Computational analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations.

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Chih-Chieh Chen

Full Text Available BACKGROUND: The issue of whether patients diagnosed with metastatic colorectal cancer who harbor KRAS codon 13 mutations could benefit from the addition of anti-epidermal growth factor receptor therapy remains under debate. The aim of the current study was to perform computational analysis to investigate the structural implications of the underlying mutations caused by c.38G>A (p.G13D on protein conformation. METHODS: Molecular dynamics (MD simulations were performed to understand the plausible structural and dynamical implications caused by c.35G>A (p.G12D and c.38G>A (p.G13D. The potential of mean force (PMF simulations were carried out to determine the free energy profiles of the binding processes of GTP interacting with wild-type (WT KRAS and its mutants (MT. RESULTS: Using MD simulations, we observed that the root mean square deviation (RMSD increased as a function of time for the MT c.35G>A (p.G12D and MT c.38G>A (p.G13D when compared with the WT. We also observed that the GTP-binding pocket in the c.35G>A (p.G12D mutant is more open than that of the WT and the c.38G>A (p.G13D proteins. Intriguingly, the analysis of atomic fluctuations and free energy profiles revealed that the mutation of c.35G>A (p.G12D may induce additional fluctuations in the sensitive sites (P-loop, switch I and II regions. Such fluctuations may promote instability in these protein regions and hamper GTP binding. CONCLUSIONS: Taken together with the results obtained from MD and PMF simulations, the present findings implicate fluctuations at the sensitive sites (P-loop, switch I and II regions. Our findings revealed that KRAS mutations in codon 13 have similar behavior as KRAS WT. To gain a better insight into why patients with metastatic colorectal cancer (mCRC and the KRAS c.38G>A (p.G13D mutation appear to benefit from anti-EGFR therapy, the role of the KRAS c.38G>A (p.G13D mutation in mCRC needs to be further investigated.

A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1.

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Stevens, Servi J C; Blom, Eveline W; Siegelaer, Ingrid T J; Smeets, Eric E J G L

2015-04-01

We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10 Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.

Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism

DEFF Research Database (Denmark)

Litjens, Nicolle H R; van der Plas, Mariena J A; Ravensbergen, Bep

2004-01-01

Psoriasis is a type-1 T cell-mediated, chronic inflammatory disease. Since interleukin (IL)-12p70 promotes the development of type-1 T cells, we investigated whether psoriasis is associated with an increased production of this cyctokine by blood cells. Results revealed that the production of IL-12p....... The frequencies of the various genotypes for the promoter region of the gene encoding IL-12p40 (IL12B) did not differ between psoriasis patients and controls. No association was observed between the various IL12B promoter genotypes and the LPS-stimulated production of IL-12p70 or IL-12p40 by blood cells. Together......, psoriasis is not associated with a promoter polymorphism in the IL12B gene nor with the production of IL-12p70 by LPS-stimulated blood cells....

Identification of endogenous surrogate ligands for human P2Y12 receptors by in silico and in vitro methods

International Nuclear Information System (INIS)

Nonaka, Yosuke; Hiramoto, Takeshi; Fujita, Norihisa

2005-01-01

Endogenous ligands acting on a human P2Y 12 receptor, one of the G-protein coupled receptors, were searched by in silico screening against our own database, which contains more than 500 animal metabolites. The in silico screening using the docking software AutoDock resulted in selection of cysteinylleukotrienes (CysLTs) and 5-phosphoribosyl 1-pyrophosphate (PRPP), with high free energy changes, in addition to the known P2Y 12 ligands such as 2MeSADP and ADP. These candidates were subjected to an in vitro Ca 2+ assay using the CHO cells stably expressing P2Y 12 -G 16 α fusion proteins. We found that CysLTE4 and PRPP acted on the P2Y 12 receptor as agonists with the EC 50 values of 1.3 and 7.8 nM, respectively. Furthermore, we analyzed the phylogenetic relationship of the P2Y, P2Y-like, and CysLT receptors based on sequence alignment followed by evolutionary analyses. The analyses showed that the P2Y 12 , P2Y 13 , P2Y 14 , GPR87, CysLT-1, and CysLT-2 receptors formed a P2Y-related receptor subfamily with common sequence motifs in the transmembrane regions

Chromosome r(10(p15.3q26.12 in a newborn child: case report

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Jonasson Jon

2009-12-01

Full Text Available Abstract Background Ring chromosome 10 is a rare cytogenetic finding. Of the less than 10 reported cases we have found in the literature, none was characterized using high-resolution microarray analysis. Ring chromosomes are frequently unstable due to sister chromatid exchanges and mitotic failures. When mosaicism is present, the interpretation of genotype-phenotype correlations becomes extremely difficult. Results We report on a newborn girl with growth retardation, microcephaly, congenital heart defects, dysmorphic features and psychomotor retardation. Karyotyping revealed a non-mosaic apparently stable ring chromosome 10 replacing one of the normal homologues in all analyzed metaphases. High-resolution oligonucleotide microarray analysis showed a de novo approximately 12.5 Mb terminal deletion 10q26.12 -> qter and a corresponding 285 kb terminal deletion of 10pter -> p15.3. Conclusion This case demonstrates that an increased nuchal translucency thickness detected by early ultrasonography should preferably lead to not only QF-PCR for the diagnosis of Down syndrome but also karyotyping. In the future, microarray analysis, which needs further evaluation, might become the method of choice. The clinical phenotype of our patient was in agreement with that of patients with a terminal 10q deletion. For the purpose of genotype-phenotype analysis, there seems to be no need for a "ring syndrome" concept.

Specific heat of filled skutterudite PrOs4P12

International Nuclear Information System (INIS)

Matsuhira, Kazuyuki; Doi, Yoshihiro; Wakeshima, Makoto; Hinatsu, Yukio; Kihou, Kunihiro; Sekine, Chihiro; Shirotani, Ichimin

2005-01-01

We report the specific heat of filled skutterudite compounds PrOs 4 P 12 and LaOs 4 P 12 down to 1.8K. The specific heat divided by temperature C(T)/T in PrOs 4 P 12 shows a shoulder around 13K. This shoulder is caused by a Schottky anomaly due to a crystalline electric field effect. The electronic specific heat coefficients γ of PrOs 4 P 12 and LaOs 4 P 12 are estimated to be 56.5 and 21.6mJ/K 2 mol, respectively. The value of γ in PrOs 4 P 12 is 2.6 times larger than that in LaOs 4 P 12

Not para-, not peri-, but centric inversion of chromosome 12

DEFF Research Database (Denmark)

Silahtaroglu, A N; Hacihanefioglu, S; Güven, G S

1998-01-01

a break in the alphoid repeats followed by an inversion within the short arm, resulting in a pseudodicentric chromosome. Further FISH analyses using telomeric and subtelomeric probes showed that the other breakpoint was in the subtelomeric region of the short arm. The karyotype is designated 47,XXY,inv(12......)(p10p13.3). To our knowledge this is the first report of a case of "centric inversion"....

Sequence Ready Characterization of the Pericentromeric Region of 19p12

Energy Technology Data Exchange (ETDEWEB)

Evan E. Eichler

2006-08-31

Current mapping and sequencing strategies have been inadequate within the proximal portion of 19p12 due, in part, to the presence of a recently expanded ZNF (zinc-finger) gene family and the presence of large (25-50 kb) inverted beta-satellite repeat structures which bracket this tandemly duplicated gene family. The virtual of absence of classically defined “unique” sequence within the region has hampered efforts to identify and characterize a suitable minimal tiling path of clones which can be used as templates required for finished sequencing of the region. The goal of this proposal is to develop and implement a novel sequence-anchor strategy to generate a contiguous BAC map of the most proximal portion of chromosome 19p12 for the purpose of complete sequence characterization. The target region will be an estimated 4.5 Mb of DNA extending from STS marker D19S450 (the beginning of the ZNF gene cluster) to the centromeric (alpha-satellite) junction of 19p11. The approach will entail 1) pre-selection of 19p12 BAC and cosmid clones (NIH approved library) utilizing both 19p12 -unique and 19p12-SPECIFIC repeat probes (Eichler et al., 1998); 2) the generation of a BAC/cosmid end-sequence map across the region with a density of one marker every 8kb; 3) the development of a second-generation of STS (sequence tagged sites) which will be used to identify and verify clonal overlap at the level of the sequence; 4) incorporation of these sequence-anchored overlapping clones into existing cosmid/BAC restriction maps developed at Livermore National Laboratory; and 5) validation of the organization of this region utilizing high-resolution FISH techniques (extended chromatin analysis) on monochromosomal 19 somatic cell hybrids and parental cell lines of source material. The data generated will be used in the selection of the most parsimonious tiling path of BAC clones to be sequenced as part of the JGI effort on chromosome 19 and should serve as a model for the sequence

High-resolution physical map for chromosome 16q12.1-q13, the Blau syndrome locus

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Bonavita Gina

2002-08-01

Full Text Available Abstract Background The Blau syndrome (MIM 186580, an autosomal dominant granulomatous disease, was previously mapped to chromosome 16p12-q21. However, inconsistent physical maps of the region and consequently an unknown order of microsatellite markers, hampered us from further refining the genetic locus for the Blau syndrome. To address this problem, we constructed our own high-resolution physical map for the Blau susceptibility region. Results We generated a high-resolution physical map that provides more than 90% coverage of a refined Blau susceptibility region. The map consists of four contigs of sequence tagged site-based bacterial artificial chromosomes with a total of 124 bacterial artificial chromosomes, and spans approximately 7.5 Mbp; however, three gaps still exist in this map with sizes of 425, 530 and 375 kbp, respectively, estimated from radiation hybrid mapping. Conclusions Our high-resolution map will assist genetic studies of loci in the interval from D16S3080, near D16S409, and D16S408 (16q12.1 to 16q13.

Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

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Muniz, Valdirene S; Baptista-Dos-Reis, Renata; Benjamim, Claudia F; Mata-Santos, Hilton A; Pyrrho, Alexandre S; Strauch, Marcelo A; Melo, Paulo A; Vicentino, Amanda R R; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F; Figueiredo, Rodrigo T; Neves, Josiane S

2015-01-01

Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.

Pericentric inversion of chromosome 12; a three family study

DEFF Research Database (Denmark)

Haagerup, Annette; Hertz, Jens Michael

1992-01-01

A pericentric inversion of chromosome 12 has been followed in three large independently ascertained Danish families. Out of a total number of 52 persons examined, 25 were found to carry the inversion. The breakpoints in all three families were localized to p13 and q13, resulting in more than one...... rate is calculated to be 0.58, which is not significantly different from an expected segregation rate of 0.5. In family 3, an additional inversion of a chromosome 9 has been found in 4 individuals. Our results are discussed in relation to previous findings and with respect to the genetic counselling...... of families with pericentric inversions....

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

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Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

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Naiel, Abdulbasit [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom); Vetter, Michael [MetaSystems, Altlussheim 68804 (Germany); Plekhanova, Olga [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Fleischman, Elena; Sokova, Olga [N.N. Blokhin Russian Cancer Research Center Russian Academy of Medical Science, Moscow 115478 (Russian Federation); Tsaur, Grigory [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Research Institute of Medical Cell Technologies, Ekaterinburg 620149 (Russian Federation); Harbott, Jochen [Oncogenetic Laboratory, Department of Paediatric Haematology and Oncology, Justus Liebig University, Giessen 35392 (Germany); Tosi, Sabrina, E-mail: sabrina.tosi@brunel.ac.uk [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom)

2013-03-11

The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.

A de novo 11p12-p15.4 duplication in a patient with pharmacoresistant epilepsy, mental retardation, and dysmorphisms.

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Coppola, Antonietta; Striano, Pasquale; Gimelli, Stefania; Ciampa, Clotilde; Santulli, Lia; Caranci, Ferdinando; Zuffardi, Orsetta; Gimelli, Giorgio; Striano, Salvatore; Zara, Federico

2010-03-01

We report a 22-year-old male patient with pharmacoresistant epilepsy, mental retardation and dysmorphisms. Standard cytogenetic analysis revealed a de novo interstitial duplication of the short arm of chromosome 11 (11p). High density array-CGH analysis showed that the rearrangement spans about 35Mb on chromosome 11p12-p15.4. Duplications of 11p are rare and usually involve the distal part of the chromosome arm (11p15), being not associated with epilepsy, whereas our patient showed a unique epileptic phenotype associated with mental retardation and dysmorphic features. The role of some rearranged genes in epilepsy pathogenesis in this patient is also discussed.

Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.

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Inda, María del Mar; Fan, Xing; Muñoz, Jorge; Perot, Christine; Fauvet, Didier; Danglot, Giselle; Palacio, Ana; Madero, Pilar; Zazpe, Idoya; Portillo, Eduardo; Tuñón, Teresa; Martínez-Peñuela, José María; Alfaro, Jorge; Eiras, José; Bernheim, Alain; Castresana, Javier S

2003-01-01

Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss. Copyright 2002 Wiley-Liss, Inc.

Characterization of a recurrent t(1;2)(p36;p24) in human uterine leiomyoma.

NARCIS (Netherlands)

Rijk, A. van; Sweers, M.A.; Huys, E.; Kersten, M.; Merkx, G.F.M.; Geurts van Kessel, A.H.M.; Debiec-Rychter, M.; Schoenmakers, E.F.P.M.

2009-01-01

Uterine leiomyomas are the most common neoplasms in women of reproductive age. Approximately 40% of these neoplasms show recurring structural cytogenetic anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24), and anomalies affecting 6p21 or 10q22. Using positional cloning strategies,

Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus.

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Shah, Z H; Migliosi, V; Miller, S C; Wang, A; Friedman, T B; Jacobs, H T

1998-03-15

We have mapped the chromosomal locations of three human nuclear genes for putative components of the apparatus of mitochondrial gene expression, using a combination of in situ hybridization and interspecies hybrid mapping. The genes RPMS12 (mitoribosomal protein S12, a conserved protein component of the mitoribosomal accuracy center), TUFM (mitochondrial elongation factor EF-Tu), and AFG3L1 (similar to the yeast genes Afg3 and Rca1 involved in the turnover of mistranslated or misfolded mtDNA-encoded polypeptides) were initially characterized by a combination of database sequence analysis, PCR, cloning, and DNA sequencing. RPMS12 maps to chromosome 19q13.1, close to the previously mapped gene for autosomal dominant hearing loss DFNA4. The TUFM gene is located on chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very close to the centromere of chromosome 17. AFG3L1 is located on chromosome 16q24, very close to the telomere. By virtue of their inferred functions in mitochondria, these genes should be regarded as candidates of disorders sharing features with mitochondrial disease syndromes, such as sensorineural deafness, diabetes, and retinopathy.

Non-stoichiometry in the KMo2P3O12-tunnel structure: The oxide K0.75MoNbP3O12

International Nuclear Information System (INIS)

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

1990-01-01

K 0.75 MoNbP 3 O 12 , M r =503.009, orthorhombic, Pbcm, a=8.8518 (5), b=9.1453 (11), c=12.5174 (11) A, V=1013.3 (3) A 3 , Z=4, D x =3.300 Mg m -3 , λ(Mo Kα)=0.71073 A, μ=3.13 mm -1 , F(000)=953, T=294 K, R=0.029, wR=0.033 for 1235 observed reflections. This compound is isostructural with KMo 2 P 3 O 12 -type oxides. Its framework is built up from MoO 6 octahedra and PO 4 tetrahedra which delimit tunnels running along b. Different from KMo 2 P 3 O 12 , the tunnels are partly occupied by the potassium ions which are distributed at random. (orig.)

Defining the pathogenesis of the human Atp12p W94R mutation using a Saccharomyces cerevisiae yeast model.

Science.gov (United States)

Meulemans, Ann; Seneca, Sara; Pribyl, Thomas; Smet, Joel; Alderweirldt, Valerie; Waeytens, Anouk; Lissens, Willy; Van Coster, Rudy; De Meirleir, Linda; di Rago, Jean-Paul; Gatti, Domenico L; Ackerman, Sharon H

2010-02-05

Studies in yeast have shown that a deficiency in Atp12p prevents assembly of the extrinsic domain (F(1)) of complex V and renders cells unable to make ATP through oxidative phosphorylation. De Meirleir et al. (De Meirleir, L., Seneca, S., Lissens, W., De Clercq, I., Eyskens, F., Gerlo, E., Smet, J., and Van Coster, R. (2004) J. Med. Genet. 41, 120-124) have reported that a homozygous missense mutation in the gene for human Atp12p (HuAtp12p), which replaces Trp-94 with Arg, was linked to the death of a 14-month-old patient. We have investigated the impact of the pathogenic W94R mutation on Atp12p structure/function. Plasmid-borne wild type human Atp12p rescues the respiratory defect of a yeast ATP12 deletion mutant (Deltaatp12). The W94R mutation alters the protein at the most highly conserved position in the Pfam sequence and renders HuAtp12p insoluble in the background of Deltaatp12. In contrast, the yeast protein harboring the corresponding mutation, ScAtp12p(W103R), is soluble in the background of Deltaatp12 but not in the background of Deltaatp12Deltafmc1, a strain that also lacks Fmc1p. Fmc1p is a yeast mitochondrial protein not found in higher eukaryotes. Tryptophan 94 (human) or 103 (yeast) is located in a positively charged region of Atp12p, and hence its mutation to arginine does not alter significantly the electrostatic properties of the protein. Instead, we provide evidence that the primary effect of the substitution is on the dynamic properties of Atp12p.

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

Energy Technology Data Exchange (ETDEWEB)

McDonald, J.D.; Daneshvar, L.; Willert, J.R. [Univ. of California, San Franciso, CA (United States)] [and others

1994-09-01

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

12C(d,p) 13C reaction at Esub(d) = 30 MeV to the positive-parity states in 13C

International Nuclear Information System (INIS)

Ohnuma, H.; Hoshino, N.; Mikoshiba, O.

1985-07-01

The 12 C(d, p) 13 C reaction has been studied at Esub(d) = 30 MeV. All the known positive-parity states of 13 C below 10 MeV in excitation energy, including the 7/2 + and 9/2 + states, are observed in this reaction. The angular distributions for these positive-parity bound and unbound states are analyzed in CCBA frame work. The 13 C wave functions, which reproduce the resonant and non-resonant scattering of neutrons from 12 C, also give good accounts of the experimentally observed angular distributions and energy spectra of outgoing protons in the 12 C(d, p) 13 C reaction. In most cases the cross section magnitude and the angular distribution shape are primarily determined by the 0 + x j component, even if it is only a small fraction of the total wave function. An exception is the 7/2 + state, where the main contribution comes from the 2 + x dsub(5/2) component. The inclusion of the 4 + state in 12 C and the gsub(9/2) and gsub(7/2) neutron components in the n + 12 C system has very small effects on the low-spin states, but is indispensable for a good fit to the 7/2 + and 9/2 + angular distributions. The transitions to the negative-parity states, 1/2 1 - , 3/2 1 - , 5/2 - , 7/2 - and 1/2 3 - , are also observed experimentally, and analyzed by DWBA. (author)

Duplication of 20p12.3 associated with familial Wolff-Parkinson-White syndrome.

Science.gov (United States)

Mills, Kimberly I; Anderson, Jacqueline; Levy, Philip T; Cole, F Sessions; Silva, Jennifer N A; Kulkarni, Shashikant; Shinawi, Marwan

2013-01-01

Wolff-Parkinson-White (WPW) syndrome is caused by preexcitation of the ventricular myocardium via an accessory pathway which increases the risk for paroxysmal supraventricular tachycardia. The condition is often sporadic and of unknown etiology in the majority of cases. Autosomal dominant inheritance and association with congenital heart defects or ventricular hypertrophy were described. Microdeletions of 20p12.3 have been associated with WPW syndrome with either cognitive dysfunction or Alagille syndrome. Here, we describe the association of 20p12.3 duplication with WPW syndrome in a patient who presented with non-immune hydrops. Her paternal uncle carries the duplication and has attention-deficit hyperactivity disorder and electrocardiographic findings consistent with WPW. The 769 kb duplication was detected by the Affymetrix Whole Genome-Human SNP Array 6.0 and encompasses two genes and the first two exons of a third gene. We discuss the potential role of the genes in the duplicated region in the pathogenesis of WPW and possible neurobehavioral abnormalities. Our data provide additional support for a significant role of 20p12.3 chromosomal rearrangements in the etiology of WPW syndrome. Copyright © 2012 Wiley Periodicals, Inc.

Differential endosomal sorting of a novel P2Y12 purinoreceptor mutant.

Science.gov (United States)

Cunningham, Margaret R; Nisar, Shaista P; Cooke, Alexandra E; Emery, Elizabeth D; Mundell, Stuart J

2013-05-01

P2Y12 receptor internalization and recycling play an essential role in ADP-induced platelet activation. Recently, we identified a patient with a mild bleeding disorder carrying a heterozygous mutation of P2Y12 (P341A) whose P2Y12 receptor recycling was significantly compromised. Using human cell line models, we identified key proteins regulating wild-type (WT) P2Y12 recycling and investigated P2Y12 -P341A receptor traffic. Treatment with ADP resulted in delayed Rab5-dependent internalization of P341A when compared with WT P2Y12 . While WT P2Y12 rapidly recycled back to the membrane via Rab4 and Rab11 recycling pathways, limited P341A recycling was observed, which relied upon Rab11 activity. Although minimal receptor degradation was evident, P341A was localized in Rab7-positive endosomes with considerable agonist-dependent accumulation in the trans-Golgi network (TGN). Rab7 activity is known to facilitate recruitment of retromer complex proteins to endosomes to transport cargo to the TGN. Here, we identified that P341A colocalized with Vps26; depletion of which blocked limited recycling and promoted receptor degradation. This study has identified key points of divergence in the endocytic traffic of P341A versus WT-P2Y12 . Given that these pathways are retained in human platelets, this research helps define the molecular mechanisms regulating P2Y12 receptor traffic and explain the compromised receptor function in the platelets of the P2Y12 -P341A-expressing patient. © 2013 John Wiley & Sons A/S.

LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast.

Science.gov (United States)

Lininger, R A; Park, W S; Man, Y G; Pham, T; MacGrogan, G; Zhuang, Z; Tavassoli, F A

1998-10-01

Papillary carcinoma of the breast is a variant of predominantly intraductal carcinoma characterized by a papillary growth pattern with fibrovascular support. Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci (including loci reported to show frequent genetic alterations in breast cancer) to determine the frequency of genetic mutations in these tumors and their precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas, 12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid epithelial hyperplasia) were retrieved from the files of the Armed Forces Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected in each case and screened for LOH at INT-2 and p53 as well as several loci on chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on chromosome 16p13 was present in 10 of 16 (63%) informative cases of either papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10 (60%) informative cases of intraductal papilloma with florid epithelial hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53 in any of the papillary carcinomas or papillomas with florid IDH. In conclusion, a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in both papillary carcinomas of the breast as well as in papillomas with florid IDH, including a case with LOH present simultaneously in both components. These findings suggest that chromosome 16p contains a tumor suppressor gene that frequently is mutated early in papillary neoplasia.

A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15(p11.2;q22.1

Directory of Open Access Journals (Sweden)

Dalvi Rupa

2016-01-01

Full Text Available BACKGROUND: Balanced non-robertsonian translocation (RT, involving acrocentric chromosomes, is a rare event and only a few cases are reported. Most of the RTs are balanced involving acrocentric chromosomes with the breakpoints (q10;q10. MATERIALS AND METHODS: Chromosome analysis was performed as per standard procedure – Giemsa-trypsin banding with 500 band resolution was analyzed for chromosome identification. RESULTS: In the present study, we report a rare balanced non-RTs involving chromosomes 13 and 15 with cytogenetic finding of 46, XX, t(13;15(p11.2;q22.1. CONCLUSION: To the best of our knowledge, this is the first such report of an unusual non-RT of t(13:15 with (p11.2;q22.1 break points.

Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

Science.gov (United States)

Wafa, Abdulsamad; As'sad, Manar; Liehr, Thomas; Aljapawe, Abdulmunim; Al Achkar, Walid

2017-04-07

The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20. Moreover, the translocation t(1;19) correlates with known clinical high risk factors, such as elevated white blood cell count, high serum lactate dehydrogenase levels, and central nervous system involvement; early reports indicated that patients with translocation t(1;19) had a poor outcome under standard treatment. We report the case of a 15-year-old Syrian boy with pre-B cell acute lymphoblastic leukemia with abnormal karyotype with a der(19)t(1;19)(q21.1;p13.3) and two yet unreported chromosomal aberrations: an interstitial deletion 6q12 to 6q26 and a der(13)t(1;13)(q21.1;p13). According to the literature, cases who are translocation t(1;19)-positive have a significantly higher incidence of central nervous system relapse than patients with acute lymphoblastic leukemia without the translocation. Of interest, central nervous system involvement was also seen in our patient. To the best of our knowledge, this is the first case of childhood pre-B cell acute lymphoblastic leukemia with an unbalanced translocation t(1;19) with two additional chromosomal aberrations, del(6)(q12q26) and t(1;13)(q21.3;p13), which seem to be recurrent and could influence clinical outcome. Also the present case confirms the impact of the translocation t(1;19) on central nervous system relapse, which should be studied for underlying mechanisms in future.

The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3

Energy Technology Data Exchange (ETDEWEB)

Kapfhamer, D.; Sufalko, D.; Warren, S. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

1996-08-01

Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene. 31 refs., 2 figs.

IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis

Directory of Open Access Journals (Sweden)

Jin Kyeong Choi

2017-10-01

Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE, the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord. In addition, in vitro exposure of encephalitogenic cells to IL-12p35 suppressed their capacity to induce EAE by adoptive transfer. Importantly, the IL-12p35-mediated expansion of Treg and Breg cells and its amelioration of EAE correlated with inhibition of cytokine-induced activation of STAT1/STAT3 pathways. Moreover, IL-12p35 inhibited lymphocyte proliferation by suppressing the expressions of cell-cycle regulatory proteins. Taken together, these results suggest that IL-12p35 can be exploited as a novel biologic for treating central nervous system autoimmune diseases and offers the promise of ex vivo production of large amounts of Tregs and Bregs for immunotherapy.

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

DEFF Research Database (Denmark)

Hoff, C; Mollenhauer, J; Waldau, B

2001-01-01

Chromosome arm 17p is frequently altered in a variety of human cancers, especially in breast cancer, and allelic imbalances (AIs) in the region 17p13.1 do not always coincide with mutations in the TP53 gene. A second interval that frequently shows AIs at 17p is the chromosomal band 17p13.3. This ......Chromosome arm 17p is frequently altered in a variety of human cancers, especially in breast cancer, and allelic imbalances (AIs) in the region 17p13.1 do not always coincide with mutations in the TP53 gene. A second interval that frequently shows AIs at 17p is the chromosomal band 17p13...

Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

Science.gov (United States)

Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

1994-01-01

Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

Study of the (p,pd), (p,pt) and (p,p3He) reactions on 12C and 16O at 75MeV

International Nuclear Information System (INIS)

Grossiord, J.Y.; Bedjidian, M.; Guichard, A.; Gusakow, M.; Pizzi, J.R.

1975-01-01

The (p,pd), (p,pt) and (p,p 3 He) quasi-free scattering reactions have been studied on 12 C and 16 O targets at 75MeV. The low lying excitation levels of the residual nuclei have been observed. The appearance of T=1 states in 10 B and 14 N and of positive parity states in 13 N and 13 C can only be explained by reaction mechanisms more complex than a simple quasi-free scattering. A comparison of relative values of experimental spectroscopic factors with theoretical calculations has been made in the case of the most populated states [fr

A case of microdeletion of 19p13 with intellectual disability, hypertrichosis, synophrys, and protruding front teeth

DEFF Research Database (Denmark)

Jelsig, Anne Marie; Brasch Andersen, Charlotte; Kibæk, Maria

2012-01-01

We present a de novo 1.4 Mb deletion of chromosome 19p13.11-p13.12 in a 16 year old boy with intellectual disability, autistic features, microcephaly, hearing impairment, hypertrichosis, synophrys, protruding front teeth, and other dysmorphic features. By comparing our patient to reported cases...

The E7-associated cell-surface antigen: a marker for the 11p13 chromosomal deletion associated with aniridia-Wilms tumor.

OpenAIRE

Scoggin, C H; Fisher, J H; Shoemaker, S A; Morse, H; Leigh, T; Riccardi, V M

1985-01-01

Unbalanced interstitial deletions of the p13 region of human chromosome 11 have been associated with congenital hypoplasia or aplasia of the iris, mental retardation, ambiguous genitalia, and predisposition to Wilms tumor of the kidney. Utilizing somatic cell hybrids containing either the normal or abnormal chromosome 11 from a child with Wilms tumor and aniridia, we previously mapped the E7 cell-surface antigen to the 11p1300-to-11p15.1 region. To localize even further the site of this antig...

Leiomyoma of uterus in a patient with ring chromosome 12: Case presentation and literature review

Energy Technology Data Exchange (ETDEWEB)

Hajianpour, M.J.; Habibian, R.; Hajianpour, A.K. [Children`s Hospital, Los Angeles, CA (United States)] [and others

1996-05-17

We report on a 30-year-old woman with de novo ring chromosome 12 mosaicism, 46,XX,r(12)(p13.3q24.3)/46,XX. In addition to the clinical manifestations generally observed in {open_quotes}ring syndrome{close_quotes} cases such as growth retardation, short stature, microcephaly, and mental deficiency, she had a broad nasal bridge, micrognathia with overbite, underdeveloped breasts, mild dorsal scoliosis, clinodactyly of the fifth fingers with a single interdigital crease, symphalangism of thumbs, tapering fingers, mild cutaneous syndactyly between the second and third toes, multiple cafe-au-lait spots, sebaceous acne on the face and back, and mild dystrophic toenails. She developed a large, pedunculated uterine leiomyoma at age 28 years. To our knowledge, uterine leiomyoma in association with r(12) has not been reported previously. However, a gain of chromosome 12 and translocations involving 12q14-15 have been described. 12 refs., 5 figs., 2 tabs.

Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.

Science.gov (United States)

Coignet, L J; Lima, C S; Min, T; Streubel, B; Swansbury, J; Telford, N; Swanton, S; Bowen, A; Nagai, M; Catovsky, D; Fonatsch, C; Dyer, M J

1999-07-01

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.

The new ternary pnictides Er12Ni30P21 and Er13Ni25As19: Crystal structures and magnetic properties

International Nuclear Information System (INIS)

Oryshchyn, Stepan; Babizhetskyy, Volodymyr; Zhak, Olga; Zelinska, Mariya; Pivan, Jean-Yves; Duppel, Viola; Simon, Arndt; Kienle, Lorenz

2010-01-01

The new ternary pnictides Er 12 Ni 30 P 21 and Er 13 Ni 25 As 19 have been synthesized from the elements. They crystallize with hexagonal structures determined from single-crystal X-ray data for Er 12 Ni 30 P 21 (space group P6 3 /m, a=1.63900(3) nm, c=0.37573(1) nm, Z=1, R F =0.062 for 1574 F-values and 74 variable parameters), and for Er 13 Ni 25 As 19 (Tm 13 Ni 25 As 19 -type structure, space group P6-bar , a=1.6208(1) nm, c=0.38847(2) nm, Z=1, R F =0.026 for 1549 F-values and 116 variable parameters). These compounds belong to a large family of hexagonal structures with a metal-metalloid ratio of 2:1. HRTEM investigations were conducted to probe for local ordering of the disordered structure at the nanoscale. The magnetic properties of the phosphide Er 12 Ni 30 P 21 have been studied in the temperature of range 2 eff =9.59 μ B corresponds to the theoretical value of Er 3+ . - Graphical abstract: The new ternary pnictides Er 12 Ni 30 P 21 and Er 13 Ni 25 As 19 have been synthesized from the elements. They crystallize with hexagonal structures determined from single-crystal X-ray data. The compounds belong to a large family of structures with a metal-metalloid ratio of 2:1. HRTEM investigations were conducted to probe for local ordering of the disordered structure at the nanoscale. Display Omitted

ALOX12 in Human Toxoplasmosis

Science.gov (United States)

Witola, William H.; Liu, Susan Ruosu; Montpetit, Alexandre; Welti, Ruth; Hypolite, Magali; Roth, Mary; Zhou, Ying; Mui, Ernest; Cesbron-Delauw, Marie-France; Fournie, Gilbert J.; Cavailles, Pierre; Bisanz, Cordelia; Boyer, Kenneth; Withers, Shawn; Noble, A. Gwendolyn; Swisher, Charles N.; Heydemann, Peter T.; Rabiah, Peter; Muench, Stephen P.

2014-01-01

ALOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a nonheme lipoxygenase family of dioxygenases. ALOX12 catalyzes the addition of oxygen to arachidonic acid, producing 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can be reduced to the eicosanoid 12-HETE (12-hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes, including catecholamine synthesis, vasoconstriction, neuronal function, and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of ALOX12 are associated with diseases including schizophrenia, atherosclerosis, and cancers, but the mechanisms have not been defined. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region with ALOX12 centromeric is also present in humans. Here we report that the human ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P, <0.000309], rs312462 [P, <0.028499], rs6502998 [P, <0.029794], and rs434473 [P, <0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock down ALOX12. In ALOX12 knockdown cells, ALOX12 RNA expression decreased and levels of the ALOX12 substrate, arachidonic acid, increased. ALOX12 knockdown attenuated the progression of T. gondii infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line. These findings suggest that ALOX12 influences host responses to T. gondii infection in human cells. ALOX12 has been shown in other studies to be important in numerous diseases. Here we demonstrate the critical role ALOX12 plays in T. gondii infection in humans. PMID:24686056

Magnetic properties of the filled skutterudite-type structure compounds GdRu4P12 and TbRu4P12 synthesized under high pressure

OpenAIRE

Sekine, C; Uchiumi, T; Shirotani, I; Matsuhira, kazuyuki; Sakakibara, T; Goto, T; Yagi, T

2000-01-01

We have succeeded in synthesizing filled skutterudite-type structure compounds GdRu4P12 and TbRu4P12 under high pressure. The magnetic properties of GdRu4P12 and TbRu4P12 have been studied by means of electrical resistivity, magnetic susceptibility, and magnetization measurements. Magnetic experiments suggest that the Gd and Tb ions in the compounds have trivalent state. The compound GdRu4P12 displays features that suggest the occurrence of antiferromagnetic ordering below TN=22 K. In TbRu4P1...

A gene for late-onset fundus flavimaculatus with macular dystrophy maps to chromosome 1p13

Energy Technology Data Exchange (ETDEWEB)

Gerber, S.; Rozet, J.M.; Bonneau, D.; Souied, E.; Camuzat, A.; Munnich, A.; Kaplan, J. [Hopital des Enfants Malades, Paris (France); Dufier, J.L. [Hopital Laeennec, Paris (France); Amalric, P. [Consultation d`Ophtalmologie, Albi (France); Weissenbach, J. [Genethon, Evry (France)

1995-02-01

Fundus flavimaculatus with macular dystrophy is an autosomal recessive disease responsible for a progressive loss of visual acuity in adulthood, with pigmentary changes of the macula, perimacular flecks, and atrophy of the retinal pigmentary epithelium. Since this condition shares several clinical features with Stargardt disease, which has been mapped to chromosome 1p21-p13, we tested the disease for linkage to chromosome 1p. We report the mapping of the disease locus to chromosome 1p13-p21, in the genetic interval defined by loci D1S435 and D1S415, in four multiplex families (maximum lod score 4.79 at recombination fraction 0 for probe AFM217xb2 at locus D1S435). Thus, despite differences in the age at onset, clinical course, and severity, fundus flavimaculatus with macular dystrophy and Stargardt disease are probably allelic disorders. This result supports the view that allelic mutations produce a continuum of macular dystrophies, with onset in early childhood to late adulthood. 16 refs., 3 figs., 1 tab.

Effects of interleukins 2 and 12 on TBT-induced alterations of MAP kinases p38 and p44/42 in human natural killer cells.

Science.gov (United States)

Aluoch, Aloice O; Whalen, Margaret M

2006-01-01

NK cells are lymphocytes in the non-adaptive immune system that protect the body against intracellular pathogens and eliminate tumor cells. Tributyltin (TBT) is a toxic chemical that has been detected in human foods as well as in human blood. The role of TBT in immunosuppression has been described, including inhibition of the human NK-cell cytotoxic function. Previous studies indicated that exposure of NK cells to TBT for 1 h induced progressive and irreversible inhibition of cytotoxic function. However, it was found that if NK cells were incubated in TBT-free media with either IL-2 or IL-12, loss of cytotoxic function was prevented/reversed within 24 h. Molecular studies established that loss of cytotoxic function is accompanied by alteration of MAP kinases (MAPKs) p38 and p44/42 phosphorylation. This study examined whether interleukin-mediated recovery of cytotoxicity involved reversal of tributyltin-altered p38 and p44/42 phosphorylation. The results indicated that there was no substantial IL-2 prevention/reversal of the TBT-induced alteration of phosphorylation of either p38 or p44/42 after either a 24 or 48 h recovery period. Additionally, IL-12 caused no substantial prevention/reversal of the TBT-induced alteration of phosphorylation of the MAPKs seen after either 24 or 48 h. These data suggest that IL-2 and/or IL-12-mediated recovery of NK cytotoxic function is not a result of prevention/reversal of TBT-induced phosphorylation of p38 and p44/42 MAPKs at the 24 or 48 h time points. Copyright 2005 John Wiley & Sons, Ltd.

Sirenomelia with a de novo balanced translocation 46,X,t(X;16)(p11.23;p12.3).

Science.gov (United States)

Kurosawa, Kenji; Tanoshima-Takei, Miki; Yamamoto, Toshiyuki; Ishikawa, Hiroshi; Masuno, Mitsuo; Tanaka, Yukichi; Yamanaka, Michiko

2012-06-01

We report a female fetus with sirenomelia with 46,X,t(X;16)(p11.23;p12.3) de novo. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes were employed for narrowing down the breakpoint regions. On chromosome 16, the breakpoint was mapped in the region of RP11-453F10 (19 920 640-20 118 153 bp from 16pter). On chromosome X, the breakpoint was mapped in the region of RP11-794A15 (47 333 744-47 524 066 bp from Xpter). This is the first case report of sirenomelia associated with translocations. The abnormal phenotype, associated with a balanced translocation, was caused by deletion or breakage of dosage-sensitive genes of the breakpoint, disruption of an imprinted gene, or uniparental disomy. Although the parental origin of normal 16 and der(16) remained undetermined, this case will provide insight into the pathogenetic mechanism of sirenomelia. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

Structural and functional organization of the HF.10 human zinc finger gene (ZNF35) located on chromosome 3p21-p22

DEFF Research Database (Denmark)

Lanfrancone, L; Pengue, G; Pandolfi, P P

1992-01-01

We report the structural and functional characterization of the HF.10 zinc finger gene (ZNF35) in normal human cells, as well as a processed pseudogene. The HF.10 gene spans about 13 kb and it is interrupted by three introns. All 11 zinc finger DNA-binding domains are contiguously encoded within...... and partial nucleotide sequencing of the HF.10 pseudogene indicated that it has arisen by retroposition of spliced HF.10 mRNA. In situ hybridization experiments revealed that both the functional locus and the pseudogene map to chromosome 3p21p22, a region that is frequently deleted in small cell lung...... and renal carcinomas. Hybridization of the HF.10 gene and the HF.10 pseudogene DNA probes to metaphases from a small cell lung carcinoma cell line with the 3p deletion revealed that both loci are part of the deleted chromosome region....

Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP- and thrombin-induced human platelet activation

Science.gov (United States)

Nylander, Sven; Mattsson, Christer; Ramström, Sofia; Lindahl, Tomas L

2004-01-01

The objective of this study was to investigate if there is a synergistic effect of a combination of P2Y12 and P2Y1 inhibition and P2Y12 and thrombin inhibition, on ADP- and thrombin-induced platelet activation, respectively. The rationale being that these combinations will cause a concurrent inhibition of both Gαq and Gαi signalling.Blood from healthy volunteers was preincubated with AR-C69931MX, a reversible P2Y12 antagonist; MRS2179, a reversible P2Y1 antagonist; or melagatran, a direct reversible thrombin inhibitor; alone or in various combinations prior to activation with ADP or thrombin. Platelet function in whole blood was assessed by flow cytometry using the antibody PAC-1 to estimate the expression of active αIIbβ3 (the fibrinogen receptor GPIIb/IIIa). A synergistic effect was evaluated by comparing the concentrations in the different combinations with those of corresponding equipotent concentrations of each single inhibitor alone. The equipotent single concentrations were experimentally obtained from concentration response curves performed in parallel.A synergistic effect regarding inhibition of ADP-induced platelet activation (10 μM) was obtained with different combinations of AR-C69931MX and MRS2179.Inhibition of thrombin-induced platelet activation (2 nM) with combinations of AR-C69931MX and the thrombin inhibitor melagatran did also result in a strong synergistic effect.To our knowledge, this is the first time that data supporting a synergistic effect has been published for the inhibitor combinations described.Whether this synergistic effect in vitro also results in an improved antithrombotic effect in vivo with or without an increased risk of bleeding remains to be studied in well-conducted clinical studies. PMID:15265806

HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13

DEFF Research Database (Denmark)

Asad, Samina; Nikamo, Pernilla; Gyllenberg, Alexandra

2012-01-01

We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD≤2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D...

The differential cross section of the 12C(p,p)12C reaction near the resonance at energy 1.726 MeV

International Nuclear Information System (INIS)

Duvanov, S.M.; Kobzev, A.P.

1996-01-01

New experimental results on the differential cross section of the 12 C(p,p) 12 C reaction near the separate resonance at 1726 keV were obtained for the 170 deg scattering angle. The cross section measured with a thin target has been used for computer simulation of the spectra measured for a defined initial proton energy for two thick targets. The precision measurements of the proton energies have been carried out using the resonance of 27 Al(p,γ) 28 Si reaction at 1726.0 keV. The energy scale of the excitation function of the 12 C(p,p) 12 C reaction near the resonance at 1726 keV has been defined more exactly. It will improve the precision of depth profiling of carbon in solids. 11 refs., 5 figs., 1 tab

Integral measurement of the $^{12}$C(n,p)$^{12}$B reaction up to 10 GeV

CERN Document Server

Žugec, P; Bosnar, D; Ventura, A; Mengoni, A; Altstadt, S; Andrzejewski, J; Audouin, L; Barbagallo, M; Bécares, V; Bečvář, F; Belloni, F; Berthoumieux, E; Billowes, J; Boccone, V; Brugger, M; Calviani, M; Calviño, F; Cano-Ott, D; Carrapiço, C; Cerutti, F; Chiaveri, E; Chin, M; Cortés, G; Cortés-Giraldo, M.A; Cosentino, L; Diakaki, M; Domingo-Pardo, C; Dressler, R; Duran, I; Eleftheriadis, C; Ferrari, A; Finocchiaro, P; Fraval, K; Ganesan, S; García, A R; Giubrone, G; Gómez-Hornillos, M B; Gonçalves, I F; González-Romero, E; Griesmayer, E; Guerrero, C; Gunsing, F; Gurusamy, P; Heinitz, S; Jenkins, D G; Jericha, E; Käppeler, F; Karadimos, D; Kivel, N; Kokkoris, M; Krtička, M; Kroll, J; Langer, C; Lederer, C; Leeb, H; Leong, L S; Meo, S Lo; Losito, R; Manousos, A; Marganiec, J; Martínez, T; Massimi, C; Mastinu, P; Mastromarco, M; Mendoza, E; Milazzo, P M; Mingrone, F; Mirea, M; Mondalaers, W; Musumarra, A; Paradela, C; Pavlik, A; Perkowski, J; Plompen, A; Praena, J; Quesada, J; Rauscher, T; Reifarth, R; Riego, A; Roman, F; Rubbia, C; Sarmento, R; Saxena, A; Schillebeeckx, P; Schmidt, S; Schumann, D; Tagliente, G; Tain, J L; Tarrío, D; Tassan-Got, L; Tsinganis, A; Valenta, S; Vannini, G; Variale, V; Vaz, P; Versaci, R; Vermeulen, M J; Vlachoudis, V; Vlastou, R; Wallner, A; Ware, T; Weigand, M; Weiß, C; Wright, T

2016-01-01

The integral measurement of the $^{12}$C(n,p)$^{12}$B reaction was performed at the neutron time of flight facility n_TOF at CERN. The total number of $^{12}$B nuclei produced per neutron pulse of the n_TOF beam was determined using the activation technique in combination with a time of flight technique. The cross section is integrated over the n_TOF neutron energy spectrum from reaction threshold at 13.6 MeV to 10 GeV. Having been measured up to 1 GeV on basis of the $^{235}$U(n,f) reaction, the neutron energy spectrum above 200 MeV has been reevaluated due to the recent extension of the cross section reference for this particular reaction, which is otherwise considered a standard up to 200 MeV. The results from the dedicated GEANT4 simulations have been used to evaluate the neutron flux from 1 GeV up to 10 GeV. The experimental results related to the $^{12}$C(n,p)$^{12}$B reaction are compared with the evaluated cross sections from major libraries and with the predictions of different GEANT4 models, which m...

A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors

International Nuclear Information System (INIS)

Sastre-Garau, X.; Couturier, J.; Favre, M.; Orth, G.

1995-01-01

The SW756 cell line, derived from an invasive cancer of the uterine cervix, harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been located in chromosome band 12q13. By in situ hybridization experiments with tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now localize the integrated viral sequences in 12q14-q15. Interestingly, we have previously localized integrated HPV16 sequences in the same chromosomal region in SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region 12q14-q15 could thus correspond to a preferential site for the integration of HPV DNA in genital tumors. (authors). 29 refs., 2 figs

A de novo 10p11.23-p12.1 deletion recapitulates the phenotype observed in WAC mutations and strengthens the role of WAC in intellectual disability and behavior disorders.

Science.gov (United States)

Abdelhedi, Fatma; El Khattabi, Laila; Essid, Nouha; Viot, Geraldine; Letessier, Dominique; Lebbar, Aziza; Dupont, Jean-Michel

2016-07-01

Chromosomal microarray analysis has become a powerful diagnostic tool in the investigation of patients with intellectual disability leading to the discovery of dosage sensitive genes implicated in the manifestation of various genomic disorders. Interstitial deletions of the short arm of chromosome 10 represent rare genetic abnormalities, especially those encompassing the chromosomal region 10p11-p12. To date, only 10 postnatal cases with microdeletion of this region have been described, and all patients shared a common phenotype, including intellectual disability, abnormal behavior, distinct dysmorphic features, visual impairment, and cardiac malformations. WAC was suggested to be the main candidate gene for intellectual disability associated with 10 p11-p12 deletion syndrome. Here, we describe a new case of de novo 10p11.23-p12.1 microdeletion in a patient with intellectual disability, abnormal behavior, and distinct dysmorphic features. Our observation allows us to redefine the smallest region of overlap among patients reported so far, with a size of 80 Kb and which contains only the WAC gene. These findings strengthen the hypothesis that haploinsufficency of WAC gene might be likely responsible for intellectual disability and behavior disorders. Our data also led us to propose a clinical pathway for patients with this recognizable genetic syndrome depending on the facial dysmorphisms. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q in Finnish multiplex families.

Science.gov (United States)

Auranen, M; Nieminen, T; Majuri, S; Vanhala, R; Peltonen, L; Järvelä, I

2000-05-01

The role of genetic factors in the etiology of the autistic spectrum of disorders has clearly been demonstrated. Ten chromosomal regions, on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q have potentially been linked to autism.1-8 We have analyzed these chromosomal regions in a total of 17 multiplex families with autism originating from the isolated Finnish population by pairwise linkage analysis and sib-pair analysis. Mild evidence for putative contribution was found only with the 1p chromosomal region in the susceptibility to autism. Our data suggest that additional gene loci exist for autism which will be detectable in and even restricted to the isolated Finnish population.

Assignment of the gene for human tetranectin (TNA) to chromosome 3p22-->p21.3 by somatic cell hybrid mapping

DEFF Research Database (Denmark)

Durkin, M E; Naylor, S L; Albrechtsen, R

1997-01-01

Tetranectin is a plasminogen-binding protein that is induced during the mineralization phase of osteogenesis. By screening a human chromosome 3 somatic cell hybrid mapping panel, we have localized the human tetranectin gene (TNA) to 3p22-->p21.3, which is distinct from the loci of two human...

A familial Cri-du-Chat/5p deletion syndrome resulted from rare maternal complex chromosomal rearrangements (CCRs and/or possible chromosome 5p chromothripsis.

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Heng Gu

Full Text Available Cri-du-Chat syndrome (MIM 123450 is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs, diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5(p13.3p15.33 spanning ≈ 26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5 (q23;p14.1p15.31,ins(21;5(q21;p13.3p14.1,ins(21;5(q21;p15.31p15.33,inv(7(p22q32dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5 identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5. Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

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Clara Quintas

2018-05-01

Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41.

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Tana Taechalertpaisarn

Full Text Available The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.

Four small supernumerary marker chromosomes derived from chromosomes 6, 8, 11 and 12 in a patient with minimal clinical abnormalities: a case report

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Hamid Ahmed B

2010-08-01

Full Text Available Abstract Introduction Small supernumerary marker chromosomes are still a problem in cytogenetic diagnostic and genetic counseling. This holds especially true for the rare cases with multiple small supernumerary marker chromosomes. Most such cases are reported to be clinically severely affected due to the chromosomal imbalances induced by the presence of small supernumerary marker chromosomes. Here we report the first case of a patient having four different small supernumerary marker chromosomes which, apart from slight developmental retardation in youth and non-malignant hyperpigmentation, presented no other clinical signs. Case presentation Our patient was a 30-year-old Caucasian man, delivered by caesarean section because of macrosomy. At birth he presented with bilateral cryptorchidism but no other birth defects. At age of around two years he showed psychomotor delay and a bilateral convergent strabismus. Later he had slight learning difficulties, with normal social behavior and now lives an independent life as an adult. Apart from hypogenitalism, he has multiple hyperpigmented nevi all over his body, short feet with pes cavus and claw toes. At age of 30 years, cytogenetic and molecular cytogenetic analysis revealed a karyotype of 50,XY,+min(6(:p11.1-> q11.1:,+min(8(:p11.1->q11.1:,+min(11(:p11.11->q11:,+min(12(:p11.2~12->q10:, leading overall to a small partial trisomy in 12p11.1~12.1. Conclusions Including this case, four single case reports are available in the literature with a karyotype 50,XN,+4mar. For prenatally detected multiple small supernumerary marker chromosomes in particular we learn from this case that such a cytogenetic condition may be correlated with a positive clinical outcome.

HRAS1-selected chromosome transfer generates markers that colocalize aniridia- and genitourinary dysplasia-associated translocation breakpoints and the Wilms tumor gene within band 11p13.

OpenAIRE

Porteous, D J; Bickmore, W; Christie, S; Boyd, P A; Cranston, G; Fletcher, J M; Gosden, J R; Rout, D; Seawright, A; Simola, K O

1987-01-01

We show that chromosome-mediated gene transfer can provide an enriched source of DNA markers for predetermined, subchromosomal regions of the human genome. Forty-four human DNA recombinants isolated from a HRAS1-selected chromosome-mediated gene transformant map exclusively to chromosome 11, with several sublocalizing to the Wilms tumor region at 11p13. We present a detailed molecular map of the deletion chromosomes 11 from five WAGR (Wilms tumor/aniridia/genitourinary abnormalities/mental re...

Isolation of IL-12p70-competent human monocyte-derived dendritic cells

DEFF Research Database (Denmark)

Søndergaard, Jonas Nørskov; Pedersen, Susanne Brix

2012-01-01

that moDCs generated under standard conditions develop into two subsets based on CD1a-expression with the CD1a+ moDCs being the main IL-12p70 producers. This has however not been generally accepted, which we show here because the subset described as CD1a-negative does express CD1a, but at a lower level...... is not available to many laboratories and has incompatibility with clinical settings, a more widely useable technique is warranted. Therefore we tested if magnetic-activated cell sorting is useful for the purpose, and show that it is possible to isolate IL-12p70-competent CD1a-hi moDCs to a...

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

Science.gov (United States)

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

2007-04-26

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

Partial 2p deletion in a girl with a complex chromosome rearrangement involving chromosomes 2, 6, 11, and 21.

OpenAIRE

Young, R S; Medrano, M A; Hansen, K L

1985-01-01

We describe the clinical and cytogenetic findings of a 9 1/2 month old girl with a complex chromosome rearrangement resulting in a probable deletion of band 2p14. She does not resemble other reported cases of del(2p).

Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation.

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Bibiana Bielekova

Full Text Available Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF derived from 16 untreated patients with highly active multiple sclerosis (MS we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72 and a confirmatory cohort (n = 167 of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC curve analysis in conjunction with principal component analysis (PCA, which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND in comparison to non-inflammatory neurological disorder patients (NIND at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924.Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically

An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets.

Science.gov (United States)

Nisar, Shaista; Daly, Martina E; Federici, Augusto B; Artoni, Andrea; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

2011-11-17

The platelet P2Y(12) purinoceptor (P2Y(12)R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y(12)R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)-binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y(12)R (P341A) that is associated with reduced expression of the P2Y(12)R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y(12)R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic.

Homologous alpha satellite sequences on human acrocentric chromosomes with selectivity for chromosomes 13, 14, and 21: implications for recombination between nonhomologues and Robertsonian translocations

Energy Technology Data Exchange (ETDEWEB)

Choo, K H; Vissel, B; Brown, R; Filby, R G; Earle, E

1988-02-25

The authors report a new subfamily of alpha satellite DNA (pTRA-2) which is found on all the human acrocentric chromosomes. The alphoid nature of the cloned DNA was established by partial sequencing. Southern analysis of restriction enzyme-digested DNA fragments from mouse/human hybrid cells containing only human chromosome 21 showed that the predominant higher-order repeating unit for pTRA-2 is a 3.9 kb structure. Analysis of a consensus in situ hybridization profile derived from 13 normal individuals revealed the localization of 73% of all centromeric autoradiographic grains over the five acrocentric chromosomes, with the following distribution: 20.4%, 21.5%, 17.1%, 7.3% and 6.5% on chromosomes 13, 14, 21, 15 and 22 respectively. An average of 1.4% of grains was found on the centromere of each of the remaining 19 nonacrocentric chromosomes. These results indicate the presence of a common subfamily of alpha satellite DNA on the five acrocentric chromosomes and suggest an evolutionary process consistent with recombination exchange of sequences between the nonhomologues. The results further suggests that such exchanges are more selective for chromosomes 13, 14 and 21 than for chromosomes 15 and 22. The possible role of centromeric alpha satellite DNA in the aetiology of 13q14q and 14q21q Robertsonian translocation involving the common and nonrandom association of chromosomes 13 and 14, and 14 and 21 is discussed.

Isotope shift of 40,42,44,48Ca in the 4s 2S1/2 → 4p 2P3/2 transition

Science.gov (United States)

Gorges, C.; Blaum, K.; Frömmgen, N.; Geppert, Ch; Hammen, M.; Kaufmann, S.; Krämer, J.; Krieger, A.; Neugart, R.; Sánchez, R.; Nörtershäuser, W.

2015-12-01

We report on improved isotope shift measurements of the isotopes {}{40,42,{44,48}}Ca in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}3/2 (D2) transition using collinear laser spectroscopy. Accurately known isotope shifts in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}1/2(D1) transition were used to calibrate the ion beam energy with an uncertainty of {{Δ }}U≈ +/- 0.25 {{V}}. The accuracy in the D2 transition was improved by a factor of 5-10. A King-plot analysis of the two transitions revealed that the field shift factor in the D2 line is about 1.8(13)% larger than in the D1 transition which is ascribed to relativistic contributions of the 4{{{p}}}1/2 wave function.

CARD15 single nucleotide polymorphisms 8, 12 and 13 are not increased in ethnic Danes with sarcoidosis

DEFF Research Database (Denmark)

Milman, Nils; Nielsen, Ole Haagen; Hviid, Thomas Vauvert F

2007-01-01

and SNP13, respectively, were performed by capillary electrophoresis single-strand confirmation polymorphism in 53 patients with histologically verified sarcoidosis and in 103 healthy controls. RESULTS: The frequencies of CARD15 mutations in sarcoidosis patients were: SNP8, 4/106 chromosomes (3.8%); SNP12...... with Crohn's disease. OBJECTIVES: To evaluate whether ethnic Danes with sarcoidosis have an increased frequency of CARD15 mutations compared to healthy control subjects. METHODS: Genotyping for CARD15 mutations R702W, G908R, and L1007fsinsC, also designated single nucleotide polymorphism (SNP) SNP8, SNP12......, 2/106 chromosomes (1.9%); SNP13, 2/106 chromosomes (1.9%); SNP8+SNP12+SNP13, 8/106 chromosomes (7.6%). All 8 patients were heterozygous. The frequencies in controls were: SNP8, 9/206 chromosomes (4.4%); SNP12, 2/206 chromosomes (1.0%); SNP13, 4/206 chromosomes (1.9%); SNP8+SNP12+SNP13, 15...

Molecular mechanisms of platelet P2Y(12) receptor regulation.

Science.gov (United States)

Cunningham, Margaret R; Nisar, Shaista P; Mundell, Stuart J

2013-02-01

Platelets are critical for haemostasis, however inappropriate activation can lead to the development of arterial thrombosis, which can result in heart attack and stroke. ADP is a key platelet agonist that exerts its actions via stimulation of two surface GPCRs (G-protein-coupled receptors), P2Y(1) and P2Y(12). Similar to most GPCRs, P2Y receptor activity is tightly regulated by a number of complex mechanisms including receptor desensitization, internalization and recycling. In the present article, we review the molecular mechanisms that underlie P2Y(1) and P2Y(12) receptor regulation, with particular emphasis on the structural motifs within the P2Y(12) receptor, which are required to maintain regulatory protein interaction. The implications of these findings for platelet responsiveness are also discussed.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

Science.gov (United States)

Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

Directory of Open Access Journals (Sweden)

Arnt-Ove Hovden

Full Text Available Dendritic cells (DC used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

Integral measurement of the {sup 12}C(n, p){sup 12}B reaction up to 10 GeV

Energy Technology Data Exchange (ETDEWEB)

Zugec, P.; Bosnar, D. [University of Zagreb, Department of Physics, Faculty of Science, Zagreb (Croatia); Colonna, N.; Barbagallo, M.; Mastromarco, M.; Tagliente, G.; Variale, V. [Istituto Nazionale di Fisica Nucleare, Bari (Italy); Ventura, A. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Mengoni, A. [ENEA, Bologna (Italy); Altstadt, S.; Langer, C.; Lederer, C.; Reifarth, R.; Schmidt, S.; Weigand, M. [Johann-Wolfgang-Goethe Universitaet, Frankfurt (Germany); Andrzejewski, J.; Marganiec, J.; Perkowski, J. [Uniwersytet Lodzki, Lodz (Poland); Audouin, L.; Leong, L.S.; Tassan-Got, L. [Centre National de la Recherche Scientifique/IN2P3 - IPN, Orsay (France); Becares, V.; Cano-Ott, D.; Garcia, A.R.; Gonzalez-Romero, E.; Martinez, T.; Mendoza, E. [Centro de Investigaciones Energeticas Medioambientales y Tecnologicas (CIEMAT), Madrid (Spain); Becvar, F.; Krticka, M.; Kroll, J.; Valenta, S. [Charles University, Prague (Czech Republic); Belloni, F.; Mondalaers, W.; Plompen, A.; Schillebeeckx, P. [European Commission JRC, Institute for Reference Materials and Measurements, Geel (Belgium); Berthoumieux, E.; Fraval, K.; Gunsing, F. [CEA/Saclay - IRFU, Gif-sur-Yvette (France); Billowes, J.; Ware, T.; Wright, T. [University of Manchester, Manchester (United Kingdom); Boccone, V.; Brugger, M.; Calviani, M.; Cerutti, F.; Chiaveri, E.; Chin, M.; Ferrari, A.; Guerrero, C.; Losito, R.; Roman, F.; Rubbia, C.; Tsinganis, A.; Versaci, R.; Vlachoudis, V.; Weiss, C. [CERN, Geneva (Switzerland); Calvino, F.; Cortes, G.; Gomez-Hornillos, M.B.; Riego, A. [Universitat Politecnica de Catalunya, Barcelona (Spain); Carrapico, C.; Goncalves, I.F.; Sarmento, R.; Vaz, P. [Universidade de Lisboa, C2TN-Instituto Superior Tecnico, Lisboa (Portugal); Cortes-Giraldo, M.A.; Praena, J.; Quesada, J. [Universidad de Sevilla, Sevilla (Spain); Cosentino, L.; Finocchiaro, P. [INFN - Laboratori Nazionali del Sud, Catania (Italy); Diakaki, M.; Karadimos, D.; Kokkoris, M.; Vlastou, R. [National Technical University of Athens (NTUA), Athens (Greece); Domingo-Pardo, C.; Giubrone, G.; Tain, J.L. [CSIC-Universidad de Valencia, Instituto de Fisica Corpuscular, Valencia (Spain); Dressler, R.; Heinitz, S.; Kivel, N.; Schumann, D. [Paul Scherrer Institut, Villigen (Switzerland); Duran, I.; Tarrio, D. [Universidade de Santiago de Compostela, Santiago de Compostela (Spain); Eleftheriadis, C.; Manousos, A. [Aristotle University of Thessaloniki, Thessaloniki (Greece); Ganesan, S.; Gurusamy, P.; Saxena, A. [Bhabha Atomic Research Centre (BARC), Mumbai (India); Griesmayer, E.; Jericha, E.; Leeb, H. [Atominstitut der Oesterreichischen Universitaeten, Technische Universitaet Wien, Wien (Austria); Jenkins, D.G.; Vermeulen, M.J. [University of York, York, Heslington (United Kingdom); Kaeppeler, F. [Karlsruhe Institute of Technology (KIT), Institut fuer Kernphysik, Karlsruhe (Germany); Lo Meo, S. [Istituto Nazionale di Fisica Nucleare, Bologna (Italy); ENEA, Bologna (Italy); Massimi, C.; Mingrone, F.; Vannini, G. [Dipartimento di Fisica, Universita di Bologna (IT); INFN, Bologna (IT); Mastinu, P. [Laboratori Nazionali di Legnaro, Istituto Nazionale di Fisica Nucleare, Legnaro (IT); Milazzo, P.M. [Istituto Nazionale di Fisica Nucleare, Trieste (IT); Mirea, M. [Horia Hulubei National Institute of Physics and Nuclear Engineering - IFIN HH, Magurele (RO); Musumarra, A. [Universita di Catania, Dipartimento di Fisica e Astronomia DFA, Catania (IT); INFN-Laboratori Nazionali del Sud, Catania (IT); Paradela, C. [European Commission JRC, Institute for Reference Materials and Measurements, Geel (BE); Universidade de Santiago de Compostela, Santiago de Compostela (ES); Pavlik, A. [Faculty of Physics, University of Vienna, Wien (AT); Rauscher, T. [University of Hertfordshire, Centre for Astrophysics Research, School of Physics, Astronomy and Mathematics, Hatfield (GB); University of Basel, Department of Physics, Basel (CH); Wallner, A. [Faculty of Physics, University of Vienna, Wien (AT); Australian National University, Research School of Physics and Engineering, Canberra (AU)

2016-04-15

The integral measurement of the {sup 12}C(n, p){sup 12}B reaction was performed at the neutron time-of-flight facility nTOF at CERN. The total number of {sup 12}B nuclei produced per neutron pulse of the nTOF beam was determined using the activation technique in combination with a time-of-flight technique. The cross section is integrated over the nTOF neutron energy spectrum from reaction threshold at 13.6 MeV to 10 GeV. Having been measured up to 1GeV on basis of the {sup 235}U(n, f) reaction, the neutron energy spectrum above 200 MeV has been re-evaluated due to the recent extension of the cross section reference for this particular reaction, which is otherwise considered a standard up to 200 MeV. The results from the dedicated GEANT4 simulations have been used to evaluate the neutron flux from 1 GeV up to 10 GeV. The experimental results related to the {sup 12}C(n, p){sup 12}B reaction are compared with the evaluated cross sections from major libraries and with the predictions of different GEANT4 models, which mostly underestimate the {sup 12}B production. On the contrary, a good reproduction of the integral cross section derived from measurements is obtained with TALYS-1.6 calculations, with optimized parameters. (orig.)

Correlation between the 12C+12C, 12C+13C, and 13C+13C fusion cross sections

Science.gov (United States)

Notani, M.; Esbensen, H.; Fang, X.; Bucher, B.; Davies, P.; Jiang, C. L.; Lamm, L.; Lin, C. J.; Ma, C.; Martin, E.; Rehm, K. E.; Tan, W. P.; Thomas, S.; Tang, X. D.; Brown, E.

2012-01-01

The fusion cross section for 12C+13C has been measured down to Ec.m.=2.6 MeV, at which the cross section is of the order of 20 nb. By comparing the cross sections for the three carbon isotope systems, 12C+12C, 12C+13C, and 13C+13C, it is found that the cross sections for 12C+13C and 13C+13C provide an upper limit for the fusion cross section of 12C+12C over a wide energy range. After calibrating the effective nuclear potential for 12C+12C using the 12C+13C and 13C+13C fusion cross sections, it is found that a coupled-channels calculation with the ingoing wave boundary condition (IWBC) is capable of predicting the major peak cross sections in 12C+12C. A qualitative explanation for this upper limit is provided by the Nogami-Imanishi model and by level density differences among the compound nuclei. It is found that the strong resonance found at 2.14 MeV in 12C+12C exceeds this upper limit by a factor of more than 20. The preliminary result from the most recent measurement shows a much smaller cross section at this energy, which agrees with our predicted upper limit.

Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

Energy Technology Data Exchange (ETDEWEB)

Trask, B.J.; Friedman, C. [Univ. of Washington, Seattle, WA (United States); Giorgi, D. [CNRS, Montpelier (France)] [and others

1994-09-01

We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

Proportional Counter Calibration and Analysis for 12C + p Resonance Scattering

Science.gov (United States)

Nelson, Austin; Rogachev, Grigory; Uberseder, Ethan; Hooker, Josh; Koshchiy, Yevgen

2014-09-01

Light exotic nuclei provide a unique opportunity to test the predictions of modern ab initio theoretical calculations near the drip line. In ab initio approaches, nuclear structure is described starting from bare nucleon-nucleon and three-nucleon interactions. Calculations are very heavy and can only be performed for the lightest nuclei (A objective of this project was to test the performance and perform position calibration of this proportional counter array. The test was done using 12C beam. The excitation function for 12C + p elastic scattering was measured and calibration of the proportional counter was performed using known resonances in 13N. The method of calibration, including solid angle calculations, normalization corrections, and position calibration will be presented. Light exotic nuclei provide a unique opportunity to test the predictions of modern ab initio theoretical calculations near the drip line. In ab initio approaches, nuclear structure is described starting from bare nucleon-nucleon and three-nucleon interactions. Calculations are very heavy and can only be performed for the lightest nuclei (A objective of this project was to test the performance and perform position calibration of this proportional counter array. The test was done using 12C beam. The excitation function for 12C + p elastic scattering was measured and calibration of the proportional counter was performed using known resonances in 13N. The method of calibration, including solid angle calculations, normalization corrections, and position calibration will be presented. Funded by DOE and NSF-REU Program; Grant No. PHY-1263281.

Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

Science.gov (United States)

Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

2012-07-13

We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization.

Calculation of astrophysical S-factor and reaction rate in 12C(p, γ)13N reaction

Science.gov (United States)

Moghadasi, A.; Sadeghi, H.; Pourimani, R.

2018-02-01

The 12C(p, γ)13N reaction is the first process in the CNO cycle. Also it is a source of low-energy solar neutrinos in various neutrino experiments. Therefore, it is of high interest to gain data of the astrophysical S-factor in low energies. By applying Faddeev's method, we calculated wave functions for the bound state of 13N. Then the cross sections for resonance and non-resonance were calculated through using Breit-Wigner and direct capture cross section formulae, respectively. After that, we calculated the total S-factor and compared it with previous experimental data, revealing a good agreement altogether. Then, we extrapolated the S-factor in zero energy and the result was 1.32 ± 0.19 (keV.b). In the end, we calculated reaction rate and compared it with NACRE data.

Postirradiation examination of capsules P13R and P13S

International Nuclear Information System (INIS)

Scott, C.B.; Harmon, D.P.; Holzgraf, J.F.

1976-01-01

Capsules P13R and P13S were the seventh and eighth in a series of irradiation tests conducted under the ERDA-sponsored HTGR Fuels and Core Development Program. Reference type LHTGR fuel fabricated with a broad spectrum of property and process variables was irradiated to extreme temperature and fluence conditions. Postirradiation examination revealed that the bonded fuel rods exhibited good stability after irradiation to fast neutron fluences of 12.4 x 10 21 n/cm 2 (E greater than 0.18 MeV), which is 55 percent beyond the LHTGR peak design fast neutron fluence of 8.0 x 10 21 n/cm 2 . Thermal cycling to high temperatures did not adversely affect fuel rod integrity. Particle batches with coating designs representative of the design requirements envisioned for the LHTGR exhibited excellent irradiation performance. Ten batches of fissile and fertile particles were irradiated without coating failure to fast neutron exposures which exceeded the LHTGR peak design exposure by 35 to 52 percent. Capsules P13R and P13S were considered to be very successful qualification tests of LHTGR fuel components. These results provided a substantial data base for the LHTGR Fuel Product Specification and Performance Models used in HTGR core design studies, and demonstrated the excellent irradiation performance of reference LHTGR fuel to well beyond peak design exposures

Partial inelasticity coefficients of negative pions in p, d, α, 12C + 12C and p, 12C + 181Ta collisions at 4.2 GeV/c per nucleon

International Nuclear Information System (INIS)

Olimov, K.K.; Olimov, K.; Gulamov, K.G.; Olimov, A.K.; Lutpullaev, S.L.; Yuldashev, B.S.; Haseeb, M.Q.

2015-01-01

The partial inelasticity coefficients of the negative pions were determined in minimum bias p, d, α, 12 C + 12 C and p, 12 C + 18 Ta collisions at 4.2A GeV/c taking into account the average number of participant nucleons of a projectile nucleus. In nucleus–nucleus collisions, the average values of partial inelasticity coefficients (〈K(π-)〉) of the negative pions did not depend on the mass numbers of projectile and target nuclei. Increase of 〈K(π - )〉 in going from p + 12 C to d, α, 12 C + 12 C collisions was due to an additional source of production of fast negative pions in nucleus–nucleus collisions — a charge exchange conversion of one or more neutrons of a projectile nucleus into a proton and π - . Linking the experimental results of the present analysis at intermediate energy with those obtained at high and ultra-high energies, it was concluded that the average values of partial inelasticity coefficients of pions in nucleon–nucleus and nucleus–nucleus collisions manifest a transitive behavior. At intermediate energies, the values of 〈K(π - )〉 were smaller by a factor of two and more as compared to those at high energies, and they increased further with increasing incident energy, reaching a plateau at E 0 > 100A GeV. (author)

Formidling af praksisforløbet på Modul 12

DEFF Research Database (Denmark)

2013-01-01

De studerende skal efter endt praksisforløb udarbejde et blogindlæg, som kommenteres af 3 andre medstuderendes grupper, samt vejleder. Dette materiale skal anvendes som baggrund for deres modulprøve på modul 12......De studerende skal efter endt praksisforløb udarbejde et blogindlæg, som kommenteres af 3 andre medstuderendes grupper, samt vejleder. Dette materiale skal anvendes som baggrund for deres modulprøve på modul 12...

Isolation of a cosmid sublibrary for a region of chromosome 12 frequently amplified in human cancers using a complex chromosome microdissection probe

Energy Technology Data Exchange (ETDEWEB)

Elkahloun, A.G.; Meltzer, P.S.; Guan, Xin-Yuan [National Institutes of Health, Bethesda, MD (United States)] [and others

1996-02-01

Chromosome-specific cosmid libraries are in extremely useful resource for positional cloning projects. Once a particular region of interest has been identified, it would be of value to have an approach for isolating chromosome band-specific cosmids that could be assembled into a sublibrary for rapid screening. We constructed a region-specific sublibrary of 700 cosmids by screening a chromosome 12-specific cosmid library with a complex probe generated by degenerate oligonucleotide-primed PCR of a microdissected homogeneously staining region containing sequences amplified from chromosome 12q13-q15. Based on fluorescence in situ hybridization, approximately 60% of the cosmids in the sublibrary were derived from the microdissected region. To demonstrate further the utility of the sublibrary, a 150-kb contig containing the SAS and CDK4 genes was constructed, as well as several additional contigs between CDK4 and MDM2. This study demonstrates the possibility of utilizing probes generated by microdissection for assembling band-specific libraries that are amendable to rapid screening with multiple markers.

High-resolution YAC-cosmid-STS map of human chromosome 13.

Science.gov (United States)

Cayanis, E; Russo, J J; Kalachikov, S; Ye, X; Park, S H; Sunjevaric, I; Bonaldo, M F; Lawton, L; Venkatraj, V S; Schon, E; Soares, M B; Rothstein, R; Warburton, D; Edelman, I S; Zhang, P; Efstratiadis, A; Fischer, S G

1998-01-01

We have assembled a high-resolution physical map of human chromosome 13 DNA (approximately 114 Mb) from hybridization, PCR, and FISH mapping data using a specifically designed set of computer programs. Although the mapping of 13p is limited, 13q (approximately 98 Mb) is covered by an almost continuous contig of 736 YACs aligned to 597 contigs of cosmids. Of a total of 10,789 cosmids initially selected from a chromosome 13-specific cosmid library (16,896 colonies) using inter-Alu PCR probes from the YACs and probes for markers mapped to chromosome 13, 511 were assembled in contigs that were established from cross-hybridization relationships between the cosmids. The 13q YAC-cosmid map was annotated with 655 sequence tagged sites (STSs) with an average spacing of 1 STS per 150 kb. This set of STSs, each identified by a D number and cytogenetic location, includes database markers (198), expressed sequence tags (93), and STSs generated by sequencing of the ends of cosmid inserts (364). Additional annotation has been provided by positioning 197 cosmids mapped by FISH on 13q. The final (comprehensive) map, a list of STS primers, and raw data used in map assembly are available at our Web site (genome1.ccc.columbia.edu/ approximately genome/) and can serve as a resource to facilitate accurate localization of additional markers, provide substrates for sequencing, and assist in the discovery of chromosome 13 genes associated with hereditary diseases.

Crystal growth and structure of KLnP/sub 4/O/sub 12/

International Nuclear Information System (INIS)

Guangyan, H.; Shuzhen, L.; Shuying, Y.; Mingyu, C.

1985-01-01

Potassium rare earth tetraphosphates KLnP/sub 4/O/sub 12/ are a kind of polyphosphates of rare earths with unique properties and structures. KNdP/sub 4/O/sub 12/ is a high-Nd-concentration laser material with a non-centrosymmetric space group P2, yielding linear and nonlinear optical properties. α-KErP/sub 4/O/sub 12/ might be used as a material for engineering device purpose. KTbP/sub 4/O/sub 12/ can emit strong green fluorescence, it might be a kind of a new crystal material for laser or luminescence. In order to search for new crystal materials and to study the correlations among the composition, structures and the properties of rare earth compounds, the crystal growth of KLnP/sub 4/O/sub 12/ and their structures are studied in this paper

WARM SPITZER PHOTOMETRY OF THREE HOT JUPITERS: HAT-P-3b, HAT-P-4b AND HAT-P-12b

Energy Technology Data Exchange (ETDEWEB)

Todorov, Kamen O. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Deming, Drake [Department of Astronomy, University of Maryland at College Park, College Park, MD 20742 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Lewis, Nikole K. [Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cowan, Nicolas B. [Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Desert, Jean-Michel [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Sada, Pedro V. [Department of Physics and Mathematics, University of Monterrey, Monterrey (Mexico); Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

2013-06-20

We present Warm Spitzer/IRAC secondary eclipse time series photometry of three short-period transiting exoplanets, HAT-P-3b, HAT-P-4b and HAT-P-12b, in both the available 3.6 and 4.5 {mu}m bands. HAT-P-3b and HAT-P-4b are Jupiter-mass objects orbiting an early K and an early G dwarf star, respectively. For HAT-P-3b we find eclipse depths of 0.112%+0.015%-0.030% (3.6 micron) and 0.094%+0.016%-0.009% (4.5 {mu}m). The HAT-P-4b values are 0.142%+0.014%-0.016% (3.6 micron) and 0.122%+0.012%-0.014% 4.5 {mu}m). The two planets' photometry is consistent with inefficient heat redistribution from their day to night sides (and low albedos), but it is inconclusive about possible temperature inversions in their atmospheres. HAT-P-12b is a Saturn-mass planet and is one of the coolest planets ever observed during secondary eclipse, along with the hot Neptune GJ 436b and the hot Saturn WASP-29b. We are able to place 3{sigma} upper limits on the secondary eclipse depth of HAT-P-12b in both wavelengths: <0.042% (3.6 {mu}m) and <0.085% (4.5 {mu}m). We discuss these results in the context of the Spitzer secondary eclipse measurements of GJ 436b and WASP-29b. It is possible that we do not detect the eclipses of HAT-P-12b due to high eccentricity, but find that weak planetary emission in these wavelengths is a more likely explanation. We place 3{sigma} upper limits on the |e cos {omega}| quantity (where e is eccentricity and {omega} is the argument of periapsis) for HAT-P-3b (<0.0081) and HAT-P-4b (<0.0042), based on the secondary eclipse timings.

Antibody response in vaccinated pregnant mares to recent G3BP[12] and G14P[12] equine rotaviruses

Directory of Open Access Journals (Sweden)

Nemoto Manabu

2012-11-01

Full Text Available Abstract Background Both the G3P[12] and the G14P[12] type of equine group A rotavirus (RVA have recently become predominant in many countries, including Japan. G3 types are classified further into G3A and G3B. The G3A viruses have been circulating in Europe, Australia, and Argentina, and the G3B viruses have been circulating in Japan. However, only an inactivated vaccine containing a single G3BP[12] strain is commercially available in Japan. To assess the efficacy of the current vaccine against recently circulating equine RVA strains, we examined antibody responses in pregnant mares to recent G3BP[12] and G14P[12] strains by virus neutralization test. Findings After vaccination in five pregnant mares, the geometric mean serum titers of virus-neutralizing antibody to recent G3BP[12] strains increased 5.3- to 7.0-fold and were similar to that against homologous vaccine strain. Moreover, antibody titers to recent G14P[12] strains were also increased 3.0- to 3.5-fold. Conclusions These results suggest that inoculation of mares with the current vaccine should provide foals with virus-neutralizing antibodies against not only the G3BP[12] but also the G14P[12] RVA strain via the colostrum.

Differential cross section measurement of elastic scattering 12C(p,p)12C in the astrophysical range of energy

International Nuclear Information System (INIS)

Baktibayev, M.K.; Burminskii, V.P.; Burtebaev, N.; Dzazairov -Kakhramanov, V.; Hassan, S.F.; Satpaev, N.K.; Zazulin, D.M.

2004-01-01

Full text: The fulfillment of planned works on measurements of differential cross sections of elastic scattering of protons on nuclear 12 C at the energy region of 350†1050 keV suggests the preparation of thin self - supporting carbon target. The self - supporting target is necessary in order to perform investigations in the total angular range. In the future last data will be used in order to determine optical potentials and scattering phases for this nuclear in the energy range of astrophysical interest. There was prepared target layer of the 12 C with natural composition of carbon and of thickness of 17.4 μg/cm 2 . The spraying was conducted in the vacuum evaporation installation (VUP - 4) by an electron bombardment method. Carbon was sprayed on a glass plate with previously deposited of layer salt. After a heating during 12 hours at the temperature of 150 o C the film of carbon was floated from glass plate and self - supporting target has been picked up on the specially prepared target frame. In order to determine thickness of target there was used the resonance chamber, installed in the protons channel of the accelerator RAC - 2 - 1 (INP NNC RK), with the help of which there was measured energy loss of the protons beam during the passage through target, disposed in the central chamber. For this purpose there was used the reaction 27 Al(p,γ) 28 Si with narrow resonance with E R = 992 keV and with detection of gamma-quanta with E γ = 1779 keV. On shift of the resonance E R =992 keV in the reaction 27 Al(p,γ) 28 Si, which takes place owing to protons energy loss in the thickness of carbon film, and using table values of brake quantities S(E p )[MeV·cm 2 /g] [1], there was determined thickness of this fine film. Such the method allows to determine thicknesses of films in the interval of (10 † 100) mcg/cm 2 with the accuracy of not worse than 5%. In the present work there were carried out measurements of angular distributions of cross sections of the

Wolf-Hirschhorn (4p-) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion.

Science.gov (United States)

Chen, Chih-Ping; Su, Yi-Ning; Chen, Yi-Yung; Su, Jun-Wei; Chern, Schu-Rern; Chen, Yu-Ting; Chen, Wen-Lin; Chen, Li-Feng; Wang, Wayseen

2011-12-01

To present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) associated with microduplications at 8p and 10p in a fetus with an apparently pure 4p deletion. A 35-year-old gravida 2, para 1 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Her husband was 38 years of age. There was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(4p16.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 6.5-Mb deletion at 4p16.3-p16.1, a 1.2-Mb microduplication at 8p22-p21.3, and a 1.1-Mb microduplication at 10p15.3, or arr cgh 4p16.3p16.1 (0-6,531,998 bp)×1, 8p22p21.3 (18,705,388-19,940,445 bp)×3, 10p15.3 (0-1,105,065 bp)×3. Polymorphic DNA marker analysis confirmed a paternal origin of 4p deletion. Prenatal ultrasound revealed facial dysmorphism and hypospadias. The aCGH analysis of the parents revealed no genomic imbalance. Fluorescence in situ hybridization study showed an unbalanced reciprocal translocation between chromosomes 4 and 10 at bands 4p16.1 and 10p15.3. The cytogenetic result, thus, was 46,XY,der(4)t(4;10)(p16.1;p15.3),dup(8)(p21.3p22). The parents elected to terminate the pregnancy, and a 470-g malformed fetus was delivered. The present case provides evidence that an apparently pure 4p deletion can be associated with subtle chromosome imbalances in other chromosomes. Copyright © 2011. Published by Elsevier B.V.

Inflammation and elevation of interleukin-12p40 in patients with schizophrenia

Directory of Open Access Journals (Sweden)

Nora eBedrossian

2016-03-01

Full Text Available Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning, which suggests that it likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological contributors for psychiatric disorders, including schizophrenia. Although the role of inflammation in schizophrenia is becoming evident, the number of studies in this area is relatively scarce, especially in Lebanon, and increased procedural thoroughness is needed. Cytokines play a key role in the activation of the immune system and strongly influence neurotransmission. Previous investigation of plasma levels showed dysregulation of interleukin (IL-12. However, genotypical variations of this interleukin have not been investigated for patients with schizophrenia yet. Thus, in this paper, we aimed to compute and assess IL-12p40 levels in the sera of individuals with schizophrenia from different provinces in Lebanon and compare it to controls. Healthy subjects comprised 60 individuals with a male/female (M/F ratio of 31/29, whereas patients with schizophrenia consisted of 63 subjects with an M/F ratio of 30/33. The mean age for healthy controls was 30 years, whereas that for patients with schizophrenia was 35 years. A standardized ELISA technique was used to measure the concentration of IL-12p40 in all collected sera (n=123. The mean IL-12p40 levels in patients with schizophrenia were significantly higher than in healthy controls (p=0.002. Healthy females had a significantly higher concentration of IL-12p40 than healthy males (p=0.009. Female patients with schizophrenia had significantly higher concentrations of IL-12p40 than their male counterparts (p<0.001, healthy females (p=0.018 and healthy males (p<0.001, respectively. Male patients with schizophrenia had significantly higher concentrations of IL-12p40 than healthy males (p=0.023. The study’s results suggest that IL-12p40

WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with Gα12/13.

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Arthofer, Elisa; Hot, Belma; Petersen, Julian; Strakova, Katerina; Jäger, Stefan; Grundmann, Manuel; Kostenis, Evi; Gutkind, J Silvio; Schulte, Gunnar

2016-10-01

Frizzleds (FZDs) are unconventional G protein-coupled receptors that belong to the class Frizzled. They are bound and activated by the Wingless/Int-1 lipoglycoprotein (WNT) family of secreted lipoglycoproteins. To date, mechanisms of signal initiation and FZD-G protein coupling remain poorly understood. Previously, we showed that FZD6 assembles with Gαi1/Gαq (but not with Gαs, Gαo and Ga12/13), and that these inactive-state complexes are dissociated by WNTs and regulated by the phosphoprotein Dishevelled (DVL). Here, we investigated the inactive-state assembly of heterotrimeric G proteins with FZD4, a receptor important in retinal vascular development and frequently mutated in Norrie disease or familial exudative vitreoretinopathy. Live-cell imaging experiments using fluorescence recovery after photobleaching show that human FZD4 assembles-in a DVL-independent manner-with Gα12/13 but not representatives of other heterotrimeric G protein subfamilies, such as Gαi1, Gαo, Gαs, and Gαq The FZD4-G protein complex dissociates upon stimulation with WNT-3A, WNT-5A, WNT-7A, and WNT-10B. In addition, WNT-induced dynamic mass redistribution changes in untransfected and, even more so, in FZD4 green fluorescent protein-transfected cells depend on Gα12/13 Furthermore, expression of FZD4 and Gα12 or Gα13 in human embryonic kidney 293 cells induces WNT-dependent membrane recruitment of p115-RHOGEF (RHO guanine nucleotide exchange factor, molecular weight 115 kDa), a direct target of Gα12/13 signaling, underlining the functionality of an FZD4-Gα12/13-RHO signaling axis. In summary, Gα12/13-mediated WNT/FZD4 signaling through p115-RHOGEF offers an intriguing and previously unappreciated mechanistic link of FZD4 signaling to cytoskeletal rearrangements and RHO signaling with implications for the regulation of angiogenesis during embryonic and tumor development. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells.

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Tina Zavašnik-Bergant

Full Text Available Dendritic cells (DC play a pivotal role as antigen presenting cells (APC and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70 during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii.

Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II.

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Jeske, Y W A; So, A; Kelemen, L; Sukor, N; Willys, C; Bulmer, B; Gordon, R D; Duffy, D; Stowasser, M

2008-04-01

1. There are two types of familial hyperaldosteronism (FH): FH-I and FH-II. FH-I is caused by a hybrid CYP11B1/CYP11B2 gene mutation. The genetic cause of FH-II, which is more common, is unknown. Adrenal hyperplasia and adenomas are features. We previously reported linkage of FH-II to a approximately 5 Mb region on chromosome 7p22. We subsequently reported finding no causative mutations in the retinoblastoma-associated Kruppel-associated box gene (RBaK), a candidate at 7p22 involved in tumorigenesis and cell cycle control. 2. In the current study we investigated RBaK regulatory regions and two other candidate genes: postmeiotic segregation increased 2 (PMS2, involved in DNA mismatch repair and tumour predisposition) and guanine nucleotide-binding protein alpha-12 (GNA12, a transforming oncogene). 3. The GNA12 and PMS2 genes were examined in two affected (A1, A2) and two unaffected (U1, U2) subjects from a large 7p22-linked FH-II family (family 1). No mutations were found. 4. The RBaK and PMS2 distal promoters were sequenced to -2150 bp from the transcription start site for RBaK and-2800 bp for PMS2. Five unreported single nucleotide polymorphisms (SNPs) were found in subjects A1, A2 but not in U1 or U2; A(-2031 bp)T, T(-2030 bp)G, G(-834 bp)C, C(-821 bp)G in RBaK and A(-876 bp)G in PMS2. Additional affected and unaffected subjects from family 1 and from two other 7p22-linked FH-II families and 58 unrelated normotensive control subjects were genotyped for these SNPs. 5. The five novel SNPs were found to be present in a significant proportion of normotensive controls. The four RBaK promoter SNPs were found to be in linkage disequilibrium in the normal population. The RBaK promoter (-)2031T/2030G/834C/821T allele was found to be in linkage disequilibrium with the causative mutation in FH-II family 1, but not in families 2 and 3. The PMS2 promoter (-)876G allele was also found to be linked to affected phenotypes in family 1. 6. The RBaK and PMS2 promoter SNPs alter the

Convergence and divergence of tumor-suppressor and proto-oncogenes in chimpanzee from human chromosome 17

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Verma, R.S.; Ramesh, K.H. [Long Island College Hospital, Brooklyn, NY (United States)

1994-09-01

Due to the emergence of molecular technology, the phylogenetic evolution of the human genome via apes has become a saltatory even. In the present investigation, cosmid probes for P53, Charcot-Marie-Tooth [CMTIA], HER-2/NEU and myeloperoxidase [MPO] were used. Probes mapping to these genetic loci are well-defined on human chromosome 17 [HSA 17]. We localized these genes on chimpanzee [Pan troglodyte] chromosomes by FISH technique employing two different cell lines. Our results indicate that chimpanzee chromosome 19 [PTR 19] differs from HSA 17 by a pericentric inversion. The P53 gene assigned to HSA 17p13.1 is localized on PTR 19p15 and the MPO sequence of HSA 17q21.3-23 hybridized to PTR 19q23. Perplexing enough, HER-2/NEU assigned to HSA 17q11.2 localized to PTR 19p12. Obviously, there is convergence of P53 and MPO regions and distinctive divergence of HER-2/NEU and CMT1A regions of human and chimpanzee. This investigation has demonstrated the pronounced genetic shuffling which occurred during the origin of HSA 17. Molecular markers should serve as evolutionary punctuations in defining the precise sequence of genetic events that led to the evolution of other chromosomes whose genomic synteny, although similar, have surprisingly evolved through different mechanisms.

Rock bream (Oplegnathus fasciatus) IL-12p40: identification, expression, and effect on bacterial infection.

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Zhang, Lu; Zhang, Bao-Cun; Hu, Yong-Hua

2014-08-01

IL-12p40, also called IL-12β, is a subunit of the proinflammatory cytokines interleukin (IL)-12 and IL-23. In teleost, IL-12p40 homologues have been identified in several species, however, the biological function of fish IL-12p40 is essentially unknown. In this work, we reported the identification and analysis of an IL-12p40, OfIL-12p40, from rock bream (Oplegnathus fasciatus). OfIL-12p40 is composed of 361 amino acids and possesses a conserved IL-12p40 domain and a WSxWS signature motif characteristic of known IL-12p40. Constitutive expression of OfIL-12p40 occurred in multiple tissues and was highest in kidney. Experimental infection with bacterial pathogen upregulated the expression of OfIL-12p40 in kidney and spleen in a time-dependent manner. Purified recombinant OfIL-12p40 (rOfIL-12p40) stimulated the respiratory burst activity of peripheral blood leukocytes in a dose-dependent manner. rOfIL-12p40 also enhanced the resistance of rock bream against bacterial infection and upregulated the expression of innate immune genes in kidney. Taken together, these results indicate that OfIL-12p40 possesses cytokine-like property and plays a role in immune defense against bacterial infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study for the charge symmetric systems, 12C+13N and 12C+13C with the orthogonalized coupled-reaction-channel method

International Nuclear Information System (INIS)

Imanishi, B.; Denisov, V.; Motobayashi, T.

1996-10-01

The charge-symmetric scattering systems, 12 C+ 13 N and 12 C+ 13 C have been investigated by using the orthogonalized coupled-reaction-channel (OCRC) method with the basis functions of the elastic, inelastic and transfer channels defined by the single-particle states, 1p1/2, 2s1/2, 1d5/2 and 1d3/2 of the valence nucleon in 13 N or 13 C. The data of the elastic scattering of 13 N on 12 C measured by Lienard et al. have been explained consistently with the data of the elastic and inelastic scattering of the 12 C+ 13 C system. The CRC effects both on the above systems are very strong, although those on the 12 C+ 13 N system are fairly weaker than the 12 C+ 13 C system. The role of the highly excited single-particle states 1d3/2 is particularly important in the formation of a specific CRC scheme, i.e., the formation of the covalent molecules due to the hybridization caused by the mixing of the different parity single-particle states. The fusion cross sections of the 12 C+ 13 C system at energies below the Coulomb barrier are strongly enhanced as a result of the strong CRC effects as compared with those of the 12 C+ 12 C system, while in 12 C+ 13 N system the enhancement of the sub-barrier fusion has not been observed. The above absorption mechanism for the 12 C+ 13 C system explains the lack of the molecular-resonance phenomena observed in the 12 C+ 12 C system. We check the effects of the dipole (E1) transition of the valence nucleon in 13 N (and also in 13 C) due to the core-core Coulomb interaction in the scattering at sub-barrier energies. The effects are not appreciable. (author)

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

International Nuclear Information System (INIS)

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

1988-01-01

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

The distal region of 11p13 and associated genetic diseases

NARCIS (Netherlands)

Mannens, M.; Hoovers, J. M.; Bleeker-Wagemakers, E. M.; Redeker, E.; Bliek, J.; Overbeeke-Melkert, M.; Saunders, G.; Williams, B.; van Heyningen, V.; Junien, C.

1991-01-01

The distal region of human chromosome band 11p13 is believed to contain a cluster of genes involved in the development of the eye, kidney, urogenital tract, and possibly the nervous system. Genetic abnormalities of this region can lead to Wilms tumor, aniridia, urogenital abnormalities, and mental

Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes.

Science.gov (United States)

Heinzen, Erin L; Radtke, Rodney A; Urban, Thomas J; Cavalleri, Gianpiero L; Depondt, Chantal; Need, Anna C; Walley, Nicole M; Nicoletti, Paola; Ge, Dongliang; Catarino, Claudia B; Duncan, John S; Kasperaviciūte, Dalia; Tate, Sarah K; Caboclo, Luis O; Sander, Josemir W; Clayton, Lisa; Linney, Kristen N; Shianna, Kevin V; Gumbs, Curtis E; Smith, Jason; Cronin, Kenneth D; Maia, Jessica M; Doherty, Colin P; Pandolfo, Massimo; Leppert, David; Middleton, Lefkos T; Gibson, Rachel A; Johnson, Michael R; Matthews, Paul M; Hosford, David; Kälviäinen, Reetta; Eriksson, Kai; Kantanen, Anne-Mari; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J; Wieser, Heinz-Gregor; Zumsteg, Dominik; Ortega, Marcos; Wood, Nicholas W; Huxley-Jones, Julie; Mikati, Mohamad; Gallentine, William B; Husain, Aatif M; Buckley, Patrick G; Stallings, Ray L; Podgoreanu, Mihai V; Delanty, Norman; Sisodiya, Sanjay M; Goldstein, David B

2010-05-14

Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12

OpenAIRE

Kilarski, L. L.; Achterberg, S.; Devan, W. J.; Traylor, M.; Malik, R.; Lindgren, A.; Pare, G.; Sharma, P.; Slowik, A.; Thijs, V.; Walters, M.; Worrall, B. B.; Sale, M. M.; Algra, A.; Kappelle, L. J.

2014-01-01

textabstractResults: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p 5 7.12 3 10-11) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p 5 0.695).Conclusion: Our resu...

Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia.

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Pengchong Jiang

Full Text Available Nerve injury is accompanied by a liberation of diverse nucleotides, some of which act as 'find/eat-me' signals in mediating neuron-glial interplay. Intercellular Ca2+ wave (ICW communication is the main approach by which glial cells interact and coordinate with each other to execute immune defense. However, the detailed mechanisms on how these nucleotides participate in ICW communication remain largely unclear. In the present work, we employed a mechanical stimulus to an individual BV-2 microglia to simulate localized injury. Remarkable ICW propagation was observed no matter whether calcium was in the environment or not. Apyrase (ATP/ADP-hydrolyzing enzyme, suramin (broad-spectrum P2 receptor antagonist, 2-APB (IP3 receptor blocker and thapsigargin (endoplasmic reticulum calcium pump inhibitor potently inhibited these ICWs, respectively, indicating the dependence of nucleotide signals and P2Y receptors. Then, we detected the involvement of five naturally occurring nucleotides (ATP, ADP, UTP, UDP and UDP-glucose by desensitizing receptors. Results showed that desensitization with ATP and ADP could block ICW propagation in a dose-dependent manner, whereas other nucleotides had little effect. Meanwhile, the expression of P2Y receptors in BV-2 microglia was identified and their contributions were analyzed, from which we suggested P2Y12/13 receptors activation mostly contributed to ICWs. Besides, we estimated that extracellular ATP and ADP concentration sensed by BV-2 microglia was about 0.3 μM during ICWs by analyzing calcium dynamic characteristics. Taken together, these results demonstrated that the nucleotides ATP and ADP were predominant signal transmitters in mechanical stimulation-induced ICW communication through acting on P2Y12/13 receptors in BV-2 microglia.

Comparative mapping in the beige-satin region of mouse chromosome 13

Energy Technology Data Exchange (ETDEWEB)

Perou, C.M.; Pryor, R.; Kaplan, J. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)] [and others

1997-01-15

The proximal end of mouse chromosome (Chr) 13 contains regions conserved on human chromosomes 1q42-q44, 6p23-p21, and 7p22-p13. This region also contains mutations that may be models for human disease, including beige (human Chediak-Higashi syndrome). An interspecific backcross of SB/Le and Mus spretus mice was used to generate a molecular genetic linkage map of mouse chromosome 13 with an emphasis on the proximal region including beige (bg) and satin (sa). This map provides the gene order of the two phenotypic markers bg and sa relative to restriction fragment length polymorphisms and simple sequence length polymorphisms in 131 backcross animals. In parallel, we have created a physical map of the region using Nidogen (Nid) as a molecular starting point for cloning a YAC contig that was used to identify the beige gene. The physical map provides the fine-structure order of genes and anonymous DNA fragments that was not resolved by the genetic linkage mapping. The results show that the bg region of mouse Chr 13 is highly conserved on human Chr 1q42-q44 and provide a starting point for a complete functional analysis of the entire bg-sa interval. 37 refs., 4 figs., 1 tab.

NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation

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Labhart Paul

2007-05-01

Full Text Available Abstract Background p53 is recognized as a critical regulator of the cell cycle and apoptosis. Mounting evidence also suggests a role for p53 in differentiation of cells including neuronal precursors. We studied the transcriptional role of p53 during nerve growth factor-induced differentiation of the PC12 line into neuron-like cells. We hypothesized that p53 contributed to PC12 differentiation through the regulation of gene targets distinct from its known transcriptional targets for apoptosis or DNA repair. Results Using a genome-wide chromatin immunoprecipitation cloning technique, we identified and validated 14 novel p53-regulated genes following NGF treatment. The data show p53 protein was transcriptionally activated and contributed to NGF-mediated neurite outgrowth during differentiation of PC12 cells. Furthermore, we describe stimulus-specific regulation of a subset of these target genes by p53. The most salient differentiation-relevant target genes included wnt7b involved in dendritic extension and the tfcp2l4/grhl3 grainyhead homolog implicated in ectodermal development. Additional targets included brk, sdk2, sesn3, txnl2, dusp5, pon3, lect1, pkcbpb15 and other genes. Conclusion Within the PC12 neuronal context, putative p53-occupied genomic loci spanned the entire Rattus norvegicus genome upon NGF treatment. We conclude that receptor-mediated p53 transcriptional activity is involved in PC12 differentiation and may suggest a contributory role for p53 in neuronal development.

A 1.37-Mb 12p11.22-p11.21 deletion coincident with a 367-kb 22q11.2 duplication detected by array comparative genomic hybridization in an adolescent girl with autism and difficulty in self-care of menstruation.

Science.gov (United States)

Chen, Chih-Ping; Lin, Shuan-Pei; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Lee, Chen-Chi; Wang, Wayseen

2014-03-01

To present an array comparative genomic hybridization (aCGH) characterization of a 12p11.22-p11.21 microdeletion and 22q11.2 microduplication in an adolescent girl with autism, mental retardation, facial dysmorphism, microcephaly, behavior problems, and an apparently balanced reciprocal translocation of t(8;12)(q24.3;p11.2). A 13-year-old girl was referred to the hospital because of autism, mental retardation, and difficulty in the self-care of her menstruation. Cytogenetic analysis revealed an apparently balanced reciprocal translocation and a karyotype of 46,XX,t(8;12) (q24.3;p11.2)dn. The girl manifested microcephaly, hypertelorism, flat facial profile, prominent forehead, thick scalp hair, upslanting palpebral fissures, broad nasal bridge, bulbous nose, right simian crease, bilateral clinodactyly of the fifth fingers, bilateral pes cavus, learning difficulties, mental retardation, emotional instability, cognitive impairment, behavior problems, jumping-like gaits, and autistic spectrum disorder. aCGH was performed to evaluate genomic imbalance in this patient. aCGH analysis revealed a 1.37-Mb 12p11.22-p11.21 microdeletion or arr [hg 19] 12p11.22-p11.21 (30,645,008-32,014,774)×1 and a 367-kb 22q11.21 microduplication or arr [hg 19] 22q11.21 (18,657,470-19,024,306)×3. The 1.37-Mb 12p11.22-p11.21 microdeletion encompassed 26 genes including IPO8, CAPRIN2, and DDX11, and the 367-kb 22q11.21 microduplication encompassed 20 genes including USP18, DGCR6, PRODH, and DGCR2. An apparently balanced translocation may be in fact affected by concurrent deletion and duplication in two different chromosomal regions. Our presentation provides information on diagnostic phenotype of 12p11.22-p11.21 microdeletion and 22q11.2 microduplication. Copyright © 2014. Published by Elsevier B.V.

Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

Science.gov (United States)

Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

2016-08-01

Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

Identification of a novel gene family that includes the interferon-inducible human genes 6–16 and ISG12

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Parker Nadeene

2004-01-01

Full Text Available Abstract Background The human 6–16 and ISG12 genes are transcriptionally upregulated in a variety of cell types in response to type I interferon (IFN. The predicted products of these genes are small (12.9 and 11.5 kDa respectively, hydrophobic proteins that share 36% overall amino acid identity. Gene disruption and over-expression studies have so far failed to reveal any biochemical or cellular roles for these proteins. Results We have used in silico analyses to identify a novel family of genes (the ISG12 gene family related to both the human 6–16 and ISG12 genes. Each ISG12 family member codes for a small hydrophobic protein containing a conserved ~80 amino-acid motif (the ISG12 motif. So far we have detected 46 family members in 25 organisms, ranging from unicellular eukaryotes to humans. Humans have four ISG12 genes: the 6–16 gene at chromosome 1p35 and three genes (ISG12(a, ISG12(b and ISG12(c clustered at chromosome 14q32. Mice have three family members (ISG12(a, ISG12(b1 and ISG12(b2 clustered at chromosome 12F1 (syntenic with human chromosome 14q32. There does not appear to be a murine 6–16 gene. On the basis of phylogenetic analyses, genomic organisation and intron-alignments we suggest that this family has arisen through divergent inter- and intra-chromosomal gene duplication events. The transcripts from human and mouse genes are detectable, all but two (human ISG12(b and ISG12(c being upregulated in response to type I IFN in the cell lines tested. Conclusions Members of the eukaryotic ISG12 gene family encode a small hydrophobic protein with at least one copy of a newly defined motif of ~80 amino-acids (the ISG12 motif. In higher eukaryotes, many of the genes have acquired a responsiveness to type I IFN during evolution suggesting that a role in resisting cellular or environmental stress may be a unifying property of all family members. Analysis of gene-function in higher eukaryotes is complicated by the possibility of

Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino-terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence.

Science.gov (United States)

Freimuth, P; Anderson, C W

1993-03-01

The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide.

Academic Training Lectures | The Cosmological Constant Problem | 12-13 November

CERN Multimedia

2015-01-01

Please note that the next series of Academic Training Lectures will take place on the 12 and 13 November. The lectures will be given by Antonio Padilla (University of Nottingham, UK). The Cosmological Constant Problem (1/2) on Thursday, 12 November from 11:00 a.m. to 12:30 p.m. https://indico.cern.ch/event/453187/ The Cosmological Constant Problem (2/2) on Friday, 13 November from 11:00 a.m. to 12:30 p.m. https://indico.cern.ch/event/453188/ at CERN, Council Chamber (503-1-001)  Description: I will review the cosmological constant problem as a serious challenge to our notion of naturalness in Physics. Weinberg’s no go theorem is worked through in detail. I review a number of proposals possibly including Linde's universe multiplication, Coleman's wormholes, the fat graviton, and SLED, to name a few. Large distance modifications of gravity are also discussed, with causality considerations pointi...

Platelets Express Activated P2Y12 Receptor in Patients With Diabetes Mellitus.

Science.gov (United States)

Hu, Liang; Chang, Lin; Zhang, Yan; Zhai, Lili; Zhang, Shenghui; Qi, Zhiyong; Yan, Hongmei; Yan, Yan; Luo, Xinping; Zhang, Si; Wang, Yiping; Kunapuli, Satya P; Ye, Hongying; Ding, Zhongren

2017-08-29

Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood. We measured P2Y 12 expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus. We also assayed platelet P2Y 12 activation by measuring cAMP and VASP phosphorylation. The antiplatelet and antithrombotic effects of AR-C78511 and cangrelor were compared in rats. Finally, we explored the role of the nuclear factor-κB pathway in regulating P2Y 12 receptor expression in megakaryocytes. Platelet P2Y 12 levels are 4-fold higher in patients with type 2 diabetes mellitus compared with healthy subjects. P2Y 12 expression correlates with ADP-induced platelet aggregation (r=0.89, P diabetes mellitus is constitutively activated. Although both AR-C78511, a potent P2Y 12 inverse agonist, and cangrelor have similar antiplatelet efficacy on platelets from healthy subjects, AR-C78511 exhibits more powerful antiplatelet effects on diabetic platelets than cangrelor (aggregation ratio 36±3% versus 49±5%, respectively, P diabetes mellitus than cangrelor (thrombus weight 4.9±0.3 mg versus 8.3±0.4 mg, respectively, P diabetes mellitus. Platelet P2Y 12 receptor expression is significantly increased and the receptor is constitutively activated in patients with type 2 diabetes mellitus, which contributes to platelet hyperactivity and limits antiplatelet drug efficacy in type 2 diabetes mellitus. © 2017 American Heart Association, Inc.

Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families.

Science.gov (United States)

Logue, Mark W; Bauver, Sarah R; Knowles, James A; Gameroff, Marc J; Weissman, Myrna M; Crowe, Raymond R; Fyer, Abby J; Hamilton, Steven P

2012-04-01

Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy-clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543-553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. Copyright © 2012 Wiley Periodicals, Inc.

Synthesis, characterization, and photocatalytic properties of Ni12P5 hollow microspheres

Science.gov (United States)

Liu, Shuling; Han, Xiaoli; Zhang, Hongzhe; Liu, Hui

2017-05-01

Ni12P5 hollow microspheres were prepared by a simple mixed cetyltrimethyl ammonium bromide/sodium dodecyl sulfate surfactant-assisted hydrothermal route. The as-prepared Ni12P5 microstructures were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). It was interesting to find that cetyltrimethyl ammonium bromide/sodium dodecyl sulfate could form a micro-reactor by the mixed micelles in the aqueous solution, which served as a soft template for Ni12P5 hollow microspheres with a diameter of 2 6 μm. Moreover, the as-prepared Ni12P5 hollow microspheres exhibited a good photocatalytic degradation activity for some organic dyes (such as Rhodamine B, Methylene Blue, Pyronine B, and Safranine T), and the degradation ratio could achieve more than 80%.

Suppression of Zeeman relaxation in cold collisions of 2P1/2 atoms

International Nuclear Information System (INIS)

Tscherbul, T. V.; Dalgarno, A.; Buchachenko, A. A.; Lu, M.-J.; Weinstein, J. D.

2009-01-01

We present a combined experimental and theoretical study of angular momentum depolarization in cold collisions of 2 P atoms in the presence of an external magnetic field. We show that collision-induced Zeeman relaxation of Ga( 2 P 1/2 ) and In( 2 P 1/2 ) atoms in cold 4 He gas is dramatically suppressed compared to atoms in 2 P 3/2 states. Using rigorous quantum-scattering calculations based on ab initio interaction potentials, we demonstrate that Zeeman transitions in collisions of atoms in 2 P 1/2 electronic states occur via couplings to the 2 P 3/2 state induced by the anisotropy of the interaction potential. Our results suggest the feasibility of sympathetic cooling and magnetic trapping of 2 P 1/2 -state atoms, such as halogens, thereby opening up exciting areas of research in precision spectroscopy and cold-controlled chemistry.

Application of B{sub 12}N{sub 12} and B{sub 12}P{sub 12} as two fullerene-like semiconductors for adsorption of halomethane: Density functional theory study

Energy Technology Data Exchange (ETDEWEB)

Rad, Ali Shokuhi, E-mail: a.shokuhi@gmail.com [Islamic Azad University, Department of Chemical Engineering, Qaemshahr Branch (Iran, Islamic Republic of)

2017-01-15

We examined and discussed the interaction of two halomethanes (mono-chloromethane (MCM), and mono-fluoromethane (MFM)) with B{sub 12}N{sub 12} and B{sub 12}P{sub 12} fullerene-like nanocages as semiconductor based on density functional theory (DFT). We calculated adsorption energies and followed the changes in the electronic structure of semiconductors upon adsorption of MCM and MFM. We found that the adsorption on the B{sub 12}N{sub 12} nano-cluster is energetically more favorable compared to B{sub 12}P{sub 12} nano-cluster. Also for both systems we found higher values of adsorption energy for MFM than for MCM. We found that upon adsorption of above-mentioned species on these two fullerene-like semiconductors, the HOMO–LUMO distributions and also the gap energy for each system did not change significantly, which correspond to the physisorption process. As a result, B{sub 12}N{sub 12} is a more appropriate nano-cluster to be used as a selective sensor for halomethanes, especially for MFM.

Copy number variations of chromosome 16p13.1 region associated with schizophrenia

DEFF Research Database (Denmark)

Ingason, A; Rujescu, D; Cichon, S

2011-01-01

.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion...... carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity...

Recombinant DNA probe (PheA12) from the hc-(ERBA) gene on chromosome 3 detects a high frequency RFLP

Energy Technology Data Exchange (ETDEWEB)

Bale, A E; Usala, S; Weinberger, C; Weintraub, B D; McBride, O W [National Institutes of Health, Bethesda, MD (USA)

1988-08-11

A cDNA probe (phe A12), a 1.5 kb fragment, was obtained by screening a gt10 library with the v-erb-A gene, subcloned into pUC 8. BamHI identifies constant bands at 23 kb, 21 kb, 13 kb, and 7.0 kb and a simple two-allele polymorphism with a band at either 5.3 kb (A1) or 2.8 kb (A2). EcoRV identifies constant bands at 15 kb and 8.9 kb and two separate two-allele polymorphisms--13.5 kb (B1) vs. 10.5 kb (B2) and 3.3 kb (C1) vs. 1.6 kb (C2). It was mapped to chromosome 3 using laser sorted chromosomes. Co-dominant inheritance and cosegregation of BamHI and EcoRV polymorphism was demonstrated in 20 individuals in one large kindred.

File list: InP.Bld.10.AllAg.CH12 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.10.AllAg.CH12 mm9 Input control Blood CH12 SRX140380,SRX185839,SRX145049,SR...X153161,SRX140381,SRX097685 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.CH12.bed ...

Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

DEFF Research Database (Denmark)

Hertz, Jens Michael; Jensen, P H

1985-01-01

A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25)....

Kaberla kalmistu 12.-13. sajandi klaashelmed / Irita Kallis

Index Scriptorium Estoniae

Kallis, Irita

2010-01-01

Kaberla kalmistult leitud klaashelmestest, põhitähelepanu on 12.-13. saj. matuste inventari hulka kuulunud leiumaterjalil. Ülevaade helmeste esimemisvariatsioonidest helmekeedes, võimalikust tähendusest ja väärtusest ning samatüübiliste helmeste dateeringutest naaberaladel

Local distortion induced metal-to-insulator phase transition in PrRu4P12

International Nuclear Information System (INIS)

Cao, D.; Heffner, R.H.; Jeong, I.-K.; Bauer, E.D.; Bridges, F.; Yuhasz, W.M.; Maple, M.B.

2005-01-01

Extended x-ray absorption fine structure (EXAFS) experiments have been carried out on PrRu 4 P 12 and PrOs 4 P 12 to study the metal-to-insulator (MI) phase transition in PrRu 4 P 12 . No Pr displacement was observed across the MI transition temperature from the EXAFS data. Instead, our EXAFS data clearly show that a Ru displacement is associated with this MI transition. The very high Debye temperature for the Ru-P bond (Θ D =690 K) suggests that a slight rotation/displacement of relatively rigid RuP 6 octahedra leads to this small Ru displacement, which accompanies the MI transition at 62 K in PrRu 4 P 12

Isolation of probes specific to human chromosomal region 6p21 from immunoselected irradiation-fusion gene transfer hybrids

International Nuclear Information System (INIS)

Ragoussis, J.; Jones, T.A.; Sheer, D.; Shrimpton, A.E.; Goodfellow, P.N.; Trowsdale, J.; Ziegler, A.

1991-01-01

A hybrid cell line (R21/B1) containing a truncated human chromosome 6 (6pter-6q21) and a human Y chromosome on a hamster background was irradiated and fused to A23 (TK-) or W3GH (HPRT-) hamster cells. Clones containing expressed HLA class I genes (4/40) were selected using monoclonal antibodies. These clones were recloned and analyzed with a panel of probes from the HLA region. One hybrid (4G6) contained the entire HLA complex. Two other hybrids (4J4 and 4H2) contained only the HLA class I region, while the fourth hybrid (5P9) contained HLA class I and III genes in addition to other genes located in the 6p21 chromosomal region. In situ hybridization showed that the hybrid cells contained more than one fragment of human DNA. Alu and LINE PCR products were derived from these cells and compared to each other as well as to products from two somatic cell hybrids having the 6p21 region in common. The PCR fragments were then screened on conventional Southern blots of the somatic cell hybrids to select a panel of novel probes encompassing the 6p21 region. In addition, the origin of the human DNA fragments in hybrid 4J4 was determined by regional mapping of PCR products

Use of a human chromosome 11 radiation hybrid panel to map markers at 11q13

International Nuclear Information System (INIS)

Withers, D.; Richard, C. III; Meeker, T.C.; Maurer, S.; Evans, G.; Myers, R.M.; Cox, D.R.

1990-01-01

A human/hamster hybrid cell line containing human chromosome 11 was X-irradiated and 102-independent derivative lines were recovered. These 'radiation hybrids' contain random fragments of human chromosome 11. This radiation hybrid panel was used to score the retention of markers at band 11q13. Statistical analysis of marker co-retention patterns in the radiation hybrid panel permits a preliminary ordering and mapping of the markers used. The best order for six scored markers is: proximal - CD5 - CD20 - PGA - HST - BCL1 - SEA - distal. Additional markers are currently being scored. The six 11q13 markers above are spread over approximately 10-12 mB of DNA. The mapping data has implications for the identification of the bcl-1 gene. bcl-1 is the site of chromosome breakage in translocations associated with B lymphocytic malignancy. bcl-1 markers map at least 4 Mb away from any of four genes previously hypothesized to be activated by such translocations, thereby making them unlikely candidates for activation

p53 binds human telomeric G-quadruplex in vitro

Czech Academy of Sciences Publication Activity Database

Adámik, Matěj; Kejnovská, Iva; Bažantová, Pavla; Petr, Marek; Renčiuk, Daniel; Vorlíčková, Michaela; Brázdová, Marie

2016-01-01

Roč. 128, SEPT2016 (2016), s. 83-91 ISSN 0300-9084 R&D Projects: GA ČR GA13-36108S; GA ČR(CZ) GP14-33947P Institutional support: RVO:68081707 Keywords : crystal-structure * human-chromosomes * supercoiled dna Subject RIV: BO - Biophysics Impact factor: 3.112, year: 2016

Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family

NARCIS (Netherlands)

Henry, I.; Hoovers, J.; Barichard, F.; Berthéas, M. F.; Puech, A.; Prieur, F.; Gessler, M.; Bruns, G.; Mannens, M.; Junien, C.

1993-01-01

The combined use of qualitative and quantitative analysis of 11p13 polymorphic markers together with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric

Peripheral pn production and decay angular distributions in the reaction pi /sup -/p to (pn)p at 12 GeV/c incident momentum

CERN Document Server

Ghidini, B; Cantore, A; Di Corato, M; Donald, R A; Eades, John; Edwards, D N; Edwards, M E; French, Bernard R; Fry, J R; Houlden, M A; Mandelli, L; Moebes, J P; Müller, K; Navach, F; Palano, A; Palazzi-Cerrina, C; Paul, E; Picciarelli, V; Renneberg, W; Rühmer, W; Smith, I; Zito, G

1978-01-01

The reaction pi /sup -/p to (pn)p/sub s/, where p/sub s/ is a slow proton, was measured at 12 GeV/c incident momentum with the CERN-OMEGA spectrometer. Both antiproton and proton were identified uniquely by electronics information. 1844 events with four-momentum transfer squared in the range 0.13p to (pp)n/sub s/ (where n/sub s/ is a slow neutron) in the same t range. (12 refs).

Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells.

Science.gov (United States)

Seto-Young, D; Avtanski, D; Varadinova, M; Park, A; Suwandhi, P; Leiser, A; Parikh, G; Poretsky, L

2011-06-01

Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (pprogesterone production by 13-18% (pprogesterone production by 17-20% (pprogesterone production by 20-30% (pprogesterone production by 40-60% (pprogesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis. © Georg Thieme Verlag KG Stuttgart · New York.

Analyzing power measurements for the /sup 13/C(p vector,d)/sup 12/C reaction at 200 and 400 MeV

Energy Technology Data Exchange (ETDEWEB)

Liljestrand, R P; Cameron, J M; Hutcheon, D A; MacDonald, R; McDonald, W J; Miller, C A; Olsen, W C [Alberta Univ., Edmonton (Canada); Kraushaar, J J; Shepard, J R [Colorado Univ., Boulder (USA). Nuclear Physics Lab.; Rogers, J G [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

1981-02-26

Cross sections and analyzing powers for the /sup 13/C(p vector,d) reaction have been measured at 200 and 400 MeV to the O/sup +/, ground state and 2/sup +/, 4.44 MeV state of /sup 12/C. While the cross sections are rather structureless, DWBA calculations in exact finite range account well for both the magnitude and shape of the angular distributions. On the other hand, the measured analyzing powers are in serious disagreement with the DWBA calculations.

Ring chromosome 13

DEFF Research Database (Denmark)

Brandt, C A; Hertz, Jens Michael; Petersen, M B

1992-01-01

A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...

File list: InP.Emb.05.AllAg.Mitotic_cycle_12 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Emb.05.AllAg.Mitotic_cycle_12 dm3 Input control Embryo Mitotic cycle 12 SRX7500...69 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Emb.05.AllAg.Mitotic_cycle_12.bed ...

File list: InP.Emb.10.AllAg.Mitotic_cycle_12 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Emb.10.AllAg.Mitotic_cycle_12 dm3 Input control Embryo Mitotic cycle 12 SRX7500...69 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Emb.10.AllAg.Mitotic_cycle_12.bed ...

Study of the (p,pd), (p,pt) and (p,p3He) reactions on 12C and 16O at 75MeV

International Nuclear Information System (INIS)

Grossiord, Jean-Yves.

1976-01-01

These experiments have been performed at the Louvain-la-Neuve cyclotron (Belgium). Protons were detected by a two-detector telescope (one of them being a 7mm thick intrinsic germanium detector) and detection of d, t, 3 He was made with a three-detector telescope. The energy signals coming from these detectors together with the time difference between the two outgoing particles were registered on magnetic tapes. An off-line analysis of these data enabled to construct the excitation spectra of the residual nuclei 10 B, 9 B, 9 Be and 14 N, 13 N, 13 C; the energy resolution was about 400keV. For some of the levels of these nuclei, it has been possible to extract the momentum distribution of the corresponding cluster in 12 C and 16 O. The quasi-free scattering mechanism with distorted waves gives a good representation of the measured distributions and then seems to represent correctly the reaction mechanism. Moreover, assuming for the two and three particle spectroscopic amplitudes the values computed in the framework of the shell model with an effective interaction, it appears that the off-shell scattering cross-sections values are close to the free scattering cross-sections values taken at a proton energy which gives the same relative impulsion p-x as in the incident channel of the three body reaction. Finally, other informations can be obtained from the comparison of these data with experimental results from transfer reactions (p, 3 He) and (p,α): in particular, the population of the T=1 levels of 10 B (1.74MeV) and 14 N(2.31MeV) can be explained by the scattering of a proton on an n-p pair in singlet state (S=0) followed by a transition to the triplet state [fr

P2Y12 receptor-mediated activation of spinal microglia and p38MAPK pathway contribute to cancer-induced bone pain

Directory of Open Access Journals (Sweden)

Liu MJ

2017-02-01

Full Text Available Mingjuan Liu,1 Ming Yao,1,2 Hanqi Wang,1 Longsheng Xu,1 Ying Zheng,1 Bing Huang,1 Huadong Ni,1 Shijie Xu,1 Xuyan Zhou,1 Qingquan Lian2 1Department of Anesthesiology and Pain Medicine, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, 2Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Cancer-induced bone pain (CIBP is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown.Methods: The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms. Using the bone cancer model inoculated with Walker 256 tumor cells into the left tibia of Sprague Dawley rat, we blocked spinal P2Y12R through intrathecal administration of its selective antagonist MRS2395 (400 pmol/µL, 15 µL.Results: We found that not only the ionized calcium-binding adapter molecule 1 (Iba-1-positive microglia in the ipsilateral spinal cord but also mechanical allodynia was significantly inhibited. Furthermore, it decreased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK and the production of proinflammatory cytokines interleukin-1β (IL-1β and interleukin-6 (IL-6, whereas it increased tumor necrosis factor-α (TNF-α.Conclusion: Taken together, our present results suggest that microglial P2Y12R in the spinal cord may contribute to CIBP by the activation of spinal microglia and p38MAPK pathway, thus identifying a potential therapeutic target for the treatment of CIBP. Keywords: P2Y12 receptor, cancer-induced bone pain, p38MAPK pathway, cytokines

Mapping of the human APOB gene to chromosome 2p and demonstration of a two-allele restriction fragment length polymorphism

International Nuclear Information System (INIS)

Huang, L.; Miller, D.A.; Bruns, G.A.P.; Breslow, J.L.

1986-01-01

ApoB is a large glycoprotein with an apparent molecular mass of 550 kDa on NaDodSO 4 /PAGE. Recently, apoB cDNA clones have been isolated from an expression library made with mRNA from a human hepatoma cell line. These clones, which were all 1.5-1.6 kilobases (kb) long and corresponded to the 3' end of apoB mRNA, were used to demonstrate that hepatic apoB mRNA is ≅ 22 kb long. In the current report, a probe derived from one of these cDNA clones, pB8, was used for in situ hybridization experiments to map the human gene for apoB, APOB, to the distal half of the short arm of chromosome 2. This probe was also used to analyze somatic cell hybrids and, in agreement with the in situ hybridization studies, concordancy was demonstrated with chromosome 2. In addition, two hybrids with chromosome 2 translocations that contain only the short arm reacted with the pB8 probe. A third hybrid with a complex rearrangement of chromosome 2, which deleted an interstitial region and the tip of the short arm of chromosome 2, did not react. These data indicate that APOB maps to either 2p21-p23 or 2p24-pter. In further studies, DNA from normal individuals, digested with the restriction endonuclease EcoRI and subjected to Southern blot analysis with the pB8 probe, revealed a two-allele restriction fragment length polymorphism (RFLP). The mapping studies provide the means for understanding the relationship of the APOB locus to others in the human genome, whereas the demonstration of an APOB RFLP increases their ability to assess the role of this locus in determining plasma lipoprotein levels

Quantitative evaluation of interleukin-12 p40 gene expression in peripheral blood mononuclear cells.

Science.gov (United States)

Conte, Enrico; Nigro, Luciano; Fagone, Evelina; Drago, Francesco; Cacopardo, Bruno

2008-01-01

The heterodimeric cytokine IL-12 (composed of a p35 and a p40 subunit) is produced primarily by monocytes, macrophages and B cells. In vitro and in vivo experiments have demonstrated the crucial role of IL-12 in initiating and establishing both innate immunity and T cell-mediated resistance to intracellular pathogens, including Leishmania donovani, Toxoplasma gondii, Listeria monocytogenes, and Mycobacterium tuberculosis. Assessment of cytokine expression has thus become crucial to understand host responses to infections. In this study, by using the reverse transcriptase-real time PCR we developed a highly specific and sensitive assay to quantitatively evaluate IL-12p40 mRNA transcription levels in peripheral blood mononuclear cells (PBMCs) stimulated with PHA vs. unstimulated cells. We also used the ELISA to evaluate bioactive IL-12 release in culture supernatants. We provide evidence that IL-12 p40 mRNA levels were significantly up-regulated in PHA-activated PBMCs. These results were correlated with data of IL-12 levels obtained by ELISA.

An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12.

Directory of Open Access Journals (Sweden)

Bridget H Maher

Full Text Available Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1 × 10(-5 ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92 × 10(-4, whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65 × 10(-4. Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women's Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05.Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63 × 10(-5 is located within the 5'UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men.

Directory of Open Access Journals (Sweden)

Nick Orr

2011-09-01

Full Text Available Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS have recently identified common single nucleotide polymorphisms (SNPs that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35 (odds ratio (OR  = 1.30, p = 7.98×10⁻⁴, rs10941679 (5p12 (OR = 1.26, p = 0.007, rs9383938 (6q25.1 (OR = 1.39, p = 0.004, rs2981579 (FGFR2 (OR = 1.18, p = 0.03, and rs3803662 (TOX3 (OR = 1.48, p = 4.04×10⁻⁶. Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs--rs13387042 (2q35, rs3803662 (TOX3, and rs6504950 (COX11--showed significant differences in ORs (p<0.05 between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development.

A 1.37-Mb 12p11.22–p11.21 deletion coincident with a 367-kb 22q11.2 duplication detected by array comparative genomic hybridization in an adolescent girl with autism and difficulty in self-care of menstruation

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2014-03-01

Conclusion: An apparently balanced translocation may be in fact affected by concurrent deletion and duplication in two different chromosomal regions. Our presentation provides information on diagnostic phenotype of 12p11.22–p11.21 microdeletion and 22q11.2 microduplication.

Correlation between chromosome 9p21 locus deletion and prognosis in clinically localized prostate cancer.

Science.gov (United States)

Barros, Érika Aparecida Felix de; Pontes-Junior, José; Reis, Sabrina Thalita; Lima, Amanda Eunice Ramos; Souza, Isida C; Salgueiro, Jose Lucas; Fontes, Douglas; Dellê, Humberto; Coelho, Rafael Ferreira; Viana, Nayara Izabel; Leite, Kátia Ramos Moreira; Nahas, William C; Srougi, Miguel

2017-05-04

Some studies have reported that deletions at chromosome arm 9p occur frequently and represent a critical step in carcinogenesis of some neoplasms. Our aim was to evaluate the deletion of locus 9p21 and chromosomes 3, 7 and 17 in localized prostate cancer (PC) and correlate these alterations with prognostic factors and biochemical recurrence after surgery. We retrospectively evaluated surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Biochemical recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and the mean postoperative follow-up was 123 months. The deletions were evaluated using fluorescence in situ hybridization with centromeric and locus-specific probes in a tissue microarray containing 2 samples from each patient. We correlated the occurrence of any deletion with pathological stage, Gleason score, ISUP grade group, PSA and biochemical recurrence. We observed a loss of any probe in only 8 patients (7.2%). The most common deletion was the loss of locus 9p21, which occurred in 6.4% of cases. Deletions of chromosomes 3, 7 and 17 were observed in 2.3%, 1.2% and 1.8% patients, respectively. There was no correlation between chromosome loss and Gleason score, ISUP, PSA or stage. Biochemical recurrence occurred in 83% cases involving 9p21 deletions. Loss of 9p21 locus was significantly associated with time to recurrence (p = 0.038). We found low rates of deletion in chromosomes 3, 7 and 17 and 9p21 locus. We observed that 9p21 locus deletion was associated with worse prognosis in localized PC treated by radical prostatectomy.

Crystal structure of 5,7,12,14-tetrahydro-5,14:7,12-bis([1,2]benzenopentacene-6,13-dione

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Mohammad Nozari

2016-12-01

Full Text Available The lattice of 5,7,12,14-tetrahydro-5,14:7,12-bis([1,2]benzenopentacene-6,13-dione, C34H20O2, at 173 K has triclinic (P-1 symmetry and crystallizes with four independent half-molecules in the asymmetric unit. Each molecule is generated from a C17H10O substructure through an inversion center at the centroid of the central quinone ring, generating a wide H-shaped molecule, with a dihedral angle between the mean planes of the terminal benzene rings in each of the two symmetry-related pairs over the four molecules of 68.6 (1 (A, 65.5 (4 (B, 62.3 (9 (C, and 65.8 (8° (D, an average of 65.6 (1°. This compound has applications in gas-separation membranes constructed from polymers of intrinsic microporosity (PIM. The title compound is a product of a double Diels–Alder reaction between anthracene and p-benzoquinone followed by dehydrogenation. It has also been characterized by cyclic voltammetry and rotating disc electrode polarography, FT–IR, high resolution mass spectrometry, elemental analysis, and 1H NMR.

Cloning and comparative mapping of a human chromosome 4-specific alpha satellite DNA sequence

Energy Technology Data Exchange (ETDEWEB)

D' Aiuto, L.; Marzella, R.; Archidiacono, N.; Rocchi, M. (Universita di Bari (Italy)); Antonacci, R. (Instituto Anatomia Umana Normale, Modena (Italy))

1993-11-01

The authors have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed. 33 refs., 4 figs.

An Overview of the Literature: Research in P-12 Engineering Education

Science.gov (United States)

Mendoza Díaz, Noemi V.; Cox, Monica F.

2012-01-01

This paper presents an extensive overview of preschool to 12th grade (P-12) engineering education literature published between 2001 and 2011. Searches were conducted through education and engineering library engines and databases as well as queries in established publications in engineering education. More than 50 publications were found,…

Characterization of a de novo duplication of 11p14----p13, using fluorescent in situ hybridization and southern hybridization

NARCIS (Netherlands)

Speleman, F.; Mannens, M.; Redeker, B.; Vercruyssen, M.; van Oostveldt, P.; Leroy, J.; Slater, R.

1991-01-01

A de novo 11p+ chromosome was found in a child with mild mental retardation but no other remarkable dysmorphic characteristics. Banding studies suggested a duplication of regions 11p13 and 11p14 or regions 11p14 and 11p15. Using fluorescent in situ hybridization and digital imaging microscopy, we

The Deoxygenation Pathways of Palmitic Acid into Hydrocarbons on Silica-Supported Ni12P5 and Ni2P Catalysts

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Wenjun Zhou

2018-04-01

Full Text Available Pure Ni12P5/SiO2 and pure Ni2P/SiO2 catalysts were obtained by adjusting the Ni and P molar ratios, while Ni/SiO2 catalyst was prepared as a reference against which the deoxygenation pathways of palmitic acid were investigated. The catalysts were characterized by N2 adsorption, X-ray diffraction (XRD, X-ray photoelectron spectroscopy (XPS, transmission election microscopy (TEM, infrared spectroscopy of pyridine adsorption (Py-IR, H2-adsorption and temperature-programmed desorption of hydrogen (H2-TPD. The crystallographic planes of Ni(111, Ni12P5(400, Ni2P(111 were found mainly exposed on the above three catalysts, respectively. It was found that the deoxygenation pathway of palmitic acid mainly proceeded via direct decarboxylation (DCO2 to form C15 on Ni/SiO2. In contrast, on the Ni12P5/SiO2 catalyst, there were two main competitive pathways producing C15 and C16, one of which mainly proceeded via the decarbonylation (DCO to form C15 accompanying water formation, and the other pathway produced C16 via the dehydration of hexadecanol intermediate, and the yield of C15 was approximately twofold that of C16. Over the Ni2P/SiO2 catalyst, two main deoxygenation pathways formed C15, one of which was mainly the DCO pathway and the other was dehydration accompanying the hexadecanal intermediate and then direct decarbonylation without water formation. The turn over frequency (TOF followed the order: Ni12P5/SiO2 > Ni/SiO2 > Ni2P/SiO2.

Chromosomal mutations and chromosome loss measured in a new human-hamster hybrid cell line, ALC: studies with colcemid, ultraviolet irradiation, and 137Cs gamma-rays

Science.gov (United States)

Kraemer, S. M.; Waldren, C. A.; Chatterjee, A. (Principal Investigator)

1997-01-01

Small mutations, megabase deletions, and aneuploidy are involved in carcinogenesis and genetic defects, so it is important to be able to quantify these mutations and understand mechanisms of their creation. We have previously quantified a spectrum of mutations, including megabase deletions, in human chromosome 11, the sole human chromosome in a hamster-human hybrid cell line AL. S1- mutants have lost expression of a human cell surface antigen, S1, which is encoded by the M1C1 gene at 11p13 so that mutants can be detected via a complement-mediated cytotoxicity assay in which S1+ cells are killed and S1- cells survive. But loss of genes located on the tip of the short arm of 11 (11p15.5) is lethal to the AL hybrid, so that mutants that have lost the entire chromosome 11 die and escape detection. To circumvent this, we fused AL with Chinese hamster ovary (CHO) cells to produce a new hybrid, ALC, in which the requirement for maintaining 11p15.5 is relieved, allowing us to detect mutations events involving loss of 11p15.5. We evaluated the usefulness of this hybrid by conducting mutagenesis studies with colcemid, 137Cs gamma-radiation and UV 254 nm light. Colcemid induced 1000 more S1- mutants per unit dose in ALC than in AL; the increase for UV 254 nm light was only two-fold; and the increase for 137Cs gamma-rays was 12-fold. The increase in S1- mutant fraction in ALC cells treated with colcemid and 137Cs gamma-rays were largely due to chromosome loss and 11p deletions often containing a breakpoint within the centromeric region.

Chromosomal localization of the human diazepam binding inhibitor gene

International Nuclear Information System (INIS)

DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.

1988-01-01

The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the γ-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes

Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p.

Science.gov (United States)

Gawlik-Kuklinska, Katarzyna; Wierzba, Jolanta; Wozniak, Agnieszka; Iliszko, Mariola; Debiec-Rychter, Maria; Dubaniewicz-Wybieralska, Miroslawa; Limon, Janusz

2008-01-01

We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed. The proband's phenotype and cytogenetic findings are compared with previously reported cases with proximal 4p deletion syndrome. The syndrome is associated with normal growth, varying degrees of mental retardation, characteristic facial appearance and minor dysmorphic features. Additionally, our patient developed a seizure disorder due to abnormal neuronal migration, i.e., periventricular heterotopia.

File list: InP.Emb.20.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: InP.Emb.10.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Emb.10.AllAg.Mitotic_cycle_12-14 dm3 Input control Embryo Mitotic cycle 12-14 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Emb.10.AllAg.Mitotic_cycle_12-14.bed ...

File list: InP.Emb.50.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Emb.50.AllAg.Mitotic_cycle_12-14 dm3 Input control Embryo Mitotic cycle 12-14 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Emb.50.AllAg.Mitotic_cycle_12-14.bed ...

Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

DEFF Research Database (Denmark)

Milne, Roger L; Goode, Ellen L; García-Closas, Montserrat

2011-01-01

-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively......BACKGROUND: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association...... and histopathology were assessed using logistic regression. RESULTS: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive...

IL-12 and IL-23 modulate plasticity of FoxP3+ regulatory T cells in human Leprosy.

Science.gov (United States)

Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Sharma, Alpana; Rao, D N

2017-03-01

Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host's immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host by producing IL-10 and TGF-β cytokines. In leprosy, plasticity of Tregs remain unstudied. This is the first study describing the conversion of Tregs into Th1-like and Th17-like cells using in vitro cytokine therapy in leprosy patients. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA), rIL-12 and rIL-23 for 48h. Expression of FoxP3 in CD4 + CD25 + Tregs, intracellular cytokines IFN-γ, TGF-β, IL-10 and IL-17 in Tregs cells were evaluated by flow cytometry (FACS) after stimulation. rIL-12 treatment increases the levels of pStat4 in Tregs and IFN-γ production. In the presence of rIL-23, pStat3 + and IL-17A + cells increase. rIL-12 and r-IL-23 treatment downregulated the FoxP3 expression, IL-10 and TGF-β production by Tregs and enhances the expression of co-stimulatory molecules (CD80, CD86). In conclusion rIL-12 converts Tregs into IFN-γ producing cells through STAT-4 signaling while rIL-23 converts Tregs into IL-17 producing cells through STAT-3 signaling in leprosy patients. This study may helpful to provide a new avenue to overcome the immunosuprression in leprosy patients using in vitro cytokine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor.

Science.gov (United States)

Aungraheeta, Riyaad; Conibear, Alexandra; Butler, Mark; Kelly, Eamonn; Nylander, Sven; Mumford, Andrew; Mundell, Stuart J

2016-12-08

Ticagrelor is a potent antagonist of the P2Y 12 receptor (P2Y 12 R) and consequently an inhibitor of platelet activity effective in the treatment of atherothrombosis. Here, we sought to further characterize its molecular mechanism of action. Initial studies showed that ticagrelor promoted a greater inhibition of adenosine 5'-diphosphate (ADP)-induced Ca 2+ release in washed platelets vs other P2Y 12 R antagonists. This additional effect of ticagrelor beyond P2Y 12 R antagonism was in part as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of G s -coupled adenosine A 2A receptors. This contributed to an increase in basal cyclic adenosine monophosphate (cAMP) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P). In addition, ticagrelor increased platelet cAMP and VASP-P in the absence of ADP in an adenosine receptor-independent manner. We hypothesized that this increase originated from a direct effect on basal agonist-independent P2Y 12 R signaling, and this was validated in 1321N1 cells stably transfected with human P2Y 12 R. In these cells, ticagrelor blocked the constitutive agonist-independent activity of the P2Y 12 R, limiting basal G i -coupled signaling and thereby increasing cAMP levels. These data suggest that ticagrelor has the pharmacological profile of an inverse agonist. Based on our results showing insurmountable inhibition of ADP-induced Ca 2+ release and forskolin-induced cAMP, the mode of antagonism of ticagrelor also appears noncompetitive, at least functionally. In summary, our studies describe 2 novel modes of action of ticagrelor, inhibition of platelet ENT1 and inverse agonism at the P2Y 12 R that contribute to its effective inhibition of platelet activation. © 2016 by The American Society of Hematology.

Measurement of continuum spectrum from {sup 12}C(p,p`x) at energy of 392 MeV

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Hiroki; Konishi, Daisuke; Uozumi, Yusuke; Wakabayashi, Genichiro; Sakae, Takeji; Matoba, Masaru [Kyushu Univ., Fukuoka (Japan); Nohtomi, Akihiro; Maki, Takashi; Koori, Norihiko

1998-03-01

Continuum spectra from {sup 12}C(p,p`x) reaction at 392 MeV were measured by using plastic and GSO(Ce) scintillators. The spectra of energy-angle double differential cross sections are compared with that of Quantum Molecular Dynamics (QMD) simulation. Significant differences were found in the results at the forward angles. (author)

LPS-induced systemic inflammation is more severe in P2Y12 null mice.

Science.gov (United States)

Liverani, Elisabetta; Rico, Mario C; Yaratha, Laxmikausthubha; Tsygankov, Alexander Y; Kilpatrick, Laurie E; Kunapuli, Satya P

2014-02-01

Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade.

Hydrogen sulfide protects against chemical hypoxia-induced injury by inhibiting ROS-activated ERK1/2 and p38MAPK signaling pathways in PC12 cells.

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Aiping Lan

Full Text Available Hydrogen sulfide (H(2S has been proposed as a novel neuromodulator and neuroprotective agent. Cobalt chloride (CoCl(2 is a well-known hypoxia mimetic agent. We have demonstrated that H(2S protects against CoCl(2-induced injuries in PC12 cells. However, whether the members of mitogen-activated protein kinases (MAPK, in particular, extracellular signal-regulated kinase1/2(ERK1/2 and p38MAPK are involved in the neuroprotection of H(2S against chemical hypoxia-induced injuries of PC12 cells is not understood. We observed that CoCl(2 induced expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α, decreased cystathionine-β synthase (CBS, a synthase of H(2S expression, and increased generation of reactive oxygen species (ROS, leading to injuries of the cells, evidenced by decrease in cell viability, dissipation of mitochondrial membrane potential (MMP , caspase-3 activation and apoptosis, which were attenuated by pretreatment with NaHS (a donor of H(2S or N-acetyl-L cystein (NAC, a ROS scavenger. CoCl(2 rapidly activated ERK1/2, p38MAPK and C-Jun N-terminal kinase (JNK. Inhibition of ERK1/2 or p38MAPK or JNK with kinase inhibitors (U0126 or SB203580 or SP600125, respectively or genetic silencing of ERK1/2 or p38MAPK by RNAi (Si-ERK1/2 or Si-p38MAPK significantly prevented CoCl(2-induced injuries. Pretreatment with NaHS or NAC inhibited not only CoCl(2-induced ROS production, but also phosphorylation of ERK1/2 and p38MAPK. Thus, we demonstrated that a concurrent activation of ERK1/2, p38MAPK and JNK participates in CoCl(2-induced injuries and that H(2S protects PC12 cells against chemical hypoxia-induced injuries by inhibition of ROS-activated ERK1/2 and p38MAPK pathways. Our results suggest that inhibitors of ERK1/2, p38MAPK and JNK or antioxidants may be useful for preventing and treating hypoxia-induced neuronal injury.

File list: InP.Myo.20.AllAg.C2C12 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Myo.20.AllAg.C2C12 mm9 Input control Muscle C2C12 SRX262224,SRX262225,SRX148229...695944 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Myo.20.AllAg.C2C12.bed ...

Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.

Directory of Open Access Journals (Sweden)

Per Johansson

Full Text Available The role of inflammation in Alzheimer's disease (AD and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF samples.Consecutive patients with AD (n = 30, stable mild cognitive impairment (SMCI, n = 11, other dementias (n = 11, and healthy controls (n = 18 were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6, IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A, and three chemokines were measured using a multiplex panel.After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52 and controls (n = 18; p = 0.002. Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively. In the total study population (n = 70, CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42 and phosphorylated tau protein (P-tau whereas in AD patients (n = 30, CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01.Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.

Crystal structure of (Al,V)4(P4O12)3, archetype of double cubic ring tetraphosphate

International Nuclear Information System (INIS)

Yakubovich, O. V.; Biralo, G. V.; Dimitrova, O. V.

2012-01-01

The crystal structure of the (Al,V) 4 (P 4 O 12 ) 3 solid solution, obtained in the single-crystal form by hydrothermal synthesis in the Al(OH) 3 -VO 2 -NaCl-H 3 PO 4 -H 2 O system, has been solved by X-ray diffraction analysis (Xcalibur-S-CCD diffractometer, R = 0.0257): a = 13.7477(2) Å, sp. gr. I 4 bar 3d, Z = 4, and ρ calcd = 2.736 g/cm 3 . It is shown that the crystal structure of the parent cubic Al 4 (P 4 O 12 ) 3 modification can formally be considered an archetype for the formation of double isosymmetric tetraphosphates on its basis.

A new rapid method for quantification of nitrogen in human serum employing the 14N(p,p' γ)14N reaction: application to human pregnancy

International Nuclear Information System (INIS)

Nikkenien, P.; Hyvoenen-Dabek, M.; Raeisaenen, J.; Haenninen, R.; Dabek, J.T.

1985-01-01

The total nitrogen concentrations in dried serum from 54 pregnant women and 17 newborn babies were determined by a new application of the 14 N(p,p'γ) 14 N reaction resonance at 3.9 MeV. The samples were bombarded in a He atmosphere by 4.1 MeV protons from a tandem Van de Graaff accelerator. The mean dry-weight nitrogen concentration in serum sampled during early pregnancy (6-12 weeks; 13.9 g per 100 g+-5.4%) was significantly higher than that in serum sampled during late pregnancy (38-42 weeks: 13.0 g per 100 g+-3.9%, p<0.001) than that in serum taken from the umbilical cord (13.3 g per 100 g+-4.6%, p<0.01). The nitrogen levels measured using this rapid nuclear technique, applied for the first time to human serum analysis, agree well with parallel Kjeldahl analyses. (author)

5p13 microduplication syndrome: a new case and better clinical definition of the syndrome.

Science.gov (United States)

Novara, Francesca; Alfei, Enrico; D'Arrigo, Stefano; Pantaleoni, Chiara; Beri, Silvana; Achille, Valentina; Sciacca, Francesca L; Giorda, Roberto; Zuffardi, Orsetta; Ciccone, Roberto

2013-01-01

Chromosome 5p13 duplication syndrome (OMIM #613174), a contiguous gene syndrome involving duplication of several genes on chromosome 5p13 including NIPBL (OMIM 608667), has been described in rare patients with developmental delay and learning disability, behavioral problems and peculiar facial dysmorphisms. 5p13 duplications described so far present with variable sizes, from 0.25 to 13.6 Mb, and contain a variable number of genes. Here we report another patient with 5p13 duplication syndrome including NIPBL gene only. Proband's phenotype overlapped that reported in patients with 5p13 microduplication syndrome and especially that of subjects with smaller duplications. Moreover, we better define genotype-phenotype relationship associated with this duplication and confirmed that NIPBL was likely the major dosage sensitive gene for the 5p13 microduplication phenotype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Pallister–Killian syndrome: Cytogenetics and molecular investigations of mosaic tetrasomy 12p in prenatal chorionic villus and in amniocytes. Strategy of prenatal diagnosis

Directory of Open Access Journals (Sweden)

Francesco Libotte

2016-12-01

Conclusion: New molecular cytogenetic techniques array comparative genomic hybridization and fluorescence in-situ hybridization in association with conventional karyotype are pivotal innovative tools to search for chromosomic anomalies and for a complete prenatal diagnosis, especially in cases such as PKS where array comparative genomic hybridization analysis alone could not show mosaicism of i(12p.

cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)

International Nuclear Information System (INIS)

Glasser, S.W.; Korfhagen, T.R.; Weaver, T.E.; Clark, J.C.; Pilot-Matias, T.; Meuth, J.; Fox, J.L.; Whitsett, J.A.

1988-01-01

In hyaline membrane disease of premature infants, lack of surfactant leads to pulmonary atelectasis and respiratory distress. Hydrophobic surfactant proteins of M/sub r/ = 5000-14,000 have been isolated from mammalian surfactants which enhance the rate of spreading and the surface tension lowering properties of phospholipids during dynamic compression. The authors have characterized the amino-terminal amino acid sequence of pulmonary proteolipids from ether/ethanol extracts of bovine, canine, and human surfactant. Two distinct peptides were identified and termed SPL(pVal) and SPL(Phe). An oligonucleotide probe based on the valine-rich amino-terminal amino acid sequence of SPL(pVal) was utilized to isolate cDNA and genomic DNA encoding the human protein, termed surfactant proteolipid SPL(pVal) on the basis of its unique polyvaline domain. The primary structure of a precursor protein of 20,870 daltons, containing the SPL(pVal) peptide, was deduced from the nucleotide sequence of the cDNAs. Hybrid-arrested translation and immunoprecipitation of labeled translation products of human mRNA demonstrated a precursor protein, the active hydrophobic peptide being produced by proteolytic processing. Two classes of cDNAs encoding SPL(pVal) were identified. Human SPL(pVal) mRNA was more abundant in the adult than in fetal lung. The SPL(pVal) gene locus was assigned to chromosome 8

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Science.gov (United States)

2012-01-01

Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. PMID:22348646

Oxidative stress-induced metabolic changes in mouse C2C12 myotubes studied with high-resolution 13C, 1H, and 31P NMR spectroscopy

DEFF Research Database (Denmark)

Straadt, Ida K; Young, Jette F; Petersen, Bent O

2010-01-01

In this study, stress in relation to slaughter was investigated in a model system by the use of (13)C, (1)H, and (31)P nuclear magnetic resonance (NMR) spectroscopy for elucidating changes in the metabolites in C2C12 myotubes exposed to H(2)O(2)-induced stress. Oxidative stress resulted in lower...... to lower levels of the unlabeled ((12)C) lactate were identified in the (1)H spectra after stress exposure. These data indicate an increase in de novo synthesis of alanine, concomitant with a release of lactate from the myotubes to the medium at oxidative stress conditions. The changes in the metabolite...

Genetic mapping of a new race specific resistance allele effective to Puccinia hordei at the Rph9/Rph12 locus on chromosome 5HL in barley.

Science.gov (United States)

Dracatos, Peter M; Khatkar, Mehar S; Singh, Davinder; Park, Robert F

2014-12-20

Barley is an important cereal crop cultivated for malt and ruminant feed and in certain regions it is used for human consumption. It is vulnerable to numerous foliar diseases including barley leaf rust caused by the pathogen Puccinia hordei. A temporarily designated resistance locus RphCantala (RphC) identified in the Australian Hordeum vulgare L. cultivar 'Cantala' displayed an intermediate to low infection type (";12 = N") against the P. hordei pathotype 253P- (virulent on Rph1, Rph2, Rph4, Rph6, Rph8 and RphQ). Phenotypic assessment of a 'CI 9214' (susceptible) x 'Stirling' (RphC) (CI 9214/Stirling) doubled haploid (DH) population at the seedling stage using P. hordei pathotype 253P-, confirmed that RphC was monogenically inherited. Marker-trait association analysis of RphC in the CI 9214/Stirling DH population using 4,500 DArT-seq markers identified a highly significant (-log10Pvalue > 17) single peak on the long arm of chromosome 5H (5HL). Further tests of allelism determined that RphC was genetically independent of Rph3, Rph7, Rph11, Rph13 and Rph14, and was an allele of Rph12 (Rph9.z), which also maps to 5HL. Multipathotype tests and subsequent pedigree analysis determined that 14 related Australian barley varieties (including 'Stirling' and 'Cantala') carry RphC and that the likely source of this resistance is via a Czechoslovakian landrace LV-Kvasice-NA-Morave transferred through common ancestral cultivars 'Hanna' and 'Abed Binder'. RphC is an allele of Rph12 (Rph9.z) and is therefore designated Rph9.am. Bioinformatic analysis using sequence arrays from DArT-seq markers in linkage disequilibrium with Rph9.am identified possible candidates for further gene cloning efforts and marker development at the Rph9/Rph12/Rph9.am locus.

Luminescence properties of LiPrxCe1-xP4O12

International Nuclear Information System (INIS)

Shalapska, T.; Stryganyuka, G.; Trotsc, D.; Demkiv, T.; Gektin, A.; Voloshinovskii, A.; Dorenbos, P.

2010-01-01

LiPr 1-x Ce x P 4 O 12 (x=0, 0.002, 0.02; 0.1) powder samples were prepared using the melt solution technique. Luminescent parameters of LiPr 1-x Ce x P 4 O 12 phosphors have been investigated under ultraviolet-vacuum ultraviolet (3-12 eV) synchrotron radiation and X-rays excitation at room and near liquid He temperatures. Excitation luminescence spectra of Ce 3+ emission, luminescent spectra and decay curves from the lower excited state levels of the 4f 1 5d 1 and 5d 1 electronic configuration of the Pr 3+ and Ce 3+ , respectively, clearly indicate energy transfer from Pr 3+ to Ce 3+ . Energy migration proceeds via the Pr-sublattice followed by nonradiation transfer from Pr 3+ to Ce 3+ ions.

Hsp12p and PAU genes are involved in ecological interactions between natural yeast strains.

Science.gov (United States)

Rivero, Damaríz; Berná, Luisa; Stefanini, Irene; Baruffini, Enrico; Bergerat, Agnes; Csikász-Nagy, Attila; De Filippo, Carlotta; Cavalieri, Duccio

2015-08-01

The coexistence of different yeasts in a single vineyard raises the question on how they communicate and why slow growers are not competed out. Genetically modified laboratory strains of Saccharomyces cerevisiae are extensively used to investigate ecological interactions, but little is known about the genes regulating cooperation and competition in ecologically relevant settings. Here, we present evidences of Hsp12p-dependent altruistic and contact-dependent competitive interactions between two natural yeast isolates. Hsp12p is released during cell death for public benefit by a fast-growing strain that also produces a killer toxin to inhibit growth of a slow grower that can enjoy the benefits of released Hsp12p. We also show that the protein Pau5p is essential in the defense against the killer effect. Our results demonstrate that the combined action of Hsp12p, Pau5p and a killer toxin is sufficient to steer a yeast community. © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L.

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Rebecca A Nebel

Full Text Available Microcephaly and macrocephaly are overrepresented in individuals with autism and are thought to be disease-related risk factors or endophenotypes. Analysis of DNA microarray results from a family with a low functioning autistic child determined that the proband and two additional unaffected family members who carry a rare inherited 760 kb duplication of unknown clinical significance at 19p13.12 are macrocephalic. Consideration alongside overlapping deletion and duplication events in the literature provides support for a strong relationship between gene dosage at this locus and head size, with losses and gains associated with microcephaly (p=1.11x10(-11 and macrocephaly (p=2.47x10(-11, respectively. Data support A kinase anchor protein 8 and 8-like (AKAP8 and AKAP8L as candidate genes involved in regulation of head growth, an interesting finding given previous work implicating the AKAP gene family in autism. Towards determination of which of AKAP8 and AKAP8L may be involved in the modulation of head size and risk for disease, we analyzed exome sequencing data for 693 autism families (2591 individuals where head circumference data were available. No predicted loss of function variants were observed, precluding insights into relationship to head size, but highlighting strong evolutionary conservation. Taken together, findings support the idea that gene dosage at 19p13.12, and AKAP8 and/or AKAP8L in particular, play an important role in modulation of head size and may contribute to autism risk. Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk.

Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human fetal aortic smooth muscle cells

International Nuclear Information System (INIS)

Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

1979-01-01

Cultured human fetal aortic smooth muscle cells derived from the abdominal aorta converted benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) via cytochrome P-450-dependent monooxygenation to metabolites detectable by both a highly sensitive radiometric assay and high pressure liquid chromatography (HPLC). Cells incubated with 3 H-BaP transformed this substrate primarily to phenols. 14 C-DMBA was converted to metabolites that cochromatographed with 12-hydroxymethyl-methylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7- 7,12-dihydroxymethylbenz[a]anthracene, and trans-8,9-dihydrodiol-7,12-DMBA. Exposure of cells in culture to 13 μM 1,2-benz[a]anthracene resulted in increased oxidative metabolism of both BaP and DMBA. In the case of BaP, total phenol formation was increased, while with DMBA all metabolites detected by HPLC were increased. Support for the potential role of metabolism of polycyclic aromatic hydrocarbons by aortic smooth muscle cells in the etiology of atherosclerosis was obtained

Photon cascade luminescence from Pr3+ ions in LiPrP4O12 polyphosphate

International Nuclear Information System (INIS)

Shalapska, T; Stryganyuk, G; Romanyshyn, Yu; Demchenko, P; Voloshinovskii, A; Trots, D; Gektin, A; Dorenbos, P

2010-01-01

The spectral-kinetic properties of luminescence from LiY 1-x Pr x P 4 O 12 (x = 1, 0.1) phosphors are studied in the 10-300 K temperature range upon excitation within the UV-VUV spectral range. The luminescence observed for LiPrP 4 O 12 at low temperatures is attributed to both intra-configurational 4f 2 → 4f 2 and inter-configurational 4f5d → 4f 2 radiative transitions of Pr 3+ . The temperature dependence of emission and the decay kinetics of Pr 3+ luminescence from LiY 1-x Pr x P 4 O 12 (x = 1, 0.1) phosphors are explained by temperature stimulated transitions from the 1 S 0 to the Pr 3+ 4f5d state. At low temperatures, the energy potential barrier between the 1 S 0 and 4f5d states is 0.014 eV for LiPrP 4 O 12 . The spectral overlap of the 1 S 0 and 4f5d states of Pr 3+ in LiY 0.9 Pr 0.1 P 4 O 12 determines the luminescence properties in the entire temperature range studied.

12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech.

Science.gov (United States)

Thevenon, Julien; Callier, Patrick; Andrieux, Joris; Delobel, Bruno; David, Albert; Sukno, Sylvie; Minot, Delphine; Mosca Anne, Laure; Marle, Nathalie; Sanlaville, Damien; Bonnet, Marlène; Masurel-Paulet, Alice; Levy, Fabienne; Gaunt, Lorraine; Farrell, Sandra; Le Caignec, Cédric; Toutain, Annick; Carmignac, Virginie; Mugneret, Francine; Clayton-Smith, Jill; Thauvin-Robinet, Christel; Faivre, Laurence

2013-01-01

Speech sound disorders are heterogeneous conditions, and sporadic and familial cases have been described. However, monogenic inheritance explains only a small proportion of such disorders, in particular in cases with childhood apraxia of speech (CAS). Deletions of Speech delay was found in all patients, which could be defined as CAS when patients had been evaluated by a speech therapist (5/9 patients). Intellectual deficiency was found in 5/9 patients only, and often associated with psychiatric manifestations of various severity. Two such deletions were inherited from an apparently healthy parent, but reevaluation revealed abnormal speech production at least in childhood, suggesting variable expressivity. The ELKS/ERC1 gene, which encodes for a synaptic factor, is found in the smallest region of overlap. These results reinforce the hypothesis that deletions of the 12p13.33 locus may be responsible for variable phenotypes including CAS associated with neurobehavioural troubles and that the presence of CAS justifies a genetic work-up.

Stress Hormone Cortisol Enhances Bcl2 Like-12 Expression to Inhibit p53 in Hepatocellular Carcinoma Cells.

Science.gov (United States)

Wu, Weizhong; Liu, Sanguang; Liang, Yunfei; Zhou, Zegao; Bian, Wei; Liu, Xueqing

2017-12-01

The pathogenesis of hepatocellular carcinoma (HC) is unclear. It is suggested that psychological stress associates with the pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53 protein. This study tests a hypothesis that the major stress hormone, cortisol, inhibits the expression of p53 in HC cells (HCC) via up regulating the expression of Bcl2L12. Peripheral blood samples were collected from patients with HC to be analyzed for the levels of cortisol. HCC were cultured to assess the role of cortisol in the regulation of the expression of Bcl2L12 and p53 in HCC. We observed that the serum cortisol levels were higher in HC patients. Expression of Bcl2L12 in HCC was correlated with serum cortisol. Cortisol enhanced the Bcl2L12 expression in HCC. Bcl2L12 binding to the TP53 promoter was correlated with p53 expression in HCC. Cortisol increased the Bcl2L12 expression in HCC to inhibit p53 expression. Stress hormone cortisol suppresses p53 in HCC via enhancing Bcl2L12 expression in HCC. The results suggest that cortisol may be a therapeutic target for the treatment of HC.

Clinicopathological significance of PTPN12 expression in human breast cancer

International Nuclear Information System (INIS)

Yuan, Xunyi; Yuan, Zhentao; Jiang, Dandan; Li, Funian

2012-01-01

Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients

DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer.

Science.gov (United States)

Ma, Stephanie; Chan, Yuen Piu; Woolcock, Bruce; Hu, Liang; Wong, Kai Yau; Ling, Ming Tat; Bainbridge, Terry; Webber, Douglas; Chan, Tim Hon Man; Guan, Xin-Yuan; Lam, Wan; Vielkind, Juergen; Chan, Kwok Wah

2009-05-15

Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis. (c) 2008 Wiley-Liss, Inc.

Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis

International Nuclear Information System (INIS)

Yuan, Bo; Cui, Jinquan; Wang, Wuliang; Deng, Kehong

2016-01-01

Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation. -- Highlights: •Gα12/Gα13 is upregulated in cervical cancer cell lines. •Gα12/Gα13 is not involved in cervical cancer cell proliferation. •Gα12/Gα13 promotes cervical cancer cell invasion. •The role of Rho G proteins in G12-promoted cervical cancer cell invasion. •G12 promotes cell invasion through activation of the ROCK-JNK signaling axis.

The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus.

Science.gov (United States)

Ishak, Intan H; Riveron, Jacob M; Ibrahim, Sulaiman S; Stott, Rob; Longbottom, Joshua; Irving, Helen; Wondji, Charles S

2016-04-20

Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells

Directory of Open Access Journals (Sweden)

Ziyin Lu

2017-10-01

Full Text Available This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy, and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted. The ratio of LC3-II/I and autophagic vacuoles were significantly increased at 24 h, but autophagy flux was blocked. The cleavage of caspase3 and PARP (poly ADP-ribose polymerase were enhanced, while PC-12-sip53 cells exposed to 3-MA showed down-regulation of apoptosis. By contrast, the expression of autophagy-related genes and protein reduced in p53 overexpressing cells following a time dependent manner. Meanwhile, there was an increase in the expression of activated caspase3 and PARP, condensed and fragmented nuclei were evident. Conclusively, the data supported that silencing of p53 promotes impaired autophagy, which acts as a pro-apoptotic induction factor in PC-12 cells treated with colistin for 24 h, and overexpression of p53 inhibits autophagy and accelerates apoptosis. Hence, it has been suggested that p53 could not act as a neuro-protective target in colistin-induced neurotoxicity.

Role of S100A12 in the pathogenesis of osteoarthritis

Energy Technology Data Exchange (ETDEWEB)

Nakashima, Motoshige [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Sakai, Tadahiro, E-mail: tadsakai@med.nagoya-u.ac.jp [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Hiraiwa, Hideki; Hamada, Takashi; Omachi, Takaaki [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Ono, Yohei [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd., Greenville, NC 27834 (United States); Inukai, Norio [Department of Orthopaedic Surgery, Nishio Municipal Hospital, 6 Kumami-cho, Nishio 445-8510 (Japan); Ishizuka, Shinya; Matsukawa, Tetsuya; Oda, Tomoyuki; Takamatsu, Akira; Yamashita, Satoshi; Ishiguro, Naoki [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

2012-06-08

Highlights: Black-Right-Pointing-Pointer This is the first report of S100A12 expression in human OA articular cartilages. Black-Right-Pointing-Pointer Exogenous S100A12 increased the production of MMP13 and VEGF in OA chondrocytes. Black-Right-Pointing-Pointer Soluble RAGE suppressed the increased production of MMP13 and VEGF. Black-Right-Pointing-Pointer p38MAPK and NF-{kappa}B inhibitors abrogated S100A12-induced MMP13 and VEGF production. Black-Right-Pointing-Pointer S100A12 may contribute to OA progression by increasing MMP13 and VEGF production. -- Abstract: S100A12 is a member of the S100 protein family, which are intracellular calcium-binding proteins. Although there are many reports on the involvement of S100A12 in inflammatory diseases, its presence in osteoarthritic cartilage has not been reported. The purpose of this study was to investigate the expression of S100A12 in human articular cartilage in osteoarthritis (OA) and to evaluate the role of S100A12 in human OA chondrocytes. We analyzed S100A12 expression by immunohistochemical staining of cartilage samples obtained from OA and non-OA patients. In addition, chondrocytes were isolated from knee cartilage of OA patients and treated with recombinant human S100A12. Real-time RT-PCR was performed to analyze mRNA expression. Protein production of matrix metalloproteinase 13 (MMP-13) and vascular endothelial growth factor (VEGF) in the culture medium were measured by ELISA. Immunohistochemical analyses revealed that S100A12 expression was markedly increased in OA cartilages. Protein production and mRNA expression of MMP-13 and VEGF in cultured OA chondrocytes were significantly increased by treatment with exogenous S100A12. These increases in mRNA expression and protein production were suppressed by administration of soluble receptor for advanced glycation end products (RAGE). Both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-{kappa}B (NF-{kappa}B) inhibitors also suppressed the increases

Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

International Nuclear Information System (INIS)

Hidalgo, Alfredo; Monroy, Alberto; Arana, Rosa Ma; Taja, Lucía; Vázquez, Guelaguetza; Salcedo, Mauricio

2003-01-01

Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation. We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients. All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma

Ab initio investigations of the electronic structures and chemical bonding in LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7}

Energy Technology Data Exchange (ETDEWEB)

Matar, Samir F. [CNRS, ICMCB, UPR 9048, F‐33600 Pessac (France); Université de Bordeaux, ICMCB, UPR 9048, F‐33600 Pessac (France); Al-Alam, Adel; Ouaini, Naïm [Université Saint-Esprit de Kaslik (USEK), Groupe OCM (Optimization et Caractérisation des Matériaux), CSR-USEK, CNRS-L, Jounieh (Lebanon); Pöttgen, Rainer, E-mail: pottgen@uni-muenster.de [Institut für Anorganische und Analytische Chemie, Universität Münster, Corrensstraße 30, D-48149 Münster (Germany)

2013-06-15

The electronic structures of the metal-rich phosphides LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7} were studied by DFT calculations. Both phosphides consist of three-dimensional [Co{sub 6}P{sub 4}] and [Co{sub 12}P{sub 7}] polyanionic networks which leave hexagonal channels for the lithium atoms. COOP data show strong Co–P and Co–Co bonding within the polyanions. The lithium atoms have trigonal prismatic phosphorus coordination. Total energy calculations indicate stability upon de-lithiation towards the Co{sub 6}P{sub 4} and Co{sub 12}P{sub 7} substructures - Graphical abstract: The cobalt–phosphorus networks in LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7}. - Highlights: • Chemical bonding resolved in the metal-rich phosphides LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7}. • Strong covalent Co–P bonding character in the [Co{sub 6}P{sub 4}] and [Co{sub 12}P{sub 7}] substructures. • Total energy calculations indicate stability of the de-lithiated substructures.

Telomere healing following DNA polymerase arrest-induced breakages is likely the main mechanism generating chromosome 4p terminal deletions.

Science.gov (United States)

Hannes, Femke; Van Houdt, Jeroen; Quarrell, Oliver W; Poot, Martin; Hochstenbach, Ron; Fryns, Jean-Pierre; Vermeesch, Joris R

2010-12-01

Constitutional developmental disorders are frequently caused by terminal chromosomal deletions. The mechanisms and/or architectural features that might underlie those chromosome breakages remain largely unexplored. Because telomeres are the vital DNA protein complexes stabilizing linear chromosomes against chromosome degradation, fusion, and incomplete replication, those terminal-deleted chromosomes acquired new telomeres either by telomere healing or by telomere capture. To unravel the mechanisms leading to chromosomal breakage and healing, we sequenced nine chromosome 4p terminal deletion boundaries. A computational analysis of the breakpoint flanking region, including 12 previously published pure terminal breakage sites, was performed in order to identify architectural features that might be involved in this process. All terminal 4p truncations were likely stabilized by telomerase-mediated telomere healing. In the majority of breakpoints multiple genetic elements have a potential to induce secondary structures and an enrichment in replication stalling site motifs were identified. These findings suggest DNA replication stalling-induced chromosome breakage during early development is the first mechanistic step leading toward terminal deletion syndromes. © 2010 Wiley-Liss, Inc.

[μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′]bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]cyanidocopper(I} methanol disolvate

Directory of Open Access Journals (Sweden)

Rong Wang

2010-08-01

Full Text Available The title centrosymmetric complex, [Cu2(CN2(C26H24P23]·2CH3OH, consists of two five-membered [Cu(dppeCN] rings [dppe is 1,2-bis(diphenylphosphinoethane] bridged by one μ2-dppe ligand, and two methanol solvent molecules. The angles around the central metal atom indicate that each CuI atom is located in the center of a distorted tetrahedron. The coordination sphere of each CuI atom is formed by three P atoms from two dppe ligands, and one C atom from the cyanide ligand. The crystal structure is stabilized by O—H...N hydrogen bonds, which are formed by the O—H donor group from methanol and the N-atom acceptor from a cyanide ligand.

Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets.

Science.gov (United States)

Bijak, Michal; Szelenberger, Rafal; Dziedzic, Angela; Saluk-Bijak, Joanna

2018-02-10

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets' aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets' ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet

Study of the p+{sup 12}C reaction at energies up to 30 MeV

Energy Technology Data Exchange (ETDEWEB)

Harada, Masahide; Yamamoto, A.; Yoshioka, S. [Kyushu Univ., Fukuoka (Japan)] [and others

1998-03-01

Double differential cross sections of charged-particles emitted in the p+{sup 12}C reaction were measured in the energy region from 14 to 26 MeV. The observed continuous components of emitted protons and {alpha}-particles were analyzed by assuming sequential decay of intermediate reaction products and/or simultaneous breakup process. It was found that the three body simultaneous decay, p+{alpha}+{sup 8}Be, and the sequential decay via p+{sup 12}C{sup *}{sub 3-} and {alpha}+{sup 9}B{sub g.s.} are most important in the proton-induced breakup of {sup 12}C for energies up to 30 MeV. (author)

Low-temperature sol-gel synthesis of NaZr2P3O12

International Nuclear Information System (INIS)

Agrawal, D.K.; Adair, J.H.

1990-01-01

The NZP family of new low-expansion materials has attracted wide interest for its potential in advanced technological applications. NaZr 2 P 3 O 12 , which is the parent composition of this family, has been synthesized by the solution sol-gel method using special precursor solutions, which led to its formation (although poorly crystalline) at temperatures as low as 120 degrees C. The lowest temperature of formation of a single phase of NaZr 2 P 3 O 12 with a high degree of crystallinity was found to be 600 degrees C

Evaluation of 5P12-RANTES analogue expression in Nicotiana benthamiana

CSIR Research Space (South Africa)

Mawela, KG

2012-10-10

Full Text Available 100 200 300 400 500 600 700 Apoplast Cytosol pICH11599 (-ve control) 5P 12 (? g /k g F W ) 3 dpi 6 dpi 9 dpi (B) Bacterial vector system 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Cytosol ER Chloroplast pICH11599 (-ve... MTS tetrazolium compound, {3-(4,5-dimethyl-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium} Efficacy testing Table 1 Summary of IC50 values of the HIV-1 pseudovirions screened. Sample identification ZM53 (targets CCR5) IC50 (?g...

Forward $\\pi^{+-}$ production in p-$O_2$ and p-$N_2$ interactions at 12 GeV/c

CERN Document Server

Catanesi, M.G.; Edgecock, R.; Ellis, M.; Gossling, C.; Bunyatov, S.; Krasnoperov, A.; Popov, B.; Tereschenko, V.; Di Capua, E.; Vidal-Sitjes, G.; Artamonov, A.; Giani, S.; Gilardoni, S.; Gorbunov, P.; Grant, A.; Grossheim, A.; Ivanchenko, A.; Ivanchenko, V.; Kayis-Topaksu, A.; Panman, J.; Papadopoulos, I.; Tcherniaev, E.; Tsukerman, I.; Wiebusch, C.; Zucchelli, P.; Blondel, A.; Borghi, S.; Morone, M.C.; Prior, G.; Schroeter, R.; Meurer, C.; Gastaldi, U.; Mills, G.B.; Graulich, J.S.; Gregoire, G.; Bonesini, M.; Ferri, F.; Kirsanov, M.; Bagulya, A.; Grichine, V.; Polukhina, N.; Palladino, V.; Coney, L.; Schmitz, D.; Barr, G.; Bobisut, F.; Gibin, D.; Guglielmi, A.; Mezzetto, M.; Dumarchez, J.; Dore, U.; Orestano, D.; Pastore, F.; Tonazzo, A.; Tortora, L.; Booth, C.; Howlett, L.; Bogomilov, M.; Kolev, D.; Tsenov, R.; Piperov, Stefan; Temnikov, P.; Apollonio, M.; Chimenti, P.; Giannini, G.; Burguet-Castell, J.; Cervera-Villanueva, A.; Gomez-Cadenas, J.J.; Martin-Albo, J.; Sorel, M.

2008-01-01

Measurements of double-differential charged pion production cross-sections in interactions of 12 GeV/c protons on O_2 and N_2 thin targets are presented in the kinematic range 0.5 GeV/c < p_{\\pi} < 8 GeV/c and 50 mrad < \\theta_{\\pi} < 250 mrad (in the laboratory frame) and are compared with p--C results. For p--N_2 (p--O_2) interactions the analysis is performed using 38576 (7522) reconstructed secondary pions. The analysis uses the beam instrumentation and the forward spectrometer of the HARP experiment at CERN PS. The measured cross-sections have a direct impact on the precise calculation of atmospheric neutrino fluxes and on the improved reliability of extensive air shower simulations by reducing the uncertainties of hadronic interaction models in the low energy range. In particular, the present results allow the common hypothesis that p--C data can be used to predict the p--N_2 and p--O_2 pion production cross-sections to be tested.

THE {sup 12}C + {sup 12}C REACTION AND THE IMPACT ON NUCLEOSYNTHESIS IN MASSIVE STARS

Energy Technology Data Exchange (ETDEWEB)

Pignatari, M. [Department of Physics, University of Basel, Klingelbergstrasse 82, CH-4056 Basel (Switzerland); Hirschi, R.; Bennett, M. [Astrophysics Group, EPSAM Institute, Keele University, Keele, ST5 5BG (United Kingdom); Wiescher, M.; Beard, M. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States); Gallino, R. [Universita' di Torino, Torino, Via Pietro Giuria 1, I-10126 Torino (Italy); Fryer, C.; Rockefeller, G. [Computational Physics and Methods (CCS-2), LANL, Los Alamos, NM 87545 (United States); Herwig, F.; Timmes, F. X., E-mail: marco.pignatari@unibas.ch [The Joint Institute for Nuclear Astrophysics, Notre Dame, IN 46556 (United States)

2013-01-01

Despite much effort in the past decades, the C-burning reaction rate is uncertain by several orders of magnitude, and the relative strength between the different channels {sup 12}C({sup 12}C, {alpha}){sup 20}Ne, {sup 12}C({sup 12}C, p){sup 23}Na, and {sup 12}C({sup 12}C, n){sup 23}Mg is poorly determined. Additionally, in C-burning conditions a high {sup 12}C+{sup 12}C rate may lead to lower central C-burning temperatures and to {sup 13}C({alpha}, n){sup 16}O emerging as a more dominant neutron source than {sup 22}Ne({alpha}, n){sup 25}Mg, increasing significantly the s-process production. This is due to the chain {sup 12}C(p, {gamma}){sup 13}N followed by {sup 13}N({beta} +){sup 13}C, where the photodisintegration reverse channel {sup 13}N({gamma}, p){sup 12}C is strongly decreasing with increasing temperature. Presented here is the impact of the {sup 12}C+{sup 12}C reaction uncertainties on the s-process and on explosive p-process nucleosynthesis in massive stars, including also fast rotating massive stars at low metallicity. Using various {sup 12}C+{sup 12}C rates, in particular an upper and lower rate limit of {approx}50,000 higher and {approx}20 lower than the standard rate at 5 Multiplication-Sign 10{sup 8} K, five 25 M {sub Sun} stellar models are calculated. The enhanced s-process signature due to {sup 13}C({alpha}, n){sup 16}O activation is considered, taking into account the impact of the uncertainty of all three C-burning reaction branches. Consequently, we show that the p-process abundances have an average production factor increased up to about a factor of eight compared with the standard case, efficiently producing the elusive Mo and Ru proton-rich isotopes. We also show that an s-process being driven by {sup 13}C({alpha}, n){sup 16}O is a secondary process, even though the abundance of {sup 13}C does not depend on the initial metal content. Finally, implications for the Sr-peak elements inventory in the solar system and at low metallicity are

SRS-sensor 13C/12C isotops measurements for detecting Helicobacter Pylori

Science.gov (United States)

Grishkanich, Aleksandr; Chubchenko, Yan; Elizarov, Valentin; Zhevlakov, Aleksandr; Konopelko, Leonid

2018-02-01

We developed SRS-sensor 13C/12C isotops measurements detecting Helicobacter Pylori for medical diagnostics of human health. Measuring of absolute 13C/12C isotope amount ratios allows to explore the topical problems of the modern world, alcoholic beverages and tobacco, medical diagnostics of human health. SRS method is used to measure the ratio of carbon isotopes in the exhaled carbon dioxide, which is used to diagnose the human infection of Helicobacter pylori and the influence of the Helicobacter pylori bacterium on the occurrence of gastritis, gastric and duodenal ulcers. A method for the analysis of human infection with Helicobacter pylori was developed on the basis of measurements of the ratio of 13C / 12C carbon isotopes in human exhaled air with a high level of measurement accuracy. The article reviews the work in the field of provision comparability of absolute 13C/12C isotope amount ratios in the environment and food. The analysis of the technical and metrological characteristics of traditional and perspective instruments for measuring isotope ratios is presented. The provision of comparability of absolute 13C/12C isotope amount ratios is carried by gravimetrically prepared reference standards. The key features and emerging issues are discussed.

Chromosomal localization of two novel repetitive sequences isolated from the Chenopodium quinoa Willd. genome.

Science.gov (United States)

Kolano, B; Gardunia, B W; Michalska, M; Bonifacio, A; Fairbanks, D; Maughan, P J; Coleman, C E; Stevens, M R; Jellen, E N; Maluszynska, J

2011-09-01

The chromosomal organization of two novel repetitive DNA sequences isolated from the Chenopodium quinoa Willd. genome was analyzed across the genomes of selected Chenopodium species. Fluorescence in situ hybridization (FISH) analysis with the repetitive DNA clone 18-24J in the closely related allotetraploids C. quinoa and Chenopodium berlandieri Moq. (2n = 4x = 36) evidenced hybridization signals that were mainly present on 18 chromosomes; however, in the allohexaploid Chenopodium album L. (2n = 6x = 54), cross-hybridization was observed on all of the chromosomes. In situ hybridization with rRNA gene probes indicated that during the evolution of polyploidy, the chenopods lost some of their rDNA loci. Reprobing with rDNA indicated that in the subgenome labeled with 18-24J, one 35S rRNA locus and at least half of the 5S rDNA loci were present. A second analyzed sequence, 12-13P, localized exclusively in pericentromeric regions of each chromosome of C. quinoa and related species. The intensity of the FISH signals differed considerably among chromosomes. The pattern observed on C. quinoa chromosomes after FISH with 12-13P was very similar to GISH results, suggesting that the 12-13P sequence constitutes a major part of the repetitive DNA of C. quinoa.

Chromosomal Abnormalities Associated With Omphalocele

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2007-03-01

Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

The platelet P2Y(12) receptor under normal and pathological conditions. Assessment with the radiolabeled selective antagonist [(3)H]PSB-0413.

Science.gov (United States)

Ohlmann, Philippe; Lecchi, Anna; El-Tayeb, Ali; Müller, Christa E; Cattaneo, Marco; Gachet, Christian

2013-03-01

Various radioligands have been used to characterize and quantify the platelet P2Y(12) receptor, which share several weaknesses: (a) they are metabolically unstable and substrates for ectoenzymes, (b) they are agonists, and (c) they do not discriminate between P2Y(1) and P2Y(12). We used the [(3)H]PSB-0413 selective P2Y(12) receptor antagonist radioligand to reevaluate the number of P2Y(12) receptors in intact platelets and in membrane preparations. Studies in humans showed that: (1) [(3)H]PSB-0413 bound to 425 ± 50 sites/platelet (K (D) = 3.3 ± 0.6 nM), (2) 0.5 ± 0.2 pmol [(3)H]PSB-0413 bound to 1 mg protein of platelet membranes (K (D) = 6.5 ± 3.6 nM), and (3) competition studies confirmed the known features of P2Y(12), with the expected rank order of potency: AR-C69931MX > 2MeSADP ≫ ADPβS > ADP, while the P2Y(1) ligand MRS2179 and the P2X(1) ligand α,β-Met-ATP did not displace [(3)H]PSB-0413 binding. Patients with severe P2Y(12) deficiency displayed virtually no binding of [(3)H]PSB-0413 to intact platelets, while a patient with a dysfunctional P2Y(12) receptor had normal binding. Studies in mice showed that: (1) [(3)H]PSB-0413 bound to 634 ± 87 sites/platelet (K (D) = 14 ± 4.5 nM) and (2) 0.7 pmol ± 0.3 [(3)H]PSB-0413 bound to 1 mg protein of platelet membranes (K (D) = 9.1 ± 5.3 nM). Clopidogrel and other thiol reagents like pCMBS or DTT abolished the binding both to intact platelets and membrane preparations. Therefore, [(3)H]PSB-0413 is an accurate and selective tool for radioligand binding studies aimed at quantifying P2Y(12) receptors, to identify patients with P2Y(12) deficiencies or quantify the effect of P2Y(12) targeting drugs.

Synthetic Swan band profile of (1,0) of 12C12C and (0,0) of 12C12C and 12C13C in comets

International Nuclear Information System (INIS)

Swamy, K.S.K.

1987-01-01

The statistical equilibrium calculations of the 12 C 13 C molecule based on the resonance fluorescence process give similar results to those of the normal molecule. Therefore the assumption that the observed intensities of bands of the normal and the isotopic molecule differ only by their abundance ratio is reasonable. The synthetic profile of the (1,0) Swan band of 12 C 13 C (0,0) band of 12 C 12 C and 12 C 13 C have been calculated. The relative merits of using the rotational structure of the (1,0) or (0,0) band for the determination of the isotopic ratio 12 C/ 13 C is discussed briefly. (author)

AML with t(7;12)(q36;p13) is associated with infancy and trisomy 19. Data from NOPHO-AML and review of the literature

DEFF Research Database (Denmark)

Espersen, Anne Dorte Lerche; Noren-Nyström, Ulrika; Abrahamsson, Jonas

2018-01-01

The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children ...). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation...

Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors.

Science.gov (United States)

El-Tayeb, Ali; Griessmeier, Kerstin J; Müller, Christa E

2005-12-15

The selective antagonist radioligand [(3)H]2-propylthioadenosine-5'-adenylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl) anhydride ([(3)H]PSB-0413) was prepared by catalytic hydrogenation of its propargyl precursor with a high specific radioactivity of 74Ci/mmol. In preliminary saturation binding studies, [(3)H]PSB-0413 showed high affinity for platelet P2Y(12) receptors with a K(D) value of 4.57nM. Human platelets had a high density of P2Y(12) receptors exhibiting a B(max) value of 7.66pmol/mg of protein.

Partial Duplication of Chromosome 8p

African Journals Online (AJOL)

rme

The partial chromosome 8p duplication is a rare syndrome and is ... abnormality of maternal origin that ... second trimester by vaginal bleeding and ... echocardiography, brain CT scan and. MRI. Fig. 1:Conventional karyotype of case 3 showing.

Nfkb1 inhibits LPS-induced IFN-β and IL-12 p40 production in macrophages by distinct mechanisms.

Directory of Open Access Journals (Sweden)

Xixing Zhao

Full Text Available Nfkb1-deficient murine macrophages express higher levels of IFN-β and IL-12 p40 following LPS stimulation than control macrophages, but the molecular basis for this phenomenon has not been completely defined. Nfkb1 encodes several gene products including the NF-κB subunit p50 and its precursor p105. p50 is derived from the N-terminal of 105, and p50 homodimers can exhibit suppressive activity when overexpressed. The C-terminal region of p105 is necessary for LPS-induced ERK activation and it has been suggested that ERK activity inhibits both IFN-β and IL-12 p40 following LPS stimulation. However, the contributions of p50 and the C-terminal domain of p105 in regulating endogenous IFN-β(Ifnb and IL-12 p40 (Il12b gene expression in macrophages following LPS stimulation have not been directly compared.We have used recombinant retroviruses to express p105, p50, and the C-terminal domain of p105 (p105ΔN in Nfkb1-deficient murine bone marrow-derived macrophages at near endogenous levels. We found that both p50 and p105ΔN inhibited expression of Ifnb, and that inhibition of Ifnb by p105ΔN depended on ERK activation, because a mutant of p105ΔN (p105ΔNS930A that lacks a key serine necessary to support ERK activation failed to inhibit. In contrast, only p105ΔN but not p50 inhibited Il12b expression. Surprisingly, p105ΔNS930A retained inhibitory activity for Il12b, indicating that ERK activation was not necessary for inhibition. The differential effects of p105ΔNS930A on Ifnb and Il12b expression inversely correlated with the function of one of its binding partners, c-Rel. This raised the possibility that p105ΔNS930A influences gene expression by interfering with the function of c-Rel.These results demonstrate that Nfkb1 exhibits multiple gene-specific inhibitory functions following TLR stimulation of murine macrophages.

Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network.

Science.gov (United States)

Keegan, Caroline; Krutzik, Stephan; Schenk, Mirjam; Scumpia, Philip O; Lu, Jing; Pang, Yan Ling Joy; Russell, Brandon S; Lim, Kok Seong; Shell, Scarlet; Prestwich, Erin; Su, Dan; Elashoff, David; Hershberg, Robert M; Bloom, Barry R; Belisle, John T; Fortune, Sarah; Dedon, Peter C; Pellegrini, Matteo; Modlin, Robert L

2018-05-01

Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-γ, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70. Copyright © 2018 by The American Association of Immunologists, Inc.

Dissolution kinetics of heulandite at pH 2--12 and 25 degrees C

International Nuclear Information System (INIS)

Ragnarsdottir, K.V.

1993-01-01

Because of their favourable cation exchange reactions, heulandite and clinoptilolite have been suggested as being capable of immobilizing radionuclides and therefore could possibly act as an important barrier for nuclear waste. Recent studies of laboratory-reacted minerals indicate, however, that hydrated surface layers tend to accumulate highly hydrolyzable heavy elements. These hydrated layers may therefore be the most important retardants for radionuclides. The dissolution rate of heulandite depends strongly on pH. Based on silica release, the logarithm of the steady-state dissolution rate at pH 2 is -13.1 mol cm -2 s -1 . The logarithm of the rate decreases to -15.8 mol cm -2 s -1 at pH 7.2 and increases again to -14.6 mol cm -2 s -1 at pH 12.2. At low pH, Al is released preferentially to silica; but at intermediate and high pH, the release of silica appears to be congruent relative to Al. The change in dissolution rate with pH indicates that at low pH, the dissolution mechanism is controlled by the detachment of a positively charged Al species, >Al-OH 2 + . Below pH 5, however, a silica-rich surface layer is formed requiring diffusion through the layer. At intermediate and high pH, it is likely that the dissolution rate is controlled by the detachment of a negatively charged silica species, >Si - O - . The reaction order of the hydrogen ion under low pH conditions is 0.7, and the reaction order of the OH - ion is 0.3 at high pH. The measured dissolution rates indicate that a 1 mm heulandite crystal would dissolve in 300,000 yrs if the solution composition is maintained undersaturated. 75 refs., 11 figs., 3 tabs

Karyotype and chromosomal polymorphism of Camptochironomous tentans (diptera, chironomidae)

International Nuclear Information System (INIS)

Sejsebaev, A.T.; Bakhtin, M.M.; Rakhimbaeva, K.T.

2000-01-01

Particular features of chromosomal polymorphism and cytogenetic differentiations have been studied in three natural populations of Camptochironomous tentans affecting the Semipalatinsk test site. For the first time C. tentans population from water-bodies of the Degelen mountain massif was found to contain a unique rarely observed inverse sequence of chromosomal disks (p'ten B85, p'ten D3, p'ten Ck, p'ten FK) and a series of special homozygous (p'ten C1.1; p'ten D2.2) and heterozygous (p'ten B1.5; p'ten D1.2; p'ten D1.3; p'ten F1.3; p'ten F1K) inversions which could be the result of Chironomini adaptation to the radioactive environment. (author)

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

Science.gov (United States)

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

A familial pericentric inversion of chromosome 11 associated with a microdeletion of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or eye anomalies.

Science.gov (United States)

Balay, Lara; Totten, Ellen; Okada, Luna; Zell, Sidney; Ticho, Benjamin; Israel, Jeannette; Kogan, Jillene

2016-01-01

Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L, and ELP4 are previously reported to have downstream transcriptional effects on the expression of PAX6, due to a downstream regulatory region (DRR). Currently, no clear genotype-phenotype correlations have been established allowing for conclusive information regarding the exact location of the PAX6 DRR, though its location has been approximated in mouse models to be within the Elp4 gene. Of the clinical reports currently published examining patients with intact PAX6 genes but harboring deletions identified in genes downstream of PAX6, 100% indicate phenotypes which include aniridia, whereas approximately half report additional eye deformities, autism, or intellectual disability. In this clinical report, we present a 12-year-old male patient, his brother, and mother with pericentric inversions of chromosome 11 associated with submicroscopic interstitial deletions of 11p13 and duplications of 11q22.3. The inversions were identified by standard cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The patient's phenotype includes intellectual disability, speech abnormalities, and autistic behaviors, but interestingly neither the patient, his brother, nor mother have aniridia or other eye anomalies. To the best of our knowledge, these findings in three family members represent the only reported cases with 11p13 deletions downstream of PAX6 not demonstrating phenotypic characteristics of aniridia or abnormal eye development. Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6. © 2015 Wiley Periodicals, Inc.

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

Energy Technology Data Exchange (ETDEWEB)

Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree; Crowell, Susan R.; Corley, Richard A.

2017-03-01

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase I metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 µM), and higher intrinsic clearance at lower substrate concentrations (<0.07 µM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.

Induction of P450 3A1/2 and 2C6 by gemfibrozil in Sprague-Dawley rats.

Science.gov (United States)

Liu, Aiming; Yang, Julin; Zhao, Xin; Jiao, Xiaolan; Zhao, Weihong; Ma, Qing; Tang, Zhiyuan; Dai, Renke

2011-01-01

Fibrates are a group of peroxisome proliferator-activated receptor α agonists used in the treatment of dyslipidemia; however, they have been reported to cause species-related hepatocarcinogenesis and clinical myotoxicity. Gemfibrozil is one of the most commonly used fibrates, and it shows the highest risk for myotoxicity among the fibrates. The inhibitory drug-drug interaction mechanism associated with gemfibrozil has been explored recently, and the induction of human P450 3A4 and 2C8 has been reported. In this study, in vivo induction of rat P450 by gemfibrozil was studied in Sprague-Dawley rats. After the rats were dosed with gemfibrozil by oral gavage, microsomes were prepared. The metabolic activities of P450 3A1/2, 2C6, and 2D2 were assayed using probe substrates, and the systemic concentration of gemfibrozil during its administration was determined. P450 3A1/2 and 2C6 activities were induced 32-77% in the rats by gemfibrozil when the exposure concentration was in the clinical range. These data indicate that the inducibility of homologous P450 isoforms by gemfibrozil is similar in Sprague-Dawley rats and in humans. Inductive drug-drug interactions and inhibitory actions are involved in the co-administration of gemfibrozil with other drugs, which suggests the relevance for a fibrate-toxicology investigation.

Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in 'Escherichia coli' K-12

International Nuclear Information System (INIS)

Walker, G.C.

1977-01-01

The drug resistance plasmid pKM101 plays a major role in the Ames Salmonella/microsome carcinogen detecting system by enhancing chemical mutagenesis. It is shown that in Escherichia coli K-12 the plasmid pKM101 enhances both spontaneous and methyl methanesulfonate-caused reversion of an ochre mutation, bacterial survival after ultaviolet irradiation, and reactivation of ultraviolet-irradiated lambda in unirradiated cells. All these effects are shown to be dependent on the recA + lexA + genotype but not on the recB + recC + or recF + genotypes. The recA lexA-dependence of the plasmid-mediated repair and mutagenesis suggests an interaction with the cell's inducible error-prone repair system. The presence of pKM101 is shown to cause an additional increase in methyl methanesulfonate mutagenesis in a tif mutant beyond that caused by growth at 42 0 . The presence of the plasmid raises the level of the Weigle-reactivation curve for the reactivation of ultraviolet-irradiated lambda in E. coli and causes a shift of the maximum to a higher UV fluence. These observations suggest that pKM101 does not exert its effects by altering the regulation of the cell's error-prone repair system but rather by supplying a mechanistic component or components. (orig.) [de

Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations.

Science.gov (United States)

Sotomatsu, M; Hayashi, Y; Kawamura, M; Yugami, S; Shitara, T

1993-10-01

A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.

Recurrent duplications of 17q12 associated with variable phenotypes

DEFF Research Database (Denmark)

Mitchell, Elyse; Douglas, Andrew; Kjaegaard, Susanne

2015-01-01

The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information......, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing...... to phenotypic variability....

Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism.

Science.gov (United States)

Bosch, Nina; Morell, Marta; Ponsa, Immaculada; Mercader, Josep Maria; Armengol, Lluís; Estivill, Xavier

2009-12-14

The human chromosome 8p23.1 region contains a 3.8-4.5 Mb segment which can be found in different orientations (defined as genomic inversion) among individuals. The identification of single nucleotide polymorphisms (SNPs) tightly linked to the genomic orientation of a given region should be useful to indirectly evaluate the genotypes of large genomic orientations in the individuals. We have identified 16 SNPs, which are in linkage disequilibrium (LD) with the 8p23.1 inversion as detected by fluorescent in situ hybridization (FISH). The variability of the 8p23.1 orientation in 150 HapMap samples was predicted using this set of SNPs and was verified by FISH in a subset of samples. Four genes (NEIL2, MSRA, CTSB and BLK) were found differentially expressed (pinversion occurred. Moreover, an impact of 8p23.1 inversion on gene expression levels cannot be ruled out, since four genes from this region have statistically significant different expression levels depending on the inversion status. FISH results in lymphoblastoid cell lines suggest the presence of mosaicism regarding the 8p23.1 inversion.

Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus (QTL30 on rat chromosome 12: identification of fry as a candidate Mcs gene.

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Xuefeng Ren

Full Text Available Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop and susceptible Fischer 344 (F344 strains, we mapped a novel mammary carcinoma susceptibility (Mcs30 locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker. The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs, one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

Characterization of a chromosome-specific chimpanzee alpha satellite subset: Evolutionary relationship to subsets on human chromosomes

Energy Technology Data Exchange (ETDEWEB)

Warburton, P.E.; Gosden, J.; Lawson, D. [Western General Hospital, Edinburgh (United Kingdom)] [and others

1996-04-15

Alpha satellite DNA is a tandemly repeated DNA family found at the centromeres of all primate chromosomes examined. The fundamental repeat units of alpha satellite DNA are diverged 169- to 172-bp monomers, often found to be organized in chromosome-specific higher-order repeat units. The chromosomes of human (Homo sapiens (HSA)), chimpanzee (Pan troglodytes (PTR) and Pan paniscus), and gorilla (Gorilla gorilla) share a remarkable similarity and synteny. It is of interest to ask if alpha satellite arrays at centromeres of homologous chromosomes between these species are closely related (evolving in an orthologous manner) or if the evolutionary processes that homogenize and spread these arrays within and between chromosomes result in nonorthologous evolution of arrays. By using PCR primers specific for human chromosome 17-specific alpha satellite DNA, we have amplified, cloned, and characterized a chromosome-specific subset from the PTR chimpanzee genome. Hybridization both on Southern blots and in situ as well as sequence analysis show that this subset is most closely related, as expected, to sequences on HSA 17. However, in situ hybridization reveals that this subset is not found on the homologous chromosome in chimpanzee (PTR 19), but instead on PTR 12, which is homologous to HSA 2p. 40 refs., 3 figs.

RNA of Enterococcus faecalis Strain EC-12 Is a Major Component Inducing Interleukin-12 Production from Human Monocytic Cells.

Directory of Open Access Journals (Sweden)

Ryoichiro Nishibayashi

Full Text Available Interleukin-12 (IL-12 is an important cytokine for the immunomodulatory effects of lactic acid bacteria (LAB. Using murine immune cells, we previously reported that the RNA of Enterococcus faecalis EC-12, a LAB strain exerting probiotic-like beneficial effects, is the major IL-12-inducing immunogenic component. However, it was recently revealed that bacterial RNA can be a ligand for Toll-like receptor (TLR 13, which is only expressed in mice. Because TLR13 is not expressed in humans, the immuno-stimulatory and -modulatory effects of LAB RNA in human cells should be augmented excluding TLR13 contribution. In experiment 1 of this study, the role of LAB RNA in IL-12 induction in human immune cells was studied using three LAB strains, E.faecalis EC-12, Lactobacillus gasseri JCM5344, and Bifidobacterium breve JCM1192. RNase A treatment of heat-killed LAB significantly decreased the IL-12 production of human peripheral blood mononuclear cells on stimulation, while RNase III treatment revealed virtually no effects. Further, IL-12 production against heat-killed E. faecalis EC-12 was abolished by depleting monocytes. These results demonstrated that single stranded RNA (ssRNA of LAB is a strong inducer of IL-12 production from human monocytes. In experiment 2, major receptor for ssRNA of E. faecalis EC-12 was identified using THP-1 cells, a human monocytic cell line. The type of RNA molecules of E. faecalis EC-12 responsible for IL-12 induction was also identified. IL-12 production induced by the total RNA of E. faecalis EC-12 was significantly reduced by the treatment of siRNA for TLR8 but not for TLR7. Furthermore, both 23S and 16S rRNA, but not mRNA, of E. faecalis EC-12 markedly induced IL-12 production from THP-1 cells. These results suggested that the recognition of ssRNA of E. faecalis EC-12 was mediated by TLR8 and that rRNA was the RNA molecule that exhibited IL-12-inducing ability in human cells.

Chitosan coated alginate-xanthan gum bead enhanced pH and thermotolerance of Lactobacillus plantarum LAB12.

Science.gov (United States)

Fareez, Ismail M; Lim, Siong Meng; Mishra, Rakesh K; Ramasamy, Kalavathy

2015-01-01

The vulnerability of probiotics at low pH and high temperature has limited their optimal use as nutraceuticals. This study addressed these issues by adopting a physicochemical driven approach of incorporating Lactobacillus plantarum LAB12 into chitosan (Ch) coated alginate-xanthan gum (Alg-XG) beads. Characterisation of Alg-XG-Ch, which elicited little effect on bead size and polydispersity, demonstrated good miscibility with improved bead surface smoothness and L. plantarum LAB12 entrapment when compared to Alg, Alg-Ch and Alg-XG. Sequential incubation of Alg-XG-Ch in simulated gastric juice and intestinal fluid yielded high survival rate of L. plantarum LAB12 (95%) at pH 1.8 which in turn facilitated sufficient release of probiotics (>7 log CFU/g) at pH 6.8 in both time- and pH-dependent manner. Whilst minimising viability loss at 75 and 90 °C, Alg-XG-Ch improved storage durability of L. plantarum LAB12 at 4 °C. The present results implied the possible use of L. plantarum LAB12 incorporated in Alg-XG-Ch as new functional food ingredient with health claims. Copyright © 2014 Elsevier B.V. All rights reserved.

[Effect of lipopolysaccharides extracted from Porphyromonas endodontalis on the expression of p38 and ERK1/2 in osteoblast].

Science.gov (United States)

Lv, You; Jia, Ge; Qiu, Li-hong; Bao, Mu-rong; Yu, Ya-qiong; Guo, Yan

2012-08-01

To investigate the effect of lipopolysaccharides (LPS) extracted from Porphyromonas endodontalis(P.e) on the expression of p38 and ERK1/2 in osteoblast. MC3T3-E1 cells were stimulated with 10 μg/mL P.e-LPS for 0,5,15,30,60,180 min. The phosphorylation of p38 and ERK1/2 was measured by Western blot. Statistical analysis was performed using one- way ANOVA and Dunnett t test with SPSS11.0 software package. 10 μg/mL LPS could significantly activate p38 MAPK. The peak of phosphorylated p38 was detected at 5 to 30 min(P<0.01) and returned to baseline within 60 min; the level of phosphorylated ERK1/2 increased after the stimulation of LPS for 5 min and reached maximum at 15 min (P<0.01) and declined after 30 min. P.e-LPS can induce the expression of p38 and ERK1/2 in osteoblast MC3T3-E1, which indicates that P.e-LPS may play an important role in osteoblast through p38 and ERK1/2.

Local and non-local equivalent potentials for p-12C scattering

International Nuclear Information System (INIS)

Lovell, A.; Amos, K.

2000-01-01

A Newton-Sabatier fixed energy inversion scheme has been used to equate inherently non-local p- 12 C potentials at a variety of energies to pion threshold, with exactly phase equivalent local ones. Those energy dependent local potentials then have been recast in the form of non-local Frahn-Lemmer interactions

Luminescence and excited state dynamics in Bi3+-doped LiLaP4O12 phosphates

International Nuclear Information System (INIS)

Babin, V.; Chernenko, K.; Demchenko, P.; Mihokova, E.; Nikl, M.; Pashuk, I.; Shalapska, T.; Voloshinovskii, A.; Zazubovich, S.

2016-01-01

Photo- and X-ray-excited luminescence characteristics of Bi-doped LiLaP 4 O 12 phosphates with different bismuth contents (from 1 to 25 at% in the melt) are investigated in the 4.2–300 K temperature range and compared with the characteristics of the undoped LiLaP 4 O 12 phosphate. The broad 2.95 eV emission band of LiLaP 4 O 12 :Bi excited around 5.4 eV is found to arise from the bismuth dopant. Relatively large FWHM and Stokes shift of the emission band and especially the data on the low-temperature decay kinetics of the 2.95 eV emission and its temperature dependence, indicating a very small spin-orbit splitting energy of the corresponding excited state, allow the conclusion that this emission arises from the radiative decay of the triplet state of an exciton localized around a Bi 3+ ion. No spectral bands are observed, arising from the electron transitions between the energy levels of Bi 3+ ions. Phenomenological model is proposed for the description of the excited state dynamics of the Bi 3+ -related localized exciton in LiLaP 4 O 12 :Bi and the parameters of the triplet localized exciton state are determined. Keywords: Photoluminescence; Time-resolved spectroscopy; Excited states; Bi 3+ centers; LiLaP 4 O 12 :Bi powders

Chromosome break points of T-lymphocytes from atomic bomb survivors

International Nuclear Information System (INIS)

Tanaka, Kimio; Kamada, Nanao; Kuramoto, Atsushi; Ohkita, Takeshi

1980-01-01

Chromosome break points of T-lymphocytes were investigated for 9 atomic bomb survivors estimated to be irradiated with 100 - 630 red. Chromosome aberration was found in 199 cells out of 678 cells investigated, with non-random distribution. The types of the chromosome aberration were, transfer: 56%, deficit: 38%, additional abnormality 3%, and reverse: 2%. High and low incidence of chromosome aberrations were observed at the chromosome numbers of 22, 21, and 13, and 11, 12, and 4, respectively. The aberration numbers per arm were high in 22q, 21q, and 18p and low in 11q, 5p, and 12q. For the distribution of aberration number within a chromosome, 50.7% was observed at the terminal portion and 73% was at the pale band appeared by Q-partial-stain method, suggesting the non-random distribution. The incidence of aberration number in 22q was statistically significant (P 1 chromosome in chronic myelocytic leukemia. The non-random distribution of chromosome break points seemed to reflect the selection effect since irradiation. (Nakanishi, T.)

CpG Oligonucleotide and Interleukin 2 stimulation enables higher cytogenetic abnormality detection rates than 12-o-tetradecanolyphorbol-13-acetate in Asian patients with B-cell chronic lymphocytic leukemia (B-CLL).

Science.gov (United States)

Liaw, Fiona Pui San; Lau, Lai Ching; Lim, Alvin Soon Tiong; Lim, Tse Hui; Lee, Geok Yee; Tien, Sim Leng

2014-12-01

The present study was designed to compare abnormality detection rates using DSP30 + IL2 and 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Asian patients with B-CLL. Hematological specimens from 47 patients (29 newly diagnosed, 18 relapsed) were established as 72 h-DSP30 + IL2 and TPA cultures. Standard methods were employed to identify clonal aberrations by conventional cytogenetics (CC). The B-CLL fluorescence in situ hybridization (FISH) panel comprised ATM, CEP12, D13S25, and TP53 probes. DSP30 + IL2 cultures had a higher chromosomal abnormality detection rate (67 %) compared to TPA (44 %, p 0.05). Thirteen cases with abnormalities were found exclusively in DSP30 + IL2 cultures compared to one found solely in TPA cultures. DSP30 + IL2 cultures were comparable to the FISH panel in detecting 11q-, +12 and 17p- but not 13q-. It also has a predilection for 11q- bearing leukemic cells compared to TPA. FISH had a higher abnormality detection rate (84.1 %) compared to CC (66.0 %) with borderline significance (p = 0.051), albeit limited by its coverage. In conclusion, DSP30 + IL2 showed a higher abnormality detection rate. However, FISH is indispensable to circumvent low mitotic indices and detect subtle abnormalities.

The ribosome-bound chaperones RAC and Ssb1/2p are required for accurate translation in Saccharomyces cerevisiae.

Science.gov (United States)

Rakwalska, Magdalena; Rospert, Sabine

2004-10-01

The chaperone homologs RAC (ribosome-associated complex) and Ssb1/2p are anchored to ribosomes; Ssb1/2p directly interacts with nascent polypeptides. The absence of RAC or Ssb1/2p results in a similar set of phenotypes, including hypersensitivity against the aminoglycoside paromomycin, which binds to the small ribosomal subunit and compromises the fidelity of translation. In order to understand this phenomenon we measured the frequency of translation termination and misincorporation in vivo and in vitro with a novel reporter system. Translational fidelity was impaired in the absence of functional RAC or Ssb1/2p, and the effect was further enhanced by paromomycin. The mutant strains suffered primarily from a defect in translation termination, while misincorporation was compromised to a lesser extent. Consistently, a low level of soluble translation termination factor Sup35p enhanced growth defects in the mutant strains. Based on the combined data we conclude that RAC and Ssb1/2p are crucial in maintaining translational fidelity beyond their postulated role as chaperones for nascent polypeptides.

Early evidence (ca. 12,000 B.P.) for feasting at a burial cave in Israel

OpenAIRE

Munro, Natalie D.; Grosman, Leore

2010-01-01

Feasting is one of humanity's most universal and unique social behaviors. Although evidence for feasting is common in the early agricultural societies of the Neolithic, evidence in pre-Neolithic contexts is more elusive. We found clear evidence for feasting on wild cattle and tortoises at Hilazon Tachtit cave, a Late Epipaleolithic (12,000 calibrated years B.P.) burial site in Israel. This includes unusually high densities of butchered tortoise and wild cattle remains in two structures, the u...

Weak transitions in the quasi-elastic reaction 12C(e,e'p)11B

International Nuclear Information System (INIS)

Steenhoven, G. van der; Blok, H.P.; Vrije Univ., Amsterdam; Jans, E.; Lapikas, L.; Quint, E.N.M.; Witt Huberts, P.K.A. de

1988-01-01

In a high-resolution quasi-elastic 12 C(e,e'p) 11 B experiment several weak transitions have been observed to excited final states with spin and parity characteristic of direct knockout from orbitals above the 1p shell. The momentum distributions, which have been measured in parallel kinematics at an outgoing-proton energy of 70 MeV in the range of missing momentum - 170 ≤ p m ≤ 210 MeV/c, show the shape expected for a single-step knockout process. It is demonstrated that the interference between a direct-knockout process and a two-step process leading to the same final state in the (e,e'p) reaction may cause important modifications of the deduced spectroscopic factors. Explicit coupled-channels (CC) calculations show that the spectroscopic factor for the transition to the 7 - /2 state at 6.743 MeV is reduced by a factor of 6, whereas the spectroscopic factors of the other weak transitions observed in the present experiment are uncertain by a factor of 2 due to CC-effects. Since the strength of these transitions is larger than can be explained by a pure two-step process, we interpret the observation of these transitions as direct evidence for the existence of ground-state correlations in 12 C. The total spectroscopic strength in the E x region between 6 and 12 MeV amounts to 0.1, or 4.1% of the observed strength for 1p knockout in the low E x region. Two peaks have been identified in the missing-energy spectrum that hitherto have not been reported: A narrow peak at E x =9.82 (3) MeV with an l=0 character and a broad structure centered at about 11.5 MeV with an l=1 character. The missing-energy spectrum between E x =12 and 24 MeV corresponding to 1s 1/2 knockout has also been analyzed. The deduced momentum distribution shows evidence for the onset of a two-nucleon mechanism beyond the two-particle emission threshold. (orig.)

Ba{sub 2}Cu{sub 2}Te{sub 2}P{sub 2}O{sub 13}: A new telluro-phosphate with S=1/2 Heisenberg chain

Energy Technology Data Exchange (ETDEWEB)

Xia, Mingjun [Beijing Center for Crystal Research and Development, Key Laboratory of Functional Crystals and Laser Technology, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Shen, Shipeng; Lu, Jun; Sun, Young [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Li, R.K., E-mail: rkli@mail.ipc.ac.cn [Beijing Center for Crystal Research and Development, Key Laboratory of Functional Crystals and Laser Technology, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China)

2015-10-15

A new telluro-phosphate compound Ba{sub 2}Cu{sub 2}Te{sub 2}P{sub 2}O{sub 13} with S=1/2 Heisenberg chain has been successfully synthesized by solid state reaction and grown by flux method. Single crystal X-ray diffraction reveals that Ba{sub 2}Cu{sub 2}Te{sub 2}P{sub 2}O{sub 13} crystallizes into a monoclinic space group C2/c and cell parameters of a=17.647(3) Å, b=7.255(2) Å, c=9.191(2) Å and β=100.16 (3)°. In the structure of Ba{sub 2}Cu{sub 2}Te{sub 2}P{sub 2}O{sub 13}, one dimensional [CuTePO{sub 7}]{sup 3−} chains are formed by tetrahedral PO{sub 4} and trigonal bi-pyramidal TeO{sub 4} joining square planar CuO{sub 4} groups. Those [CuTePO{sub 7}]{sup 3−} chains are inter-connected by sharing one oxygen atom from the TeO{sub 4} group to form two dimensional layers. Magnetic susceptibility and specific heat measurements confirm that the title compound is a model one dimensional Heisenberg antiferromagnetic chain system. - Graphical abstract: Ba{sub 2}Cu{sub 2}Te{sub 2}P{sub 2}O{sub 13}, containing (CuTePO{sub 7}){sup 3−} chains formed by PO{sub 4} and TeO{sub 4} joining CuO{sub 4} groups, shows typical 1D Heisenberg antiferromagnetic chain model behavior as confirmed by magnetic measurements. - Highlights: • New telluro-phosphate Ba{sub 2}Cu{sub 2}Te{sub 2}P{sub 2}O{sub 13} has been grown. • It features layered structure composed of [CuTePO{sub 7}]{sup 3−} chains and TeO{sub 4} groups. • It shows the Heisenberg antiferromagnetic chain behavior. • It is transparent in the range of 1000–2500 nm with a UV absorption edge of 393 nm.

Duplication 4p and deletion 4p (Wolf-Hirschhorn syndrome) due to complementary gametes from a 3:1 segregation of a maternal balanced t(4;13)(p16;q11) translocation.

Science.gov (United States)

Takeno, S S; Corbani, M; Andrade, J A D; Smith, M de A C; Brunoni, D; Melaragno, M I

2004-08-30

We present clinical and cytogenetic data on a family with a t(4;13)(p16;q11) translocation present in four generations. The balanced translocation resulted in one individual with monosomy 4p and one individual with trisomy 4p, due to 3:1 segregation. The male patient with trisomy 4p was fertile and transmitted the extra chromosome to his daughter. Copyright 2004 Wiley-Liss, Inc.

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

Science.gov (United States)

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia A L; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B A; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-09-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. Copyright © 2012 Wiley Periodicals, Inc.

13C/12C ratios in human urine concrementes

International Nuclear Information System (INIS)

Hoefs, J.; Armbruster, T.

1978-01-01

Oxalate, uric acid, and phosphate stones have been analyzed for their carbon isotope composition. The oxalate stones show delta 13 C values between -17.0 and -19.5 pro mille, the uric acid stones between -14.9 and -19.4 pro mille, and the phosphate stones between -13.0 and -23.9 pro mille. It is proposed that endogenic rather than exogenic sources are responsible for the 13 C/ 12 C ratios of the stones. The isotopic composition of the phosphate stones seems to be influenced primarily by bacterial activity. (orig.) [de

Chromosome number in Brazilian germplasm accessions of Paspalum hydrophilum, P. modestum and P. palustre (Gramineae; Paniceae

Directory of Open Access Journals (Sweden)

Pozzobon Marisa T.

2003-01-01

Full Text Available This paper compiles results of chromosome counts of Paspalum hydrophilum, P. modestum and P. palustre. Four Brazilian accessions of P. modestum have shown 2n = 2x = 20 chromosomes, a number already found in one accession from Argentina and in two from Brazil. Three other Brazilian accessions showed tetraploid level (2n = 4x = 40, which was previously unknown in this species. In P. hydrophilum, only one of the accessions analyzed presented tetraploid level, initially established for the species from plants collected in Argentina. Five additional accessions from Brazil showed the diploid number, previously detected in a single Brazilian population. A tetraploid cytotype was found in P. palustre, previously known as a diploid species. In addition to confirming the occurrence of distinct ploidy levels for all three species, the results establish the predominance of the diploid level in P. hydrophilum and P. modestum accessions collected in Brazil.

Calibration of an analyzing magnet using the 12C(d, p0)13C nuclear reaction with a thick carbon target

Science.gov (United States)

Andrade, E.; Canto, C. E.; Rocha, M. F.

2017-09-01

The absolute energy of an ion beam produced by an accelerator is usually determined by an electrostatic or magnetic analyzer, which in turn must be calibrated. Various methods for accelerator energy calibration are extensively reported in the literature, like nuclear reaction resonances, neutron threshold, and time of flight, among others. This work reports on a simple method to calibrate the magnet associated to a vertical 5.5 MV Van de Graaff accelerator. The method is based on bombarding with deuteron beams a thick carbon target and measuring with a surface barrier detector the particle energy spectra produced. The analyzer magnetic field is measured for each spectrum and the beam energy is deduced by the best fit of the simulation of the spectrum with the SIMNRA code that includes 12C(d,p0)13C nuclear cross sections.

P2Y12R-Dependent Translocation Mechanisms Gate the Changing Microglial Landscape

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Ukpong B. Eyo

2018-04-01

Full Text Available Summary: Microglia are an exquisitely tiled and self-contained population in the CNS that do not receive contributions from circulating monocytes in the periphery. While microglia are long-lived cells, the extent to which their cell bodies are fixed and the molecular mechanisms by which the microglial landscape is regulated have not been determined. Using chronic in vivo two-photon imaging to follow the microglial population in young adult mice, we document a daily rearrangement of the microglial landscape. Furthermore, we show that the microglial landscape can be modulated by severe seizures, acute injury, and sensory deprivation. Finally, we demonstrate a critical role for microglial P2Y12Rs in regulating the microglial landscape through cellular translocation independent of proliferation. These findings suggest that microglial patrol the CNS through both process motility and soma translocation. : Using a chronic in vivo imaging approach, Eyo et al. show that the physical positions of brain microglia change daily and that these changes increase following certain experimental manipulations. The mechanism underlying these changes involves cell translocation controlled by microglial-specific P2Y12 receptors. Keywords: microglia, P2Y12, seizures, epilepsy, whisker trimming, microglial landscape, two photon chronic imaging

6 CFR 13.12 - Notice of hearing.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Notice of hearing. 13.12 Section 13.12 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.12 Notice of hearing. (a) When the ALJ receives the Complaint and answer, the ALJ will promptly serve a...

Geraniol attenuates 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammation in mouse skin: possible role of p38 MAP Kinase and NF-κB.

Science.gov (United States)

Khan, Abdul Quaiyoom; Khan, Rehan; Qamar, Wajhul; Lateef, Abdul; Rehman, Muneeb U; Tahir, Mir; Ali, Farrah; Hamiza, Oday O; Hasan, Syed Kazim; Sultana, Sarwat

2013-06-01

Abnormal production of reactive oxygen species (ROS) and proinflammatory cytokines often act as trigger for development of most of the chronic human diseases including cancer via up-regulation of transcription factors and activation of MAP kinases. We investigated the protective effects of geraniol (GOH) against 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced oxidative and inflammatory responses, expression of p38MAPK, NF-κB and COX-2 in mouse skin. Animals were divided into four groups I-IV (n=6). Group II and III received topical application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day, for two days. Group III was pre-treated with GOH (250 μg) topically 30 min prior to each TPA administration. While group I and IV were given acetone (0.2 ml) and GOH respectively. Our results show that GOH significantly inhibited TPA induced lipid peroxidation (LPO), inflammatory responses, proinflammatory cytokine release, up regulates reduced glutathione (GSH) content and the activity of different antioxidant enzymes. Interestingly, GOH also inhibited TPA induced altered activity of p38MAPK. Further, TPA induced altered expression of NF-κB (p65) and COX-2 was also attenuated by GOH. Thus, our results suggest that GOH attenuates early tumor promotional changes, and it may serve as one of the various ways to prevent carcinogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Ground-state correlations in 12C and the mechanism of the (e,e'p) reaction

International Nuclear Information System (INIS)

Steenhoven, G. van der.

1987-01-01

In this thesis the results of an investigation into two aspects of the mechanism of the quasi-elastic (e,e'p) reaction: the interaction between the incident electron and the bound proton and the residual nucleus (final-state interaction (FSI)), are presented and used in the extraction of nuclear-structure information from (e,e'p) measurements on 12 C. The experiments were carried out at NIKHEF-K with a high-resolution spectrometer. Two kinds of experiments have been performed on 12 C. The first was aimed at obtaining accurate momentum distributions for various final states in 11 B. Some special measurements were carried out in order to vary the parameters influencing the FSI. The role of coupled-channels effects in the 12 C(e,e'p) 11 Be reaction is discussed. It is discussed whether some of the weak transitions observed in this reaction, can be associated with knockout from normally unoccupied shell-model orbitals. The second experiment on 12 C was devoted to the e-p coupling. These measurements were supplemented with data taken on 6 Li. The latter measurement allowed for measuring simultaneously knockout from the relatively dense 4 He core and the relatively dilute deuteron. In this way the density dependence of the e-p coupling in the nucleus could be studied. The results of these experiments have been compared to various models that take into account the effect of the nuclear medium upon the e-p coupling. The possible role of charge-exchange and meson-exchange currents in the interpretation of these experiments is also considered. A brief survey of the formalism of the quasi-elastic (e,e'p) reaction is also presented. (author). 196 refs.; 53 figs.; 21 tabs

Comet 169P/NEAT(=2002EX12): More Dead Than Alive

Science.gov (United States)

Kasuga, T.; Balam, D. D.; Wiegert, P. A.

2011-10-01

The Jupiter family comet 169P/NEAT (previously known as asteroid 2002 EX12) has a dynamical association with the ?-Capriconid meteoroid stream. In this paper, we present photometric observations of comet 169P/NEAT to further investigate the physical characters of its disintegration state related to the stream. The comet shows a point-like surface brightness profile limiting contamination due to coma emission at ˜ 4% at most, indicating no evidence of outgassing. An upper limit on the fraction of the surface that could be sublimating water ice of disintegration of the parent at every return.

NLO NRQCD disfavors the interpretation of X(3872) as {chi}{sub c1}(2P)

Energy Technology Data Exchange (ETDEWEB)

Butenschoen, Mathias [Wien Univ. (Austria). Fakultaet fuer Physik; He, Zhi-Guo; Kniehl, Bernd A. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

2013-03-15

We study {chi}{sub c1}(2P) inclusive hadroproduction at next-to-leading order (NLO) within the factorization formalism of nonrelativistic quantum chromodynamics (NRQCD), including both the color-singlet {sup 3}P{sub 1}{sup [1]} and color-octet {sup 3}S{sub 1}{sup [8]} c anti c Fock states. Assuming the recently discovered X(3872) hadron to be the 2P (1{sup ++}) charmonium state, we perform a fit to the cross sections measured by the CDF, CMS, and LHCb Collaborations. We either obtain an unacceptably high value of {chi}{sup 2} or a value of vertical stroke R{sub 2P}{sup '}(0) vertical stroke incompatible with well-established potential models. We thus conclude that NLO NRQCD is incompatible with the hypothesis X(3872){identical_to}{chi}{sub c1}(2P).

Inference of past atmospheric delta13C and P/sub CO2/ from 13C/12C measurements in tree rings

International Nuclear Information System (INIS)

Leavitt, S.W.

1982-01-01

Carbon dioxide release from fossil-fuel burning is significant enough that we may soon experience perceptible changes in climate with important human consequences. An accurate reconstruction of past 13 C/ 12 C ratios of atmospheric CO 2 may provide key constraints on the historical activity of the biosphere as CO 2 source or sink. Tree rings appear to be a repository of this information but there is much noise in the collection of previous reconstructions, presumably associated with site selection, radial variability, choice of representative wood chemical constituent, and subtle effects of climate on fractionation. This study attempts to avoid these pitfalls and develop a 50-yr delta 13 C/sub ATM/ record from juniper trees (genus Juniperus), in fact, by taking advantage of the influence of climate on fractionation. Trees were harvested from suitable sites in close proximity to weather stations with monthly records of temperature and precipitation. The most useful relationships for at most 7 of the 10 sites were delta 13 C with December temperature or precipitation, because the coefficients were nearly constant from one interval to the next and the intercepts differed. Local pollution effects are believed responsible for the three anomalous sites. The separation of these regression lines of different intervals is interpreted as the response of the trees to the changing delta 13 C of atmospheric CO 2 so that delta 13 C/sub ATM/ curves are constructed from this spacing. The shape of the best-fit reconstruction suggests the biosphere has acted as CO 2 source to about 1965 and may now be a net sink

/sup 13/C(p vector,d)/sup 12/C and /sup 208/Pb(p vector,d)/sup 207/Pb reactions at 123 MeV

Energy Technology Data Exchange (ETDEWEB)

Kraushaar, J J; Shepard, J R [Colorado Univ., Boulder (USA). Nuclear Physics Lab.; Miller, D W; Jacobs, W W; Jones, W P; Devins, D W [Indiana Univ., Bloomington (USA). Dept. of Physics

1983-02-01

Cross-section and analyzing power angular distributions have been measured for /sup 13/C(p vector,d) and /sup 208/Pb(p vector, d) at 123 MeV to the strong low-lying residual states in both final nuclei. The data have been compared with the results of both zero- and exact-finite-range distorted wave calculations and some serious discrepancies were noted for the analyzing powers. For the case of the /sup 13/C calculations, marked improvement in the description of the data was achieved with the use of a damping factor in the nuclear interior.

A 1.7-Mb YAC contig around the human BDNF gene (11p13): integration of the physical, genetic, and cytogenetic maps in relation to WAGR syndrome

Energy Technology Data Exchange (ETDEWEB)

Rosier, M.F.; Martin, A.; Houlgatte, R. [Genetique Moleculaire et Biologie du Development, Villejuif (France)] [and others

1994-11-01

WAGR (Wilms tumor, aniridia, genito-urinary abnormalities, mental retardation) syndrome in humans is associated with deletions of the 11p13 region. The brain-derived neurotrophic factor (BDNF) gene maps to this region, and its deletion seems to contribute to the severity of the patient`s mental retardation. Yeast artificial chromosomes (YACs) carrying the BDNF gene have been isolated and characterized. Localization of two known exons of this gene leads to a minimal estimation of its size of about 40 kb. Chimerism of the BDNF YACs has been investigated by fluorescence in situ hybridization and chromosome assignment on somatic cell hybrids. Using the BDNF gene, YAC end sequence tagged sites (STS), and Genethon microsatellite markers, the authors constructed a 1.7-Mb contig and refined the cytogenetic map at 11p13. The resulting integrated physical, genetic, and cytogenetic map constitutes a resource for the characterization of genes that may be involved in the WAGR syndrome. 42 refs., 2 figs., 3 tabs.

Measurement of the $^{12}$C($n,p$)$^{12}$B cross section at n_TOF (CERN) by in-beam activation analysis

CERN Document Server

Žugec, P.; Bosnar, D.; Mengoni, A.; Altstadt, S.; Andrzejewski, J.; Audouin, L.; Barbagallo, M.; Bécares, V.; Bečvář, F.; Belloni, F.; Berthoumieux, E.; Billowes, J.; Boccone, V.; Brugger, M.; Calviani, M.; Calviño, F.; Cano-Ott, D.; Carrapiço, C.; Cerutti, F.; Chiaveri, E.; Chin, M.; Cortés, G.; Cortés-Giraldo, M.A.; Cosentino, L.; Diakaki, M.; Domingo-Pardo, C.; Dressler, R.; Duran, I.; Eleftheriadis, C.; Ferrari, A.; Finocchiaro, P.; Fraval, K.; Ganesan, S.; García, A.R.; Giubrone, G.; Gómez-Hornillos, M.B.; Gonçalves, I.F.; González-Romero, E.; Griesmayer, E.; Guerrero, C.; Gunsing, F.; Gurusamy, P.; Heinitz, S.; Jenkins, D.G.; Jericha, E.; Käppeler, F.; Karadimos, D.; Kivel, N.; Kokkoris, M.; Krtička, M.; Kroll, J.; Langer, C.; Lederer, C.; Leeb, H.; Leong, L.S.; Lo Meo, S.; Losito, R.; Manousos, A.; Marganiec, J.; Martínez, T.; Massimi, C.; Mastinu, P.; Mastromarco, M.; Mendoza, E.; Milazzo, P.M.; Mingrone, F.; Mirea, M.; Mondalaers, W.; Musumarra, A.; Paradela, C.; Pavlik, A.; Perkowski, J.; Plompen, A.; Praena, J.; Quesada, J.; Rauscher, T.; Reifarth, R.; Riego, A.; Roman, F.; Rubbia, C.; Sarmento, R.; Saxena, A.; Schillebeeckx, P.; Schmidt, S.; Schumann, D.; Tagliente, G.; Tain, J.L.; Tarrío, D.; Tassan-Got, L.; Tsinganis, A.; Valenta, S.; Vannini, G.; Variale, V.; Vaz, P.; Ventura, A.; Versaci, R.; Vermeulen, M.J.; Vlachoudis, V.; Vlastou, R.; Wallner, A.; Ware, T.; Weigand, M.; Weiß, C.; Wright, T.

2014-01-01

The integral cross section of the $^{12}$C($n,p$)$^{12}$B reaction has been determined for the first time in the neutron energy range from threshold to several GeV at the n_TOF facility at CERN. The measurement relies on the activation technique, with the $\\beta$-decay of $^{12}$B measured over a period of four half-lives within the same neutron bunch in which the reaction occurs. The results indicate that model predictions, used in a variety of applications, are mostly inadequate. The value of the integral cross section reported here can be used as a benchmark for verifying or tuning model calculations.

Paternal uniparental isodisomy of chromosome 11p15.5 within the pancreas causes isolated hyperinsulinaemic hypoglycaemia

Directory of Open Access Journals (Sweden)

Sarah E Flanagan

2011-11-01

Full Text Available BackgroundLoss of function mutations in the genes encoding the pancreatic β-cell ATP-sensitive potassium (KATP channel are identified in approximately 80% of patients with diazoxide-unresponsive hyperinsulinaemic-hypoglycaemia (HH. For a small number of patients HH can occur as part of a multisystem disease such as Beckwith-Wiedemann syndrome (BWS. In approximately 20% of patients, BWS results from chromosome 11 paternal uniparental disomy (UPD, which causes dysregulation of imprinted growth regulation genes at 11p15.5. There is a considerable range in the clinical features and phenotypic severity associated with BWS which is likely to be due to somatic mosaicism. The cause of HH in these patients is not known.Research Design and methodsWe undertook microsatellite analysis of 12 markers spanning chromosome 11p in two patients with severe HH and diffuse disease requiring a pancreatectomy. In both patients mutations in the KATP channel genes had not been identified. ResultsWe identified segmental paternal UPD in DNA extracted from pancreatic tissue in both patients. UPD was not observed in DNA extracted from the patient’s leukocytes or buccal samples. In both cases the UPD encompassed the differentially methylated region at chromosome 11p15.5. Despite this neither patient had any further features of BWS.ConclusionsPaternal UPD of the chromosome 11p15.5 differentially methylated region limited to the pancreatic tissue may represent a novel cause of isolated diazoxide unresponsive HH. Loss of heterozygosity studies should therefore be considered in all patients with severe HH who have undergone pancreatic surgery when KATP channel mutation(s have not been identified.

Rosiglitazone attenuates NF-κB-dependent ICAM-1 and TNF-α production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation

International Nuclear Information System (INIS)

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia; Song, Tao; You, Yu; Tang, Zhen-Yan; Li, Yuan-Jian; Zhang, Guo-Gang

2007-01-01

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-κB) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-κB-mediated sICAM-1, TNF-α production and the possible involvement of ERK 1/2 /p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-α in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-κB inhibitor; PD98059, MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK 1/2 /p38MAPK pathway and NF-κB activity in HUVECs. The results show that Hcy activated both ERK 1/2 /p38MAPK pathway and NF-κB-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK 1/2 /p38MAPK phosphorylation, suggesting that Hcy-induced ERK 1/2 /p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-κB activation was mediated by activation of ERK 1/2 /p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-κB-mediated sICAM-1 and TNF-α production induced by Hcy via inhibition of ERK 1/2 /p38MAPK pathway

11p Microdeletion including WT1 but not PAX6, presenting with cataract, mental retardation, genital abnormalities and seizures: a case report

Directory of Open Access Journals (Sweden)

Baekgaard Peter

2009-02-01

Full Text Available Abstract WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities and mental retardation and Potocki-Shaffer syndrome are rare contiguous gene deletion syndromes caused by deletions of the 11p14-p12 chromosome region. We present a patient with mental retardation, unilateral cataract, bilateral ptosis, genital abnormalities, seizures and a dysmorphic face. Cytogenetic analysis showed a deletion on 11p that was further characterized using FISH and MLPA analyses. The deletion (11p13-p12 located in the area between the deletions associated with the WAGR and Potocki-Shaffer syndromes had a maximum size of 8.5 Mb and encompasses 44 genes. Deletion of WT1 explains the genital abnormalities observed. As PAX6 was intact the cataract observed cannot be explained by a deletion of this gene. Seizures have been described in Potocki-Shaffer syndrome while mental retardation has been described in both WAGR and Potocki-Shaffer syndrome. Characterization of this patient contributes further to elucidate the function of the genes in the 11p14-p12 chromosome region.

The collision cross sections for excitation energy transfer in Rb*(5P3/2)+K(4S1/2)→Rb(5S1/2)+K*(4PJ) processes

International Nuclear Information System (INIS)

Horvatic, V.; Vadla, C.; Movre, M.

1993-01-01

The collisional excitation transfer for the processes Rb * (5P 3/2 ) + K(4S 1/2 ) → Rb(5S 1/2 ) + K * (4P J ), J = 1/2, 3/2, was investigated using two-photon laser excitation techniques with a thermionic heat-pipe diode as a detector. The population densities of the K 4P J levels induced by collisions with excited Rb atoms as well as those produced by direct laser excitation of the potassium atoms were probed through the measurement of the thermionic signals generated due to the ionization of the potassium atoms emerging from the K(4P J ) → K(7S 1/2 ) excitation channel. (orig./WL)

[A case of mosaic ring chromosome 4 with subtelomeric 4p deletion].

Science.gov (United States)

Kim, Jeong Hyun; Oh, Phil Soo; Na, Hye Yeon; Kim, Sun-Hee; Cho, Hyoun Chan

2009-02-01

Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2

Human chromosome 9 can complement UV sensitivity of xeroderma pigmentosum group A cells

International Nuclear Information System (INIS)

Ishizaki, Kanji; Sasaki, Masao S.; Ikenaga, Mituo; Nakamura, Yusuke

1990-01-01

A single human chromosome derived from normal human fibroblasts and tagged with the G418 resistance gene was transferred into SV40-transformed xeroderma pigmentosum group A (XP-A) cells via microcell fusion. When chromosome 1 or 12 was transferred, UV sensitivity of microcell hybrid cells was not changed. By contrast, after transferring chromosome 9,7 of 11 reipient clones were as UV-resistant as normal human cells. Four other clones were still as UV-sensitive as the parental XP-A cells. Southern hybridization analysis using a polymorphic probe, pEKZ19.3, which is homologous to a sequence of the D9S17 locus on chromosome 9, has confirmed that at least a part of normal human chromosome 9 was transferred into the recipient clones. However, amounts iof UV-induced unscheduled DNA synthesis in the UV-resistant clones were only one-third of those in normal human cells. These results indicate that a gene on chromosome 9 can confer complementation of high UV sensitivity of XP-A cells although it is still possible that 2 or more genes might be involved in the defective-repair phenotypes of XP-A. (author). 20 refs.; 3 figs.; 1 tab

Resilience to audiogenic seizures is associated with p-ERK1/2 dephosphorylation in the subiculum of Fmr1 knockout mice

Directory of Open Access Journals (Sweden)

Giulia eCuria

2013-04-01

Full Text Available Young, but not adult, Fmr1 knockout (KO mice display audiogenic seizures (AGS that can be prevented by inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation. In order to identify the cerebral regions involved in these phenomena, we characterized the response to AGS in Fmr1 KO mice and wild type (WT controls at postnatal day (P 45 and P90. To characterize the diverse response to AGS in various cerebral regions, we evaluated the activity markers FosB/ΔFosB and phosphorylated ERK1/2 (p-ERK1/2. Wild running (100% of tested mice followed by clonic/tonic seizures (30% were observed in P45 Fmr1 KO mice, but not in WT mice. In P90 Fmr1 KO mice, wild running was only present in 25% of tested animals. Basal FosB/ΔFosB immunoreactivity was higher (P<0.01 vs WT in the CA1 and subiculum of P45 Fmr1 KO mice. Following the AGS test, FosB/ΔFosB expression consistently increased in most of the analyzed regions in both groups at P45, but not at P90. Interestingly, FosB/ΔFosB immunoreactivity was significantly higher in P45 Fmr1 KO mice in the medial geniculate body (P<0.05 vs WT and CA3 (P<0.01. Neurons presenting with immunopositivity to p-ERK1/2 were more abundant in the subiculum of Fmr1 KO mice in control condition (P<0.05 vs WT, in both age groups. In this region, p-ERK1/2-immunopositive cells significantly decreased (-75%, P<0.01 in P90 Fmr1 KO mice exposed to the AGS test, but no changes were found in P45 mice or in other brain regions. In both age groups of WT mice, p-ERK1/2-immunopositive cells increased in the subiculum after exposure to the acoustic test. Our findings illustrate that FosB/ΔFosB markers are overexpressed in the medial geniculate body and CA3 in Fmr1 KO mice experiencing AGS, and that p-ERK1/2 is markedly decreased in the subiculum of Fmr1 KO mice resistant to AGS induction. These findings suggest that resilience to AGS is associated with dephosphorylation of p-ERK1/2 in the subiculum of mature Fmr1 KO mice.

Sperm FISH analysis of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat complex chromosome rearrangement.

Science.gov (United States)

Ferfouri, F; Boitrelle, F; Clement, P; Molina Gomes, D; Selva, J; Vialard, F

2014-06-01

Complex chromosome rearrangements (CCR) with two independent chromosome rearrangements are rare. Although CCRs lead to high unbalanced gamete rates, data on meiotic segregation in this context are scarce. A male patient was referred to our clinic as part of a family screening programme prompted by the observation of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat karyotype in his brother. Karyotyping identified the same CCR. Sperm FISH (with locus-specific probes for the segments involved in the translocations and nine chromosomes not involved in both rearrangements) was used to investigate the rearrangements meiotic segregation products and establish whether or not an inter-chromosomal effect was present. Sperm nuclear DNA fragmentation was also evaluated. For rob(13;14) and der(Y), the proportions of unbalanced products were, respectively, 26.4% and 60.6%. Overall, 70.3% of the meiotic segregation products were unbalanced. No evidence of an inter-chromosomal effect was found, and the sperm nuclear DNA fragmentation rate was similar to our laboratory's normal cut-off value. In view of previously published sperm FISH analyses of Robertsonian translocations (and even though the mechanism is still unknown), we hypothesise that cosegregation of der(Y) and rob(13;14) could modify rob(13;14) meiotic segregation. © 2013 Blackwell Verlag GmbH.

12/15 Lipoxygenase regulation of colorectal tumorigenesis is determined by the relative tumor levels of its metabolite 12-HETE and 13-HODE in animal models.

Science.gov (United States)

Chang, Jian; Jiang, Li; Wang, Yinqiu; Yao, Bing; Yang, Shilin; Zhang, Bixiang; Zhang, Ming-Zhi

2015-02-20

Colorectal cancer (CRC) continues to be a major cause of morbidity and mortality. The arachidonic acid (AA) pathway and linoleic acid (LA) pathway have been implicated as important contributors to CRC development and growth. Human 15-lipoxygenase 1 (15-LOX-1) converts LA to anti-tumor 13-S-hydroxyoctadecadienoic acid (13-HODE)and 15-LOX-2 converts AA to 15-hydroxyeicosatetraenoic acid (15-HETE). In addition, human 12-LOX metabolizes AA to pro-tumor 12-HETE. In rodents, the function of 12-LOX and 15-LOX-1 and 15-LOX-2 is carried out by a single enzyme, 12/15-LOX. As a result, conflicting conclusions concerning the role of 12-LOX and 15-LOX have been obtained in animal studies. In the present studies, we determined that PD146176, a selective 15-LOX-1 inhibitor, markedly suppressed 13-HODE generation in human colon cancer HCA-7 cells and HCA-7 tumors, in association with increased tumor growth. In contrast, PD146176 treatment led to decreases in 12-HETE generation in mouse colon cancer MC38 cells and MC38 tumors, in association with tumor inhibition. Surprisingly, deletion of host 12/15-LOX alone led to increased MC38 tumor growth, in association with decreased tumor 13-HODE levels, possibly due to inhibition of 12/15-LOX activity in stroma. Therefore, the effect of 12/15-LOX on colorectal tumorigenesis in mouse models could be affected by tumor cell type (human or mouse), relative 12/15 LOX activity in tumor cells and stroma as well as the relative tumor 13-HODE and 12-HETE levels.

Cell killing and chromosomal aberration induced by heavy-ion beams in cultured human tumor cells

International Nuclear Information System (INIS)

Takakura, K.; Funada, A.; Mohri, M.; Lee, R.; Aoki, M.; Furusawa, Y.; Gotoh, E.

2003-01-01

Full text: To clarify the relation between cell death and chromosomal aberration in cultured human tumor cells irradaited with heavy-ion beams. The analyses were carried out on the basis of the linear energy transfer (LET) values of heavy ion beams as radiation source. Exponentially growing human tumor cells, Human Salivary Gland Tumor cells (HSG cells), were irradiated with various high energy heavy ions, such as 13 keV/micrometer carbon (C) ions as low LET charged particle radiation source, 120 keV/ micrometer carbon (C) ions and 440 keV/micrometer iron (Fe) ions as high LET charged particle radiation sources.The cell death was analysed by the colony formation method, and the chromosomal aberration and its repairing kinetics was analysed by prematurely chromosome condensation method (PCC method) using calyculin A. Chromatid-type breaks, isochromatid breaks and exchanges were scored for the samples from the cells keeping with various incubation time after irradiation. The LET dependence of the cell death was similar to that of the chromosome exchange formation after 12 hours incubation. A maximum peak was around 120 keV/micrometer. However it was not similar to the LET dependence of isochromatid breaks or chromatid breaks after 12 hours incubation. These results suggest that the exchanges formed in chromosome after irradiation should be one of essential causes to lead the cell death. The different quality of induced chromosome damage between high-LET and low-LET radiation was also shown. About 89 % and 88 % chromatid breaks induced by X rays and 13 keV/micrometer C ions were rejoined within 12 hours of post-irradiation, though only 71% and 58 % of chromatid breaks induced by 120 keV/micrometer C ions and 440 keV/micrometer Fe ions were rejoined within 12 hours of post-irradiation

WASP-12b AND HAT-P-8b are members of triple star systems

Energy Technology Data Exchange (ETDEWEB)

Bechter, Eric B.; Crepp, Justin R.; Matthews, Christopher T. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556 (United States); Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Johnson, John Asher [Department of Planetary Science, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Hinkley, Sasha; Muirhead, Philip S.; Montet, Benjamin T.; Morton, Timothy D. [Department of Astronomy, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Howard, Andrew W., E-mail: ebechter@nd.edu [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)

2014-06-10

We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M {sub ☉} using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

WASP-12b and HAT-P-8b are Members of Triple Star Systems

Science.gov (United States)

Bechter, Eric B.; Crepp, Justin R.; Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Hinkley, Sasha; Muirhead, Philip S.; Johnson, John Asher; Howard, Andrew W.; Montet, Benjamin T.; Matthews, Christopher T.; Morton, Timothy D.

2014-06-01

We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M ⊙ using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

WASP-12b AND HAT-P-8b are members of triple star systems

International Nuclear Information System (INIS)

Bechter, Eric B.; Crepp, Justin R.; Matthews, Christopher T.; Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Johnson, John Asher; Hinkley, Sasha; Muirhead, Philip S.; Montet, Benjamin T.; Morton, Timothy D.; Howard, Andrew W.

2014-01-01

We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M ☉ using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

Small atomic displacements in the molybdenophosphates AMo2P3O12 (A = K, Rb, Tl)

International Nuclear Information System (INIS)

Leclaire, A.; Raveau, B.

1988-01-01

KMo 2 P 3 O 12 , M r = 515.90, orthorhombic, Pbnm, a = 17.6398(14), b = 9.1761(4), c = 12.3000(8) A, V = 1990.9(4) A 3 , Z=8, D x = 3.44 Mg m -3 , λ(Mo Kα) = 0.71069 A, μ = 3.42 mm -1 , F(000) = 1952. T = 294 K, R = 0.028 for 2123 reflections. RbMo 2 P 3 O 12 , M r = 562.26, orthorhombic, Pbcm, a = 8.8314(8), b = 9.2368(7), c = 12.3051(9) A, V = 1003.8(4) A 3 , Z=4, D x = 3.72 Mg m -3 , λ(Mo Kα) = 0.71069 A, μ = 8.08 mm -1 , F(000) = 1048, T = 294 K, R = 0.044 for 2073 reflections. The Mo 2 P 3 O 12 frameworks of the K, Rb and Tl compounds are almost the same. The main difference is in the position of the alkaline-earth ions in the tunnels, which induces, in the potassium compound, a superstructure along a. The alkaline-earth ions are slightly displaced as their size decreases in order that the A-O distances may agree with the sum of the ionic radii. (orig.)

Familial partial duplication (1)(p21p31)

Energy Technology Data Exchange (ETDEWEB)

Hoechstetter, L.; Soukup, S.; Schorry, E.K. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)

1995-11-20

A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30-year-old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed. 8 refs., 5 figs., 1 tab.

Chromosomal localization of the human and mouse hyaluronan synthase genes

Energy Technology Data Exchange (ETDEWEB)

Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others

1997-05-01

We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

Spectroscopic constants and the potential energy curve of the iodine weakly bound 0+g state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

International Nuclear Information System (INIS)

Akopyan, M E; Baturo, V V; Lukashov, S S; Poretsky, S A; Pravilov, A M

2013-01-01

The stepwise three-step three-colour aser excitation scheme and rotational as well as rovibrational energy transfer processes in the 0 + g state induced by collisions with He and Ar atoms are used for determination of rovibronic level energies of the weakly bound 0 + g state correlating with the I( 2 P 1/2 ) + I( 2 P 1/2 ) dissociation limit. Dunham coefficients of the state, Y i0 (i = 0–3), Y i1 (i = 0–3) and Y 02 for the v 0 g + = 0–16 and J 0 g + ≈ 14–135 ranges as well as the dissociation energy of the state, D e , and equilibrium I–I distance of the state, R e , are determined. The potential energy curve of the state constructed using these constants is also reported. (paper)

μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′-bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]bromidocopper(I} acetone disolvate

Directory of Open Access Journals (Sweden)

Wen-Juan Shi

2008-10-01

Full Text Available In the crystal structure of the title compound, [Cu2Br2(dppe3]·2CH3COCH3 [dppe is 1,2-bis(diphenylphosphinoethane, C26H24P2], the two Cu centers are bridged by a dppe ligand and each metal center carries one chelating dppe unit, with the fourth coordination site available for the Br− anion. The molecule is centrosymmetric, with the center of symmetry located between the methylene C atoms of the bridging dppe ligand. The crystal structure is stabilized by intramolecular C—H...Br hydrogen bonds and intermolecular π–π interactions, with a centroid-to-centroid distance of 3.2055 (1 Å.

Structural, Mechanical, Anisotropic, and Thermal Properties of AlAs in oC12 and hP6 Phases under Pressure

Directory of Open Access Journals (Sweden)

Wei Zhang

2018-05-01

Full Text Available The structural, mechanical, anisotropic, and thermal properties of oC12-AlAs and hP6-AlAs under pressure have been investigated by employing first-principles calculations based on density functional theory. The elastic constants, bulk modulus, shear modulus, Young’s modulus, B/G ratio, and Poisson’s ratio for oC12-AlAs and hP6-AlAs have been systematically investigated. The results show that oC12-AlAs and hP6-AlAs are mechanically stable within the considered pressure. Through the study of lattice constants (a, b, and c with pressure, we find that the incompressibility of oC12-AlAs and hP6-AlAs is the largest along the c-axis. At 0 GPa, the bulk modulus B of oC12-AlAs, hP6-AlAs, and diamond-AlAs are 76 GPa, 75 GPa, and 74 Gpa, respectively, indicating that oC12-AlAs and hP6-AlAs have a better capability of resistance to volume than diamond-AlAs. The pressure of transition from brittleness to ductility for oC12-AlAs and hP6-AlAs are 1.21 GPa and 2.11 GPa, respectively. The anisotropy of Young’s modulus shows that oC12-AlAs and hP6-AlAs have greater isotropy than diamond-AlAs. To obtain the thermodynamic properties of oC12-AlAs and hP6-AlAs, the sound velocities, Debye temperature, and minimum thermal conductivity at considered pressure were investigated systematically. At ambient pressure, oC12-AlAs (463 K and hP6-AlAs (471 K have a higher Debye temperature than diamond-AlAs (433 K. At T = 300 K, hP6-AlAs (0.822 W/cm·K−1 has the best thermal conductivity of the three phases, and oC12-AlAs (0.809 W/cm·K−1 is much close to diamond-AlAs (0.813 W/cm·K−1.

Transcriptional down-regulation of thromboxane A(2) receptor expression via activation of MAPK ERK1/2, p38/NF-kappaB pathways

DEFF Research Database (Denmark)

Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2009-01-01

culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions....... Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappaB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D...

Transcriptional Down-Regulation of Thromboxane A(2) Receptor Expression via Activation of MAPK ERK1/2, p38/NF-kappaB Pathways

DEFF Research Database (Denmark)

Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2008-01-01

culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions....... Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappaB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D...

Aneuploidy in immortalized human mesenchymal stem cells with non-random loss of chromosome 13 in culture.

Science.gov (United States)

Takeuchi, Masao; Takeuchi, Kikuko; Ozawa, Yutaka; Kohara, Akihiro; Mizusawa, Hiroshi

2009-01-01

Aneuploidy (an abnormal number of chromosomes) is commonly observed in most human cancer cells, highlighting the need to examine chromosomal instability in tumorigenesis. Previously, the immortalized human mesenchymal stem cell line UE6E7T-3 was shown to undergo a preferential loss of one copy of chromosome 13 after prolonged culture. Here, the loss of chromosome 13 was found to be caused by chromosome missegregation during mitosis, which involved unequal segregation, exclusion of the misaligned chromosome 13 on the metaphase plate, and trapping of chromosome 13 in the midbody region, as observed by fluorescence in situ hybridization. Near-diploid aneuploidy, not tetraploidy, was the direct result. The loss of chromosome 13 was non-random, and was detected by analysis of microsatellites and single nucleotide polymorphism-based loss of heterozygosity (LOH). Of the five microsatellite loci on chromosome 13, four loci showed microsatellite instability at an early stage in culture, and LOH was apparent at a late stage in culture. These results suggest that the microsatellite mutations cause changes in centromere integrity provoking loss of this chromosome in the UE6E7T-3 cell line. Thus, these results support the use of this cell line as a useful model for understanding the mechanism of aneuploid formation in cell cultures.

Mycobacterium tuberculosis promotes Th17 expansion via regulation of human dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms upon exogenous IFN-γ

DEFF Research Database (Denmark)

Søndergaard, Jonas Nørskov; Laursen, Janne Marie; Rosholm, Lisbeth Buus

2014-01-01

) are some of the first cells to interact with Mtb and they play an essential role in development of protective immunity against Mtb. Given that Mtb-infected macrophages have difficulties in degrading Mtb, they need help from IFN-γ-producing CD4+ T cells propagated via IL-12p70-producing DCs. Here we report...... that Mtb modifies human DC plasticity by expanding a CD14+ DC subset with weak IL-12p70-producing capacity. The CD14+ Mtb-promoted subset was furthermore poor inducers of IFN-γ by naive CD4+ T cells, but instead prompted IL-17A-producing RORγT+ CD4+ T cells. Mtb-derived peptidoglycan and mannosylated...... conclude that Mtb exploits DC plasticity to reduce production of IL-12p70, and that this process is entirely divertible by exogenous IFN-γ. These data suggest that strategies to increase local IFN-γ production in the lungs of tuberculosis patients may boost host immunity toward Mtb....

Quasielastic C-12(e,e ' p) reaction at high momentum transfer

NARCIS (Netherlands)

Morrison, JH; Baghaei, H; Bertozzi, W; Gilad, S; Glickman, J; Hyde-Wright, CE; Kalantar-Nayestanaki, N; Lourie, RW; Penn, S; Ulmer, PE; Weinstein, LB; Cottman, BH; Ghedira, L; Winhold, EJ; Calarco, J.R.; Wise, J; Boberg, P; Chang, CC; Zhang, D; Aniol, K; Epstein, MB; Margaziotis, DJ; Finn, JM; Perdrisat, C; Punjabi, P.

We measured the C-12(e,e'p) cross section as a function of missing energy in parallel kinematics for (q,omega)=(970 MeV/c, 330 MeV) and (990 MeV/c, 475 MeV). At omega=475 MeV, at the maximum of the quasielastic peak, there is a large continuum (E-m>50 MeV) cross section extending out to the deepest

13 CFR 117.12 - Mediation.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Mediation. 117.12 Section 117.12... Mediation. (a) SBA shall, after ensuring that the complaint falls within the coverage of this Act and all... clearly within an exception, promptly refer the complaint to the Federal Mediation and Conciliation...

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

Science.gov (United States)

Thevenon, Julien; Monnier, Nicole; Callier, Patrick; Dieterich, Klaus; Francoise, Michel; Montgomery, Tara; Kjaergaard, Susanne; Neas, Katherine; Dixon, Joanne; Dahm, Thomas Lee; Huet, Frédéric; Ragon, Clémence; Mosca-Boidron, Anne-Laure; Marle, Nathalie; Duplomb, Laurence; Aubriot-Lorton, Marie-Hélène; Mugneret, Francine; Vokes, Steve A; Tucker, Haley W; Lunardi, Joël; Faivre, Laurence; Jouk, Pierre Simon; Thauvin-Robinet, Christel

2014-12-01

Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay. © 2014 Wiley Periodicals, Inc.

P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

International Nuclear Information System (INIS)

Hwang, Melissa; Peddibhotla, Sirisha; McHenry, Peter; Chang, Peggy; Yochum, Zachary; Park, Ko Un; Sears, James Cooper; Vargo-Gogola, Tracy

2012-01-01

Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis

P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Hwang, Melissa [Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617 (United States); Peddibhotla, Sirisha [Department of Molecular and Human Genetics, Baylor College of Medicine, John P. McGovern Campus, NABS-0250, Houston, TX 77030 (United States); McHenry, Peter [Department of Biology, Southwestern Adventist University, 100 W. Hillcrest, Keene, TX 76059 (United States); Chang, Peggy; Yochum, Zachary; Park, Ko Un; Sears, James Cooper; Vargo-Gogola, Tracy, E-mail: vargo-gogola.1@nd.edu [Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617 (United States)

2012-04-25

Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis.

Magnetic properties and magnetocaloric effects in Mn1.2Fe0.8P1-xGex compounds

International Nuclear Information System (INIS)

Ou, Z Q; Wang, G F; Lin Song; Tegus, O; Brueck, E; Buschow, K H J

2006-01-01

We have studied the magnetic properties and magnetocaloric effects in the Mn 1.2 Fe 0.8 P 1-x Ge x compounds with x = 0.2, 0.22, 0.3, 0.4 and 0.5. X-ray diffraction patterns show that the Mn 1.2 Fe 0.8 P 1-x Ge x compounds crystallize in the hexagonal Fe 2 P-type crystal structure. The magnetic moments of the Mn 1.2 Fe 0.8 P 1-x Ge x compounds measured at 5 K and 5 T increase with increasing Ge content. The Curie temperature increases strongly and the magnetic entropy change has a maximum around 233 K for the compound with x = 0.22, which is about 19 and 31 J kg -1 K -1 for a field change of 2 and 5 T, respectively

Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

Energy Technology Data Exchange (ETDEWEB)

Lennon, G.G.; Giorgi, D.; Martin, J.R. [Lawrence Livermore National Lab., CA (United States)] [and others

1994-09-01

Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

14 CFR 291.44 - BTS Schedule P-12(a), Fuel Consumption by Type of Service and Entity.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false BTS Schedule P-12(a), Fuel Consumption by... TRANSPORTATION Reporting Rules § 291.44 BTS Schedule P-12(a), Fuel Consumption by Type of Service and Entity. (a.... (e)(1) The cost of fuel shall include shrinkage, but excludes: (i) “Throughput” and “in to plane...

Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

Directory of Open Access Journals (Sweden)

Moriyama Mariko

2012-08-01

Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

Frequency metrology on the 4s(2)S(1/2)-4p(2)P(1/2) transition in Ca-40(+) for a comparison with quasar data

NARCIS (Netherlands)

Wolf, A.L.; van den Berg, S.A.; Gohle, C.; Salumbides, E.J.; Ubachs, W.M.G.; Eikema, K.S.E.

2008-01-01

High accuracy frequency metrology on the 4s S 12 2 -4p P 12 2 transition in calcium ions is performed using laser cooled and crystallized ions in a linear Paul trap. Calibration is performed with a frequency comb laser, resulting in a transition frequency of f=755 222 766.2 (1.7) MHz. The accuracy

Poor adherence to P2Y12 antagonists increased cardiovascular risks in Chinese PCI-treated patients.

Science.gov (United States)

Sun, Yang; Li, Chenze; Zhang, Lina; Hu, Dong; Zhang, Xudong; Yu, Ting; Tao, Min; Wang, Dao Wen; Shen, Xiaoqing

2017-03-01

Low adherence to secondary prevention medications (ATM) of patients after acute coronary syndrome (ACS) is associated with poor clinical outcomes. However, literature provides limited data on assessment of ATM and risks associated with poor in Chinese patients with ACS. In the current work, ATM was assessed in consecutively recruited patients with ACS in Tongji Hospital from November 5, 2013 to December 31, 2014. A total of 2126 patients were classified under low adherence (proportion of days covered (PDC) C50%) groups based on their performance after discharge. All patients were followed up at the 1st, 6th, and 12th month of discharge while recording ATM and major adverse cardiac events (MACE). Bivariate logistic regression was used to identify the factors associated with ATM. Cox regression was used to analyze the association between ATM and MACE within one year after discharge. Results showed that coronary artery bypass grafting (CABG) alone had significantly lower proportion of high adherence to P2Y12 antagonists (83.0% vs. 90.7%, P < 0.01) than patients treated with percutaneous coronary intervention (PCI) only. Moreover, in patients undergoing PCI, high adherence to P2Y12 antagonists decreased the risk of MACE (hazard ratio = 0.172, 95% confidence interval: 0.039-0.763; P = 0.021). In conclusion, PCI-treated patients are more prone to remaining adherent to medications than CABG-treated patients. High adherence to P2Y12 antagonists was associated with lower risk of MACE.

IL-1β Upregulates StAR and Progesterone Production Through the ERK1/2- and p38-Mediated CREB Signaling Pathways in Human Granulosa-Lutein Cells.

Science.gov (United States)

Dang, Xuan; Zhu, Qinling; He, Yaqiong; Wang, Yuan; Lu, Yao; Li, Xiaoxue; Qi, Jia; Wu, Hasiximuke; Sun, Yun

2017-10-01

The proinflammatory cytokine interleukin-1β (IL-1β) may be involved in several ovulation-associated events, such as protease synthesis, prostaglandin production, and steroidogenesis in granulosa cells. However, the exact effect of IL-1β on progesterone synthesis in granulosa cells and the underlying mechanism remain unclear. By using cultured granulosa-lutein cells collected from women undergoing in vitro fertilization or intracytoplasmic sperm injection, we found that IL-1β upregulated steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis in granulosa-lutein cells, which was comparable with luteinizing hormone effect and could be abolished by an IL-1 receptor antagonist. Moreover, IL-1β activated the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB), and knockdown of CREB attenuated the induction of StAR expression and progesterone synthesis by IL-1β in granulosa-lutein cells. Furthermore, IL-1β activated the extracellular signal-regulated kinase (ERK)1/2 and p38 pathways and inhibition of the ERK1/2 and p38 pathways attenuated the IL-1β-induced phosphorylation of CREB, StAR expression, and progesterone synthesis in granulosa-lutein cells. In conclusion, IL-1β could upregulate StAR expression and stimulate progesterone biosynthesis through increase in CREB phosphorylation via activating the ERK1/2 and p38 pathways in human granulosa-lutein cells. Copyright © 2017 Endocrine Society.

Activation of MEK 1/2 and p42/44 MAPK by Angiotensin II in Hepatocyte Nucleus and their Potentiation by Ethanol

Science.gov (United States)

Aroor, Annayya R.; Lee, Youn Ju; Shukla, Shivendra D.

2009-01-01

Hepato-subcellular effect of Ang II and ethanol on the p42/44 MAP Kinase and MEK1/2 were investigated in the nucleus of rat hepatocytes. Hepatocytes were treated with ethanol (100 mM) for 24 hr and stimulated with angiotensin II (Ang II, 100 nM, 5 min). The levels of p42/44 MAPK and MEK1/2 were monitored in the nuclear fraction using antibodies. Ang II itself caused significant accumulation of phospho-p42/44 MAPK in the nucleus without any significant translocation of p42/44 MAPK protein there by suggesting activation of p42/44 MAPK in the nucleus. Ang II caused marked accumulation of phospho-MEK 1/2 in the nucleus without any significant accumulation of MEK1/2 protein. Ratio of phospho-MEK 1/2 to MEK 1/2 protein in the nucleus after Ang II treatment was 2.4 times greater than control suggesting phosphorylation of MEK 1/2 inside the nucleus. Ethanol had no effect on the protein level or the activation of p42/44 MAPK in the nucleus. Ethanol treatment potentiated nuclear activation of p42/44 MPAK by Ang II but not translocation of p42/44 MAPK protein. This was accompanied by potentiation of Ang II stimulated accumulation of phospho-MEK 1/2 in the nucleus by ethanol. MEK 1/2 inhibitor, U-0126 inhibited Ang II response or its potentiation by ethanol. These results suggest that Ang II mediated accumulation of phospho-p42/44 MAPK in the hepatocyte nucleus involves MEK 1/2 dependent activation and this effect is potentiated by ethanol. PMID:19560630

Fourier spectroscopy of the 12C2, 13C2, and 12C13C (0-0) swan bands

International Nuclear Information System (INIS)

Amiot, C.

1983-01-01

The (0-0) band of the C 2 Swan electronic system d 3 Pi/sub g/→a 3 Pi/sub u/ has been recorded by Fourier spectroscopy. The three isotopes species 12 C 2 , 13 C 2 , and 12 C 13 C were investigated. The observed wavenumbers were reduced to molecular parameters using a nonlinear least-square fitting procedure. Well-known perturbations at N' = 47 and N' = 51 again observed in the e 12 C 2 d 3 Pi/sub g/ (v = 0) level. Perturbations of the same kind are present in the 13 C 2 spectrum at N' = 34 and N' = 44,48,52. The 12 C 13 C spectrum exhibits in the observed spectral range a unique perturbation for N' = 41

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

Science.gov (United States)

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

2008-10-01

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

Twelve single nucleotide polymorphisms on chromosome 19q13.2-13.3

DEFF Research Database (Denmark)

Yin, Jiaoyang; Vogel, Ulla; Gerdes, Lars Ulrik

2003-01-01

The genetic susceptibility to basal cell carcinoma (BCC) among Danish psoriatic patients was investigated in association studies with 12 single nucleotide polymorphisms on chromosome 19q13.2-3. The results show a significant association between BCC and the A-allele of a polymorphism in ERCCI exon4...

The internal and external responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in patients with prostate cancer.

Science.gov (United States)

Choi, Edmond P H; Wong, Carlos K H; Wan, Eric Y F; Tsu, James H L; Chin, W Y; Kung, Kenny; Yiu, M K

2016-09-01

To examine the responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in prostate cancer patients because there is a lack of evidence to support their responsiveness in this patient population. One hundred sixty-eight subjects with prostate cancer were surveyed at baseline and at 6 months using the SF-12 v2 and FACT-P version 4. Internal responsiveness was assessed using paired t test and generalized estimating equation. External responsiveness was evaluated using receiver operating characteristic curve analysis. The internal responsiveness of the FACT-P and SF-12 v2 to detect positive change was satisfactory. The FACT-P and SF-12 v2 could not detect negative change. The FACT-P and the SF-12 v2 performed the best in distinguishing between improved general health and worsened general health. The FACT-P performed better in distinguishing between unchanged general health and worsened general health. The SF-12 v2 performed better in distinguishing between unchanged general health and improved general health. Positive change detected by these measures should be interpreted with caution as they might be too responsive to detect "noise," which is not clinically significant. The ability of the FACT-P and the SF-12 v2 to detect negative change was disappointing. The internal and external responsiveness of the social well-being of the FACT-P cannot be supported, suggesting that it is not suitable to longitudinally monitor the social component of HRQOL in prostate cancer patients. The study suggested that generic and disease-specific measures should be used together to complement each other.

p75NTR enhances PC12 cell tumor growth by a non-receptor mechanism involving downregulation of cyclin D2

International Nuclear Information System (INIS)

Fritz, Melinda D.; Mirnics, Zeljka K.; Nylander, Karen D.; Schor, Nina F.

2006-01-01

p75NTR is a member of the tumor necrosis superfamily of proteins which is variably associated with induction of apoptosis and proliferation. Cyclin D2 is one of the mediators of cellular progression through G1 phase of the cell cycle. The present study demonstrates the inverse relationship between expression of cyclin D2 and expression of p75NTR in PC12 cells. Induction of p75NTR expression in p75NTR-negative PC12 cells results in downregulation of cyclin D2; suppression of p75NTR expression with siRNA in native PC12 cells results in upregulation of cyclin D2. The effects of p75NTR on cyclin D2 expression are mimicked in p75NTR-negative cells by transfection with the intracellular domain of p75NTR. Cyclin-D2-positive PC12 cell cultures grow more slowly than cyclin-D2-negative cultures, and induction of expression of cyclin D2 slows the culture growth rate of cyclin-D2-negative cells. Finally, subcutaneous murine xenografts of cyclin-D2-negative, p75NTR-positive PC12 cells more frequently and more rapidly produce tumors than the analogous xenografts of cyclin-D2-positive, p75NTR-negative cells. These results suggest that p75NTR suppresses cyclin D2 expression in PC12 cells by a mechanism distinct from its function as a nerve growth factor receptor and that cyclin D2 expression decreases cell culture and xenografted tumor growth

Incidence and Clinical Features of Early Stent Thrombosis in the Era of New P2y12 Inhibitors (PLATIS-2.

Directory of Open Access Journals (Sweden)

Elad Asher

Full Text Available Early stent thrombosis (EST (≤ 30 days after stent implantation is a relatively rare but deleterious complication of percutaneous coronary intervention (PCI. Administration of newer P2Y12 inhibitors (prasugrel and ticagrelor combined with aspirin has been shown to reduce the incidence of sub-acute and late stent thrombosis, compared with clopidogrel. We investigated the "real life" incidence of EST in patients from a large acute coronary syndrome (ACS national registry, where newer P2Y12 inhibitors are widely used. Patients were derived from the ACS Israeli Survey (ACSIS, conducted during 2006, 2008, 2010 and 2013. Major adverse cardiac events (MACE at 30days were defined as all-cause death, recurrent ACS, EST and stroke.Of the 4717 ACS patients who underwent PCI and stenting, 83% received clopidogrel and 17% newer P2Y12 inhibitors. The rate of EST was similar in both groups (1.7% in the newer P2Y12 inhibitor group vs. 1.4% in the clopidogrel-treated patients, p = 0.42. Results were consistent after multivariate analysis (adjusted HR = 1.06 [p = 0.89]. MACE occurred in 6.4% in the newer P2Y12 inhibitor group compared with 9.2% in the clopidogrel group (P<0.01. However, multivariate logistic regression modeling showed that treatment with newer P2Y12 inhibitors was not significantly associated with the secondary endpoint of MACE when compared with clopidogrel therapy [OR = 1.26 95%CI (0.93-1.73, P = 0.136]. The incidence of "real life" EST at 1month is relatively low, and appears to be similar in patients who receive newer P2Y12 inhibitors as well as in those who receive clopidogrel.

Incidence and Clinical Features of Early Stent Thrombosis in the Era of New P2y12 Inhibitors (PLATIS-2)

Science.gov (United States)

Asher, Elad; Abu-Much, Arsalan; Goldenberg, Ilan; Segev, Amit; Sabbag, Avi; Mazin, Israel; Shlezinger, Meital; Atar, Shaul; Zahger, Doron; Polak, Arthur; Beigel, Roy; Matetzky, Shlomi

2016-01-01

Early stent thrombosis (EST) (≤ 30 days after stent implantation) is a relatively rare but deleterious complication of percutaneous coronary intervention (PCI). Administration of newer P2Y12 inhibitors (prasugrel and ticagrelor) combined with aspirin has been shown to reduce the incidence of sub-acute and late stent thrombosis, compared with clopidogrel. We investigated the “real life” incidence of EST in patients from a large acute coronary syndrome (ACS) national registry, where newer P2Y12 inhibitors are widely used. Patients were derived from the ACS Israeli Survey (ACSIS), conducted during 2006, 2008, 2010 and 2013. Major adverse cardiac events (MACE) at 30days were defined as all-cause death, recurrent ACS, EST and stroke.Of the 4717 ACS patients who underwent PCI and stenting, 83% received clopidogrel and 17% newer P2Y12 inhibitors. The rate of EST was similar in both groups (1.7% in the newer P2Y12 inhibitor group vs. 1.4% in the clopidogrel-treated patients, p = 0.42). Results were consistent after multivariate analysis (adjusted HR = 1.06 [p = 0.89]). MACE occurred in 6.4% in the newer P2Y12 inhibitor group compared with 9.2% in the clopidogrel group (P<0.01). However, multivariate logistic regression modeling showed that treatment with newer P2Y12 inhibitors was not significantly associated with the secondary endpoint of MACE when compared with clopidogrel therapy [OR = 1.26 95%CI (0.93–1.73), P = 0.136]. The incidence of "real life" EST at 1month is relatively low, and appears to be similar in patients who receive newer P2Y12 inhibitors as well as in those who receive clopidogrel. PMID:27310147

Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

Science.gov (United States)

Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

2018-01-01

Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is

Preparation and characterization of a supported system of Ni2P/Ni12P5 nanoparticles and their use as the active phase in chemoselective hydrogenation of acetophenone

Science.gov (United States)

Costa, Dolly C.; Soldati, Analía L.; Pecchi, Gina; Bengoa, José Fernando; Marchetti, Sergio Gustavo; Vetere, Virginia

2018-05-01

Ni2P/Ni12P5 nanoparticles were obtained by thermal decomposition of nickel organometallic salt at low temperature. The use of different characterization techniques allowed us to determine that this process produced a mixture of two nickel phosphide phases: Ni2P and Ni12P5. These nickel phosphides nanoparticles, supported on mesoporous silica, showed activity and high selectivity for producing the hydrogenation of the acetophenone carbonyl group to obtain 1-phenylethanol. This is a first report that demonstrates the ability of supported Ni2P/Ni12P5 nanoparticles to produce the chemoselective hydrogenation of acetophenone. We attribute these special catalytic properties to the particular geometry of the Ni–P sites on the surface of the nanoparticles. This is an interesting result because the nickel phosphides have a wide composition range (from Ni3P to NiP3), with different crystallographic structures, therefore we think that different phases could be active and selective to hydrogenate many important molecules with more than one functional group.

Conformational changes of the N-terminal part of Mason-Pfizer monkey virus p12 protein during multimerization

International Nuclear Information System (INIS)

Knejzlik, Zdenek; Ulbrich, Pavel; Strohalm, Martin; Lastuvkova, Hana; Kodicek, Milan; Sakalian, Michael; Ruml, Tomas

2009-01-01

The Mason-Pfizer monkey virus is a prototype Betaretrovirus with the defining characteristic that it assembles spherical immature particles from Gag-related polyprotein precursors within the cytoplasm of the infected cell. It was shown previously that the N-terminal part of the Gag p12 domain (wt-Np12) is required for efficient assembly. However, the precise role for p12 in mediating Gag-Gag interaction is still poorly understood. In this study we employed detailed circular dichroism spectroscopy, electron microscopy and ultracentrifugation analyses of recombinant wt-Np12 prepared by in vitro transcription and translation. The wt-Np12 domain fragment forms fibrillar structures in a concentration-dependent manner. Assembly into fibers is linked to a conformational transition from unfolded or another non-periodical state to α-helix during multimerization.

Pericentric Inversion of Chromosome 9 in an Infant With Ambiguous Genitalia.

Science.gov (United States)

Sotoudeh, Arya; Rostami, Parastoo; Nakhaeimoghadam, Maryam; Mohsenipour, Reihaneh; Rezaei, Nima

2017-10-01

Pericentric inversion of Chromosome 9 is one of the most common chromosomal abnormalities, which could be associated with various manifestations in some cases. Herein, a patient is presented with ambiguous genitalia that karyotyping revealed pericentric inversion of Chromosome 9 (p12,q13). Pericentric inversion of Chromosome 9 could be considered in the list of differential diagnosis of those with ambiguous genitalia, while chromosomal karyotype and culture could be recommended in children with ambiguous genitalia.

Heavy particle excitation of the 2s22p52P3/2-2s22p52P1/2 transition in fluorine-like Fe XVIII and Ni XX

International Nuclear Information System (INIS)

Keenan, F.P.; Reid, R.H.G.

1989-01-01

Cross sections and rate coefficients for excitation of the 2s 2 2p 52 P 3/2 -2s 2 2p 52 P 1/2 transition in fluorine-like Fe XVIII and Ni XX by proton (p), deuteron (d), triton (t) and α-particle (α) impact have been calculated using the close-coupled impact parameter method. At temperatures close to or below those of maximum Fe XVIII and Ni XX fractional abundance in ionisation equilibrium, the p,d and t rates are found to be comparable and are much greater than the rates due to α collisions. However, at high temperatures the situation is reversed, with the α rates being about a factor of two larger than those due to the other particles. The effects of adopting the present atomic data in calculations of the electron density or ion temperature sensitive emission line ratios are briefly discussed. (author)

12 CFR 583.13 - Office.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Office. 583.13 Section 583.13 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING SAVINGS AND LOAN HOLDING COMPANIES § 583.13 Office. The term Office means the Office of Thrift Supervision. ...

DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed.

Science.gov (United States)

Hitchins, Megan P; Bentley, Louise; Monk, David; Beechey, Colin; Peters, Jo; Kelsey, Gavin; Ishino, Fumitoshi; Preece, Michael A; Stanier, Philip; Moore, Gudrun E

2002-12-01

Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified within this region to date. GRB10 demonstrates an intricate tissue- and isoform-specific imprinting profile in humans, with paternal expression in fetal brain and maternal expression of one isoform in skeletal muscle. The mouse homolog is maternally transcribed. The GRB10 protein is a potent growth inhibitor and represents a candidate for SRS, which is characterized by pre- and postnatal growth retardation and a spectrum of additional dysmorphic features. Since imprinted genes tend to be grouped in clusters, we investigated the imprinting status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were found to replicate asynchronously, suggestive of imprinting, SNP expression analyses showed that neither gene was imprinted in multiple human fetal tissues. The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region. With the intent of using mouse Grb10 as an imprinted control, biallelic expression was consistently observed in fetal, postnatal, and adult brain of these mice, in contrast to the maternal-specific transcription previously demonstrated in brain in inter-specific F1 progeny. This may be a further example of over-expression of maternally derived transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted gene identified within 7p11.2-p13.

Crystallization and preliminary X-ray analysis of human S100A13

Energy Technology Data Exchange (ETDEWEB)

Imai, Fabiana Lica [Department of Chemistry, Faculty of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522 (Japan); Nagata, Koji [Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Yonezawa, Naoto [Department of Chemistry, Faculty of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522 (Japan); Yu, Jinyan; Ito, Eriko; Kanai, Saeko [Graduate School of Science and Technology, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522 (Japan); Tanokura, Masaru [Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan); Nakano, Minoru, E-mail: mnakano@faculty.chiba-u.jp [Department of Chemistry, Faculty of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522 (Japan)

2006-11-01

Human S100A13 protein was cloned, expressed, purified and crystallized by the hanging-drop vapour-diffusion method. The crystals obtained belonged to space group P2{sub 1}2{sub 1}2{sub 1} and diffracted to a resolution of 1.8 Å. S100A13 is a member of the S100 family of EF-hand-containing calcium-binding proteins and plays an important role in the secretion of fibroblast growth factor-1 and interleukin 1α, two pro-angiogenic factors released by the endoplasmic reticulum/Golgi-independent non-classical secretory pathway. Human S100A13 was heterologously expressed in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using PEG 3350 as the precipitant. The crystals diffracted X-rays from a synchrotron-radiation source to 1.8 Å resolution and the space group was assigned as primitive orthorhombic P2{sub 1}2{sub 1}2{sub 1}.

Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?

Science.gov (United States)

Karmous-Benailly, Houda; Tabet, Anne-Claude; Thaly, Adeline; Dupuy, Olivier; Huten, Yolène; Luton, Dominique; Baumann, Clarisse; Delezoide, Anne-Lise

2005-03-01

Trisomy of the short arm of chromosome 4 is a well-known syndrome, and several observations have been made in the last 30 years. Herein, we report a new observation of trisomy 4p in a fetus with a semi-lobar holoprosencephaly (HPE), dysmorphic features and multiple malformations. The diagnosis of HPE was made, at 33 weeks' gestation, on the fetus of a healthy G1P0 woman. Amniocentesis was performed for chromosome analysis and additional material was found on a chromosome 22. The couple elected to terminate the pregnancy and fetal examination was realized. Conventional and molecular cytogenetic studies were performed on the fetus and the parents, which showed that the additional material found on one chromosome 22 corresponded to the short arm of chromosome 4 and therefore led us to establish a diagnosis of trisomy 4p inherited from the malsegregation of a paternal translocation t(4;22)(q12;q11.1). The etiology of HPE is very heterogeneous; it includes non-genetic factors such as maternal diabetes and genetic causes. HPE cases have been described in association with many chromosomal anomalies, trisomy 13 being the most frequent. However, to our knowledge, HPE has never been previously reported in association with a trisomy involving solely the short arm of chromosome 4. Copyright 2005 John Wiley & Sons, Ltd.

12 CFR 404.13 - Definitions.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Definitions. 404.13 Section 404.13 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Access to Records Under the Privacy Act of 1974 § 404.13 Definitions. For purposes of this subpart, the following definitions shall apply...

Redox induces diverse effects on recombinant human wild-type PrP and mutated PrP with inserted or deleted octarepeats.

Science.gov (United States)

Shi, Qi; Chen, Cao; Zhang, Bao-Yun; Zhou, Wei; Xiao, Kang; Dong, Xiao-Ping

2018-04-01

Normal prion protein (PrP) contains two cysteines at amino acids 179 and 214, which may form intra‑ and interpeptide disulfide bonds. To determine the possible effects of this disulfide bridge on the biochemical features of PrP, prokaryotic recombinant human wild‑type PrP (PG5), and mutated PrPs with seven extra octarepeats (PG12) or with all five octarepeats removed (PG0), were subjected to redox in vitro. Sedimentation assays revealed a large portion of aggregation in redox‑treated PG5, but not in PG0 and PG12. Circular dichroism analysis detected increased β‑sheet and decreased α‑helix in PG5 subjected to redox, increased random‑coil and decreased β‑sheet in PG0, and increased random‑coil, but limited changes to β‑sheet content, in PG12. Thioflavin T fluorescence tests indicated that fluorescent value was increased in PG5 subjected to redox. In addition, proteinase K (PK) digestions indicated that PK resistance was stronger in PG12 and PG0 compared with in PG5; redox enhanced the PK resistance of all three PrP constructs, particularly PG0 and PG12. These data indicated that formation of a disulfide bond induces marked alterations in the secondary structure and biochemical characteristics of PrP. In addition, the octarepeat region within the PrP peptide markedly influences the effects of redox on the biochemical phenotypes of PrP, thus highlighting the importance of the number of octarepeats in the biological functions of PrP.

46 CFR 12.15-13 - Deck engine mechanic.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Deck engine mechanic. 12.15-13 Section 12.15-13 Shipping... ENDORSEMENTS Qualified Member of the Engine Department § 12.15-13 Deck engine mechanic. (a) An applicant for an endorsement as deck engine mechanic shall be a person holding an MMC or MMD endorsed as junior engineer. The...

Non-disjunction of chromosome 13

DEFF Research Database (Denmark)

Bugge, Merete; Collins, Andrew; Hertz, Jens Michael

2007-01-01

We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII...... recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms...... that determine non-disjunction of human chromosomes, consistent with the diversity of findings for other trisomies. Udgivelsesdato: 2007-Aug-15...

Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells

International Nuclear Information System (INIS)

Moore, Stephen R.; Papworth, David; Grosovsky, Andrew J.

2006-01-01

Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression. We report here the karyotypic examination of 296 instability-associated chromosomal rearrangement breaksites (IACRB) from 118 unstable TK6 human B lymphoblast, and isogenic derivative, clones. When we tested whether IACRB were distributed across the chromosomes based on target size, a significant non-random distribution was evident (p < 0.00001), and three IACRB hotspots (chromosomes 11, 12, and 22) and one IACRB coldspot (chromosome 2) were identified. Statistical analysis at the chromosomal band-level identified four IACRB hotspots accounting for 20% of all instability-associated breaks, two of which account for over 14% of all IACRB. Further, analysis of independent clones provided evidence within 14 individual clones of IACRB clustering at the chromosomal band level, suggesting a predisposition for further breaks after an initial break at some chromosomal bands. All of these events, independently, or when taken together, were highly unlikely to have occurred by chance (p < 0.000001). These IACRB band-level cluster hotspots were observed independent of radiation quality, dose, or cellular p53 status. The non-random distribution of instability-associated chromosomal rearrangements described here significantly differs from the distribution that was observed in a first-division post-irradiation metaphase analysis (p = 0.0004). Taken together, these results suggest that genomic instability may be in part driven by chromosomal cis mechanisms

P2Y2 Receptor and EGFR Cooperate to Promote Prostate Cancer Cell Invasion via ERK1/2 Pathway.

Science.gov (United States)

Li, Wei-Hua; Qiu, Ying; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

2015-01-01

As one member of G protein-coupled P2Y receptors, P2Y2 receptor can be equally activated by extracellular ATP and UTP. Our previous studies have proved that activation of P2Y2 receptor by extracellular ATP could promote prostate cancer cell invasion and metastasis in vitro and in vivo via regulating the expressions of some epithelial-mesenchymal transition/invasion-related genes (including IL-8, E-cadherin, Snail and Claudin-1), and the most significant change in expression of IL-8 was observed after P2Y2 receptor activation. However, the signaling pathway downstream of P2Y2 receptor and the role of IL-8 in P2Y2-mediated prostate cancer cell invasion remain unclear. Here, we found that extracellular ATP/UTP induced activation of EGFR and ERK1/2. After knockdown of P2Y2 receptor, the ATP -stimulated phosphorylation of EGFR and ERK1/2 was significantly suppressed. Further experiments showed that inactivation of EGFR and ERK1/2 attenuated ATP-induced invasion and migration, and suppressed ATP-mediated IL-8 production. In addition, knockdown of IL-8 inhibited ATP-mediated invasion and migration of prostate cancer cells. These findings suggest that P2Y2 receptor and EGFR cooperate to upregulate IL-8 production via ERK1/2 pathway, thereby promoting prostate cancer cell invasion and migration. Thus blocking of the P2Y2-EGFR-ERK1/2 pathway may provide effective therapeutic interventions for prostate cancer.

Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

Directory of Open Access Journals (Sweden)

Payne CM

2011-05-01

Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

Recurring DNA copy number gain at chromosome 9p13 plays a role in the activation of multiple candidate oncogenes in progressing oral premalignant lesions

International Nuclear Information System (INIS)

Towle, Rebecca; Tsui, Ivy F L; Zhu, Yuqi; MacLellan, Sara; Poh, Catherine F; Garnis, Cathie

2014-01-01

Genomic alteration at chromosome 9p has been previously reported as a frequent and critical event in oral premalignancy. While this alteration is typically reported as a loss driven by selection for CDKN2A deactivation (at 9p21.3), we detect a recurrent DNA copy number gain of ∼2.49 Mbp at chromosome 9p13 in oral premalignant lesions (OPLs) that later progressed to invasive lesions. This recurrent alteration event has been validated using fluorescence in situ hybridization in an independent set of OPLs. Analysis of publicly available gene expression datasets aided in identifying three oncogene candidates that may have driven selection for DNA copy number increases in this region (VCP, DCTN3, and STOML2). We performed in vitro silencing and activation experiments for each of these genes in oral cancer cell lines and found that each gene is independently capable of upregulating proliferation and anchorage-independent growth. We next analyzed the activity of each of these genes in biopsies of varying histological grades that were obtained from a diseased oral tissue field in a single patient, finding further molecular evidence of parallel activation of VCP, DCTN3, and STOML2 during progression from normal healthy tissue to invasive oral carcinoma. Our results support the conclusion that DNA gain at 9p13 is important to the earliest stages of oral tumorigenesis and that this alteration event likely contributes to the activation of multiple oncogene candidates capable of governing oral cancer phenotypes

Comparative mapping of DNA probes derived from the V{sub k} immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization

Energy Technology Data Exchange (ETDEWEB)

Arnold, N.; Wienberg, J.; Ermert, K. [Universitaet Muenchen (Germany)] [and others

1995-03-01

Fluorescence in situ hybridization (FISH) of cosmid clones of human V{sub K} gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the K locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo Pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen-q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V{sub K}I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V{sub K} region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution. 18 refs., 2 figs.

Identification of two distinct chromosome 12-derived amplification units in neuroblastoma cell line NGP

NARCIS (Netherlands)

van Roy, N.; Forus, A.; Myklebost, O.; Cheng, N. C.; Versteeg, R.; Speleman, F.

1995-01-01

The neuroblastoma cell line NGP contains two homogeneously staining regions (hsr). One of these hsrs contains MYCN sequences. Reverse painting experiments demonstrated that the second HSR consisted of two chromosome 12-derived amplification units, located at 12q14-15 and 12q24. Southern blot and

Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

Directory of Open Access Journals (Sweden)

Mirjam E Belderbos

Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

Science.gov (United States)

Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

2012-01-01

Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

UVB induces IL-12 transcription in human keratinocytes in vivo and in vitro

International Nuclear Information System (INIS)

Enk, C.D.; Blauvet, A.; Katz, S.I.; Mahanty, S.

1996-01-01

Human epidermal cells produce a wide range of cytokines, including those characteristic of Th2-like responses such as interleukin (IL)-4 and IL-10. As well, keratinocytes have recently been shown to produce Th1-like cytokines such as IL-12. Exposure to UVB has profound effects on the skin and systemic immune system, which is in part mediated by secretion of tumor necrosis factor (TNF)-α by epidermal cells. Because IL-12 induces production of TNF-α by certain cells of the immune system, we sought to determine whether UVB is an inducer of IL-12 gene expression in epidermal cells. Human epidermal cells were exposed to UVB radiation in vivo, isolated by suction blister technique and trypsinization and transcription of the IL-12 p35 and p40 chains was examined by RT-PCR. (Author)

Excitation functions of the systems 12C+14C and 13C+12C

International Nuclear Information System (INIS)

Haindl, E.

1975-01-01

The excitation functions of the systems 12 C+ 14 C and 13 C+ 12 C are investigated for different exit channels. The excitation functions measured do not show correlated structures as in the system 12 C+ 12 C. (WL/AK) [de

Partial Trisomy 16p (16p12.2→pter and Partial Monosomy 22q (22q13.31 →qter Presenting With Fetal Ascites and Ventriculomegaly: Prenatal Diagnosis and Array Comparative Genomic Hybridization Characterization

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2010-12-01

Conclusion: Partial trisomy 16p can be associated with fetal ascites and ventriculomegaly in the second trimester. Prenatal sonographic detection of fetal ascites in association with ventriculomegaly should alert chromosomal abnormalities and prompt cytogenetic investigation, which may lead to the identification of an unexpected parental translocation involving chromosomal segments associated with cerebral and vascular abnormalities.

12/15 lipoxygenase regulation of colorectal tumorigenesis is determined by the relative tumor levels of its metabolite 12-HETE and 13-HODE in animal models

OpenAIRE

Chang, Jian; Jiang, Li; Wang, Yinqiu; Yao, Bing; Yang, Shilin; Zhang, Bixiang; Zhang, Ming-Zhi

2014-01-01

Colorectal cancer (CRC) continues to be a major cause of morbidity and mortality. The arachidonic acid (AA) pathway and linoleic acid (LA) pathway have been implicated as important contributors to CRC development and growth. Human 15-lipoxygenase 1 (15-LOX-1) converts LA to anti-tumor 13-S-hydroxyoctadecadienoic acid (13-HODE)and 15-LOX-2 converts AA to 15-hydroxyeicosatetraenoic acid (15-HETE). In addition, human 12-LOX metabolizes AA to pro-tumor 12-HETE. In rodents, the function of 12-LOX ...

Sp1/3 and NF-1 mediate basal transcription of the human P2X1 gene in megakaryoblastic MEG-01 cells

Directory of Open Access Journals (Sweden)

Ennion Steven J

2006-03-01

Full Text Available Abstract Background P2X1 receptors play an important role in platelet function as they can induce shape change, granule centralization and are also involved in thrombus formation. As platelets have no nuclei, the level of P2X1 expression depends on transcriptional regulation in megakaryocytes, the platelet precursor cell. Since nothing is known about the molecular mechanisms regulating megakaryocytic P2X1 expression, this study aimed to identify and functionally characterize the P2X1 core promoter utilized in the human megakaryoblastic cell line MEG-01. Results In order to identify cis-acting elements involved in the transcriptional regulation of P2X1 expression, the ability of 4.7 kb P2X1 upstream sequence to drive luciferase reporter gene expression was tested. Low promoter activity was detected in proliferating MEG-01 cells. This activity increased 20-fold after phorbol-12-myristate-13-acetate (PMA induced differentiation. A transcription start site was detected 365 bp upstream of the start codon by primer extension. Deletion analysis of reporter constructs indicated a core promoter located within the region -68 to +149 bp that contained two Sp1 sites (named Sp1a and Sp1b and an NF-1 site. Individual mutations of Sp1b or NF-1 binding sites severely reduced promoter activity whereas triple mutation of Sp1a, Sp1b and NF-1 sites completely abolished promoter activity in both untreated and PMA treated cells. Sp1/3 and NF-1 proteins were shown to bind their respective sites by EMSA and interaction of Sp1/3, NF-1 and TFIIB with the endogenous P2X1 core promoter in MEG-01 cells was demonstrated by chromatin immunoprecipitation. Alignment of P2X1 genes from human, chimp, rat, mouse and dog revealed consensus Sp1a, Sp1b and NF-1 binding sites in equivalent positions thereby demonstrating evolutionary conservation of these functionally important sites. Conclusion This study has identified and characterized the P2X1 promoter utilized in MEG-01 cells and

The P2Y12 Receptor Antagonist Ticagrelor Reduces Lysosomal pH and Autofluorescence in Retinal Pigmented Epithelial Cells From the ABCA4-/- Mouse Model of Retinal Degeneration

Directory of Open Access Journals (Sweden)

Wennan Lu

2018-04-01

Full Text Available The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4-/- mouse model of Stargardt’s disease, an early onset retinal degeneration. Lowering lysosomal pH through cAMP-dependent pathways decreases accumulation of autofluorescent material in RPE cells in vitro, but identification of an appropriate receptor is crucial for manipulating this pathway in vivo. As the P2Y12 receptor for ADP is coupled to the inhibitory Gi protein, we asked whether blocking the P2Y12 receptor with ticagrelor could restore lysosomal acidity and reduce autofluorescence in compromised RPE cells from ABCA4-/- mice. Oral delivery of ticagrelor giving rise to clinically relevant exposure lowered lysosomal pH in these RPE cells. Ticagrelor also partially reduced autofluorescence in the RPE cells of ABCA4-/- mice. In vitro studies in ARPE-19 cells using more specific antagonists AR-C69931 and AR-C66096 confirmed the importance of the P2Y12 receptor for lowering lysosomal pH and reducing autofluorescence. These observations identify P2Y12 receptor blockade as a potential target to lower lysosomal pH and clear lysosomal waste in RPE cells.

A first-principles study on the adsorption behavior of amphetamine on pristine, P- and Al-doped B12N12 nano-cages

Science.gov (United States)

Bahrami, Aidin; Seidi, Shahram; Baheri, Tahmineh; Aghamohammadi, Mohammad

2013-12-01

The first-principles computations using density functional theory (DFT) calculations at the M062X/6-311++G** level have been applied to scrutinize the adsorption behavior of amphetamine (AMP) molecule on the external surface of pristine, P- and Al-doped B12N12 nano-cages. In order to gain insight into the binding features of pristine and doped B12N12 complexes as adsorbent with AMP, the structural and electronic parameters as well as the Atoms in Molecules (AIM) properties were examined. The results showed that AMP prefers to adsorb via its nitrogen atom on the Lewis acid sites of B and Al atoms of the nano-cages. On the basis of calculated density of states, the interaction of AMP with the external wall of B12N12 leads to the remarkable differences in their conductivities. Presence of polar solvent increases the AMP adsorption on the nano-cage. In addition, AIM based analyses indicated an electrostatic nature for N-B interaction in Amph-B12N12 and partial covalent for N-Al in AMP-B11AlN12. Based on calculated results, the B12N12 and B11AlN12 nano-cages are expected to be a potential efficient adsorbent as well as sensors for adsorption of AMP in environmental systems.

Common variation at 10p12.31 near MLLT10 influences meningioma risk

DEFF Research Database (Denmark)

Dobbins, Sara E; Broderick, Peter; Melin, Beatrice

2011-01-01

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12....

Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the dic(9;20)(p11-13;q11) show recurrent involvement of genes at 20q11.21.

Science.gov (United States)

An, Qian; Wright, Sarah L; Moorman, Anthony V; Parker, Helen; Griffiths, Mike; Ross, Fiona M; Davies, Teresa; Harrison, Christine J; Strefford, Jon C

2009-08-01

The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia. Although it results in loss of material from 9p and 20q, the molecular targets on both chromosomes have not been fully elucidated. From an initial cohort of 58 with acute lymphoblastic leukemia patients with this translocation, breakpoint mapping with fluorescence in situ hybridization on 26 of them revealed breakpoint heterogeneity of both chromosomes. PAX5 has been proposed to be the target gene on 9p, while for 20q, FISH analysis implicated the involvement of the ASXL1 gene, either by a breakpoint within (n=4) or centromeric (deletion, n=12) of the gene. Molecular copy-number counting, long-distance inverse PCR and direct sequence analysis identified six dic(9;20) breakpoint sequences. In addition to the three previously reported: PAX5-ASXL1, PAX5-C20ORF112 and PAX5-KIF3B; we identified three new ones in this study: sequences 3' of PAX5 disrupting ASXL1, and ZCCHC7 disrupted by sequences 3' of FRG1B and LOC1499503. This study provides insight into the breakpoint complexity underlying dicentric chromosomal formation in acute lymphoblastic leukemia and highlights putative target gene loci.

Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70

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Bigalke Iris

2007-04-01

Full Text Available Abstract Background For optimal T cell activation it is desirable that dendritic cells (DCs display peptides within MHC molecules as signal 1, costimulatory molecules as signal 2 and, in addition, produce IL-12p70 as signal 3. IL-12p70 polarizes T cell responses towards CD4+ T helper 1 cells, which then support the development of CD8+ cytotoxic T lymphocytes. We therefore developed new maturation cocktails allowing DCs to produce biologically active IL-12p70 for large-scale cancer vaccine development. Methods After elutriation of leukapheresis products in a closed bag system, enriched monocytes were cultured with GM-CSF and IL-4 for six days to generate immature DCs that were then matured with cocktails, containing cytokines, interferon-gamma, prostaglandin E2, and a ligand for Toll-like receptor 8, with or without poly (I:C. Results Mature DCs expressed appropriate maturation markers and the lymph node homing chemokine receptor, CCR7. They retained full maturity after culture for two days without maturation cocktails and following cryopreservation. TLR ligand stimulation induced DCs capable of secreting IL-12p70 in primary cultures and after one day of coculture with CD40L-expressing fibroblasts, mimicking an encounter with T cells. DCs matured with our new cocktails containing TLR8 ligand, with or without poly (I:C, induced alloresponses and stimulated virus-specific T cells after peptide-pulsing. DCs matured in cocktails containing TLR8 ligand without poly (I:C could also be loaded with RNA as a source of antigen, whereas DCs matured in cocktails containing poly (I:C were unable to express proteins following RNA transfer by electroporation. Conclusion Our new maturation cocktails allowed easy DC harvesting, stable maturation and substantial recoveries of mature DCs after cryopreservation. Our procedure for generating DCs is easily adaptable for GMP-compliance and yields IL-12p70-secreting DCs suitable for development of cancer vaccines using