had CSNK1A1 mutations. All these mutations were missense and presented in a highly conserved region that is implicated in ATP catalysis. Serial sampling and response to lenalidomide treatment showed that CSNK1A1 mutations were highly associated with the del(5q) clone. Only one patient with a CSNK1A1 mutation showed complete cytogenetic response to lenalidomide. Four (57%) of the seven patients carrying a CSNK1A1 mutation showed disease progression coupled with an increase in mutant allele burden (all four were on lenalidomide). We detected coexisting myelodysplastic syndrome-related gene mutations in patients with CSNK1A1 mutations, including TP53. Similar to the effect of TP53 mutations on progression of del(5q) abnormality, mutant CSNK1A1 also gives rise to a poor prognosis in del(5q) abnormality, for which a coupled increase in P53 activation is suggested. CSNK1A1 mutations in del(5q) disease are important in the context of therapeutic manipulation and need incorporation into future prospective

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

    PubMed

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

    2014-08-01

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

  1. Loss of heterozygosity on chromosome 22q and 17p correlates with aggressiveness of meningiomas.

    PubMed

    Kim, J H; Lee, S H; Rhee, C H; Park, S Y; Lee, J H

    1998-11-01

    According to reported cytogenetic studies, there is a significant association between chromosomal aberrations and aggressiveness in meningiomas. With the method of restriction fragment length polymorphism analysis (RFLP), we examined tumor specific LOH on chromosome 17p and 22q in 30 cases of intracranial meningiomas. There were eight cases of meningiomas with aggressive characteristics, such as invasive meningioma, malignant meningioma, hemangiopericytic meningioma, and multiple meningiomas with central neurofibromatosis. Twenty-five of 30 cases (83%) were constitutionally heterozygous for at least one of the chromosome 22q DNA markers and sixteen of 25 informative cases (64%) displayed loss of heterozygosity (LOH). All of the 8 informative cases (100%) of meningiomas with aggressive characteristics, showed LOH on chromosome 22q whereas non-aggressive cases revealed LOH in eight of 17 informative cases (47%). At the loci on chromosome 17p, only two cases of malignant meningionas showed LOH. Our results suggest that the inactivations of putative tumor suppressor genes on chromosome 22q and 17p may correlate with aggressiveness and malignant transformation of meningiomas.

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

    PubMed Central

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

    1996-01-01

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

  3. Interstitial deletion of chromosome 5, del(5q), in a newborn with Down syndrome and an unusual hematologic disorder.

    PubMed

    Adams, R H; Lemons, R S; Thangavelu, M; Le Beau, M M; Christensen, R D

    1989-08-01

    A newborn with Down syndrome was noted on the 1st day of life to have an elevated white blood cell count of 79,900/mm3 with 62% lymphoblasts and a platelet count of 61,000/mm3, consistent with either transient myeloproliferative disorder of Down syndrome (TMD) or acute leukemia. Karyotype analysis of a bone marrow aspirate revealed that 20% of the cells had a 47,XY, +21 karyotype, and 80% had a 47,XY, +21, del(5)(q13q31) complement. Cytochemical and immunophenotyping of the peripheral blasts were consistent with the presence of an acute undifferentiated precursor blast clone. Results of clonogenic assays of hematopoietic progenitors from this patient's bone marrow were similar to those of patients with TMD. This patient's hematologic abnormalities resolved spontaneously without treatment by week 10 of life. This is the first report of an interstitial deletion of 5q associated with a hematologic abnormality present in an infant at birth.

  4. Calcification of basal ganglia in a patient with partial trisomy 5q and partial monosomy 18q.

    PubMed

    Nakayama, T; Sakakihara, Y; Hanaoka, S; Akagi, K; Kamoshita, S

    1993-08-01

    A patient with partial trisomy for the distal segment of the long arm of chromosome 5 (q35.1-->qter) with partial 18q monosomy is presented. The mother of the patient was phenotypically normal and was proved to be a carrier of a reciprocal translocation of the long arm of chromosomes 5 and 18 46,XX,t(5;18)(q35.1;q23). The patient shows mild mental retardation, short stature, mild obesity, dysmorphic face, eczema, minor malformations of the extremities, and bilateral intracranial calcification in the basal ganglia. Most of the clinical manifestations of the patient are compatible with the previously reported clinical features of partial trisomy of the distal segment of 5q. However, the calcification of bilateral basal ganglia has not been reported for this chromosomal anomaly.

  5. [Application of array comparative genomic hybridization in prenatal diagnosis of a case with 5q35 deletion syndrome].

    PubMed

    Feng, Zhanqi; Hu, Heping; Mao, Changqing; Wang, Dingzhan; Liu, Lei; Liu, Shiling; Jing, Zhian; Liu, Hongyan

    2017-04-10

    To use combined G-banding and array-comparative genomic hybridization (aCGH) for the prenatal diagnosis of a fetus with 5q35 deletion syndrome. Chromosomal karotypes of the fetus and parents were analyzed with G-banding analysis. aCGH was performed to detect minor chromosomal structural abnormalities. The karyotype of the fetus was ascertained as 46, XY, t(5;10)(q35;p13), and the karyotypes of the parents were normal. aCGH has identified a de novo 1.68 Mb deletion at 5q35.2q35.3 and a 1.44 Mb duplication at 10p14p13. aCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations and is a useful supplement for G banding karyptyping analysis.

  6. "Cri-du-chat" syndrome in a patient born to a mother with a paracentric inversion of chromosome 5q.

    PubMed

    Bourthoumieu, Sylvie; Esclaire, Françoise; Terro, Faraj; Baclet, Marie Claire; Bedu, Antoine; Dufetelle, Brigitte; Gilbert, Brigitte; Barthe, Dominique; Yardin, Catherine

    2003-01-01

    We report the case of a female child presented at birth with hypotonia, growth retardation and respiratory distress. Chromosome study from peripheral blood showed a 46,XX,del(5)(p14pter) karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced paracentric inversion of long arms of one chromosome 5, giving the karyotype 46,XX,inv(5)(q12q32), whereas paternal karyotype was normal. The maternal abnormality was confirmed by fluorescence in situ hybridization (FISH) and was not present in the daughter's metaphases. Microsatellite analysis in the proposita and her parents permitted us to conclude that the deleted chromosome 5 was paternal in origin, as usually described. Therefore, as might have been expected, maternal paracentric inversion of chromosome 5q and "cri-du-chat syndrome" presented by the daughter were not related.

  7. Heavy quark mass expansion for the operator Q¯γ5Q and the charm content of η,η'

    NASA Astrophysics Data System (ADS)

    Franz, M.; Pobylitsa, P. V.; Polyakov, M. V.; Goeke, K.

    1999-05-01

    Recently in the context of studies of the intrinsic charm content of the nucleon and of the η' meson two groups have arrived at different results for the 1/m3 term of the heavy quark expansion for operator Q¯γ5Q differing by the factor of six. We show that the form of both results violates certain general principles. Using the expression for the axial anomaly with the finite Pauli-Villars regularization we obtain a new expression for the 1/m3 term of the heavy quark expansion for Q¯γ5Q. With this new result we obtain an estimate for the constant fη'(c)~- 12mc21<0 4παsGμνaG~μν,aη'>~-2 MeV

  8. Neonatal spinal muscular atrophy with diaphragmatic paralysis is unlinked to 5q11.2-q13.

    PubMed Central

    Novelli, G; Capon, F; Tamisari, L; Grandi, E; Angelini, C; Guerrini, P; Dallapiccola, B

    1995-01-01

    Two sibs affected by the severe neonatal form of spinal muscular atrophy (SMA) with diaphragmatic paralysis are described. The two sibs were discordant for the haplotypes determined by DNA markers flanking the SMA locus. This supports non-linkage of SMA to chromosome 5 in this family and indicates that the uncommon SMA type I variant associated with early onset respiratory failure maps outside the 5q11.2-q13.3 region. Images PMID:7783173

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

    DTIC Science & Technology

    2016-10-01

    Public Release ; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Myelodysplastic syndromes (MDS) are a group of diseases affecting bone...AWARD NUMBER: W81XWH-15-1-0335 TITLE: The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes PRINCIPAL... Release ; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as

  10. MDR-1 expression and deletions of chromosomes 7 and 5(Q) separately indicate adverse prognosis in AML.

    PubMed

    Baldus, C; Fietz, T; Rieder, H; Schwartz, S; Thiel, E; Knauf, W

    2001-02-01

    In order to assess any correlation between MDR-1 expression and chromosomal aberrations, and to define their impact on clinical outcome in newly diagnosed AML pts, we investigated bone marrow and peripheral blood samples of 49 consecutive pts admitted to our hospital. Monosomy 7, trisomy 8 and 5q- were evaluated by means of interphase fluorescence in situ hybridization (FISH). Monosomy 7 was present in 6 pts, trisomy 8 in 5 pts, and 5q- in 6 pts. More than one aberration was seen in 7 pts. Chromosomal aberrations were mostly found in older pts (12/14 >60 years; p=0.03) and in pts with CD34 positive leukemic blasts (13/14 coexpressed CD34, p=0.0004). In 25 pts also standard G-banding analysis was performed leading to concordant results regarding chromosomes 7, 8 and 5. Flow cytometry identifyed MDR-1 positivity (MDR+) in 16 pts. MDR-1 expression appeared to be a characteristic feature in CD34+ AML (12/16 were CD34+ and MDR+ pts; p=0.013). No correlation, however, was found between chromosomal aberrations and MDR-1 expression. Pts with aberrations of either chromosomes 7, 8 or 5 detected by FISH (FISH+) were predominantly resistant to induction therapy (6/8 pts, p=0.004). A lower rate of complete remission (CR) was also seen in pts with MDR-1 expression (p=0.006). MDR+/FISH+ pts (n=3) were all refractory to remission induction, while all MDR-/FISH- pts (n=19) achieved CR (p=0.0006). MDR-1+ as well as pts with aberrations of chromosomes 7, and 5(q) showed a significantly decreased probability of overall survival. In conclusion, MDR-1 expression as well as abnormalities of chromosomes 7, and 5(q) predict poor clinical outcome in AML. The identification of these prognostic factors provides useful information for risk adapted treatment strategies.

  11. Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders

    PubMed Central

    Joslin, John M.; Fernald, Anthony A.; Tennant, Thelma R.; Davis, Elizabeth M.; Kogan, Scott C.; Anastasi, John; Crispino, John D.

    2007-01-01

    Loss of a whole chromosome 5 or a deletion of the long arm, del(5q), is a recurring abnormality in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). To identify a leukemia-related gene on chromosome 5, we previously delineated a 970-kb segment of 5q31 that is deleted in all patients examined, and prepared a transcript map of this region. EGR1 is a candidate tumor suppressor gene within the commonly deleted segment of 5q, and encodes a zinc finger transcription factor. To test the hypothesis that loss of function of Egr1 is an initiating event in the pathogenesis of AML/MDS, Egr1-deficient mice were treated with a potent DNA alkylating agent, N-ethyl-nitrosourea (ENU), to induce secondary cooperating mutations. Egr1+/− and Egr1−/− mice treated with ENU developed immature T-cell lymphomas (CD4+, CD8+) or a myeloproliferative disorder (MPD) at increased rates and with shorter latencies than that of wild-type littermates. The MPD was characterized by an elevated white blood cell count, anemia, and thrombocytopenia with ineffective erythropoiesis. Biallelic mutations of Egr1 were not observed in MPDs in Egr1+/− mice. Our data suggest that haploinsufficiency for Egr1 plays a role in murine leukemogenesis, and in the development of AML/MDS characterized by abnormalities of chromosome 5. PMID:17420284

  12. Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression

    PubMed Central

    Jädersten, Martin; Saft, Leonie; Pellagatti, Andrea; Göhring, Gudrun; Wainscoat, James S.; Boultwood, Jacqueline; Porwit, Anna; Schlegelberger, Brigitte; Hellström-Lindberg, Eva

    2009-01-01

    Clonal heterogeneity has not been described in patients with myelodysplastic syndrome with isolated del(5q), for which lenalidomide has emerged as a highly potent treatment. However, transformation to acute myeloid leukemia is occasionally observed, particularly in patients without a cytogenetic response to lenalidomide. We performed molecular studies in a patient with classical 5q- syndrome with complete erythroid and partial cytogenetic response to lenalidomide, who evolved to high-risk myelodysplastic syndrome with complex karyotype. Immunohistochemistry of pre-treatment marrow biopsies revealed a small fraction of progenitors with overexpression of p53 and sequencing confirmed a TP53 mutation. TP53 mutated subclones have not previously been described in myelodysplastic syndrome with isolated del(5q) and indicates a previously unknown heterogeneity of this disease. The aberrant subclone remained stable during the treatment with lenalidomide and expanded at transformation, suggesting that this pre-existing cell population had molecular features which made it insensitive to lenalidomide and prone to disease progression. PMID:19797731

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

    PubMed

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

    2014-10-01

    Pierre Robin sequence (PRS) is an aetiologically distinct subgroup of cleft palate. We aimed to define the critical genomic interval from five different 5q22-5q31 deletions associated with PRS or PRS-associated features and assess each gene within the region as a candidate for the PRS component of the phenotype. Clinical array-based comparative genome hybridisation (aCGH) data were used to define a 2.08 Mb minimum region of overlap among four de novo deletions and one mother-son inherited deletion associated with at least one component of PRS. Commonly associated anomalies were talipes equinovarus (TEV), finger contractures and crumpled ear helices. Expression analysis of the orthologous genes within the PRS critical region in embryonic mice showed that the strongest candidate genes were FBN2 and PHAX. Targeted aCGH of the critical region and sequencing of these genes in a cohort of 25 PRS patients revealed no plausible disease-causing mutations. In conclusion, deletion of ∼2 Mb on 5q23 region causes a clinically recognisable subtype of PRS. Haploinsufficiency for FBN2 accounts for the digital and auricular features. A possible critical region for TEV is distinct and telomeric to the PRS region. The molecular basis of PRS in these cases remains undetermined but haploinsufficiency for PHAX is a plausible mechanism. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. 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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) with superimposed 5q-syndrome.

    PubMed

    Ziarkiewicz, Mateusz; Dwilewicz-Trojaczek, Jadwiga; Pastwińska, Anna; Chmarzyńska, Elżbieta; Paszkowska-Kowalewska, Małgorzata; Koperski, Łukasz; Jędrzejczak, Wiesław Wiktor; Ziarkiewicz-Wróblewska, Bogna

    2010-01-01

    Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) is a rare entity belonging to myeloproliferative/myelodysplastic syndromes. Myelodysplastic syndrome (MDS) with isolated del(5q) is a category of MDS characterized by better prognosis and specific morphology. Herein we describe a 69-year-old male with anaemia and thrombocytosis presenting with coexisting features of both these rare diseases. After the description of the clinical data, we summarize the histopathologic, cytogenetic and molecular findings, as well as introduced treatment. Next, we discuss possible diagnostic options with reference to the relevant literature.

  18. 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

  19. Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries.

    PubMed

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

    2013-01-01

    Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries. Copyright © 2013 S. Karger AG, Basel.

  20. Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34(+) cells from patients with del(5q) myelodysplastic syndrome.

    PubMed

    Venner, Christopher P; Woltosz, Joanna Wegrzyn; Nevill, Thomas J; Deeg, H Joachim; Caceres, Gisela; Platzbecker, Uwe; Scott, Bart L; Sokol, Lubomir; Sung, Sandy; List, Alan F; Karsan, Aly

    2013-03-01

    We examined whether lenalidomide exposure up-regulates miRNAs and mRNAs, previously shown to play a role in the disease phenotype of del(5q) myelodysplastic syndrome, in pre-treatment CD34(+) marrow cells. We hypothesized that increased expression would predict for clinical response. Changes in miR-143, miR-145, miR-146a, miR-146b, miR-378, miR-584, SPARC and RPS14 were examined in del(5q) (n=10) and non-del(5q) (n=18) myelodysplastic syndrome patient samples. Significantly increased expression of miR-143 (1.8-fold and 1.5-fold in del(5q) and non-del(5q), respectively), and miR-145 (1.9-fold and 1.6-fold in del(5q) and non-del(5q), respectively) was observed. In the del(5q) myelodysplastic syndrome cohort, transfusion independence correlated with a 1.3-fold or more increase in miR-145 expression and response over 12 months correlated with a 1.5-fold or more increase. Knockdown of miR-143 and miR-145 in cord blood CD34(+) cells resulted in increased erythroid progenitor activity. Lenalidomide selectively abrogated progenitor activity in cells depleted of miR-143 and miR-145 supporting a key role for miR-143/145 in the sensitivity to lenalidomide of del(5q) myelodysplastic syndrome patients.

  1. Partial proximal trisomy of the long arm of chromosome 5 (q13 leads to q22) resulting from maternal insertion der ins (10;5).

    PubMed

    Gilgenkrantz, S; Dulucq, P; Bresson, J L; Gouget, A; Pernot, C; Gregoire, M J

    1981-12-01

    Five members of our study family were carriers of a balanced insertion (10;5) (q22;q13;q22). One of the children had psychomotor retardation and malformations resulting from a partial trisomy of the proximal long arm of chromosome 5, having received the maternal der(10). Amniocentesis identified another case of partial proximal trisomy in a fetus of a subsequent pregnancy. This clinical and family study is compared with two other published cases of proximal trisomy 5q.

  2. Acute Myeloid Leukemia With t(v;5q33) Is Associated With Poor Overall Survival and Often Lacks Myelodysplastic Features.

    PubMed

    Yabe, Mariko; Tang, Guilin; Garcia-Manero, Guillermo; Loghavi, Sanam; Lu, Xinyan; Miranda, Roberto N; Medeiros, L Jeffrey; Kantarjian, Hagop M; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-06-01

    Acute myeloid leukemia (AML) with specific balanced 5q33 translocations are classified as AML with myelodysplasia-related changes regardless of their morphologic findings or antecedent hematologic disease, but the clinicopathologic features of such cases remain poorly understood. From > 2000 cases of hematological malignancies seen at our institution between 2000 and 2013, we identified 9 AML patients with 5q33 translocations with variable partner loci, t(v;5q33). The study group included 8 men and 1 woman, with a median age of 64 years (range, 19-87 years). Four patients had an antecedent myeloproliferative neoplasm (MPN). Cytogenetic analysis showed t(v;5q33) as a sole chromosomal abnormality in 4 (44%) patients, t(v;5q33) and del(3)(q21;q26.2) in 1 (11%) patient, and a complex karyotype in 4 (44%) patients. Only 1 patient had morphologic features of myelodysplasia in 2 or more lineages. Follow-up was available for 7 patients and the median overall survival (OS) was 12 months. Patients with a history of MPN had a significantly shorter OS compared with those with de novo AML (11 vs. 20 months; P = .0445). There was no correlation between complex karyotype and OS in this small group of AML patients (P = .5904). The t(v;5q33) is a rare cytogenetic aberration in AML. Although associated with a poor outcome, AML with t(v;5q33) usually lacks morphologic evidence of multilineage dysplasia. Patients who have AML with t(v;5q33) after MPN have a worse OS compared with those with de novo AML. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5.

    PubMed

    Ono, K; Ohashi, Y; Nakano, H; Togashi, H; Kannari, Y; Isono, S

    1993-09-01

    A male infant with partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5 (46,XY,rec(5), dup q,inv(5)(p15.1q35.1)pat) is reported together with the oral findings. The phenotype was chiefly the cri-du-chat syndrome. Severe retardation of mental and motor development, microencephaly, cardiac malformation, crying and facial appearance unique to the cri-du-chat syndrome were observed. Perioral and intraoral findings included thin upper lip, down-turning corners of mouth, micrognathia, shallow palate, and cleft of soft palate. Anterior deciduous teeth were small and canine deciduous teeth were conic. The row of deciduous teeth showed a flat arch-like shape that was very wide but short in length. No abnormality was noted in the number of deciduous teeth or the timing of eruption.

  4. 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.

  5. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. In patients with myelodysplastic syndromes with del(5q), factors other than age and sex contribute to the prognostic advantage, which diminishes over time.

    PubMed

    Lauseker, Michael; Schemenau, Jennifer; Strupp, Corinna; Kündgen, Andrea; Gattermann, Norbert; Hasford, Joerg; Germing, Ulrich

    2015-09-01

    This study aimed to determine the extent to which the prognostic advantage of myelodysplastic syndromes (MDS) with del(5q) is due to the more favourable age and sex distribution of patients in that group when compared to other MDS subtypes. A total of 1912 MDS patients from the Duesseldorf registry with less than 5% blasts in the bone marrow were evaluable and had complete covariates. As endpoints, overall survival and progression to acute myeloid leukaemia (AML) were considered. Cox models were computed for both outcomes. A multivariate Cox model for survival confirmed higher age and male sex as risk factors. In addition, we found a survival advantage of 9·1 years for MDS del(5q) patients compared to refractory cytopenia with unilineage dysplasia, while the survival advantage of MDS del(5q) over refractory cytopenia with multilineage dysplasia was 18·6 years. Considering progression to AML, we did not find any significant differences between the World Health Organization classification subtypes. Our analyses show that the higher survival probabilities of MDS del(5q) patients are not only due to age and sex, although higher age and male sex were also important risk factors. Interestingly, it seems that the survival advantage of MDS del(5q) decreases over time. © 2015 John Wiley & Sons Ltd.

  9. Aberrant overexpression of CD14 on granulocytes sensitizes the innate immune response in mDia1 heterozygous del(5q) MDS

    PubMed Central

    Keerthivasan, Ganesan; Mei, Yang; Zhao, Baobing; Zhang, Ling; Harris, Chad E.; Gao, Juehua; Basiorka, Ashley A.; Schipma, Matthew J.; McElherne, James; Yang, Jing; Verma, Amit K.; Pellagatti, Andrea; Boultwood, Jacqueline; List, Alan F.; Williams, David A.

    2014-01-01

    The myelodysplastic syndromes (MDSs) include a spectrum of stem cell malignancies characterized by an increased risk of developing acute myeloid leukemia. Heterozygous loss of chromosome 5q (del[5q]) is the most common cytogenetic abnormality in MDS. DIAPH1 is localized to 5q31 and encodes one of the formin proteins, mDia1, which is involved in linear actin polymerization. Mice with mDia1 deficiency develop hematologic features with age mimicking human myeloid neoplasm, but its role in the pathogenesis of MDS is unclear. Here we report that mDia1 heterozygous and knockout mice develop MDS phenotypes with age. In these mice, CD14 was aberrantly overexpressed on granulocytes in a cell-autonomous manner, leading to a hypersensitive innate immune response to lipopolysaccharide (LPS) stimuli through CD14/Toll-like receptor 4 signaling. Chronic stimulation with LPS accelerated the development of MDS in mDia1 heterozygous and knockout mice that can be rescued by lenalidomide. Similar findings of CD14 overexpression were observed on the bone marrow granulocytes of del(5q) MDS patients. Mechanistically, mDia1 deficiency led to a downregulation of membrane-associated genes and a specific upregulation of CD14 messenger RNA in granulocytes, but not in other lineages. These results underscore the significance of mDia1 heterozygosity in deregulated innate immune responses in del(5q) MDS. PMID:24891322

  10. Identification, by Homozygosity Mapping, of a Novel Locus for Autosomal Recessive Congenital Ichthyosis on Chromosome 17p, and Evidence for Further Genetic Heterogeneity

    PubMed Central

    Krebsová, Alice; Küster, Wolfgang; Lestringant, Gilles G.; Schulze, Bernt; Hinz, Britta; Frossard, Philippe M.; Reis, André; Hennies, Hans Christian

    2001-01-01

    Autosomal recessive congenital ichthyosis (ARCI) comprises a group of severe disorders of keratinization, characterized by variable erythema and skin scaling. It is known for its high degree of genetic and clinical heterogeneity. Mutations in the gene for keratinocyte transglutaminase (TGM1) on chromosome 14q11 were shown in patients with ARCI, and a second locus was described, on chromosome 2q, in families from northern Africa. Three other loci for ARCI, on chromosomes 3p and 19p, were identified recently. We have embarked on a whole-genome scan for further loci for ARCI in four families from Germany, Turkey, and the United Arab Emirates. A novel ARCI locus was identified on chromosome 17p, between the markers at D17S938 and D17S1856, with a maximum LOD score of 3.38, at maximum recombination fraction 0.00, at D17S945, under heterogeneity. This locus is linked to the disease in the Turkish family and in the German family. Extensive genealogical studies revealed that the parents of the German patients with ARCI were eighth cousins. By homozygosity mapping, the localization of the gene could then be refined to the 8.4-cM interval between D17S938 and D17S1879. It could be shown, however, that ARCI in the two Arab families is linked neither to the new locus on chromosome 17p nor to one of the five loci known previously. Our findings give evidence of further genetic heterogeneity that is not linked to distinctive phenotypes. PMID:11398099

  11. Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line.

    PubMed

    Teles Alves, Inês; Hiltemann, Saskia; Hartjes, Thomas; van der Spek, Peter; Stubbs, Andrew; Trapman, Jan; Jenster, Guido

    2013-06-01

    The VCaP cell line is widely used in prostate cancer research as it is a unique model to study castrate resistant disease expressing high levels of the wild type androgen receptor and the TMPRSS2-ERG fusion transcript. Using next generation sequencing, we assembled the structural variations in VCaP genomic DNA and observed a massive number of genomic rearrangements along the q arm of chromosome 5, characteristic of chromothripsis. Chromothripsis is a recently recognized phenomenon characterized by extensive chromosomal shattering in a single catastrophic event, mainly detected in cancer cells. Various structural events identified on chromosome 5q of VCaP resulted in gene fusions. Out of the 18 gene fusion candidates tested, 15 were confirmed on genomic level. In our set of gene fusions, only rarely we observe microhomology flanking the breakpoints. On RNA level, only five transcripts were detected and NDUFAF2-MAST4 was the only resulting in an in-frame fusion transcript. Our data indicate that although a marker of genomic instability, chromothripsis might lead to only a limited number of functionally relevant fusion genes.

  12. Patient with dup(5)(q35.2-q35.3) reciprocal to the common Sotos syndrome deletion and review of the literature.

    PubMed

    Žilina, Olga; Reimand, Tiia; Tammur, Pille; Tillmann, Vallo; Kurg, Ants; Õunap, Katrin

    2013-04-01

    The recent implementation of array techniques in research and clinical practice has revealed the existence of recurrent reciprocal deletions and duplications in several genome loci. The most intriguing feature is that some reciprocal genomic events can result in opposite phenotypic outcome. One of such examples is 5q35.2-q35.3. Deletions in this locus lead to Sotos syndrome characterized by childhood overgrowth with advanced bone age, craniofacial dysmorphic features including macrocephaly, and learning difficulties; while duplications have been proposed to manifest in opposite phenotype related to growth. Here, we report a patient with 5q35.2-q35.3 duplication and compare her clinical phenotype with five previously described cases. Short stature since the birth, microcephaly, brachydactyly, delayed bone age, mild to moderate intellectual disability and mild facial dysmorphism seem to be characteristic features of 5q35.2-q35.3 duplication. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Identification of Novel Candidate Oncogenes in Chromosome Region 17p11.2-p12 in Human Osteosarcoma

    PubMed Central

    Both, Joeri; Wu, Thijs; Bras, Johannes; Schaap, Gerard R.; Baas, Frank; Hulsebos, Theo J. M.

    2012-01-01

    Osteosarcoma is the most common primary malignancy of bone. The tumours are characterized by high genomic instability, including the occurrence of multiple regions of amplifications and deletions. Chromosome region 17p11.2–p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region. Considering the complexity and variation of the amplification profiles for this segment, the involvement of additional causative oncogenes is to be expected. The aim of the present investigation is to identify novel candidate oncogenes in 17p11.2–p12. We selected 26 of in total 85 osteosarcoma samples (31%) with amplification events in 17p11.2–p12, using quantitative PCR for 8 marker genes. These were subjected to high-resolution SNP array analysis and subsequent GISTIC analysis to identify the most significantly amplified regions. Two major amplification peaks were found in the 17p11.2–p12 region. Overexpression as a consequence of gene amplification is a major mechanism for oncogene activation in tumours. Therefore, to identify the causative oncogenes, we next determined expression levels of all genes within the two segments using expression array data that could be generated for 20 of the selected samples. We identified 11 genes that were overexpressed through amplification in at least 50% of cases. Nine of these, c17orf39, RICH2, c17orf45, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1, demonstrated a significant association between copy number and expression level. We conclude that these genes, including COPS3 and PMP22, are candidate oncogenes in 17p11.2–p12 of importance in osteosarcoma tumourigenesis. PMID:22292074

  14. Identification of novel candidate oncogenes in chromosome region 17p11.2-p12 in human osteosarcoma.

    PubMed

    Both, Joeri; Wu, Thijs; Bras, Johannes; Schaap, Gerard R; Baas, Frank; Hulsebos, Theo J M

    2012-01-01

    Osteosarcoma is the most common primary malignancy of bone. The tumours are characterized by high genomic instability, including the occurrence of multiple regions of amplifications and deletions. Chromosome region 17p11.2-p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region. Considering the complexity and variation of the amplification profiles for this segment, the involvement of additional causative oncogenes is to be expected. The aim of the present investigation is to identify novel candidate oncogenes in 17p11.2-p12. We selected 26 of in total 85 osteosarcoma samples (31%) with amplification events in 17p11.2-p12, using quantitative PCR for 8 marker genes. These were subjected to high-resolution SNP array analysis and subsequent GISTIC analysis to identify the most significantly amplified regions. Two major amplification peaks were found in the 17p11.2-p12 region. Overexpression as a consequence of gene amplification is a major mechanism for oncogene activation in tumours. Therefore, to identify the causative oncogenes, we next determined expression levels of all genes within the two segments using expression array data that could be generated for 20 of the selected samples. We identified 11 genes that were overexpressed through amplification in at least 50% of cases. Nine of these, c17orf39, RICH2, c17orf45, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1, demonstrated a significant association between copy number and expression level. We conclude that these genes, including COPS3 and PMP22, are candidate oncogenes in 17p11.2-p12 of importance in osteosarcoma tumourigenesis.

  15. Partial proximal trisomy of the long arm of chromosome 5 (q13 leads to q22) resulting from maternal insertion der ins (10;5).

    PubMed Central

    Gilgenkrantz, S; Dulucq, P; Bresson, J L; Gouget, A; Pernot, C; Gregoire, M J

    1981-01-01

    Five members of our study family were carriers of a balanced insertion (10;5) (q22;q13;q22). One of the children had psychomotor retardation and malformations resulting from a partial trisomy of the proximal long arm of chromosome 5, having received the maternal der(10). Amniocentesis identified another case of partial proximal trisomy in a fetus of a subsequent pregnancy. This clinical and family study is compared with two other published cases of proximal trisomy 5q. Images PMID:7334508

  16. 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

  17. Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial.

    PubMed

    Almeida, Antonio; Fenaux, Pierre; Garcia-Manero, Guillermo; Goldberg, Stuart L; Gröpper, Stefanie; Jonasova, Anna; Vey, Norbert; Castaneda, Carmen; Zhong, Jianhua; Beach, C L; Santini, Valeria

    2018-01-11

    The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3-4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = .817) or hemorrhagic events (p = 1.000). Grade 3-4 non-hematologic TEAEs were rare (the incidence of grade 3-4 pneumonia, e.g. was 5.6% in the lenalidomide group and 2.5% in the placebo group). Common grade 1-2 non-hematologic TEAEs did not require dose modifications or treatment discontinuation. Acute myeloid leukemia and second primary malignancies incidence was similar across treatment groups. Lenalidomide had a predictable and manageable safety profile in lower-risk non-del(5q) MDS patients ineligible/refractory to ESAs. Guidance on managing lenalidomide-related TEAEs is provided to help maintain patients on therapy to achieve maximum clinical benefit. ClinicalTrials.gov identifier: NCT01029262.

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

    PubMed

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

    2016-05-11

    Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. Copyright © 2016, American Association for the Advancement of Science.

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

    SciTech Connect

    Fukushima, Yoshimitsu; Ohashi, Hirofumi; Wakui, Keiko

    1995-07-03

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

  20. Fortuitous FISH diagnosis of an interstitial microdeletion (5)(q31.1q31.2) in a girl suspected to present a cri-du-chat syndrome.

    PubMed

    Mosca, A L; Callier, P; Leheup, B; Marle, N; Jalloul, M; Coffinet, L; Feillet, F; Valduga, M; Jonveaux, P; Mugneret, F

    2007-06-15

    Constitutional interstitial deletions of 5q are relatively rare and most are poorly characterized cytogenetically. Consequently a definite karyotype-phenotype correlation is difficult to establish. We report on a new case of a girl presenting with an abnormal cry, upslanting palpebral fissures, hypertelorism, anteverted nostrils, microretrognathia, growth retardation, and an adenoid cyst at the base of the tongue. The first suspected diagnosis was cri-du-chat syndrome because of the mewing cry. Standard cytogenetic analyses were interpreted as normal, but FISH studies using the probe of cri-du-chat syndrome with the control probe EGR1 (5q31.2)/D5S23 (Abbott) revealed a 5q31.2 microdeletion which was then confirmed by CGH-array (Abbott). FISH studies using PACs and BACs clones (Rocchi, Italia) enabled us to characterize the breakpoints of the deleted region. Cytogenetic analysis with FISH studies revealed a normal karyotype with normal 5q31 region in both parents. This case is compared with the other cases reported in the literature.

  1. NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively

    SciTech Connect

    Tamimi, R.M.; Montgomery-Dyer, K.; Tapscott, S.J.

    1997-03-01

    NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD. NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. 16 refs., 2 figs.

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

    PubMed

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

    2012-09-13

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

  3. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1.

    PubMed

    Monemi, Sharareh; Spaeth, George; DaSilva, Alexander; Popinchalk, Samuel; Ilitchev, Elena; Liebmann, Jeffrey; Ritch, Robert; Héon, Elise; Crick, Ronald Pitts; Child, Anne; Sarfarazi, Mansoor

    2005-03-15

    Glaucoma is a leading cause of blindness in virtually every country. Development of an accurate diagnostic test for presymptomatic detection of individuals at risk is an urgent requisition for this condition. Herein, we report mapping of a new adult-onset primary open-angle glaucoma (POAG) locus on 5q22.1 (GLC1G) and identification of its defective gene. Mutation screening of seven candidate genes from the GLC1G critical region (approximately 2 Mb between D5S1466 and D5S2051) identified only one significant alteration in the WDR36 (WD40-repeat 36) gene. This mutation (i.e. D658G) was segregated in all affected members of our first GLC1G-linked family but it was absent in 476 normal control chromosomes. Further screening of WDR36 in a total of 130 POAG families revealed 24 DNA variations. Overall, four mutations (N355S, A449T, R529Q and D658G) were identified in 17 (5.02-6.92%) unrelated POAG subjects, 11 with high-pressure and six with low-pressure glaucoma. These mutations were absent in a minimum of 200 normal control chromosomes and, further they were conserved between WDR36 orthologues in mouse, rat, dog, chimp and human. WDR36 is a novel gene with 23 exons, which encodes for 951 amino acids and a protein with multiple G-beta WD40 repeats. By northern blotting, two distinct mRNA transcripts of 5.9 and 2.5 kb were observed in human heart, placenta, liver, skeletal muscle, kidney and pancreas. WDR36 gene expression in lens, iris, sclera, ciliary muscles, ciliary body, trabecular meshwork, retina and optic nerve were established by RT-PCR. In mouse, two transcripts of 3.5 and 2.9 kb showed analogous expression patterns to human. mRNA expressions were detected in 7-, 11-, 15- and 17-day-old developing mouse embryos. In summary, WDR36 is a novel causative gene for adult-onset POAG at the GLC1G locus. Specific ocular expressions and observed mutations are consistent with WDR36 role in etiology of both high- and low-pressure glaucoma.

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

    PubMed

    González-González, María; Muñoz-Bellvis, Luís; Mackintosh, Carlos; Fontanillo, Celia; Gutiérrez, M Laura; Abad, M Mar; Bengoechea, Oscar; Teodosio, Cristina; Fonseca, Emilio; Fuentes, Manuel; De Las Rivas, Javier; Orfao, Alberto; Sayagués, José María

    2012-01-01

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

  5. Prognostic Impact of del(17p) and del(22q) as Assessed by Interphase FISH in Sporadic Colorectal Carcinomas

    PubMed Central

    González-González, María; Muñoz-Bellvis, Luís; Mackintosh, Carlos; Fontanillo, Celia; Gutiérrez, M. Laura; Abad, M. Mar; Bengoechea, Oscar; Teodosio, Cristina; Fonseca, Emilio; Fuentes, Manuel; De Las Rivas, Javier

    2012-01-01

    Background Most sporadic colorectal cancer (sCRC) deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC. Methodology/Principal Findings We prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 1, 7, 8, 13, 14, 17, 18, 20, and 22 by iFISH in 58 sCRC patients: thirty-one non-metastatic (54%) vs. 27 metastatic (46%) disease. From a total of 18 probes, significant differences emerged only for the 17p11.2 and 22q11.2 chromosomal regions. Patients with liver metastatic sCRC showed an increased frequency of del(17p11.2) (10% vs. 67%;p<.001) and del(22q11.2) (0% vs. 22%;p = .02) versusnon-metastatic cases. Multivariate analysis of prognostic factors for overall survival (OS) showed that the only clinical and cytogenetic parameters that had an independent adverse impact on patient outcome were the presence of del(17p) with a 17p11.2 breakpoint and del(22q11.2). Based on these two cytogenetic variables, patients were classified into three groups: low- (no adverse features), intermediate- (one adverse feature) and high-risk (two adverse features)- with significantly different OS rates at 5-years (p<.001): 92%, 53% and 0%, respectively. Conclusions/Significance Our results unravel the potential implication of del(17p11.2) in sCRC patients with liver metastasis as this cytogenetic alteration appears to be intrinsically related to an increased metastatic potential and a poor outcome, providing additional prognostic information to that associated with other cytogenetic alterations such as del(22q11.2). Additional prospective studies in larger series of patients would be required to confirm the clinical utility of the new prognostic markers identified. PMID:22912721

  6. 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

  7. Underground study of the O17(p,γ)F18 reaction relevant for explosive hydrogen burning

    NASA Astrophysics Data System (ADS)

    Di Leva, A.; Scott, D. A.; Caciolli, A.; Formicola, A.; Strieder, F.; Aliotta, M.; Anders, M.; Bemmerer, D.; Broggini, C.; Corvisiero, P.; Elekes, Z.; Fülöp, Zs.; Gervino, G.; Guglielmetti, A.; Gustavino, C.; Gyürky, Gy.; Imbriani, G.; José, J.; Junker, M.; Laubenstein, M.; Menegazzo, R.; Napolitani, E.; Prati, P.; Rigato, V.; Roca, V.; Somorjai, E.; Salvo, C.; Straniero, O.; Szücs, T.; Terrasi, F.; Trezzi, D.; LUNA Collaboration

    2014-01-01

    Background: The O17(p,γ)F18 reaction affects the production of key isotopes (e.g., F18 and O18) in the explosive hydrogen burning that powers classical novae. Under these explosive conditions, the reaction rate is dominated by contributions from a narrow resonance at Ec .m.=183keV and by the combined contributions of direct capture and low-energy tails of broad resonances. At present, the astrophysical reaction rate is not well constrained because of the lack of data in the energy region appropriate to classical novae. Purpose: This study aims at the measurement of the O17(p,γ)F18 reaction cross section in order to determine its reaction rate in the temperature region appropriate to explosive hydrogen burning in novae. Method: The O17(p,γ)F18 reaction cross section was measured using both the prompt detection of the emitted γ rays and an activation technique. Measurements were carried out at the Laboratory for Underground Nuclear Astrophysics (Gran Sasso, Italy) where the strongly reduced cosmic-ray-induced background allows for improved sensitivity compared to previous studies. Results: The O17(p,γ)F18 reaction cross section was measured in the range Ec .m.=160 to 370keV. The strength of the Ec .m.=183keV resonance, ωγ =1.67±0.12μeV, was determined with unprecedented precision. The total S factor was obtained through a combined fit of prompt γ-ray and activation results. An overall global fit including other existing data sets was also carried out and a recommended astrophysical reaction rate is presented. Conclusions: The reaction rate uncertainty attained in this work is now below the required precision for nova models. We verified, following a full set of hydrodynamic nova models, that the abundances of oxygen and fluorine isotopes obtained with the present reaction rate are determined with 10% precision and put firmer constraints on observational signatures of novae events.

  8. Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling.

    PubMed

    Varney, Melinda E; Niederkorn, Madeline; Konno, Hiroyasu; Matsumura, Takayuki; Gohda, Jin; Yoshida, Nobuaki; Akiyama, Taishin; Christie, Susanne; Fang, Jing; Miller, David; Jerez, Andres; Karsan, Aly; Maciejewski, Jaroslaw P; Meetei, Ruhikanta A; Inoue, Jun-ichiro; Starczynowski, Daniel T

    2015-10-19

    TRAF-interacting protein with forkhead-associated domain B (TIFAB) is a haploinsufficient gene in del(5q) myelodysplastic syndrome (MDS). Deletion of Tifab results in progressive bone marrow (BM) and blood defects, including skewed hematopoietic stem/progenitor cell (HSPC) proportions and altered myeloid differentiation. A subset of mice transplanted with Tifab knockout (KO) HSPCs develop a BM failure with neutrophil dysplasia and cytopenia. In competitive transplants, Tifab KO HSPCs are out-competed by wild-type (WT) cells, suggesting a cell-intrinsic defect. Gene expression analysis of Tifab KO HSPCs identified dysregulation of immune-related signatures, and hypersensitivity to TLR4 stimulation. TIFAB forms a complex with TRAF6, a mediator of immune signaling, and reduces TRAF6 protein stability by a lysosome-dependent mechanism. In contrast, TIFAB loss increases TRAF6 protein and the dynamic range of TLR4 signaling, contributing to ineffective hematopoiesis. Moreover, combined deletion of TIFAB and miR-146a, two genes associated with del(5q) MDS/AML, results in a cooperative increase in TRAF6 expression and hematopoietic dysfunction. Re-expression of TIFAB in del(5q) MDS/AML cells results in attenuated TLR4 signaling and reduced viability. These findings underscore the importance of efficient regulation of innate immune/TRAF6 signaling within HSPCs by TIFAB, and its cooperation with miR-146a as it relates to the pathogenesis of hematopoietic malignancies, such as del(5q) MDS/AML. © 2015 Varney et al.

  9. The phenotypic spectrum of duplication 5q35.2-q35.3 encompassing NSD1: is it really a reversed Sotos syndrome?

    PubMed

    Dikow, Nicola; Maas, Bianca; Gaspar, Harald; Kreiss-Nachtsheim, Martina; Engels, Hartmut; Kuechler, Alma; Garbes, Lutz; Netzer, Christian; Neuhann, Teresa M; Koehler, Udo; Casteels, Kristina; Devriendt, Koen; Janssen, Johannes W G; Jauch, Anna; Hinderhofer, Katrin; Moog, Ute

    2013-09-01

    Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID). Microduplications of 5q35.2-q35.3 including NSD1 have been reported in only five patients so far and described clinically as a reversed Sos resulting from a hypothetical gene dosage effect of NSD1. Here, we report on nine patients from five families with interstitial duplication 5q35 including NSD1 detected by molecular karyotyping. The clinical features of all 14 individuals are reviewed. Patients with microduplications including NSD1 appear to have a consistent phenotype consisting of short stature, microcephaly, learning disability or mild to moderate ID, and distinctive facial features comprising periorbital fullness, short palpebral fissures, a long nose with broad or long nasal tip, a smooth philtrum and a thin upper lip vermilion. Behavioral problems, ocular and minor hand anomalies may be associated. Based on our findings, we discuss the possible etiology and conclude that it is possible, but so far unproven, that a gene dosage effect of NSD1 may be the major cause. Copyright © 2013 Wiley Periodicals, Inc.

  10. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q.

    PubMed

    Raza, Azra; Reeves, James A; Feldman, Eric J; Dewald, Gordon W; Bennett, John M; Deeg, H Joachim; Dreisbach, Luke; Schiffer, Charles A; Stone, Richard M; Greenberg, Peter L; Curtin, Peter T; Klimek, Virginia M; Shammo, Jamile M; Thomas, Deborah; Knight, Robert D; Schmidt, Michele; Wride, Kenton; Zeldis, Jerome B; List, Alan F

    2008-01-01

    Lenalidomide is approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndromes (MDSs) associated with a chromosome 5q deletion with or without additional cytogenetic abnormalities. We report results of a multicenter, phase 2 trial evaluating lenalidomide therapy for transfusion-dependent patients with low- or int-1-risk MDS without deletion 5q. Eligible patients had 50,000/mm(3) or more platelets and required 2 U or more RBCs within the previous 8 weeks; 214 patients received 10 mg oral lenalidomide daily or 10 mg on days 1 to 21 of a 28-day cycle. The most common grade 3/4 adverse events were neutropenia (30%) and thrombocytopenia (25%). Using an intention-to-treat analysis, 56 (26%) patients achieved transfusion independence (TI) after a median of 4.8 weeks of treatment with a median duration of TI of 41.0 weeks. In patients who achieved TI, the median rise in hemoglobin was 32 g/L (3.2 g/dL; range, 10-98 g/L [1.0-9.8 g/dL]) from baseline. A 50% or greater reduction in transfusion requirement occurred in 37 additional patients, yielding a 43% overall rate of hematologic improvement (TI response + ||>or= 50% reduction in transfusion requirement). Lenalidomide has clinically meaningful activity in transfusion-dependent patients with low- or int-1-risk MDS who lack the deletion 5q karyotypic abnormality.

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

    PubMed

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

    2014-05-01

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

  12. 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.

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

    SciTech Connect

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

    1995-11-01

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

  14. Progression in patients with low- and intermediate-1-risk del(5q) myelodysplastic syndromes is predicted by a limited subset of mutations

    PubMed Central

    Scharenberg, Christian; Giai, Valentina; Pellagatti, Andrea; Saft, Leonie; Dimitriou, Marios; Jansson, Monika; Jädersten, Martin; Grandien, Alf; Douagi, Iyadh; Neuberg, Donna S.; LeBlanc, Katarina; Boultwood, Jacqueline; Karimi, Mohsen; Jacobsen, Sten Eirik W.; Woll, Petter S.; Hellström-Lindberg, Eva

    2017-01-01

    A high proportion of patients with lower-risk del(5q) myelodysplastic syndromes will respond to treatment with lenalidomide. The median duration of transfusion-independence is 2 years with some long-lasting responses, but almost 40% of patients progress to acute leukemia by 5 years after starting treatment. The mechanisms underlying disease progression other than the well-established finding of small TP53-mutated subclones at diagnosis remain unclear. We studied a longitudinal cohort of 35 low- and intermediate-1-risk del(5q) patients treated with lenalidomide (n=22) or not (n=13) by flow cytometric surveillance of hematopoietic stem and progenitor cell subsets, targeted sequencing of mutational patterns, and changes in the bone marrow microenvironment. All 13 patients with disease progression were identified by a limited number of mutations in TP53, RUNX1, and TET2, respectively, with PTPN11 and SF3B1 occurring in one patient each. TP53 mutations were found in seven of nine patients who developed acute leukemia, and were documented to be present in the earliest sample (n=1) and acquired during lenalidomide treatment (n=6). By contrast, analysis of the microenvironment, and of hematopoietic stem and progenitor cells by flow cytometry was of limited prognostic value. Based on our data, we advocate conducting a prospective study aimed at investigating, in a larger number of cases of del(5q) myelodysplastic syndromes, whether the detection of such mutations before and after lenalidomide treatment can guide clinical decision-making. PMID:27884971

  15. 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

    ... 7 Agriculture 13 2010-01-01 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...

  16. Measurement of the 183 keV resonance in O17(p,α)N14 using a novel technique

    NASA Astrophysics Data System (ADS)

    Moazen, B. H.; Bardayan, D. W.; Blackmon, J. C.; Chae, K. Y.; Chipps, K.; Domizioli, C. P.; Fitzgerald, R.; Greife, U.; Hix, W. R.; Jones, K. L.; Kozub, R. L.; Lingerfelt, E. J.; Livesay, R. J.; Nesaraja, C. D.; Pain, S. D.; Roberts, L. F.; Shriner, J. F., Jr.; Smith, M. S.; Thomas, J. S.

    2007-06-01

    We have developed a novel technique for measurements of low-energy (p,α) reactions using heavy-ion beams and a differentially pumped windowless gas target. We applied this new approach to study the 183 keV resonance in the O17(p,α)N14 reaction. We report a (center-of-mass) resonance energy of Er=183.5(+0.1)/(-0.4) keV and a resonance strength of ωγpα=(1.70±0.15) meV, and we set an upper limit (95% confidence) on the total width of the state of Γ<0.1 keV. This resonance is important for the O17(p,α)N14 reaction rate, and we find that F18 production is significantly decreased in low-mass ONeMg novae but less affected in more energetic novae. We also report the first determination of the stopping power for oxygen ions in hydrogen gas near the peak of the Bragg curve (E=193 keV/u) to be (63±1)×10-15 eV cm2.

  17. Loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in malays with malignant glioma.

    PubMed

    Zainuddin, Norafiza; Jaafart, Hasnan; Isa, Mohd Nizam; Abdullah, Jafri Malin

    2004-01-01

    Recent advances in neuro-oncology have revealed different pathways of molecular oncogenesis in malignant gliomas including loss of heterozygosity on chromosomal regions harboring tumor suppressor genes. In the present study, we performed polymerase chain reaction-loss of heterozygosity (PCR-LOH) analysis using microsatellite markers to identify loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in the Malays with malignant gliomas. Of 12 cases with allelic losses, seven (58.3%) cases showed LOH on chromosome 10q, three (25.0%) cases showed LOH on chromosome 9p, four (33.3%) cases showed LOH on chromosome 17p and two (16.7%) cases showed LOH on chromosome 13q. The cases include five (41.7%) cases of glioblastoma multiforme, three (25.0%) cases of anaplastic astrocytoma, three (25.0%) cases of anaplastic oligodendroglioma and one (8.3%) case of anaplastic ependymoma. Four cases showed loss of heterozygosity on more than one locus. Our findings showed that loss of heterozygosity on specific chromosomal regions contributes to the molecular pathway of glioma progression in Malay population. In addition, these data provide useful evidence of molecular genetic alterations of malignant glioma in South East Asian patients, particularly in the East Coast of Malaysia.

  18. A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11.

    PubMed

    Ogdie, Matthew N; Macphie, I Laurence; Minassian, Sonia L; Yang, May; Fisher, Simon E; Francks, Clyde; Cantor, Rita M; McCracken, James T; McGough, James J; Nelson, Stanley F; Monaco, Anthony P; Smalley, Susan L

    2003-05-01

    Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is a common, highly heritable neurobehavioral disorder of childhood onset, characterized by hyperactivity, impulsivity, and/or inattention. As part of an ongoing study of the genetic etiology of ADHD, we have performed a genomewide linkage scan in 204 nuclear families comprising 853 individuals and 270 affected sibling pairs (ASPs). Previously, we reported genomewide linkage analysis of a "first wave" of these families composed of 126 ASPs. A follow-up investigation of one region on 16p yielded significant linkage in an extended sample. The current study extends the original sample of 126 ASPs to 270 ASPs and provides linkage analyses of the entire sample, using polymorphic microsatellite markers that define an approximately 10-cM map across the genome. Maximum LOD score (MLS) analysis identified suggestive linkage for 17p11 (MLS=2.98) and four nominal regions with MLS values >1.0, including 5p13, 6q14, 11q25, and 20q13. These data, taken together with the fine mapping on 16p13, suggest two regions as highly likely to harbor risk genes for ADHD: 16p13 and 17p11. Interestingly, both regions, as well as 5p13, have been highlighted in genomewide scans for autism.

  19. Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma.

    PubMed

    Both, Joeri; Wu, Thijs; Ten Asbroek, Anneloor L M A; Baas, Frank; Hulsebos, Theo J M

    2016-01-01

    Osteosarcomas are primary tumors of bone that most often develop in adolescents. They are characterized by complex genomic changes including amplifications, deletions, and translocations. The chromosome region 17p11.2p12 is frequently amplified in human high grade osteosarcomas (25% of cases), suggesting the presence of one or more oncogenes. In previous studies, we identified 9 candidate oncogenes in this region (GID4, ARGHAP44, LRRC75A-AS1, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1). The aim of the present study was to determine their oncogenic properties. Therefore, we generated osteosarcoma cell lines overexpressing these genes, except for LRRC75A-AS1 and PRPSAP2, and subjected these to functional oncogenic assays. We found that TOP3A, SHMT1, and RASD1 overexpression provided increased proliferation and that ARGHAP44, COPS3, and PMP22 overexpression had a stimulatory effect on migration and invasion of the cells. COPS3 and PMP22 overexpression additionally improved the ability of the cells to form new colonies. No oncogenic effect could be demonstrated for GID4 overexpression. We conclude that the concerted amplification-mediated overexpression of these genes in 17p11.2p12 may contribute to the oncogenic process in malignant osteosarcoma. © 2016 S. Karger AG, Basel.

  20. 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.

  1. 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

  2. A novel locus for Leber congenital amaurosis (LCA4) with anterior keratoconus mapping to chromosome 17p13.

    PubMed

    Hameed, A; Khaliq, S; Ismail, M; Anwar, K; Ebenezer, N D; Jordan, T; Mehdi, S Q; Payne, A M; Bhattacharya, S S

    2000-03-01

    A two-generation consanguineous Pakistani family with autosomal recessive Leber congenital amaurosis (LCA, MIM 204,000) and keratoconus was identified. All affected individuals have bilateral keratoconus and congenital pigmentary retinopathy. The goal of this study was to link the disease phenotype in this family. Genomic DNA was amplified across the polymorphic microsatellite poly-CA regions identified by markers. Polymerase chain reaction (PCR) products were separated by nondenaturing polyacrylamide gel electrophoresis. Alleles were assigned to individuals, which allowed calculation of LOD scores using the Cyrillic and MLINK software program. The retinal guanylate cyclase (RETGC-1, GDB symbol GUC2D) and pigment epithelium-derived factor (PEDF) genes were analyzed by heteroduplex analysis and direct sequencing for mutations in diseased individuals. Based on a whole genome linkage analysis the first locus for this combined phenotype has been mapped to chromosome 17p13. Linkage analysis gave a two point LOD score of 3.21 for marker D17S829. Surrounding this marker is a region of homozygosity of 15.77 cM, between the markers D17S1866 and D17S960; however, the crossover for the marker D17S1529 refines the region to 10.77 cM within which the disease gene is predicted to lie. Mutation screening of the nearby RETGC-1 gene, which has been shown to be associated with LCA1, revealed no mutations in the affected individuals of this family. Similarly, another prime candidate in the region PEDF was also screened for mutations. The factor has been shown to be involved in the photoreceptor differentiation and neuronal survival. No mutations were found in this gene either. Furthermore, RETGC-1 was physically excluded from the critical disease region based on the existing physical map. It is therefore suggested that this combined phenotype maps to a new locus and is due to an as yet uncharacterized gene within the 17p13 chromosomal region.

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

    SciTech Connect

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

    1994-09-01

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

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

    SciTech Connect

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

    1994-09-01

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

  5. Antiferromagnetic Kondo lattice compound CePt3P

    PubMed Central

    Chen, Jian; Wang, Zhen; Zheng, Shiyi; Feng, Chunmu; Dai, Jianhui; Xu, Zhu’an

    2017-01-01

    A new ternary platinum phosphide CePt3P was synthesized and characterized by means of magnetic, thermodynamic and transport measurements. The compound crystallizes in an antiperovskite tetragonal structure similar to that in the canonical family of platinum-based superconductors APt3P (A = Sr, Ca, La) and closely related to the noncentrosymmetric heavy fermion superconductor CePt3Si. In contrast to all the superconducting counterparts, however, no superconductivity is observed in CePt3P down to 0.5 K. Instead, CePt3P displays a coexistence of antiferromagnetic ordering, Kondo effect and crystalline electric field effect. A field-induced spin-flop transition is observed below the magnetic ordering temperature TN1 of 3.0 K while the Kondo temperature is of similar magnitude as TN1. The obtained Sommerfeld coefficient of electronic specific heat is γCe = 86 mJ/mol·K2 indicating that CePt3P is a moderately correlated antiferromagnetic Kondo lattice compound. PMID:28157184

  6. Antiferromagnetic Kondo lattice compound CePt3P.

    PubMed

    Chen, Jian; Wang, Zhen; Zheng, Shiyi; Feng, Chunmu; Dai, Jianhui; Xu, Zhu'an

    2017-02-03

    A new ternary platinum phosphide CePt 3 P was synthesized and characterized by means of magnetic, thermodynamic and transport measurements. The compound crystallizes in an antiperovskite tetragonal structure similar to that in the canonical family of platinum-based superconductors APt 3 P (A = Sr, Ca, La) and closely related to the noncentrosymmetric heavy fermion superconductor CePt 3 Si. In contrast to all the superconducting counterparts, however, no superconductivity is observed in CePt 3 P down to 0.5 K. Instead, CePt 3 P displays a coexistence of antiferromagnetic ordering, Kondo effect and crystalline electric field effect. A field-induced spin-flop transition is observed below the magnetic ordering temperature T N1 of 3.0 K while the Kondo temperature is of similar magnitude as T N1 . The obtained Sommerfeld coefficient of electronic specific heat is γ Ce  = 86 mJ/mol·K 2 indicating that CePt 3 P is a moderately correlated antiferromagnetic Kondo lattice compound.

  7. Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data.

    PubMed

    Sharma, V; Michel, S; Gaertner, V; Franke, A; Vogelberg, C; von Berg, A; Bufe, A; Heinzmann, A; Laub, O; Rietschel, E; Simma, B; Frischer, T; Genuneit, J; Zeilinger, S; Illig, T; Schedel, M; Potaczek, D P; Kabesch, M

    2014-08-01

    Genome-wide association studies (GWAS) repeatedly identified 1q23 (FCER1A), 5q31 (RAD50-IL13 and IL4), and 12q13 (STAT6) as major susceptibility loci influencing the regulation of total serum IgE levels. As GWAS may be insufficient to capture causal variants, we performed fine-mapping and re-genotyping of the three loci using 1000 Genomes Project datasets. Linkage disequilibrium tagging polymorphisms and polymorphisms of putative functional relevance were genotyped by chip technology (24 polymorphisms) or MALDI-TOF-MS (40 polymorphisms) in at least 1303 German children (651 asthmatics). The effect of polymorphisms on total serum IgE, IgE percentiles, and atopic diseases was assessed, and a risk score model was applied for gene-by-gene interaction analyses. Functional effects of putative causal variants from these three loci were studied in silico. Associations from GWAS were confirmed and extended. For 1q23 and 5q31, the majority of associations were found with mild to moderately elevated IgE levels, while in the 12q13 locus, single-nucleotide polymorphisms (SNPs) were associated with strongly elevated IgE levels. Gene-by-gene interaction analyses suggested that the presence of mutations in all three loci increases the risk for elevated IgE up to fourfold. This fine-mapping study confirmed previous associations and identified novel associations of SNPs in 1q23, 5q31, and 12q13 with different levels of serum IgE and their concomitant contribution to IgE regulation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. 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.

  9. Size-tunable, hexagonal plate-like Cu3P and Janus-like Cu-Cu3P nanocrystals.

    PubMed

    De Trizio, Luca; Figuerola, Albert; Manna, Liberato; Genovese, Alessandro; George, Chandramohan; Brescia, Rosaria; Saghi, Zineb; Simonutti, Roberto; Van Huis, Marijn; Falqui, Andrea

    2012-01-24

    We describe two synthesis approaches to colloidal Cu(3)P nanocrystals using trioctylphosphine (TOP) as phosphorus precursor. One approach is based on the homogeneous nucleation of small Cu(3)P nanocrystals with hexagonal plate-like morphology and with sizes that can be tuned from 5 to 50 nm depending on the reaction time. In the other approach, metallic Cu nanocrystals are nucleated first and then they are progressively phosphorized to Cu(3)P. In this case, intermediate Janus-like dimeric nanoparticles can be isolated, which are made of two domains of different materials, Cu and Cu(3)P, sharing a flat epitaxial interface. The Janus-like nanoparticles can be transformed back to single-crystalline copper particles if they are annealed at high temperature under high vacuum conditions, which makes them an interesting source of phosphorus. The features of the Cu-Cu(3)P Janus-like nanoparticles are compared with those of the striped microstructure discovered more than two decades ago in the rapidly quenched Cu-Cu(3)P eutectic of the Cu-P alloy, suggesting that other alloy/eutectic systems that display similar behavior might give origin to nanostructures with flat, epitaxial interface between domains of two diverse materials. Finally, the electrochemical properties of the copper phosphide plates are studied, and they are found to be capable of undergoing lithiation/delithiation through a displacement reaction, while the Janus-like Cu-Cu(3)P particles do not display an electrochemical behavior that would make them suitable for applications in batteries. © 2011 American Chemical Society

  10. 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

  11. Cell intrinsic and extrinsic factors synergize in mice with haploinsufficiency for Tp53, and two human del(5q) genes, Egr1 and Apc.

    PubMed

    Stoddart, Angela; Wang, Jianghong; Fernald, Anthony A; Karrison, Theodore; Anastasi, John; Le Beau, Michelle M

    2014-01-09

    Therapy-related myeloid neoplasms (t-MN) are a late complication of the successful use of cytotoxic therapy for patients with cancer. A heterozygous deletions of the long arm of chromosome 5 [del(5q)], observed in 40% of patients, is associated with prior exposure to alkylating agents, and a high frequency of TP53 loss or mutation. In previous studies, we demonstrated that haploinsufficiency of 2 del(5q) genes, Egr1, and Apc, individually play a role in the pathogenesis of hematologic disease in mice. We now show that loss of one copy of Egr1 or Tp53 in an Apc haploinsufficient background (Apc (del/+)) accelerated the development of a macrocytic anemia with monocytosis, early features of t-MN. The development of anemia was significantly accelerated by treatment of mice with the alkylating agent, N-ethyl-N-nitrosourea (ENU), regardless of the levels of expression of Egr1 and Tp53. Transplantation of either wild type; Egr1(+/-); Tp53(+/-); Apc(del/+); or Egr1(+/-), Apc(del/+) bone marrow cells into lethally irradiated Apc(del/+) recipients resulted in rapid development of anemia that was further accelerated by administration of ENU to recipients, demonstrating that the Apc(del/+)-induced anemia was cell extrinsic and potentiated by ENU mutagenesis. These data emphasize the synergistic role of cell intrinsic and cell extrinsic (microenvironment) factors in the pathogenesis of t-MN, and raise awareness of the deleterious effects of cytotoxic therapy on the stromal microenvironment.

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

    SciTech Connect

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

    1993-06-01

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

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

    SciTech Connect

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

    1993-05-01

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

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

    SciTech Connect

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

    1993-06-01

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

  15. Synthesis of halogenated polyhedral phosphaboranes. Crystal structure of closo-1,7-P2B10Cl10.

    PubMed

    Keller, W; Sawitzki, G; Haubold, W

    2000-03-20

    The 12-vertex closo-phosphaborane 1,7-P2B10Cl10 (1) has been prepared in low yield from the pyrolysis reaction of B2Cl4 with PCl3 at temperatures above 400 degrees C. A single-crystal X-ray structure determination of 1 (monoclinic space group P2(1)/n with a = 9.239(2) A, b = 16.786(3) A, c = 15.739(3) a, beta = 93.25(3) degrees, and Z = 4) confirmed that, consistent with its 26 skeletal electron count, the phosphaborane adopts a distorted icosahedral structure with the phosphorus atoms in the 1,7-positions. Crystals of 1 contain toluene in a 1:1 molar ratio embedded between each P atom of neighboring cluster molecules. Alteration of the pyrolytic conditions resulted in the formation of the phosphaboranes P4B8Cl6 (2) and P2B8Cl8 (3), which were characterized spectroscopically. Copyrolysis of B2Cl4 with a mixture of PCl3 and AsCl3 at 450 degrees C generated the six-vertex arsaphosphaborane AsPB4Cl4 (4) and traces of the icosahedral arsaphosphaborane AsPB10Cl10. These compounds are examples of heteroboranes which contain two different group-15 atoms within a single molecule.

  16. Interstitial deletion 5p14.1-p15.2 and 5q14.3-q23.2 in a patient with clubfoot, blepharophimosis, arthrogryposis, and multiple congenital abnormalities.

    PubMed

    Balta, Burhan; Erdogan, Murat; Ergul, Ayse B; Sahin, Yavuz; Ozcan, Alper

    2017-10-01

    Interstitial deletions of the short and long arms of chromosome 5 are rare cytogenetic abnormalities. The 5p distal deletion is a genetic disorder characterized by a high-pitched cat-like cry, microcephaly, epicanthal folds, micrognathia, severe intellectual disability and motor delays. Previously, more than 46 patients with the 5q deletion have been reported. Here, we report de novo interstitial deletions involving 5p14.1-p15.2 and 5q14.3-q23.2 in a patient with multiple congenital abnormalities, including blepharophimosis, arthrogryposis, short neck, round face, pelvic kidney, agenesis of the corpus callosum, and clubfoot. The deletions were characterized using GTG banding and aCGH microarray analysis. Concurrent 5p and 5q interstitial deletions in humans have not been previously reported. We also discussed the relationship between the 5q deleted region and clubfeet. © 2017 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2014-01-01

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

  18. Meta-analysis of the efficacy of treatments for newly diagnosed and relapsed/refractory multiple myeloma with del(17p)

    PubMed Central

    Liu, Jinghua; Yang, Hui; Liang, Xiaochan; Wang, Yuxin; Hou, Jian; Liu, Yanqin; Wang, Jigang; Zhou, Fan

    2017-01-01

    We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25.7 vs. 12-14.6 months) and overall survival (OS) (62% vs. 8% at 36 months) than those treated with PD (bortezomib and dexamethasone) or VAD (vincristine, adriamycin, and dexamethasone). PFS among RRMM patients with del(17p) treated with D (single-agent dexamethasone), Rd/VRd (lenalidomide and dexamethasone/bortezomib and Rd), KRd (carfilzomib and Rd), IRd (ixazomib and Rd), ERd (elotuzumab and Rd), or P+D (pomalidomide and dexamethasone) was 1.1, 2-14.9, 24.5, 15.7, 21.2, and 4.6-7.3 months, respectively. The OS of patients treated with D or K (single-agent carfilzomib), Rd/VRd, ERd, or P+D was 7.7, 7, 4.7–36.4, > 42.3, and 12–12.6 months, respectively. PFS among RRMM patients without del(17p) treated with D, Rd/VRd, ERd, or P+D was 2.3, 8.2-14.8, 18.5, and 4.2 months, while OS was 9, 23-40.8, 42.3, and 14 months, respectively. Thus bortezomib maintenance therapy improves the prognosis of NDMM patients with del(17p). Combined treatment with carfilzomib or elotuzumab and Rd, or pomalidomide with low-dose dexamethasone, improves the outcomes of RRMM patients with del(17p). PMID:28977957

  19. Meta-analysis of the efficacy of treatments for newly diagnosed and relapsed/refractory multiple myeloma with del(17p).

    PubMed

    Liu, Jinghua; Yang, Hui; Liang, Xiaochan; Wang, Yuxin; Hou, Jian; Liu, Yanqin; Wang, Jigang; Zhou, Fan

    2017-09-22

    We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I 2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) ( P = 0.1, I 2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25.7 vs. 12-14.6 months) and overall survival (OS) (62% vs. 8% at 36 months) than those treated with PD (bortezomib and dexamethasone) or VAD (vincristine, adriamycin, and dexamethasone). PFS among RRMM patients with del(17p) treated with D (single-agent dexamethasone), Rd/VRd (lenalidomide and dexamethasone/bortezomib and Rd), KRd (carfilzomib and Rd), IRd (ixazomib and Rd), ERd (elotuzumab and Rd), or P+D (pomalidomide and dexamethasone) was 1.1, 2-14.9, 24.5, 15.7, 21.2, and 4.6-7.3 months, respectively. The OS of patients treated with D or K (single-agent carfilzomib), Rd/VRd, ERd, or P+D was 7.7, 7, 4.7-36.4, > 42.3, and 12-12.6 months, respectively. PFS among RRMM patients without del(17p) treated with D, Rd/VRd, ERd, or P+D was 2.3, 8.2-14.8, 18.5, and 4.2 months, while OS was 9, 23-40.8, 42.3, and 14 months, respectively. Thus bortezomib maintenance therapy improves the prognosis of NDMM patients with del(17p). Combined treatment with carfilzomib or elotuzumab and Rd, or pomalidomide with low-dose dexamethasone, improves the outcomes of RRMM patients with del(17p).

  20. 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.

  1. Evidence for a pleiotropic QTL on chromosome 5q13 influencing both time to asthma onset and asthma score in French EGEA families.

    PubMed

    Bouzigon, Emmanuelle; Ulgen, Ayse; Dizier, Marie-Hélène; Siroux, Valérie; Lathrop, Mark; Kauffmann, Francine; Pin, Isabelle; Demenais, Florence

    2007-07-01

    Although many genome screens have been conducted for asthma as a binary trait, there is limited information regarding the genetic factors underlying variation of asthma expression. Phenotypes related to variable disease expression include time to asthma onset and variation in clinical expression as measured by an asthma score built from EGEA data. A recent genome scan conducted for this score led to detection of a new region (18p11) not revealed by analysis of dichotomous asthma. Our goal was to characterize chromosomal regions harboring genes underlying time to asthma onset and to search for pleiotropic QTL influencing both time to asthma onset and the asthma score. We conducted a genome-wide linkage screen for time to asthma onset, modeled by martingale residuals from Cox survival model, in EGEA families with at least two asthmatic sibs. This was followed by a bivariate linkage scan of these residuals and asthma score. Univariate linkage analysis was performed using the Maximum Likelihood Binomial method that we extended to bivariate analysis. This screen revealed two regions potentially linked to time to asthma onset, 1p31 (LOD = 1.70, P = 0.003) and 5q13 (LOD = 1.87, P = 0.002). Bivariate linkage analysis led to a substantial improvement of the linkage signal on 5q13 (P = 0.00007), providing evidence for a pleiotropic QTL influencing both variation of time to asthma onset and of clinical expression. Use of quantitative phenotypes of variable disease expression and suitable statistical methodology can improve the power to detect new regions harboring genes which may play an important role in onset and course of disease.

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

    SciTech Connect

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

    1993-10-01

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

  3. 5q- syndrome-like features as the first manifestation of myelodysplastic syndrome in a patient with an unbalanced whole-arm translocation der(5;19)(p10;q10).

    PubMed

    Ureshino, Hiroshi; Kizuka, Haruna; Kusaba, Kana; Sano, Haruhiko; Nishioka, Atsujiro; Shindo, Takero; Kubota, Yasushi; Ando, Toshihiko; Kojima, Kensuke; Kimura, Shinya

    2017-05-01

    Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before. Bone marrow aspirate (BM) revealed low blast counts with trilineage dysplastic cells, and fluorescent in situ hybridization revealed the loss of colony-stimulating factor 1 receptor (CSF1R) signals at 5q33-34. Although the initial manifestation was 5q- syndrome, G-banded metaphase analysis and spectral karyotyping analysis revealed der(5;19)(p10;q10). Consequently, a diagnosis of therapy-related MDS (t-MDS) was made. She failed to respond to azacitidine and lenalidomide therapy. Consequently, transfusion-dependent anemia and thrombocytopenia developed with increasing myeloblasts. Cytarabine, aclarubicin, and granulocyte colony-stimulating factor therapy also failed, and unfortunately the patient died. Thus, MDS with der(5;19)(p10;q10) may represent a platinum agent-related t-MDS that is highly resistant to chemotherapy.

  4. 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.

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

    SciTech Connect

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

    2009-12-21

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

  6. Photoinduced Kondo effect in CeZn3P3

    NASA Astrophysics Data System (ADS)

    Kitagawa, J.; Kitajima, D.; Shimokawa, K.; Takaki, H.

    2016-01-01

    The Kondo effect, which originates from the screening of a localized magnetic moment by a spin-spin interaction, is widely observed in nonartificial magnetic materials, artificial quantum dots, and carbon nanotubes. In devices based on quantum dots or carbon nanotubes that target quantum information applications, the Kondo effect can be tuned by a gate voltage, a magnetic field, or light. However, the manipulation of the Kondo effect in nonartificial materials has not been thoroughly studied; in particular, the artificial creation of the Kondo effect remains unexplored. Per this subject study, however, a route for the optical creation of the Kondo effect in the nonartificial material p -type semiconductor CeZn3P3 is presented. The Kondo effect emerges under visible-light illumination of the material by a continuous-wave laser diode and is ultimately revealed by photoinduced electrical resistivity, which clearly exhibits a logarithmic temperature dependency. By contrast, a La-based compound (LaZn3P3 ) displays only normal metallic behavior under similar illumination. The photoinduced Kondo effect, which occurs at higher temperatures when compared with the Kondo effect in artificial systems, provides a potential range of operation for not only quantum information/computation devices but also for operation of magneto-optic devices, thereby expanding the range of device applications based on the Kondo effect.

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

    SciTech Connect

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

    1987-05-01

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

  8. Photoabsorption of Mg above the 3p threshold

    NASA Astrophysics Data System (ADS)

    Fung, H. S.; Wu, H. H.; Yih, T. S.; Fang, T. K.; Chang, T. N.

    2001-11-01

    We present the results of a joint experimental and theoretical study on the absolute photoabsorption cross sections from the ground state leading to resonance structures between the Mg+ 3p 2P and Mg+ 4s 2S thresholds. The absolute cross sections are determined by measuring the light attenuation through a heatpipe using the synchrotron radiation. The observed spectra are compared and analyzed with the help of a B-spline based multichannel K-matrix calculation. A hidden 3d4p 1P resonance missing from the observed spectrum is examined in detail. In addition, a nearly degenerate overlap between 3d5f and 4s8p 1P resonances near 77.6 nm is carefully analyzed.

  9. Kinetics of O/super 3P/ + CO + M recombination.

    NASA Technical Reports Server (NTRS)

    Slanger, T. G.; Wood, B. J.; Black, G.

    1972-01-01

    Measurement of rate coefficients over the temperature range from 250 to 370 K for the three-body recombination of O(super 3P) with CO. Earlier results at 300 K have been re-evaluated and were found to have been influenced by unknown impurities in the CO, which have now been removed by more elaborate purification methods. For CO as the third body, the rate constant is given by K = 6.5 x 10 to the minus 33rd exp (-4340 plus or minus 550/RT) cm to the 6th power per sq molecule per sec. For N2 and CO2, the 296 K rate constants are 2.3 and 6.2 x 10 to the minus 36th cm to the 6th power per sq molecule per sec, respectively.

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

    NASA Technical Reports Server (NTRS)

    Golub, Morton A.

    1992-01-01

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

  11. 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

  12. 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

  13. Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience.

    PubMed

    Hebraud, Benjamin; Magrangeas, Florence; Cleynen, Alice; Lauwers-Cances, Valerie; Chretien, Marie-Lorraine; Hulin, Cyrille; Leleu, Xavier; Yon, Edwige; Marit, Gerald; Karlin, Lionel; Roussel, Murielle; Stoppa, Anne-Marie; Belhadj, Karim; Voillat, Laurent; Garderet, Laurent; Macro, Margaret; Caillot, Denis; Mohty, Mohamad; Facon, Thierry; Moreau, Philippe; Attal, Michel; Munshi, Nikhil; Corre, Jill; Minvielle, Stephane; Avet-Loiseau, Herve

    2015-03-26

    In multiple myeloma, cytogenetic changes are important predictors of patient outcome. In this setting, the most important changes are deletion 17p, del(17p), and translocation of chromosomes 4 and 14, t(4;14), conferring a poor outcome. However, a certain degree of heterogeneity is observed in the survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either t(4;14) (157 patients) or del(17p) (110 patients), 25 patients presenting both abnormalities, using single nucleotide polymorphism array. In patients with t(4;14), del(1p32), del22q, and >30 chromosomal structural changes negatively impacted progression-free survival (PFS). For overall survival (OS), del(13q14), del(1p32), and the number of chromosomal structural changes worsened the prognosis of patients. For patients with del(17p), del6q worsened the prognosis of patients, whereas trisomy 15 and monosomy 14 were found to have a protective effect on PFS. For OS, del(1p32) worsened the prognosis of patients, whereas having >8 numerical changes was found to have a protective effect on survival. This study, which is the largest series of high-risk patients analyzed with the most modern genomic technique, identified 1 main factor negatively impacting survival: del(1p32).

  14. Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience

    PubMed Central

    Hebraud, Benjamin; Magrangeas, Florence; Cleynen, Alice; Lauwers-Cances, Valerie; Chretien, Marie-Lorraine; Hulin, Cyrille; Leleu, Xavier; Yon, Edwige; Marit, Gerald; Karlin, Lionel; Roussel, Murielle; Stoppa, Anne-Marie; Belhadj, Karim; Voillat, Laurent; Garderet, Laurent; Macro, Margaret; Caillot, Denis; Mohty, Mohamad; Facon, Thierry; Moreau, Philippe; Attal, Michel; Munshi, Nikhil; Corre, Jill; Minvielle, Stephane

    2015-01-01

    In multiple myeloma, cytogenetic changes are important predictors of patient outcome. In this setting, the most important changes are deletion 17p, del(17p), and translocation of chromosomes 4 and 14, t(4;14), conferring a poor outcome. However, a certain degree of heterogeneity is observed in the survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either t(4;14) (157 patients) or del(17p) (110 patients), 25 patients presenting both abnormalities, using single nucleotide polymorphism array. In patients with t(4;14), del(1p32), del22q, and >30 chromosomal structural changes negatively impacted progression-free survival (PFS). For overall survival (OS), del(13q14), del(1p32), and the number of chromosomal structural changes worsened the prognosis of patients. For patients with del(17p), del6q worsened the prognosis of patients, whereas trisomy 15 and monosomy 14 were found to have a protective effect on PFS. For OS, del(1p32) worsened the prognosis of patients, whereas having >8 numerical changes was found to have a protective effect on survival. This study, which is the largest series of high-risk patients analyzed with the most modern genomic technique, identified 1 main factor negatively impacting survival: del(1p32). PMID:25636340

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

    PubMed Central

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

    2016-01-01

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

  16. Complex karyotype is a stronger predictor than del(17p) for an inferior outcome in relapsed or refractory chronic lymphocytic leukemia patients treated with ibrutinib-based regimens.

    PubMed

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

    2015-10-15

    Ibrutinib is active in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). In patients treated with ibrutinib for R/R CLL, del(17p), identified by interphase fluorescence in situ hybridization (FISH), is associated with inferior progression-free survival despite equivalent initial response rates. Del(17p) is frequently associated with a complex metaphase karyotype (CKT); the prognostic significance of CKT in ibrutinib-treated patients has not been reported. This study reviewed 88 patients treated for R/R CLL at The University of Texas MD Anderson Cancer Center with investigational ibrutinib-based regimens from 2010 to 2013. Pretreatment FISH and lipopolysaccharide-stimulated metaphase cytogenetic analysis were performed on bone marrow. An adequate pretreatment metaphase karyotype was available for 56 of the 88 patients. The karyotype was complex in 21 of the 56 cases; 17 of the 21 had del(17p) according to FISH. The overall response rate, including partial remission with persistent lymphocytosis, was 94%; 18% had complete responses. In a multivariate analysis (MVA), only CKT was significantly associated with event-free survival (EFS; hazard ratio [HR], 6.6 [95% CI 1.7-25.6]; P = .006). Fludarabine-refractory CLL (HR, 6.9 [95% CI 1.8-27.1], P = .005) and CKT (HR 5.9 [95% CI 1.6-22.2], P = .008) were independently associated with inferior overall survival (OS) in MVA. Del(17p) by FISH was not significantly associated with EFS or OS in MVA. CKT is a powerful predictor of outcomes for ibrutinib-treated patients with R/R CLL and may be a stronger predictor of biological behavior than del(17p) by FISH. Because of their relatively poor outcomes, patients with CKT are ideal candidates for studies of consolidative treatment strategies or novel treatment combinations. © 2015 American Cancer Society.

  17. Admixture mapping of quantitative trait loci for BMI in African Americans: evidence for loci on chromosomes 3q, 5q, and 15q.

    PubMed

    Basu, Analabha; Tang, Hua; Arnett, Donna; Gu, C Charles; Mosley, Tom; Kardia, Sharon; Luke, Amy; Tayo, Bamidele; Cooper, Richard; Zhu, Xiaofeng; Risch, Neil

    2009-06-01

    Obesity is a heritable trait and a major risk factor for highly prevalent common diseases such as hypertension and type 2 diabetes. Previously we showed that BMI was positively correlated with African ancestry among the African Americans (AAs) in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program (FBPP). In a set of 1,344 unrelated AAs, using Individual Ancestry (IA) estimates at 284 marker locations across the genome, we now present a quantitative admixture mapping analysis of BMI. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and the European American (EA) in the FBPP as the European ancestral population. The analysis was based on a common set of 284 microsatellite markers genotyped in all three groups. We considered the quantitative trait, BMI, as the response variable in a regression analysis with the marker location specific excess European ancestry as the explanatory variable. After suitably adjusting for different covariates such as sex, age, and network, we found strong evidence for a positive association with European ancestry at chromosome locations 3q29 and 5q14 and a negative association on chromosome 15q26. To our knowledge, this is the largest quantitative admixture mapping effort in terms of sample size and marker locus involvement for the trait. These results suggest that these regions may harbor genes influencing BMI in the AA population.

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

    PubMed

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

    2015-11-28

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

  19. Three rearrangements of chromosome 5 in a patient with myelodysplastic syndrome: an atypical deletion 5q, a complex intrachromosomal rearrangement of chromosome 5, and a paracentric inversion of chromosome 5.

    PubMed

    Douet-Guilbert, Nathalie; Basinko, Audrey; Eveillard, Jean-Richard; Morel, Frédéric; Le Bris, Marie-Josée; Guéganic, Nadia; Bovo, Clément; Herry, Angèle; Berthou, Christian; De Braekeleer, Marc

    2010-12-01

    We report the case of a 74-year-old man who sought care for de novo myelodysplastic syndrome (RAEB-1). Conventional cytogenetic techniques showed a karyotype with two different deletions of the long arm of chromosome 5 distributed in three clones: 46,XY,del(1)(p34),del(5)(q14q23)[2]/46,XY,del(1)(p34),del(5)(q14q34)[10]/46,idem,inv(5)(q?11q?34)[7]. Precise characterization of the breakpoints, delineation of the deleted regions, identification of the complex intrachromosomal rearrangement of chromosome 5, and sequential accumulation of chromosomal abnormalities were elucidated by several fluorescence in situ hybridization analyses. We also assessed the clinical, biological, and cytogenetic evolution under lenalidomide treatment and after its interruption. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2011-01-01

    We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband's karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter-,5qter+).arr 5q34q35(163,328,000-180,629,000)×3, 9p24p23(194,000-12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication. Copyright © 2010 S. Karger AG, Basel.

  1. 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

  2. A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa.

    PubMed

    Sobota, Rafal S; Stein, Catherine M; Kodaman, Nuri; Maro, Isaac; Wieland-Alter, Wendy; Igo, Robert P; Magohe, Albert; Malone, LaShaunda L; Chervenak, Keith; Hall, Noemi B; Matee, Mecky; Mayanja-Kizza, Harriet; Joloba, Moses; Moore, Jason H; Scott, William K; Lahey, Timothy; Boom, W Henry; von Reyn, C Fordham; Williams, Scott M; Sirugo, Giorgio

    2017-06-01

    One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection. Among these individuals, 244 tested were tuberculin skin test (TST) positive either at enrollment or during the >8 year follow up, while 225 were not. We identified a genome-wide significant association between a dominant model of rs877356 and binary TST status in the combined cohort (Odds ratio = 0.2671, p = 1.22x10-8). Association was replicated with similar significance when examining TST induration as a continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from IL9. Two-locus analyses of association of variants near rs877356 showed a haplotype comprised of rs877356 and an IL9 missense variant, rs2069885, had the most significant association (p = 1.59x10-12). We also replicated previously linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells and TH2 cells during inflammatory responses, providing a possible link between airway inflammation and protection from MTB infection. Our results indicate that studying uninfected, HIV-positive participants with extensive exposure increases the power to detect associations in complex infectious disease.

  3. 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

  4. Epitope shared by functional variant of organic cation/carnitine transporter, OCTN1, Campylobacter jejuni and Mycobacterium paratuberculosis may underlie susceptibility to Crohn's disease at 5q31.

    PubMed

    Lamhonwah, Anne-Marie; Ackerley, Cameron; Onizuka, Russell; Tilups, Aina; Lamhonwah, Daniel; Chung, Cilla; Tao, Ke Sheng; Tellier, Raymond; Tein, Ingrid

    2005-12-02

    Campylobacter jejuni and Mycobacterium paratuberculosis have been implicated in the pathogenesis of Crohn's disease. The presence of bacterial metabolites in the colonic lumen causing a specific breakdown of fatty acid oxidation in colonic epithelial cells has been suggested as an initiating event in inflammatory bowel disease (IBD). l-Carnitine is a small highly polar zwitterion that plays an essential role in fatty acid oxidation and ATP generation in intestinal bioenergetic metabolism. The organic cation/carnitine transporters, OCTN1 and OCTN2, function primarily in the transport of l-carnitine and elimination of cationic drugs in the intestine. High-resolution linkage disequilibrium mapping has identified a region of about 250kb in size at 5q31 (IBD5) encompassing the OCTN1 and -2 genes, to confer susceptibility to Crohn's disease. Recently, two variants in the OCTN1 and OCTN2 genes have been shown to form a haplotype which is associated with susceptibility to Crohn's. We show that OCTN1 and OCTN2 are strongly expressed in target areas for IBD such as ileum and colon. Further, we have now identified a nine amino acid epitope shared by this functional variant of OCTN1 (Leu503Phe) (which decreases the efficiency of carnitine transport), and by C. jejuni (9 aa) and M. paratuberculosis (6 aa). The prevalence of this variant of OCTN1 (Phe503:Leu503) is 3-fold lower in unaffected individuals of Jewish origin (1:3.44) compared to unaffected individuals of non-Jewish origin (1:1). We hypothesize that a specific antibody raised to this epitope during C. jejuni or M. paratuberculosis enterocolitis would cross-react with the intestinal epithelial cell functional variant of OCTN1, an already less efficient carnitine transporter, leading to an impairment of mitochondrial beta-oxidation which may then serve as an initiating event in IBD. This impairment of l-carnitine transport by OCTN1 may respond to high-dose l-carnitine therapy.

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

    SciTech Connect

    Clines, G.; Lovett, M.

    1994-09-01

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

  6. Measurement of O17(p,γ)F18 between the narrow resonances at Erlab=193 and 519 keV

    NASA Astrophysics Data System (ADS)

    Newton, J. R.; Iliadis, C.; Champagne, A. E.; Cesaratto, J. M.; Daigle, S.; Longland, R.

    2010-04-01

    The O17(p,γ)F18 reaction sensitively influences hydrogen burning nucleosynthesis in a number of stellar sites, including classical novae. These thermonuclear explosions, taking place in close binary star systems, produce peak temperatures in the range of T=100-400 MK. Recent results indicate that the thermonuclear rates for this reaction in this particular temperature range are dominated by the direct capture process. We report on the measurement of the O17(p,γ)F18 cross section between the narrow resonances at Erlab=193 and 519 keV, where the S factor is expected to vary smoothly with energy. We extract the direct capture contribution from the total cross section and demonstrate that earlier data are inconsistent with our results.

  7. 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

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

    DTIC Science & Technology

    2001-07-01

    bodies are scattered throughout the cell, and are heavily clustered around the nucleus. A similar pattern was obtained in immortalized HOSE cells...Gilbert, D. J., Copeland, malayi, 09561 from P. falciparum, and 15266 from rice. Clustering of N. G., Gilks, C. B., Zweidler-McKay, P., Grimes, H. L... clustered around the nucleus. Attempts to create on l7pl3, including TP53 at 17p13.1 and a more telomeric region at cell lines that stably expressed

  9. 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

  10. 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

  11. Trisomy of 19.4 Mb region of chromosome 22 and subtelomeric 17p identified in a male without clinical affectation.

    PubMed

    Morales, Carme; Soler, Anna; Margarit, Ester; Madrigal, Irene; Sánchez, Aurora

    2007-10-15

    Supernumerary marker chromosomes (SMCs) have a reported frequency in the prenatal and newborn population ranging from 0.04% to 0.08% and about 37% of diagnosed SMCs are associated with an abnormal phenotype. Around 7.5% of them are derived from chromosome 22. SMCs(22) that result in tri- or tetrasomy of band 22q11.2 are associated with Cat-eye syndrome (CES), a syndrome of variable penetrance and affectation. CES-like phenotype has been also related to 22q11.2 interstitial duplications and der(22) syndrome. The 22q11.2 region, also involved in the velocardiofacial microdeletional syndrome, presents high susceptibility to chromosomal rearrangements due to the presence of low-copy repeats sequences (LCR22). Another region in the genome rich in LCR is 17p and five recurrent disorders have been mapped on the region 17p11-p13. Some chromosomal imbalances affecting the 17p13.3 subtelomeric region have been reported, related to cryptic unbalanced translocations and associated, in most cases, to mental retardation and dysmorphic features. We report on a healthy male carrier of a SMC that was identified as a +der(22)t(17;22)(p13.3;q11.2) consequence of an abnormal 3:1 segregation of the paternal t(17;22) and we have determined the approximate size of the trisomic regions, comparing the obtained results with other reported imbalances involving 22q11.2 and 17pter. Copyright (c) 2007 Wiley-Liss, Inc.

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

    NASA Astrophysics Data System (ADS)

    Sekanina, Zdenek

    2009-10-01

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

  13. 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.

  14. First Direct Measurement of the O17(p,γ)F18 Reaction Cross Section at Gamow Energies for Classical Novae

    NASA Astrophysics Data System (ADS)

    Scott, D. A.; Caciolli, A.; Di Leva, A.; Formicola, A.; Aliotta, M.; Anders, M.; Bemmerer, D.; Broggini, C.; Campeggio, M.; Corvisiero, P.; Elekes, Z.; Fülöp, Zs.; Gervino, G.; Guglielmetti, A.; Gustavino, C.; Gyürky, Gy.; Imbriani, G.; Junker, M.; Laubenstein, M.; Menegazzo, R.; Marta, M.; Napolitani, E.; Prati, P.; Rigato, V.; Roca, V.; Somorjai, E.; Salvo, C.; Straniero, O.; Strieder, F.; Szücs, T.; Terrasi, F.; Trezzi, D.

    2012-11-01

    Classical novae are important contributors to the abundances of key isotopes, such as the radioactive F18, whose observation by satellite missions could provide constraints on nucleosynthesis models in novae. The O17(p,γ)F18 reaction plays a critical role in the synthesis of both oxygen and fluorine isotopes, but its reaction rate is not well determined because of the lack of experimental data at energies relevant to novae explosions. In this study, the reaction cross section has been measured directly for the first time in a wide energy range Ec.m.≃200-370keV appropriate to hydrogen burning in classical novae. In addition, the Ec.m.=183keV resonance strength, ωγ=1.67±0.12μeV, has been measured with the highest precision to date. The uncertainty on the O17(p,γ)F18 reaction rate has been reduced by a factor of 4, thus leading to firmer constraints on accurate models of novae nucleosynthesis.

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

    SciTech Connect

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

    1995-11-01

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

  16. Tumor Protein 53 Gene Mutations Without 17p13 Deletion Have No Significant Clinical Implications in Chronic Lymphocytic Leukemia. Detection of a New Mutation.

    PubMed

    Diamantopoulos, Panagiotis T; Samara, Stavroula; Kollia, Panagoula; Giannakopoulou, Nefeli; Sofotasiou, Maria; Kalala, Fani; Kodandreopoulou, Elina; Zervakis, Panagiotis; Vassilakopoulos, Theodoros; Siakantaris, Marina; Mantzourani, Marina; Angelopoulou, Maria; Kyrtshonis, Marie-Christine; Korkolopoulou, Penelope; Patsouris, Efstathios; Viniou, Nora-Athina

    2017-05-01

    The tumor protein p53 (TP53) gene may be inactivated through 17p13 deletion, somatic mutations, or both. In chronic lymphocytic leukemia (CLL) although 17p13 deletion is correlated with poor prognosis, the role of sole TP53 mutations remains controversial. We carried out a mutation analysis of TP53 gene in 72 patients with CLL. Seventy-one (98.6%) patients carried the polymorphic site c.215C>G, p.Pro72Arg, but its presence was not correlated with overall survival (OS). Moreover, 19 (26.4%) patients carried a mutation of TP53. Among the eight detected mutations, to our knowledge, one (c.587G>A) has never been reported in the past. There was a correlation of the mutation burden with the stage of the disease (p=0.022), but not with OS. None of the detected mutations was individually correlated with OS. The clinical significance of TP53 mutations is still a matter of debate and larger studies and meta-analyses are required to reach an unequivocal conclusion. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. 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

  18. Prognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene

    PubMed Central

    Liscia, D S; Morizio, R; Venesio, T; Palenzona, C; Donadio, M; Callahan, R

    1999-01-01

    Several studies indicate that the short arm of chromosome 17 is one of the most frequently altered regions in sporadic breast carcinomas (45–60%). In the present report the 17p13.3-ter locus in tumour DNA of breast cancer patients, along with their matching normal lymphocyte DNA, have been mapped with four markers (D17S5, D17S379, ABR and D17S34), spanning nearly 3 cM of the telomer. Sixty-five of 143 heterozygous tumours had lost at least one of the markers at the minimum region of loss (45%). High levels of loss of these distal markers on 17p13.3 are independent of TP53 mutations and are associated with tumour cell proliferation. A follow-up period of over 7 years demonstrates that loss of these markers correlates both with disease-free (P = 0.004) and overall survival (P = 0.007). In addition we show that for disease-free survival the prognostic power of this genetic alteration is second only to axillary lymph node involvement (3.1 vs 6.3 relative risk), and is a better predictor than the mutational status of TP53 (1.6 relative risk). Our results are further evidence of the presence, within the region, of at least a second tumour suppressor gene distal to TP53, that might be targeted by deletions. © 1999 Cancer Research Campaign PMID:10360661

  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 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

  20. 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

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

    PubMed Central

    Engdahl, Elin; Dunn, Nicky; Niehusmann, Pitt; Wideman, Sarah; Wipfler, Peter; Becker, Albert J.; Ekström, Tomas J.; Almgren, Malin

    2017-01-01

    ABSTRACT 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

  2. 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

  3. Astrophysical reaction rate for F17(p,γ)Ne18 from the transfer reaction C13(O17,O18)C12

    NASA Astrophysics Data System (ADS)

    Al-Abdullah, T.; Carstoiu, F.; Chen, X.; Clark, H. L.; Gagliardi, C. A.; Lui, Y.-W.; Mukhamedzhanov, A.; Tabacaru, G.; Tokimoto, Y.; Trache, L.; Tribble, R. E.; Zhai, Y.

    2014-02-01

    The asymptotic normalization coefficients of the bound states Jπ=(01+,21+,41+,22+) in O18 are extracted from the peripheral neutron transfer reaction C13(O17,O18)C12. They are then converted to their mirror states in Ne18, which are further used to evaluate the astrophysical S factor for the proton capture reaction F17(p,γ)Ne18. The elastic-scattering cross sections have been measured in both incoming and outgoing channels in order to extract the optical potentials needed for distorted-wave-Born-approximation calculations. The S factor is found to be S1-17(0)=2.17±0.37 keV b. The contribution of the direct capture rate to this reaction is estimated, and its consequences on the production of F18 at stellar energies in ONe novae are discussed.

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

    PubMed

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

    2012-08-13

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

  5. CHARMM TIP3P Water Model Suppresses Peptide Folding by Solvating the Unfolded State.

    PubMed

    Boonstra, Sander; Onck, Patrick R; Giessen, Erik van der

    2016-04-21

    The accuracy of molecular dynamics simulations depends on the underlying force field, defined by the form and parametrization of the interparticle potential functions and the water model. The treatment of the solvent is crucial in molecular dynamics force fields, as hydrophobic interactions and hydrogen bonding are important molecular forces. The widely used CHARMM force field was originally parametrized using a modified version of the TIP3P water model (mTIP3P), including Lennard-Jones interactions between hydrogens and oxygens. The latest version, CHARMM36, was optimized using the standard TIP3P water model (sTIP3P) for proteins, while mTIP3P is still being used for lipids. Our replica exchange molecular dynamics simulations on dynamic peptides show that the CHARMM36 force field with mTIP3P water yields less realistic folding than with sTIP3P water. Analysis of the dimensions and hydrogen bonding of the unfolded state reveals that the peptides are more solvated and extended in mTIP3P, due to a higher solvation energy of the peptide in this water model. We recommend using CHARMM36 with sTIP3P when simulating peptides, folded proteins, and natively unfolded proteins, but combinations of proteins with lipids would require a reparametrization to make their water models compatible.

  6. 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

  7. Ab initio calculations of the 33S 3p4 3PJ and 33S-/37, 35Cl 3p5 2PoJ hyperfine structures

    NASA Astrophysics Data System (ADS)

    Carette, T.; Godefroid, M. R.

    2011-05-01

    We present highly correlated multi-configuration Hartree-Fock (MCHF) calculations of the hyperfine structure of the 3p5 2PoJ levels of 33S- and 35, 37Cl. We obtain good agreement with observation. The hyperfine structure of the neutral sulphur 33S 3p4 3PJ lowest multiplet that has never been measured to the knowledge of the authors is also estimated theoretically. We discuss some interesting observations made on the description of the atomic core in MCHF theory.

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

    PubMed

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

    2016-07-01

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

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

    SciTech Connect

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

    2012-11-15

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

  10. 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.

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

    SciTech Connect

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

    1994-05-15

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

  12. Detection of Novel t(12;17)(p12;p13) in Relapsed Refractory Acute Myeloid Leukemia by Anchored Multiplex PCR(AMP)-based Next-Generation Sequencing.

    PubMed

    Badar, Talha; Johnson, Laura; Trifilo, Katelyn; Wang, Helen; Kudlow, Brian A; Padron, Eric; Pappenhausen, Peter R; Hussaini, Mohammad O

    2017-02-09

    Although several technologies can be used to detect gene fusions, anchored multiplex PCR next-generation sequencing (AMP-NGS) offers the advantage of novel fusion detection and the ability to multiplex multitudinous genes. We applied AMP-NGS technology in the evaluation of a 56-year-old gentleman with myelodysplastic syndrome transformed acute myeloid leukemia (AML). Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy. At progression patients had normal cytogenetics but NGS profiling showed ETV6 c.416_417del CT frame shift and U2AF1 S34F mutations. Patient attains brief remission of 2 months after induction chemotherapy and then he was refractory to 2 salvage chemotherapy regimens. Reassessment after failing second salvage, identified t(12;17)(p13;p13)[20] by karyotype. It was postulated that the 12p13 locus might represent a new rearrangement of ETV6. AMP-NGS confirmed involvement of the ETV6 with discovery of a novel fusion partner, HIC1. The detection of the novel fusion partners was supported by the breakpoints originally observed by karyotype. This discovery of ETV6-HIC1 gene fusion by AMP-NGS technology provided new insight into a leukemogenic pathway in AML. Future use of this technology can serve as an adjunct tool in workup of patients with AML and can also help in formulating therapeutic strategies.

  13. PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation

    PubMed Central

    Wu, Yanwei; Cheng, Shiya; Zhao, Hongyu; Zou, Wei; Yoshina, Sawako; Mitani, Shohei; Zhang, Hong; Wang, Xiaochen

    2014-01-01

    Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18 in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P turnover in autophagosome maturation and/or autolysosome formation. Subject Categories: Autophagy & Cell Death; Membrane & Intracellular Transport PMID:25124690

  14. Further evidence for clustering of human GABA[sub A] receptor subunit genes: Localization of the [alpha][sub 6]-subunit gene (GABRA6) to distal chromosome 5q by linkage analysis

    SciTech Connect

    Hicks, A.A.; Kamphuis, W.; Darlison, M.G.

    1994-03-15

    GABA[sub A] receptors are hetero-oligomeric ion-channel complexes that are composed of combinations of [alpha], [beta], [gamma], and [delta] subunits and play a major role in inhibitory neurotransmission in the mammalian brain. The authors report here a microsatellite polymorphism within the human [alpha][sub 6]-subunit gene (GABRA6). Mapping of this marker in a human-hamster hybrid cell-line panel and typing of the repeat in the Centre d'Etude du Polymorphisme Humain (CEPH) reference families enabled the localization of this gene to chromosome 5q and established its linkage to the GABA[sub A] receptor [alpha][sub 1]-subunit gene (GA-BRA1) with a maximum lod score (Z[sub max]) ofmore » 39.87 at a [theta] of 0.069 (males) and 0.100 (females). These results reveal the clustering of GABRA6, GABRA1, and the GABA[sub A] receptor [gamma][sub 2]-subunit gene (GABRG2) on distal chromosome 5q. 17 refs., 1 fig., 1 tab.« less

  15. Association Study of Reported Significant Loci at 5q35.3, 7p14.3, 13q14.1 and 16p12.3 with Urolithiasis in Chinese Han Ethnicity

    PubMed Central

    Wang, Lujia; Feng, Chenchen; Ding, Guanxiong; Lin, Xiaoling; Gao, Peng; Jiang, Haowen; Xu, Jianfeng; Ding, Qiang; Wu, Zhong

    2017-01-01

    In this study, we aimed to validate the association of 8 reported significant loci at 5q35.3, 7p14.3, 13q14.1 and 16p12.3 with urolithiasis in Chinese Han population. We performed case-control association analysis using 624 patients with nephrolithiasis and 1008 control subjects. We selected single-nucleotide polymorphism (SNPs) including rs12654812 and rs11746443 from 5q32.3; rs12669187 and rs1000597 from 7q14.3; rs7981733, rs4142110 and rs17646069 from 13q14.1 and rs4293393 from 16p12.3 which were previously reported to be associated with nephrolithiasis. We found none of these eight reported SNPs were significant associated with urolithiasis risk in Chinese Han population, which suggested that differences could exist in the mechanisms of calcium urolithiasis between Chinese and Japanese Ethnics. The A allele of rs12669187 was significantly correlated with increased level of serum magnesium. The C allele of rs1000597 was associated with higher levels of serum creatinine, uric acid, calcium and lower urine pH level. The T allele of rs4142110 was correlated with higher levels of serum magnesium, phosphorus, and lower AKP level. The G alleles of rs4293393 was associated with higher serum CO2 level. The risk alleles of these SNPs were proved to be associated with the electrolytes metabolism that may result in the formation of urolithiasis. PMID:28361944

  16. 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.

  17. 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.

  18. Direct Binding to Rsp5p Regulates Ubiquitination-independent Vacuolar Transport of Sna3p

    PubMed Central

    Watson, Hadiya

    2007-01-01

    The sorting of integral membrane proteins such as carboxypeptidase S (Cps1p) into the luminal vesicles of multivesicular bodies (MVBs) in Saccharomyces cerevisiae requires ubiquitination of their cytosolic domains by the ubiquitin ligases Rsp5p and/or Tul1p. An exception is Sna3p, which does not require ubiquitination for entry into MVBs. The mechanism underlying this ubiquitination-independent MVB sorting pathway has not yet been characterized. Here, we show that Sna3p sorting into the MVB pathway depends on a direct interaction between a PPAY motif within its C-terminal cytosolic tail and the WW domains of Rsp5p. Disruption of this interaction inhibits vacuolar targeting of Sna3p and causes its accumulation in a compartment that overlaps only partially with MVBs. Surprisingly, Sna3p does require a functional ubiquitin-ligase HECT domain within Rsp5p; however, the dependence of Sna3p on HECT domain activity is distinct from that of Cps1p. Last, we show that Sna3p requires neither Tul1p nor the transmembrane adaptor protein Bsd2p for its MVB sorting. Our data demonstrate that Sna3p follows a novel ubiquitination-independent, but Rsp5p-mediated, sorting pathway to the vacuole. PMID:17332499

  19. 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.

  20. 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.

  1. Functional Characterization of MicroRNA-27a-3p Expression in Human Polycystic Ovary Syndrome.

    PubMed

    Wang, Mingming; Sun, Jing; Xu, Bo; Chrusciel, Marcin; Gao, Jun; Bazert, Maciei; Stelmaszewska, Joanna; Xu, Yunyun; Zhang, Hongwen; Pawelczyk, Leszek; Sun, Fei; Tsang, Suk Ying; Rahman, Nafis; Wolczynski, Slawomir; Li, Xiangdong

    2018-01-01

    The goal of this study was to characterize the function of microRNA-27a-3p (miR-27a-3p) in polycystic ovary syndrome (PCOS). miR-27a-3p expression was analyzed in excised granulosa cells (GCs) from 21 patients with PCOS and 12 normal patients undergoing in vitro fertilization cycle treatments and in 17 nontreated cuneiform ovarian resection PCOS samples and 13 control ovarian samples from patients without PCOS. We found that the expression of miR-27a-3p was significantly increased in both excised GCs and the ovaries of patients with PCOS compared with the controls. Insulin treatment of the human granulosa-like tumor cell line (KGN) resulted in decreased downregulated expression of miR-27a-3p, and this effect appeared to be mediated by signal transducer and activator of transcription STAT1 and STAT3. The overexpression of miR-27a-3p in KGN cells inhibited SMAD5, which in turn decreased cell proliferation and promoted cell apoptosis. After KGN cells were stimulated with insulin for 48 hours, there was increased expression of SMAD5 protein and decreased apoptosis. Additionally, knockdown/overexpression of SMAD5 in KGN cells reduced/increased cell number and promoted/inhibited cell apoptosis. Insulin-stimulated primary GCs isolated from patients with PCOS, in contrast to normal GCs or KGN cells, did not exhibit decreased miR-27a-3p expression. The differences in the expression levels in KGN cells and human PCOS GCs are likely explained by increased miR-27a-3p expression in the GCs caused by insulin resistance in PCOS. Taken together, our data provided evidence for a functional role of miR-27a-3p in the GCs' dysfunction that occurs in patients with PCOS. Copyright © 2018 Endocrine Society.

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

    SciTech Connect

    Orsi, Roberto

    2005-07-15

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

  3. Dynamics of the formin for3p in actin cable assembly.

    PubMed

    Martin, Sophie G; Chang, Fred

    2006-06-20

    Formins are a conserved family of actin nucleators responsible for the assembly of diverse actin structures such as cytokinetic rings and filopodia. In the fission yeast Schizosaccharomyces pombe, the formin for3p is necessary for the formation of actin cables, which are bundles of short parallel actin filaments that regulate cell polarity. These filaments are largely organized with their barbed ends facing the cell tip, where for3p is thought to function in their assembly. Here, using a functional for3p-3GFP fusion expressed at endogenous levels, we find that for3p localizes to small dots that appear transiently at cell tips and then move away on actin cables at a rate of 0.3 microm/s. These movements were dependent on the continuous assembly of actin in cables, on the ability of for3p to bind actin within its FH2 domain, and on profilin and bud6p, two formin binding proteins that promote formin activity. Bud6p transiently colocalizes with for3p at the cell tip and stays behind at the cell tip when for3p detaches. These findings suggest a new model for actin cable assembly: a for3p particle is activated and promotes the assembly of a short actin filament at the cell tip for only seconds. For3p and the actin filament may then be released from the cell tip and carried passively into the cell interior by retrograde flow of actin filaments in the cable. These studies reveal a complex and dynamic cycle of formin regulation and actin cable assembly in vivo.

  4. 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.

  5. Neonlike Ar and Cl 3p-3s emission from a theta-pinch plasma

    NASA Technical Reports Server (NTRS)

    Elton, R. C.; Datla, R. U.; Roberts, J. R.; Bhatia, A. K.

    1989-01-01

    Time-resolved extreme-UV emission from sixteen 3p-3s transitions, some of the type in which lasing has been demonstrated in heavier elements, is measured for neonlike Ar(8+) and Cl(7+). These observations are made on a hydrogen theta-pinch plasma with a 5 pct admixture of argon or freon (for Cl). Fourteen 3d-3p spectral lines are also detected. The measured intensities are compared to theoretical predictions. There is no evidence of anomalously intense lines originating on 2p5 3p J = 2 upper levels compared to J = 0, as observed in gain experiments.

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

    PubMed Central

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

    2008-01-01

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

  7. 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.

  8. A 3p26-3p25 genetic linkage finding for DSM-IV major depression in heavy smoking families

    PubMed Central

    Pergadia, Michele L.; Glowinski, Anne L.; Wray, Naomi R.; Agrawal, Arpana; Saccone, Scott F.; Loukola, Anu; Broms, Ulla; Korhonen, Tellervo; Penninx, Brenda W.J.H.; Grant, Julia D.; Nelson, Elliot C.; Henders, Anjali K.; Schrage, Andrew J.; Chou, Yi-Ling; Keskitalo-Vuokko, Kaisu; Zhu, Qin; Gordon, Scott D.; Vink, Jacqueline M.; de Geus, Eco J.C.; MacGregor, Stuart; Liu, Jimmy Z.; Willemsen, Gonneke; Medland, Sarah E.; Boomsma, Dorret I.; Montgomery, Grant W.; Rice, John P.; Goate, Alison M.; Heath, Andrew C.; Kaprio, Jaakko; Martin, Nicholas G.; Madden, Pamela A.F.

    2012-01-01

    Objective The authors tested for genetic linkage of DSM-IV-diagnosed major depressive disorder in families that were ascertained for cigarette smoking. Method Within a study that targeted families characterized by a history of smoking, analyses derived a subset of 91 Australian families with two or more offspring with a history of DSM-IV major depressive disorder (affected sibling pairs, N=187) and 25 Finnish families (affected sibling pairs, N=33). Within this affected sibling pair design, the authors conducted nonparametric linkage analysis. Results In the Australian heavy smoking families, the authors found a genome-wide significant multipoint LOD score of 4.14 for major depressive disorder on chromosome 3 at 24.9 cM (3p26-3p25). Conclusions Genome-wide significant linkage was detected for major depressive disorder on chromosome 3p in a sample ascertained for smoking. A linkage peak at this location was also observed in an independent study of major depressive disorder. PMID:21572167

  9. 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.

  10. 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.

  11. LncRNA XIST regulates myocardial infarction by targeting miR-130a-3p.

    PubMed

    Zhou, Tao; Qin, Guowei; Yang, Liehong; Xiang, Daokang; Li, Suining

    2017-12-11

    The study was employed to probe long non-coding RNA X-inactive specific transcript RNA (lncRNA XIST) expression profile and its influence on cell cycle, proliferation and apoptosis in myocardial cells. We also aimed to explore the possible meditating relationship between XIST, PDE4D and miR-130a-3p. Gene differential analysis was carried out using Human LncRNA Microarray V3.0. Quantitative real-time PCR (qRT-PCR) was used to test mRNA expressions of XIST, miR-130a-3p and PDE4D in normal cells and post-myocardial infarction (MI) cells. Western blot was applied to determine the protein expression profile of PED4D. Changes in viability and cell cycle/apoptosis of post-MI myocardial cells after silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry, respectively. The targeting relationship between miR-130a-3p and XIST, PDE4D in myocardial cells were verified by dual luciferase reporter assay. Simulated MI environment was constructed by performing anoxic preconditioning in normal cells to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were overexpressed in post-MI myocardial cells, while miR-130a-3p was underexpressed in post-MI myocardial cells. High-expressed XIST and PDE4D both promoted myocardial cell apoptosis. High-expressed XIST also inhibited myocardial cell proliferation. XIST down-regulated miR-130a-3p and PDE4D was a direct target of miR-130a-3p. LncRNA XIST promotes MI by targeting miR-130a-3p. MI induced by PDE4D can be reversed by miR-130a-3p. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. High-pressure and doping studies of the superconducting antiperovskite SrPt3P

    NASA Astrophysics Data System (ADS)

    Jawdat, BenMaan I.; Lv, Bing; Zhu, Xiyu; Xue, Yuyi; Chu, Ching-wu

    2015-03-01

    We report the results of our investigation of SrPt3P , a recently discovered strong-coupling superconductor with Tc=8.4 K, by application of high physical pressure and by chemical doping. We study hole-doped SrPt3P , which was theoretically predicted to have a higher Tc, resistively, magnetically, and calorimetrically. Here we present the results of these studies and discuss their implications.

  13. Large linkage analysis in 100 families with autosomal recessive spinal muscular atrophy (SMA) and 11 EPH families using 15 polymorphic loci in the region 5q11. 2-q13. 3

    SciTech Connect

    Wirth, B.; Pick, E.; Leutner, A.

    1994-03-01

    The autosomal recessive proximal spinal muscular atrophy (SMA) gene was mapped to the region 5q11.2-q.13.3 in 1990. Here, the authors present a large genetic linkage study of 100 SMA families and 11 CEPH families using 14 polymorphic simple sequence repeats (SSRs) and one RFLP in the region 5q11.2-q.13.3. The genetic interval between the closest SMA flanking loci D5S435 and D5S557 comprises 1 cM at z[sub max] = 27.94. Two recombinants were identified between the SMA gene and the closest telomeric marker D5S557. The first places the SMA gene centromeric to this marker; the second suggests a double recombinant at D5S557,more » which is very unlikely. More likely explanations are discussed in the paper. No recombinant was found between D5S435 and the SMA gene. They localized a recently described polymorphic marker, D5S351, close to the SMA. Due to its high PIC value of 0.70, it represents a very useful marker for prenatal diagnosis. In addition, they developed a new reverse primer for the nearest centromeric locus D5S435, a useful marker for prenatal diagnosis, which has been very difficult to amplify in the past. Three of the markers presented here are newly developed polymorphic SSRs (one tetranucleotide repeat, D5s507/W15CATT, and two dinucleotide repeats, D5S544/C88.2GT and D5S682/C88.3GT). These markers are too far from the SMA gene to be relevant for cloning; nevertheless, as part of the human genome project, they are contributing to the fine genetic mapping of the region 5q11.2-q.13.3. The most likely order of the loci based on two-point and multipoint linkage analyses as well as on specific recombination events and physical mapping studies is D5S76-D5S507-D5S6-D5S125-D5S680-D5S435-SMA-D5S557-D5S35 -15[prime]MAP1B-3[prime]MAP1B-JK53CA1/2-(D5S127-D5S39)-(D5S544-D5S682). In general, the genetic distances obtained from the SMA and CEPH families are comparable. 25 refs., 4 figs., 5 tabs.« less

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

    PubMed Central

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

    2016-01-01

    Therapy of melanoma patients harboring activating mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) oncogene with a combination of BRAF and MEK inhibitors is plagued by the development of drug resistance. Mutational events, as well as adaptive mechanisms, contribute to the development of drug resistance. In this context we uncover here the role of a miRNA, miR-579-3p. We first show that low expression of miR-579-3p is a negative prognostic factor correlating with poor survival. Expression levels of miR-579-3p decrease from nevi to stage III/IV melanoma samples and even further in cell lines resistant to BRAF/MEK inhibitors. Mechanistically, we demonstrate that miR-579-3p acts as an oncosuppressor by targeting the 3′UTR of two oncoproteins: BRAF and an E3 ubiquitin protein ligase, MDM2. Moreover miR-579-3p ectopic expression impairs the establishment of drug resistance in human melanoma cells. Finally, miR-579-3p is strongly down-regulated in matched tumor samples from patients before and after the development of resistance to targeted therapies. PMID:27503895

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

    PubMed

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

    2016-08-23

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-11

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

  19. 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

  20. MicroRNA-155-3p Mediates TNF-α-Inhibited Cementoblast Differentiation.

    PubMed

    Wang, X; Sun, H; Liao, H; Wang, C; Jiang, C; Zhang, Y; Cao, Z

    2017-11-01

    Periodontitis is a prevalent and chronic inflammatory disease that is interrelated with systemic health. Periodontitis can be promoted by tumor necrosis factor α (TNF-α). Cementum, a vital part of the periodontium, is a bone-like mineralized tissue that is produced by cementoblasts. Our laboratory previously revealed that TNF-α inhibits cementoblast differentiation and mineralization. However, how TNF-α modulates cementoblast differentiation and mineralization remains largely unknown. MicroRNA-155 (miR-155) is induced and regulates TNF-α-inhibited osteogenic differentiation. In this study, we found that miR-155-3p was increased during TNF-α-stimulated OCCM-30 cells and involved in cementoblast differentiation and mineralization. Overexpression of miR-155-3p suppressed cementoblast mineralization. Bioinformatics analysis revealed that potassium channel tetramerization domain containing 1 ( Kctd1) is a candidate target gene of miR-155-3p. Moreover, miR-155-3p overexpression suppressed KCTD1 levels. Meanwhile, its knockdown increased KCTD1 expression. Transfection with miR-155-3p also inhibited the luciferase activity of 3'-untranslated regions in the Kctd1 wild type but not the mutant. These data indicated that Kctd1 is a direct and novel target of miR-155-3p. The Wnt signaling pathway inhibits cementoblast differentiation, and we further demonstrated that miR-155-3p partially modulates cementoblast differentiation through the canonical Wnt signaling pathway. In addition to the gain/loss function assay of miR-155-3p, the luciferase activity assay of canonical Wnt signaling was performed. The assays revealed that miR-155-3p increased β-catenin-mediated transcriptional activation. Overall, our data clarified that miR-155-3p mediated TNF-α-inhibited cementoblast differentiation by targeting Kctd1, at least partially through canonical Wnt signaling pathway. These findings reveal the expanded function of miRNAs in cementoblast differentiation and mineralization.

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

    PubMed Central

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

    2014-01-01

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

  2. MicroRNA-133a-3p exerts inhibitory effects on gallbladder carcinoma via targeting RBPJ.

    PubMed

    Huang, Yuan; Wu, Yaoshi; Dong, Jiahong; Han, Dongdong; Yang, Shiwei; Jiang, Lin

    2016-01-01

    Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues. Transient over-expression of miR-133a-3p inhibited the proliferation, migration and invasion abilities of GBC cells. Luciferase activity assay indicated that miR-133a-3p negatively regulated the expression of recombination signal-binding protein Jκ (RBPJ) directly, which is a key downstream transcription factor in the Notch signaling pathway. Moreover, PBPJ expression was up-regulated and negatively related to miR-133a-3p expression in GBC, and silencing of RBPJ achieved the effects as after miR-133a-3p over-expression. RBPJ over-expression could markedly reverse the inhibitory effects of miR-133a-3p on the proliferation, migration and invasion of GBC cells. Our findings indicate that miR-133a-3p acts as a tumor suppressor through directly targeting RBPJ in GBC.

  3. MicroRNA-133a-3p exerts inhibitory effects on gallbladder carcinoma via targeting RBPJ

    PubMed Central

    Huang, Yuan; Wu, Yaoshi; Dong, Jiahong; Han, Dongdong; Yang, Shiwei; Jiang, Lin

    2016-01-01

    Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues. Transient over-expression of miR-133a-3p inhibited the proliferation, migration and invasion abilities of GBC cells. Luciferase activity assay indicated that miR-133a-3p negatively regulated the expression of recombination signal-binding protein Jκ (RBPJ) directly, which is a key downstream transcription factor in the Notch signaling pathway. Moreover, PBPJ expression was up-regulated and negatively related to miR-133a-3p expression in GBC, and silencing of RBPJ achieved the effects as after miR-133a-3p over-expression. RBPJ over-expression could markedly reverse the inhibitory effects of miR-133a-3p on the proliferation, migration and invasion of GBC cells. Our findings indicate that miR-133a-3p acts as a tumor suppressor through directly targeting RBPJ in GBC. PMID:27904763

  4. Clinical manifestations of trisomy 5q.

    PubMed Central

    Kumar, D; Heath, P R; Blank, C E

    1987-01-01

    A patient with a small deletion of the short arm and a partial duplication of the long arm of chromosome 5 is described. The main clinical features include craniofacial dysmorphism, growth failure, developmental retardation, and congenital heart defect. The mother and male sib each carried an inv(5) (p15.3q35) but were phenotypically normal. The possible clinical manifestations of partial duplication of the long arm of chromosome 5 are discussed with a review of previous published reports. Images PMID:3573004

  5. HEC-5Q: System Water Quality Modeling.

    DTIC Science & Technology

    1986-01-01

    optional time dependent. The time independent data include: physical description of the reservoir (i.e., elevation, volume, surface area, discharge...SIM TEMP ............. SH ASIA e5 .A 𔄃 SIM TEMP 25- TT 0 ------- O -A I A 2C 7) ’ TEMP M X - H,’K ch T A 2. A.5(9 06𔃿 T Ef.’Pl A - SHA STA 2 79...8217CBS TEMP IN D E ,I "~- -",20 - oi K1 !󈧶 00 1S 20 0250 300 . 50 400 D.- P1HNFE Figure 3 SHASTA RESERVOIR TEMPERATURE PROFILES 2 0

  6. Genetics Home Reference: 5q minus syndrome

    MedlinePlus

    ... progress to a fast-growing blood cancer called acute myeloid leukemia (AML). Progression to AML occurs less commonly in ... NIH Resources (2 links) National Cancer Institute: Adult Acute Myeloid Leukemia National Cancer Institute: Myelodysplastic Syndromes Educational Resources (4 ...

  7. Site-directed mutagenesis of Asp853 in Pdr3p transcriptional activator from Saccharomyces cerevisiae.

    PubMed

    Dzugasova, Vladimira; Borecka, Silvia; Batova, Monika; Pilisiova, Ruzena; Hervayova, Nora; Subik, Julius

    2010-05-01

    The PDR3 gene encodes one of the main transcriptional activators involved in the control of multidrug resistance in the yeast Saccharomyces cerevisiae. Recently, it has been demonstrated that a specific D853Y mutation results in the loss of transactivation activity of Pdr3p and its conversion to multicopy suppressor of multidrug resistance. In this study, the Asp853 in Pdr3p was replaced by eight different amino acids and the function of mutated proteins was analysed. Different levels of complementation of cycloheximide hypersensitivity and expression of autoregulated PDR3 and its PDR5 target in the pdr1Deltapdr3Delta mutant strain, ranging from that of the wild-type to loss-of-function alleles, were observed in pdr3 mutants containing Pro, Glu, Arg, Asn, Ser, Leu, Phe, Ile or Tyr instead of Asp853 in Pdr3p. The introduction of the D853Y mutation into gain-of-function Pdr3p suppressed the transcription of the PDR3 and PDR5 genes and reduced both the rhodamine 6G efflux rate and the drug resistance level in corresponding double mutants. The results indicate that, while Pdr3p can tolerate several substitutions of Asp853, the occurrence of a hydrophobic amino acid at this position has an adverse effect on its function. Copyright (c) 2010 John Wiley & Sons, Ltd.

  8. Zn3P2 and Cu2O Substrates for Solar Energy Conversion

    NASA Astrophysics Data System (ADS)

    Kimball, Gregory Michael

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

  9. Puf3p induces translational repression of genes linked to oxidative stress.

    PubMed

    Rowe, William; Kershaw, Christopher J; Castelli, Lydia M; Costello, Joseph L; Ashe, Mark P; Grant, Christopher M; Sims, Paul F G; Pavitt, Graham D; Hubbard, Simon J

    2014-01-01

    In response to stress, the translation of many mRNAs in yeast can change in a fashion discordant with the general repression of translation. Here, we use machine learning to mine the properties of these mRNAs to determine specific translation control signals. We find a strong association between transcripts acutely translationally repressed under oxidative stress and those associated with the RNA-binding protein Puf3p, a known regulator of cellular mRNAs encoding proteins targeted to mitochondria. Under oxidative stress, a PUF3 deleted strain exhibits more robust growth than wild-type cells and the shift in translation from polysomes to monosomes is attenuated, suggesting puf3Δ cells perceive less stress. In agreement, the ratio of reduced:oxidized glutathione, a major antioxidant and indicator of cellular redox state, is increased in unstressed puf3Δ cells but remains lower under stress. In untreated conditions, Puf3p migrates with polysomes rather than ribosome-free fractions, but this is lost under stress. Finally, reverse transcriptase-polymerase chain reaction (RT-PCR) of Puf3p targets following affinity purification shows Puf3p-mRNA associations are maintained or increased under oxidative stress. Collectively, these results point to Puf3p acting as a translational repressor in a manner exceeding the global translational response, possibly by temporarily limiting synthesis of new mitochondrial proteins as cells adapt to the stress.

  10. Thermal rate constants for the O(3P) + HBr and O(3P) + DBr reactions: transition-state theory and quantum mechanical calculations.

    PubMed

    de Oliveira-Filho, Antonio G S; Ornellas, Fernando R; Peterson, Kirk A; Mielke, Steven L

    2013-12-05

    The O((3)P) + HBr → OH + Br and O((3)P) + DBr → OD + Br reactions are studied on a recent high-quality ab initio-based potential energy surface. Thermal rate constants over the 200-1000 K temperature range, calculated using variational transition-state theory (VTST) with the small-curvature tunneling (SCT) correction and quantum mechanical methods with the J-shifting approximation (QM/JS) for zero total angular momentum (J = 0), are reported. These results are compared to the available experimental data, which lie in the ranges of 221-554 and 295-419 K for O + HBr and O + DBr, respectively. The rate constants, in cm(3) molecule(-1) s(-1) and at 298 K, for the O + HBr reaction are 3.66 × 10(-14) for VTST, 3.80 × 10(-14) for QM/JS, and 3.66 × 10(-14) for the average of eight experimental measurements.

  11. Λ-Doublet Propensities for Reactions on Competing A' and A″ Potential Energy Surfaces: O(3P) + N2and O(3P) + HCl.

    PubMed

    Jambrina, Pablo G; Menéndez, M; Zanchet, A; García, E; Aoiz, F J

    2018-03-02

    This work presents scattering calculations for the O( 3 P) + N 2 ( 1 Σ) → NO( 2 Π) + N( 4 S) and for the O( 3 P) + HCl( 1 Σ) → OH( 2 Π) + Cl( 2 P) reactions with a focus on the prediction of the Λ-doublet populations in which NO and OH are produced. Both reactions can take place on two competing potential energy surfaces of symmetries 3 A' and 3 A″ that correlate reagents with products but with very distinct topographies. As a result, they exhibit very different dynamical behaviors and total reactivity. Using a method that relates the reaction yield on the two competing surfaces to the Λ-doublet populations through the explicit consideration of the stereodynamics of the reaction, we predict that the population of NO and OH on the two Λ-doublet sates is surprisingly similar for both systems. These results contradict the model that assumes that collisions on the 3 A' and 3 A″ would give rise to products in the Π(A') and Π(A″) states, respectively.

  12. 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.

  13. Rotational surprisals and energy disposal from statistical simulations of the crossed beam reaction C ( 3P) + NO → CN (υ) + O( 3P)

    NASA Astrophysics Data System (ADS)

    Wallin, Elisabeth; Ander Elofson, Per; Holmlid, Leif

    1994-07-01

    Statistical simulations of the crossed molecular beam experiments by Naulin . (1991) on the reaction C ( 3P) + NO → CN (υ) + O( 3P) are carried out using the RRKM-SA algorithm. this study is complementary to the previous calculations by Wallin . (1992) on the same system, but a more extensive comparison with the experiments is performed. In addition to vibrational quantum number distributions, rotational surprisal parameters and fractional values of the total energy in vibration, rotation and translation are presented. Excellent agreement with experiments is obtained for both the rotational surprisal and the fractional values of the total energy by using artificially small potential parameters. This means much smaller impact parameters and thereby also lower values of the angular momenta. The use of free parameters for the fitting is usually not necessary for the successful application of the computational algorithm. This clearly indicates that dynamical non-statistical features are operative for the present reaction. All vibrational quantum numbers are populated up to the excitation limit but the calculated distributions depart considerably from the experimental results at υ = 2 and υ = 3. It is concluded that if a barrier other than the centrifugal barrier exists in the entrance channel it cannot be larger than 0.046 eV.

  14. 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.

  15. The production of O(3P) in the 157 nm photodissociation of CO2

    NASA Astrophysics Data System (ADS)

    Zhu, Yi-Fei; Gordon, Robert J.

    1990-03-01

    The branching ratio was measured for the production of O(3P) in the photodissociation of CO2 at 157 nm. A gas mixture consisting of CO2, H2, and Ar was irradiated with an F2 excimer laser, while the relative concentration of O(3P) was monitored continuously using atomic resonance fluorescence. The O(1D) product was removed by either reacting with H2 or by being quenched by CO2. At a high H2/CO2 ratio, a residual O(3P) signal persisted which was due to the nascent photofragments of CO2. A mechanism is proposed based on curve crossing from the 1B2 to the 3B2 potential energy surfaces of CO2. Since the 1B2 state is bent, a substantial fraction of the absorbed energy is initially in bending motion, resulting in a long-lived chaotic trajectory which has many opportunities to cross over to the triplet surface.

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Demore, W. B.

    1972-01-01

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

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

    PubMed

    Weber, Daniel G; 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.

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

    NASA Technical Reports Server (NTRS)

    Golub, Morton A.; Wydeven, Theodore

    1988-01-01

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

  20. Metallic Ni3 P/Ni Co-Catalyst To Enhance Photocatalytic Hydrogen Evolution.

    PubMed

    Zhao, Jun Jie; Liu, Peng Fei; Wang, Yu Lei; Li, Yu Hang; Zu, Meng Yang; Wang, Chong Wu; Wang, Xue Lu; Fang, Li Jun; Zeng, Hui Dan; Yang, Hua Gui

    2017-11-27

    Metallic Ni3 P/Ni can be used as a co-catalyst to replace noble metal Pt for efficient photocatalytic hydrogen evolution, due to its excellent trapping-electron ability. The applications of metallic Ni3 P/Ni co-catalyst on CdS, Zn0.5 Cd0.5 S, TiO2 (Degussa P25) and g-C3 N4 are further confirmed, indicating its versatile applicability nature like Pt. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    SciTech Connect

    Orsi, Roberto

    2004-02-15

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

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

    SciTech Connect

    Khasenov, M U

    2011-03-31

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

  3. 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.

  4. 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.

  5. 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

  6. Fluorescent FYVE Chimeras to Quantify PtdIns3P Synthesis During Autophagy.

    PubMed

    Yakhine-Diop, S M S; Martínez-Chacón, G; González-Polo, R A; Fuentes, J M; Niso-Santano, M

    2017-01-01

    Autophagy is the major cellular process of degradation and is modulated by several signaling pathways. Phosphatidylinositol 3-kinase (PtdIns3K) class III (Vps34) and PtdIns3K class I regulate the autophagy pathway positively and negatively, respectively. Both classes of PtdIns3K participate in the synthesis of phosphatidylinositol 3-phosphate (PtdIns3P), which plays a crucial role in autophagosome biogenesis and membrane traffic. PtdIns3P is a membrane phospholipid that is associated with endogenous FYVE domain-containing proteins. Indeed, such interactions facilitate autophagosome fusion with lysosomes and subsequent cargo degradation. During starvation-induced autophagy, the expression of FYVE domain-containing proteins increases, and their binding to PtdIns3P is strengthened. Nonetheless, not all FYVE domain proteins are related to the induction of autophagy. This method report presents the quantification of PtdIns3P synthesis by using cells either transiently transfected with or stably expressing FYVE-dsRed. © 2017 Elsevier Inc. All rights reserved.

  7. Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement.

    PubMed

    Kangas, Reeta; Morsiani, Cristina; Pizza, Grazia; Lanzarini, Catia; Aukee, Pauliina; Kaprio, Jaakko; Sipilä, Sarianna; Franceschi, Claudio; Kovanen, Vuokko; Laakkonen, Eija K; Capri, Miriam

    2018-01-05

    Tissue-specific effects of 17β-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause- and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls. Seven miRs, expressed in both adipose tissue and serum, were selected for validation phase in 34 women from a different cohort. An age/menopause-related increase of miRs-16-5p, -451a, -223-3p, -18a-5p, -19a-3p,-486-5p and -363-3p was found in the adipose tissue, but not in serum. MiR-19a-3p, involved in adipocyte development and estrogen signaling, resulted to be higher in HRT users in comparison with non-users. Among the identified targets, AKT1, BCL-2 and BRAF proteins showed lower expression in both HRT and No HRT users in comparison with premenopausal women. Unexpectedly, ESR1 protein expression was not modified although its mRNA was lower in No HRT users compared to premenopausal women and HRT users. Thus, both HRT and menopause appear to affect adipose tissue homeostasis via miR-mediated mechanism.

  8. Thermal transport through Zn3P2 nanowire-BN microparticle/nanoparticle composites and hybrids

    NASA Astrophysics Data System (ADS)

    Vasiraju, Venkata; Norris, David; Vaddiraju, Sreeram

    2017-07-01

    Composites and hybrids of BN and Zn3P2 nanowires were made by consolidating respectively BN micropowder-Zn3P2 nanowire mixtures and non-conformally BN decorated Zn3P2 nanowires. The intent here is to study whether mere solid-state mixing of a thermal conductor and a thermal insulator leads to the engineering of the thermal conductivities of the resulting composites and hybrids. The results demonstrated that contrary to intuition, mere mixing of two materials, a thermal conductor (BN) and a thermal insulator (Zn3P2 nanowires), does not result in composites and hybrids that have thermal conductivities higher than those of the thermal insulator and lower than those of the thermal conductor. This contrary result is especially true in instances where microparticles or nanoparticles of a high thermal conductivity material are introduced into a matrix of the thermal insulator for achieving spatially uniform composites/hybrids and engineering the resulting materials’ thermal conductivities. Here, both the size of the filler material and the type of interfaces formed between the matrix and the filler material play a major role in determining the ultimate thermal conductivities of the composites/hybrids. Imperfect interface formed between materials that have high lattice mismatches lead to lowering of the thermal conductivities of the composites/hybrids.

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

    SciTech Connect

    Orsi, Roberto

    2002-11-15

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

  10. Energetics and dynamics of the reactions of O(3P) with dimethyl methylphosphonate and sarin.

    PubMed

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

    2009-12-10

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

  11. Escape of O(3P), O(1D), and O(1S) from the Martian atmosphere

    NASA Astrophysics Data System (ADS)

    Fox, Jane L.; Hać, Aleksander B.

    2018-01-01

    We have computed here the escape probabilities, fluxes and rates for hot O atoms that are initially produced in the ground state and the first two excited metastable states, O(1D)and O(1S), in the Martian thermosphere by dissociative recombination of O2+. In order to compare our results with those of our previous calculations and with those of others, we have employed here the pre-MAVEN models that we have used previously. To compute the escape probabilities, we have employed the Monte Carlo escape code that has been described previously, but we here use for the first time energy-dependent elastic cross sections for collisions of the energetic O atoms with each of the twelve background species in our model. We also incorporate three mechanisms that interchange identities of the O(3P) and O(1D) atoms, including collisional excitation of O(3P) to O(1D), quenching of O(1D) to O(3P), and excitation exchange of O(1D) with O(3P). We find that the escape probabilities of O atoms that are produced initially as O(1D) are reduced compared to those in which these processes are not included, but the escape probabilities of O atoms that are initially produced as O(3P) are not significantly reduced. As a guide for our future research and those of other investigators, we review here what is known about the interactions of O atoms with other species in which the energies of the O atoms are altered, and several other sources of hot and escaping O, many of which have been suggested by other investigators. We will incorporate these data in a future MAVEN-like model.

  12. 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

  13. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents.

    PubMed

    Santini, Valeria; Almeida, Antonio; Giagounidis, Aristoteles; Gröpper, Stefanie; Jonasova, Anna; Vey, Norbert; Mufti, Ghulam J; Buckstein, Rena; Mittelman, Moshe; Platzbecker, Uwe; Shpilberg, Ofer; Ram, Ron; Del Cañizo, Consuelo; Gattermann, Norbert; Ozawa, Keiya; Risueño, Alberto; MacBeth, Kyle J; Zhong, Jianhua; Séguy, Francis; Hoenekopp, Albert; Beach, C L; Fenaux, Pierre

    2016-09-01

    This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile

  14. Submicroscopic deletion of 5q involving tumor suppressor genes (CTNNA1, HSPA9) and copy neutral loss of heterozygosity associated with TET2 and EZH2 mutations in a case of MDS with normal chromosome and FISH results

    PubMed Central

    2014-01-01

    Advances in genome-wide molecular cytogenetics allow identification of novel submicroscopic DNA copy number alterations (aCNAs) and copy-neutral loss of heterozygosity (cnLOH) resulting in homozygosity for known gene mutations in myeloid neoplasms. We describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH results. Oligo-SNP array analysis revealed a hemizygous deletion of 896 kb at chromosome 5q31.2, representing the smallest 5q deletion reported to date. The deletion involved multiple genes, including two tumor suppressor candidate genes (CTNNA1 and HSPA9) that are associated with MDS/AML. The SNP-array study also detected 3 segments of somatic cnLOH: one involved the entire long arm of chromosome 4; the second involved the distal half of the long arm of chromosome 7, and the third encompassed the entire chromosome 22 (UPD 22). Sequence analysis revealed mutations in TET2 (4q), EZH2 (7q), ASXL1 (20q11.21), and RUNX1 (21q22.3). Coincidently, TET2 and EZH2 were located at segments of cnLOH resulting in their homozygosity. Loss of heterozygosity affecting these two chromosomes and mutations in TET2 and EZH2 are indicative of a myelodysplastic syndrome with a poor prognosis. Deletion of the tumor suppressor genes CTNNA1 and HSPA9 is also likely to contribute to a poor prognosis. Furthermore, the original cnLOHs in multiple chromosomes and additional cnLOH 14q in the follow-up study suggest genetic evolution of the disease and poor prognosis. This study attests to the fact that some patients with a myelodysplastic syndrome who exhibit a normal karyotype may have underlying genetic abnormalities detectable by chromosomal microarray and/or targeted mutation analyses. PMID:25177364

  15. 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.

  16. 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

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

    SciTech Connect

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

    1994-01-01

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

  18. 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.

  19. Redox mechanism in the binary transition metal phosphide Cu3P

    NASA Astrophysics Data System (ADS)

    Mauvernay, B.; Doublet, M.-L.; Monconduit, L.

    2006-05-01

    The electrochemical behaviour of the binary transition metal phosphide Cu3P towards lithium is investigated through galvano- and potentiostatic measurements. Obtained through high-temperature synthesis, this system shows a better volumetric capacity than graphite and a good capacity retention. In situ X-ray diffraction and first-principles electronic structure calculations are combined with the electrochemical results to show that the complete insertion of 3Li+ in the Cu3P electrode proceeds with the formation of three intermediate phases of lithium composition LixCu(3-x)P (x=1,2,3). The extra capacity previously observed in discharge is now clearly assigned to lithium insertion into the CuP2 impurity and to SEI reactions.

  20. 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

  1. The intramolecular kinetic isotope effect for the reaction O(3P) + HD

    NASA Astrophysics Data System (ADS)

    Robie, Daniel C.; Arepalli, Sivaram; Presser, Nathan; Kitsopoulos, Theofanis; Gordon, Robert J.

    1990-06-01

    The branching ratio for the reaction O(3P) + HD to produce OH and OD was measured over the temperature range 339-500 K using a discharge-flow reactor. The OH and OD products were detected using LIF under steady-state conditions. It was found that the OH/OD ratio increased rapidly with decreasing temperature, in qualitative agreement with theory, showing that the reaction is dominated by tunneling below 400 K.

  2. Temperature dependence and mechanism of the reaction between O(3P) and chlorine dioxide

    NASA Technical Reports Server (NTRS)

    Colussi, A. J.; Sander, S. P.; Fiedl, R. R.

    1992-01-01

    Second-order rate constants for the decay of O(3P) in excess chlorine dioxide, k(II), were measured as a function of total pressure (20-600 Torr argon) and temperature (248-312 K), using flash photolysis-atomic resonance fluorescence. Results indicate that k(II) is pressure dependent with a value, K(b), that is nonzero at zero pressure, and both the third-order rate constant and k(b) have negative temperature dependences.

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

    PubMed

    Smith, Iain

    2016-01-01

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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

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

    PubMed

    Sonda, Nada; Simonato, Francesca; Peranzoni, Elisa; Calì, Bianca; Bortoluzzi, Stefania; Bisognin, Andrea; Wang, Ena; Marincola, Francesco M; Naldini, Luigi; Gentner, Bernhard; Trautwein, Christian; Sackett, Sara Dutton; Zanovello, Paola; Molon, Barbara; Bronte, Vincenzo

    2013-06-27

    Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP∗ isoform of C/EBPβ transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBPβ LAP∗ by noncanonical binding to its 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both in vitro and in vivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Ab initio and dynamics study of the O(3P) + NH3 and O(3P) + N2H4 reactions at hyperthermal collision energies.

    PubMed

    Troya, Diego; Mosch, Marianne; O'Neill, Kayleigh A

    2009-12-17

    The reactions between ground-state oxygen atoms (O((3)P)) and the ammonia (NH(3)) and hydrazine (N(2)H(4)) molecules have been studied using electronic-structure and dynamics calculations. Ab initio calculations have been used to characterize the primary reaction channels accessible at hyperthermal energies. These reaction channels are i) hydrogen abstraction, O + NH(3)(N(2)H(4)) --> OH + NH(2)(N(2)H(3)), ii) H-elimination O + NH(3)(N(2)H(4)) --> H + ONH(2)(ON(2)H(3)), and iii) N-N breakage (in the reaction involving hydrazine), O + N(2)H(4) --> ONH(2) + NH(2). Hydrogen abstraction is the lowest-barrier process, followed by N-N breakage and H-elimination. Comparison of our highest-accuracy calculations (CCSD(T)/CBS//MP2/aug-cc-pVDZ) with a variety of lower-cost electronic-structure methods shows that the BHandHLYP method, in combination with the 6-31G* basis set, captures remarkably well the essential features of the potential-energy surface of all of the reaction channels investigated in this work. Using directly the BHandHLYP/6-31G* combination, we have propagated quasiclassical trajectories to characterize the dynamics of the O + NH(3) and O + N(2)H(4) reactions at hyperthermal energies. The trajectory calculations reveal that hydrogen abstraction is the dominant reaction channel, with cross sections between a factor of 2 and an order of magnitude larger than those for the H-elimination and N-N breakage channels. The dynamics calculations also indicate that most of the energy is partitioned into products relative translation but significant vibrational excitation of products is possible as well. Analysis of angular distributions and opacity functions suggests that whereas the hydrogen-abstraction reactions proceed through a mechanism with a substantial component of stripping dynamics, H-elimination and N-N breakage are dominated by rebound dynamics.

  10. 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

  11. Physiological and excessive mechanical compression of articular cartilage activates Smad2/3P signaling.

    PubMed

    Madej, W; van Caam, A; Blaney Davidson, E N; van der Kraan, P M; Buma, P

    2014-07-01

    Transforming growth factor beta (TGF-β) in articular cartilage can signal via two routes, the ALK5/Smad2/3P and the ALK1/Smad1/5/8P route, the first being protective and the latter favoring chondrocyte terminal differentiation. Since biomechanical factors are known to play an essential role in osteoarthritis (OA) initiation and progression, we investigated if excessive mechanical compression can alter TGF-β signaling in cartilage shifting it from ALK5/Smad2/3P to ALK1/Smad1/5/8P pathway, favoring terminal differentiation of chondrocytes. Articular cartilage explants were harvested from bovine metacarpophalangeal joints. After equilibration, explants were subjected to unconfined dynamic mechanical compression (1 Hz) with 3 MPa (physiological) or 12 MPa (excessive) stress. After different time intervals samples were frozen and mRNA levels of selected genes were examined using real-time polymerase chain reaction. In articular cartilage compressed with 3 MPa and also 12 MPa stress the expression of Smad2/3P responsive genes bSerpine1, bSmad7 and bAlk5 was up-regulated, whereas the expression of Smad1/5/8P responsive gene bId1 was down-regulated. Furthermore, the expression of bTgfb1 was significantly up-regulated in both compression groups. When ALK5/Smad2/3P pathway was blocked with a selective ALK4/5/7 inhibitor, the effect of excessive mechanical compression on bSmad7 and bAlk5 expression was prevented. Here we show that excessive mechanical compression alone is not able to shift TGF-β signaling toward the ALK1/Smad1/5/8P pathway. In contrast, we show that mechanical compression not only with physiological but also with excessive stress can activate Smad2/3P signaling, which is known to be protective for articular cartilage and to block chondrocyte terminal differentiation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  12. Chromosome 1 amplification has similar prognostic value to del(17p13) and t(4;14)(p16;q32) in multiple myeloma patients: analysis of real-life data from the Polish Myeloma Study Group.

    PubMed

    Grzasko, Norbert; Hajek, Roman; Hus, Marek; Chocholska, Sylwia; Morawska, Marta; Giannopoulos, Krzysztof; Czarnocki, Krzysztof; Druzd-Sitek, Agnieszka; Pienkowska-Grela, Barbara; Rygier, Jolanta; Usnarska-Zubkiewicz, Lidia; Dytfeld, Dominik; Kubicki, Tadeusz; Jurczyszyn, Artur; Korpysz, Maciej; Dmoszynska, Anna

    2017-09-01

    The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48.0 and 23.3 months, respectively. According to the presence of amp(1q21), t(4;14)(p16;q32), and del(17p13) and the International Staging System (ISS), we stratified patients into low-risk, intermediate-risk and high-risk groups. A median PFS was 52.9, 25.6, and 10.0 months, respectively; a median OS was not reached, 64.0 and 25.0 months, respectively. In conclusion, our study confirmed the prognostic value of cytogenetic changes and showed that prognostic models based on ISS and cytogenetic studies should include not only del(17p13) and t(4;14)(p16;q32), but also amp(1q21).

  13. miR-409-3p suppresses breast cancer cell growth and invasion by targeting Akt1

    SciTech Connect

    Zhang, Guoqiang; Liu, Zengyan; Xu, Hao; Yang, Qifeng

    2016-01-08

    Altered levels and functions of microRNAs (miRNAs) are correlated with carcinogenesis. While miR-409-3p has been shown to play important roles in several cancer types, its function in the context of breast cancer (BC) remains unknown. In this study, miR-409-3p was significantly downregulated in BC tissues and cell lines, compared with the corresponding control counterparts. Overexpression of miR-409-3p inhibited BC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Notably, miR-409-3p induced downregulation of Akt1 protein through binding to its 3′ untranslated region (UTR). Conversely, restoring Akt1 expression rescued the suppressive effects of miR-409-3p. Our data collectively indicate that miR-409-3p functions as a tumor suppressor in BC through downregulating Akt1, supporting the targeting of the novel miR-409-3p/Akt1 axis as a potentially effective therapeutic approach for BC. - Highlights: • miR-409-3p inhibits proliferation, migration and invasion of BC cells. • miR-409-3p suppresses tumor growth in nude mice. • Akt1 is a direct downstream target of miR-409-3p. • Ectopic expression of Akt1 reverses the effects of miR-409-3p on cell proliferation, migration and invasion.

  14. Ab Initio and Dynamics Study of the O(3P) + NH3 and O(3P) + N2H4 Reactions at Hyperthermal Collision Energies

    NASA Astrophysics Data System (ADS)

    Troya, Diego; Mosch, Marianne; O'Neill, Kayleigh A.

    2009-11-01

    The reactions between ground-state oxygen atoms (O(3P)) and the ammonia (NH3) and hydrazine (N2H4) molecules have been studied using electronic-structure and dynamics calculations. Ab initio calculations have been used to characterize the primary reaction channels accessible at hyperthermal energies. These reaction channels are i) hydrogen abstraction, O + NH3(N2H4) → OH + NH2(N2H3), ii) H-elimination O + NH3(N2H4) → H + ONH2(ON2H3), and iii) N-N breakage (in the reaction involving hydrazine), O + N2H4 → ONH2 + NH2. Hydrogen abstraction is the lowest-barrier process, followed by N-N breakage and H-elimination. Comparison of our highest-accuracy calculations (CCSD(T)/CBS//MP2/aug-cc-pVDZ) with a variety of lower-cost electronic-structure methods shows that the BHandHLYP method, in combination with the 6-31G* basis set, captures remarkably well the essential features of the potential-energy surface of all of the reaction channels investigated in this work. Using directly the BHandHLYP/6-31G* combination, we have propagated quasiclassical trajectories to characterize the dynamics of the O + NH3 and O + N2H4 reactions at hyperthermal energies. The trajectory calculations reveal that hydrogen abstraction is the dominant reaction channel, with cross sections between a factor of 2 and an order of magnitude larger than those for the H-elimination and N-N breakage channels. The dynamics calculations also indicate that most of the energy is partitioned into products relative translation but significant vibrational excitation of products is possible as well. Analysis of angular distributions and opacity functions suggests that whereas the hydrogen-abstraction reactions proceed through a mechanism with a substantial component of stripping dynamics, H-elimination and N-N breakage are dominated by rebound dynamics.

  15. Oxidative Destruction of Multilayer Diisopropyl Methylphosphonate Films by O(3P) Atomic Oxygen.

    PubMed

    Thompson, Rebecca S; Langlois, Grant G; Sibener, S J

    2018-01-18

    We present work detailing the oxidative destruction of the nerve agent simulant diisopropyl methylphosphonate (DIMP) with O(3P) using time-resolved, in situ reflection absorption infrared spectroscopy (RAIRS) and X-ray photoelectron spectroscopy (XPS). Thermally annealed DIMP films deposited on Au(111) are observed to react upon exposure to a supersonic beam containing O(3P) with average translational energies of 0.12 eV. The reaction is initiated by a hydrogen abstraction from one of three possible sites on DIMP, and then progresses through various secondary reactions with resultant hydroxyl radicals, carbon-centered DIMP-derived radicals, and nondissociated O2 in the beam. These reactions are accompanied by uptake of oxygen into the film, leading to new hydrogen bonding with the DIMP phosphoryl group. The generated product also presents greater thermal stability than pristine DIMP, suggesting the formation of a distribution of oligomeric and polymeric products. As reactivity is observed to decrease upon continued O(3P) exposure, this product likely forms a protective layer at the vacuum-film interface, hindering destruction of thicker films. Importantly, the rate of reaction and general reactivity trends are the same between DIMP and the smaller simulant dimethyl methylphosphonate (DMMP). The comparable reaction rates of the two molecules coupled with oxygen's inability to erode thick films all the way down to the substrate have specific implications for the development of oxidation-based decontamination strategies for these and other organophosphates in the solid phase. The findings presented in this paper add significant new fundamental understanding of the oxidative chemistry of such species, knowledge needed in order to develop efficacious nerve agent decontamination strategies as well as the refinement of existing models for the dispersal, adsorption, persistence, and destruction of organophosphates in the environment.

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

    SciTech Connect

    Zhao, Liang; Zhang, Yubao

    2015-02-13

    Recent research indicates that non-coding microRNAs (miRNAs) help regulate basic cellular processes in many types of cancer cells. We hypothesized that overexpression of miR-342-3p might affect proliferation of hepatocellular carcinoma (HCC) cells. After confirming overexpression of miR-342-3p with qRT-PCR, MTT assay showed that HCC cell proliferation was significantly inhibited by miR-342-3p, and that it significantly decreased BrdU-positive cell proliferation by nearly sixfold. Searching for targets using three algorithms we found that miR-342-3p is related to the NF-κB pathway and luciferase assay found that IKK-γ, TAB2 and TAB3 are miR-342-3p target genes. Results of western blot on extracted nuclear proteins of HepG2 and HCT-116 cells showed that miR-342-3p reduced and miR-342-3p-in increased p65 nuclear levels and qRT-PCR found that NF-κB pathway downstream genes were downregulated by miR-342-3p and upregulated by miR-342-3p-in, confirming that miR-342 targets NF-κB pathway. Overexpression of Ikk-γ, TAB2 and TAB3 partially rescued HCC cells proliferation inhibited by miR-342-3p. Using the GSE54751 database we evaluated expression from 10 HCC samples, which strongly suggested downregulation of miR-342-3p and we also found inverse expression between miR-342-3p and its targets IKK-γ, TAB2 and TAB3 from 71 HCC samples. Our results show that miR-342-3p has a significant role in HCC cell proliferation and is suitable for investigation of therapeutic targets. - Highlights: • MiR-342-3p suppresses hepatocellular carcinoma cell proliferation. • MiR-342-3p targets IKK-γ, TAB2 and TAB3 genes. • MiR-342-3p downregulates NF-kB signaling pathway. • MiR-342-3p is downregulated in clinical hepatocellular carcinoma samples. • The expression of miR-342-3p and its target gene is inversely related.

  17. 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

  18. 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

  19. Persistent photoconductivity in high resistive Zn{sub 3}P{sub 2}

    SciTech Connect

    Sierański, K.; Szatkowski, J., E-mail: jan.szatkowski@pwr.wroc.pl; Pawlikowski, J. M.

    2014-02-28

    Resistivity and photoconductivity of p-type Zn{sub 3}P{sub 2} polycrystals grown by closed tube vapour transport method have been investigated. Persistent photoconductivity (PPC) has been observed at temperatures T < 200 K. At 77 K, the photoconduction persists for over 10{sup 3} s after termination of the light. The PPC buildup and decay kinetics have been measured at 77 K and analyzed in the frame of large lattice-relaxed deep levels. We have determined the spectral dependence for the optical cross section and obtain an optical ionization energy of 0.83 eV.

  20. Dynamics of O(3P) Reactions with Gaseous Liquid and Solid Hydrocarbons

    DTIC Science & Technology

    2006-03-01

    Ef) for O(3P) atoms scattered off 300 K liquid squalane at different incident energies Ei of 5.0, 11.2, 71.0 and 120.5 kcal/mol. For each of these E... squalane before desorbing with an energy distribution consistent with the liquid’s 300 K temperature. We have initiated an investigation of these...homogeneity, this is a more straightforward surface to model than liquid squalane , and accordingly it is deemed to be most productive to initially probe

  1. Dynamics of the reaction of O(3P) atoms with alkylthiol self-assembled monolayers.

    PubMed

    Waring, Carla; Bagot, Paul A J; Räisänen, Minna T; Costen, Matthew L; McKendrick, Kenneth G

    2009-04-23

    We have studied the dynamics of the reactions of O((3)P) atoms with alkylthiol self-assembled monolayers (SAMs). Superthermal O((3)P) atoms, with a fairly broad distribution of laboratory-frame kinetic energies (mean = 16 kJ mol(-1), fwhm = 26 kJ mol(-1)), were generated by 355 nm photolysis of NO(2) introduced at a low pressure above the SAM surface. Nascent OH v' = 0 products were detected by laser-induced fluorescence. SAMs of two different alkyl chain lengths, C(6) and C(18), were studied. The existence of SAM layers, and their robustness under our experimental conditions during the relevant measurement period, were confirmed by scanning-tunneling microscopy (STM). Reaction at the SAM surface was verified as the authentic source of the hydroxyl radicals using a perdeuterated C(6)D(13)-SAM sample. The OH appearance profiles as a function of photolysis-probe delay, and the rotational-state distributions at their peaks, were compared with those of liquid squalane (C(30)H(62), 2,6,10,15,19,23-hexamethyltetracosane). The reactivity of the SAMs and of squalane was found to be comparable. We conclude that the O((3)P) atoms must be able to access the more reactive secondary hydrogen atoms along the alkyl chains of the SAMs. We find no perceptible differences in reactivity or product energy disposal between the two SAM chain lengths. Both produce a substantial fraction of the OH with relatively high velocities, which must result from direct, impulsive reaction. There is also a slower component, with velocities consistent with a thermal, trapping-desorption mechanism. The proportion of this component appears to be lower for SAMs than for squalane. This would be compatible with the expected greater smoothness of the SAM surface at the molecular scale. We find little evidence for significant rotational excitation of the OH products, although the details of any correlation between translational and rotational energy release require further investigation. We compare our

  2. Scaling of collisionally pumped 3s-3p lasers in the neon isoelectronic sequence

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

    Atomic-number scaling in the 3p-3s population-inversion and plasma parameters of neonlike ions of Si, Ar, Ti, Fe, Ge, and Kr is investigated theoretically. The population levels are calculated; the Z-scaling relationships are defined; the results are presented in tables and graphs; and the implications for the laser gain are explored. Laser gain in excess of 1/cm are predicted for all ions except Si V, with a peak of 30/cm for Fe XVII at electron density 10 to the 21st/cu cm.

  3. 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

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

    SciTech Connect

    Zhang, Jun; Hou, Wengen; Chai, Mingxiang; Zhao, Hongxing; Jia, Jinling; Sun, Xiaohui; Zhao, Bin; Wang, Ran

    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 decreased 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.

  5. Overexpression of miR-130a-3p/301a-3p attenuates high glucose-induced MPC5 podocyte dysfunction through suppression of TNF-α signaling.

    PubMed

    Jiang, Yan; Wang, Wei; Liu, Zong-Yang; Xie, Yi; Qian, Yuan; Cai, Xue-Ni

    2018-01-01

    Tumor necrosis factor (TNF)-α has been reported to be important in glomerulonephritis, which is closely associated with podocyte dysfunction and apoptosis. However, the precise mechanisms by which TNF-α expression are regulated remain unclear. The purpose of the present study was to investigate the role of microRNA (miR)-130a-3p/301a-3p in the post-transcriptional control of TNF-α expression and high glucose (HG)-induced podocyte dysfunction. Mice MPC5 podocytes were incubated with HG and transfected with miR-130a-3p/301a-3p mimics or inhibitors, reactive oxygen species (ROS) levels were measured by flow cytometry assay, and the mRNA and protein levels were assayed by using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The targeted genes were predicted by a bioinformatics algorithm and verified using a dual luciferase reporter assay. It was observed that miR-130a-3p/301a-3p was a novel regulator of TNF-α in mouse podocytes. miR-130a-3p/301a-3p mimics inhibited TNF-α 3'-untranslated region luciferase reporter activity, in addition to endogenous TNF-α protein expression. Furthermore, forced expression of miR-130a-3p or miR-301a-3p resulted in the downregulation of ROS and malondialdehyde (MDA) and the upregulation of superoxide dismutase (SOD) 1 in the presence of HG. Inhibition of TNF-α level prevented a remarkable reduction in SOD activity and a marked increase in ROS and MDA levels in HG-treated podocytes. Furthermore, TNF-α loss-of-function significantly reversed HG-induced podocyte apoptosis. These data demonstrated a novel up-stream role for miR-130a-3p/301a-3p in TNF-α-mediated podocyte dysfunction and apoptosis in the presence of HG.

  6. High pressure crystal growth of the antiperovskite centrosymmetric superconductor SrPt3P

    NASA Astrophysics Data System (ADS)

    Zhigadlo, Nikolai D.

    2016-12-01

    Bulk single crystals of SrPt3P have been grown for the first time by a self-flux method at 2 GPa and 1500 °C using the cubic-anvil, high-pressure and high-temperature technique. The grown black crystals were found to have either a plate-like or pillar-like morphology with maximum dimensions of 1×0.6×0.3 mm3. According to a goniometric study the crystals are elongated in the ab-plane with the c-axis perpendicular to the plane. The crystal structure was confirmed by X-ray diffraction (P4/nmm, #129, Z=2, a=b=5.7927(2) Å, c=5.3729(2) Å and V=180.290(11) Å3). Temperature dependent susceptibility measurements showed a single-phase behaviour and a superconducting transition temperature of 8.6 K. This value for single crystals is slightly higher than that previously reported for polycrystalline SrPt3P. The sharpness of the susceptibility drop (∆Tc=0.07 K) supports a high homogeneity of obtained crystals.

  7. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

    PubMed Central

    Ahmed, Shahana; Thomas, Gilles; Ghoussaini, Maya; Healey, Catherine S; Humphreys, Manjeet K; Platte, Radka; Morrison, Jonathan; Maranian, Melanie; Pooley, Karen A; Luben, Robert; Eccles, Diana; Evans, D Gareth; Fletcher, Olivia; Johnson, Nichola; Silva, Isabel dos Santos; Peto, Julian; Stratton, Michael R; Rahman, Nazneen; Jacobs, Kevin; Prentice, Ross; Anderson, Garnet L; Rajkovic, Aleksandar; Curb, J David; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Diver, W Ryan; Bojesen, Stig; Nordestgaard, Børge G; Flyger, Henrik; Dörk, Thilo; Schürmann, Peter; Hillemanns, Peter; Karstens, Johann H; Bogdanova, Natalia V; Antonenkova, Natalia N; Zalutsky, Iosif V; Bermisheva, Marina; Fedorova, Sardana; Khusnutdinova, Elza; Kang, Daehee; Yoo, Keun-Young; Noh, Dong Young; Ahn, Sei-Hyun; Devilee, Peter; van Asperen, Christi J; Tollenaar, R A E M; Seynaeve, Caroline; Garcia-Closas, Montserrat; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Hopper, John L; Southey, Melissa C; Smith, Letitia; Spurdle, Amanda B; Schmidt, Marjanka K; Broeks, Annegien; van Hien, Richard R; Cornelissen, Sten; Milne, Roger L; Ribas, Gloria; González-Neira, Anna; Benitez, Javier; Schmutzler, Rita K; Burwinkel, Barbara; Bartram, Claus R; Meindl, Alfons; Brauch, Hiltrud; Justenhoven, Christina; Hamann, Ute; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Olson, Janet E; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; English, Dallas R; Hankinson, Susan E; Cox, David G; Kraft, Peter; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Sigurdson, Alice; Doody, Michele; Bhatti, Parveen; Alexander, Bruce H; Hooning, Maartje J; van den Ouweland, Ans M W; Oldenburg, Rogier A; Schutte, Mieke; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Yuqing; Cox, Angela; Elliott, Graeme; Brock, Ian; Reed, Malcolm W R; Shen, Chen-Yang; Yu, Jyh-Cherng; Hsu, Giu-Cheng; Chen, Shou-Tung; Anton-Culver, Hoda; Ziogas, Argyrios; Andrulis, Irene L; Knight, Julia A; kConFab; Beesley, Jonathan; Goode, Ellen L; Couch, Fergus; Chenevix-Trench, Georgia; Hoover, Robert N; Ponder, Bruce A J; Hunter, David J; Pharoah, Paul D P; Dunning, Alison M; Chanock, Stephen J; Easton, Douglas F

    2009-01-01

    Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage1. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08–1.13, P = 4.1 × 10−23) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92–0.97, P = 1.4 × 10−8). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q. PMID:19330027

  8. LETTER TO THE EDITOR: First theoretical study of the 3p absorption cross section of free ?

    NASA Astrophysics Data System (ADS)

    Dolmatov, V. K.

    1996-09-01

    Multielectron calculations for the 3p absorption cross section of free 0953-4075/29/18/001/img2 are reported for the first time. The calculations were performed within the `spin-polarized' random-phase approximation with exchange. Reasons are given why the 0953-4075/29/18/001/img3 giant resonance of 0953-4075/29/18/001/img4 is incomparably broader than that of Cr, whereas the rest of the 0953-4075/29/18/001/img5 Rydberg structure of 0953-4075/29/18/001/img4 is incomparably weaker compared to Cr. Good agreement with experimental data is obtained with regard to the 0953-4075/29/18/001/img7 resonance structure, and qualitative agreement with regard to the rest of the 0953-4075/29/18/001/img8 Rydberg structures. Surprisingly strong quantitative discrepancies between the theoretical and experimental data are found in the high-frequency shoulder of the giant 0953-4075/29/18/001/img3 resonance. Additional investigations of the 0953-4075/29/18/001/img10 absorption, both experimental and theoretical, could help to understand better what is `wrong' with the 3p absorption of 0953-4075/29/18/001/img4.

  9. 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.

  10. Absolute rate parameters for the reaction of ground state atomic oxygen with carbonyl sulfide. [using O(3P) monitoring

    NASA Technical Reports Server (NTRS)

    Klemm, R. B.; Stief, L. J.

    1974-01-01

    The rate parameters for the reaction of O(3P) with carbonyl sulfide, O(3P) + OCS yields CO + SO have been determined directly by monitoring O(3P) using the flash photolysis-resonance fluorescence technique. The value for k sub 1 was measured over a temperature range of 263 - 502 K and the data were fitted to an Arrhenuis expression with good linearity.

  11. 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.

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

    SciTech Connect

    Brown, A.; Schwartz, C.; Rogers, R.C.

    1994-09-01

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

  13. Fabrication of novel copper phosphide (Cu 3P) hollow spheres by a simple solvothermal method

    NASA Astrophysics Data System (ADS)

    Wang, Xinjun; Han, Kun; Gao, Youjun; Wan, Fuquan; Jiang, Kai

    2007-09-01

    Novel copper phosphide (Cu 3P) hollow spheres have been successfully fabricated in ethylene glycol (EG) by a solvothermal process at low temperature, using newborn copper hydroxide (Cu(OH) 2) and elemental phosphorus as starting materials. The phase composition and morphology of the products were characterized by means of X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It is found that reaction temperature, reaction solvents and starting materials play important roles in the formation of the products. It is suggested that the reaction proceeds through a typical solvent-assisted coordination and reduction process, in which EG serves as not only a reducing reagent but also a complexing solvent. The possible mechanism is discussed.

  14. The EGFR/miR-338-3p/EYA2 axis controls breast tumor growth and lung metastasis

    PubMed Central

    Liang, Yingchun; Xu, Xiaojie; Wang, Tao; Li, Ying; You, Wenye; Fu, Jing; Liu, Yang; Jin, Shuai; Ji, Quanbo; Zhao, Wei; Song, Qi; Li, Ling; Hong, Tian; Huang, Junjian; Lyu, Zhaohui; Ye, Qinong

    2017-01-01

    Dysregulation of the epidermal growth factor receptor (EGFR) promotes cancer cell growth, invasion and metastasis. However, its relevant downstream effectors are still limited. Here, we show that EGFR promotes breast tumor growth and metastasis by downregulating the tumor suppressor micoRNA-338-3p (miR-338-3p) and activating the EYA2 (EYA transcriptional coactivator and phosphatase 2) oncoprotein. EGFR represses miR-338-3p expression largely through HIF1α transcription factor. miR-338-3p inhibits EYA2 expression by binding to the 3′-untranslated region of EYA2. EGFR increases EYA2 expression via HIF1α repression of miR-338-3p. Through the miR-338-3p/EYA2 pathway, EGFR increases breast cancer cell growth, epithelial-to-mesenchymal transition, migration, invasion and lung metastasis in vitro and in a allograft tumor mouse model in vivo. In breast cancer patients, miR-338-3p expression negatively correlates with the expression of EGFR and EYA2, EGFR status positively associates with EYA2 expression, and miR-338-3p and EYA2 predict breast cancer lung metastasis when expressed in primary breast cancers. These data suggest that the miR-338-3p/EYA2 axis contributes to EGFR-mediated tumor growth and lung metastasis and that miR-338-3p activation or EYA2 inhibition or combination therapy targeting EGFR/miR-338-3p/EYA2 axis may be a promising way to treat patients with metastatic cancer. PMID:28703807

  15. miR-409-3p suppresses breast cancer cell growth and invasion by targeting Akt1

    SciTech Connect

    Zhang, Guoqiang; Department of Thyroid and Breast Surgery, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603; Liu, Zengyan

    2016-01-08

    Altered levels and functions of microRNAs (miRNAs) are correlated with carcinogenesis. While miR-409-3p has been shown to play important roles in several cancer types, its function in the context of breast cancer (BC) remains unknown. In this study, miR-409-3p was significantly downregulated in BC tissues and cell lines, compared with the corresponding control counterparts. Overexpression of miR-409-3p inhibited BC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Notably, miR-409-3p induced downregulation of Akt1 protein through binding to its 3′ untranslated region (UTR). Conversely, restoring Akt1 expression rescued the suppressive effects of miR-409-3p. Our data collectively indicate thatmore » miR-409-3p functions as a tumor suppressor in BC through downregulating Akt1, supporting the targeting of the novel miR-409-3p/Akt1 axis as a potentially effective therapeutic approach for BC. - Highlights: • miR-409-3p inhibits proliferation, migration and invasion of BC cells. • miR-409-3p suppresses tumor growth in nude mice. • Akt1 is a direct downstream target of miR-409-3p. • Ectopic expression of Akt1 reverses the effects of miR-409-3p on cell proliferation, migration and invasion.« less

  16. miRNA-338-3p suppresses cell growth of human colorectal carcinoma by targeting smoothened

    PubMed Central

    Sun, Kai; Deng, Hai-Jun; Lei, Shang-Tong; Dong, Jing-Qing; Li, Guo-Xin

    2013-01-01

    AIM: To investigate the regulative effect of miRNA-338-3p (miR-338-3p) on cell growth in colorectal carcinoma (CRC). METHODS: The lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed. The recombinant viral vector encoding the pre-miR-338-3p or miR-338-3p-inhibitor and the two packaging plasmids psPAX2 and pMD2.G were cotransfected into human embryonic kidney 293T cells to package lentivirus. The supernatant containing the lentivirus particles was harvested to determine the viral titer, and this supernatant was then used to transduce CRC-derived cell line, SW-620. Flow cytometry was utilized for sorting the green fluorescent protein (GFP)+ cells to establish the SW-620 cell line stably expressing pre-miR-338-3p or miR-338-3p-inhibitor. Moreover, the expression of miR-338-3p was determined by real-time reverse transcriptase polymerase chain reaction, and Western blotting was used to detect the expression of the smoothened (SMO, the possible target of miR-338-3p) protein in SW-620 cells. Furthermore, the status of CRC cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry, respectively. RESULTS: Restriction enzyme digestion and DNA sequencing demonstrated that the lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed successfully. GFP was expressed after the SW-620 cells were transduced by the lentivirus. Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p was significantly increased (relative expression 3.91 ± 0.51 vs 2.36 ± 0.44, P < 0.01). Furthermore, overexpression of miR-338-3p inhibited the expression of SMO protein in SW-620 cells, which showed obviously suppressed proliferation ability [cellular proliferation inhibition rate (CPIR) 61.9% ± 5.2% vs 41.6% ± 4.8%, P < 0.01]. Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p

  17. miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA.

    PubMed

    Hua, Shengni; Liu, Chengdong; Liu, Li; Wu, Dehua

    2018-02-12

    Cancer cells are addictively dependent on glycolysis even in an oxygen-rich condition. However, the mechanism underlying micro (mi)RNA regulation of aerobic glycolysis in cancer cells has not been fully understood. Here, we demonstrated that the expression of miR-142-3p was lower in hepatocellular carcinoma (HCC) as compared to adjacent non-tumor samples, which was confirmed in The Cancer Genome Atlas (TCGA) HCC cohorts and Gene Expression Omnibus (GEO) datasets. Function and pathway analysis showed that miR-142-3p was most relevent with metabolism. As predicted, the overexpression of miR-142-3p inhibited aerobic glycolysis and thus proliferation of HCC cells. Mechanistically, we identified lactate dehydrogenase A (LDHA), one of the important catalyticase for aerobic glycolysis, as the target of miR-142-3p. Exogenous expression of miR-142-3p reduced the protein levels of LDHA in both SK-Hep-1 and Huh7 cells. Dual luciferase report assays showed the expression of LDHA was directly modulated by miR-142-3p. miR-142-3p-induced deduction of aerobic glycolysis and proliferation were reversed by LDHA overexpression. Taken together, these results indicate that miR-142-3p could act as a tumor suppressor in HCC by targeting LDHA, suggesting new therapeutic targets for HCC treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1.

    PubMed

    Wang, Xiuqin; Guo, Yanqing; Wang, Chunyan; Yu, Hong; Yu, Xiuxiang; Yu, Hongbo

    2016-10-01

    Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and joint inflammation in which microRNAs are significantly involved. Previous studies have reported that miR-142-3p is a novel mediator of inflammatory signaling pathways, but whether miR-142-3p regulates OA remains unknown. In this study, we aimed to investigate the potential role of miR-142-3p in OA and the underlying molecular mechanism. We showed that miR-142-3p was significantly reduced in the articular cartilage tissues from experimental OA mice. The expression of miR-142-3p was also decreased in chondrocytes treated with lipopolysaccharide (LPS) in vitro. Moreover, the overexpression of miR-142-3p significantly inhibited cell apoptosis, nuclear factor (NF)-kB, and the production of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α induced by LPS. Interestingly, bioinformatics analysis demonstrated that high mobility group box 1 (HMGB1), an important inflammatory mediator of OA, was predicted as a target of miR-142-3p, which was validated by dual-luciferase reporter assay. The high expression of HMGB1 in chondrocytes induced by LPS was significantly inhibited by miR-142-3p overexpression. Furthermore, the restoration of HMGB1 markedly abrogated the effect of miR-142-3p. In OA mice, the overexpression of miR-142-3p by lentivirus-mediated gene transfer significantly inhibited HMGB1 expression, NF-kB signaling, and proinflammatory cytokines. Moreover, the overexpression of miR-142-3p significantly alleviated OA progression in OA mice in vivo. Taken together, our study suggests that miR-142-3p inhibits chondrocyte apoptosis and inflammation in OA by inhibiting the HMGB1-mediated NF-kB signaling pathway. The overexpression of miR-142-3p impedes the OA progression in mice in vivo indicating that miR-142-3p is a potential molecular target for OA treatment.

  19. Immunological Reactivity of Blood from Healthy Humans to the rAls3p-N Vaccine Protein

    PubMed Central

    Baquir, Beverlie; Lin, Lin; Ibrahim, Ashraf S.; Fu, Yue; Avanesian, Valentina; Tu, Ang; Edwards, John; Spellberg, Brad

    2010-01-01

    We determined reactivity of human blood to a vaccine based on the recombinant N-terminus of candidal Als3p (rAls3p-N) in preparation for future clinical trials. Healthy donor plasma had high immunoglobulin G titers (median, 1:51,200) and lower immunoglobulin A (median, 1:3,200) and immunoglobulin E (median, 1:128) titers to rAls3p-N by enzyme-linked immunosorbent assay. rAls3p-N stimulated interferon γ (IFN-γ) and interleukin (IL)–17, but not IL-4, from donor lymphocytes by enzyme-linked immunosorbent spot assay and IL-12 p70, IFN-γ, IL-17, and IL-10 by cytometric bead array. Donors reacted to diverse immunodominant epitopes. Thus, facile humoral and cellular assays can monitor immune responses to the rAls3p-N vaccine in planned clinical trials. PMID:20039802

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

    PubMed

    Paskulin, Diego Davila; Giacomazzi, Juliana; Achatz, Maria Isabel; Costa, Sandra; Reis, Rui Manoel; Hainaut, Pierre; dos Santos, Sidney Emanuel Batista; Ashton-Prolla, Patricia

    2015-01-01

    Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial history. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Iberic origin, distant in about 72-84 generations (2000 years assuming a 25 years intergenerational distance) and thus pre-dating European migration to Brazil. So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.

  1. Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13).

    PubMed

    Panagopoulos, Ioannis; Gorunova, Ludmila; Davidson, Ben; Heim, Sverre

    2015-02-28

    Multicystic mesothelioma is a rare disease of unknown etiology and pathogenesis. Nothing has been known about the cytogenetic and molecular genetic features of these tumors. Here we present the first cytogenetically analyzed multicystic mesothelioma with the karyotype 46,XX,t(7;17)(p13;q23),t(8;11)(q23;p13). RNA-sequencing showed that the t(7;17)(p13;q23) generated a chimeric TNS3-MAP3K3 gene, which codes for a chimeric protein kinase, as well as the reciprocal MAP3K3-TNS3 in which the region of TNS3 coding for the SH2_Tensin_like region and the tensin phosphotyrosine-binding domain is under the control of the MAP3K3 promoter. The other translocation, t(8;11)(q23;p13), generated a chimeric ZFPM2-ELF5 gene which codes for a chimeric transcription factor in which the first 40 amino acids of ELF5 are replaced by the first 100 amino acids of ZFPM2. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcripts. The finding of acquired clonal chromosome abnormalities in cells cultured from the lesion and the presence of the TNS3-MAP3K3 chimeric protein kinase and the ZFPM2-ELF5 chimeric transcription factor confirm the neoplastic nature of multicystic mesothelioma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

    Paskulin, Diego Davila; Giacomazzi, Juliana; Achatz, Maria Isabel; Costa, Sandra; Reis, Rui Manoel; Hainaut, Pierre; dos Santos, Sidney Emanuel Batista; Ashton-Prolla, Patricia

    2015-01-01

    Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial history. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Iberic origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenerational distance) and thus pre-dating European migration to Brazil. So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil. PMID:26618902

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

    SciTech Connect

    Gu, Haihua; Yang, Tao; Fu, Shaozi; Chen, Xiaofan; Guo, Lei; Ni, Yiming

    2014-01-31

    Highlights: • We examined the level of miR-490-3p in A549 lung cancer cells compared with normal bronchial epithelial cell line. • We are the first to show the function of miR-490-3p in A549 lung cancer cells. • We demonstrate CCND1 may be one of the targets of miR-490-3p. - Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3′-untranslated region (3′UTR). In this study, we found that miR-490-3p is significantly down-regulated in A549 lung cancer cells compared with the normal bronchial epithelial cell line. To better characterize the role of miR-490-3p in A549 cells, we performed a gain-of-function analysis by transfecting the A549 cells with chemically synthesized miR-490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation via G1-phase arrest. We also found that forced expression of miR-490-3P decreased both mRNA and protein levels of CCND1, which plays a key role in G1/S phase transition. In addition, the dual-luciferase reporter assays indicated that miR-490-3P directly targets CCND1 through binding its 3′UTR. These findings indicated miR-490-3P could be a potential suppressor of cellular proliferation.

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

    PubMed Central

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

    2015-01-01

    In Saccharomyces cerevisiae, Avt3p and Avt4p mediate the extrusion of several amino acids from the vacuolar lumen into the cytosol. SpAvt3p of Schizosaccharomyces pombe, a homologue of these vacuolar amino acid transporters, has been indicated to be involved in spore formation. In this study, we confirmed that GFP-SpAvt3p localized to the vacuolar membrane in S. pombe. The amounts of various amino acids increased significantly in the vacuolar pool of avt3Δ cells, but decreased in that of avt3+-overexpressing avt3Δ cells. These results suggest that SpAvt3p participates in the vacuolar compartmentalization of amino acids in S. pombe. To examine the export activity of SpAvt3p, we expressed the avt3+ gene in S. cerevisiae cells. We found that the heterologously overproduced GFP-SpAvt3p localized to the vacuolar membrane in S. cerevisiae. Using the vacuolar membrane vesicles isolated from avt3+-overexpressing S. cerevisiae cells, we detected the export activities of alanine and tyrosine in an ATP-dependent manner. These activities were inhibited by the addition of a V-ATPase inhibitor, concanamycin A, thereby suggesting that the activity of SpAvt3p is dependent on a proton electrochemical gradient generated by the action of V-ATPase. In addition, the amounts of various amino acids in the vacuolar pools of S. cerevisiae cells were decreased by the overproduction of SpAvt3p, which indicated that SpAvt3p was functional in S. cerevisiae cells. Thus, SpAvt3p is a vacuolar transporter that is involved in the export of amino acids from S. pombe vacuoles. PMID:26083598

  5. miR144-3p inhibits PMVECs excessive proliferation in angiogenesis of hepatopulmonary syndrome via Tie2.

    PubMed

    Yang, Congwen; Lv, Keyi; Chen, Bin; Yang, Yong; Ai, Xiangfa; Yu, Hongfu; Yang, Yihui; Yi, Bin; Lu, Kaizhi

    2018-02-14

    Increasing evidence show microRNAs (miRNAs) are associated with hepatopulmonary syndrome (HPS). The aim of this study was to investigate the role of miR-144 in the angiogenesis of HPS, as well as to identify its underlying mechanism. The expression levels of miR-144-3p were assessed in pulmonary micro-vascular endothelial cells (PMVECs), as well as in lung tissues from rats with HPS. We predicted the potential target of miR-144-3p. Tyrosine kinase 2(Tie2) was identified as a target gene of miR144-3p, which has an essential role in the angiogenesis of lung vessel. In addition, the effects of miR-144-3p regulated on Tie2 was examined. The upregulation and down-regulation of miR-144-3p can affect the proliferation of PMVECs. We found that the levels of miR-144-3p were frequently downregulated in HPS tissues and cell lines, and overexpression of miR-144-3p dramatically inhibited PMVECs proliferation and cell cycle. We further verified the Tie2 as a novel and direct target of miR-144-3p in HPS. miR-144-3p can negatively regulate PMVECs proliferation by Tie2 expression. In addition, overexpression of miR-144-3p may prove beneficial as a therapeutic strategy for HPS treatment. Copyright © 2018. Published by Elsevier Inc.

  6. Photodetachment of O^- Yielding O(1D_2, {}^3P) Atoms, Viewed with Velocity Map Imaging

    NASA Astrophysics Data System (ADS)

    Gibson, Stephen T.; Laws, Benjamin A.; Lewis, Brenton R.; Duong, Ly

    2016-06-01

    lectron photodetachment of O^-(2P3/2,1/2) is measured using velocity-map imaging at wavelengths near 350 nm, where detachment yields both O(^1D_2) and O(^3P2,1,0) atoms, simultaneously, producing slow (˜ 0.1 eV) and fast electrons (˜ 2 eV). The photoelectron spectrum resolves the fine-structure transitions, which together with the well known atomic fine-structure splittings, and intensity ratios, provide an excellent test of the spectral quality of the velocity-map imaging technique. Although the photoelectron angular distribution for the two atomic limits have the same negative anisotropy sign, the energy dependence differs. The variation is qualitatively in accordance with R-matrix cross section calculations, that indicate a more gradual d-wave onset for the ^1D limit. However, more exact evaluation is only possible with information about the matrix element phases. Research supported by the Australian Research Council Discovery Project GrantDP160102585. physics.nist.gov/cgi-bin/ASD/energy1.pl O. Scharf and M. R. Godefried, arXiv:0808.3529v1 O. Zatsarinny and K. Bartschat, Phys. Rev. A, 73, 022714 (2006). doi:10.1103/PhysRevA.73.022714

  7. Semiconducting cubic titanium nitride in the Th3P4 structure

    NASA Astrophysics Data System (ADS)

    Bhadram, Venkata S.; Liu, Hanyu; Xu, Enshi; Li, Tianshu; Prakapenka, Vitali B.; Hrubiak, Rostislav; Lany, Stephan; Strobel, Timothy A.

    2018-01-01

    We report the discovery of a long-sought-after phase of titanium nitride with stoichiometry Ti3N4 using diamond anvil cell experiments combined with in situ high-resolution x-ray diffraction and Raman spectroscopy techniques, supported by ab initio calculations. Ti3N4 crystallizes in the cubic Th3P4 structure [space group I 4 ¯3 d (220)] from a mixture of TiN and N2 above ≈75 GPa and ≈2400 K. The density (≈5.22 g/cc) and bulk modulus (K0=290 GPa) of cubic-Ti3N4 (c -Ti3N4 ) 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 -Ti3N4 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 -Ti3N4 phase is not recoverable to ambient pressure due to dynamic instabilities, but recovery of Ti3N4 in the defect rocksalt (or related) structure may be feasible.

  8. Hg( 3P 1) Photosensitization of trimethylsilane in the presence of alcohol

    NASA Astrophysics Data System (ADS)

    Safarik, I.; Jodhan, A.; Strausz, O. P.; Bell, T. N.

    1987-12-01

    The reaction between CH 3OH or C 2H 5OH and 1,1-dimethylsilaethene, the disproportionation product of the trimethylsilyl radical, has been studied to establish its efficiency for quantitative measurement of the disproportionation reaction. It has been found that standing in a Pyrex vessel, in mixtures of (CH 3) 3SiH - the usual precursor of the (CH 3) 3Si radical - and CH 3OH or C 2H 5OH, a dark surface reaction takes place giving H 2, (CH 3) 3SiSi(CH 3) 3 and (CH 3) 3SiOR. Using the Hg( 3P 1) photosensitization of (CH 3) 3 SiH as a source of (CH 3) 3Si radicals in the presence of 10-20 Torr CH 3OH or 10 Torr C 2H 5OH, the (CH 3) 3SiOR product yield increased linearly with increasing photolysis time but did not vanish when extrapolated to zero time. After minimizing this interfering dark reaction and applying a correction for its contribution we determined the value kd/ kc = 0.10±0.01 for the disproportionation-combination reactions of the trimethylsilyl radical.

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

    SciTech Connect

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

    2018-01-01

    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

  10. Fourier transform infrared-probed O(3P) microreactor: demonstration with ethylene reactions in argon matrix.

    PubMed

    Gossage, John L; Gomes, Jewel A G; Cocke, David L; Li, Kuyen; Lin, Che-Jen; Tadmor, Rafael; Basu, Abir; Bhat, Shagun; Tandel, Satish; Jayabalu, Prashanth; Balu, Harimadhav

    2004-10-01

    To demonstrate the development of an oxygen atom microreactor in the form of liquid-helium-cooled solid argon matrix deposited on an infrared (IR) window, the oxidation of ethylene by mobile O atoms has been investigated. O atom diffusion through the argon matrix is confirmed and used to examine ethylene-oxygen atom reactions. In a bench-scale matrix isolation system probed with a Fourier transform infrared (FT-IR) spectrometer, matrices of solid Ar at 8-10 K doped with NO2 and ethylene have been prepared on a ZnSe window within an evacuated cryostat. The matrices have been photolyzed using 350-450 nm photons, and the reaction products resulting from the reaction of O(3P), one of the photolysis products of NO2, with ethylene have been identified using FT-IR and a Gaussian 98W simulation program. These products include oxirane, acetaldehyde, ethyl nitrite radical, and ketene. The temperature effect in the range of 10-30 K on the products formed has also been investigated. The reaction mechanisms are discussed and the viability of the solid Ar matrix being a low temperature microreactor to examine reaction mechanisms of mobile oxygen atoms is elaborated.

  11. 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.

  12. Direct dynamics simulations of O(3P) + HCl at hyperthermal collision energies.

    PubMed

    Camden, Jon P; Schatz, George C

    2006-12-28

    The dynamics of the O(3P) + HCl reaction at hyperthermal collision energies were investigated using the quasiclassical trajectory method. Stationary points on the OClH 3A" and 3A' potential energy surfaces (PESs) were also examined. The lowest transition state leading to OCl + H on the 3A" surface is 2.26 eV above the reagents at the CCSD(T)/cc-pVTZ level of theory. This saddle point is bent and product-like. Direct dynamics calculations at the MP2/cc-pVTZ level of theory were used to investigate the excitation functions for OH + Cl, OCl + H, and O + H + Cl formation. OCl is formed mainly from small-impact-parameter collisions, and the OCl + H excitation function peaks around 5 eV, where it is similar in magnitude to the OH + Cl excitation function. The shape of the OCl + H excitation function is discussed, and features are identified that should be general to hyperthermal collision dynamics.

  13. Time-resolved spectroscopy of the Mercury 6 3P1 state

    NASA Technical Reports Server (NTRS)

    Halstead, J. A.; Reeves, R. R.

    1981-01-01

    The time-resolved fluorescence was observed from the Hg 6 3P1 state under the influence of the earth's magnetic field and with applied fields of up to 14 G. Modulation of the fluorescence decay signal was observed as a function of both time and space and can be interpreted in terms of a classical precession of the excited atom about the magnetic field or as quantum beats resulting from interference between coherently populated Zeeman sublevels. This modulation was studied for each of the five resolvable components of the hyperfine structure separately. The fluorescence from the even isotopes was determined to be almost completely modulated while the fluorescence from the odd isotopes was only partially modulated. The frequency of modulation of the fluorescence from the mercury-202 isotope was observed as a function of the applied magnetic field and a value for the Lande factor of 1.46 + or - 0.03 was obtained. This is within experimental error of the accepted value of 1.486. In addition, the frequency of modulation as a function of applied magnetic field was determined for each of the three resolvable components with more than one contributing isotopic hyperfine line. An investigation of the effect of radiation trapping on the degree modulation was also made.

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

    PubMed

    Kim, Dongwook; Schatz, George C

    2007-06-14

    Hyperthermal collisions (5 eV) of ground-state atomic oxygen [O ((3)P)] with a liquid-saturated hydrocarbon, squalane (C(30)H(62)), have been studied using QM/MM hybrid "on-the-fly" direct dynamics. The surface structure of the liquid squalane is obtained from a classical molecular dynamics simulation using the OPLS-AA force field. The MSINDO semiempirical Hamiltonian is combined with OPLS-AA for the QM/MM calculations. In order to achieve a more consistent and efficient simulation of the collisions, we implemented a dynamic partitioning of the QM and MM atoms in which atoms are assigned to QM or MM regions based on their proximity to "seed" (open-shell) atoms that determine where bond making/breaking can occur. In addition, the number of seed atoms is allowed to increase or decrease as time evolves so that multiple reactive events can be described. The results show that H abstraction is the most important process for all incident angles, with H elimination, double H abstraction, and C-C bond cleavage also being important. A number of properties of these reactive channels, as well as inelastic nonreactive scattering, are investigated, including angular and translational energy distributions, the effect of incident collision angle, variation with depth of the reactive event within the liquid, with the reaction site on the hydrocarbon, and the effect of dynamics before and after reaction (direct reaction versus trapping reaction-desorption).

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

    NASA Astrophysics Data System (ADS)

    Allan, Mhairi; Bagot, Paul A. J.; Köhler, Sven P. K.; Reed, Stewart K.; Westacott, Robin E.; Costen, Matthew L.; McKendrick, Kenneth G.

    2007-09-01

    Recent progress that has been made towards understanding the dynamics of collisions at the gas-liquid interface is summarized briefly. We describe in this context a promising new approach to the experimental study of gas-liquid interfacial reactions that we have introduced. This is based on laser-photolytic production of reactive gas-phase atoms above the liquid surface and laser-spectroscopic probing of the resulting nascent products. This technique is illustrated for reaction of O(3P) atoms at the surface of the long-chain liquid hydrocarbon squalane (2,6,10,15,19,23-hexamethyltetracosane). Laser-induced fluorescence detection of the nascent OH has revealed mechanistically diagnostic correlations between its internal and translational energy distributions. Vibrationally excited OH molecules are able to escape the surface. At least two contributions to the product rotational distributions are identified, confirming and extending previous hypotheses of the participation of both direct and trapping-desorption mechanisms. We speculate briefly on future experimental and theoretical developments that might be necessary to address the many currently unanswered mechanistic questions for this, and other, classes of gas-liquid interfacial reaction.

  16. Utilising the `3P-model' to Characterise the Discipline of Didactics of Science

    NASA Astrophysics Data System (ADS)

    Adúriz-Bravo, Agustín; Izquierdo-Aymerich, Mercè

    In our research within didactics of science, we have been exploring contributions of the so called cognitive models from contemporary philosophy of science. We have used these philosophical frameworks on different levels. As an outcome, we have formulated a model of didactics of science according to which this discipline adapts and transforms theoretical contributions from different scholarly fields. In this paper, we concentrate on this description of didactics of science, which we have called the 3P-model (i.e., philosophy + psychology + pedagogy). This model of the internal functioning of the discipline may be useful to make innovations in science curriculum design and re-conceptualise the role of science teachers as professionals. We see didactics of science as a set of interrelated activities, performed by different individuals, and ranging from theoretical production to practice of science education at school. We find the concept of technoscience suitable to account for this diversity of goals. According to this concept, scientific disciplines are identified both with generation of knowledge and with active intervention on the world. Within current didactics of science, we recognise several kinds of research, having goals more or less directed to practical intervention in science education.

  17. Genomic characterization of uncommon human G3P[6] rotavirus strains causing diarrhea in children in Italy in 2009.

    PubMed

    Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M

    2015-07-01

    Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis in young children, causing up to 450,000 deaths worldwide, mostly in developing countries. Most of RVA human infections in developed countries are related to five major G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. During the surveillance activity of RotaNet-Italy, three uncommon G3P[6] RVA strains, designated as RVA/Human-wt/ITA/NA01/2009/G3P[6], RVA/Human-wt/ITA/NA06/2009/G3P[6], and RVA/Human-wt/ITA/NA19/2009/G3P[6], were identified in the stools of children with diarrhea hospitalized in Southern Italy in 2009. Samples NA01, NA06 and NA19 were characterized as genotype G3P[6]. To investigate the three strains further, partial sequencing of the eleven genomic segments was performed. RVA strains NA01, NA06 and NA19 were found to share the rare genotype constellation: G3-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2, which had not been reported previously in continental Italy. The phylogenetic analysis of the eleven genomic segments showed no evidence of zoonosis or inter-species reassortment at the origin of the Italian G3P[6] strains, indicating that they possessed DS-1-like genomic constellations similar to those detected previously in human cases in Africa and Europe. The analysis of the hypervariable regions of VP7 and VP4 (VP8*) revealed high amino acid identity between the Italian G3P[6] RVA strains involved in this study. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    SciTech Connect

    Yu, Peng; Wu, Dingguo; You, Yu; Sun, Jing; Lu, Lele; Tan, Jiaxing; Bie, Ping

    2015-08-15

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associated with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.

  19. miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin

    SciTech Connect

    Das, Dibash K.; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065

    2016-11-01

    Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and themore » androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa. - Graphical abstract: miR-1207-3p/FNDC1/FN1/AR is a novel regulatory pathway in prostate cancer. - Highlights: • Expression of microRNA-1207-3p is significantly lost in prostate cancer (PCa) cells. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • FNDC1, FN1, and AR are concurrently overexpressed in metastatic PCa.« less

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

    SciTech Connect

    Yu, Peng; Wu, Dingguo; You, Yu

    2015-08-15

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associatedmore » with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.« less

  1. miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin

    SciTech Connect

    Das, Dibash K.; Naidoo, Michelle; Ilboudo, Adeodat; Park, Jong Y.; Ali, Thahmina; Krampis, Konstantinos; Robinson, Brian D.; Osborne, Joseph R.; Ogunwobi, Olorunseun O.

    2016-11-01

    Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and the androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa. - Graphical abstract: miR-1207-3p/FNDC1/FN1/AR is a novel regulatory pathway in prostate cancer. - Highlights: • Expression of microRNA-1207-3p is significantly lost in prostate cancer (PCa) cells. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • FNDC1, FN1, and AR are concurrently overexpressed in metastatic PCa.

  2. Study of the {gamma}{gamma} decays of the {chi}{sub c2}(1{sup 3}P{sub 2}) and {chi}{sub c0}(1{sup 3}P{sub 0}) charmonium resonances

    SciTech Connect

    Ambrogiani, M.; Argiro, S.; Bagnasco, S.

    2000-09-01

    We report the branching ratios of the {chi}{sub c2}(1{sup 3}P{sub 2}) and {chi}{sub c0}(1{sup 3}P{sub 0}) charmonium resonances to two photons using event samples collected by Fermilab experiment E835 in the reactions p(bar sign)p{yields}{chi}{sub c2}(1{sup 3}P{sub 2})[{chi}{sub c0}(1{sup 3}P{sub 0})]. Our result for the {chi}{sub c2} is B({chi}{sub c2}{yields}{gamma}{gamma})=(1.35{+-}0.25{+-}0.12)x10{sup -4}. We set a 95% upper limit for the {chi}{sub c0} branching ratio B({chi}{sub c0}{yields}{gamma}{gamma}) at 2.09x10{sup -4}. (c) 2000 The American Physical Society.

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

    SciTech Connect

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

    2009-06-19

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

  4. Role of downregulated miR-133a-3p expression in bladder cancer: a bioinformatics study

    PubMed Central

    Gao, Li; Li, Sheng-Hua; Tian, Yi-Xin; Zhu, Qing-Qing; Chen, Gang; Pang, Yu-Yan; Hu, Xiao-Hua

    2017-01-01

    It has been discovered that miR-133a-3p acts as a tumor suppressor in bladder cancer (BC). Nevertheless, the function of miR-133a-3p in BC remains unclarified. Thus, we carried out this study to validate the expression of miR-133a-3p in BC and provide insights into the molecular mechanism underlying it. To assess the expression of miR-133a-3p in BC, we searched eligible studies from literature and Gene expression Omnibus (GEO) to perform a meta-analysis. We also plotted the summary receiver operating characteristic (SROC) curve to evaluate the diagnostic ability of miR-133a-3p in BC. Additionally, the potential target genes of miR-133a-3p were acquired from 14 online software programs and GEO database. Protein-protein interaction (PPI) network was created to identify the hub genes. Then, Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to investigate the regulatory network of the target genes. From the meta-analysis, miR-133a-3p was remarkably downregulated in BC tissues compared with that in non-cancer tissues (standard mean difference =−3.84, 95% confidence interval =−6.99–0.29). Moreover, results from SROC suggested that miR-133a-3p exhibited the ability to diagnose BC (area under curve =0.8418). As for the bioinformatics study, 488 genes were chosen as the potential targets of miR-133a-3p in BC, among which 10 genes were defined as hub genes (all degrees >5). Further GO and KEGG pathway analysis indicated that the target genes of miR-133a-3p aggregated in specific biological process and pathways. In conclusion, miR-133a-3p possessed great diagnostic potential with its downregulation in BC, and miR-133a-3p might serve as a novel biomarker for BC. PMID:28790856

  5. Role of downregulated miR-133a-3p expression in bladder cancer: a bioinformatics study.

    PubMed

    Gao, Li; Li, Sheng-Hua; Tian, Yi-Xin; Zhu, Qing-Qing; Chen, Gang; Pang, Yu-Yan; Hu, Xiao-Hua

    2017-01-01

    It has been discovered that miR-133a-3p acts as a tumor suppressor in bladder cancer (BC). Nevertheless, the function of miR-133a-3p in BC remains unclarified. Thus, we carried out this study to validate the expression of miR-133a-3p in BC and provide insights into the molecular mechanism underlying it. To assess the expression of miR-133a-3p in BC, we searched eligible studies from literature and Gene expression Omnibus (GEO) to perform a meta-analysis. We also plotted the summary receiver operating characteristic (SROC) curve to evaluate the diagnostic ability of miR-133a-3p in BC. Additionally, the potential target genes of miR-133a-3p were acquired from 14 online software programs and GEO database. Protein-protein interaction (PPI) network was created to identify the hub genes. Then, Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to investigate the regulatory network of the target genes. From the meta-analysis, miR-133a-3p was remarkably downregulated in BC tissues compared with that in non-cancer tissues (standard mean difference =-3.84, 95% confidence interval =-6.99-0.29). Moreover, results from SROC suggested that miR-133a-3p exhibited the ability to diagnose BC (area under curve =0.8418). As for the bioinformatics study, 488 genes were chosen as the potential targets of miR-133a-3p in BC, among which 10 genes were defined as hub genes (all degrees >5). Further GO and KEGG pathway analysis indicated that the target genes of miR-133a-3p aggregated in specific biological process and pathways. In conclusion, miR-133a-3p possessed great diagnostic potential with its downregulation in BC, and miR-133a-3p might serve as a novel biomarker for BC.

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

    DOE PAGES

    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.

  7. 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.

  8. 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

  9. Theoretical investigation of exchange and recombination reactions in O(3P)+NO(2Pi) collisions.

    PubMed

    Ivanov, M V; Zhu, H; Schinke, R

    2007-02-07

    We present a detailed dynamical study of the kinetics of O(3P)+NO(2Pi) collisions including O atom exchange reactions and the recombination of NO2. The classical trajectory calculations are performed on the lowest 2A' and 2A" potential energy surfaces, which were calculated by ab initio methods. The calculated room temperature exchange reaction rate coefficient, kex, is in very good agreement with the measured one. The high-pressure recombination rate coefficient, which is given by the formation rate coefficient and to a good approximation equals 2kex, overestimates the experimental data by merely 20%. The pressure dependence of the recombination rate, kr, is described within the strong-collision model by assigning a stabilization probability to each individual trajectory. The measured falloff curve is well reproduced over five orders of magnitude by a single parameter, i.e., the strong-collision stabilization frequency. The calculations also yield the correct temperature dependence, kr proportional, T-1.5, of the low-pressure recombination rate coefficient. The dependence of the rate coefficients on the oxygen isotopes are investigated by incorporating the difference of the zero-point energies between the reactant and product NO radicals, DeltaZPE, into the potential energy surface. Similar isotope effects as for ozone are predicted for both the exchange reaction and the recombination. Finally, we estimate that the chaperon mechanism is not important for the recombination of NO2, which is in accord with the overall T-1.4 dependence of the measured recombination rate even in the low temperature range.

  10. 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

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

    SciTech Connect

    Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; Hong, Kunlun

    2015-02-05

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

  12. Invasive Meningococcal Disease in Québec, Canada, Due to an Emerging Clone of ST-269 Serogroup B Meningococci with Serotype Antigen 17 and Serosubtype Antigen P1.19 (B:17:P1.19)

    PubMed Central

    Law, Dennis K. S.; Lorange, Manon; Ringuette, Louise; Dion, Réjean; Giguère, Michel; Henderson, Averil M.; Stoltz, Jan; Zollinger, Wendell D.; De Wals, Philippe; Tsang, Raymond S. W.

    2006-01-01

    During periods of endemic meningococcal disease, serogroup B Neisseria meningitidis is responsible for a significant percentage of invasive diseases, and no particular clone or strain predominates (F. E. Ashton and D. A. Caugant, Can. J. Microbiol. 47: 293-289, 2001), However, in the winter of 2004 to 2005, a cluster of serogroup B meningococcal disease occurred in one region in the province of Québec, Canada. The N. meningitidis strain responsible for this cluster of cases was identified as sequence type ST-269 with the antigenic formula B:17:P1.19. Retrospective analysis of isolates from 2000 onwards showed that this clone first emerged in the province of Québec in 2003. The emergence of this clone of serogroup B meningococci occurred after a mass vaccination against serogroup C N. meningitidis, suggesting possible capsule replacement. PMID:16891487

  13. Invasive meningococcal disease in Quebec, Canada, due to an emerging clone of ST-269 serogroup B meningococci with serotype antigen 17 and serosubtype antigen P1.19 (B:17:P1.19).

    PubMed

    Law, Dennis K S; Lorange, Manon; Ringuette, Louise; Dion, Réjean; Giguère, Michel; Henderson, Averil M; Stoltz, Jan; Zollinger, Wendell D; De Wals, Philippe; Tsang, Raymond S W

    2006-08-01

    During periods of endemic meningococcal disease, serogroup B Neisseria meningitidis is responsible for a significant percentage of invasive diseases, and no particular clone or strain predominates (F. E. Ashton and D. A. Caugant, Can. J. Microbiol. 47: 293-289, 2001), However, in the winter of 2004 to 2005, a cluster of serogroup B meningococcal disease occurred in one region in the province of Québec, Canada. The N. meningitidis strain responsible for this cluster of cases was identified as sequence type ST-269 with the antigenic formula B:17:P1.19. Retrospective analysis of isolates from 2000 onwards showed that this clone first emerged in the province of Québec in 2003. The emergence of this clone of serogroup B meningococci occurred after a mass vaccination against serogroup C N. meningitidis, suggesting possible capsule replacement.

  14. Atomic composition of the hydrophobic and hydrophilic membrane sides of self-assembled SC3p hydrophobin.

    PubMed Central

    Wösten, H A; de Vries, O M; van der Mei, H C; Busscher, H J; Wessels, J G

    1994-01-01

    The hydrophobin SC3p of Schizophyllum commune self-assembles into a 10-nm-thick amphipathic membrane at hydrophilic-hydrophobic interfaces. X-ray photoelectron spectroscopy of the hydrophobic membrane side of SC3p, assembled in vitro, showed an atomic composition similar to the calculated composition of SC3p when glycosylation was taken into account. The atomic composition measured at the hydrophilic membrane side deviated from that at the hydrophobic side and indicated the presence of a lower number of peptide bonds. High levels of S and N were detected only on mycelia carrying hydrophobic aerial hyphae, as expected with assembled SC3p present at the surface of these hyphae. PMID:7961474

  15. Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling

    PubMed Central

    Jean, Steve; Cox, Sarah; Schmidt, Eric J.; Robinson, Fred L.; Kiger, Amy

    2012-01-01

    Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control. PMID:22648168

  16. 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.

  17. Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14.

    PubMed

    Ji, Ming-Liang; Zhang, Xue-Jun; Shi, Pei-Liang; Lu, Jun; Wang, Shan-Zheng; Chang, Qing; Chen, Hui; Wang, Chen

    2016-04-01

    Accumulating evidence suggests that microRNAs (miRNAs) play an important role in intervertebral disc degeneration (IDD), but the precise role of specific miRNAs involved in this disease remains elusive. The purpose of this study was to identify IDD-specific miRNAs, followed by functional validation of results. MiRNA expression profile was determined in nucleus pulposus (NP) tissues from patients with IDD and controls, employing Solexa sequencing and quantitative real-time PCR (qRT-PCR). Biological functions of differential expression miRNAs were further investigated in vitro and in vivo. Luciferase reporter assays and Western blotting were performed to determine miRNA targets. We identified 28 miRNAs that were differentially expressed in patients compared with controls. Following qRT-PCR confirmation, miR-193a-3p was significantly down-regulated in degenerative NP tissues. Moreover, its level was correlated with grade of disc degeneration. Through gain- and loss-of-function studies, miR-193a-3p was demonstrated to significantly promote type II collagen expression in NP cells. Knockdown of MMP14 induced effects on NP cells similar to those induced by miR-193a-3p. Bioinformatics target prediction identified MMP14 as a putative target of miR-193a-3p. Furthermore, luciferase reporter assays and Western blotting demonstrated that miR-193a-3p directly targets MMP14. MiR-193a-3p inhibited IDD in vitro and in vivo. The downregulation of miR-193a-3p induces the expression of MMP14, which promotes loss of type II collagen and thereby contributes to the development of human IDD. Our findings extend the role of miR-193a-3p in the pathogenesis of IDD and provide a potential novel therapeutic target for degenerative disc disease. Intervertebral disc degeneration (ICC)-specific miRNA profile generated by next generation sequencing. Downregulation of miR-193a-3p promoted loss of type II collagen by directly targeting MMP14 in IDD. miR-193a-3p inhibited IDD in vitro and in vivo. mi

  18. Subtelomere FISH in 50 children with mental retardation and minor anomalies, identified by a checklist, detects 10 rearrangements including a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33.

    PubMed

    Walter, Sabine; Sandig, Klaus; Hinkel, Georg K; Mitulla, Beate; Ounap, Katrin; Sims, Giles; Sitska, Mari; Utermann, Barbara; Viertel, Petra; Kalscheuer, Vera; Bartsch, Oliver

    2004-08-01

    Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed by subtelomere fluorescence in situ hybridization (FISH), are a significant cause of idiopathic mental retardation (MR). Some 20 subtelomere studies, including more than 2,500 subjects, have been reported. The studies are not directly comparable because different techniques and patient ascertainment criteria were used, but an analysis of 14 studies showed that aberrations were detected in 97 out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 4.60-6.84%). We performed a subtelomere FISH study of 50 unrelated children ascertained by a checklist that evaluates MR or developmental delay, dysmorphism, growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced familial translocations or inversions, two unbalanced de novo translocations, and two de novo deletions. Patient 5 showed multiple anomalies (large head, vision defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect, mild transient homocysteinemia) and a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced rearrangement associated with a disease phenotype is a novel one. FISH mapping using panels of overlapping BAC clones identified a number of candidate genes at or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and three genes of unknown function at 20q13.33. Only the homocysteinemia could be speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified degree of MR tested positive, suggesting that the checklist approach could be especially useful within this group of patients. Copyright 2004 Wiley-Liss, Inc.

  19. MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells.

    PubMed

    Wu, Xiu-Juan; Zhao, Zong-Feng; Kang, Xiao-Jing; Wang, Hong-Juan; Zhao, Juan; Pu, Xiong-Ming

    2016-06-14

    Kaposi's sarcoma is a highly vascular tumor of lymphatic endothelial origin. Many deregulated miRNAs, including miR-126-3p, have been identified in Kaposi's sarcoma tissues. miR-126-3p is the most highly endothelial-specific miRNA that regulates vascular integrity and angiogenesis. In this study, we aimed to determine the effect of miR-126-3p on Kaposi's sarcoma cells through transfection of a miRNA mimic and inhibitor. Moreover, we searched the target gene (PIK3R2) of miR-126-3p using bioinformatics software and further verified PIK3R2 using luciferase reporter assays, Real-time quantitative PCR (qRT-PCR) and western blot. The results demonstrated that miR-126-3p inhibited cell proliferation, arrested cell cycle progression, induced cell apoptosis, and inhibited cell invasion of SLK cells. The bioinformatics analysis and luciferase reporter assay revealed that PIK3R2 mRNA is a direct target of miR-126-3p. Moreover, the level of expression of the PIK3R2 gene was downregulated in SLK cells transfected with miR-126-3p siRNAs. Therefore, our data demonstrated that miR-126-3p is a tumor suppressor miRNA that acts by targeting PIK3R2 in Kaposi's sarcoma cells. These findings contribute to our understanding of the molecular mechanisms underlying Kaposi's sarcoma.

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

    NASA Astrophysics Data System (ADS)

    Huang, Hai; Hou, Li-Chao; Zhao, Bin-Peng

    2016-09-01

    We study the magnetic properties of two-band degenerate-gaps superconductors with two-band isotropic Ginzburg-Landau theory. The exact solutions of upper critical field and London penetration depth are obtained, and the calculations reproduce the experimental data of the recently observed superconducting crystal SrPt3P in a broad temperature range. It directly underlies that SrPt3P is a multi-band superconductor with equal gaps in two Fermi surface sheets.

  1. miRNA-337-3p suppresses neuroblastoma progression by repressing the transcription of matrix metalloproteinase 14

    PubMed Central

    Pu, Jiarui; Li, Dan; Qu, Hongxia; Jiao, Wanju; Zhao, Jihe; Huang, Kai; Zheng, Liduan; Tong, Qiangsong

    2015-01-01

    Recent evidence shows the emerging roles of endogenous microRNAs (miRNAs) in repressing gene transcription. However, the miRNAs inhibiting the transcription of matrix metalloproteinase 14 (MMP-14), a membrane-anchored MMP crucial for the tumorigenesis and aggressiveness, still remain largely unknown. In this study, through mining computational algorithm program and genome-wide Argonaute profiling dataset, we identified one binding site of miRNA-337-3p (miR-337-3p) within the MMP-14 promoter. We demonstrated that miR-337-3p was under-expressed and inversely correlated with MMP-14 expression in clinical specimens and cell lines of neuroblastoma (NB), the most common extracranial solid tumor in childhood. Patients with high miR-337-3p expression had greater survival probability. miR-337-3p suppressed the promoter activity, nascent transcription, and expression of MMP-14, resulting in decreased levels of vascular endothelial growth factor, in cultured NB cell lines. Mechanistically, miR-337-3p recognized its binding site and recruited Argonaute 2 to facilitate the enrichment of repressive epigenetic markers and decrease the binding of RNA polymerase II and specificity protein 1 on the MMP-14 promoter. Gain- and loss-of-function studies demonstrated that miR-337-3p suppressed the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. In addition, restoration of MMP-14 expression rescued the NB cells from changes in these biological features. Taken together, these data indicate that miR-337-3p directly binds the MMP-14 promoter to repress its transcription, thus suppressing the progression of NB. PMID:26084291

  2. miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression.

    PubMed

    Zheng, Liduan; Chen, Yajun; Ye, Lin; Jiao, Wanju; Song, Huajie; Mei, Hong; Li, Dan; Yang, Feng; Li, Huanhuan; Huang, Kai; Tong, Qiangsong

    2017-08-21

    Recent evidence shows the emerging roles of promoter-targeting endogenous microRNAs (miRNAs) in regulating gene transcription. However, miRNAs affecting the transcription of matrix metalloproteinase 14 (MMP-14) in gastric cancer remain unknown. Herein, through integrative mining of public datasets, we identified the adjacent targeting sites of Yin Yang 1 (YY1) and miRNA-584-3p (miR-584-3p) within MMP-14 promoter. We demonstrated that YY1 directly targeted the MMP-14 promoter to facilitate its expression in gastric cancer cells. In contrast, miR-584-3p recognized its complementary site within MMP-14 promoter to suppress its expression. Mechanistically, miR-584-3p interacted with Argonaute 2 to recruit enhancer of zeste homolog 2 and euchromatic histone lysine methyltransferase 2, resulting in enrichment of repressive epigenetic markers and decreased binding of YY1 to MMP-14 promoter. miR-584-3p inhibited the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cells through repressing YY1-facilitated MMP-14 expression. In clinical gastric cancer tissues, the expression of YY1 and miR-584-3p was positively or negatively correlated with MMP-14 levels. In addition, miR-584-3p and YY1 were independent prognostic factors associated with favorable and unfavorable outcome of gastric cancer patients, respectively. These data demonstrate that miR-584-3p directly targets the MMP-14 promoter to repress YY1-facilitated MMP-14 expression and inhibits the progression of gastric cancer.

  3. Arf3p GTPase is a key regulator of Bud2p activation for invasive growth in Saccharomyces cerevisiae.

    PubMed

    Hsu, Jia-Wei; Lee, Fang-Jen S

    2013-08-01

    The regulation and signaling pathways involved in the invasive growth of yeast have been studied extensively because of their general applicability to fungal pathogenesis. Bud2p, which functions as a GTPase-activating protein (GAP) for Bud1p/Rsr1p, is required for appropriate budding patterns and filamentous growth. The regulatory mechanisms leading to Bud2p activation, however, are poorly understood. In this study, we report that ADP-ribosylation factor 3p (Arf3p) acts as a regulator of Bud2p activation during invasive growth. Arf3p binds directly to the N-terminal region of Bud2p and promotes its GAP activity both in vitro and in vivo. Genetic analysis shows that deletion of BUD1 suppresses the defect of invasive growth in arf3Δ or bud2Δ cells. Lack of Arf3p, like that of Bud2p, causes the intracellular accumulation of Bud1p-GTP. The Arf3p-Bud2p interaction is important for invasive growth and facilitates the Bud2p-Bud1p association in vivo. Finally, we show that under glucose depletion-induced invasion conditions in yeast, more Arf3p is activated to the GTP-bound state, and the activation is independent of Arf3p guanine nucleotide-exchange factor Yel1p. Thus we demonstrate that a novel spatial activation of Arf3p plays a role in regulating Bud2p activation during glucose depletion-induced invasive growth.

  4. microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual specificity phosphatase 6 expression

    PubMed Central

    Lee, Heejin; Kim, Chongtae; Kang, Hoin; Tak, Hyosun; Ahn, Sojin; Yoon, Sungjoo Kim; Kuh, Hyo-Jeong; Kim, Wook; Lee, Eun Kyung

    2017-01-01

    Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression. PMID:28496200

  5. microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual specificity phosphatase 6 expression.

    PubMed

    Lee, Heejin; Kim, Chongtae; Kang, Hoin; Tak, Hyosun; Ahn, Sojin; Yoon, Sungjoo Kim; Kuh, Hyo-Jeong; Kim, Wook; Lee, Eun Kyung

    2017-05-12

    Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression.

  6. 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.

  7. MicroRNA-299-3p promotes the sensibility of lung cancer to doxorubicin through directly targeting ABCE1.

    PubMed

    Zheng, Dawei; Dai, Yan; Wang, Song; Xing, Xiaoyu

    2015-01-01

    MicroRNAs (miRNAs) are a class of endogenous, small non-coding RNAs which play important roles in various biological and cellular processes, including chemoresistance. The expression level of miR-299-3p was dysregulated in doxorubicin-resistance lung cancer cell lines. However, the exact role of miR-299-3p in doxorubicin-resistance is still unknown. In the present study, miR-299-3p was down-expressed in doxorubicin-resistant or -sensitive lung cancer samples and it was identified to directly targeted adenosine triphosphate binding cassette E1 (ABCE1) 3'-untranslated region (UTR) in lung cancer H69 cells by luciferase assay. After transfection of miR-299-3p mimics or ABCE1-siRNA, MTT assay confirmed that the H69/ADR cell proliferation was inhibited, as well as the enhanced cell inhibitory rate in the presence of doxorubicin. H69/ADR cell apoptosis rate was promoted after miR-299-3p or ABCE1-siRNA transfection. The results indicated that miR-299-3p promotes the sensibility of lung cancer to doxorubicin through suppression of ABCE1, at least partly. Therefore, the disordered decreased of miR-299-3p and resulting ABCE1 up-expression may contribute to chemoresistance of lung cancer, and miR-299-3p-ABCE1 may represent a new potential therapeutic target for the treatment of chemoresistance of lung cancer.

  8. MicroRNA-299-3p promotes the sensibility of lung cancer to doxorubicin through directly targeting ABCE1

    PubMed Central

    Zheng, Dawei; Dai, Yan; Wang, Song; Xing, Xiaoyu

    2015-01-01

    MicroRNAs (miRNAs) are a class of endogenous, small non-coding RNAs which play important roles in various biological and cellular processes, including chemoresistance. The expression level of miR-299-3p was dysregulated in doxorubicin-resistance lung cancer cell lines. However, the exact role of miR-299-3p in doxorubicin-resistance is still unknown. In the present study, miR-299-3p was down-expressed in doxorubicin-resistant or -sensitive lung cancer samples and it was identified to directly targeted adenosine triphosphate binding cassette E1 (ABCE1) 3’-untranslated region (UTR) in lung cancer H69 cells by luciferase assay. After transfection of miR-299-3p mimics or ABCE1-siRNA, MTT assay confirmed that the H69/ADR cell proliferation was inhibited, as well as the enhanced cell inhibitory rate in the presence of doxorubicin. H69/ADR cell apoptosis rate was promoted after miR-299-3p or ABCE1-siRNA transfection. The results indicated that miR-299-3p promotes the sensibility of lung cancer to doxorubicin through suppression of ABCE1, at least partly. Therefore, the disordered decreased of miR-299-3p and resulting ABCE1 up-expression may contribute to chemoresistance of lung cancer, and miR-299-3p-ABCE1 may represent a new potential therapeutic target for the treatment of chemoresistance of lung cancer. PMID:26617714

  9. MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma.

    PubMed

    Wu, Manya; Huang, Chaoyuan; Huang, Xinping; Liang, Rong; Feng, Yan; Luo, Xiaoling

    2017-10-01

    In our previous studies, the Illumine Soledad massively parallel signature sequencing of miRNomes in non‑tumor and hepatocellular carcinoma (HCC) tissues revealed that microRNA (miR)-144-3p was significantly downregulated in HCC, but its role in HCC development, especially angiogenesis, remains unclear. In this investigation, we found recovering miR‑144‑3p expression can significantly suppress the growth, migration and induced angiogenic capacity of HCC cells through both in vivo and in vitro experiments. Moreover, clinical correlation analysis showed that low expression of miR‑144‑3p was positively correlated to poor disease-free survival (DFS) of HCC patients. Mechanistically, serum and glucocorticoid kinase 3 (SGK3), the putative targets of miR‑144‑3p, was predicted by Target Scan database and identified to be suppressed by miR‑144‑3p so that inhibiting the activation of mTOR-VEGF downstream signals was activated by the phosphoinositide 3-kinase (PI3K)-independent pathway. Hence, we concluded that miR‑144‑3p, which is frequently downregulated in HCC, can inhibit proliferation, migration and repress angiogenesis by regulating SGK3 activation with PI3K independent signal pathway, and acts as a prognostic factor for HCC patients.

  10. miR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation.

    PubMed

    Luo, Ying; Dong, Hai-Ying; Zhang, Bo; Feng, Zhao; Liu, Yi; Gao, Yu-Qi; Dong, Ming-Qing; Li, Zhi-Chao

    2015-02-01

    Activation of pulmonary adventitial fibroblasts plays a key role in the pulmonary vascular remodeling in hypoxic pulmonary hypertension. Previous studies showed that miRNAs participated in the regulation of fibroblast activation. This study explored the role of miR-29 in the activation of pulmonary adventitial fibroblasts and the therapeutic potential in hypoxic pulmonary hypertension. We found that hypoxia-induced pulmonary adventitial fibroblasts activation was accompanied with a drastic decrease of miR-29a-3p expression. Knockdown of hypoxia-inducible factor-1 α or Smad3 reversed the hypoxia-induced decrease of miR-29-3p in cultured pulmonary adventitial fibroblasts. In vitro, miR-29a-3p mimic inhibited the hypoxia-induced proliferation, migration, and secretion of pulmonary adventitial fibroblasts, suppressed the hypoxia-induced expression of α-smooth muscle actin and extracellular matrix collagen in pulmonary adventitial fibroblasts; however, miR-29a-3p inhibitor mimicked the effect of hypoxia on the activation of pulmonary adventitial fibroblasts. Further studies revealed that preventative or therapeutic administration of miR-29a-3p significantly decreased pulmonary artery pressure and right ventricle hypertrophy index and ameliorated pulmonary vascular remodeling in hypoxic pulmonary hypertension rats. These findings suggest that miR-29a-3p regulates the activation and phenotype of pulmonary adventitial fibroblasts in hypoxia and has preventative and therapeutic potential in hypoxic pulmonary hypertension. © 2014 American Heart Association, Inc.

  11. 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.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

    Grozdanov, Tasko P.; McCarroll, Ronald; Roueff, Evelyne

    2016-05-01

    formation of ND+. The calculated value is consistent with the available experimental data. Conclusions: The present results allow for the determination of reaction rate coefficients for any given distribution of specific fine structure and rotational state populations of the reactants. In interstellar conditions, where N+ is in its 3P0 state and para- and ortho-H2 respectively in J = 0 and J = 1. Our results enable a study of the influence of the ortho/para evolution of molecular hydrogen on the formation of nitrogen compounds.

  14. 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.

  15. MicroRNA-214-3p: A link between autophagy and endothelial cell dysfunction in atherosclerosis.

    PubMed

    Wang, J; Wang, W-N; Xu, S-B; Wu, H; Dai, B; Jian, D-D; Yang, M; Wu, Y-T; Feng, Q; Zhu, J-H; Zhang, L; Zhang, L

    2018-03-01

    Endothelial cell injury assumes a fundamental part in the pathogenesis of atherosclerosis, and endothelial cell autophagy has protective effects on the development of atherosclerosis, although the underlying molecular regulation mechanism is indistinct. This study aimed to investigate whether microRNA-214-3p (miR-214-3p) is involved in the endothelial cell autophagy regulation of atherosclerosis. We utilized ApoE -/- mice provided with a high-fat diet (HFD) as atherosclerosis model. We analysed the level of miR-214-3p and the levels of autophagy-related protein 5 (ATG5) and autophagy-related protein 12 (ATG12) in the purified CD31 + endothelial cells from mouse aorta. Bioinformatics analysis and a dual-luciferase reporter assay were performed to confirm the binding target of miR-214-3p. In vitro study, human umbilical vein endothelial cells (HUVECs) were transfected with miR-214-3p mimics/inhibitor and stimulated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) for 12 hours to initiate a stress-repairing autophagic process. In mouse models, we identified an inverse correlation between miR-214-3p, ATG5 and ATG12. We observed that in young HUVECs, ox-LDL-initiated autophagy was repressed by miR-214-3p overexpression, as evaluated by autophagic protein analysis, microtubule-associated protein 1 light chain 3B-II (LC3B-II) immunofluorescence assay and transmission electron microscopy (TEM). Also, miR-214-3p promoted ox-LDL accumulation in HUVECs and THP-1 monocyte adhesion. Conversely, in old HUVECs, suppression of miR-214-3p preserved the ability to initiate a protective autophagy reaction to the ox-LDL stimulation. miR-214-3p regulates ox-LDL-initiated autophagy in HUVECs by directly targeting the 3'UTR of ATG5 and may have a suitable role in the pathogenesis of atherosclerosis. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  16. 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.

  17. The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory.

    PubMed

    Sim, Su-Eon; Lim, Chae-Seok; Kim, Jae-Ick; Seo, Daekwan; Chun, Heejung; Yu, Nam-Kyung; Lee, Jaehyun; Kang, SukJae Joshua; Ko, Hyoung-Gon; Choi, Jun-Hyeok; Kim, TaeHyun; Jang, Eun-Hae; Han, Joohyun; Bak, Myeong Seong; Park, Jong-Eun; Jang, Deok-Jin; Baek, Daehyun; Lee, Yong-Seok; Kaang, Bong-Kiun

    2016-08-17

    MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression in many tissues. Although a number of brain-enriched miRNAs have been identified, only a few specific miRNAs have been revealed as critical regulators of synaptic plasticity, learning, and memory. miR-9-5p/3p are brain-enriched miRNAs known to regulate development and their changes have been implicated in several neurological disorders, yet their role in mature neurons in mice is largely unknown. Here, we report that inhibition of miR-9-3p, but not miR-9-5p, impaired hippocampal long-term potentiation (LTP) without affecting basal synaptic transmission. Moreover, inhibition of miR-9-3p in the hippocampus resulted in learning and memory deficits. Furthermore, miR-9-3p inhibition increased the expression of the LTP-related genes Dmd and SAP97, the expression levels of which are negatively correlated with LTP. These results suggest that miR-9-3p-mediated gene regulation plays important roles in synaptic plasticity and hippocampus-dependent memory. Despite the abundant expression of the brain-specific microRNA miR-9-5p/3p in both proliferating and postmitotic neurons, most functional studies have focused on their role in neuronal development. Here, we examined the role of miR-9-5p/3p in adult brain and found that miR-9-3p, but not miR-9-5p, has a critical role in hippocampal synaptic plasticity and memory. Moreover, we identified in vivo binding targets of miR-9-3p that are involved in the regulation of long-term potentiation. Our study provides the very first evidence for the critical role of miR-9-3p in synaptic plasticity and memory in the adult mouse. Copyright © 2016 the authors 0270-6474/16/368641-12$15.00/0.

  18. On the Fine Structure Splitting of the 3p43d 4D5/2 and 3p43d 4D7/2 Levels of Fe X

    NASA Astrophysics Data System (ADS)

    Judge, Philip G.; Hutton, Roger; Li, Wenxian; Brage, Tomas

    2016-12-01

    We study UV spectra obtained with the SO82-B slit spectrograph on board SKYLAB to estimate the fine structure (FS) splitting of the Cl-like 3{{{p}}}43{{d}}{}4{{{D}}}5/2 and 3{{{p}}}43{{d}}{}4{{{D}}}7/2 levels of Fe x. The splitting is of interest because the Zeeman effect mixes these levels, producing a “magnetically induced transition” (MIT) from 3{{{p}}}43{{d}}{}4{{{D}}}7/2 to 3{{{p}}}5{}2{{{P}}}3/2{{o}} for modest magnetic field strengths characteristic of the active solar corona. We estimate the splitting using the Ritz combination formula applied to two lines in the UV region of the spectrum close to 1603.2 Å, which decay from the level 3{{{p}}}4{(}1{{D}})3{{d}}{}2{{{G}}}7/2 to these two lower levels. The MIT and accompanying spin-forbidden transition lie near 257 Å. By careful inspection of a deep exposure obtained with the S082B instrument, we derive a splitting of ≲ 7+/- 3 cm-1. The upper limit arises because of a degeneracy between the effects of non-thermal line broadening and FS splitting for small values of the latter parameter. Although the data were recorded on photographic film, we solved for optimal values of line width and splitting of 8.3 ± 0.9 and 3.6 ± 2.7 cm-1.

  19. Spectroscopic characterization of the unusually strongly bound, doubly excited van der Waals state, Mg(3pπ3pπ 3PJ)ṡKr[3Σ-

    NASA Astrophysics Data System (ADS)

    Leung, Allen W. K.; McCaffrey, John G.; Breckenridge, W. H.

    1998-11-01

    The unusual doubly excited van der Waal's state, Mg(3pπ3pπ 3PJ)ṡKr[3Σ-], has been characterized using a laser-vaporization, supersonic-jet source and R2PI (Resonance Two-Photon Ionization) spectroscopy. This state is very strongly bound (De=3966 cm-1) and has a short bond length (Re=2.45 Å) compared to its singly excited analogue, Mg(3s3pπ 3PJ)ṡKr[3Π0-], for which De=267 cm-1 and Re=3.48 Å. In fact, this state is even more than twice as strongly bound as the ground-state Mg(3s)+ṡKr ion, where De=1949 cm-1 and Re≈2.8 Å. Possible reasons for the strong van der Waal's bonding are discussed, and it is concluded that the lack of σ-σ repulsion because there is no Mg(3sσ) valence electron must be a major factor; the similar ionic van der Waal's state Mg+(3pπ)ṡKr[2Π], which would be obtained by removing one of the Mg(3pπ) electrons, is even more strongly bound, with De≈7200 cm-1 [J. S. Pilgrim, C. S. Yeh, K. R. Berry, and M. A. Duncan, J. Chem. Phys. 100, 7945 (1994)].

  20. MiR-25-3p attenuates the proliferation of tongue squamous cell carcinoma cell line Tca8113.

    PubMed

    Xu, Jia-Ying; Yang, Li-Li; Ma, Chao; Huang, Yuan-Liang; Zhu, Gui-Xiang; Chen, Qi-Lin

    2013-09-01

    To investigate the effects of miR-25-3p on the occurrence, development and proliferation of tongue squamous cell carcinoma cells. To establish tongue squamous cell carcinoma cell line Tca8113 that stably and highly express miR-25-3p using recombinant retroviral vector-mediated gene transfer method. The proliferation of transfected Tca8113 was detected by thiazolyl blue tetrazolium bromide (MTT) and cell colony formation assays. cyclinD1, p21(cip1) and p27(kip1) mRNA expressions in the transfected Tca-8113 were detected by quantitative PCR. cyclinD1, p21, p27(kip1), AKT, p-AKT, FOXO1 and p-FOXO1 expressions in the transfected Tca8113 were detected by western blot analysis. In addition, miR-25-3p expression in the tongue squamous cell carcinoma cell line and tissue specimen was also detected by quantitative PCR. Quantitative PCR showed that miR-25-3p expression in the tongue squamous cell carcinoma cell lines and tissue specimen was significantly lower than that in the adjacent tissue. MTT and cell colony formation assays showed that after miR-25-3p overexpression, the proliferation of transfected Tca8113 was obviously attenuated. Western blot analysis and quantitative PCR showed that after miR-25-3p overexpression, p21(cip1) and p27(kip1) expressions were upregulated, while cyclinD1, AKT, FOXO1 expressions were downregulated, and AKT and FOXO1 phosphorylation was inactivated in the transfected Tca8113 cells. MiR-25-3p inhibited the proliferation of tongue squamous cell carcinoma cells and regulated cell cycle-related protein expression, playing an important role in the occurrence and development of squamous cell carcinoma of the tongue. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  1. miR-193a-3p interaction with HMGB1 downregulates human endothelial cell proliferation and migration

    PubMed Central

    Khoo, Cheen P.; Roubelakis, Maria G.; Schrader, Jack B.; Tsaknakis, Grigorios; Konietzny, Rebecca; Kessler, Benedikt; Harris, Adrian L.; Watt, Suzanne M.

    2017-01-01

    Circulating endothelial colony forming cells (ECFCs) contribute to vascular repair where they are a target for therapy. Since ECFC proliferative potential is increased in cord versus peripheral blood and to define regulatory factors controlling this proliferation, we compared the miRNA profiles of cord blood and peripheral blood ECFC-derived cells. Of the top 25 differentially regulated miRNAs selected, 22 were more highly expressed in peripheral blood ECFC-derived cells. After validating candidate miRNAs by q-RT-PCR, we selected miR-193a-3p for further investigation. The miR-193a-3p mimic reduced cord blood ECFC-derived cell proliferation, migration and vascular tubule formation, while the miR-193a-3p inhibitor significantly enhanced these parameters in peripheral blood ECFC-derived cells. Using in silico miRNA target database analyses combined with proteome arrays and luciferase reporter assays of miR-193a-3p mimic treated cord blood ECFC-derived cells, we identified 2 novel miR-193a-3p targets, the high mobility group box-1 (HMGB1) and the hypoxia upregulated-1 (HYOU1) gene products. HMGB1 silencing in cord blood ECFC-derived cells confirmed its role in regulating vascular function. Thus, we show, for the first time, that miR-193a-3p negatively regulates human ECFC vasculo/angiogenesis and propose that antagonising miR-193a-3p in less proliferative and less angiogenic ECFC-derived cells will enhance their vasculo/angiogenic function. PMID:28276476

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

    PubMed Central

    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. PMID:28861150

  3. 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

  4. miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer*

    PubMed Central

    Epis, Michael R.; Giles, Keith M.; Barker, Andrew; Kendrick, Tulene S.; Leedman, Peter J.

    2009-01-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is frequently overexpressed in prostate cancer and is associated with disease progression and poor survival. We have identified two specific miR-331-3p target sites within the ERBB-2 mRNA 3′-untranslated region and show that miR-331-3p expression is decreased in prostate cancer tissue relative to normal adjacent prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331-3p reduced ERBB-2 mRNA and protein expression and blocked downstream phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection blocked the androgen receptor signaling pathway in prostate cancer cells, reducing activity of an androgen-stimulated prostate-specific antigen promoter and blocking prostate-specific antigen expression. Our findings provide insight into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p has the capacity to regulate signaling pathways critical to the development and progression of prostate cancer cells. PMID:19584056

  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. 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.

  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. Interface engineering of a CeO2-Cu3P nanoarray for efficient alkaline hydrogen evolution.

    PubMed

    Wang, Zao; Du, Huitong; Liu, Zhiang; Wang, Hui; Asiri, Abdullah M; Sun, Xuping

    2018-02-01

    It is of great importance to design and develop highly active electrocatalysts for the hydrogen evolution reaction (HER) under alkaline conditions. In this work, we report the development of a CeO2-Cu3P nanoarray supported on nickel foam (CeO2-Cu3P/NF) as an excellent HER catalyst with the demand of an overpotential of only 148 mV to deliver a geometrical catalytic current density of 20 mA cm-2 in 1.0 M KOH. Remarkably, this catalyst also shows strong long-term electrochemical durability for at least 100 h with nearly 100% Faradaic efficiency. Density functional theory calculations reveal that the CeO2-Cu3P/NF hybrid has a lower water dissociation energy and a more thermo-neutral hydrogen adsorption free energy.

  9. HIF-1α:CRAT:miR-144-3p axis dysregulation promotes osteoarthritis chondrocyte apoptosis and VLCFA accumulation.

    PubMed

    Song, Jinsoo; Kang, Yeon-Ho; Yoon, Sik; Chun, Churl-Hong; Jin, Eun-Jung

    2017-09-19

    The functional role(s) of peroxisomes in osteoarthritis remains unclear. We demonstrated that peroxisomal dysfunction in osteoarthritis is responsible for very-long-chain fatty acid (VLCFA) accumulation. Through gene-profiling analyses, we identified CRAT as the gene responsible for this event. CRAT expression was suppressed in osteoarthritis chondrocytes, and its knockdown yielded pathological osteoarthritic characteristics, including VLCFA accumulation, apoptosis, autophagic inhibition, and mitochondrial dysfunction. Subsequent miRNA profiling revealed that peroxisomal dysfunction upregulates miR-144-3p, which overlapped with the osteoarthritis pathological characteristics observed upon CRAT knockdown. Moreover, knocking down HIF-1α in normal chondrocytes suppressed CRAT expression while stimulating miR-144-3p. Our data indicate that deregulation of a HIF-1a:CRAT:miR-144-3p axis impairs peroxisomal function during the pathogenesis of osteoarthritis.

  10. miR-142-3p Is a Key Regulator of IL-1β-Dependent Synaptopathy in Neuroinflammation.

    PubMed

    Mandolesi, Georgia; De Vito, Francesca; Musella, Alessandra; Gentile, Antonietta; Bullitta, Silvia; Fresegna, Diego; Sepman, Helena; Di Sanza, Claudio; Haji, Nabila; Mori, Francesco; Buttari, Fabio; Perlas, Emerald; Ciotti, Maria Teresa; Hornstein, Eran; Bozzoni, Irene; Presutti, Carlo; Centonze, Diego

    2017-01-18

    MicroRNAs (miRNA) play an important role in post-transcriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter (WM) pathology. However, little is known about their role in gray matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE. Particularly, we observed that miR-142-3p is increased in the CSF of patients with active MS and in EAE brains. We propose miR-142-3p as a molecular mediator of the IL-1β-dependent downregulation of the glial glutamate-aspartate transporter (GLAST), which causes an enhancement of the glutamatergic transmission in the EAE cerebellum. The synaptic abnormalities mediated by IL-1β and the clinical and neuropathological manifestations of EAE disappeared in miR-142 knock-out mice. Furthermore, we observed that in vivo miR-142-3p inhibition, either by a preventive and local treatment or by a therapeutic and systemic strategy, abolished IL-1β- and GLAST-dependent synaptopathy in EAE wild-type mice. Consistently, miR-142-3p was responsible for the glutamatergic synaptic alterations caused by CSF of patients with MS, and CSF levels of miR-142-3p correlated with prospective MS disease progression. Our findings highlight miR-142-3p as key molecular player in IL-1β-mediated synaptic dysfunction, possibly leading to excitotoxic damage in both EAE and MS diseases. Inhibition of miR-142-3p could be neuroprotective in MS. Current studies suggest the role of glutamate excitotoxicity in the development and progression of multiple sclerosis (MS) and of its mouse model experimental

  11. Influence of semiconductor surface condition on electrical and photoelectric properties of Al-Zn3P2 contacts

    NASA Astrophysics Data System (ADS)

    Mirowska, Nella; Adamczyk, Miroslaw

    1999-04-01

    Zinc phosphide Zn3P2 has been intensively investigated as one of the most promising materials for applications in low-cost solar energy converters and broad- range photodetectors. The Schottky barriers formed by Al on Zn3P2 p-type crystals have been studied. Substantial differences were observed depending on whether the semiconductor surface was chemically etched, mechanically polished or/and heat treated at 523 K. Measurements of current-voltage characteristics and photovoltaic spectrum of Al-Zn3P2 contacts at room temperature have been used for determination of some electrical parameters of junctions as well as optical transitions and hole concentration in the semiconductor. The value of barrier height, (Phi) B, changed from 0.76 to 0.78 eV, the junction depth--from about 3 to 79 micrometers , and the contact resistance--from 5.9 X 103 to 858 X 103 (Omega) . The hole concentration of examined polycrystalline samples was equal to 2 X 1013 divided by 5 X 1015 cm. The condition of semiconductor surface seems to have an essential influence on obtained electrical parameters of Al-Zn3P2 junctions and their spectral characteristics. To understand the problems connected with metal-Zn3P2 interface layer formation, the free enthalpy, (Delta) GR, was calculated. The analysis of the results, obtained especially for the Mg and Al, have indicated that Al is also a good candidate for formation of rectifying contacts to Zn3P2.

  12. Loss of MicroRNA-489-3p promotes osteosarcoma metastasis by activating PAX3-MET pathway.

    PubMed

    Liu, Qifei; Yang, Guochun; Qian, Yuying

    2017-04-01

    Osteosarcoma (OS) remains one deadly disease for many affected patients. MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-489-3p in osteosarcoma (OS) metastasis. MiR-489-3p expression was downregulated in OS cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-489-3p significantly suppressed OS cell invasion and metastasis both in vitro and in vivo. Mechanistically, paired box gene 3 (PAX3) was identified as a functional target of miR-489-3p in OS cells. MiR-489-3p inhibited OS metastasis by negatively regulating expression of PAX3. In addition, PAX3 expression was markedly higher in OS tissues than in adjacent non-cancerous tissues. Transwell assays and in vivo metastasis assays demonstrated that overexpression of PAX3 significantly promoted the invasiveness and pulmonary metastasis of OS cells. On the other hand, downregulation of PAX3 markedly reduced cell metastatic potential. Mechanistic investigations indicated that prometastasis function of PAX3 was mediated by upregulating downstream target MET tyrosine kinase receptor. In conclusion, our results reveal that miR-489-3p-PAX3-MET signaling is critical to OS metastasis. Targeting the pathway described here may open new therapeutic prospects to restrict the metastatic potential of OS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Half-metallic ferromagnetism in Fe-doped Zn3P2 from first-principles calculations

    NASA Astrophysics Data System (ADS)

    Jaiganesh, G.; Jaya, S. Mathi

    2014-04-01

    Using the first-principles calculations based on the density functional theory, we have studied the magnetism and electronic structure of Fe-doped Zinc Phosphide (Zn3P2). Our results show that the half-metallic ground state and ferromagnetic stability for the small Fe concentrations considered in our study. The stability of the doped material has been studied by calculating the heat of formation and analyzing the minimum total energies in nonmagnetic and ferromagnetic phases. A large value of the magnetic moment is obtained from our calculations and our calculation suggests that the Fe-doped Zn3P2 may be a useful material in semiconductor spintronics.

  14. Accurate long-range coefficients for two excited like isotope He atoms: He(2 {sup 1}P)-He(2 {sup 1}P), He(2 {sup 1}P)-He(2 {sup 3}P), and He(2 {sup 3}P)-He(2 {sup 3}P)

    SciTech Connect

    Zhang, J.-Y.; Yan, Z.-C.; Vrinceanu, D.; Babb, J. F.; Sadeghpour, H. R.

    2007-07-15

    A general formalism is used to express the long-range potential energies in inverse powers of the separation distance between two like atomic or molecular systems with P symmetries. The long-range molecular interaction coefficients are calculated for the molecular symmetries {delta}, {pi}, and {sigma}, arising from the following interactions: He(2 {sup 1}P)-He(2 {sup 1}P), He(2 {sup 1}P)-He(2 {sup 3}P), and He(2 {sup 3}P)-He(2 {sup 3}P). The electric quadrupole-quadrupole term C{sub 5}, the van der Waals (dispersion) term C{sub 6}, and higher-order terms C{sub 8} and C{sub 10} are calculated ab initio using accurate variational wave functions in Hylleraas coordinates with finite nuclear mass effects. A comparison is made with previously published results where available.

  15. High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.

    PubMed

    Wistuba, I I; Maitra, A; Carrasco, R; Tang, M; Troncoso, P; Minna, J D; Gazdar, A F

    2002-08-12

    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.

  16. 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....

  17. Histidine Methylation of Yeast Ribosomal Protein Rpl3p Is Required for Proper 60S Subunit Assembly

    PubMed Central

    Al-Hadid, Qais; Roy, Kevin; Munroe, William; Dzialo, Maria C.; Chanfreau, Guillaume F.

    2014-01-01

    Histidine protein methylation is an unusual posttranslational modification. In the yeast Saccharomyces cerevisiae, the large ribosomal subunit protein Rpl3p is methylated at histidine 243, a residue that contacts the 25S rRNA near the P site. Rpl3p methylation is dependent upon the presence of Hpm1p, a candidate seven-beta-strand methyltransferase. In this study, we elucidated the biological activities of Hpm1p in vitro and in vivo. Amino acid analyses reveal that Hpm1p is responsible for all of the detectable protein histidine methylation in yeast. The modification is found on a polypeptide corresponding to the size of Rpl3p in ribosomes and in a nucleus-containing organelle fraction but was not detected in proteins of the ribosome-free cytosol fraction. In vitro assays demonstrate that Hpm1p has methyltransferase activity on ribosome-associated but not free Rpl3p, suggesting that its activity depends on interactions with ribosomal components. hpm1 null cells are defective in early rRNA processing, resulting in a deficiency of 60S subunits and translation initiation defects that are exacerbated in minimal medium. Cells lacking Hpm1p are resistant to cycloheximide and verrucarin A and have decreased translational fidelity. We propose that Hpm1p plays a role in the orchestration of the early assembly of the large ribosomal subunit and in faithful protein production. PMID:24865971

  18. 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

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION 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...

  19. Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric ependymoma.

    PubMed

    Margolin-Miller, Yulia; Yanichkin, Natalia; Shichrur, Keren; Toledano, Helen; Ohali, Anat; Tzaridis, Theophilos; Michowitz, Shalom; Fichman-Horn, Suzana; Feinmesser, Meora; Pfister, Stefan M; Witt, Hendrik; Tabori, Uri; Bouffet, Eric; Ramaswamy, Vijay; Hawkins, Cynthia; Taylor, Michael D; Yaniv, Isaac; Avigad, Smadar

    2017-08-01

    Ependymoma is a malignant pediatric brain tumor, often incurable under the current treatment regimen. We aimed to evaluate the expression of microRNAs (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic molecular markers which would lead to potential therapeutic targets. Following miR-array expression analysis, we focused on 9 miRs that correlated with relapse which were further validated by quantitative real-time PCR (qRT-PCR) in a cohort of 67 patients. Western blotting and immunohistochemistry were used to measure target protein expression in 20 and 34 tumor samples, respectively. High expression of miR-124-3p significantly correlated with the lower progression-free survival (PFS) of 16% compared to 67% in those expressing low levels (P = .002). Interestingly, in the group of patients with local disease (n = 56) expression levels of this miR distinguished 2 subgroups with a significantly different outcome (P = .001). miR-124-3p was identified as an independent prognostic factor of relapse in the multivariate analysis performed in the whole cohort and in the group with localized disease. In the localized group, a patient expressing high levels of miR-124-3p had a 4.1-fold increased risk for relapse (P = .005). We demonstrated the direct binding of miR-124-3p to its target TP53INP1. Negative TP53INP1 protein levels correlated with a poor outcome (P = .034). We propose miR-124-3p and TP53INP1 as new biomarkers for prognostic stratification that may be possible therapeutic targets for ependymoma. © 2017 Wiley Periodicals, Inc.

  20. Origin of Outstanding Phase and Moisture Stability in a Na3P1-xAsxS4 Superionic Conductor.

    PubMed

    Shang, Shun-Li; Yu, Zhaoxin; Wang, Yi; Wang, Donghai; Liu, Zi-Kui

    2017-05-17

    Sodium ion (Na) solid-state electrolytes (SSEs) are critical to address notorious safety issues associated with liquid electrolytes used in the current Na ion batteries. Fulfilling multiple innovations is a grand challenge but is imperative for advanced Na ion SSEs, such as a combination of high ionic conductivity and excellent chemical stability. Here, our first-principles and phonon calculations reveal that Na3P1-xAsxS4 (0 ≤ x ≤ 1) is a solid-state superionic conductor stabilized at 0 K by zero-point vibrational energy and at finite temperatures by vibrational and configurational entropies. Especially, our integrated first-principles and experimental approach indicates that Na3P1-xAsxS4 is dry-air stable. Additionally, the alloying element arsenic greatly enhances the moisture (i.e., H2O) stability of Na3P1-xAsxS4 by shifting the reaction products from the easy-forming oxysulfides (such as Na3POS3 and Na3PO2S2 with H2S release) to the difficult-forming hydrates (such as Na3P1-xAsxS4·nH2O with n = 8 and/or 9) due mainly to a weaker As-O affinity compared to that of P-O. The present work demonstrates that alloying is able to achieve multiple innovations for solid-state electrolytes, such as a desirable superionic conductor with not only a high ionic conductivity (for example, 1.46 mS/cm at room temperature achieved in Na3P0.62As0.38S4) but also an excellent chemical stability with respect to temperature, composition, and moisture.

  1. The spectrum of optically allowed transitions from the 3p63d ground state of Ti IV

    NASA Astrophysics Data System (ADS)

    Kingston, A. E.; Hibbert, A.

    2006-05-01

    Recent experiments on the photoionization of Ti IV (Schippers S et al 2004 J. Phys. B: At. Mol. Opt. Phys. 37 L209-16) and the photorecombination of Ti V (Schippers S et al 1998 J. Phys. B: At. Mol. Opt. Phys. 31 4873-86) have obtained the excitation energies and spontaneous transition probabilities (A-values) for a number of the 3p53d2 and 3p53d4s autoionization states of Ti IV. The direct measurements of the spectrum of Ti IV excited in a vacuum spark (Ryabtsev A N et al 2005 Opt. Spectrosc. 98 519-27) have provided a more complete list of these excitation energies and the A-values for J-J transitions of these excited states to the 3p63d ground state. This paper presents ab initio calculations for the transition energies and A-values between individual J levels of the ground state of Ti IV and the J levels for both the bound (3d)6nl states and the bound and resonance states 3p53d2 and 3p53d4s. The calculations were carried with configuration interaction wavefunctions and relativistic effects were included using the Breit-Pauli approximation. Generally there is good agreement between the calculated transition energies and all the experimental transition energies. There are considerable differences between the A-values obtained by the different experimental groups and the agreement between the theoretical and experimental A-values is variable.

  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. Carbon source-dependent alteration of Puf3p activity mediates rapid changes in the stabilities of mRNAs involved in mitochondrial function.

    PubMed

    Miller, Melanie A; Russo, Joseph; Fischer, Anthony D; Lopez Leban, Florencia A; Olivas, Wendy M

    2014-04-01

    The Puf family of RNA-binding proteins regulates gene expression primarily by interacting with the 3' untranslated region (3' UTR) of targeted mRNAs and inhibiting translation and/or stimulating decay. Physical association and computational analyses of yeast Puf3p identified >150 potential mRNA targets involved in mitochondrial function. However, only COX17 has been established as a target of Puf3p-mediated deadenylation and decapping. We have identified 10 new targets that are rapidly degraded in a Puf3p-dependent manner. We also observed changes in Puf3p activity in response to environmental conditions. Puf3p promotes rapid degradation of mRNA targets in the fermentable carbon source dextrose. However, Puf3p-mediated decay activity is inhibited in carbon sources that require mitochondrial function for efficient cell growth. In addition, the activity of Puf3p is rapidly altered by changing the carbon source. PUF3 expression is not decreased at the RNA or protein level by different carbon sources and localization is not significantly altered, suggesting that Puf3p activity is regulated posttranslationally. Finally, under conditions when Puf3p is unable to stimulate decay, Puf3p can still bind its target mRNAs. Together, these experiments provide insight into the carbon source-specific control of Puf3p activity and how such alterations allow Puf3p to dynamically regulate mitochondrial function.

  4. BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71.

    PubMed

    Velu, Arul Balaji; Chen, Guang-Wu; Hsieh, Po-Ting; Horng, Jim-Tong; Hsu, John Tsu-An; Hsieh, Hsing-Pang; Chen, Tzu-Chun; Weng, Kuo-Feng; Shih, Shin-Ru

    2014-12-01

    Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease with severe neurological complications. Because no clinical drug is available for treating EV71 infections, developing an efficient antiviral medication against EV71 infection is crucial. This study indicated that 6-bromo-2-[1-(2,5-dimethylphenyl)-5-methyl-1H-pyrazol-4-yl] quinoline-4-carboxylic acid (BPR-3P0128) exhibits excellent antiviral activity against EV71 (EC50 = 0.0029 μM). BPR-3P0128 inhibits viral replication during the early post infection stage, targets EV71 RNA-dependent RNA polymerase and VPg uridylylation, and also reduces viral RNA accumulation levels and inhibits viral replication of EV71. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 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

  6. Wakefield Simulation of CLIC PETS Structure Using Parallel 3D Finite Element Time-Domain Solver T3P

    SciTech Connect

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

    2009-06-19

    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).

  7. Development of MAG3 p-nitrophenyl ester for technetium-99m and rhenium-188 labeling of amines and peptides

    SciTech Connect

    Guhlke, S.; Diekmann, D.; Biersack, H.J.

    1994-09-01

    Conjugate labeling by active ester chemistry is a well-established method for labeling peptides and proteins with technetium and rhenium. The easy preparation and high conjugations yields presented in this paper show that both {sup 188}Re and {sup 99m}Tc-MAG{sub 3} p-nitrophenyl esters are promising agents for labeling a wide range of biomolecules for radio therapy or diagnostic imaging.

  8. Hst3p, a histone deacetylase, promotes maintenance of Saccharomyces cerevisiae chromosome III lacking efficient replication origins.

    PubMed

    Irene, Carmela; Theis, James F; Gresham, David; Soteropoulos, Patricia; Newlon, Carol S

    2016-02-01

    Long gaps between active replication origins probably occur frequently during chromosome replication, but little is known about how cells cope with them. To address this issue, we deleted replication origins from S. cerevisiae chromosome III to create chromosomes with long interorigin gaps and identified mutations that destabilize them [originless fragment maintenance (Ofm) mutations]. ofm6-1 is an allele of HST3, a sirtuin that deacetylates histone H3K56Ac. Hst3p and Hst4p are closely related, but hst4Δ does not cause an Ofm phenotype. Expressing HST4 under the control of the HST3 promoter suppressed the Ofm phenotype of hst3Δ, indicating Hst4p, when expressed at the appropriate levels and/or at the correct time, can fully substitute for Hst3p in maintenance of ORIΔ chromosomes. H3K56Ac is the Hst3p substrate critical for chromosome maintenance. H3K56Ac-containing nucleosomes are preferentially assembled into chromatin behind replication forks. Deletion of the H3K56 acetylase and downstream chromatin assembly factors suppressed the Ofm phenotype of hst3, indicating that persistence of H3K56Ac-containing chromatin is deleterious for the maintenance of ORIΔ chromosomes, and experiments with synchronous cultures showed that it is replication of H3K56Ac-containing chromatin that causes chromosome loss. This work shows that while normal chromosomes can tolerate hyperacetylation of H3K56Ac, deacetylation of histone H3K56Ac by Hst3p is required for stable maintenance of a chromosome with a long interorigin gap. The Ofm phenotype is the first report of a chromosome instability phenotype of an hst3 single mutant.

  9. 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

  10. 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.

  11. 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.

  12. Strong coupling superconductivity at 8.4 K in an antiperovskite phosphide SrPt3P.

    PubMed

    Takayama, T; Kuwano, K; Hirai, D; Katsura, Y; Yamamoto, A; Takagi, H

    2012-06-08

    We report the discovery of a family of ternary platinum phosphides APt3P (A = Ca, Sr, and La), which crystallize in an antiperovskite-based structure closely related to that of the heavy fermion superconductor CePt3Si. All three phosphides showed superconductivity at low temperatures and the highest critical temperature T(c) = 8.4  K was observed for SrPt3P. The analysis of specific heat C(T) for SrPt3P shows clear evidence for very strong coupling s-wave superconductivity with a large ratio between superconducting gap Δ0 and T(c), 2Δ0/k(B)T(c) ∼ 5, and the presence of low-energy phonons. The presence of multiple Fermi surface pockets was inferred from the nonlinear magnetic field dependence of Hall resistivity, which we argue might play a role in realizing the strong coupling of charge carriers with the low-lying phonons.

  13. Synthesis, structure, chemical doping and high pressure studies of the SrPt3 P with unique structure features

    NASA Astrophysics Data System (ADS)

    Jawdat, Benmaan; Lv, Bing; Zhu, Xiyu; Xue, Yuyi; Chu, Ching

    2013-03-01

    Superconductivity up to 8.4K was reported by Takayama et al.[3] in APt3P (A =Sr, Ca and La) in 2012 with structural information based only on X-ray powder refinement. The compounds are suggested to crystallize in an antiperovskite-based structure closely related to that of the heavy fermion superconductor CePt3Si but are nonpolar unlike CePt3Si. Both small single crystals and polycrystalline samples of SrPt3P, the compound with the highest Tc of this class of materials, are synthesized through solid state reactions. In this presentation, full and detailed structural information will be revealed based on X-ray single crystal analysis. Different chemical doping on different sites and high pressure studies have been carried out on the compound of SrPt3P. The results and its implication will be presented and discussed. Research at Houston is supported in part by US AFOSR, the State of Texas, T.L.L. Temple Foundation and John and Rebecca Moores Endowment.

  14. 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

  15. DEG1, encoding the tRNA:pseudouridine synthase Pus3p, impacts HOT1-stimulated recombination in Saccharomyces cerevisiae.

    PubMed

    Hepfer, C E; Arnold-Croop, S; Fogell, H; Steudel, K G; Moon, M; Roff, A; Zaikoski, S; Rickman, A; Komsisky, K; Harbaugh, D L; Lang, G I; Keil, R L

    2005-12-01

    In Saccharomyces cerevisiae, HOT1-stimulated recombination has been implicated in maintaining homology between repeated ribosomal RNA genes. The ability of HOT1 to stimulate genetic exchange requires RNA polymerase I transcription across the recombining sequences. The trans-acting nuclear mutation hrm3-1 specifically reduces HOT1-dependent recombination and prevents cell growth at 37 degrees . The HRM3 gene is identical to DEG1. Excisive, but not gene replacement, recombination is reduced in HOT1-adjacent sequences in deg1Delta mutants. Excisive recombination within the genomic rDNA repeats is also decreased. The hypo-recombination and temperature-sensitive phenotypes of deg1Delta mutants are recessive. Deletion of DEG1 did not affect the rate of transcription from HOT1 or rDNA suggesting that while transcription is necessary it is not sufficient for HOT1 activity. Pseudouridine synthase 3 (Pus3p), the DEG1 gene product, modifies the anticodon arm of transfer RNA at positions 38 and 39 by catalyzing the conversion of uridine to pseudouridine. Cells deficient in pseudouridine synthases encoded by PUS1, PUS2 or PUS4 displayed no recombination defects, indicating that Pus3p plays a specific role in HOT1 activity. Pus3p is unique in its ability to modulate frameshifting and readthrough events during translation, and this aspect of its activity may be responsible for HOT1 recombination phenotypes observed in deg1 mutants.

  16. 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.

  17. Drosophila Mtm and class II PI3K coregulate a PI(3)P pool with cortical and endolysosomal functions

    PubMed Central

    Velichkova, Michaella; Juan, Joe; Kadandale, Pavan; Jean, Steve; Ribeiro, Inês; Raman, Vignesh; Stefan, Chris

    2010-01-01

    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. PMID:20696708

  18. Dynamics of the O(3P,1D) + SiH4 reaction: A trajectory surface hopping study

    NASA Astrophysics Data System (ADS)

    Ghosh, Subhendu; Mandal, Mrinmoy; Maiti, Biswajit

    2017-12-01

    A quasiclassical trajectory surface hopping (TSH) method is employed to study the O(3P,1D) + SiH4 reaction with special emphasis on the contribution of nonadiabatic path in the formation of various products. Tully's fewest switches algorithm is used to compute nonadiabatic transitions. Our calculation showed that while the H formation is the most important channel for the O(3P) reaction with SiH4, the OH formation is the dominating channel for the O(1D) reaction, at an initial collision energy of 8 kcal/mol. Comparison with a recent crossed molecular beam experiment shows qualitative agreement so as to primary product branching ratios, except for the formation of H2O from the O(1D) reaction that was not detected experimentally. In addition our calculation revealed a major contribution (∼50%) of the H3SiO + H channel from the O(3P) + SiH4 reaction through an addition complex H4SiO intermediate which was also not explored, experimentally.

  19. Genetic characterization of a novel G3P[14] rotavirus strain causing gastroenteritis in 12 year old Australian child.

    PubMed

    Donato, Celeste M; Manuelpillai, Nicholas M; Cowley, Daniel; Roczo-Farkas, Susie; Buttery, Jim P; Crawford, Nigel W; Kirkwood, Carl D

    2014-07-01

    A genotype G3P[14] rotavirus strain was identified in a 12year old child presenting to the Emergency Department of the Royal Children's Hospital, Melbourne, with gastroenteritis. G3P[14] strains have been previously identified in rabbits in Japan, China, the USA and Italy and a single lapine-like strain from a child in Belgium. Full genome sequence analysis of RVA/Human-wt/AUS/RCH272/2012/G3P[14] (RCH272) revealed that the strain contained the novel genome constellation G3-P[14]-I2-R3-C3-M3-A9-N2-T6-E2-H3. The genome was genetically divergent to previously characterized lapine viruses and the genes were distantly related to a range of human bovine-like strains and animal strains of bovine, bat and canine/feline characteristics. The VP4, VP6, NSP2, NSP3, NSP4 and NSP5 genes of RCH272 clustered within bovine lineages in the phylogenetic analysis and shared moderate genetic similarity with an Australian bovine-like human strain RVA/Human-tc/AUS/MG6/1993/G6P[14]. Bayesian coalescent analysis suggested these genes of RCH272 and RVA/Human-tc/AUS/MG6/1993/G6P[14] were derived from a population of relatively homogenous bovine-like ancestral strains circulating between 1943 and 1989. The VP7, VP1, VP2 and NSP1 genes shared moderate genetic similarity with the Chinese strain RVA/Bat-tc/CHN/MSLH14/2011/G3P[3] and the VP3 gene clustered within a lineage comprised of canine and feline strains. This strain may represent the direct transmission from an unknown host species or be derived via multiple reassortment events between strains originating from various species. The patient lived in a household containing domesticated cats and dogs and in close proximity to a colony of Gray-headed Flying-foxes. However, without screening numerous animal populations it is not possible to determine the origins of this strain. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Large-Scale CI (3P1-- 3P0) and CO (J=3--2) Observations of the W51 Complex Region with the Mt. Fuji Submillimeter-Wave Telescope

    NASA Astrophysics Data System (ADS)

    Arikawa, Y.; Tatematsu, K.; Sekimoto, Y.; Aso, Y.; Noguchi, T.; Shi, S. C.; Miyazawa, K.; Yamamoto, S.; Ikeda, M.; Maezawa, T.; Ito, T.; Saito, G.; Saito, S.; Ozeki, H.; Fujiwara, H.; Inatani, J.; Ohishi, M.

    1999-12-01

    We report mapping observations of CO (J=3-2) at 345.796 GHz and CI (3P1-3P0) at 492.161 GHz toward the W51 complex region using Mt. Fuji submillimeter-wave telescope. The mapped region is a {80' x 80'} area covering W51A, W51B, and W51C (SNR). The distribution of the CI emission is similar to that of the CO emission. The intensity map integrated over velocity from VLSR = 45 km s-1 to 55 km s-1 shows two intensity maxima, which coincide with two compact HII regions in W51A (G49.5-0.4 and G49.4-0.3). The intensity map integated over velocity from VLSR = 65 km s-1 to 72 km s-1 shows a molecular cloud elongated along W51A and W51B, which contains three clumps (one in W51A, the others in W51B). One of these clumps is associated with the non-thermal emission and an OH (1720 MHz) maser, and the interaction of SNR with the molecular cloud. The CI/CO integrated intensity ratio is 0.3-0.4 in W51A and W51B (HII region), while > 0.6 in W51B (OH maser). This result might imply that the interaction of SNR with the molecular cloud enhances the CI abundance.

  1. Genomewide Genetic Linkage Analysis Confirms the Presence of Susceptibility Loci for Schizophrenia, on Chromosomes 1q32.2, 5q33.2, and 8p21-22 and Provides Support for Linkage to Schizophrenia, on Chromosomes 11q23.3-24 and 20q12.1-11.23

    PubMed Central

    Gurling, Hugh M. D.; Kalsi, Gursharan; Brynjolfson, Jon; Sigmundsson, Thordur; Sherrington, Robin; Mankoo, Baljinder S.; Read, Timothy; Murphy, Patrice; Blaveri, Ekaterina; McQuillin, Andrew; Petursson, Hannes; Curtis, David

    2001-01-01

    We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at ∼10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia. PMID:11179014

  2. 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.

  3. Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade

    PubMed Central

    Ma, Jianhui; Meng, Yan; Kwiatkowski, David J.; Chen, Xinxin; Peng, Haiyong; Sun, Qian; Zha, Xiaojun; Wang, Fang; Wang, Ying; Jing, Yanling; Zhang, Shu; Chen, Rongrong; Wang, Lianmei; Wu, Erxi; Cai, Guifang; Malinowska-Kolodziej, Izabela; Liao, Qi; Liu, Yuqin; Zhao, Yi; Sun, Qiang; Xu, Kaifeng; Dai, Jianwu; Han, Jiahuai; Wu, Lizi; Zhao, Robert Chunhua; Shen, Huangxuan; Zhang, Hongbing

    2009-01-01

    The receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) pathway is frequently altered in cancer, but the underlying mechanism leading to tumorigenesis by activated mTOR remains less clear. Here we show that mTOR is a positive regulator of Notch signaling in mouse and human cells, acting through induction of the STAT3/p63/Jagged signaling cascade. Furthermore, in response to differential cues from mTOR, we found that Notch served as a molecular switch to shift the balance between cell proliferation and differentiation. We determined that hyperactive mTOR signaling impaired cell differentiation of murine embryonic fibroblasts via potentiation of Notch signaling. Elevated mTOR signaling strongly correlated with enhanced Notch signaling in poorly differentiated but not in well-differentiated human breast cancers. Both human lung lymphangioleiomyomatosis (LAM) and mouse kidney tumors with hyperactive mTOR due to tumor suppressor TSC1 or TSC2 deficiency exhibited enhanced STAT3/p63/Notch signaling. Furthermore, tumorigenic potential of cells with uncontrolled mTOR signaling was suppressed by Notch inhibition. Our data therefore suggest that perturbation of cell differentiation by augmented Notch signaling might be responsible for the underdifferentiated phenotype displayed by certain tumors with an aberrantly activated RTK/PI3K/AKT/mTOR pathway. Additionally, the STAT3/p63/Notch axis may be a useful target for the treatment of cancers exhibiting hyperactive mTOR signaling. PMID:20038814

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

    PubMed

    Köhler, Sven P K; Allan, Mhairi; Kelso, Hailey; Henderson, David A; McKendrick, Kenneth G

    2005-01-08

    OH/OD product state distributions arising from the reaction of gas-phase O(3P) atoms at the surface of the liquid hydrocarbon squalane C30H62/C30D62 have been measured. The O(3P) atoms were generated by 355 nm laser photolysis of NO2 at a low pressure above the continually refreshed liquid. It has been shown unambiguously that the hydroxyl radicals detected by laser-induced fluorescence originate from the squalane surface. The gas-phase OH/OD rotational populations are found to be partially sensitive to the liquid temperature, but do not adapt to it completely. In addition, rotational temperatures for OH/OD(v'=1) are consistently colder (by 34+/-5 K) than those for OH/OD(v'=0). This is reminiscent of, but less pronounced than, a similar effect in the well-studied homogeneous gas-phase reaction of O(3P) with smaller hydrocarbons. We conclude that the rotational distributions are composed of two different components. One originates from a direct abstraction mechanism with product characteristics similar to those in the gas phase. The other is a trapping-desorption process yielding a thermal, Boltzmann-like distribution close to the surface temperature. This conclusion is consistent with that reached previously from independent measurements of OH product velocity distributions in complementary molecular-beam scattering experiments. It is further supported by the temporal profiles of OH/OD laser-induced fluorescence signals as a function of distance from the surface observed in the current experiments. The vibrational branching ratios for (v'=1)/(v'=0) for OH and OD have been found to be (0.07+/-0.02) and (0.30+/-0.10), respectively. The detection of vibrationally excited hydroxyl radicals suggests that secondary and/or tertiary hydrogen atoms may be accessible to the attacking oxygen atoms. 2005 American Institute of Physics.

  5. 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.

  6. Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer.

    PubMed

    Lando, Malin; Fjeldbo, Christina S; Wilting, Saskia M; C Snoek, Barbara; Aarnes, Eva-Katrine; Forsberg, Malin F; Kristensen, Gunnar B; Steenbergen, Renske Dm; Lyng, Heidi

    2015-01-01

    Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n = 149, n = 121), using Illumina 450K methylation arrays. The aim was to investigate whether hyperm-ethylation was frequent and could contribute to gene silencing and disease aggressiveness either alone or combined with loss. By comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue, 26 out of 41 genes were found to be hypermethylated in both cohorts. The frequency of patients with hypermethylation of these genes was found to be higher at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were transcriptionally downregulated in cancer compared to normal tissue, whereof 6 genes showed a significant correlation between methylation and expression. Integrated analysis of methylation, gene dosage, and expression of the 26 hypermethylated genes identified 3 regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern (C3orf14, GPR27, ZNF717), a gene dosage driven pattern (THOC7, PSMD6), and a combined methylation and gene dosage driven pattern (FHIT, ADAMTS9, LRIG1). In survival analysis, patients with both hypermethylation and loss of LRIG1 had a worse outcome compared to those harboring only hypermethylation or none of the events. C3orf14 emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may exert a selection pressure during carcinogenesis alone or combined with loss. Information on both events could lead to improved

  7. ARTICLE Influence of Vibrational Excitation on Stereodynamics for O(3P)+D2→OD+D Reaction

    NASA Astrophysics Data System (ADS)

    Liu, Shi-li; Shi, Ying

    2010-12-01

    Theoretical investigations on the stereodynamics of the O(3P)+D2 reaction have been calculated by means of the quasi-classical trajectory to study the product rotational polarization at collision energy of 104.5 kJ/mol on the potential energy surface of the ground 3A″ triplet state. The vector properties including angular momentum alignment distributions and four polarization dependent generalized differential cross-sections of product have been presented. Furthermore, the influence of reagent vibrational excitation on the product vector properties has also been studied. The results indicate that the vector properties are sensitively affected by reagent vibrational excitation.

  8. Crossed-Beams and Theoretical Studies of Hyperthermal Reactions of O(3P) with HCl and H2O

    NASA Astrophysics Data System (ADS)

    Zhang, Jianming; Brunsvold, Amy L.; Upadhyaya, Hari P.; Minton, Timothy K.; Camden, Jon P.; Paci, Jeffrey T.; Schatz, George C.

    2011-05-01

    The reactions of O(3P) with HCl and H2O at hyperthermal collision energies (45-116 kcal mol-1) have been investigated with crossed-molecular beams experiments and direct dynamics quasiclassical trajectory calculations. Both reactive systems may proceed by two analogous primary pathways, (1) H-atom abstraction to produce OH and either Cl or OH and (2) H-atom elimination to produce H and either ClO or HO2. The H-atom elimination reactions are highly endoergic, and they have been observed experimentally for the first time. The H-atom abstraction reaction follows a stripping mechanism, in which the reagent O atom approaches the target molecule at large impact parameters and the OH product is scattered in the forward direction with respect to the initial direction of the reagent O atom. The H-atom elimination reaction requires low impact parameter collisions. The excitation function for ClO or HO2 increases from threshold to a maximum around 115 kcal mol-1 and then begins to decrease when the product can be formed with sufficient internal energy to undergo secondary dissociation. At collision energies slightly above threshold for H-atom elimination, the ClO or HO2 product scatters primarily in the backward direction, but as the collision energy increases, the fraction of these products that scatter in the forward and sideways directions increases. The dependence of the angular distribution of ClO or HO2 on collision energy is a result of the fact that only certain trajectories, where an H atom on the target molecule is oriented toward the incoming reagent O atom, can release enough energy in translation to lead to stable ClO or HO2 at higher collision energies. These trajectories lead to forward and sideways scattering of ClO or HO2. Moreover, these trajectories do not follow the minimum path and involve larger translational energy release. Therefore, they become dominant at higher collision energies because they lead to lower internal energies and more stable ClO or HO

  9. MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6

    SciTech Connect

    Sun, Chengcao; Li, Shujun; Yang, Cuili; Xi, Yongyong; Wang, Liang; Zhang, Feng; Li, Dejia

    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 of 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.

  10. Manganese toxicity and Saccharomyces cerevisiae Mam3p, a member of the ACDP (ancient conserved domain protein) family.

    PubMed

    Yang, Mei; Jensen, Laran T; Gardner, Allison J; Culotta, Valeria C

    2005-03-15

    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.

  11. Elevated Circulating miR-150 and miR-342-3p in Patients with Irritable Bowel Syndrome

    PubMed Central

    Fourie, Nicolaas H.; Peace, Ralph Michael; Abey, Sarah K.; Sherwin, LeeAnne B.; Rahim-Williams, Bridgett; Smyser, Paul A.; Wiley, John W.; Henderson, Wendy A.

    2014-01-01

    Background and Aims MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression and are thus of interest as diagnostic markers, and as clues to etiology and targets of intervention. This pilot study examined whether circulating miRNAs are differentially expressed in patients with IBS. Methods miRNA microarrays (Nanostring) were run on the whole blood of 43 participants. Results hsa-miR-150 and hsa-miR-342-3p were found to be significantly elevated (FDR adjusted p ≤ 0.05, ≥1.6 fold change) in IBS patients compared to healthy controls. Neither of these miRNAs showed any relationship to race or sex. hsa-miR-150 is associated with inflammatory bowel disorders and pain, and interacts with a protein kinase (AKT2) through which it may affect inflammatory pathways. hsa-miR-342-3p is predicted to interact with mRNAs involved in pain signaling, colonic motility, and smooth muscle function. Conclusions This preliminary study reports the association of two miRNAs, detected in whole blood, with IBS. These miRNAs link to pain and inflammatory pathways both of which are thought to be dysregulated in IBS. Larger samples sizes are needed to confirm their importance and potential as biomarkers. PMID:24768587

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

    SciTech Connect

    Huff, W.R.A.; Moler, E.J.; Kellar, S.A.

    1997-04-01

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

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

    PubMed

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

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10-30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased ( p < 0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.

  14. 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.

  15. MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma

    SciTech Connect

    Wang, Xinsheng; Jiang, Fuquan; Song, Haitao

    2016-02-12

    Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renalmore » cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC. - Highlights: • MiR-200a-3p is downregulated in renal cell carcinoma. • MiR-200a-3p regulates cell proliferation through inducing apoptosis. • MiR-200a-3p is involved in cell cycle regulation. • SPAG9 is a potential target of miR-200a-3p.« less

  16. MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma

    SciTech Connect

    Wang, Xinsheng; Jiang, Fuquan; Song, Haitao; Li, Xu; Xian, Jiantao; Gu, Xinquan

    2016-02-12

    Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC. - Highlights: • MiR-200a-3p is downregulated in renal cell carcinoma. • MiR-200a-3p regulates cell proliferation through inducing apoptosis. • MiR-200a-3p is involved in cell cycle regulation. • SPAG9 is a potential target of miR-200a-3p.

  17. Determination of transition probabilities for the 3p → 3s transition array in neon using laser induced breakdown spectroscopy

    SciTech Connect

    Asghar, Haroon; Ali, Raheel; Baig, M. Aslam

    2013-12-15

    We present here a study of the optical emission spectra of the laser produced neon plasma generated by a Nd:YAG laser at 1064 nm. The spectra were recorded using the laser induced breakdown spectroscopy 2000 detection system comprising of five spectrometers covering the entire visible region. The observed spectra yield all the optically allowed transitions between the 2p{sup 5}3p upper and 2p{sup 5}3s lower configurations based levels. The relative line strengths of all the dipole allowed transitions have been determined using the intensity ratios and compared with the J-file sum rule. The absolute transition probabilities have been calculated by usingmore » the lifetimes of the upper levels and the intensities of the observed spectral lines and show good agreement with the literature values.« less

  18. Determination of transition probabilities for the 3p → 3s transition array in neon using laser induced breakdown spectroscopy

    SciTech Connect

    Asghar, Haroon; Ali, Raheel; Baig, M. Aslam

    2013-12-15

    We present here a study of the optical emission spectra of the laser produced neon plasma generated by a Nd:YAG laser at 1064 nm. The spectra were recorded using the laser induced breakdown spectroscopy 2000 detection system comprising of five spectrometers covering the entire visible region. The observed spectra yield all the optically allowed transitions between the 2p{sup 5}3p upper and 2p{sup 5}3s lower configurations based levels. The relative line strengths of all the dipole allowed transitions have been determined using the intensity ratios and compared with the J-file sum rule. The absolute transition probabilities have been calculated by using the lifetimes of the upper levels and the intensities of the observed spectral lines and show good agreement with the literature values.

  19. 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.

  20. Measurement of Hadronically Produced $^3P$ State Charmonium at $\\sqrt{s}$ = 23.7-GeV

    SciTech Connect

    Tesarek, Richard James

    1993-01-01

    Fermilab experiment E705 measured the inclusive production ratio for the two higher mass $1^3 P_1$ charmonium states, $\\sigma_{x1} / \\sigma_{ x2}$, for 300 GeV /c proton and ,$\\pi^{\\pm}$ beams interacting with a lithium target. Our measured ratios of $0.08^{+0.25}_{-0.15}$ and $0.52^{+0.52}_{-0.28}$ for proton a.nd pion induced reactions, respectively, show good agreement with previous experiments. The production ratio for proton data is consistant with a gluon fusion model for p-wave charmonium, while the pion ratio could be represented by a strict color evaporation model or an admixture of different mechanisms.

  1. Unusual mechanisms can dominate reactions at hyperthermal energies: an example from O(3P) + HCl --> ClO + H.

    PubMed

    Zhang, Jianming; Camden, Jon P; Brunsvold, Amy L; Upadhyaya, Hari P; Minton, Timothy K; Schatz, George C

    2008-07-16

    An unusual mechanism in the reaction, O(3P) + HCl --> ClO + H, dominates at hyperthermal collision energies. This mechanism applies to collision geometries in which the H atom in the HCl molecule is oriented toward the reagent O atom. As the Cl-O bond forms, the H atom experiences a strong repulsive force from both the O and Cl atoms. The ClO product scatters forward with respect to the initial velocity of the O atom, and the H atom scatters backward. This mechanism accounts for more than half the reactive trajectories at energies >110 kcal mol-1, but it does not involve motion near the minimum energy path, which favors an SN2-like reaction mechanism where the H atom is oriented away from the reagent O atom during the collision.

  2. 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.

  3. 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.

  4. Direct dynamics investigation of the reaction S(3P) + CH4 → CH3 + SH(2Π)

    NASA Astrophysics Data System (ADS)

    Alves, Tiago Vinicius; Alves, Marcel Martins; Roberto-Neto, Orlando; Ornellas, Fernando R.

    2014-01-01

    Geometries, frequencies, and energies of the hydrogen abstraction reaction S(3P) + CH4 were computed using DFT methods, coupled-cluster theory, various basis sets, and an extrapolation scheme to assess the complete basis set limit (CBS) energies. The M05-2X/MG3S approach gives values of the classical barrier height (28.3 kcal mol-1) and reaction energy (23.9 kcal mol-1) in good agreement with the CCSD(T)/CBSD-Q results, i.e., 30.2 and 24.7 cal mol-1, respectively. At the range of 1140-1480 K, the VTST thermal rate constants are in agreement with experiment and, in general, the ratio between experimental and the CVT/SCT values varies from 1.9 to 1.3.

  5. 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 an