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Sample records for 3a 3b 4a

  1. 75 FR 910 - Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ...-42-AD; Amendment 39-16144; AD 2009-26-09] RIN 2120-AA64 Airworthiness Directives; General Electric... existing airworthiness directive (AD) for General Electric Company (GE) CF34-1A, -3A, -3A1, -3A2, -3B, and... General Electric Company via Lockheed Martin Technology Services, 10525 Chester Road, Suite C,...

  2. Updating P300: An Integrative Theory of P3a and P3b

    PubMed Central

    Polich, John

    2009-01-01

    The empirical and theoretical development of the P300 event-related brain potential (ERP) is reviewed by considering factors that contribute to its amplitude, latency, and general characteristics. The neuropsychological origins of the P3a and P3b subcomponents are detailed, and how target/standard discrimination difficulty modulates scalp topography is discussed. The neural loci of P3a and P3b generation are outlined, and a cognitive model is proffered: P3a originates from stimulus-driven frontal attention mechanisms during task processing, whereas P3b originates from temporal-parietal activity associated with attention and appears related to subsequent memory processing. Neurotransmitter actions associating P3a to frontal/dopaminergic and P3b to parietal/norepinephrine pathways are highlighted. Neuroinhibition is suggested as an overarching theoretical mechanism for P300, which is elicited when stimulus detection engages memory operations. PMID:17573239

  3. Facility 3B, interior detail of selfclosing door into Facility 3A, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Facility 3B, interior detail of self-closing door into Facility 3A, wood support columns at east end of room, view facing north-northeast - U.S. Naval Base, Pearl Harbor, Instrument Shop & Electrical Shop Lean-to, Avenue E, between Sixth & Seventh Streets, Pearl City, Honolulu County, HI

  4. Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations

    PubMed Central

    Vanderver, Adeline; van Spaendonk, Rosalina M.L.; Schiffmann, Raphael; Brais, Bernard; Bugiani, Marianna; Sistermans, Erik; Catsman-Berrevoets, Coriene; Kros, Johan M.; Pinto, Pedro Soares; Pohl, Daniela; Tirupathi, Sandya; Strømme, Petter; de Grauw, Ton; Fribourg, Sébastien; Demos, Michelle; Pizzino, Amy; Naidu, Sakkubai; Guerrero, Kether; van der Knaap, Marjo S.; Bernard, Geneviève

    2014-01-01

    Objective: To study the clinical and radiologic spectrum and genotype–phenotype correlation of 4H (hypomyelination, hypodontia, hypogonadotropic hypogonadism) leukodystrophy caused by mutations in POLR3A or POLR3B. Methods: We performed a multinational cross-sectional observational study of the clinical, radiologic, and molecular characteristics of 105 mutation-proven cases. Results: The majority of patients presented before 6 years with gross motor delay or regression. Ten percent had an onset beyond 10 years. The disease course was milder in patients with POLR3B than in patients with POLR3A mutations. Other than the typical neurologic, dental, and endocrine features, myopia was seen in almost all and short stature in 50%. Dental and hormonal findings were not invariably present. Mutations in POLR3A and POLR3B were distributed throughout the genes. Except for French Canadian patients, patients from European backgrounds were more likely to have POLR3B mutations than other populations. Most patients carried the common c.1568T>A POLR3B mutation on one allele, homozygosity for which causes a mild phenotype. Systematic MRI review revealed that the combination of hypomyelination with relative T2 hypointensity of the ventrolateral thalamus, optic radiation, globus pallidus, and dentate nucleus, cerebellar atrophy, and thinning of the corpus callosum suggests the diagnosis. Conclusions: 4H is a well-recognizable clinical entity if all features are present. Mutations in POLR3A are associated with a more severe clinical course. MRI characteristics are helpful in addressing the diagnosis, especially if patients lack the cardinal non-neurologic features. PMID:25339210

  5. Neural generators of the auditory evoked potential components P3a and P3b.

    PubMed

    Wronka, Eligiusz; Kaiser, Jan; Coenen, Anton M L

    2012-01-01

    The aim of the present study was to define the scalp topography of the two subcomponents of the P3 component of the auditory evoked potential elicited in a three-stimulus oddball paradigm and to identify their cortical generators using the standardized low resolution electromagnetic tomography (sLORETA). Subjects were presented with a random sequence of auditory stimuli and instructed to respond to an infrequently occurring target stimulus inserted into a sequence of frequent standard and rare non-target stimuli. Results show that the magnitude of the frontal P3a is determined by the relative physical difference among stimuli, as it was larger for the stimulus more deviant from the standard. Major neural generators of the P3a were localized within frontal cortex and anterior cingulate gyrus. In contrast to this, the P3b, showing maximal amplitude at parietal locations, was larger for stimuli demanding a response than for the rare non-target. Major sources of the P3b included the superior parietal lobule and the posterior part of the cingulate gyrus. Our findings are in line with the hypothesis that P3a is related to alerting activity during the initial allocation of attention, while P3b is related to activation of a posterior network when the neuronal model of perceived stimulation is compared with the attentional trace. PMID:22508084

  6. Cross-talk between the NR3B and NR4A families of orphan nuclear receptors

    SciTech Connect

    Lammi, Johanna; Rajalin, Ann-Marie; Huppunen, Johanna; Aarnisalo, Piia . E-mail: piia.aarnisalo@helsinki.fi

    2007-07-27

    Estrogen-related receptors (NR3B family) and Nurr1, NGFI-B, and Nor1 (NR4A family) are orphan nuclear receptors lacking identified natural ligands. The mechanisms regulating their transcriptional activities have remained elusive. We have previously observed that the members of NR3B and NR4A families are coexpressed in certain cell types such as osteoblasts and that the ability of Nurr1 to transactivate the osteopontin promoter is repressed by ERRs. We have now studied the cross-talk between NR3B and NR4A receptors. We show that NR3B and NR4A receptors mutually repress each others' transcriptional activity. The repression involves intact DNA-binding domains and dimerization interfaces but does not result from competition for DNA binding or from heterodimerization. The activation functions of NR3B and NR4A receptors are dispensable for the cross-talk. In conclusion, we report that cross-talk between NR3B and NR4A receptors is a mechanism modulating the transcriptional activities of these orphan nuclear receptors.

  7. Functional Analysis of KIF3A and KIF3B during Spermiogenesis of Chinese Mitten Crab Eriocheir sinensis

    PubMed Central

    Lu, Yang; Wang, Qi; Wang, Da-Hui; Zhou, Hong; Hu, Yan-Jun; Yang, Wan-Xi

    2014-01-01

    Background Spermatogenesis represents the transformation process at the level of cellular development. KIF3A and KIF3B are believed to play some roles in the assembly and maintenance of flagella, intracellular transport of materials including organelles and proteins, and other unknown functions during this process. During spermatogenesis in Eriocheir sinensis, if the sperm shaping machinery is dependent on KIF3A and KIF3B remains unknown. Methodology/Principal Findings The cDNA of KIF3A and KIF3B were obtained by designing degenerate primers, 3′RACE, and 5′RACE. We detected the genetic presence of kif3a and kif3b in the heart, muscle, liver, gill, and testis of E. sinensis through RT-PCR. By western blot analysis, the protein presence of KIF3A and KIF3B in heart, muscle, gill, and testis reflected the content in protein level. Using in situ hybridization and immunofluorescence, we could track the dynamic location of KIF3A and KIF3B during different developmental phases of sperm. KIF3A and KIF3B were found surrounding the nucleus in early spermatids. In intermediate spermatids, these proteins expressed at high levels around the nucleus and extended to the final phase. During the nuclear shaping period, KIF3A and KIF3B reached their maximum in the late spermatids and were located around the nucleus and concentrated in the acrosome to some extent. Conclusions/Significance Our results revealed that KIF3A and KIF3B were involved in the nuclear and cellular morphogenesis at the levels of mRNA and protein. These proteins can potentially facilitate the intracellular transport of organelles, proteins, and other cargoes. The results represent the functions of KIF3A and KIF3B in the spermatogenesis of Crustacea and clarify phylogenetic relationships among the Decapoda. PMID:24870586

  8. Haploinsufficiency of SF3B4, a Component of the Pre-mRNA Spliceosomal Complex, Causes Nager Syndrome

    PubMed Central

    Bernier, Francois P.; Caluseriu, Oana; Ng, Sarah; Schwartzentruber, Jeremy; Buckingham, Kati J.; Innes, A. Micheil; Jabs, Ethylin Wang; Innis, Jeffrey W.; Schuette, Jane L.; Gorski, Jerome L.; Byers, Peter H.; Andelfinger, Gregor; Siu, Victoria; Lauzon, Julie; Fernandez, Bridget A.; McMillin, Margaret; Scott, Richard H.; Racher, Hilary; Majewski, Jacek; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael J.; Parboosingh, Jillian S.

    2012-01-01

    Nager syndrome, first described more than 60 years ago, is the archetype of a class of disorders called the acrofacial dysostoses, which are characterized by craniofacial and limb malformations. Despite intensive efforts, no gene for Nager syndrome has yet been identified. In an international collaboration, FORGE Canada and the National Institutes of Health Centers for Mendelian Genomics used exome sequencing as a discovery tool and found that mutations in SF3B4, a component of the U2 pre-mRNA spliceosomal complex, cause Nager syndrome. After Sanger sequencing of SF3B4 in a validation cohort, 20 of 35 (57%) families affected by Nager syndrome had 1 of 18 different mutations, nearly all of which were frameshifts. These results suggest that most cases of Nager syndrome are caused by haploinsufficiency of SF3B4. Our findings add Nager syndrome to a growing list of disorders caused by mutations in genes that encode major components of the spliceosome and also highlight the synergistic potential of international collaboration when exome sequencing is applied in the search for genes responsible for rare Mendelian phenotypes. PMID:22541558

  9. GSK3A Is Redundant with GSK3B in Modulating Drug Resistance and Chemotherapy-Induced Necroptosis

    PubMed Central

    Grassilli, Emanuela; Ianzano, Leonarda; Bonomo, Sara; Missaglia, Carola; Cerrito, Maria Grazia; Giovannoni, Roberto; Masiero, Laura; Lavitrano, Marialuisa

    2014-01-01

    Glycogen Synthase Kinase-3 alpha (GSK3A) and beta (GSK3B) isoforms are encoded by distinct genes, are 98% identical within their kinase domain and perform similar functions in several settings; however, they are not completely redundant and, depending on the cell type and differentiative status, they also play unique roles. We recently identified a role for GSK3B in drug resistance by demonstrating that its inhibition enables necroptosis in response to chemotherapy in p53-null drug-resistant colon carcinoma cells. We report here that, similarly to GSK3B, also GSK3A silencing/inhibition does not affect cell proliferation or cell cycle but only abolishes growth after treatment with DNA-damaging chemotherapy. In particular, blocking GSK3A impairs DNA repair upon exposure to DNA-damaging drugs. As a consequence, p53-null cells overcome their inability to undergo apoptosis and mount a necroptotic response, characterized by absence of caspase activation and RIP1-independent, PARP-dependent AIF nuclear re-localization. We therefore conclude that GSK3A is redundant with GSK3B in regulating drug-resistance and chemotherapy-induced necroptosis and suggest that inhibition of only one isoform, or rather partial inhibition of overall cellular GSK3 activity, is enough to re-sensitize drug-resistant cells to chemotherapy. PMID:24984063

  10. Bacillus thuringiensis serovar mogi (flagellar serotype 3a3b3d), a novel serogroup with a mosquitocidal activity.

    PubMed

    Roh, Jong Yul; Liu, Qin; Lee, Dae Weon; Tao, Xueying; Wang, Yong; Shim, Hee Jin; Choi, Jae Young; Seo, Jong Bok; Ohba, Michio; Mizuki, Eiichi; Je, Yeon Ho

    2009-11-01

    The flagellated vegetative cells of the Bacillus thuringiensis strain K4 were agglutinated with the H3 reference antiserum and further, agglutinated with 3b and 3d monospecific factor sera but non-reactive for 3c and 3e factor sera. This creates a new serogroup with flagellar antigenic structure of 3a3b3d: B. thuringiensis serovar mogi. The strain K4 showed high activity against dipteran larvae, Anopheles sinensis and Culex pipienspallens while no lepidopteran toxicity. It produced ovoidal parasporal inclusions (crystals) whose SDS-PAGE protein profile consisted of several bands ranging from 75 to 30kDa. Through the protein identification by nano-LC-ESI-IT MS analysis, the putative peptides of Cry19Ba, Cry40ORF2, Cry27Aa and Cry20Aa were detected.

  11. DNA methyltransferase 1, 3a, and 3b expression in hepatitis C associated human hepatocellular carcinoma and their clinicopathological association.

    PubMed

    Siddiqui, Nadir Naveed; Ul Haq, Ahtesham; Siddiqui, Owais Ali; Khan, Rizma

    2016-08-01

    Identification of biomarker will obligate a substantial influence on various cancer management and treatment. We hypothesize that genetic/proteomic and epigenetic studies should be uncovering modifications which may be independently or jointly affect the expression of the genes that are involved in the progression of liver cancer (LC). For this purpose, we examined the effect of expressional changes of DNMTs on HCV infected LC of different genotypes. We found that both mRNA and protein expression levels of DNMT1, 3a, and 3b were upregulated in genotype 1b and 3a HCV infected patients as compared to control. However, DNMT3b mRNA levels did not change in genotypes 2a, 3, and 4, but were upregulated at the protein level by genotype 1b, 2a, and 3a. Furthermore, no significant changes were observed for DNMTs investigated in sample expressing the genotypes 5 and 6. Our findings suggest that HCV at least in part by altering DNMTs expression may play a significant role in HCC progression. PMID:26850594

  12. The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay.

    PubMed

    Shum, Eleen Y; Jones, Samantha H; Shao, Ada; Dumdie, Jennifer; Krause, Matthew D; Chan, Wai-Kin; Lou, Chih-Hong; Espinoza, Josh L; Song, Hye-Won; Phan, Mimi H; Ramaiah, Madhuvanthi; Huang, Lulu; McCarrey, John R; Peterson, Kevin J; De Rooij, Dirk G; Cook-Andersen, Heidi; Wilkinson, Miles F

    2016-04-01

    Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions and can augment or diversify existing functions. Here, we report a gene duplication event that yielded another outcome--the generation of antagonistic functions. One product of this duplication event--UPF3B--is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart--UPF3A--encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches in vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A acquired repressor activity through simple impairment of a critical domain, a rapid mechanism that may have been widely used in evolution. Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events.

  13. Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells

    PubMed Central

    Liao, Jing; Karnik, Rahul; Gu, Hongcang; Ziller, Michael J.; Clement, Kendell; Tsankov, Alexander M.; Akopian, Veronika; Gifford, Casey A.; Donaghey, Julie; Galonska, Christina; Pop, Ramona; Reyon, Deepak; Tsai, Shengdar Q.; Mallard, William; Joung, J. Keith; Rinn, John L.; Gnirke, Andreas; Meissner, Alexander

    2015-01-01

    DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Here we inactivated all three catalytically active DNA methyltransferases in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing to further investigate their roles and genomic targets. Disruption of DNMT3A or DNMT3B individually, as well as of both enzymes in tandem, creates viable, pluripotent cell lines with distinct effects on their DNA methylation landscape as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome the immediate lethality, we generated a doxycycline (DOX) responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1 mutant lines. However, DOX-mediated repression of the exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death. Our data provide a comprehensive characterization of DNMT mutant ESCs, including single base genome-wide maps of their targets. PMID:25822089

  14. Biochemical genetics of opossum aldehyde dehydrogenase 3: evidence for three ALDH3A-like genes and an ALDH3B-like gene.

    PubMed

    Holmes, Roger S

    2010-04-01

    Mammalian ALDH3 isozymes participate in peroxidic and fatty aldehyde metabolism, and in anterior eye tissue UV-filtration. BLAT analyses were undertaken of the opossum genome using rat ALDH3A1, ALDH3A2, ALDH3B1, and ALDH3B2 amino acid sequences. Two predicted opossum ALDH3A1-like genes and an ALDH3A2-like gene were observed on chromosome 2, as well as an ALDH3B-like gene, which showed similar intron-exon boundaries with other mammalian ALDH3-like genes. Opossum ALDH3 subunit sequences and structures were highly conserved, including residues previously shown to be involved in catalysis and coenzyme binding for rat ALDH3A1. Eleven glycine residues were conserved for all of the opossum ALDH3-like sequences examined, including two glycine residues previously located within the stem of the rat ALDH3A1 active site funnel. Phylogeny studies of human, rat, opossum, and chicken ALDH3-like sequences indicated that the common ancestor for ALDH3A- and ALDH3B-like genes predates the appearance of birds during vertebrate evolution.

  15. Murine laminin alpha3A and alpha3B isoform chains are generated by usage of two promoters and alternative splicing.

    PubMed

    Ferrigno, O; Virolle, T; Galliano, M F; Chauvin, N; Ortonne, J P; Meneguzzi, G; Aberdam, D

    1997-08-15

    We already identified two distinct laminin alpha3A and alpha3B chain isoforms which differ in their amino-terminal ends and display different tissue-specific expression patterns. In this study we have investigated whether these two different isoforms are products of the same laminin alpha3 (lama3) gene and transcribed from one or two separate promoters. Genomic clones were isolated that encompass the sequences upstream to the 5' ends of both the alpha3A and the alpha3B cDNAs. Sequence analysis of the region upstream to the alpha3A open reading frame revealed the presence of a TATA box and potential binding sites for responsive elements. By primer extension analysis, the transcription start site of the alpha3B mRNA isoform was defined. The sequences upstream to the alpha3B mRNA transcription start site do not contain a TATA box near the transcription initiation sites, but AP-1, AP-2, and Sp1 consensus binding site sequences were identified. The genomic regions located immediately upstream of the alpha3A and alpha3B transcription start sites were shown to possess promoter activities in transfection experiments. In the promoter regions, response elements for the acute phase reactant signal and NF-interleukin 6 were found, and their possible relevance in the context of inflammation and wound healing is discussed. Our results demonstrate that the lama3 gene produces the two polypeptides by alternative splicing and contains two promoters, which regulate the production of the two isoforms alpha3A and alpha3B. PMID:9252362

  16. Neoadjuvant medium-dose methotrexate, cisplatin in category T3b-T4a (N0M0) bladder cancer.

    PubMed

    Pizzocaro, G; Pisani, E; Dormia, E; Piva, L; Maggioni, A; Minervini, G

    1990-01-01

    Between July 1985 and December 1988, 31 consecutive patients with category T3b-T4a (NOMO) urothelial cancer of the urinary bladder were entered into a phase II study of neoadjuvant chemotherapy with medium-dose methotrexate (300 mg/m2 followed by folinic acid rescue), cisplatin (100 mg/m2 continuous i.v. infusion) every 4 weeks for a total of 4 courses. Six patients did not respond to the first two courses of neoadjuvant chemotherapy and another 3 were considered non-responders after 4 courses. Three of these 9 patients progressed and could not undergo salvage cystectomy. Only 4 patients (13%) entered complete remission, and one of them refused surgery. All the 18 (58%) partial responders underwent radical cystectomy. The overall 2-year disease-free survival is 72%: it is 100% for the 4 complete responders, 76% for the 18 partial responders and 56% for the 9 nonresponders. A longer follow-up is necessary to evaluate the impact of the neoadjuvant chemotherapy on survival of category T3b-T4a (NOMO) bladder cancer. PMID:2217410

  17. Compilation, design tests: Energetic particles Satellite S-3 including design tests for S-3A, S-3B and S-3C

    NASA Technical Reports Server (NTRS)

    Ledoux, F. N.

    1973-01-01

    A compilation of engineering design tests which were conducted in support of the Energetic Particle Satellite S-3, S-3A, and S-3b programs. The purpose for conducting the tests was to determine the adequacy and reliability of the Energetic Particles Series of satellites designs. The various tests consisted of: (1) moments of inertia, (2) functional reliability, (3) component and structural integrity, (4) initiators and explosives tests, and (5) acceptance tests.

  18. Genetic diversity of spike, 3a, 3b and e genes of infectious bronchitis viruses and emergence of new recombinants in Korea.

    PubMed

    Mo, Mei-Lan; Hong, Seung-Min; Kwon, Hyuk-Joon; Kim, Il-Hwan; Song, Chang-Seon; Kim, Jae-Hong

    2013-01-31

    The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990-2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%-100.0%, 85%-100.0%, 64.0%-100.0%, 60.4%-100.0% and 83.1%-100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea.

  19. Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma.

    PubMed

    Cleven, Arjen H G; Höcker, Saskia; Briaire-de Bruijn, Inge; Szuhai, Karoly; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2015-11-01

    Specific H3F3A driver mutations and IDH2 mutations were recently described in giant cell tumor of bone (GCTB) and H3F3B driver mutations in chondroblastoma; these may be helpful as a diagnostic tool for giant cell-containing tumors of the bone. Using Sanger sequencing, we determined the frequency of H3F3A, H3F3B, IDH1, and IDH2 mutations in GCTBs (n=60), chondroblastomas (n=12), and other giant cell-containing tumors (n=24), including aneurysmal bone cyst, chondromyxoid fibroma, and telangiectatic osteosarcoma. To find an easy applicable marker for H3F3A mutation status, H3K36 trimethylation and ATRX expression were correlated with H3F3A mutations. In total, 69% of all GCTBs harbored an H3F3A (G34W/V) mutation compared with 0% of all other giant cell-containing tumors (P<0.001), whereas 70% of chondroblastomas showed an H3F3B (K36M) mutation compared with 0% of other giant cell-containing tumors (P<0.001). Diffuse H3K36 trimethylation positivity was more often seen in mutated H3F3A GCTBs compared with other giant cell-containing tumors (P=0.005). ATRX protein expression was not correlated with H3F3A mutation status. Hotspot mutations in IDH1 or IDH2 were absent. Our results show that H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of GCTB and chondroblastoma from other giant cell-containing tumors. Although H3K36 trimethylation and ATRX immunohistochemistry cannot be used as surrogate markers for H3F3A mutation status, mutations in H3F3A are associated with increased H3K36 trimethylation, suggesting that methylation at this residue may play a role in the etiology of the disease.

  20. Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma.

    PubMed

    Cleven, Arjen H G; Höcker, Saskia; Briaire-de Bruijn, Inge; Szuhai, Karoly; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2015-11-01

    Specific H3F3A driver mutations and IDH2 mutations were recently described in giant cell tumor of bone (GCTB) and H3F3B driver mutations in chondroblastoma; these may be helpful as a diagnostic tool for giant cell-containing tumors of the bone. Using Sanger sequencing, we determined the frequency of H3F3A, H3F3B, IDH1, and IDH2 mutations in GCTBs (n=60), chondroblastomas (n=12), and other giant cell-containing tumors (n=24), including aneurysmal bone cyst, chondromyxoid fibroma, and telangiectatic osteosarcoma. To find an easy applicable marker for H3F3A mutation status, H3K36 trimethylation and ATRX expression were correlated with H3F3A mutations. In total, 69% of all GCTBs harbored an H3F3A (G34W/V) mutation compared with 0% of all other giant cell-containing tumors (P<0.001), whereas 70% of chondroblastomas showed an H3F3B (K36M) mutation compared with 0% of other giant cell-containing tumors (P<0.001). Diffuse H3K36 trimethylation positivity was more often seen in mutated H3F3A GCTBs compared with other giant cell-containing tumors (P=0.005). ATRX protein expression was not correlated with H3F3A mutation status. Hotspot mutations in IDH1 or IDH2 were absent. Our results show that H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of GCTB and chondroblastoma from other giant cell-containing tumors. Although H3K36 trimethylation and ATRX immunohistochemistry cannot be used as surrogate markers for H3F3A mutation status, mutations in H3F3A are associated with increased H3K36 trimethylation, suggesting that methylation at this residue may play a role in the etiology of the disease. PMID:26457357

  1. Open-channel blockade is less effective on GluN3B than GluN3A subunit-containing NMDA receptors.

    PubMed

    McClymont, David W; Harris, John; Mellor, Ian R

    2012-07-01

    The GluN3 subunits of the N-methyl-d-aspartate (NMDA) receptor are known to reduce its Ca(2+) permeability and Mg(2+) sensitivity, however, little is known about their effects on other channel blockers. cRNAs for rat NMDA receptor subunits were injected into Xenopus oocytes and responses to NMDA and glycine were recorded using two electrode voltage clamp. Channel block of receptors containing GluN1-1a/2A, GluN1-1a/2A/3A or GluN1-1a/2A/3B subunits was characterised using Mg(2+), memantine, MK-801, philanthotoxin-343 and methoctramine. IC(50) values for Mg(2+) and memantine increased when receptors contained GluN3A subunits and were further increased when they contained GluN3B, e.g. IC(50)s at -75mV for block of GluN1-1a/2A, GluN1-1a/2A/3A and GluN1-1a/2A/3B receptors respectively were 4.2, 22.4 and 40.1μM for Mg(2+), and 2.5, 7.5 and 17.5μM for memantine. Blocking activity was found to be fully or partially restored when G or R (at the N and N+1 sites respectively) were mutated to N in GluN3A. Thus, the changes cannot be attributed to the loss of the N or N+1 sites alone, but rather involve both sites or residues elsewhere. Block by MK-801 and philanthotoxin-343 was also reduced by GluN3A, most strongly at -100mV but not at -50mV, and by GluN3B at all V(h). Methoctramine was the least sensitive to introduction of GluN3 subunits suggesting a minimal interaction with the N and N+1 sites. We conclude that GluN3B-containing receptors provide increased resistance to channel block compared to GluN3A-containing receptors and this must be due to differences outside the deep pore region (N site and deeper).

  2. Hepatitis B virus X protein upregulates DNA methyltransferase 3A/3B and enhances SOCS-1CpG island methylation.

    PubMed

    Fu, Xiaoyu; Song, Xiaoling; Li, Yanyan; Tan, Deming; Liu, Guozhen

    2016-01-01

    The aim of the present study was to investigate the effect of hepatitis B virus X protein (HBx) on the expression of DNA methyltransferase (DNMT)3A/3B and suppressors of cytokine signaling‑1 (SOCS‑1), as well as promoter CpG island methylation of the SOCS‑1 gene. Stable hepatocyte cell lines expressing the HBx gene (pcDNA‑X/QSG7701) or an empty gene (pcDNA3.0/QSG7701) were established. Reverse transcription quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression levels of DNMT3A/3B and SOCS‑1. Immunohistochemistry was used to detect the protein expression of DNMT3A/3B. Methylation‑specific PCR (MSP) was used to detect the methylation status of the SOCS‑1 gene promoter. The mRNA and protein expression levels of DNMT3A/3B were significantly higher in the pcDNA‑X/QSG7701‑transfected cells, compared with those in the pcDNA3.0/QSG7701 or non‑transfected QSG7701 cells (P<0.05), whereas the relative mRNA expression of SOCS‑1 was significantly lower in the pcDNA‑X/QSG7701 cells compared with the pcDNA3.0/QSG7701 and non‑transfected QSG7701 cells (F=19.6; P<0.05). Western blot analysis showed that the protein expression of SOCS‑1 was significantly lower in the pcDNA‑X/QSG7701 cells, compared with the pcDNA3.0/QSG7701 or non‑transfected QSG7701 cells (F=19.4; P<0.05). The results of the MSP analysis showed that SOCS‑1 promoter region methylation was present only in the pcDNA‑X/QSG7701 cells. The HBV‑X gene upregulated the mRNA and protein expression levels of DNMT3A/3B, downregulated the expression of SOCS‑1 and increased SOCS‑1 gene promoter CpG island methylation. This may provide a potential explanation of the mechanism underlying HBx-associated hepatocellular carcinoma.

  3. A Positive Regulatory Loop between foxi3a and foxi3b Is Essential for Specification and Differentiation of Zebrafish Epidermal Ionocytes

    PubMed Central

    Hsiao, Chung-Der; You, May-Su; Guh, Ying-Jey; Ma, Ming; Jiang, Yun-Jin; Hwang, Pung-Pung

    2007-01-01

    Background Epidermal ionocytes play essential roles in the transepithelial transportation of ions, water, and acid-base balance in fish embryos before their branchial counterparts are fully functional. However, the mechanism controlling epidermal ionocyte specification and differentiation remains unknown. Methodology/Principal Findings In zebrafish, we demonstrated that Delta-Notch-mediated lateral inhibition plays a vital role in singling out epidermal ionocyte progenitors from epidermal stem cells. The entire epidermal ionocyte domain of genetic mutants and morphants, which failed to transmit the DeltaC-Notch1a/Notch3 signal from sending cells (epidermal ionocytes) to receiving cells (epidermal stem cells), differentiates into epidermal ionocytes. The low Notch activity in epidermal ionocyte progenitors is permissive for activating winged helix/forkhead box transcription factors of foxi3a and foxi3b. Through gain- and loss-of-function assays, we show that the foxi3a-foxi3b regulatory loop functions as a master regulator to mediate a dual role of specifying epidermal ionocyte progenitors as well as of subsequently promoting differentiation of Na+,K+-ATPase-rich cells and H+-ATPase-rich cells in a concentration-dependent manner. Conclusions/Significance This study provides a framework to show the molecular mechanism controlling epidermal ionocyte specification and differentiation in a low vertebrate for the first time. We propose that the positive regulatory loop between foxi3a and foxi3b not only drives early ionocyte differentiation but also prevents the complete blockage of ionocyte differentiation when the master regulator of foxi3 function is unilaterally compromised. PMID:17375188

  4. Compendium of NASA data base for the Global Tropospheric Experiment's Arctic Boundary Layer Experiments ABLE-3A and ABLE-3B

    NASA Technical Reports Server (NTRS)

    Gregory, Gerald L.; Scott, A. Donald, Jr.

    1994-01-01

    The report provides a compendium of NASA aircraft data that are available from NASA's Global Tropospheric Experiment's (GTE) Arctic Boundary Layer Experiments (ABLE) conducted in July and August of 1988 (ABLE-3A) and 1990 (ABLE-3B). ABLE-3A flight experiments were based at Barrow and Bethel, Alaska, and included survey/transit flights to Thule, Greenland. ABLE-3B flight experiments were based at North Bay (Ontario) and Goose Bay, Canada, and included flights northward to Frobisher Bay, Canada. The primary purposes of the experiments were (1) the measurement of the flux of various trace gases from high-arctic ecosystems, (2) the elucidation of factors important to the production and destruction of ozone, and (3) the documentation of source and chemical signature of air common to and transported into the regions. The report provides a representation, in the form of selected data plots, of aircraft data that are available in archived format via NASA Langley's Distributed Active Archive Center. The archived data bases include data for other species measured on the aircraft as well as numerous supporting data, including meteorological observations/products, results from surface studies, satellite observations, and sondes releases.

  5. Source analysis of P3a and P3b components to investigate interaction of depression and anxiety in attentional systems

    PubMed Central

    Li, Yuezhi; Wang, Wuyi; Liu, Tiebang; Ren, Lijie; Zhou, Yunfei; Yu, Changhong; Qu, Xingda; Hu, Yong

    2015-01-01

    This study examined the impact of depressive disorders, anxiety disorders and the comorbidity of these disorders on the regional electrophysiological features of brain activity. Sixty-four-channel event-related potentials (ERP) were acquired during a visual oddball task in patients with depressive disorder, patients with anxiety disorders, patients with comorbid depressive and anxiety disorders and healthy subjects. An fMRI-constrained source model was applied to ERP to identify different cortical activities in the patient and control groups. Comorbid patients showed an abnormal frontal-greater-than-parietal P3b topography in the right hemisphere and the highest P3a amplitude at frontal and central sites at the scalp midline. For P3b, depressed patients showed decreased right-lateralized activity in the precentral sulcus (PrCS) and posterior parietal cortex (PPC). Anxious patients demonstrated hyperactive prefrontal cortices (PFC). Comorbid patients presented decreased activity in the cingulate gyrus, right PrCS and right PPC and increased activity in the left PFC and left insular (INS). For P3a, hyperactive left PrCS was found in comorbid patients. Comorbid patients showed both anxiety-related and depression-related activity. A superimposition effect of depression and anxiety was identified with (1) aggravated hypo-function of the right-lateralized dorsal attention and salience networks and (2) complicated anxiety-related hyper-function of the left-lateralized ventral attention and salience networks. PMID:26598026

  6. Compendium of NASA data base for the Global Tropospheric Experiment's Arctic Boundary Layer Experiments ABLE-3A and ABLE-3B

    SciTech Connect

    Gregory, G.L.; Scott, A.D. Jr.

    1994-11-01

    The report provides a compendium of NASA aircraft data that are available from NASA's Global Tropospheric Experiment's (GTE) Arctic Boundary Layer Experiments (ABLE) conducted in July and August of 1988 (ABLE-3A) and 1990 (ABLE-3B). ABLE-3A flight experiments were based at Barrow and Bethel, Alaska, and included survey/transit flights to Thule, Greenland. ABLE-3B flight experiments were based at North Bay (Ontario) and Goose Bay, Canada, and included flights northward to Frobisher Bay, Canada. The primary purposes of the experiments were (1) the measurement of the flux of various trace gases from high-arctic ecosystems, (2) the elucidation of factors important to the production and destruction of ozone, and (3) the documentation of source and chemical signature of air common to and transported into the regions. The report provides a representation, in the form of selected data plots, of aircraft data that are available in archived format via NASA Langley's Distributed Active Archive Center. The archived data bases include data for other species measured on the aircraft as well as numerous supporting data, including meteorological observations/products, results from surface studies, satellite observations, and sondes releases.

  7. Description and assessment of RAMONA-3B Mod. 0 Cycle 4: a computer code with three-dimensional neutron kinetics for BWR system transients

    SciTech Connect

    Wulff, W; Cheng, H S; Diamond, D J; Khatib-Rahbar, M

    1984-01-01

    This report documents the physical models and the numerical methods employed in the BWR systems code RAMONA-3B. The RAMONA-3B code simulates three-dimensional neutron kinetics and multichannel core hydraulics of nonhomogeneous, nonequilibrium two-phase flows. RAMONA-3B is programmed to calculate the steady and transient conditions in the main steam supply system for normal and abnormal operational transients, including the performances of plant control and protection systems. Presented are code capabilities and limitations, models and solution techniques, the results of development code assessment and suggestions for improving the code in the future.

  8. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.

    PubMed

    Behjati, Sam; Tarpey, Patrick S; Presneau, Nadège; Scheipl, Susanne; Pillay, Nischalan; Van Loo, Peter; Wedge, David C; Cooke, Susanna L; Gundem, Gunes; Davies, Helen; Nik-Zainal, Serena; Martin, Sancha; McLaren, Stuart; Goody, Victoria; Goodie, Victoria; Robinson, Ben; Butler, Adam; Teague, Jon W; Halai, Dina; Khatri, Bhavisha; Myklebost, Ola; Baumhoer, Daniel; Jundt, Gernot; Hamoudi, Rifat; Tirabosco, Roberto; Amary, M Fernanda; Futreal, P Andrew; Stratton, Michael R; Campbell, Peter J; Flanagan, Adrienne M

    2013-12-01

    It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions.

  9. Complement split products c3a and c4a in chronic lyme disease.

    PubMed

    Stricker, R B; Savely, V R; Motanya, N C; Giclas, P C

    2009-01-01

    Complement split products C3a and C4a are reportedly elevated in patients with acute Lyme disease. We have now examined these immunologic markers in patients with chronic Lyme disease compared to appropriate disease controls. The study population consisted of 29 healthy controls, 445 patients with chronic Lyme disease, 11 patients with systemic lupus erythematosus (SLE) and six patients with AIDS. The Lyme disease patients were divided according to predominant musculoskeletal symptoms (324 patients) or predominant neurologic symptoms (121 patients). C3a and C4a levels were measured by radioimmunoassay. All patients with chronic Lyme disease and AIDS had normal C3a levels compared to controls, whereas patients with SLE had significantly increased levels of this marker. Patients with predominant musculoskeletal symptoms of Lyme disease and AIDS patients had significantly increased levels of C4a compared to either controls, patients with predominant neurologic symptoms of Lyme disease or SLE patients. Response to antibiotic therapy in chronic Lyme disease was associated with a significant decrease in the C4a level, whereas lack of response was associated with a significant increase in this marker. In contrast, AIDS patients had persistently increased C4a levels despite antiretroviral therapy. Lyme patients with positive single-photon emission computed tomographic (SPECT) scans had significantly lower C4a levels compared to Lyme patients with normal SPECT scan results. Patients with predominant musculoskeletal symptoms of Lyme disease have normal C3a and increased C4a levels. This pattern differs from the increase in both markers seen in acute Lyme disease, and C4a changes correlate with the response to therapy in chronic Lyme disease. C4a appears to be a valuable immunologic marker in patients with persistent symptoms of Lyme disease.

  10. Marker vaccine potential of foot-and-mouth disease virus with large deletion in the non-structural proteins 3A and 3B.

    PubMed

    Biswal, Jitendra K; Subramaniam, Saravanan; Ranjan, Rajeev; Sharma, Gaurav K; Misri, Jyoti; Pattnaik, Bramhadev

    2015-11-01

    Foot-and-mouth disease (FMD) is a highly contagious, economically important disease of transboundary importance. Regular vaccination with chemically inactivated FMD vaccine is the major means of controlling the disease in endemic countries like India. However, the traditional inactivated vaccines may sometimes contain traces of FMD viral (FMDV) non-structural protein (NSP), therefore, interfering with the NSP-based serological discrimination between infected and vaccinated animals. The availability of marker vaccine for differentiating FMD infected from vaccinated animals (DIVA) would be crucial for the control and subsequent eradication of FMD in India. In this study, we constructed a negative marker FMDV serotype O virus (vaccine strain O IND R2/1975), containing dual deletions of amino acid residues 93-143 and 10-37 in the non-structural proteins 3A and 3B, respectively through reverse genetics approach. The negative marker virus exhibited similar growth kinetics and plaque morphology in cell culture as compared to the wild type virus. In addition, we also developed and evaluated an indirect ELISA (I-ELISA) targeted to the deleted 3AB NSP region (truncated 3AB) which could be used as a companion differential diagnostic assay. The diagnostic sensitivity and specificity of the truncated 3AB I-ELISA were found to be 95.5% and 96%, respectively. The results from this study suggest that the availability negative marker virus and companion diagnostic assay could open a promising new avenue for the application of DIVA compatible marker vaccine for the control of FMD in India.

  11. Marker vaccine potential of foot-and-mouth disease virus with large deletion in the non-structural proteins 3A and 3B.

    PubMed

    Biswal, Jitendra K; Subramaniam, Saravanan; Ranjan, Rajeev; Sharma, Gaurav K; Misri, Jyoti; Pattnaik, Bramhadev

    2015-11-01

    Foot-and-mouth disease (FMD) is a highly contagious, economically important disease of transboundary importance. Regular vaccination with chemically inactivated FMD vaccine is the major means of controlling the disease in endemic countries like India. However, the traditional inactivated vaccines may sometimes contain traces of FMD viral (FMDV) non-structural protein (NSP), therefore, interfering with the NSP-based serological discrimination between infected and vaccinated animals. The availability of marker vaccine for differentiating FMD infected from vaccinated animals (DIVA) would be crucial for the control and subsequent eradication of FMD in India. In this study, we constructed a negative marker FMDV serotype O virus (vaccine strain O IND R2/1975), containing dual deletions of amino acid residues 93-143 and 10-37 in the non-structural proteins 3A and 3B, respectively through reverse genetics approach. The negative marker virus exhibited similar growth kinetics and plaque morphology in cell culture as compared to the wild type virus. In addition, we also developed and evaluated an indirect ELISA (I-ELISA) targeted to the deleted 3AB NSP region (truncated 3AB) which could be used as a companion differential diagnostic assay. The diagnostic sensitivity and specificity of the truncated 3AB I-ELISA were found to be 95.5% and 96%, respectively. The results from this study suggest that the availability negative marker virus and companion diagnostic assay could open a promising new avenue for the application of DIVA compatible marker vaccine for the control of FMD in India. PMID:26260689

  12. Homologous Elements hs3a and hs3b in the 3′ Regulatory Region of the Murine Immunoglobulin Heavy Chain (Igh) Locus Are Both Dispensable for Class-switch Recombination*

    PubMed Central

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R.; Bah, Fatmata; Birshtein, Barbara K.; Eckhardt, Laurel A.

    2011-01-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3′ regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established “pairs” of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3′ regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR. PMID:21673112

  13. Sequence and expression analysis of rainbow trout CXCR2, CXCR3a and CXCR3b aids interpretation of lineage-specific conversion, loss and expansion of these receptors during vertebrate evolution

    PubMed Central

    Xu, Qiaoqing; Li, Ronggai; Monte, Milena M.; Jiang, Yousheng; Nie, Pin; Holland, Jason W.; Secombes, Chris J.; Wang, Tiehui

    2014-01-01

    The chemokine receptors CXCR1–3 bind to 11 chemokines (CXCL1–11) that are clustered on the same chromosome in mammals but are largely missing in ray-finned fish. A second CXCR1/2, and a CXCR3a and CXCR3b gene have been cloned in rainbow trout. Analysis of CXCR1–R3 genes in lobe-finned fish, ray-finned fish and tetrapod genomes revealed that the teleostomian ancestor likely possessed loci containing both CXCR1 and CXCR2, and CXCR3a and CXCR3b. Based on this synteny analysis the first trout CXCR1/2 gene was renamed CXCR1, and the new gene CXCR2. The CXCR1/R2 locus was shown to have further expanded in ray-finned fish. In relation to CXCR3, mammals appear to have lost CXCR3b and birds both CXCR3a and CXCR3b during evolution. Trout CXCR1–R3 have distinct tissue expression patterns and are differentially modulated by PAMPs, proinflammatory cytokines and infections. They are highly expressed in macrophages and neutrophils, with CXCR1 and CXCR2 also expressed in B-cells. PMID:24613851

  14. Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination.

    PubMed

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R; Bah, Fatmata; Birshtein, Barbara K; Eckhardt, Laurel A

    2011-08-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3' regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established "pairs" of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3' regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR. PMID:21673112

  15. Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination.

    PubMed

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R; Bah, Fatmata; Birshtein, Barbara K; Eckhardt, Laurel A

    2011-08-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3' regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established "pairs" of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3' regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR.

  16. 75 FR 22693 - Airworthiness Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ...; AD 2010-01-04] RIN 2120-AA64 Airworthiness Directives; General Electric Company (GE) CF34-1A, CF34-3A...;having general applicability and legal effect, most of which are keyed #0;to and codified in the Code of...-7756; fax: (781) 238-7199. SUPPLEMENTARY INFORMATION: On January 8, 2010 (75 FR 1017), we published...

  17. Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G0/G1 to S phase transition in normal and tumor cells

    PubMed Central

    Robertson, Keith D.; Keyomarsi, Khandan; Gonzales, Felicidad A.; Velicescu, Mihaela; Jones, Peter A.

    2000-01-01

    DNA methylation is essential for mammalian development, X-chromosome inactivation, and imprinting yet aberrant methylation patterns are one of the most common features of transformed cells. One of the proposed causes for these defects in the methylation machinery is overexpression of one or more of the three known catalytically active DNA methyltransferases (DNMTs) 1, 3a and 3b, yet there are clearly examples in which overexpression is minimal or non-existent but global methylation anomalies persist. An alternative mechanism which could give rise to global methylation errors is the improper expression of one or more of the DNMTs during the cell cycle. To begin to study the latter possibility we examined the expression of the mRNAs for DNMT1, 3a and 3b during the cell cycle of normal and transformed cells. We found that DNMT1 and 3b levels were significantly downregulated in G0/G1 while DNMT3a mRNA levels were less sensitive to cell cycle alterations and were maintained at a slightly higher level in tumor lines compared to normal cell strains. Enzymatic activity assays revealed a similar decrease in the overall methylation capacity of the cells during G0/G1 arrest and again revealed that a tumor cell line maintained a higher methylation capacity during arrest than a normal cell strain. These results reveal a new level of control exerted over the cellular DNA methylation machinery, the loss of which provides an alternative mechanism for the genesis of the aberrant methylation patterns observed in tumor cells. PMID:10773079

  18. Stability and specificity of heterodimer formation for the coiled-coil neck regions of the motor proteins Kif3A and Kif3B: the role of unstructured oppositely charged regions

    PubMed Central

    Chana, M.S.; Tripet, B.P.; Mant, C.T.; Hodges, R.

    2005-01-01

    We investigated the folding, stability, and specificity of dimerization of the neck regions of the kinesin-like proteins Kif3A (residues 356–416) and Kif3B (residues 351–411). We showed that the complementary charged regions found in the hinge regions (which directly follow the neck regions) of these proteins do not adopt any secondary structure in solution. We then explored the ability of the complementary charged regions to specify heterodimer formation for the neck region coiled-coils found in Kif3A and Kif3B. Redox experiments demonstrated that oppositely charged regions specified the formation of a heterodimeric coiled-coil. Denaturation studies with urea demonstrated that the negatively charged region of Kif3A dramatically destabilized its neck coiled-coil (urea1/2 value of 3.9 m compared with 6.7 m for the coiled-coil alone). By comparison, the placement of a positively charged region C-terminal to the neck coiled-coil of Kif3B had little effect on stability (urea1/2 value of 8.2 m compared with 8.8 m for the coiled-coil alone). The pairing of complementary charged regions leads to specific heterodimer formation where the stability of the heterodimeric neck coiled-coil with charged regions had similar stability (urea1/2 value of 7.8 m) to the most stable homodimer (Kif3B) with charged regions (urea1/2 value of 8.0 m) and dramatically more stable than the Kif3A homodimer with charged regions (urea1/2, value of 3.9 m). The heterodimeric coiled-coil with charged extensions has essentially the same stability as the heterodimeric coiled-coil on its own (urea1/2 values of 7.8 and 8.1 m, respectively) suggesting that specificity of heterodimerization is driven by non-specific attraction of the oppositely unstructured charged regions without affecting stability of the heterodimeric coiled-coil. PMID:15705165

  19. De novo DNA methyltransferase DNMT3b interacts with NEDD8-modified proteins.

    PubMed

    Shamay, Meir; Greenway, Melanie; Liao, Gangling; Ambinder, Richard F; Hayward, S Diane

    2010-11-19

    DNA methylation and histone modifications play an important role in transcription regulation. In cancer cells, many promoters become aberrantly methylated through the activity of the de novo DNA methyltransferases DNMT3a and DNMT3b and acquire repressive chromatin marks. NEDD8 is a ubiquitin-like protein modifier that is conjugated to target proteins, such as cullins, to regulate their activity, and cullin 4A (CUL4A) in its NEDD8-modified form is essential for repressive chromatin formation. We found that DNMT3b associates with NEDD8-modified proteins. Whereas DNMT3b interacts directly in vitro with NEDD8, conjugation of NEDD8 to target proteins enhances this interaction in vivo. DNMT3b immunoprecipitated two major bands of endogenously NEDDylated proteins at the size of NEDDylated cullins, and indeed DNMT3b interacted with CUL1, CUL2, CUL3, CUL4A, and CUL5. Moreover, DNMT3b preferentially immunoprecipitated the NEDDylated form of endogenous CUL4A. NEDD8 enhanced DNMT3b-dependent DNA methylation. Chromatin immunoprecipitation assays suggest that DNMT3b recruits CUL4A and NEDD8 to chromatin, whereas deletion of Dnmt3b reduces the association of CUL4A and NEDD8 at a repressed promoter in a cancer cell line. PMID:20847044

  20. Double plant homeodomain (PHD) finger proteins DPF3a and -3b are required as transcriptional co-activators in SWI/SNF complex-dependent activation of NF-κB RelA/p50 heterodimer.

    PubMed

    Ishizaka, Aya; Mizutani, Taketoshi; Kobayashi, Kazuyoshi; Tando, Toshio; Sakurai, Kouhei; Fujiwara, Toshinobu; Iba, Hideo

    2012-04-01

    We have previously shown that DPF2 (requiem/REQ) functions as a linker protein between the SWI/SNF complex and RelB/p52 NF-κB heterodimer and plays important roles in NF-κB transactivation via its noncanonical pathway. Using sensitive 293FT reporter cell clones that had integrated a SWI/SNF-dependent NF-κB reporter gene, we find in this study that the overexpression of DPF1, DPF2, DPF3a, DPF3b, and PHF10 significantly potentiates the transactivating activity of typical NF-κB dimers. Knockdown analysis using 293FT reporter cells that endogenously express these five proteins at low levels clearly showed that DPF3a and DPF3b, which are produced from the DPF3 gene by alternative splicing, are the most critical for the RelA/p50 NF-κB heterodimer transactivation induced by TNF-α stimulation. Our data further show that this transactivation requires the SWI/SNF complex. DPF3a and DPF3b are additionally shown to interact directly with RelA, p50, and several subunits of the SWI/SNF complex in vitro and to be co-immunoprecipitated with RelA/p50 and the SWI/SNF complex from the nuclear fractions of cells treated with TNF-α. In ChIP experiments, we further found that endogenous DPF3a/b and the SWI/SNF complex are continuously present on HIV-1 LTR, whereas the kinetics of RelA/p50 recruitment after TNF-α treatment correlate well with the viral transcriptional activation levels. Additionally, re-ChIP experiments showed DPF3a/b and the SWI/SNF complex associate with RelA on the endogenous IL-6 promoter after TNF-α treatment. In conclusion, our present data indicate that by linking RelA/p50 to the SWI/SNF complex, DPF3a/b induces the transactivation of NF-κB target gene promoters in relatively inactive chromatin contexts.

  1. Rapid detection of HCV genotyping 1a, 1b, 2a, 3a, 3b and 6a in a single reaction using two-melting temperature codes by a real-time PCR-based assay.

    PubMed

    Athar, Muhammad Ammar; Xu, Ye; Xie, Xiaoting; Xu, Zhenxing; Ahmad, Vakil; Hayder, Zulfiqar; Hussain, Syed Sajid; Liao, Yiqun; Li, Qingge

    2015-09-15

    The genotype of the hepatitis C virus (HCV) is an important indicator for antiviral therapeutic response. We hereby described development of a rapid HCV genotyping approach that enabled the identification of the six most common HCV subtypes of Asia, i.e., 1a, 1b, 2a, 3a, 3b, and 6a, in a single reaction. Using two dual-labeled, self-quenched probes that target the core region of the HCV genome, the exact subtype could be accurately identified by two-melting temperature codes determined from the two respective probes in a real-time PCR assay. Analytical sensitivity studies using armored RNA samples representing each of the six HCV subtypes showed that 5 copies/reaction of HCV RNA could be detected. The assay was evaluated using 244 HCV-positive serum samples and the results were compared with sequencing analysis. Of the 224 samples, subtype 3a (127, 52.3%) was the dominant, followed by 1b (51, 20.9%), 3b (47, 19.3%), 2a (8, 3.3%), 6a (4, 1.6%) and the least was subtype 1a (1, 0.4%). Moreover, 6 (2.5%) mixed infection samples were also detected. These results were fully concordant with sequencing analysis. We concluded that this real-time PCR-based assay could provide a rapid and reliable tool for routine HCV genotyping in most Asian countries.

  2. Order-disorder in In{sup 3+} perovskites: The example of A(In{sub 2/3}B''{sub 1/3})O{sub 3} (A=Ba, Sr; B''=W, U)

    SciTech Connect

    Larregola, S.A. Alonso, J.A.; Pinacca, R.M.; Viola, M.C.; Pedregosa, J.C.

    2008-10-15

    We describe the preparation and structural characterization of four In-containing perovskites from neutron powder diffraction (NPD) and X-ray powder diffraction (XRPD) data. Sr{sub 3}In{sub 2}B''O{sub 9} and Ba(In{sub 2/3}B''{sub 1/3})O{sub 3} (B''=W, U) were synthesized by standard ceramic procedures. The crystal structure of the W-containing perovskites and Ba(In{sub 2/3}U{sub 1/3})O{sub 3} have been revisited based on our high-resolution NPD and XRPD data, while for the new U-containing perovskite Sr{sub 3}In{sub 2}UO{sub 9} the structural refinement was carried out from high-resolution XRPD data. At room temperature, the crystal structure for the two Sr phases is monoclinic, space group P2{sub 1}/n, where the In atoms occupy two different sites Sr{sub 2}[In]{sub 2d}[In{sub 1/3}B''{sub 2/3}]{sub 2c}O{sub 6}, with a=5.7548(2) A, b=5.7706(2) A, c=8.1432(3) A, {beta}=90.01(1){sup o} for B''=W and a=5.861(1) A, b=5.908(1) A, c=8.315(2) A, {beta}=89.98(1){sup o} for B''=U. The two phases with A=Ba should be described in a simple cubic perovskite unit cell (S.G. Pm3-bar m) with In and B'' distributed at random at the octahedral sites, with a=4.16111(1) A and 4.24941(1) A for W and U compounds, respectively. - Graphical abstract: The structure of the new uranium-based double perovskite Sr{sub 3}In{sub 2}UO{sub 9} is described and the true symmetry of the other title compounds are revisited. The presence of long-range ordering in the Sr samples, by contrast with the Ba perovskites, is related with the smaller unit cell and B-B distances in the Sr oxides, promoting the electrostatic repulsions between highly charged W{sup 6+} and U{sup 6+} cations as driving force for the long-range B-site ordering.

  3. Linkage and association of haplotypes at the APOA1/C3/A4/A5 genecluster to familial combined hyperlipidemia

    SciTech Connect

    Eichenbaum-Voline, Sophie; Olivier, Michael; Jones, Emma L.; Naoumova, Rossitza P.; Jones, Bethan; Gau, Brian; Seed, Mary; Betteridge,D. John; Galton, David J.; Rubin, Edward M.; Scott, James; Shoulders,Carol C.; Pennacchio, Len A.

    2002-09-15

    Combined hyperlipidemia (CHL) is a common disorder of lipidmetabolism that leads to an increased risk of cardiovascular disease. Thelipid profile of CHL is characterised by high levels of atherogeniclipoproteins and low levels of high-density-lipoprotein-cholesterol.Apolipoprotein (APO) A5 is a newly discovered gene involved in lipidmetabolism located within 30kbp of the APOA1/C3/A4 gene cluster. Previousstudies have indicated that sequence variants in this cluster areassociated with increased plasma lipid levels. To establish whethervariation at the APOA5 gene contributes to the transmission of CHL, weperformed linkage and linkage disequilibrium (LD) tests on a large cohortof families (n=128) with familial CHL (FCHL). The linkage data producedevidence for linkage of the APOA1/C3/A4/A5 genomic interval to FCHL (NPL= 1.7, P = 0.042). The LD studies substantiated these data. Twoindependent rare alleles, APOA5c.56G and APOC3c.386G of this gene clusterwere over-transmitted in FCHL (P = 0.004 and 0.007, respectively), andthis was associated with a reduced transmission of the most commonAPOA1/C3/A4/A5 haplotype (frequency 0.4425) to affected subjects (P =0.013). The APOA5c.56G allele was associated with increased plasmatriglyceride levels in FCHL probands, whereas the second, andindependent, APOC3c.386G allele was associated with increased plasmatriglyceride levels in FCHL pedigree founders. Thus, this allele (or anallele in LD) may mark a quantitative trait associated with FCHL, as wellas representing a disease susceptibility locus for the condition. Thisstudy establishes that sequence variation in the APOA1/C3/A4/A5 genecluster contributes to the transmission of FCHL in a substantialproportion of affected families, and that these sequence variants mayalso contribute to the lipid abnormalities of the metabolic syndrome,which is present in up to 40 percent of persons with cardiovasculardisease.

  4. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a.

    PubMed Central

    Ohno, O; Mizokami, M; Wu, R R; Saleh, M G; Ohba, K; Orito, E; Mukaide, M; Williams, R; Lau, J Y

    1997-01-01

    Recent studies have focused on whether different hepatitis C virus (HCV) genotypes are associated with different profiles of pathogenicity, infectivity, and response to antiviral therapy. The establishment of a simple and precise genotyping system for HCV is essential to address these issues. A new genotyping system based on PCR of the core region with genotype-specific PCR primers for the determination of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a was developed. A total of 607 samples (379 from Japan, 63 from the United States, 53 from Korea, 35 from Taiwan, 32 from China, 20 from Hong Kong, 15 from Australia, 6 from Egypt, 3 from Bangladesh, and 1 from South Africa) were tested by both the assay of Okamoto et al. (H. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyamura, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) and this new genotyping system. Comparison of the results showed concordant results for 539 samples (88.8%). Of the 68 samples with discordant results, the nucleotide sequences of the HCV isolates were determined in 23, and their genotypes were determined by molecular evolutionary analysis. In all 23 samples, the assignment of genotype by our new genotyping system was correct. This genotyping system may be useful for large-scale determination of HCV genotypes in clinical studies. PMID:8968908

  5. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes.

    PubMed

    Castel, David; Philippe, Cathy; Calmon, Raphaël; Le Dret, Ludivine; Truffaux, Nathalène; Boddaert, Nathalie; Pagès, Mélanie; Taylor, Kathryn R; Saulnier, Patrick; Lacroix, Ludovic; Mackay, Alan; Jones, Chris; Sainte-Rose, Christian; Blauwblomme, Thomas; Andreiuolo, Felipe; Puget, Stephanie; Grill, Jacques; Varlet, Pascale; Debily, Marie-Anne

    2015-12-01

    Diffuse intrinsic pontine glioma (DIPG) is the most severe paediatric solid tumour, with no significant therapeutic progress made in the past 50 years. Recent studies suggest that diffuse midline glioma, H3-K27M mutant, may comprise more than one biological entity. The aim of the study was to determine the clinical and biological variables that most impact their prognosis. Ninety-one patients with classically defined DIPG underwent a systematic stereotactic biopsy and were included in this observational retrospective study. Histone H3 genes mutations were assessed by immunochemistry and direct sequencing, whilst global gene expression profiling and chromosomal imbalances were determined by microarrays. A full description of the MRI findings at diagnosis and at relapse was integrated with the molecular profiling data and clinical outcome. All DIPG but one were found to harbour either a somatic H3-K27M mutation and/or loss of H3K27 trimethylation. We also discovered a novel K27M mutation in HIST2H3C, and a lysine-to-isoleucine substitution (K27I) in H3F3A, also creating a loss of trimethylation. Patients with tumours harbouring a K27M mutation in H3.3 (H3F3A) did not respond clinically to radiotherapy as well, relapsed significantly earlier and exhibited more metastatic recurrences than those in H3.1 (HIST1H3B/C). H3.3-K27M-mutated DIPG have a proneural/oligodendroglial phenotype and a pro-metastatic gene expression signature with PDGFRA activation, while H3.1-K27M-mutated tumours exhibit a mesenchymal/astrocytic phenotype and a pro-angiogenic/hypoxic signature supported by expression profiling and radiological findings. H3K27 alterations appear as the founding event in DIPG and the mutations in the two main histone H3 variants drive two distinct oncogenic programmes with potential specific therapeutic targets. PMID:26399631

  6. MANYEFFV3B

    2007-05-30

    MANYEFFV3B is a program to calculate bound state properties of light nuclei, mainly A=3 and A=4 systems, using realistic nucleon-nucleon interactions and, optionally, three-nucleon interaction derived within the chiral effective field theory. Also, the program is used to generate three-body effective interaction from the realistic NN+NNN potentials to be used in shell model calculations for heavier nuclei, typically p=shell nuclei. These calculations are referred to as ab initio no-core shell model calculations. The code outputsmore » eigenvalues and optionally wave functions of the investigated nuclei. Alternatively, the code outputs the three-body effective interactions matrix elements in relative-coordinate basis that needs to be further transformed to single-particle basis by a separate code in order to be used as input to shell model codes with three-body capability (MFD, Redstick). Several passes of the code are required in calculations for A>3 nuclei if three-body effective interaction is to be generated or used and also if NNN interaction is to be included.« less

  7. NR4A3, a possibile oncogenic factor for neuroblastoma associated with CpGi methylation within the third exon

    PubMed Central

    UEKUSA, SHOTA; KAWASHIMA, HIROYUKI; SUGITO, KIMINOBU; YOSHIZAWA, SHINSUKE; SHINOJIMA, YUI; IGARASHI, JUN; GHOSH, SRIMOYEE; WANG, XAOFEI; FUJIWARA, KYOKO; IKEDA, TARO; KOSHINAGA, TSUGUMICHI; SOMA, MASAYOSHI; NAGASE, HIROKI

    2014-01-01

    Aberrant methylation of Nr4a3 exon 3 CpG island (CpGi) was initially identified during multistep mouse skin carcinogenesis. Nr4a3 is also known as a critical gene for neuronal development. Thus, we examined the Nr4a3 exon 3 CpGi methylation in mouse brain tissues from 15-day embryos, newborns and 12-week-old adults and found significant increase of its methylation and Nr4a3 expression during mouse brain development after birth. In addition, homologous region in human genome was frequently and aberrantly methylated in neuroblastoma specimens. A quantitative analysis of DNA methylation revealed that hypomethylation of CpG islands on NR4A3 exon 3, but not on exon 1 was identified in three neuroblastomas compared with matched adrenal glands. Additional analysis for 20 neuroblastoma patients was performed and 8 of 20 showed hypomethylation of the CpGi on NR4A3 exon 3. The survival rate of those 8 patients was significantly lower compared with those in patients with hypermethylation. Immunohistochemical NR4A3 expression was generally faint in neuroblastoma tissues compared with normal tissues. Moreover, the MYCN amplified NB9 cell line showed hypomethylation and low expression of NR4A3, while the non-MYCN amplified NB69 cell line showed hypermethylation and high expression. These results indicate that DNA hypomethylation of the CpGi at NR4A3 exon 3 is associated with low NR4A3 expression, and correlates with poor prognosis of neuroblastoma. Since NR4A3 upregulation associated with the hypermethylation and neuronal differentiation in mice, poor prognosis of neuroblastoma associated with NR4A3 low expression may be partly explained by dysregulation of its differentiation. PMID:24626568

  8. Boeing F3B-1

    NASA Technical Reports Server (NTRS)

    1930-01-01

    Boeing F3B-1: While most Boeing F3B-1s served aboard the U. S. Navy aircraft carriers Lexington and Saratoga, this example flew in NACA hands at the Langley Memorial Aeronautical Laboratory in the late 1920's. Also known as the Boeing Model 77, the aircraft was powered by a Pratt & Whitney Wasp radial engine.

  9. ARID3B Directly Regulates Ovarian Cancer Promoting Genes

    PubMed Central

    Bobbs, Alexander; Gellerman, Katrina; Hallas, William Morgan; Joseph, Stancy; Yang, Chao; Kurkewich, Jeffrey; Cowden Dahl, Karen D.

    2015-01-01

    The DNA-binding protein AT-Rich Interactive Domain 3B (ARID3B) is elevated in ovarian cancer and increases tumor growth in a xenograft model of ovarian cancer. However, relatively little is known about ARID3B's function. In this study we perform the first genome wide screen for ARID3B direct target genes and ARID3B regulated pathways. We identified and confirmed numerous ARID3B target genes by chromatin immunoprecipitation (ChIP) followed by microarray and quantitative RT-PCR. Using motif-finding algorithms, we characterized a binding site for ARID3B, which is similar to the previously known site for the ARID3B paralogue ARID3A. Functionality of this predicted site was demonstrated by ChIP analysis. We next demonstrated that ARID3B induces expression of its targets in ovarian cancer cell lines. We validated that ARID3B binds to an epidermal growth factor receptor (EGFR) enhancer and increases mRNA expression. ARID3B also binds to the promoter of Wnt5A and its receptor FZD5. FZD5 is highly expressed in ovarian cancer cell lines, and is upregulated by exogenous ARID3B. Both ARID3B and FZD5 expression increase adhesion to extracellular matrix (ECM) components including collagen IV, fibronectin and vitronectin. ARID3B-increased adhesion to collagens II and IV require FZD5. This study directly demonstrates that ARID3B binds target genes in a sequence-specific manner, resulting in increased gene expression. Furthermore, our data indicate that ARID3B regulation of direct target genes in the Wnt pathway promotes adhesion of ovarian cancer cells. PMID:26121572

  10. The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparit...

  11. Coriolis Interactions in the nu2, nu4a, nu4b, and nu3a States of Phosphine-d1

    PubMed

    Kshirsagar; Job

    1997-10-01

    Spectra of the nu4a (HPH bend) and nu4b (HPD bend) bands of the PH2D molecule have been recorded and analyzed. The Coriolis interactions between the two states as well as the various Coriolis interactions of the nu4a and nu4b states with the nu2 state have been included in the analysis. Several new assignments of transitions which occur with enhanced intensity in the nu2 band also have been made. The parameters of the nu4a and nu4b states, improved parameters of the nu2 state, and the interaction parameters have been determined. The data on the nu3a band of PH2D have been reanalyzed by taking into account the b-axis Coriolis interaction of the nu3a state with the 2nu2 state. Copyright 1997 Academic Press. Copyright 1997Academic Press

  12. Arid3b Is Critical for B Lymphocyte Development.

    PubMed

    Kurkewich, Jeffrey L; Klopfenstein, Nathan; Hallas, William M; Wood, Christian; Sattler, Rachel A; Das, Chhaya; Tucker, Haley; Dahl, Richard; Cowden Dahl, Karen D

    2016-01-01

    Arid3a and Arid3b belong to a subfamily of ARID (AT-rich interaction domain) transcription factors. The Arid family is involved in regulating chromatin accessibility, proliferation, and differentiation. Arid3a and Arid3b are closely related and share a unique REKLES domain that mediates their homo- and hetero-multimerization. Arid3a was originally isolated as a B cell transcription factor binding to the AT rich matrix attachment regions (MARS) of the immunoglobulin heavy chain intronic enhancer. Deletion of Arid3a results in a highly penetrant embryonic lethality with severe defects in erythropoiesis and hematopoietic stem cells (HSCs). The few surviving Arid3a-/- (<1%) animals have decreased HSCs and early progenitors in the bone marrow, but all mature lineages are normally represented in the bone marrow and periphery except for B cells. Arid3b-/- animals die around E7.5 precluding examination of hematopoietic development. So it is unclear whether the phenotype of Arid3a loss on hematopoiesis is dependent or independent of Arid3b. In this study we circumvented this limitation by also examining hematopoiesis in mice with a conditional allele of Arid3b. Bone marrow lacking Arid3b shows decreased common lymphoid progenitors (CLPs) and downstream B cell populations while the T cell and myeloid lineages are unchanged, reminiscent of the adult hematopoietic defect in Arid3a mice. Unlike Arid3a-/- mice, HSC populations are unperturbed in Arid3b-/- mice. This study demonstrates that HSC development is independent of Arid3b, whereas B cell development requires both Arid3a and Arid3b transcription factors. PMID:27537840

  13. Arid3b Is Critical for B Lymphocyte Development

    PubMed Central

    Kurkewich, Jeffrey L.; Klopfenstein, Nathan; Hallas, William M.; Wood, Christian; Sattler, Rachel A.; Das, Chhaya; Tucker, Haley; Dahl, Richard; Cowden Dahl, Karen D.

    2016-01-01

    Arid3a and Arid3b belong to a subfamily of ARID (AT-rich interaction domain) transcription factors. The Arid family is involved in regulating chromatin accessibility, proliferation, and differentiation. Arid3a and Arid3b are closely related and share a unique REKLES domain that mediates their homo- and hetero-multimerization. Arid3a was originally isolated as a B cell transcription factor binding to the AT rich matrix attachment regions (MARS) of the immunoglobulin heavy chain intronic enhancer. Deletion of Arid3a results in a highly penetrant embryonic lethality with severe defects in erythropoiesis and hematopoietic stem cells (HSCs). The few surviving Arid3a-/- (<1%) animals have decreased HSCs and early progenitors in the bone marrow, but all mature lineages are normally represented in the bone marrow and periphery except for B cells. Arid3b-/- animals die around E7.5 precluding examination of hematopoietic development. So it is unclear whether the phenotype of Arid3a loss on hematopoiesis is dependent or independent of Arid3b. In this study we circumvented this limitation by also examining hematopoiesis in mice with a conditional allele of Arid3b. Bone marrow lacking Arid3b shows decreased common lymphoid progenitors (CLPs) and downstream B cell populations while the T cell and myeloid lineages are unchanged, reminiscent of the adult hematopoietic defect in Arid3a mice. Unlike Arid3a-/- mice, HSC populations are unperturbed in Arid3b-/- mice. This study demonstrates that HSC development is independent of Arid3b, whereas B cell development requires both Arid3a and Arid3b transcription factors. PMID:27537840

  14. 18 CFR 3b.201 - Content of records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... required to be accomplished by statute or by executive order of the President. Pursuant to § 3b.3(a)(4) of..., freedom of speech and of the press, and freedom of assembly and petition. In determining whether or not...

  15. 18 CFR 3b.201 - Content of records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... required to be accomplished by statute or by executive order of the President. Pursuant to § 3b.3(a)(4) of..., freedom of speech and of the press, and freedom of assembly and petition. In determining whether or not...

  16. 18 CFR 3b.201 - Content of records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... required to be accomplished by statute or by executive order of the President. Pursuant to § 3b.3(a)(4) of..., freedom of speech and of the press, and freedom of assembly and petition. In determining whether or not...

  17. 18 CFR 3b.201 - Content of records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... required to be accomplished by statute or by executive order of the President. Pursuant to § 3b.3(a)(4) of..., freedom of speech and of the press, and freedom of assembly and petition. In determining whether or not...

  18. P3b, consciousness, and complex unconscious processing.

    PubMed

    Silverstein, Brian H; Snodgrass, Michael; Shevrin, Howard; Kushwaha, Ramesh

    2015-12-01

    How can perceptual consciousness be indexed in humans? Recent work with ERPs suggests that P3b, a relatively late component, may be a neural correlate of consciousness (NCC). This proposal dovetails with currently prevailing cognitive theory regarding the nature of conscious versus unconscious processes, which holds that the latter are simple and very brief, whereas consciousness is ostensibly required for more durable, complex cognitive processing. Using a P3b oddball paradigm, we instead show that P3b and even later, related slow wave activity occur under rigorously subliminal conditions. Additional principal component analysis (PCA) further differentiated the presence of both P3a and P3b components, demonstrating that the latter indeed occurred subliminally. Collectively, our results suggest that complex, sustained cognitive processing can occur unconsciously and that P3b is not an NCC after all.

  19. Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men.

    PubMed

    Delgado-Lista, Javier; Perez-Jimenez, Francisco; Ruano, Juan; Perez-Martinez, Pablo; Fuentes, Francisco; Criado-Garcia, Juan; Parnell, Laurence D; Garcia-Rios, Antonio; Ordovas, Jose M; Lopez-Miranda, Jose

    2010-01-01

    The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.

  20. 18 CFR 3b.4 - Government contractors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Government contractors. 3b.4 Section 3b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... PERSONAL INFORMATION General § 3b.4 Government contractors. Systems of records operated by a...

  1. 18 CFR 3b.4 - Government contractors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Government contractors. 3b.4 Section 3b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... PERSONAL INFORMATION General § 3b.4 Government contractors. Systems of records operated by a...

  2. 18 CFR 3b.4 - Government contractors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Government contractors. 3b.4 Section 3b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... PERSONAL INFORMATION General § 3b.4 Government contractors. Systems of records operated by a...

  3. 18 CFR 3b.4 - Government contractors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Government contractors. 3b.4 Section 3b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... PERSONAL INFORMATION General § 3b.4 Government contractors. Systems of records operated by a...

  4. 18 CFR 3b.4 - Government contractors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Government contractors. 3b.4 Section 3b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... PERSONAL INFORMATION General § 3b.4 Government contractors. Systems of records operated by a...

  5. Protection against cocaine toxicity in mice by the dopamine D3/D2 agonist R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol [(+)-PD 128,907].

    PubMed

    Witkin, J M; Dijkstra, D; Levant, B; Akunne, H C; Zapata, A; Peters, S; Shannon, H E; Gasior, M

    2004-03-01

    Cocaine abuse is a public health concern with seizures and death being one consequence of overdose. In the present study, dopamine D(3/)D(2) receptor agonists dose dependently and completely prevented the convulsant and lethal effects of cocaine. The D(3)-preferring agonists R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) [(+)-PD 128,907], (+)-7-hydroxy-dipropylaminotetralin, and the mixed D(3/)D(2) agonists quinpirole and quinelorane were all effective against cocaine toxicity in mice. The anticonvulsant effects of these compounds occurred at doses below those that produced motor impairment as assessed in the inverted screen test. Protection against the convulsant effects of the selective dopamine uptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy] ethyl]-4-[3-phenyl-propyl]piperazine (GBR 12909) was also conferred by (+)-PD 128,907. The possible selectivity of the effects of (+)-PD 128,907 (3 mg/kg) for these dopaminergic compounds was demonstrated by its general lack of protective efficacy against a host of convulsants acting through other neural mechanisms [pentylenetetrazol, (+)-bicuculline, and picrotoxin, 4-aminopyridine, and t-butylbiclyclophosphoorothionate, N-methyl-d-aspartate, kainate, pilocarpine, nicotine, strychnine, aminophylline, threshold electric shock, and 6-Hz electrical stimulation]. Direct and correlational evidence suggests that these effects were mediated by D(3) receptors. Protection was stereospecific and reversible by an antagonist of D(3) receptors [3-[4[1-(4-[2[4-(3-diethyamino-propoxy)-phenyl]-benzoimidazol-l-yl]-butyl)-1H-benzoimidazol-2-yl]-phenoxy]-propyl)-diethyl-amine; PD 58491] but not D(2) receptors [3[[4-(4-chlorophenyl)-4 hydroxypipeidin-1-yl]methyl-1H-indole; L-741,626]. Anticonvulsant potencies were positively associated with potencies in a functional assay of D(3) but not D(2) receptor function. Together, these findings suggest that the prevention of cocaine convulsions and lethality by

  6. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons.

    PubMed

    Wang, Qian-fei; Liu, Xin; O'Connell, Jeff; Peng, Ze; Krauss, Ronald M; Rainwater, David L; VandeBerg, John L; Rubin, Edward M; Cheng, Jan-Fang; Pennacchio, Len A

    2004-05-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well-established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well-characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL-cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human quantitative trait loci genes in a highly controlled non-human primate model.

  7. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    SciTech Connect

    Wang, Qian-fei; Liu, Xin; O'Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  8. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... finger or voice print or a photograph; (e) System of records means a group of any records under...

  9. 18 CFR 3b.222 - Identification requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... identification, the system manager will require a signed statement from the individual asserting his identity and... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Identification requirements. 3b.222 Section 3b.222 Conservation of Power and Water Resources FEDERAL ENERGY...

  10. 18 CFR 3b.222 - Identification requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Identification requirements. 3b.222 Section 3b.222 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS...

  11. 18 CFR 3b.227 - Mailing lists.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Mailing lists. 3b.227 Section 3b.227 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  12. 18 CFR 3b.223 - Fees.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Fees. 3b.223 Section 3b.223 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  13. 18 CFR 3b.5 - Legal guardians.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Legal guardians. 3b.5 Section 3b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  14. 18 CFR 3b.250 - Specific exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Specific exemptions. 3b.250 Section 3b.250 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  15. 18 CFR 3b.250 - Specific exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Specific exemptions. 3b.250 Section 3b.250 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  16. 18 CFR 3b.250 - Specific exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Specific exemptions. 3b.250 Section 3b.250 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  17. 18 CFR 3b.227 - Mailing lists.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Mailing lists. 3b.227 Section 3b.227 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  18. 18 CFR 3b.250 - Specific exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Specific exemptions. 3b.250 Section 3b.250 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  19. 18 CFR 3b.5 - Legal guardians.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Legal guardians. 3b.5 Section 3b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  20. 18 CFR 3b.5 - Legal guardians.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Legal guardians. 3b.5 Section 3b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  1. 18 CFR 3b.5 - Legal guardians.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Legal guardians. 3b.5 Section 3b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  2. 18 CFR 3b.223 - Fees.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Fees. 3b.223 Section 3b.223 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  3. 18 CFR 3b.223 - Fees.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Fees. 3b.223 Section 3b.223 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  4. 18 CFR 3b.222 - Identification requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Identification requirements. 3b.222 Section 3b.222 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS...

  5. 18 CFR 3b.223 - Fees.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Fees. 3b.223 Section 3b.223 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  6. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  7. 18 CFR 3b.223 - Fees.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Fees. 3b.223 Section 3b.223 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  8. 18 CFR 3b.5 - Legal guardians.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Legal guardians. 3b.5 Section 3b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  9. 18 CFR 3b.222 - Identification requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Identification requirements. 3b.222 Section 3b.222 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS...

  10. 18 CFR 3b.227 - Mailing lists.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Mailing lists. 3b.227 Section 3b.227 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  11. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  12. 18 CFR 3b.3 - Notice requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Notice requirements. 3b.3 Section 3b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  13. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  14. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  15. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  16. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  17. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  18. 18 CFR 3b.3 - Notice requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Notice requirements. 3b.3 Section 3b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  19. 18 CFR 3b.3 - Notice requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Notice requirements. 3b.3 Section 3b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  20. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  1. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  2. 18 CFR 3b.3 - Notice requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Notice requirements. 3b.3 Section 3b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  3. 18 CFR 3b.227 - Mailing lists.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Mailing lists. 3b.227 Section 3b.227 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... specifically authorized by law. This provision shall not be construed to require the withholding of names...

  4. 18 CFR 3b.227 - Mailing lists.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Mailing lists. 3b.227 Section 3b.227 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... specifically authorized by law. This provision shall not be construed to require the withholding of names...

  5. Isolation of eukaryotic ribosomal proteins. Purification and characterization of the 40 S ribosomal subunit proteins Sa, Sc, S3a, S3b, S5', S9, S10, S11, S12, S14, S15, S15', S16, S17, S18, S19, S20, S21, S26, S27', and S29.

    PubMed

    Collatz, E; Ulbrich, N; Tsurugi, K; Lightfoot, H N; MacKinlay, W; Lin, A; Wool, I G

    1977-12-25

    The proteins of the small subunit of rat liver ribosomes were separated into five main groups by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5. Twenty-one proteins (Sa, Sc, S3a, S3b, S5', S9, S10, S11, S12, S14, S15, S15', S16, S17, S18, S19, S20, S21, S26, S27', and S29) were isolated from three groups (A40, C40, and D40) by ion exchange chromatography on DEAE-cellulose, carboxymethylcellulose, and phosphocellulose and by filtration through Sephadex. The amount of protein obtained varied from 0.1 to 11 mg. Six of the proteins (S5', S10, S11, S18, S19, and S27') had no detectable contamination; the impurities in the others were no greater than 9%. The molecular weight of the proteins was estimated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the amino acid composition was determined.

  6. Molecular basis of the attenuated phenotype of human APOBEC3B DNA mutator enzyme.

    PubMed

    Caval, Vincent; Bouzidi, Mohamed S; Suspène, Rodolphe; Laude, Hélène; Dumargne, Marie-Charlotte; Bashamboo, Anu; Krey, Thomas; Vartanian, Jean-Pierre; Wain-Hobson, Simon

    2015-10-30

    The human APOBEC3A and APOBEC3B genes (A3A and A3B) encode DNA mutator enzymes that deaminate cytidine and 5-methylcytidine residues in single-stranded DNA (ssDNA). They are important sources of mutations in many cancer genomes which show a preponderance of CG->TA transitions. Although both enzymes can hypermutate chromosomal DNA in an experimental setting, only A3A can induce double strand DNA breaks, even though the catalytic domains of A3B and A3A differ by only 9% at the protein level. Accordingly we sought the molecular basis underlying A3B attenuation through the generation of A3A-A3B chimeras and mutants. It transpires that the N-terminal domain facilitates A3B activity while a handful of substitutions in the catalytic C-terminal domain impacting ssDNA binding serve to attenuate A3B compared to A3A. Interestingly, functional attenuation is also observed for the rhesus monkey rhA3B enzyme compared to rhA3A indicating that this genotoxic dichotomy has been selected for and maintained for some 38 million years. Expression of all human ssDNA cytidine deaminase genes is absent in mature sperm indicating they contribute to somatic mutation and cancer but not human diversity.

  7. Molecular basis of the attenuated phenotype of human APOBEC3B DNA mutator enzyme

    PubMed Central

    Caval, Vincent; Bouzidi, Mohamed S.; Suspène, Rodolphe; Laude, Hélène; Dumargne, Marie-Charlotte; Bashamboo, Anu; Krey, Thomas; Vartanian, Jean-Pierre; Wain-Hobson, Simon

    2015-01-01

    The human APOBEC3A and APOBEC3B genes (A3A and A3B) encode DNA mutator enzymes that deaminate cytidine and 5-methylcytidine residues in single-stranded DNA (ssDNA). They are important sources of mutations in many cancer genomes which show a preponderance of CG->TA transitions. Although both enzymes can hypermutate chromosomal DNA in an experimental setting, only A3A can induce double strand DNA breaks, even though the catalytic domains of A3B and A3A differ by only 9% at the protein level. Accordingly we sought the molecular basis underlying A3B attenuation through the generation of A3A-A3B chimeras and mutants. It transpires that the N-terminal domain facilitates A3B activity while a handful of substitutions in the catalytic C-terminal domain impacting ssDNA binding serve to attenuate A3B compared to A3A. Interestingly, functional attenuation is also observed for the rhesus monkey rhA3B enzyme compared to rhA3A indicating that this genotoxic dichotomy has been selected for and maintained for some 38 million years. Expression of all human ssDNA cytidine deaminase genes is absent in mature sperm indicating they contribute to somatic mutation and cancer but not human diversity. PMID:26384561

  8. 75 FR 28188 - Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ...-42-AD; Amendment 39-16144; AD 2009-26-09] RIN 2120-AA64 Airworthiness Directives; General Electric... (AD) 2009-26-09, which published in the Federal Register. That AD applies to General Electric Company... 7, 2010 (75 FR 910), we published a final rule AD, FR Doc, E9-30471, in the Federal Register....

  9. Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis.

    PubMed

    Robaina, Marcela C; Mazzoccoli, Luciano; Arruda, Viviane Oliveira; Reis, Flaviana Ruade de Souza; Apa, Alexandre Gustavo; de Rezende, Lidia Maria Magalhães; Klumb, Claudete Esteves

    2015-04-01

    Methylation of CpG islands in promoter gene regions is frequently observed in lymphomas. DNA methylation is established by DNA methyltransferases (DNMTs). DNMT1 maintains methylation patterns, while DNMT3A and DNMT3B are critical for de novo DNA methylation. Little is known about the expression of DNMTs in lymphomas. DNMT3A and 3B genes can be regulated post-transcriptionally by miR-29 family. Here, we demonstrated for the first time the overexpression of DNMT1 and DNMT3B in Burkitt lymphoma (BL) tumor samples (69% and 86%, respectively). Specifically, the treatment of two BL cell lines with the DNMT inhibitor 5-aza-dC decreased DNMT1 and DNMT3B protein levels and inhibited cell growth. Additionally, miR-29a, miR-29b and miR-29c levels were significantly decreased in the BL tumor samples. Besides, the ectopic expression of miR-29a, miR-29b and miR-29c reduced the DNMT3B expression and miR-29a and miR-29b lead to increase of p16(INK4a) mRNA expression. Altogether, our data suggest that deregulation of DNMT1, DNMT3B and miR29 may be involved in BL pathogenesis. PMID:25746661

  10. The Effect of microRNAs in the Regulation of Human CYP3A4: a Systematic Study using a Mathematical Model

    NASA Astrophysics Data System (ADS)

    Wei, Zhiyun; Jiang, Songshan; Zhang, Yiting; Wang, Xiaofei; Peng, Xueling; Meng, Chunjie; Liu, Yichen; Wang, Honglian; Guo, Luo; Qin, Shengying; He, Lin; Shao, Fengmin; Zhang, Lirong; Xing, Qinghe

    2014-03-01

    CYP3A4 metabolizes more than 50% of the drugs on the market. The large inter-individual differences of CYP3A4 expression may contribute to the variability of human drug responses. Post-transcriptional regulation of CYP3A4 is poorly understood, whereas transcriptional regulation has been studied much more thoroughly. In this study, we used multiple software programs to predict miRNAs that might bind to CYP3A4 and identified 112 potentially functional miRNAs. Then a luciferase reporter system was used to assess the effect of the overexpression of each potentially functional miRNA in HEK 293T cells. Fourteen miRNAs that significantly decreased reporter activity were measured in human liver samples (N = 27) as candidate miRNAs. To establish a more effective way to analyze in vivo data for miRNA candidates, the relationship between functional miRNA and target mRNA was modeled mathematically. Taking advantage of this model, we found that hsa-miR-577, hsa-miR-1, hsa-miR-532-3p and hsa-miR-627 could significantly downregulate the translation efficiency of CYP3A4 mRNA in liver. This study used in silico, in vitro and in vivo methods to progressively screen functional miRNAs for CYP3A4 and to enhance our understanding of molecular events underlying the large inter-individual differences of CYP3A4 expression in human populations.

  11. 18 CFR 3b.250 - Specific exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... PERSONAL INFORMATION Rules for Exemptions § 3b.250 Specific exemptions. Any system of records maintained by... identity of a confidential source who furnished the information to the Government under an express promise that his identity would be held in confidence, or, prior to September 27, 1975, under an...

  12. 18 CFR 3b.222 - Identification requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.222 Identification requirements. The... personal identifier if known to the individual. A comparison of the signatures of the requester and those in the record will be used to determine identity. (c) If the system manager determines that the...

  13. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    SciTech Connect

    Duangtum, Natapol; Junking, Mutita; Sawasdee, Nunghathai; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2011-09-16

    Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.

  14. Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells

    PubMed Central

    Tilston-Lünel, Andrew M.; Haley, Kathryn E.; Schlecht, Nicolas F.; Wang, Yanhua; Chatterton, Abigail L.D.; Moleirinho, Susana; Watson, Ailsa; Hundal, Harinder S.; Prystowsky, Michael B.; Gunn-Moore, Frank J.; Reynolds, Paul A.

    2016-01-01

    Crumbs 3 (CRB3) is a component of epithelial junctions, which has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion, and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, we describe novel data demonstrating that, as with previous studies on CRB3a, CRB3b also promotes the formation of tight junctions (TJs). However, significantly we demonstrate that the 4.1-ezrin–radixin–moesin-binding motif of CRB3b is required for CRB3b functionality and that ezrin binds to the FBM of CRB3b. Furthermore, we show that ezrin contributes to CRB3b functionality and the correct distribution of TJ proteins. We demonstrate that both CRB3 isoforms are required for the production of functionally mature TJs and also the localization of ezrin to the plasma membrane. Finally, we demonstrate that reduced CRB3b expression in head and neck squamous cell carcinoma (HNSCC) correlates with cytoplasmic ezrin, a biomarker for aggressive disease, and shows evidence that while CRB3a expression has no effect, low CRB3b and high cytoplasmic ezrin expression combined may be prognostic for HNSCC. PMID:27190314

  15. Potentiation of NK cytotoxicity by antibody-C3b/iC3b heteroconjugates.

    PubMed

    Yefenof, E; Benizri, R; Reiter, Y; Klein, E; Fishelson, Z

    1990-02-15

    The interaction of two Burkitt lymphoma lines, Raji and Rael, with human C and NK cells was analyzed. Raji cells activate the alternative C pathway (ACP) and then bind C3 fragments. Consequently, the cells become more sensitive to lysis by CR3-bearing NK cells but not to C lysis. In contrast, Rael cells are poor ACP activators, do not bind C3 fragments, and are therefore resistant to C-dependent NK lysis. As suggested earlier, the difference between Raji and Rael could be attributed to the presence or absence of CR2, respectively, on their surface. To potentiate C- and NK-dependent lysis of target cells, we generated heteroconjugates composed of a murine antitransferrin receptor mAb and of human C C3b or iC3b. Antibody-C3b conjugates induced C3 deposition on Rael cells and elevated C3 deposition on Raji cells in human serum. Both Raji and Rael cells coated with antibody-C3b conjugates were efficiently lyzed by the cytolytic ACP in human serum. This conjugate had a small enhancing effect on target cell lysis by NK cells which could be markedly increased by combined treatment of the target cell with antibody-C3b conjugate and C5-depleted human serum. On the other hand, antibody-iC3b conjugates efficiently potentiated lysis of target cells by NK cells in the absence of serum. The iC3b-directed cytotoxicity was mediated by CR3-bearing NK effector cells. Anti-C3 but not anti-mouse Ig antibodies abrogated the activity of the antibody-iC3b conjugate. These results further demonstrate that NK cytotoxicity may be potentiated by opsonizing the target cells with C3 fragments and suggest that antibody-C3b/iC3b conjugates could be potent tools for targeting and potentiation of the lytic action of both C and NK cells against tumor cells.

  16. Potentiation of NK cytotoxicity by antibody-C3b/iC3b heteroconjugates.

    PubMed

    Yefenof, E; Benizri, R; Reiter, Y; Klein, E; Fishelson, Z

    1990-02-15

    The interaction of two Burkitt lymphoma lines, Raji and Rael, with human C and NK cells was analyzed. Raji cells activate the alternative C pathway (ACP) and then bind C3 fragments. Consequently, the cells become more sensitive to lysis by CR3-bearing NK cells but not to C lysis. In contrast, Rael cells are poor ACP activators, do not bind C3 fragments, and are therefore resistant to C-dependent NK lysis. As suggested earlier, the difference between Raji and Rael could be attributed to the presence or absence of CR2, respectively, on their surface. To potentiate C- and NK-dependent lysis of target cells, we generated heteroconjugates composed of a murine antitransferrin receptor mAb and of human C C3b or iC3b. Antibody-C3b conjugates induced C3 deposition on Rael cells and elevated C3 deposition on Raji cells in human serum. Both Raji and Rael cells coated with antibody-C3b conjugates were efficiently lyzed by the cytolytic ACP in human serum. This conjugate had a small enhancing effect on target cell lysis by NK cells which could be markedly increased by combined treatment of the target cell with antibody-C3b conjugate and C5-depleted human serum. On the other hand, antibody-iC3b conjugates efficiently potentiated lysis of target cells by NK cells in the absence of serum. The iC3b-directed cytotoxicity was mediated by CR3-bearing NK effector cells. Anti-C3 but not anti-mouse Ig antibodies abrogated the activity of the antibody-iC3b conjugate. These results further demonstrate that NK cytotoxicity may be potentiated by opsonizing the target cells with C3 fragments and suggest that antibody-C3b/iC3b conjugates could be potent tools for targeting and potentiation of the lytic action of both C and NK cells against tumor cells. PMID:2303717

  17. Critical role of ARID3B in the expression of pro-apoptotic p53-target genes and apoptosis.

    PubMed

    Pratama, Endrawan; Tian, Xiaohui; Lestari, Widya; Iseki, Sachiko; Ichwan, Solachuddin J A; Ikeda, Masa-Aki

    ARID3A and ARID3B are transcriptional targets of p53. Recently, it has been reported that ARID3A plays a critical role in the transcriptional activation of pro-arrest p21 in response to DNA damage. However, the role of ARID3B in the p53 regulatory pathway remains poorly understood. Here we show that ARID3A and ARID3B specifically bind to putative ARID3-binding sites in p53 target genes in vitro and in vivo. ARID3B and, to a lesser extent, ARID3A silencing blocked transcriptional activation of pro-apoptotic p53 target genes, such as PUMA, PIG3, and p53. Furthermore, ectopic ARID3B, to a lesser extent, ARID3A expression activated the pro-apoptotic gene expression, and only ARID3B induced apoptosis. Finally, ARID3B but not ARID3A silencing blocked apoptosis induction following DNA damage. These results indicated that, although ARID3B and ARID3A share overlapping functions, ARID3B play a key role in the expression of pro-apoptotic p53-target genes and apoptosis.

  18. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B).

    PubMed

    Duangtum, Natapol; Junking, Mutita; Sawasdee, Nunghathai; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2011-09-16

    Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of α-intercalated cells of the kidney collecting duct leads to the defect of the Cl(-)/HCO(3)(-) exchange and the failure of proton (H(+)) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney α-intercalated cells. PMID:21871436

  19. Fabrication and luminescence properties of one-dimensional ZnAl{sub 2}O{sub 4} and ZnAl{sub 2}O{sub 4}: A{sup 3+} (A = Cr, Eu, Tb) microfibers by electrospinning method

    SciTech Connect

    Peng, Chong; Li, Guogang; Geng, Dongling; Shang, Mengmeng; Hou, Zhiyao; Lin, Jun

    2012-11-15

    Graphical abstract: Different color emission can be realized in one-dimensional ZnAl{sub 2}O{sub 4}: A{sup 3+} (A = Cr, Eu, Tb) microfibers fabricated by electronspinning method by changing the doping ions. Highlights: ► ZnAl{sub 2}O{sub 4}: A{sup 3+} (A = Cr, Eu, Tb) microfibers were obtained by electronspinning method. ► Luminescence properties were due to the transitions of Cr{sup 3+}, Eu{sup 3+} and Tb{sup 3+} ions. ► A new band was observed around 600 nm in CL spectra of ZnAl{sub 2}O{sub 4}: Cr{sup 3+} microfibers. -- Abstract: One-dimensional ZnAl{sub 2}O{sub 4} and ZnAl{sub 2}O{sub 4}: A{sup 3+} (A = Cr, Eu, Tb) microfibers were fabricated by electrospinning method. X-ray diffraction pattern confirmed that the fibers were composed of the cubic ZnAl{sub 2}O{sub 4} phase. Scanning electron microscopy and transmission electron microscopy results indicated that the ZnAl{sub 2}O{sub 4} microfibers annealed at 1000 °C were composed of some smaller nanoparticles and the diameters of the microfibers were in the range of 140–230 nm. Under the excitation of ultraviolet and low-voltage electron beams (3–5 kV), the ZnAl{sub 2}O{sub 4}: A{sup 3+} (A = Cr, Eu, Tb) samples showed the emission of the host and the doping ions. The evolution of the optical properties of microfibers with increasing the doping concentration was investigated in detail. Green and red emissions can be realized in ZnAl{sub 2}O{sub 4} microfibers by changing the doping ions. The ZnAl{sub 2}O{sub 4}: A{sup 3+} (A = Cr, Eu, Tb) microfibers have potential applications in full-color field emission displays.

  20. Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus.

    PubMed

    Sahu, Maitrayee; Sahu, Abhiram

    2015-11-01

    Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. Cumulative evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways including the phosphodiesterase-3B (PDE3B) pathway mediate leptin signaling in the hypothalamus. We have shown that PDE3B is localized in various hypothalamic sites implicated in the regulation of energy homeostasis and that the anorectic and body weight reducing effects of leptin are mediated by the activation of PDE3B. It is still unknown if PDE3B is expressed in the long form of the leptin-receptor (ObRb)-expressing neurons in the hypothalamus and whether leptin induces STAT3 activation in PDE3B-expressing neurons. In this study, we examined co-localization of PDE3B with ObRb neurons in various hypothalamic nuclei in ObRb-GFP mice that were treated with leptin (5mg/kg, ip) for 2h. Results showed that most of the ObRb neurons in the arcuate nucleus (ARC, 93%), ventromedial nucleus (VMN, 94%), dorsomedial nucleus (DMN, 95%), ventral premammillary nucleus (PMv, 97%) and lateral hypothalamus (LH, 97%) co-expressed PDE3B. We next examined co-localization of p-STAT3 and PDE3B in the hypothalamus in C57BL6 mice that were treated with leptin (5mg/kg, ip) for 1h. The results showed that almost all p-STAT3 positive neurons in different hypothalamic nuclei including ARC, VMN, DMN, LH and PMv areas expressed PDE3B. These results suggest the possibility for a direct role for the PDE3B pathway in mediating leptin action in the hypothalamus.

  1. Development of a new fluorescent probe: 1,3,5,7-tetramethyl-8-(4'-aminophenyl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacence for the determination of trace nitrite.

    PubMed

    Li, Mengling; Wang, Hong; Zhang, Xian; Zhang, Hua-Shan

    2004-03-01

    A new fluorescent probe, 1,3,5,7-tetramethyl-8-(4'-aminophenyl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacence (TMABODIPY) has been developed for the determination of trace nitrite in terms of the reaction of nitrite with TMABODIPY first in acidic solution and then in alkaline solution to form diazotate, a stable and highly fluorescent reagent. The method offered the advantage of specificity, sensitivity and simplicity. The linear calibration range for nitrite was 8-300 nmol l-1s with a 3 sigma detection limit of 0.65 nmol l-1. The proposed method has been applied to monitor the trace nitrite in drinking water and vegetable without extraction.

  2. Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma

    PubMed Central

    Ostler, Kelly R.; Yang, Qiwei; Looney, Timothy J.; Zhang, Li; Vasanthakumar, Aparna; Tian, Yufeng; Kocherginsky, Masha; Raimondi, Stacey L.; DeMaio, Jessica G.; Salwen, Helen R.; Gu, Song; Chlenski, Alexandre; Naranjo, Arlene; Gill, Amy; Peddinti, Radhika; Lahn, Bruce T.; Cohn, Susan L.; Godley, Lucy A.

    2012-01-01

    Epigenetic changes in pediatric neuroblastoma may contribute to the aggressive pathophysiology of this disease, but little is known about the basis for such changes. In this study, we examined a role for the DNA methyltransferase DNMT3B, in particular, the truncated isoform DNMT3B7 which is generated frequently in cancer. To investigate if aberrant DNMT3B transcripts alter DNA methylation, gene expression, and phenotypic character in neuroblastoma, we measured DNMT3B expression in primary tumors. Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas, suggesting that expression of DNMT3B7 may induce a less aggressive clinical phenotype. To test this hypothesis, we investigated the effects of enforced DNMT3B7 expression in neuroblastoma cells, finding a significant inhibition of cell proliferation in vitro and angiogenesis and tumor growth in vivo. DNMT3B7-positive cells had higher levels of total genomic methylation and a dramatic decrease in expression of the FOS and JUN family members that comprise AP1 transcription factors. Consistent with an established antagonistic relationship between AP1 expression and retinoic acid receptor activity, increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all-trans retinoic acid (ATRA) compared to controls. Our results indicate that DNMT3B7 modifies the epigenome in neuroblastoma cells to induce changes in gene expression, inhibit tumor growth, and increase sensitivity to ATRA. PMID:22815530

  3. DNMT3B7, a truncated DNMT3B isoform expressed in human tumors, disrupts embryonic development and accelerates lymphomagenesis

    PubMed Central

    Shah, Mrinal Y.; Vasanthakumar, Aparna; Barnes, Natalie Y.; Figueroa, Maria E.; Kamp, Anna; Hendrick, Christopher; Ostler, Kelly R.; Davis, Elizabeth M.; Lin, Shang; Anastasi, John; Le Beau, Michelle M.; Moskowitz, Ivan; Melnick, Ari; Pytel, Peter; Godley, Lucy A.

    2010-01-01

    Epigenetic changes are among the most common alterations observed in cancer cells, yet the mechanism by which cancer cells acquire and maintain abnormal DNA methylation patterns is not understood. Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins, some of which lack the C-terminal catalytic domain. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed two lines of transgenic mice expressing DNMT3B7, a truncated DNMT3B isoform commonly found in cancer cells. DNMT3B7 transgenic mice exhibit altered embryonic development, including lymphopenia, craniofacial abnormalities, and cardiac defects, similar to Dnmt3b-deficient animals, but rarely develop cancer. However, when DNMT3B7 transgenic are bred with Eμ-Myc transgenic mice, which model aggressive B cell lymphoma, DNMT3B7 expression increases the frequency of mediastinal lymphomas in Eμ-Myc animals. Eμ-Myc/DNMT3B7 mediastinal lymphomas have more chromosomal rearrangements, increased global DNA methylation levels, and more locus-specific perturbations in DNA methylation patterns compared to Eμ-Myc lymphomas. These data represent the first in vivo modeling of cancer-associated DNA methylation changes and suggest that truncated DNMT3B isoforms contribute to the re-distribution of DNA methylation characterizing virtually every human tumor. PMID:20587527

  4. DNMT3B7, a truncated DNMT3B isoform expressed in human tumors, disrupts embryonic development and accelerates lymphomagenesis.

    PubMed

    Shah, Mrinal Y; Vasanthakumar, Aparna; Barnes, Natalie Y; Figueroa, Maria E; Kamp, Anna; Hendrick, Christopher; Ostler, Kelly R; Davis, Elizabeth M; Lin, Shang; Anastasi, John; Le Beau, Michelle M; Moskowitz, Ivan P; Melnick, Ari; Pytel, Peter; Godley, Lucy A

    2010-07-15

    Epigenetic changes are among the most common alterations observed in cancer cells, yet the mechanism by which cancer cells acquire and maintain abnormal DNA methylation patterns is not understood. Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins, some of which lack the COOH-terminal catalytic domain. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed two lines of transgenic mice expressing DNMT3B7, a truncated DNMT3B isoform commonly found in cancer cells. DNMT3B7 transgenic mice exhibit altered embryonic development, including lymphopenia, craniofacial abnormalities, and cardiac defects, similar to Dnmt3b-deficient animals, but rarely develop cancer. However, when DNMT3B7 transgenic mice are bred with Emicro-Myc transgenic mice, which model aggressive B-cell lymphoma, DNMT3B7 expression increases the frequency of mediastinal lymphomas in Emicro-Myc animals. Emicro-Myc/DNMT3B7 mediastinal lymphomas have more chromosomal rearrangements, increased global DNA methylation levels, and more locus-specific perturbations in DNA methylation patterns compared with Emicro-Myc lymphomas. These data represent the first in vivo modeling of cancer-associated DNA methylation changes and suggest that truncated DNMT3B isoforms contribute to the redistribution of DNA methylation characterizing virtually every human tumor.

  5. Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy.

    PubMed

    Gutierrez, Mariana; Thiffault, Isabelle; Guerrero, Kether; Martos-Moreno, Gabriel Á; Tran, Luan T; Benko, William; van der Knaap, Marjo S; van Spaendonk, Rosalina M L; Wolf, Nicole I; Bernard, Geneviève

    2015-06-05

    POLR3-related (or 4H) leukodystrophy is an autosomal recessive disorder caused by mutations in POLR3A or POLR3B and is characterized by neurological and non-neurological features. In a small proportion of patients, no mutation in either gene or only one mutation is found. Analysis of the POLR3B cDNA revealed a large deletion of exons 21-22 in one case and of exons 26-27 in another case. These are the first reports of long deletions causing POLR3-related leukodystrophy, suggesting that deletions and duplications in POLR3A or POLR3B should be investigated in patients with a compatible phenotype, especially if one pathogenic variant has been identified.

  6. Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue

    PubMed Central

    Ahmad, Faiyaz; Chung, Youn Wook; Tang, Yan; Hockman, Steven C.; Liu, Shiwei; Khan, Yusuf; Huo, Kevin; Billings, Eric; Amar, Marcelo J.; Remaley, Alan T.; Manganiello, Vincent C.

    2016-01-01

    Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion of WAT macrophages, contributes pathogenesis of obesity, insulin resistance, and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 and the adaptor ASC. Inflammasome activation leads to maturation of caspase-1 and processing of IL1β, contributing to many metabolic disorders and directing adipocytes to a more insulin-resistant phenotype. Ablation of PDE3B in WAT prevents inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNFα, IL1β and proinflammatory genes. Following IP injection of lipopolysaccharide (LPS), serum levels of IL1β and TNFα were reduced in PDE3B−/−mice compared to WT. Activation of signaling cascades, which mediate inflammasome responses, were modulated in PDE3B−/−mice WAT, including smad, NFAT, NFkB, and MAP kinases. Moreover, expression of chemokine CCL2, MCP-1 and its receptor CCR2, which play an important role in macrophage chemotaxis, were reduced in WAT of PDE3B−/−mice. In addition, atherosclerotic plaque formation was significantly reduced in the aorta of apoE−/−/PDE3B−/−and LDL-R−/−/PDE3B−/−mice compared to apoE−/−and LDL-R−/−mice, respectively. Obesity-induced changes in serum-cholesterol were blocked in PDE3B−/−mice. Collectively, these data establish a role for PDE3B in modulating inflammatory response, which may contribute to a reduced inflammatory state in adipose tissue. PMID:27321128

  7. Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b.

    PubMed

    Yang, Xiaosong; Wang, Xianfeng; Liu, Dongxu; Yu, Liqing; Xue, Bingzhong; Shi, Hang

    2014-04-01

    Adipose tissue macrophages (ATMs) undergo a phenotypic switch from alternatively activated antiinflammatory M2 macrophages in lean individuals to classically activated proinflammatory M1 macrophages in obese subjects. However, the molecular mechanism underlying this process remains unclear. In this study we aim to determine whether DNA methyltransferase 3b (DNMT3b) regulates macrophage polarization and inflammation. We found that the expression of DNMT3b was significantly induced in macrophages exposed to the saturated fatty acid stearate, was higher in ATMs isolated from obese mice, but was significantly lower in alternatively activated M2 vs classically activated M1 ATMs, suggesting a role for DNMT3b in regulation of macrophage polarization and inflammation in obesity. DNMT3b knockdown promoted macrophage polarization to alternatively activated M2 phenotype and suppressed macrophage inflammation, whereas overexpressing DNMT3b did the opposite. Importantly, in a macrophage-adipocyte coculture system, we found that DNMT3b knockdown significantly improved adipocyte insulin signaling. The promoter of peroxisome proliferator activated receptor (PPAR)γ1, a key transcriptional factor that regulates macrophage polarization, is enriched with CpG sites. Chromatin immunoprecipitation assays showed that DNMT3b bound to the methylation region at PPARγ1 promoter, which was further enhanced by stearate. Moreover, pyrosequencing analysis revealed that stearate increased DNA methylation at PPARγ1, which was prevented by DNMT3b deficiency. Therefore, our data demonstrate that DNMT3b plays an important role in regulating macrophage polarization through epigenetic mechanisms. In obesity, elevated saturated fatty acids enhance DNMT3b expression, leading to DNA methylation at the PPARγ1 promoter, which may contribute to deregulated adipose tissue macrophage polarization, inflammation, and insulin resistance.

  8. Synthesis, characterization, and crystal structure of a new trisodium triborate, Na(3)[B(3)O(4)(OH)(4)].

    PubMed

    Andrieux, Jérôme; Goutaudier, Christelle; Laversenne, Laetitia; Jeanneau, Erwann; Miele, Philippe

    2010-06-01

    The preparation of a new trisodium triborate, Na(3)[B(3)O(4)(OH)(4)], and its complete characterization in terms of molecular structure and thermal behavior are reported. Synthesis of this compound was achieved either by NaBH(4) hydrolysis or by thermal treatment of Na[B(OH)(4)].2H(2)O. The crystal structure was determined by single-crystal X-ray diffraction. The trisodium triborate crystallized in the monoclinic system (a = 12.8274(6) A, b = 7.7276(4) A, c = 6.9690(3) A, and beta = 98.161(3) degrees ), space group Cc, Z = 2. The structure of Na(3)[B(3)O(4)(OH)(4)] comprised [B(3)O(4)(OH)(4)](3-) polyanions, based on B-O-containing rings with two tetracoordinated boron atoms and one tricoordinated boron atom in the fragments BO(2)(OH)(2) and BO(3), respectively. These polyanions are interconnected by four intermolecular hydrogen bonds and presented a tilt of 10.470(4) degrees compared to the a axis. Thus, they are stacked by rotation of about 180 degrees around an axis defined by the three-coordinated boron atoms and parallel to the c axis. Such polyanions were only observed previously in two synthetic compounds, M(3)[B(3)O(4)(OH)(4)].2H(2)O with M = K and Rb, which were isostructural. The originality of the present work was the synthesis and the description of a different crystallographic structure containing this polyanion. Characteristic peaks ranging from 500 to 1500 cm(-1) and around 3300 cm(-1) highlighted the presence of the B-O rings and hydroxyl groups, respectively. The decomposition temperature T = 155 degrees C was obtained by thermogravimetric analysis, and the following equivalent formula in terms of hydration degree was proposed: NaBO(2).(2)/(3)H(2)O. Na(3)[B(3)O(4)(OH)(4)] decomposed into Na(3)[B(3)O(5)(OH)(2)] in equilibrium with its vapor. PMID:20450165

  9. 18 CFR 3b.225 - Written consent for disclosure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Written consent for disclosure. 3b.225 Section 3b.225 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... United States for a civil or criminal law enforcement activity if the activity is authorized by law,...

  10. 18 CFR 3b.225 - Written consent for disclosure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Written consent for disclosure. 3b.225 Section 3b.225 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... United States for a civil or criminal law enforcement activity if the activity is authorized by law,...

  11. 18 CFR 3b.226 - Accounting of disclosures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Accounting of disclosures. 3b.226 Section 3b.226 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS...

  12. 18 CFR 3b.226 - Accounting of disclosures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Accounting of disclosures. 3b.226 Section 3b.226 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS...

  13. 18 CFR 3b.203 - Rules of conduct.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Rules of conduct. 3b.203 Section 3b.203 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  14. 18 CFR 3b.203 - Rules of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Rules of conduct. 3b.203 Section 3b.203 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  15. 18 CFR 3b.203 - Rules of conduct.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Rules of conduct. 3b.203 Section 3b.203 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  16. 18 CFR 3b.203 - Rules of conduct.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Rules of conduct. 3b.203 Section 3b.203 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  17. 18 CFR 3b.226 - Accounting of disclosures.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Accounting of disclosures. 3b.226 Section 3b.226 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS...

  18. 18 CFR 3b.203 - Rules of conduct.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Rules of conduct. 3b.203 Section 3b.203 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  19. 27 CFR 21.36 - Formula No. 3-B.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and Authorized Uses § 21.36 Formula No. 3-B. (a) Formula. To every 100 gallons of alcohol add: One gallon of pine tar, U.S.P. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations. 141... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Formula No. 3-B....

  20. 27 CFR 21.36 - Formula No. 3-B.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and Authorized Uses § 21.36 Formula No. 3-B. (a) Formula. To every 100 gallons of alcohol add: One gallon of pine tar, U.S.P. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations. 141... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Formula No. 3-B....

  1. 27 CFR 21.36 - Formula No. 3-B.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and Authorized Uses § 21.36 Formula No. 3-B. (a) Formula. To every 100 gallons of alcohol add: One gallon of pine tar, U.S.P. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations. 141... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Formula No. 3-B....

  2. 27 CFR 21.36 - Formula No. 3-B.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and Authorized Uses § 21.36 Formula No. 3-B. (a) Formula. To every 100 gallons of alcohol add: One gallon of pine tar, U.S.P. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations. 141... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Formula No. 3-B....

  3. 27 CFR 21.36 - Formula No. 3-B.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Authorized Uses § 21.36 Formula No. 3-B. (a) Formula. To every 100 gallons of alcohol add: One gallon of pine tar, U.S.P. (b) Authorized uses. (1) As a solvent: 111.Hair and scalp preparations. 141... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula No. 3-B....

  4. Knock-out mutations of Arabidopsis SmD3-b induce pleotropic phenotypes through altered transcript splicing.

    PubMed

    Swaraz, A M; Park, Young-Doo; Hur, Yoonkang

    2011-05-01

    SmD3 is a core protein of small nuclear ribonucleoprotein (snRNP) essential for splicing of primary transcripts. To elucidate function of SmD3 protein in plants, phenotypes and gene expression of SmD3 knock-out and overexpressing mutants in Arabidopsis have been analyzed. smd3-a knock-out mutant or SmD3-a and SmD3-b overexpressors did not show phenotypic alteration. Knock-out of SmD3-b resulted in the pleotropic phenotypes of delayed flowering time and completion of life cycle, reduced root growth, partially defective leaf venation, abnormal numbers of trichome branches, and changed numbers of floral organs. Microarray data revealed that the smd3-b mutant had altered expression of genes related to the above phenotypes, indirectly suggesting that changed splicing of these genes may cause the observed phenotypes. Splicing of selected genes was either totally blocked or reduced in the smd3-b mutant, indicating the important role of SmD3-b in the process. A double knock-out mutant of smd3-a and smd3-b could not be generated, indicating possible redundant function of these two genes. All data indicate that SmD3-b may be major component of the spliceosomal snRNP in Arabidopsis, but the function of SmD3-a may be redundant.

  5. Alloantibodies to glycoprotein La/LLa (anti-HPA-5a and -5b) and IIb/IIIa (anti-HPA1a, -3a and -4a) in Nigerian parous women.

    PubMed

    Jeremiah, Z A; Oburu, J E; Erhabor, O; Buseri, F I

    2011-01-01

    Human platelet antibodies are often implicated in conditions such as neonatal alloimmune thrombocytopenia (NAIT), idiopathic thrombocytopenic purpura (ITP) and platelet refractoriness; however, the frequency of such alloantibodies has not been reported in Nigeria and West Africa. A cross section of apparently healthy adult female staff at a tertiary health facility in the Niger Delta, Nigeria, was screened for alloantibodies to human platelet antigens (HPA) using the GTI PakPlus qualitative solid-phase enzyme-linked immunosorbent assay (ELISA) method. Among the 100 women screened, no anti-glycoprotein IIb/IIIa (anti-HPA-Ia,-3a and -4a) antibodies were detected; however, prevalence of anti-glycoprotein Ia/IIa (anti-HPA-5b) was 30% and pf anti-glycoprotein Ia/IIa (anti-HPA-5a) was 18%. Parity had a significant influence on the development to HPA antibodies (Fisher's Exact test: 11.683, P < 0.05; 13.577, P < 0.01). Platelet count did not have an influence on the development of antibodies (P > 0.05). Clearly, there is need to initiate platelet serology in this setting and also a need to educate women about the risk associated with frequent pregnancies. Furthermore, caution should be exercised when recruiting parous women as blood donors

  6. PROCEEDINGS: 1993 SO2 CONTROL SYMPOSIUM - VOLUME 1. SESSIONS 1, 2, 3A, AND 3B

    EPA Science Inventory

    The report documents more than 100 presentations at the 1993 SO2 Control Symposium in Boston, MA, August 24-27, 1993. The presentations covered a wide range of topics: industry's strategies for dealing with Clean Air Act Amendments of 1990, including Phase I strategies, the emiss...

  7. BOREAS Level-3b Landsat TM Imagery: At-sensor Radiances in BSQ Format

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

    For BOREAS, the level-3b Landsat TM data, along with the other remotely sensed images, were collected in order to provide spatially extensive information over the primary study areas. This information includes radiant energy, detailed land cover, and biophysical parameter maps such as FPAR and LAI. Although very similar in content to the level-3a Landsat TM products, the level-3b images were created to provide users with a directly usable at-sensor radiance image. Geographically, the level-3b images cover the BOREAS NSA and SSA. Temporally, the images cover the period of 22-Jun-1984 to 09-Jul-1996. The images are available in binary, image format files.

  8. Molecular characterization of a KIF3B-like kinesin gene in the testis of Octopus tankahkeei (Cephalopoda, Octopus).

    PubMed

    Dang, Ran; Zhu, Jun-Quan; Tan, Fu-Qing; Wang, Wei; Zhou, Hong; Yang, Wan-Xi

    2012-05-01

    KIF3B is known for maintaining and assembling cilia and flagellum. To date, the function of KIF3B and its relationship with KIF3A during spermiogenesis in the cephalopod Octopus tankahkeei remains unknown. In the present study, we characterized a gene encoding a homologue of rat KIF3B in the O. tankahkeei testis and examined its temporal and spatial expression pattern during spermiogenesis. The cDNA of KIF3B was obtained with degenerate and RACE PCR and the distribution pattern of ot-kif3b were observed with RT-PCR. The morphological development during spermiogenesis was illustrated by histological and transmission electron microscopy and mRNA expression of ot-kif3b was observed by in situ hybridization. The 2,365 nucleotides cDNA consisted of a 102 bp 5' untranslated region (UTR), a 2,208 bp open reading frame (ORF) encoding a protein of 736 amino acids, and a 55 bp 3' UTR. Multiple alignments revealed that the putative Ot-KIF3B shared 68, 68, 69, 68, and 67% identity with that of Homo sapiens, Mus musculus, Gallus gallus, Danio rerio, and Xenopus laevis, respectively, along with high identities with Ot-KIF3A in fundamental structures. Ot-kif3b transcripts appeared gradually in early spermatids, increased in intermediate spermatids and maximized in drastically remodeled and final spermatids. The kif3b gene is identified and its expression pattern is demonstrated for the first time in O. tankahkeei. Compared to ot-kif3a reported by our laboratory before, our data suggested that the putative heterodimeric motor proteins Ot-KIF3A/B may be involved in intraspermatic transport and might contribute to structural changes during spermiogenesis.

  9. Dynamic expression of transcription factor Brn3b during mouse cranial nerve development.

    PubMed

    Sajgo, Szilard; Ali, Seid; Popescu, Octavian; Badea, Tudor Constantin

    2016-04-01

    During development, transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors but rather emerge through the intersection of their expression domains. Brn3a, Brn3b, and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of retinal ganglion cells (RGC), spiral and vestibular ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the dorsal root ganglia. The present study investigates the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII, and VIII and visceromotor nuclei of nerves VII, IX, and X as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3b(KO) RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However, loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor.

  10. DNA cytosine and methylcytosine deamination by APOBEC3B: enhancing methylcytosine deamination by engineering APOBEC3B

    PubMed Central

    Fu, Yang; Ito, Fumiaki; Zhang, Gewen; Fernandez, Braulio; Yang, Hanjing; Chen, Xiaojiang S.

    2015-01-01

    APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like) is a family of enzymes that deaminates cytosine (C) to uracil (U) on nucleic acid. APOBEC3B (A3B) functions in innate immunity against intrinsic and invading retroelements and viruses. A3B can also induce genomic DNA mutations to cause cancer. A3B contains two cytosine deaminase domains (CD1, CD2), and there are conflicting reports about whether both domains are active. Here we demonstrate that only CD2 of A3B (A3BCD2) has C deamination activity. We also reveal that both A3B and A3BCD2 can deaminate methylcytosine (mC). Guided by structural and functional analysis, we successfully engineered A3BCD2 to gain over two orders of magnitude higher activity for mC deamination. Important determinants that contribute to the activity and selectivity for mC deamination have been identified, which reveals that multiple elements, rather than single ones, contribute to the mC deamination activity and selectivity in A3BCD2 and possibly other APOBECs. PMID:26195824

  11. Validation of FY-3B MWRI Rain Rate over China

    NASA Astrophysics Data System (ADS)

    Xu, B.; Jiang, L.; Shi, C.; Xie, P.; You, R.

    2012-12-01

    As part of the collaboration between China Meteorological Administration (CMA) National Meteorological Information Centre (NMIC) and NOAA Climate Prediction Center (CPC), a new system is being developed to construct half hourly satellite precipitation estimate on a 0.05olat/lon grid over China by combining NOAA series, DMSP series, and CMA FY-3B Polar Microwave rain rate with TMI rain rate. Foundation to the development of the PMW rain rate combining algorithm is the validation of those passive microwave (PMW) - based rain rate retrievals. Since FY-3B is new and not included as inputs to CMORPH, and other established high-resolution satellite precipitation products, we focus our work here on the validation and error quantification of the FY-3B PMW rain rate retrievals. This is done by comparisons with the combined PMW product (MWCOMB) of NOAA/CPC and against a gauge-based analysis of hourly precipitation over China derived from gauge reports of dense station networks. Overall, the monthly mean rain rate distribution of FY-3B agrees very well with MWCOMB except for a little under-estimate over ocean. In the latitudinal profiles, we can see a very close agreement between the FY-3B retrievals and the MWCOMB over land, but there is an obvious general under estimates over ocean. Pattern correlation between FY-3B and MWCOMB is relatively high over both land and ocean. From more works on PDF check of 30-min precipitation, over a 0.25 degree grid, we can clearly see FY3B presents lower PDF for weak precipitation, especially over ocean and reasonable agreements in PDF over land. A gauge-based analysis of hourly precipitation derived from over 30000 station reports is used to validate FY-3B PMW rain rate. In order to compare, 7 PMW rain rate of different satellite, including TMI, NOAA-18, NOAA-19, Metop-A, DMSP-S16, DMSP-S17, DMSP-S18, are also compared with the gauge-based analysis. FY-3B's bias is a little higher than NOAA-18 over whole China, western China and eastern

  12. Crystal structure of inactive form of Rab3B

    SciTech Connect

    Zhang, Wei; Shen, Yang; Jiao, Ronghong; Liu, Yanli; Deng, Lingfu; Qi, Chao

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer This is the first structural information of human Rab3B. Black-Right-Pointing-Pointer To provides a structural basis for the GDP/GTP switch in controlling the activity of Rab3. Black-Right-Pointing-Pointer The charge distribution of Rab3B indicates its unique roles in vesicular trafficking. -- Abstract: Rab proteins are the largest family of ras-related GTPases in eukaryotic cells. They act as directional molecular switches at membrane trafficking, including vesicle budding, cargo sorting, transport, tethering, and fusion. Here, we generated and crystallized the Rab3B:GDP complex. The structure of the complex was solved to 1.9 A resolution and the structural base comparison with other Rab3 members provides a structural basis for the GDP/GTP switch in controlling the activity of small GTPase. The comparison of charge distribution among the members of Rab3 also indicates their different roles in vesicular trafficking.

  13. Transcriptional repression of Sin3B by Bmi-1 prevents cellular senescence and is relieved by oncogene activation

    PubMed Central

    Bainor, Anthony J.; David, Gregory

    2014-01-01

    The Polycomb group protein Bmi-1 is an essential regulator of cellular senescence and is believed to function largely through the direct repression of the Ink4a/Arf locus. However, concurrent deletion of Ink4a/Arf does not fully rescue the defects detected in Bmi-1−/− mice, indicating that additional Bmi-1 targets remain to be identified. The expression of the chromatin associated Sin3B protein is stimulated by oncogenic stress, and is required for oncogene-induced senescence. Here we demonstrate that oncogenic stress leads to the dissociation of Bmi-1 from the Sin3B locus, resulting in increased Sin3B expression and subsequent entry into cellular senescence. Furthermore, Sin3B is required for the senescent phenotype and elevated levels of reactive oxygen species elicited upon Bmi-1 depletion. Altogether, these results identify Sin3B as a novel direct target of Bmi-1, and establish Bmi-1-driven repression of Sin3B as an essential regulator of cellular senescence. PMID:25263442

  14. Detector production for the R3B Si-tracker

    NASA Astrophysics Data System (ADS)

    Borri, M.; Lemmon, R.; Thornhill, J.; Bate, R.; Chartier, M.; Clague, N.; Herzberg, R.-D.; Labiche, M.; Lindsay, S.; Nolan, P.; Pearce, F.; Powell, W.; Wells, D.

    2016-11-01

    R3B is a fixed target experiment which will study reactions with relativistic radioactive beams at FAIR. Its Si-tracker will surround the target volume and it will detect light charged-particles like protons. The detector technology in use consists of double-sided silicon strip sensors wire bonded to the custom made R3B-ASIC. The tracker allows for a maximum of two outer layers and one inner layer. This paper reports on the production of detectors necessary to build the minimum tracking configuration: one inner layer and one outer layer.

  15. Retinoic acid negatively regulates dact3b expression in the hindbrain of zebrafish embryos

    PubMed Central

    Mandal, Amrita; Waxman, Joshua

    2014-01-01

    Wnt signaling plays important roles in normal development as well as pathophysiological conditions. The Dapper antagonist of β-catenin (Dact) proteins are modulators of both canonical and non-canonical Wnt signaling via direct interactions with Dishevelled (Dvl) and Van Gogh like-2 (Vangl2). Here, we report the dynamic expression patterns of two zebrafish dact3 paralogs during early embryonic development. Our whole mount in situ hybridization (WISH) analysis indicates that specific dact3a expression starts by the tailbud stage in adaxial cells. Later, it is expressed in the anterior lateral plate mesoderm, somites, migrating cranial neural crest, and hindbrain neurons. By comparison, dact3b expression initiates on the dorsal side at the dome stage and soon after is expressed in the dorsal forerunner cells (DFCs) during gastrulation. At later stages, dact3b expression becomes restricted to the branchial neurons of the hindbrain and to the 2nd pharyngeal arch. To investigate how zebrafish dact3 gene expression is regulated, we manipulated retinoic acid (RA) signaling during development and found it negatively regulates dact3b in the hindbrain. Our study is the first to document the expression of the paralogous zebrafish dact3 genes during early development and demonstrate dact3b can be regulated by RA signaling. Therefore, our study opens up new avenues to study Dact3 function in the development of multiple tissues and suggests a previously unappreciated cross regulation of Wnt signaling by RA signaling in the developing vertebrate hindbrain. PMID:25266145

  16. Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and human embryonic stem cells.

    PubMed

    Wissing, Silke; Montano, Mauricio; Garcia-Perez, Jose Luis; Moran, John V; Greene, Warner C

    2011-10-21

    Members of the APOBEC3 (A3) family of cytidine deaminase enzymes act as host defense mechanisms limiting both infections by exogenous retroviruses and mobilization of endogenous retrotransposons. Previous studies revealed that the overexpression of some A3 proteins could restrict engineered human Long INterspersed Element-1 (LINE-1 or L1) retrotransposition in HeLa cells. However, whether endogenous A3 proteins play a role in restricting L1 retrotransposition remains largely unexplored. Here, we show that HeLa cells express endogenous A3B and A3C, whereas human embryonic stem cells (hESCs) express A3B, A3C, A3DE, A3F, and A3G. To study the relative contribution of endogenous A3 proteins in restricting L1 retrotransposition, we first generated small hairpin RNAs (shRNAs) to suppress endogenous A3 mRNA expression, and then assessed L1 mobility using a cell-based L1 retrotransposition assay. We demonstrate that in both HeLa and hESCs, shRNA-based knockdown of A3B promotes a ∼2-3.7-fold increase in the retrotransposition efficiency of an engineered human L1. Knockdown of the other A3s produced no significant increase in L1 activity. Thus, A3B appears to restrict engineered L1 retrotransposition in a broad range of cell types, including pluripotent cells.

  17. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect

    Lerch, Thomas F.; Chapman, Michael S.

    2012-02-05

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  18. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect

    Lerch, Thomas F.; Chapman, Michael S.

    2012-05-24

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  19. 18 CFR 3b.225 - Written consent for disclosure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Written consent for... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.225 Written consent for disclosure. (a... communication to any person, or to any other agency, unless it has the written request by, or the prior...

  20. 18 CFR 3b.225 - Written consent for disclosure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Written consent for... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.225 Written consent for disclosure. (a... communication to any person, or to any other agency, unless it has the written request by, or the prior...

  1. 18 CFR 3b.225 - Written consent for disclosure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Written consent for... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.225 Written consent for disclosure. (a... communication to any person, or to any other agency, unless it has the written request by, or the prior...

  2. 18 CFR 3b.226 - Accounting of disclosures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Accounting of... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.226 Accounting of disclosures. (a) The....225(b) (5) and (7). (b) Each system manager will retain the accounting made under paragraph (a)...

  3. 18 CFR 3b.226 - Accounting of disclosures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Accounting of... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.226 Accounting of disclosures. (a) The....225(b) (5) and (7). (b) Each system manager will retain the accounting made under paragraph (a)...

  4. The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer.

    PubMed

    Liu, Jingjing; Sieuwerts, Anieta M; Look, Maxime P; van der Vlugt-Daane, Michelle; Meijer-van Gelder, Marion E; Foekens, John A; Hollestelle, Antoinette; Martens, John W M

    2016-01-01

    Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and the hypermutator phenotype. Here we evaluated whether the APOBEC3B deletion polymorphism also associates with clinical outcome of breast cancer. Copy number analysis was performed by quantitative PCR (qPCR) in primary tumors of 1,756 Dutch breast cancer patients. The APOBEC3B deletion was found in 187 patients of whom 16 carried a two-copy deletion and 171 carried a one-copy deletion. The prognostic value of the APOBEC3B deletion for the natural course of the disease was evaluated among 1,076 lymph-node negative (LNN) patients who did not receive adjuvant systemic treatment. No association was found between APOBEC3B copy number values and the length of metastasis-free survival (MFS; hazard ratio (HR) = 1.00, 95% confidence interval (CI) = 0.90-1.11, P = 0.96). Subgroup analysis by ER status also did not reveal an association between APOBEC3B copy number values and the length of MFS. The predictive value of the APOBEC3B deletion was assessed among 329 ER-positive breast cancer patients who received tamoxifen as the first-line therapy for recurrent disease and 226 breast cancer patients who received first-line chemotherapy for recurrent disease. No association between APOBEC3B copy number values and the overall response rate (ORR) to either tamoxifen (odds ratio (OR) = 0.88, 95% CI = 0.69-1.13, P = 0.31) or chemotherapy (OR = 0.97, 95% CI = 0.71-1.33, P = 0.87) was found. Thus, in contrast to APOBEC3B mRNA levels, the APOBEC3B deletion polymorphism has neither a prognostic nor a predictive value for breast cancer patients. Although a correlation exists between APOBEC3B copy number and mRNA expression, it is relatively weak. This suggests that other mechanisms exist that may

  5. The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer

    PubMed Central

    Look, Maxime P.; van der Vlugt-Daane, Michelle; Meijer-van Gelder, Marion E.; Foekens, John A.; Martens, John W. M.

    2016-01-01

    Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and the hypermutator phenotype. Here we evaluated whether the APOBEC3B deletion polymorphism also associates with clinical outcome of breast cancer. Copy number analysis was performed by quantitative PCR (qPCR) in primary tumors of 1,756 Dutch breast cancer patients. The APOBEC3B deletion was found in 187 patients of whom 16 carried a two-copy deletion and 171 carried a one-copy deletion. The prognostic value of the APOBEC3B deletion for the natural course of the disease was evaluated among 1,076 lymph-node negative (LNN) patients who did not receive adjuvant systemic treatment. No association was found between APOBEC3B copy number values and the length of metastasis-free survival (MFS; hazard ratio (HR) = 1.00, 95% confidence interval (CI) = 0.90–1.11, P = 0.96). Subgroup analysis by ER status also did not reveal an association between APOBEC3B copy number values and the length of MFS. The predictive value of the APOBEC3B deletion was assessed among 329 ER-positive breast cancer patients who received tamoxifen as the first-line therapy for recurrent disease and 226 breast cancer patients who received first-line chemotherapy for recurrent disease. No association between APOBEC3B copy number values and the overall response rate (ORR) to either tamoxifen (odds ratio (OR) = 0.88, 95% CI = 0.69–1.13, P = 0.31) or chemotherapy (OR = 0.97, 95% CI = 0.71–1.33, P = 0.87) was found. Thus, in contrast to APOBEC3B mRNA levels, the APOBEC3B deletion polymorphism has neither a prognostic nor a predictive value for breast cancer patients. Although a correlation exists between APOBEC3B copy number and mRNA expression, it is relatively weak. This suggests that other mechanisms exist

  6. In vivo redundant function of the 3' IgH regulatory element HS3b in the mouse.

    PubMed

    Bébin, Anne-Gaëlle; Carrion, Claire; Marquet, Marie; Cogné, Nadine; Lecardeur, Sandrine; Cogné, Michel; Pinaud, Eric

    2010-04-01

    In the mouse, the regulatory region located at the 3' end of the IgH locus includes four transcriptional enhancers: HS3a, HS1-2, HS3b, and HS4; the first three lie in a quasi-palindromic structure. Although the upstream elements HS3a and HS1-2 proved dispensable for Ig expression and class switch recombination (CSR), the joint deletion of HS3b and HS4 led to a consistent decrease in IgH expression in resting B cells and to a major CSR defect. Within this pair of distal enhancers, it was questionable whether HS3b and HS4 could be considered individually as elements critical for IgH expression and/or CSR. Studies in HS4-deficient mice recently revealed the role of HS4 as restricted to Igmicro-chain expression from the pre-B to the mature B cell stage and left HS3b as the last candidate for CSR regulation. Our present study finally invalidates the hypothesis that CSR could mostly rely on HS3b itself. B cells from HS3b-deficient animals undergo normal proliferation, germline transcription, and CSR upon in vitro stimulation with LPS; in vivo Ag-specific responses are not affected. In conclusion, our study highlights a major effect of the global ambiance of the IgH locus; enhancers demonstrated as being strongly synergistic in transgenes turn out to be redundant in their endogenous context.

  7. Late Type 3b Endoleak with an Endurant Endograft

    PubMed Central

    Barburoglu, Mehmet; Acunas, Bulent; Onal, Yilmaz; Ugurlucan, Murat; Sayin, Omer Ali; Alpagut, Ufuk

    2015-01-01

    Endovascular stent grafting with different commercially available stent graft systems is widely applied for the treatment of abdominal aortic aneurysms with high success rates in the current era. Various types of endoleaks are potential complications of the procedure. They usually occur in the early period. In this report, we present type 3b endoleak occurring 14 months after a successful endovascular abdominal aortic aneurysm repair with a Medtronic Endurant stent graft. PMID:26798537

  8. APOSTLE: 11 TRANSIT OBSERVATIONS OF TrES-3b

    SciTech Connect

    Kundurthy, P.; Becker, A. C.; Agol, E.; Barnes, R.; Williams, B.

    2013-02-10

    The Apache Point Survey of Transit Lightcurves of Exoplanets (APOSTLE) observed 11 transits of TrES-3b over two years in order to constrain system parameters and look for transit timing and depth variations. We describe an updated analysis protocol for APOSTLE data, including the reduction pipeline, transit model, and Markov Chain Monte Carlo analyzer. Our estimates of the system parameters for TrES-3b are consistent with previous estimates to within the 2{sigma} confidence level. We improved the errors (by 10%-30%) on system parameters such as the orbital inclination (i {sub orb}), impact parameter (b), and stellar density ({rho}{sub *}) compared to previous measurements. The near-grazing nature of the system, and incomplete sampling of some transits, limited our ability to place reliable uncertainties on individual transit depths and hence we do not report strong evidence for variability. Our analysis of the transit timing data shows no evidence for transit timing variations and our timing measurements are able to rule out super-Earth and gas giant companions in low-order mean motion resonance with TrES-3b.

  9. Heterocyst-specific flavodiiron protein Flv3B enables oxic diazotrophic growth of the filamentous cyanobacterium Anabaena sp. PCC 7120

    PubMed Central

    Ermakova, Maria; Battchikova, Natalia; Richaud, Pierre; Leino, Hannu; Kosourov, Sergey; Isojärvi, Janne; Peltier, Gilles; Flores, Enrique; Cournac, Laurent; Allahverdiyeva, Yagut; Aro, Eva-Mari

    2014-01-01

    Flavodiiron proteins are known to have crucial and specific roles in photoprotection of photosystems I and II in cyanobacteria. The filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 contains, besides the four flavodiiron proteins Flv1A, Flv2, Flv3A, and Flv4 present in vegetative cells, two heterocyst-specific flavodiiron proteins, Flv1B and Flv3B. Here, we demonstrate that Flv3B is responsible for light-induced O2 uptake in heterocysts, and that the absence of the Flv3B protein severely compromises the growth of filaments in oxic, but not in microoxic, conditions. It is further demonstrated that Flv3B-mediated photosynthetic O2 uptake has a distinct role in heterocysts which cannot be substituted by respiratory O2 uptake in the protection of nitrogenase from oxidative damage and, thus, in an efficient provision of nitrogen to filaments. In line with this conclusion, the Δflv3B strain has reduced amounts of nitrogenase NifHDK subunits and shows multiple symptoms of nitrogen deficiency in the filaments. The apparent imbalance of cytosolic redox state in Δflv3B heterocysts also has a pronounced influence on the amounts of different transcripts and proteins. Therefore, an O2-related mechanism for control of gene expression is suggested to take place in heterocysts. PMID:25002499

  10. Heterocyst-specific flavodiiron protein Flv3B enables oxic diazotrophic growth of the filamentous cyanobacterium Anabaena sp. PCC 7120.

    PubMed

    Ermakova, Maria; Battchikova, Natalia; Richaud, Pierre; Leino, Hannu; Kosourov, Sergey; Isojärvi, Janne; Peltier, Gilles; Flores, Enrique; Cournac, Laurent; Allahverdiyeva, Yagut; Aro, Eva-Mari

    2014-07-29

    Flavodiiron proteins are known to have crucial and specific roles in photoprotection of photosystems I and II in cyanobacteria. The filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 contains, besides the four flavodiiron proteins Flv1A, Flv2, Flv3A, and Flv4 present in vegetative cells, two heterocyst-specific flavodiiron proteins, Flv1B and Flv3B. Here, we demonstrate that Flv3B is responsible for light-induced O2 uptake in heterocysts, and that the absence of the Flv3B protein severely compromises the growth of filaments in oxic, but not in microoxic, conditions. It is further demonstrated that Flv3B-mediated photosynthetic O2 uptake has a distinct role in heterocysts which cannot be substituted by respiratory O2 uptake in the protection of nitrogenase from oxidative damage and, thus, in an efficient provision of nitrogen to filaments. In line with this conclusion, the Δflv3B strain has reduced amounts of nitrogenase NifHDK subunits and shows multiple symptoms of nitrogen deficiency in the filaments. The apparent imbalance of cytosolic redox state in Δflv3B heterocysts also has a pronounced influence on the amounts of different transcripts and proteins. Therefore, an O2-related mechanism for control of gene expression is suggested to take place in heterocysts.

  11. Heterocyst-specific flavodiiron protein Flv3B enables oxic diazotrophic growth of the filamentous cyanobacterium Anabaena sp. PCC 7120.

    PubMed

    Ermakova, Maria; Battchikova, Natalia; Richaud, Pierre; Leino, Hannu; Kosourov, Sergey; Isojärvi, Janne; Peltier, Gilles; Flores, Enrique; Cournac, Laurent; Allahverdiyeva, Yagut; Aro, Eva-Mari

    2014-07-29

    Flavodiiron proteins are known to have crucial and specific roles in photoprotection of photosystems I and II in cyanobacteria. The filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 contains, besides the four flavodiiron proteins Flv1A, Flv2, Flv3A, and Flv4 present in vegetative cells, two heterocyst-specific flavodiiron proteins, Flv1B and Flv3B. Here, we demonstrate that Flv3B is responsible for light-induced O2 uptake in heterocysts, and that the absence of the Flv3B protein severely compromises the growth of filaments in oxic, but not in microoxic, conditions. It is further demonstrated that Flv3B-mediated photosynthetic O2 uptake has a distinct role in heterocysts which cannot be substituted by respiratory O2 uptake in the protection of nitrogenase from oxidative damage and, thus, in an efficient provision of nitrogen to filaments. In line with this conclusion, the Δflv3B strain has reduced amounts of nitrogenase NifHDK subunits and shows multiple symptoms of nitrogen deficiency in the filaments. The apparent imbalance of cytosolic redox state in Δflv3B heterocysts also has a pronounced influence on the amounts of different transcripts and proteins. Therefore, an O2-related mechanism for control of gene expression is suggested to take place in heterocysts. PMID:25002499

  12. Cortical Connections to Single Digit Representations in Area 3b of Somatosensory Cortex in Squirrel Monkeys and Prosimian Galagos

    PubMed Central

    Liao, Chia-Chi; Gharbawie, Omar A.; Qi, Huixin; Kaas, Jon H.

    2014-01-01

    The ventral posterior nucleus of thalamus sends highly segregated inputs into each digit representation in area 3b of primary somatosensory cortex. However, the spatial organization of the connections that link digit representations of areas 3b with other somatosensory areas is less understood. Here we examined the cortical inputs to individual digit representations of area 3b in four squirrel monkeys and one prosimian galago. Retrograde tracers were injected into neurophysiologically defined representations of individual digits of area 3b. Cortical tissues were cut parallel to the surface in some cases and showed that feedback projections to individual digits overlapped extensively in the hand representations of areas 3b, 1, and parietal ventral (PV) and second somatosensory (S2) areas. Other regions with overlapping populations of labeled cells included area 3a and primary motor cortex (M1). The results were confirmed in other cases in which the cortical tissues were cut in the coronal plane. The same cases also showed that cells were primarily labeled in the infragranular and supragranular layers. Thus, feedback projections to individual digit representations in area 3b mainly originate from multiple digits and other portions of hand representations of areas 3b, 1, PV, and S2. This organization is in stark contrast to the segregated thalamocortical inputs, which originate in single digit representations and terminate in the matching digit representation in the cortex. The organization of feedback connections could provide a substrate for the integration of information across the representations of adjacent digits in area 3b. PMID:23749740

  13. The Activation of Phytophthora Effector Avr3b by Plant Cyclophilin is Required for the Nudix Hydrolase Activity of Avr3b.

    PubMed

    Kong, Guanghui; Zhao, Yao; Jing, Maofeng; Huang, Jie; Yang, Jin; Xia, Yeqiang; Kong, Liang; Ye, Wenwu; Xiong, Qin; Qiao, Yongli; Dong, Suomeng; Ma, Wenbo; Wang, Yuanchao

    2015-08-01

    Plant pathogens secrete an arsenal of effector proteins to impair host immunity. Some effectors possess enzymatic activities that can modify their host targets. Previously, we demonstrated that a Phytophthora sojae RXLR effector Avr3b acts as a Nudix hydrolase when expressed in planta; and this enzymatic activity is required for full virulence of P. sojae strain P6497 in soybean (Glycine max). Interestingly, recombinant Avr3b produced by E. coli does not have the hydrolase activity unless it was incubated with plant protein extracts. Here, we report the activation of Avr3b by a prolyl-peptidyl isomerase (PPIase), cyclophilin, in plant cells. Avr3b directly interacts with soybean cyclophilin GmCYP1, which activates the hydrolase activity of Avr3b in a PPIase activity-dependent manner. Avr3b contains a putative Glycine-Proline (GP) motif; which is known to confer cyclophilin-binding in other protein substrates. Substitution of the Proline (P132) in the putative GP motif impaired the interaction of Avr3b with GmCYP1; as a result, the mutant Avr3bP132A can no longer be activated by GmCYP1, and is also unable to promote Phytophthora infection. Avr3b elicits hypersensitive response (HR) in soybean cultivars producing the resistance protein Rps3b, but Avr3bP132A lost its ability to trigger HR. Furthermore, silencing of GmCYP1 rendered reduced cell death triggered by Avr3b, suggesting that GmCYP1-mediated Avr3b maturation is also required for Rps3b recognition. Finally, cyclophilins of Nicotiana benthamiana can also interact with Avr3b and activate its enzymatic activity. Overall, our results demonstrate that cyclophilin is a "helper" that activates the enzymatic activity of Avr3b after it is delivered into plant cells; as such, cyclophilin is required for the avirulence and virulence functions of Avr3b.

  14. Identification of high-risk Listeria monocytogenes serotypes in lineage I (serotype 1/2a, 1/2c, 3a and 3c) using multiplex PCR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: Using molecular subtyping techniques, Listeria monocytogenes is divided into three major phylogenetic lineages, and a multiplex PCR method can differentiate five L. monocytogenes subgroups: 1/2a-3a, 1/2c-3c, 1/2b-3b-7, 4b-4d-4e, and 4a-4c. In the current study, we conducted genome comparison...

  15. Crystal structure of inactive form of Rab3B

    SciTech Connect

    Zhang, Wei; Shen, Yang; Jiao, Ronghong; Liu, Yanli; Deng, Lingfu; Qi, Chao

    2012-06-28

    Rab proteins are the largest family of ras-related GTPases in eukaryotic cells. They act as directional molecular switches at membrane trafficking, including vesicle budding, cargo sorting, transport, tethering, and fusion. Here, we generated and crystallized the Rab3B:GDP complex. The structure of the complex was solved to 1.9 {angstrom} resolution and the structural base comparison with other Rab3 members provides a structural basis for the GDP/GTP switch in controlling the activity of small GTPase. The comparison of charge distribution among the members of Rab3 also indicates their different roles in vesicular trafficking.

  16. SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis

    PubMed Central

    Sivaprasad, Umasundari; Kinker, Kayla G.; Ericksen, Mark B.; Lindsey, Mark; Gibson, Aaron M.; Bass, Stacey A.; Hershey, Nicolas S.; Deng, Jingyuan; Medvedovic, Mario; Khurana Hershey, Gurjit K.

    2014-01-01

    Serine proteases are critical for epidermal barrier homeostasis and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a null mice on transepidermal water loss (TEWL), sensitization and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression supporting a role for SERPINB3/B4 in initiation of the acute inflammatory response. RNA-Seq analysis following allergen exposure identified a network of pro-inflammatory genes induced in the wild type mice that was absent in the Serpinb3a null mice. In conclusion, Serpinb3a deficiency attenuates barrier dysfunction and the early inflammatory response following cutaneous allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4 (humans) early in atopic dermatitis. PMID:25111616

  17. Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

    PubMed

    Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

    2011-08-01

    Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.

  18. Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

    PubMed

    Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

    2011-08-01

    Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities. PMID:21788512

  19. Calculation of a BWR partial ATWS using RAMONA-3B

    SciTech Connect

    Garber, D.I.; Diamond, D.J.; Cheng, H.S.

    1982-01-01

    The RAMONA-3B code has been used to simulate a boiling water reactor (BWR) transient initiated by the closure of the main steam line isolation valves in which all the control rods in one-half the core fail to scram after reactor trip. The modeling of the nuclear steam supply system included three-dimensional neutron kinetics and parallel hydraulic channels (including a bypass channel). The transient is characterized by an initial pressure spike and then by oscillations in the pressure due to the opening and closing of relief valves. These oscillations in turn affect all thermohydraulic properties in the vessel. The simulation was continued for 7 minutes of reactor time at which point boron began to accumulate in the core. The calculation demonstrates the importance of using three-dimensional neutron kinetics in conjunction with the modeling of the nuclear steam supply system for this type of transient. RAMONA-3B is unique in its ability to do this type of calculation.

  20. 50 CFR Table 3b to Part 680 - Crab Disposition or Product Codes

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Crab Disposition or Product Codes 3b Table 3b to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... ZONE OFF ALASKA Pt. 680, Table 3b Table 3b to Part 680—Crab Disposition or Product Codes...

  1. 50 CFR Table 3b to Part 680 - Crab Disposition or Product Codes

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Crab Disposition or Product Codes 3b Table 3b to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... ZONE OFF ALASKA Pt. 680, Table 3b Table 3b to Part 680—Crab Disposition or Product Codes...

  2. 50 CFR Table 3b to Part 680 - Crab Disposition or Product Codes

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Crab Disposition or Product Codes 3b Table 3b to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... ZONE OFF ALASKA Pt. 680, Table 3b Table 3b to Part 680—Crab Disposition or Product Codes...

  3. 50 CFR Table 3b to Part 680 - Crab Disposition or Product Codes

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Crab Disposition or Product Codes 3b Table 3b to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... ZONE OFF ALASKA Pt. 680, Table 3b Table 3b to Part 680—Crab Disposition or Product Codes...

  4. 50 CFR Table 3b to Part 680 - Crab Disposition or Product Codes

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Crab Disposition or Product Codes 3b Table 3b to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... ZONE OFF ALASKA Pt. 680, Table 3b Table 3b to Part 680—Crab Disposition or Product Codes...

  5. Structural and functional partitioning of bread wheat chromosome 3B.

    PubMed

    Choulet, Frédéric; Alberti, Adriana; Theil, Sébastien; Glover, Natasha; Barbe, Valérie; Daron, Josquin; Pingault, Lise; Sourdille, Pierre; Couloux, Arnaud; Paux, Etienne; Leroy, Philippe; Mangenot, Sophie; Guilhot, Nicolas; Le Gouis, Jacques; Balfourier, Francois; Alaux, Michael; Jamilloux, Véronique; Poulain, Julie; Durand, Céline; Bellec, Arnaud; Gaspin, Christine; Safar, Jan; Dolezel, Jaroslav; Rogers, Jane; Vandepoele, Klaas; Aury, Jean-Marc; Mayer, Klaus; Berges, Hélène; Quesneville, Hadi; Wincker, Patrick; Feuillet, Catherine

    2014-07-18

    We produced a reference sequence of the 1-gigabase chromosome 3B of hexaploid bread wheat. By sequencing 8452 bacterial artificial chromosomes in pools, we assembled a sequence of 774 megabases carrying 5326 protein-coding genes, 1938 pseudogenes, and 85% of transposable elements. The distribution of structural and functional features along the chromosome revealed partitioning correlated with meiotic recombination. Comparative analyses indicated high wheat-specific inter- and intrachromosomal gene duplication activities that are potential sources of variability for adaption. In addition to providing a better understanding of the organization, function, and evolution of a large and polyploid genome, the availability of a high-quality sequence anchored to genetic maps will accelerate the identification of genes underlying important agronomic traits. PMID:25035497

  6. An Overview of the NASA P-3B Airborne Laboratory

    NASA Technical Reports Server (NTRS)

    Guillory, Anthony R.; Postell, George W.

    2009-01-01

    The National Aeronautics and Space Administration (NASA) Wallops Flight Facility (WFF) P-3B Orion is a medium-lift, four engine turbo-prop aircraft that has been reconfigured from a military aircraft to an Earth Science research platform. The aircraft has a long history of supporting science missions, flying on average over 200 hours per year. Examples of research missions that have been flown aboard the aircraft are remote sensing flights to study geophysical parameters including ice-sheet topography and periodic change, soil moisture content, atmospheric aerosol constituents, and beach erosion. Missions are conducted for the purposes of calibration/validation of various NASA and international satellites that monitor climate change as well as process studies and the test of new prototype remote sensing instruments. In recent y ears the focus has been on ice surveys of the Arctic and Antarctic, soil moisture research, and measurements of atmospheric chemistry and radiation sciences. The aircraft has been conducting ice surveys of Greenland since 1993 for the purposes of topographic mapping of both the surface and basal topography. Another application of the aircraft has been for soil moisture research. Research has also been conducted using microwave radiometers and radars over various agricultural and forest lands. Recently, a mission was flown in the spring over the High-Arctic to collect air samples of haze and boreal forest fires in an effort to determine anthropogenic amounts and sources of pollution. This pa per will provide an overview of the P-3B platform and highlight recent science missions.

  7. Complement fragments C3b and iC3b coupled to latex induce a respiratory burst in human neutrophils.

    PubMed

    Hoogerwerf, M; Weening, R S; Hack, C E; Roos, D

    1990-02-01

    The complement fragments C3b and iC3b were purified from human serum by affinity chromatography with Sepharose-coupled monoclonal antibody against the C3d region of C3. The resulting preparations were more than 95% pure and contained less than 0.1% native IgG. Purified C3b and iC3b were coupled to latex beads (0.8 micron diameter) by means of F(ab')2 fragments of monoclonal antibodies against the beta chain or the C3d region of C3, thus orienting the C3b and the iC3b on the latex with the C3b- and iC3b-specific regions outwards. These particles were found to activate the respiratory burst of freshly isolated human neutrophils to 20-30% of the maximal capacity. Latex particles randomly coated with C3b or iC3b were about 3 times less stimulatory. C3b, iC3b and IgG coupled to latex in an oriented fashion were about equally effective in stimulating the respiratory burst. Neutrophils from a patient with a total deficiency of CR3 responded normally to C3b-coated latex but did not respond to iC3b-coated latex. A monoclonal antibody against the alpha chain of CR3 inhibited the activation by iC3b-coated latex and a polyclonal antibody against CR1 partially inhibited the activation by C3b-coated latex. We found an additive effect between IgG-coated latex and C3b-coated latex, regardless of the presence of IgG and C3b on the same particle or on different particles. Thus, binding of ligands to either CR1 or CR3 per se is sufficient to induce an activating signal to the NADPH oxidase in human neutrophils.

  8. The Activation of Phytophthora Effector Avr3b by Plant Cyclophilin is Required for the Nudix Hydrolase Activity of Avr3b

    PubMed Central

    Kong, Guanghui; Zhao, Yao; Jing, Maofeng; Huang, Jie; Yang, Jin; Xia, Yeqiang; Kong, Liang; Ye, Wenwu; Xiong, Qin; Qiao, Yongli; Dong, Suomeng; Ma, Wenbo; Wang, Yuanchao

    2015-01-01

    Plant pathogens secrete an arsenal of effector proteins to impair host immunity. Some effectors possess enzymatic activities that can modify their host targets. Previously, we demonstrated that a Phytophthora sojae RXLR effector Avr3b acts as a Nudix hydrolase when expressed in planta; and this enzymatic activity is required for full virulence of P. sojae strain P6497 in soybean (Glycine max). Interestingly, recombinant Avr3b produced by E. coli does not have the hydrolase activity unless it was incubated with plant protein extracts. Here, we report the activation of Avr3b by a prolyl-peptidyl isomerase (PPIase), cyclophilin, in plant cells. Avr3b directly interacts with soybean cyclophilin GmCYP1, which activates the hydrolase activity of Avr3b in a PPIase activity-dependent manner. Avr3b contains a putative Glycine-Proline (GP) motif; which is known to confer cyclophilin-binding in other protein substrates. Substitution of the Proline (P132) in the putative GP motif impaired the interaction of Avr3b with GmCYP1; as a result, the mutant Avr3bP132A can no longer be activated by GmCYP1, and is also unable to promote Phytophthora infection. Avr3b elicits hypersensitive response (HR) in soybean cultivars producing the resistance protein Rps3b, but Avr3bP132A lost its ability to trigger HR. Furthermore, silencing of GmCYP1 rendered reduced cell death triggered by Avr3b, suggesting that GmCYP1-mediated Avr3b maturation is also required for Rps3b recognition. Finally, cyclophilins of Nicotiana benthamiana can also interact with Avr3b and activate its enzymatic activity. Overall, our results demonstrate that cyclophilin is a “helper” that activates the enzymatic activity of Avr3b after it is delivered into plant cells; as such, cyclophilin is required for the avirulence and virulence functions of Avr3b. PMID:26317500

  9. Transit timing variation in exoplanet WASP-3b

    NASA Astrophysics Data System (ADS)

    Maciejewski, G.; Dimitrov, D.; Neuhäuser, R.; Niedzielski, A.; Raetz, St.; Ginski, Ch.; Adam, Ch.; Marka, C.; Moualla, M.; Mugrauer, M.

    2010-10-01

    Photometric follow-ups of transiting exoplanets may lead to discoveries of additional, less massive bodies in extrasolar systems. This is possible by detecting and then analysing variations in transit timing of transiting exoplanets. We present photometric observations gathered in 2009 and 2010 for exoplanet WASP-3b during the dedicated transit-timing-variation campaign. The observed transit timing cannot be explained by a constant period but by a periodic variation in the observations minus calculations diagram. Simplified models assuming the existence of a perturbing planet in the system and reproducing the observed variations of timing residuals were identified by three-body simulations. We found that the configuration with the hypothetical second planet of mass ~, located close to the outer 2:1 mean-motion resonance, is the most likely scenario reproducing observed transit timing. We emphasize, however, that more observations are required to constrain better the parameters of the hypothetical second planet in the WASP-3 system. For final interpretation not only transit timing but also photometric observations of the transit of the predicted second planet and high-precision radial velocity data are needed. This paper is based on observations made with the 60-cm telescope of the Rozhen National Astronomical Observatory, which is operated by the Institute of Astronomy, Bulgarian Academy of Sciences, and the 90-cm telescope of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich Schiller University. E-mail: gm@astro.uni-jena.de

  10. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  11. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  12. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  13. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  14. The RICE MINUTE-LIKE1 (RML1) gene, encoding a ribosomal large subunit protein L3B, regulates leaf morphology and plant architecture in rice

    PubMed Central

    Zheng, Ming; Wang, Yihua; Liu, Xi; Sun, Juan; Wang, Yunlong; Xu, Yang; Lv, Jia; Long, Wuhua; Zhu, Xiaopin; Guo, Xiuping; Jiang, Ling; Wang, Chunming; Wan, Jianmin

    2016-01-01

    Mutations of ribosomal proteins (RPs) are known to cause developmental abnormalities in yeast, mammals, and dicotyledonous plants; however, their effects have not been studied in rice. Here, we identifiy a ribosomal biogenesis mutant, rice minute-like1 (rml1) that displays a minute phenotype as evidenced by retarded growth and defects in the vascular system. We determine that RML1 encodes a ribosome large subunit protein 3B (RPL3B) in rice by means of map-based cloning and genetic complementation. RPL3B is abundantly expressed in all the tissues, whereas RPL3A, another RPL3 gene family member, is expressed at low levels. Notably, the expression level of RPL3A in the rml1 mutant is similar to that in the wild-type, suggesting that RPL3A provides no functional compensation for RPL3B in rml1 plants. Ribosomal profiles show that mutation of RPL3B leads to a significant reduction in free 60S ribosomal subunits and polysomes, indicating a ribosomal insufficiency in the rml1 mutant. Our results demonstrate that the ribosomal protein gene RPL3B is required for maintaining normal leaf morphology and plant architecture in rice through its regulation of ribosome biogenesis. PMID:27241493

  15. Fingersomatotopy in area 3b: an fMRI-study

    PubMed Central

    van Westen, Danielle; Fransson, Peter; Olsrud, Johan; Rosén, Birgitta; Lundborg, Göran; Larsson, Elna-Marie

    2004-01-01

    Background The primary sensory cortex (S1) in the postcentral gyrus is comprised of four areas that each contain a body map, where the representation of the hand is located with the thumb most laterally, anteriorly and inferiorly and the little finger most medially, posteriorly and superiorly. Previous studies on somatotopy using functional MRI have either used low field strength, have included a small number of subjects or failed to attribute activations to any area within S1. In the present study we included twenty subjects, who were investigated at 3 Tesla (T). We focused specifically on Brodmann area 3b, which neurons have discrete receptive fields with a potentially more clearcut somatotopic organisation. The spatial distribution for all fingers' peak activation was determined and group as well as individual analysis was performed. Results Activation maps from 18 subjects were of adequate quality; in 17 subjects activations were present for all fingers and these data were further analysed. In the group analysis the thumb was located most laterally, anteriorly and inferiorly with the other fingers sequentially positioned more medially, posteriorly and superiorly. At the individual level this somatotopic relationship was present for the thumb and little finger, with a higher variability for the fingers in between. The Euclidian distance between the first and fifth finger was 17.2 mm, between the first and second finger 10.6 mm and between the remaining fingers on average 6.3 mm. Conclusion Results from the group analysis, that is both the location of the fingers and the Euclidian distances, are well comparable to results from previous studies using a wide range of modalities. On the subject level the spatial localisation of the fingers showed a less stringent somatotopic order so that the location of a finger in a single subject cannot be predicted from the group result. PMID:15320953

  16. 18 CFR 3b.204 - Safeguarding information in manual and computer-based record systems.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... information in manual and computer-based record systems. 3b.204 Section 3b.204 Conservation of Power and Water... Collection of Records § 3b.204 Safeguarding information in manual and computer-based record systems. (a) The administrative and physical controls to protect the information in the manual and computer-based record...

  17. 18 CFR 3b.204 - Safeguarding information in manual and computer-based record systems.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... information in manual and computer-based record systems. 3b.204 Section 3b.204 Conservation of Power and Water... Collection of Records § 3b.204 Safeguarding information in manual and computer-based record systems. (a) The administrative and physical controls to protect the information in the manual and computer-based record...

  18. 18 CFR 3b.204 - Safeguarding information in manual and computer-based record systems.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... information in manual and computer-based record systems. 3b.204 Section 3b.204 Conservation of Power and Water... Collection of Records § 3b.204 Safeguarding information in manual and computer-based record systems. (a) The administrative and physical controls to protect the information in the manual and computer-based record...

  19. 18 CFR 3b.204 - Safeguarding information in manual and computer-based record systems.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... information in manual and computer-based record systems. 3b.204 Section 3b.204 Conservation of Power and Water... Collection of Records § 3b.204 Safeguarding information in manual and computer-based record systems. (a) The administrative and physical controls to protect the information in the manual and computer-based record...

  20. 18 CFR 3b.204 - Safeguarding information in manual and computer-based record systems.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... information in manual and computer-based record systems. 3b.204 Section 3b.204 Conservation of Power and Water... Collection of Records § 3b.204 Safeguarding information in manual and computer-based record systems. (a) The administrative and physical controls to protect the information in the manual and computer-based record...

  1. Extreme C-terminal sites are posttranslocationally glycosylated by the STT3B isoform of the OST.

    PubMed

    Shrimal, Shiteshu; Trueman, Steven F; Gilmore, Reid

    2013-04-01

    Metazoan organisms assemble two isoforms of the oligosaccharyltransferase (OST) that have different catalytic subunits (STT3A or STT3B) and partially nonoverlapping roles in asparagine-linked glycosylation. The STT3A isoform of the OST is primarily responsible for co-translational glycosylation of the nascent polypeptide as it enters the lumen of the endoplasmic reticulum. The C-terminal 65-75 residues of a glycoprotein will not contact the translocation channel-associated STT3A isoform of the OST complex before chain termination. Biosynthetic pulse labeling of five human glycoproteins showed that extreme C-terminal glycosylation sites were modified by an STT3B-dependent posttranslocational mechanism. The boundary for STT3B-dependent glycosylation of C-terminal sites was determined to fall between 50 and 55 residues from the C terminus of a protein. C-terminal NXT sites were glycosylated more rapidly and efficiently than C-terminal NXS sites. Bioinformatics analysis of glycopeptide databases from metazoan organisms revealed a lower density of C-terminal acceptor sites in glycoproteins because of reduced positive selection of NXT sites and negative selection of NXS sites.

  2. DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells.

    PubMed

    Duymich, Christopher E; Charlet, Jessica; Yang, Xiaojing; Jones, Peter A; Liang, Gangning

    2016-04-28

    Promoter DNA methylation is a key epigenetic mechanism for stable gene silencing, but is correlated with expression when located in gene bodies. Maintenance and de novo DNA methylation by catalytically active DNA methyltransferases (DNMT1 and DNMT3A/B) require accessory proteins such as UHRF1 and DNMT3L. DNMT3B isoforms are widely expressed, although some do not have active catalytic domains and their expression can be altered during cell development and tumourigenesis, questioning their biological roles. Here, we show that DNMT3B isoforms stimulate gene body methylation and re-methylation after methylation-inhibitor treatment. This occurs independently of the isoforms' catalytic activity, demonstrating a similar functional role to the accessory protein DNMT3L, which is only expressed in undifferentiated cells and recruits DNMT3A to initiate DNA methylation. This unexpected role for DNMT3B suggests that it might substitute for the absent accessory protein DNMT3L to recruit DNMT3A in somatic cells.

  3. TEACHING HONORS ENGLISH 3A-3B, AND U.S. HISTORY AB--A PILOT PROJECT, WORKING DRAFT.

    ERIC Educational Resources Information Center

    Pasadena City Unified School District, CA.

    AN ATTEMPT TO ENRICH THE CURRICULUM, TO INDIVIDUALIZE INSTRUCTION, AND TO INCREASE MOTIVATION IS PRESENTED. BOTH VERTICAL AND HORIZONTAL TYPES OF ENRICHMENT ARE APPLIED. TEACHERS OF ENGLISH AND U.S. HISTORY SHOULD STRESS CONCEPTS, MEANINGS, AND RELATIONSHIPS. THEY SHOULD ALSO INTRODUCE MORE INDEPENDENT STUDY AND HELP STUDENTS COMMUNICATE…

  4. 17 CFR 240.3b-16 - Definitions of terms used in Section 3(a)(1) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... constitute, maintain, or provide “a market place or facilities for bringing together purchasers and sellers... of multiple buyers and sellers; and (2) Uses established, non-discretionary methods (whether by... buyers and sellers entering such orders agree to the terms of a trade. (b) An organization,...

  5. 17 CFR 240.3b-18 - Definitions of terms used in Section 3(a)(5) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the value of the obligations in a pool of obligations used to back the securities issued through a grantor trust or other separate entity. (d) The term obligation means any note, draft, acceptance, loan... evidenced by the loan documents of the bank or its affiliates, other than its broker or dealer...

  6. Phase change paint tests on Rockwell orbiter/tank and orbiter alone configurations (OH3A/OH3B)

    NASA Technical Reports Server (NTRS)

    Quan, M.; Craig, C.

    1974-01-01

    Wind tunnel tests were conducted on scale models of the space shuttle orbiter and external tank. The tests were designed to determine the basic heating rate and interference effects on the orbiter-tank configuration and to analyze the effectiveness of the thermal protective system on the reentry vehicle. The phase change paint techniques were used to determine areodynamic heating rates. Oil flow and schlieren photographs were used for flow visualization.

  7. Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage

    PubMed Central

    Alsafadi, Samar; Houy, Alexandre; Battistella, Aude; Popova, Tatiana; Wassef, Michel; Henry, Emilie; Tirode, Franck; Constantinou, Angelos; Piperno-Neumann, Sophie; Roman-Roman, Sergio; Dutertre, Martin; Stern, Marc-Henri

    2016-01-01

    Hotspot mutations in the spliceosome gene SF3B1 are reported in ∼20% of uveal melanomas. SF3B1 is involved in 3′-splice site (3′ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1R625/K666 mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3′ss. Modelling the differential junctions in SF3B1WT and SF3B1R625/K666 cell lines demonstrates that the deregulated splice pattern strictly depends on SF3B1 status and on the 3'ss-sequence context. SF3B1WT knockdown or overexpression do not reproduce the SF3B1R625/K666 splice pattern, qualifying SF3B1R625/K666 as change-of-function mutants. Mutagenesis of predicted branchpoints reveals that the SF3B1R625/K666-promoted splice pattern is a direct result of alternative branchpoint usage. Altogether, this study provides a better understanding of the mechanisms underlying splicing alterations induced by mutant SF3B1 in cancer, and reveals a role for alternative branchpoints in disease. PMID:26842708

  8. Classical NF-κB pathway is responsible for APOBEC3B expression in cancer cells.

    PubMed

    Maruyama, Wataru; Shirakawa, Kotaro; Matsui, Hiroyuki; Matsumoto, Tadahiko; Yamazaki, Hiroyuki; Sarca, Anamaria D; Kazuma, Yasuhiro; Kobayashi, Masayuki; Shindo, Keisuke; Takaori-Kondo, Akifumi

    2016-09-23

    APOBEC3B (A3B) is a DNA cytosine deaminase and catalyzes cytosine deamination, resulting in mutations in genomic DNA. A3B is aberrantly expressed in a variety of cancers and considered to be a source of genomic mutations that contribute to cancer progression and metastasis. However, the mechanisms through which A3B expression is dysregulated in cancer cells are not fully elucidated. Here we report that the classical NF-κB pathway plays a crucial role in the transcriptional regulation of A3B in various cancer cells, including lymphoid malignancies. PMA, a strong activator of PKC, induces A3B at both mRNA and protein levels in cancer cell lines, and specific inhibitors of both PKC and IKK downregulate A3B expression. Using luciferase reporter and EMSA assays, we identify 3 NF-κΒ binding sites in the A3B promoter and reveal that NF-κB p65/p50 and p65/c-Rel heterodimers are important for A3B transcription. These results suggest that the classical NF-κB pathway is responsible for activation of A3B mRNA expression and further imply that inhibition of PKC and IKK might augment cancer treatment by reducing cancer progression and metastasis through downregulation of A3B expression. PMID:27577680

  9. Characterization of the Catalytic Domain of Human APOBEC3B and the Critical Structural Role for a Conserved Methionine.

    PubMed

    Siriwardena, Sachini U; Guruge, Thisari A; Bhagwat, Ashok S

    2015-09-25

    Human APOBEC3B deaminates cytosines in DNA and belongs to the AID/APOBEC family of enzymes. These proteins are involved in innate and adaptive immunity and may cause mutations in a variety of cancers. To characterize its ability to convert cytosines into uracils, we tested several derivatives of APOBEC3B gene for their ability to cause mutations in Escherichia coli. Through this analysis, a methionine residue at the junction of the amino-terminal domain (NTD) and the carboxy-terminal domain (CTD) was found to be essential for high mutagenicity. Properties of mutants with substitutions at this position, examination of existing molecular structures of APOBEC3 family members and molecular modeling suggest that this residue is essential for the structural stability of this family of proteins. The APOBEC3B CTD with the highest mutational activity was purified to homogeneity and its kinetic parameters were determined. Size-exclusion chromatography of the CTD monomer showed that it is in equilibrium with its dimeric form and matrix-assisted laser desorption ionization time-of-flight analysis of the protein suggested that the dimer may be quite stable. The partially purified NTD did not show intrinsic deamination activity and did not enhance the activity of the CTD in biochemical assays. Finally, APOBEC3B was at least 10-fold less efficient at mutating 5-methylcytosine (5mC) to thymine than APOBEC3A in a genetic assay and was at least 10-fold less efficient at deaminating 5mC compared to C in biochemical assays. These results shed light on the structural organization of APOBEC3B catalytic domain, its substrate specificity and its possible role in causing genome-wide mutations.

  10. Degradation of the cancer genomic DNA deaminase APOBEC3B by SIV Vif.

    PubMed

    Land, Allison M; Wang, Jiayi; Law, Emily K; Aberle, Ryan; Kirmaier, Andrea; Krupp, Annabel; Johnson, Welkin E; Harris, Reuben S

    2015-11-24

    APOBEC3B is a newly identified source of mutation in many cancers, including breast, head/neck, lung, bladder, cervical, and ovarian. APOBEC3B is a member of the APOBEC3 family of enzymes that deaminate DNA cytosine to produce the pro-mutagenic lesion, uracil. Several APOBEC3 family members function to restrict virus replication. For instance, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H combine to restrict HIV-1 in human lymphocytes. HIV-1 counteracts these APOBEC3s with the viral protein Vif, which targets the relevant APOBEC3s for proteasomal degradation. While APOBEC3B does not restrict HIV-1 and is not targeted by HIV-1 Vif in CD4-positive T cells, we asked whether related lentiviral Vif proteins could degrade APOBEC3B. Interestingly, several SIV Vif proteins are capable of promoting APOBEC3B degradation, with SIVmac239 Vif proving the most potent. This likely occurs through the canonical polyubiquitination mechanism as APOBEC3B protein levels are restored by MG132 treatment and by altering a conserved E3 ligase-binding motif. We further show that SIVmac239 Vif can prevent APOBEC3B mediated geno/cytotoxicity and degrade endogenous APOBEC3B in several cancer cell lines. Our data indicate that the APOBEC3B degradation potential of SIV Vif is an effective tool for neutralizing the cancer genomic DNA deaminase APOBEC3B. Further optimization of this natural APOBEC3 antagonist may benefit cancer therapy.

  11. Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes.

    PubMed

    Niemann, Stephan; Kanki, Hiroaki; Fukui, Yasuyuki; Takao, Keizo; Fukaya, Masahiro; Hynynen, Meri N; Churchill, Michael J; Shefner, Jeremy M; Bronson, Roderick T; Brown, Robert H; Watanabe, Masahiko; Miyakawa, Tsuyoshi; Itohara, Shigeyoshi; Hayashi, Yasunori

    2007-09-01

    NR3B is a modulatory subunit of the NMDA receptor, abundantly expressed in both cranial and spinal somatic motoneurons and at lower levels in other regions of the brain as well. Recently, we found the human NR3B gene (GRIN3B) to be highly genetically heterogeneous, and that approximately 10% of the normal European-American population lacks NR3B due to homozygous occurrence of a null allele in the gene. Therefore, it is especially important to understand the phenotypic consequences of the genetic loss of NR3B in both humans and animal models. We here provide results of behavioral analysis of mice genetically lacking NR3B, which is an ideal animal model due to homogeneity in genetic and environmental background. The NR3B(-/-) mice are viable and fertile. Consistent with the expression of NR3B in somatic motoneurons, the NR3B(-/-) mice showed a moderate but significant impairment in motor learning or coordination, and decreased activity in their home cages. Remarkably, the NR3B(-/-) mice showed a highly increased social interaction with their familiar cage mates in their home cage but moderately increased anxiety-like behaviour and decreased social interaction in a novel environment, consistent with the inhibitory role of NR3B on the functions of NMDA receptors. This work is the first reporting of the functional significance of NR3B in vivo and may give insight into the contribution of genetic variability of NR3B in the phenotypic heterogeneity among human population.

  12. Lymphoblastoid cell supernatants increase expression of C3b receptors on human polymorphonuclear leucocytes: direct binding studies with 125I-C3b.

    PubMed Central

    Berger, M; Cross, A S

    1984-01-01

    Human PMN incubated in culture supernatants of the Raji long-term human lymphoblastoid cell line showed increased rosette formation with sheep erythrocytes coated with C3b (EIgM C4b3b) but no change in rosette formation with IgG-coated erythrocytes. This suggested a specific increase in cell surface C3b receptors, which was further investigated using 125I-C3b for direct binding studies. The results confirmed that specific binding of 125I-C3b to PMN incubated in culture supernatants increased up to three- to four-fold over binding to PMN incubated in control media alone. Scatchard analysis revealed that the apparent Ka for supernatant-treated cells, 3.36 +/- 0.89 X 10(7) L/M did not differ from the Ka for cells incubated in control media, 3.76 +/- 0.75 X 10(7) L/M, suggesting an increase in a single class of C3b receptors. Kinetic studies revealed that the active factor was present within 24 hr of culture of the Raji cells, and that neutrophils incubated in culture supernatants increased their C3b receptors continuously for up to 4 hr, the longest interval tested. The effect of the culture supernatant was lost with dilution beyond eight- to 10-fold. The results suggest that culture supernatants of this long-term lymphoblastoid cell line contain soluble factors that induce increased expression of C3b receptors on PMN and may thus serve as a model for study of important physiologic effects of lymphocyte products on PMN in vivo. PMID:6230308

  13. Monitoring the Localization of MAP1LC3B by Indirect Immunofluorescence.

    PubMed

    Ktistakis, Nicholas T

    2015-08-01

    The autophagy protein MAP1LC3B (microtubule-associated proteins 1A/1B light chain 3B, hereafter referred to as LC3B), which is one of several mammalian homologs of yeast Atg8, is one of the most popular markers for autophagosome formation because its distribution changes from cytosolic/diffuse to punctate upon the induction of autophagy. In many settings, plasmids encoding fluorescently tagged LC3B are introduced into cells, and the subsequent autophagy response is monitored. However, for a variety of reasons, it would be desirable also to have a protocol to monitor the localization of endogenous LC3B under various conditions. This protocol provides such a methodology for the staining of endogenous LC3B by indirect immunofluorescence, such that autophagy responses can be monitored in mammalian cells. PMID:26240409

  14. Modeling SF3B1 Mutations in Cancer: Advances, Challenges, and Opportunities.

    PubMed

    Inoue, Daichi; Abdel-Wahab, Omar

    2016-09-12

    In this issue of Cancer Cell, Obeng et al. identify the consequences of expressing the most common mutation in the spliceosomal gene SF3B1 on hematopoiesis. The knockin mouse model described represents a valuable tool to dissect the effects of SF3B1 mutations on transformation, splicing, and less well-characterized functions of SF3B1. PMID:27622329

  15. Revisiting Elliptical Satellite Orbits to Enhance the O3b Constellation

    NASA Astrophysics Data System (ADS)

    Wood, L.; Lou, Yuxuan; Olusola, Opeoluwa

    Highly elliptical orbits can be used to provide targeted satellite coverage of locations at high latitudes. We review the history of use of these orbits for communication. How elliptical orbits can be used for broadband communication is outlined. We propose an addition of known elliptical orbits to the new equatorial O3b satellite constellation, extending O3b to cover high latitudes and the Earth's poles. We simulate the O3b constellation and compare this to recent measurement of the first real Internet traffic across the newly deployed O3b network.

  16. Synthesis and photodynamic activity of unsymmetrical A3B tetraarylporphyrins functionalized with l-glutamate and their Zn(II) and Cu(II) metal complex derivatives.

    PubMed

    Arredondo-Espinoza, Eder U; López-Cortina, Susana T; Ramírez-Cabrera, Mónica A; Balderas-Rentería, Isaías

    2016-08-01

    Four novel unsymmetrical A3B porphyrins 1, 2, 3 and 4 were synthesized following Lindsey procedure. Porphyrins 3 and 4 include one and three l-glutamate groups, respectively, and all porphyrins were metallated with Zn(II) (1a-4a) or Cu(II) (1b-4b). Porphyrins and metalloporphyrins presented values of singlet oxygen quantum yields (ΦD) ranging from 0.21 to 0.67. The tetraaryl derivatives in this study showed phototoxicity in SiHa cells with IC50 values ranging from <0.01 to 6.56±0.11μM, the metalloporphyrin 4a showed the lowest IC50 value. Comparing the phototoxic activity between all porphyrins, functionalization of porphyrins with glutamate increased 100 times phototoxic activity (1 (IC50 4.81±0.34μM) vs. 3 (IC50 0.04±0.02μM) and 2 (IC50 5.19±0.42μM) vs. 4 (IC50 0.05±0.01μM)). This increased activity could be attributed to reduced hydrophobicity and increased ΦΔ, given by functionalization with l-glutamate. Metalloporphyrins 3a (IC50 0.04±0.01μM) and 4a (IC50<0.01μM) presented the best values ​​of phototoxic activity. Therefore, functionalization and zinc metalation increased the phototoxic activity. SiHa cells treated with porphyrins 3, 4, 3a and 4a at a final concentration of 10μM, showed increased activity of caspase-3 enzyme compared to the negative control; indicating the induction of apoptosis. Differential gene expression pattern in SiHa cells was determined; treatments with metalloporphyrins 4a and 4b were performed, respectively, comparing the expression with untreated control. Treatments in both cases showed similar gene expression pattern in upregulated genes, since they share about 25 biological pathways and a large number of genes. According to the new photophysical properties related to the structural improvement and phototoxic activity, these molecules may have the potential application as photosensitizers in the photodynamic therapy.

  17. Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B

    PubMed Central

    Quist, Jelmar S.; Temiz, Nuri A.; Tutt, Andrew N. J.; Grigoriadis, Anita; Harris, Reuben S.

    2016-01-01

    Molecular, cellular, and clinical studies have combined to demonstrate a contribution from the DNA cytosine deaminase APOBEC3B (A3B) to the overall mutation load in breast, head/neck, lung, bladder, cervical, ovarian, and other cancer types. However, the complete landscape of mutations attributable to this enzyme has yet to be determined in a controlled human cell system. We report a conditional and isogenic system for A3B induction, genomic DNA deamination, and mutagenesis. Human 293-derived cells were engineered to express doxycycline-inducible A3B-eGFP or eGFP constructs. Cells were subjected to 10 rounds of A3B-eGFP exposure that each caused 80–90% cell death. Control pools were subjected to parallel rounds of non-toxic eGFP exposure, and dilutions were done each round to mimic A3B-eGFP induced population fluctuations. Targeted sequencing of portions of TP53 and MYC demonstrated greater mutation accumulation in the A3B-eGFP exposed pools. Clones were generated and microarray analyses were used to identify those with the greatest number of SNP alterations for whole genome sequencing. A3B-eGFP exposed clones showed global increases in C-to-T transition mutations, enrichments for cytosine mutations within A3B-preferred trinucleotide motifs, and more copy number aberrations. Surprisingly, both control and A3B-eGFP clones also elicited strong mutator phenotypes characteristic of defective mismatch repair. Despite this additional mutational process, the 293-based system characterized here still yielded a genome-wide view of A3B-catalyzed mutagenesis in human cells and a system for additional studies on the compounded effects of simultaneous mutation mechanisms in cancer cells. PMID:27163364

  18. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes.

    PubMed

    Visconte, Valeria; Rogers, Heesun J; Singh, Jarnail; Barnard, John; Bupathi, Manoj; Traina, Fabiola; McMahon, James; Makishima, Hideki; Szpurka, Hadrian; Jankowska, Anna; Jerez, Andres; Sekeres, Mikkael A; Saunthararajah, Yogen; Advani, Anjali S; Copelan, Edward; Koseki, Haruhiko; Isono, Kyoichi; Padgett, Richard A; Osman, Sami; Koide, Kazunori; O'Keefe, Christine; Maciejewski, Jaroslaw P; Tiu, Ramon V

    2012-10-18

    Whole exome/genome sequencing has been fundamental in the identification of somatic mutations in the spliceosome machinery in myelodysplastic syndromes (MDSs) and other hematologic disorders. SF3B1, splicing factor 3b subunit 1 is mutated in 60%-80% of refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T), 2 distinct subtypes of MDS and MDS/myeloproliferative neoplasms (MDSs/MPNs). An idiosyncratic feature of RARS/RARS-T is the presence of abnormal sideroblasts characterized by iron overload in the mitochondria, called RS. Based on the high frequency of mutations of SF3B1 in RARS/RARS-T, we investigated the consequences of SF3B1 alterations. Ultrastructurally, SF3B1 mutants showed altered iron distribution characterized by coarse iron deposits compared with wild-type RARS patients by transmission electron microscopy. SF3B1 knockdown experiments in K562 cells resulted in down-regulation of U2-type intron-splicing by RT-PCR. RNA-sequencing analysis of SF3B1 mutants showed differentially used genes relevant in MDS pathogenesis, such as ASXL1, CBL, EZH, and RUNX families. A SF3B pharmacologic inhibitor, meayamycin, induced the formation of RS in healthy BM cells. Further, BM aspirates of Sf3b1 heterozygous knockout mice showed RS by Prussian blue. In conclusion, we report the first experimental evidence of the association between SF3B1 and RS phenotype. Our data suggest that SF3B1 haploinsufficiency leads to RS formation.

  19. Magnetic and Moessbauer studies on GdCo/sub 3/B/sub 2/ and DyCo/sub 3/B/sub 2/

    SciTech Connect

    Malik, S.K.; Umarji, A.M.; Shenoy, G.K.

    1984-10-01

    Magnetization and Moessbauer studies have been carried out on GdCo/sub 3/B/sub 2/ and DyCo/sub 3/B/sub 2/. These compounds are magnetically ordered with Curie temperatures of 56/sup 0/ and 21/sup 0/K respectively. The Co atoms are either nonmagnetic or carry a small moment in these compounds. The saturation moment of DyCo/sub 3/B/sub 2/ at 5/sup 0/K is smaller than the Dy/sup 3 +/ free-ion value. From /sup 161/Dy Moessbauer studies, the measured hyperfine magnetic field at the Dy site is also observed to be smaller than the free-ion value. /sup 155/Gd Moessbauer measurements in GdCo/sub 3/B/sub 2/ reveal the presence of large crystalline electric fields at the rare earth site. This causes the moment and the hyperfine field at the Dy site in DyCo/sub 3/B/sub 2/ to be reduced from its free-ion value.

  20. 18 CFR 3b.220 - Notification of maintenance of records to individuals concerned.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Notification of maintenance of records to individuals concerned. 3b.220 Section 3b.220 Conservation of Power and Water... which the individual should reasonably be expected to know, such as, but not limited to, date of...

  1. 18 CFR 3b.220 - Notification of maintenance of records to individuals concerned.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Notification of maintenance of records to individuals concerned. 3b.220 Section 3b.220 Conservation of Power and Water... which the individual should reasonably be expected to know, such as, but not limited to, date of...

  2. 18 CFR 3b.220 - Notification of maintenance of records to individuals concerned.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Notification of maintenance of records to individuals concerned. 3b.220 Section 3b.220 Conservation of Power and Water... which the individual should reasonably be expected to know, such as, but not limited to, date of...

  3. 18 CFR 3b.220 - Notification of maintenance of records to individuals concerned.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Notification of maintenance of records to individuals concerned. 3b.220 Section 3b.220 Conservation of Power and Water... which the individual should reasonably be expected to know, such as, but not limited to, date of...

  4. 18 CFR 3b.220 - Notification of maintenance of records to individuals concerned.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Notification of maintenance of records to individuals concerned. 3b.220 Section 3b.220 Conservation of Power and Water... which the individual should reasonably be expected to know, such as, but not limited to, date of...

  5. 18 CFR 3b.221 - Access of records to individuals concerned.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Access of records to individuals concerned. 3b.221 Section 3b.221 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION...

  6. 18 CFR 3b.202 - Collection of information from individuals concerned.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Collection of information from individuals concerned. 3b.202 Section 3b.202 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  7. 18 CFR 3b.221 - Access of records to individuals concerned.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Access of records to individuals concerned. 3b.221 Section 3b.221 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION...

  8. 18 CFR 3b.202 - Collection of information from individuals concerned.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Collection of information from individuals concerned. 3b.202 Section 3b.202 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  9. 18 CFR 3b.224 - Requests to amend records and disputes thereon.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Requests to amend records and disputes thereon. 3b.224 Section 3b.224 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  10. 18 CFR 3b.221 - Access of records to individuals concerned.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Access of records to individuals concerned. 3b.221 Section 3b.221 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION...

  11. 18 CFR 3b.221 - Access of records to individuals concerned.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Access of records to individuals concerned. 3b.221 Section 3b.221 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION...

  12. 18 CFR 3b.224 - Requests to amend records and disputes thereon.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Requests to amend records and disputes thereon. 3b.224 Section 3b.224 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  13. 18 CFR 3b.224 - Requests to amend records and disputes thereon.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Requests to amend records and disputes thereon. 3b.224 Section 3b.224 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  14. 18 CFR 3b.202 - Collection of information from individuals concerned.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Collection of information from individuals concerned. 3b.202 Section 3b.202 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  15. 18 CFR 3b.224 - Requests to amend records and disputes thereon.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Requests to amend records and disputes thereon. 3b.224 Section 3b.224 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  16. 18 CFR 3b.224 - Requests to amend records and disputes thereon.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Requests to amend records and disputes thereon. 3b.224 Section 3b.224 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  17. 18 CFR 3b.202 - Collection of information from individuals concerned.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Collection of information from individuals concerned. 3b.202 Section 3b.202 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE,...

  18. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5260 Complement C3b inactivator immunological test system. (a) Identification. A complement... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Complement C3b inactivator immunological...

  19. Low-temperature flux syntheses and characterizations of two 1-D anhydrous borophosphates: Na{sub 3}B{sub 6}PO{sub 13} and Na{sub 3}BP{sub 2}O{sub 8}

    SciTech Connect

    Xiong Dingbang; Chen Haohong; Yang Xinxin; Zhao Jingtai

    2007-01-15

    Two new anhydrous sodium borophosphates with one-dimensional structure, Na{sub 3}B{sub 6}PO{sub 13}(1) and Na{sub 3}BP{sub 2}O{sub 8}(2), were synthesized by low-temperature molten salts techniques using boric acid and sodium dihydrogen phosphate as flux, respectively. The crystal structures were solved by means of single-crystal X-ray diffraction (1, orthorhombic, Pnma (no. 62), a=9.3727(4)A, b=16.2307(7)A, c=6.7232(3)A, Z=4; 2 , monoclinic, C2/c (no. 15), a=12.567(4)A, b=10.290(3)A, c=10.210(3)A, {beta}=92.492(5){sup o}, Z=8). Compound 1 is characterized by an infinite chain of {sub {approx}}{sup 1}{l_brace}[B{sub 6}PO{sub 13}]{r_brace}{sup 3-} containing eight-membered rings in which all vertexes of borate groups contribute to interconnection. Compound 2 reveals an infinite straight chain {sub {approx}}{sup 1}{l_brace}[BP{sub 2}O{sub 8}]{r_brace}{sup 3-} built of vertex-sharing four-membered rings, and chains in neighboring layers arranged along different orientations. The relations between structures and the synthetic conditions with only traced water are discussed.

  20. APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer

    PubMed Central

    Periyasamy, Manikandan; Patel, Hetal; Lai, Chun-Fui; Nguyen, Van T.M.; Nevedomskaya, Ekaterina; Harrod, Alison; Russell, Roslin; Remenyi, Judit; Ochocka, Anna Maria; Thomas, Ross S.; Fuller-Pace, Frances; Győrffy, Balázs; Caldas, Carlos; Navaratnam, Naveenan; Carroll, Jason S.; Zwart, Wilbert; Coombes, R. Charles; Magnani, Luca; Buluwela, Laki; Ali, Simak

    2015-01-01

    Summary Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER) and to repair by non-homologous end-joining (NHEJ) pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action. PMID:26411678

  1. Degradation of the cancer genomic DNA deaminase APOBEC3B by SIV Vif

    PubMed Central

    Land, Allison M.; Wang, Jiayi; Law, Emily K.; Aberle, Ryan; Kirmaier, Andrea; Krupp, Annabel; Johnson, Welkin E.; Harris, Reuben S.

    2015-01-01

    APOBEC3B is a newly identified source of mutation in many cancers, including breast, head/neck, lung, bladder, cervical, and ovarian. APOBEC3B is a member of the APOBEC3 family of enzymes that deaminate DNA cytosine to produce the pro-mutagenic lesion, uracil. Several APOBEC3 family members function to restrict virus replication. For instance, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H combine to restrict HIV-1 in human lymphocytes. HIV-1 counteracts these APOBEC3s with the viral protein Vif, which targets the relevant APOBEC3s for proteasomal degradation. While APOBEC3B does not restrict HIV-1 and is not targeted by HIV-1 Vif in CD4-positive T cells, we asked whether related lentiviral Vif proteins could degrade APOBEC3B. Interestingly, several SIV Vif proteins are capable of promoting APOBEC3B degradation, with SIVmac239 Vif proving the most potent. This likely occurs through the canonical polyubiquitination mechanism as APOBEC3B protein levels are restored by MG132 treatment and by altering a conserved E3 ligase-binding motif. We further show that SIVmac239 Vif can prevent APOBEC3B mediated geno/cytotoxicity and degrade endogenous APOBEC3B in several cancer cell lines. Our data indicate that the APOBEC3B degradation potential of SIV Vif is an effective tool for neutralizing the cancer genomic DNA deaminase APOBEC3B. Further optimization of this natural APOBEC3 antagonist may benefit cancer therapy. PMID:26544511

  2. Variation in the FcgammaR3B gene among distinct Brazilian populations.

    PubMed

    Covas, D T; Kashima, S; Guerreiro, J F; dos Santos, S E B; Zago, M A

    2005-02-01

    The FCGR3B gene codes for the FcgammaR3b receptor, which occurs in three polymorphic forms representing the human neutrophil antigens (HNA)-1a, HNA-1b, and HNA-1c. The alleles that code for these antigens are FCGR3B*1, FCGR3B*2, and FCGR3B*3, respectively. New variants of these alleles have been recently described. In order to study the frequency of these alleles and the occurrence of variant forms, we sequenced part of the FCGR3B gene in 149 individuals belonging to four distinct Brazilian populations, i.e., 60 Amerindians, 30 Whites of European descent, 30 Afro-Brazilians, and 30 Japanese. The FCGR3B*1 allele showed high frequency among Amerindians (0.850), with the value detected representing the highest frequency described thus far for this allele in population studies. Its frequency was 0.660 in the Japanese population studied, a value equal to that observed in Afro-Brazilians (0.600) and higher than that observed in Whites (0.480). The FCGR3B*3 allele was only found among Afro-Brazilians, where it occurred at a frequency of 0.080, which was lower than the frequency observed among Afro-North Americans (0.207) and Ugandans (0.166). Two variant haplotypes were detected among Amerindians and Afro-Brazilians, occurring in six individuals (four Amerindians and two Afro-Brazilians). The variant haplotype FCGR3B*1 A227G, which occurred in homozygosis in two Amerindians and in heterozygosis in two Afro-Brazilians, is described for the first time in the present report. In general, these data reveal variability in the frequency of alleles of the FCGR3B gene compared to other populations of the same genetic background in other regions of the world.

  3. Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis

    PubMed Central

    Nevarez, Lisette; Pogue, Robert; Krakow, Deborah; Cohn, Daniel H.

    2016-01-01

    The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to reduced SF3B4 synthesis and defects in mRNA splicing, primarily exon skipping. The mutations also led to reduced expression in growth plate chondrocytes of target genes, including the DLX5, DLX6, SOX9, and SOX6 transcription factor genes, which are known to be important for skeletal development. These data provide mechanistic insight toward understanding how SF3B4 mutations lead to the skeletal abnormalities observed in the acrofacial dysostoses. PMID:27622494

  4. The PKC-NFκB Signaling Pathway Induces APOBEC3B Expression in Multiple Human Cancers

    PubMed Central

    Leonard, Brandon; McCann, Jennifer L.; Starrett, Gabriel J.; Kosyakovsky, Leah; Luengas, Elizabeth M.; Molan, Amy M.; Burns, Michael B.; McDougle, Rebecca M.; Parker, Peter J.; Brown, William L.; Harris, Reuben S.

    2015-01-01

    Overexpression of the antiviral DNA cytosine deaminase APOBEC3B has been linked to somatic mutagenesis in many cancers. HPV infection accounts for APOBEC3B upregulation in cervical and head/neck cancers, but the mechanisms underlying non-viral malignancies are unclear. In this study, we investigated the signal transduction pathways responsible for APOBEC3B upregulation. Activation of protein kinase C (PKC) by the diacylglycerol (DAG) mimic phorbol-myristic acid (PMA) resulted in specific and dose-responsive increases in APOBEC3B expression and activity, which could then be strongly suppressed by PKC or NFκB inhibition. PKC activation caused the recruitment of RELB, but not RELA, to the APOBEC3B promoter implicating non-canonical NFκB signaling. Notably, PKC was required for APOBEC3B upregulation in cancer cell lines derived from multiple tumor types. By revealing how APOBEC3B is upregulated in many cancers, our findings suggest that PKC and NFκB inhibitors may be repositioned to suppress cancer mutagenesis, dampen tumor evolution, and decrease the probability of adverse outcomes such as drug resistance and metastases. PMID:26420215

  5. Role of Arabidopsis RabG3b and autophagy in tracheary element differentiation.

    PubMed

    Kwon, Soon Il; Cho, Hong Joo; Park, Ohkmae K

    2010-11-01

    The vascular system of plants consists of two conducting tissues, xylem and phloem, which differentiate from procambium cells. Xylem serves as a transporting system for water and signaling molecules and is formed by sequential developmental processes, including cell division/expansion, secondary cell wall deposition, vacuole collapse and programmed cell death (PCD). PCD during xylem differentiation is accomplished by degradation of cytoplasmic constituents, and it is required for the formation of hollow vessels, known as tracheary elements (TEs). Our recent study revealed that the small GTPase RabG3b acts as a regulator of TE differentiation through its autophagic activation. By using an Arabidopsis in vitro cell culture system, we showed that autophagy is activated during TE differentiation. Overexpression of a constitutively active RabG3b (RabG3bCA) significantly enhances both autophagy and TE differentiation, which are consistently suppressed in transgenic plants overexpressing a dominant negative form (RabG3bDN) or RabG3b RNAi (RabG3bRNAi), a brassinosteroid-insensitive mutant bri1-301 and an autophagy mutant atg5-1. On the basis of our results, we propose that RabG3b functions as a component of autophagy and regulates TE differentiation by activating the process of PCD.

  6. Assay Development for the Discovery of Semaphorin 3B Inducing Agents from Natural Product Sources

    PubMed Central

    Yong, Yeonjoong; Pan, Li; Ren, Yulin; Fatima, Nighat; Ahmed, Safia; Chang, Leng Chee; Zhang, Xiaoli; Kinghorn, A. Douglas; Swanson, Steven M.; Carcache de Blanco, Esperanza J.

    2014-01-01

    Semaphorins are a class of membrane-bound and secreted proteins. They have been found to regulate basic cell functions such as axonal growth cone guidance and recent studies have focused on their effect on tumor progression. Semaphorin 3B (Sema 3B) particularly is a secreted protein that has been known to modulate proliferation and apoptosis, processes that are critical for tumor progression and development. In spite of its importance, there is yet no high-throughput screening assay available to detect or quantify the expression of Sema 3B for natural product anticancer drug discovery purposes. Therefore, the development of a new high-throughput bioassay for the discovery of Sema 3B inducing agents from natural product sources is described herein. A wide variety of pure compounds and extracts from plants and microorganisms has been found suitable for screening using this Sema 3B assay to detect and quantify the effect of Sema 3B inducing agents and thereby identify new selective bioactive Sema 3B lead compounds for anticancer drug discovery and development. Also, this new bioassay procedure is based on a high-throughput platform using an enzyme-linked immunosorbent assay that involves the optimization of sensitivity and selectivity levels as well as accuracy, reproducibility, robustness, and cost effectiveness. PMID:25016954

  7. DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.

    PubMed

    Khorshied, Mervat Mamdooh; El-Ghamrawy, Mona Kamal

    2012-12-10

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

  8. SLC4A Transporters

    PubMed Central

    Choi, Inyeong

    2016-01-01

    SLC4A gene family proteins include bicarbonate transporters that move HCO3− across the plasma membrane and regulate intracellular pH and transepithelial movement of acid–base equivalents. These transporters are Cl/HCO3 exchangers, electrogenic Na/HCO3 cotransporters, electroneutral Na/HCO3 cotransporters, and Na+-driven Cl/HCO3 exchanger. Studies of the bicarbonate transporters in vitro and in vivo have demonstrated their physiological importance for acid–base homeostasis at the cellular and systemic levels. Recent advances in structure/function analysis have also provided valuable information on domains or motifs critical for regulation, ion translocation, and protein topology. This chapter focuses on the molecular mechanisms of ion transport along with associated structural aspects from mutagenesis of particular residues and from chimeric constructs. Structure/function studies have helped to understand the mechanism by which ion substrates are moved via the transporters. This chapter also describes some insights into the structure of SLC4A1 (AE1) and SLC4A4 (NBCe1) transporters. Finally, as some SLC4A transporters exist in concert with other proteins in the cells, the structural features associated with protein–protein interactions are briefly discussed. PMID:23177984

  9. The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer

    PubMed Central

    Law, Emily K.; Sieuwerts, Anieta M.; LaPara, Kelly; Leonard, Brandon; Starrett, Gabriel J.; Molan, Amy M.; Temiz, Nuri A.; Vogel, Rachel Isaksson; Meijer-van Gelder, Marion E.; Sweep, Fred C. G. J.; Span, Paul N.; Foekens, John A.; Martens, John W. M.; Yee, Douglas; Harris, Reuben S.

    2016-01-01

    Breast tumors often display extreme genetic heterogeneity characterized by hundreds of gross chromosomal aberrations and tens of thousands of somatic mutations. Tumor evolution is thought to be ongoing and driven by multiple mutagenic processes. A major outstanding question is whether primary tumors have preexisting mutations for therapy resistance or whether additional DNA damage and mutagenesis are necessary. Drug resistance is a key measure of tumor evolvability. If a resistance mutation preexists at the time of primary tumor presentation, then the intended therapy is likely to fail. However, if resistance does not preexist, then ongoing mutational processes still have the potential to undermine therapeutic efficacy. The antiviral enzyme APOBEC3B (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B) preferentially deaminates DNA C-to-U, which results in signature C-to-T and C-to-G mutations commonly observed in breast tumors. We use clinical data and xenograft experiments to ask whether APOBEC3B contributes to ongoing breast tumor evolution and resistance to the selective estrogen receptor modulator, tamoxifen. First, APOBEC3B levels in primary estrogen receptor–positive (ER+) breast tumors inversely correlate with the clinical benefit of tamoxifen in the treatment of metastatic ER+ disease. Second, APOBEC3B depletion in an ER+ breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. Third, APOBEC3B overexpression accelerates the development of tamoxifen resistance in murine xenograft experiments by a mechanism that requires the enzyme’s catalytic activity. These studies combine to indicate that APOBEC3B promotes drug resistance in breast cancer and that inhibiting APOBEC3B-dependent tumor evolvability may be an effective strategy to improve efficacies of targeted cancer therapies. PMID:27730215

  10. Analysis of methanobactin from Methylosinus trichosporium OB3b via ion mobility mass spectrometry.

    PubMed

    Choi, DongWon; Sesham, Ramakrishna; Kim, Yuri; Angel, Laurence A

    2012-01-01

    Methanobactins (mbs) are Low molecular mass copper binding chromopeptides analogous to pyoverdin class iron-binding siderophores. Mb produced by Methylosinus trichosporium OB3b (mb-oB3b) has been used as a model molecuLe for methanobactin although the amino acid sequence of mb-OB3b differs significantly from other characterized mbs. In particular, there is the presence of a pair of cystine residues which are absent in other characterized mbs. The role of the Cys3-Cys6 in copper binding, Cu(ll) reduction and its role on the mb-OB3b structure remains in debate. Here, we use a single-step dithiothreitol treatment as an effective method in reducing the disulfide bond allowing in-depth ion mobility-mass spectrometry (IM-MS) analysis. The IM-MS results show mb-oB3b exists in the gas-phase as three different negatively-charged states and exists in multiple conformational states, when introduced via electrospray ionization from aqueous solution near physiological pH. The disulfide bond serves a structural role and is not involved in the Cu(I/ll) binding capability of mb-OB3b, with the binding of a second Cu(I/ll) related to a further deprotonation of mb-OB3b. Overall, these findings are in good correlation with expected solution-phase behavior of mb-OB3b. The results suggest IM-MS is an effective tool for better understanding the complex nature of this intriguing peptide. PMID:23654196

  11. Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.

    PubMed

    Li, Shaoyong; Ling, Chen; Zhong, Li; Li, Mengxin; Su, Qin; He, Ran; Tang, Qiushi; Greiner, Dale L; Shultz, Leonard D; Brehm, Michael A; Flotte, Terence R; Mueller, Christian; Srivastava, Arun; Gao, Guangping

    2015-12-01

    Recombinant adeno-associated virus serotype 3B (rAAV3B) can transduce cultured human liver cancer cells and primary human hepatocytes efficiently. Serine (S)- and threonine (T)-directed capsid modifications further augment its transduction efficiency. Systemically delivered capsid-optimized rAAV3B vectors can specifically target cancer cells in a human liver cancer xenograft model, suggesting their potential use for human liver-directed gene therapy. Here, we compared transduction efficiencies of AAV3B and AAV8 vectors in cultured primary human hepatocytes and cancer cells as well as in human and mouse hepatocytes in a human liver xenograft NSG-PiZ mouse model. We also examined the safety and transduction efficacy of wild-type (WT) and capsid-optimized rAAV3B in the livers of nonhuman primates (NHPs). Intravenously delivered S663V+T492V (ST)-modified self-complementary (sc) AAV3B-EGFP vectors led to liver-targeted robust enhanced green fluorescence protein (EGFP) expression in NHPs without apparent hepatotoxicity. Intravenous injections of both WT and ST-modified rAAV3B.ST-rhCG vectors also generated stable super-physiological levels of rhesus chorionic gonadotropin (rhCG) in NHPs. The vector genome predominantly targeted the liver. Clinical chemistry and histopathology examinations showed no apparent vector-related toxicity. Our studies should be important and informative for clinical development of optimized AAV3B vectors for human liver-directed gene therapy.

  12. Behavioural correlates of the P3b event-related potential in school-age children

    PubMed Central

    Boucher, O.; Bastien, C. H.; Muckle, G.; Saint-Amour, D.; Jacobson, S. W.; Jacobson, J. L.

    2010-01-01

    The latency and amplitude of the P3b component of event-related potentials (ERPs) have been related to behavioural performance on several attention and memory tasks in adult populations. However, the extent to which these results apply to children is unknown. This study examined the neurobehavioral correlates of the P3b component in a longitudinal sample of school-age children from Arctic Québec. Children (N = 110; mean age = 11.3 years) were assessed on an ERP auditory oddball paradigm and a neurobehavioral evaluation targeting several aspects of cognition, including the Stewart Extended Continuous Performance Test (E-CPT), California Verbal Learning Test (CVLT), Stroop Color-Word Interference Test, and five subtests from the Wechsler Intelligence Scale for Children–Fourth edition (WISC-IV). P3b latency was positively related to reaction time measures and negatively associated with performance on the WISC-IV Digit Span Forward subtest. Amplitude of the P3b was associated with shorter completion time on the Stroop test and better delayed recognition memory performance among children who did not use semantic strategies on the CVLT. Profile analyses revealed no difference in scalp distribution of the P3b according to performance on these tests. The results are consistent with previous studies with older participants and suggest that, despite age-related differences in waveform and scalp distribution, the P3b component relates to similar neurocognitive processes in children and adults. PMID:20338199

  13. Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.

    PubMed

    Forneris, Federico; Wu, Jin; Xue, Xiaoguang; Ricklin, Daniel; Lin, Zhuoer; Sfyroera, Georgia; Tzekou, Apostolia; Volokhina, Elena; Granneman, Joke Cm; Hauhart, Richard; Bertram, Paula; Liszewski, M Kathryn; Atkinson, John P; Lambris, John D; Gros, Piet

    2016-05-17

    Regulators of complement activation (RCA) inhibit complement-induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i-iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations in CCP domains explain the diverse C3b-binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100° rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease-related mutations and immune evasion. PMID:27013439

  14. A meteorological interpretation of the Arctic Boundary Layer Expedition (ABLE) 3B flight series

    NASA Technical Reports Server (NTRS)

    Shipham, Mark C.; Bachmeier, A. Scott; Cahoon, Donald R., Jr.; Gregory, Gerald L.; Anderson, Bruce E.; Browell, Edward V.

    1994-01-01

    The Arctic Boundary Layer Expedition (ABLE) 3B was conducted to determine the summertime tropospheric distribution, sources, and sinks of important trace gas and aerosol species over the wetlands and boreal forests of central and eastern Canada. Isentropic trajectories and analyzed midtropospheric circulation patterns were used to group flights according to the transport histories of polar, midlatitude, or tropical air masses which were sampled. These data were then divided into bands of potential temperature levels representing the low, middle, and maximum aircraft altitudes to assess the effects of both local and long distance transport and natural and man-made pollutants to the measured chemical species. Detailed case studies are provided to depict the complex three-dimensional airflow regimes that transported air with differing chemical signatures to the study area. Mission 6 details the large-scale movement of smoke in the generally prevailing west to northwesterly airflow that was observed on the majority of flights. Mission 1 analyzes the horizontal and vertical motions of maritime Pacific air in the upper troposphere that was routinely mixed downward to the aircraft altitude. Finally, mission 14 tracks the far northward excursion of tropical air that had been associated with a Pacific typhoon. The following three factors all had important influences on the collected chemical data sets: (1) local and distant stratospheric in puts into the upper and middle troposphere; (2) biomass-burning plumes from active fires in Alaska and Canada; (3) a band of 'low ozone' upper tropospheric air that was observed by airborne differential absorption lidar (DIAL) above the aircraft maximum altitude. Other modification factors observed on some flights included urban pollution from U.S. and Canadian cities, tropical air that had been associated with a Pacific typhoon, and precipitation scavenging by clouds and rain. Many flights were affected by several of the above factors

  15. Ternary borides Nb7Fe3B8 and Ta7Fe3B8 with Kagome-type iron framework.

    PubMed

    Zheng, Qiang; Gumeniuk, Roman; Borrmann, Horst; Schnelle, Walter; Tsirlin, Alexander A; Rosner, Helge; Burkhardt, Ulrich; Reissner, Michael; Grin, Yuri; Leithe-Jasper, Andreas

    2016-06-21

    Two new ternary borides TM7Fe3B8 (TM = Nb, Ta) were synthesized by high-temperature thermal treatment of samples obtained by arc-melting. This new type of structure with space group P6/mmm, comprises TM slabs containing isolated planar hexagonal [B6] rings and iron centered TM columns in a Kagome type of arrangement. Chemical bonding analysis in Nb7Fe3B8 by means of the electron localizability approach reveals two-center interactions forming the Kagome net of Fe and embedded B, while weaker multicenter bonding present between this net and Nb atoms. Magnetic susceptibility measurements reveal antiferromagnetic order below TN = 240 K for Nb7Fe3B8 and TN = 265 K for Ta7Fe3B8. Small remnant magnetization below 0.01μB per f.u. is observed in the antiferromagnetic state. The bulk nature of the magnetic transistions was confirmed by the hyperfine splitting of the Mössbauer spectra, the sizable anomalies in the specific heat capacity, and the kinks in the resistivity curves. The high-field paramagnetic susceptibilities fitted by the Curie-Weiss law show effective paramagnetic moments μeff≈ 3.1μB/Fe in both compounds. The temperature dependence of the electrical resistivity also reveals metallic character of both compounds. Density functional calculations corroborate the metallic behaviour of both compounds and demonstrate the formation of a sizable local magnetic moment on the Fe-sites. They indicate the presence of both antiferro- and ferrromagnetic interactions.

  16. Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers.

    PubMed

    Sieuwerts, Anieta M; Willis, Scooter; Burns, Michael B; Look, Maxime P; Meijer-Van Gelder, Marion E; Schlicker, Andreas; Heideman, Marinus R; Jacobs, Heinz; Wessels, Lodewyk; Leyland-Jones, Brian; Gray, Kathryn P; Foekens, John A; Harris, Reuben S; Martens, John W M

    2014-12-01

    Recent observations connected DNA cytosine deaminase APOBEC3B to the genetic evolution of breast cancer. We addressed whether APOBEC3B is associated with breast cancer clinical outcomes. APOBEC3B messenger RNA (mRNA) levels were related in 1,491 primary breast cancers to disease-free (DFS), metastasis-free (MFS), and overall survival (OS). For independent validation, APOBEC3B mRNA expression was associated with patient outcome data in five additional cohorts (over 3,500 breast cancer cases). In univariate Cox regression analysis, increasing APOBEC3B expression as a continuous variable was associated with worse DFS, MFS, and OS (hazard ratio [HR] = 1.20, 1.21, and 1.24, respectively; all P < .001). Also, in untreated ER-positive (ER+), but not in ER-, lymph-node-negative patients, high APOBEC3B levels were associated with a poor DFS (continuous variable: HR = 1.29, P = .001; dichotomized at the median level, HR = 1.66, P = .0002). This implies that APOBEC3B is a marker of pure prognosis in ER + disease. These findings were confirmed in the analyses of five independent patient sets. In these analyses, APOBEC3B expression dichotomized at the median level was associated with adverse outcomes (METABRIC discovery and validation, 788 and 706 ER + cases, disease-specific survival (DSS), HR = 1.77 and HR = 1.77, respectively, both P < .001; Affymetrix dataset, 754 ER + cases, DFS, HR = 1.57, P = 2.46E-04; NKI295, 181 ER + cases, DFS, HR = 1.72, P = .054; and BIG 1-98, 1,219 ER + cases, breast-cancer-free interval (BCFI), HR = 1.42, P = 0.0079). APOBEC3B is a marker of pure prognosis and poor outcomes for ER + breast cancer, which strongly suggests that genetic aberrations induced by APOBEC3B contribute to breast cancer progression.

  17. Characterization of developmental Na(+) uptake in rainbow trout larvae supports a significant role for Nhe3b.

    PubMed

    Boyle, David; Blair, Salvatore D; Chamot, Danuta; Goss, Greg G

    2016-11-01

    Developing freshwater fish must compensate for the loss of ions, including sodium (Na(+)), to the environment. In this study, we used a radiotracer flux approach and pharmacological inhibitors to investigate the role of sodium/hydrogen exchange proteins (Nhe) in Na(+) uptake in rainbow trout (Oncorhynchus mykiss) reared from fertilization in soft water (0.1mM Na(+)). For comparison, a second group of embryos/larvae reared in hard water (2.2mM Na(+), higher pH and [Ca(2+)]) were also included in the experiment but were fluxed in soft water, only. Unidirectional rates of Na(+) uptake increased throughout development and were significantly higher in embryos/larvae reared in soft water. However, the mechanisms of Na(+) uptake in both groups of larvae were not significantly different, either in larvae immediately post-hatch or later in development: the broad spectrum Na(+) channel blocker amiloride inhibited 85-90% of uptake and the Nhe-inhibitor EIPA also caused near maximal inhibitions of Na(+) uptake. These data indicated Na(+) uptake was Nhe-mediated in soft water. A role of Nhe3b (but not Nhe2 or Nhe3a) in Na(+) uptake in soft water was also supported through gene expression analyses: expression of nhe3b increased throughout development in whole embryos/larvae in both groups and was significantly higher in those reared in soft water. This pattern of expression correlated well with measurements of Na(+) uptake. Together these data indicate that in part, rainbow trout embryos/larvae reared in low Na(+) soft water maintained Na(+) homeostasis by an EIPA sensitive component of Na(+) uptake, and support a primary role for Nhe3b.

  18. SF3B1 mutations constitute a novel therapeutic target in breast cancer

    PubMed Central

    Maguire, Sarah L; Leonidou, Andri; Wai, Patty; Marchiò, Caterina; Ng, Charlotte KY; Sapino, Anna; Salomon, Anne-Vincent; Reis-Filho, Jorge S; Weigelt, Britta; Natrajan, Rachael C

    2015-01-01

    Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, and pancreatic cancer, and at lower frequencies in breast cancer. To investigate whether dysfunction in RNA splicing is implicated in the pathogenesis of breast cancer, we performed a re-analysis of published exome and whole genome sequencing data. This analysis revealed that mutations in spliceosomal component genes occurred in 5.6% of unselected breast cancers, including hotspot mutations in the SF3B1 gene, which were found in 1.8% of unselected breast cancers. SF3B1 mutations were significantly associated with ER-positive disease, AKT1 mutations, and distinct copy number alterations. Additional profiling of hotspot mutations in a panel of special histological subtypes of breast cancer showed that 16% and 6% of papillary and mucinous carcinomas of the breast harboured the SF3B1 K700E mutation. RNA sequencing identified differentially spliced events expressed in tumours with SF3B1 mutations including the protein coding genes TMEM14C, RPL31, DYNL11, UQCC, and ABCC5, and the long non-coding RNA CRNDE. Moreover, SF3B1 mutant cell lines were found to be sensitive to the SF3b complex inhibitor spliceostatin A and treatment resulted in perturbation of the splicing signature. Albeit rare, SF3B1 mutations result in alternative splicing events, and may constitute drivers and a novel therapeutic target in a subset of breast cancers. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25424858

  19. FCGR3B gene frequencies among ethnic Thai blood donors from a regional hospital in Eastern Thailand.

    PubMed

    Kongmaroeng, C; Kumkaen, K

    2015-02-01

    The FCGR3B gene encodes three human neutrophil antigens which consist of HNA-1a, HNA-1b, and HNA-1c. These antigens are encoded by three alleles in the FCGR3B locus: FCGR3B*01, FCGR3B*02, and FCGR3B*03 alleles, respectively. The frequencies of FCGR3B alleles have been reported in different ethnic populations. This study compared the FCGR3B gene frequencies among 230 unrelated healthy Eastern Thai blood donors in Rayong hospital with the previously published studies. The polymerase chain reaction-sequence-specific primers method was performed to determine FCGR3B genotypes. The results showed that the allele frequencies of FCGR3B*01, FCGR3B*02, and FCGR3B*03 were 0.722, 0.274, and 0.009, respectively. The FCGR3B*01 and FCGR3B*02 frequencies found in the Eastern Thais were similar to the previous reports investigating in Northern Thais, Chinese Han, Taiwanese, and Japanese populations. Interestingly, our data showed statistically significant difference (P < 0.05) to Central Thais, Korean, Indian, Turkish, Australian, Tunisian, American, German, and Italian populations. In addition, one FCGR3Bnull , which represents a gene deletion, was also found in this study. This information is important not only for the assessment of neutrophil antibody-mediated clinical conditions and for disease association studies but also for anthropological studies.

  20. The Mitochondrial Fission Regulator DRP3B Does Not Regulate Cell Death in Plants

    PubMed Central

    YOSHINAGA, KEIKO; FUJIMOTO, MASARU; ARIMURA, SHIN-ICHI; TSUTSUMI, NOBUHIRO; UCHIMIYA, HIROFUMI; KAWAI-YAMADA, MAKI

    2006-01-01

    • Background and Aims Recent reports have described dramatic alterations in mitochondrial morphology during metazoan apoptosis. A dynamin-related protein (DRP) associated with mitochondrial outer membrane fission is known to be involved in the regulation of apoptosis. This study analysed the relationship between mitochondrial fission and regulation of plant cell death. • Methods Transgenic plants were generated possessing Arabidopsis DRP3B (K56A), the dominant-negative form of Arabidopsis DRP, mitochondrial-targeted green fluorescent protein and mouse Bax. • Key Results Arabidopsis plants over-expressing DRP3B (K56A) exhibited long tubular mitochondria. In these plants, mitochondria appeared as a string-of-beads during cell death. This indicates that DRP3B (K56A) prevented mitochondrial fission during plant cell death. However, in contrast to results for mammalian cells and yeast, Bax-induced cell death was not inhibited in DRP3B (K56A)-expressing plant cells. Similarly, hydrogen peroxide-, menadione-, darkness- and salicylic acid-induced cell death was not inhibited by DRP3B (K56A) expression. • Conclusions These results indicate that the systems controlling cell death in animals and plants are not common in terms of mitochondrial fission. PMID:16533833

  1. The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity

    PubMed Central

    Heinz, Leonhard X.; Baumann, Christoph L.; Köberlin, Marielle S.; Snijder, Berend; Gawish, Riem; Shui, Guanghou; Sharif, Omar; Aspalter, Irene M.; Müller, André C.; Kandasamy, Richard K.; Breitwieser, Florian P.; Pichlmair, Andreas; Bruckner, Manuela; Rebsamen, Manuele; Blüml, Stephan; Karonitsch, Thomas; Fauster, Astrid; Colinge, Jacques; Bennett, Keiryn L.; Knapp, Sylvia; Wenk, Markus R.; Superti-Furga, Giulio

    2015-01-01

    Summary Lipid metabolism and receptor-mediated signaling are highly intertwined processes that cooperate to fulfill cellular functions and safeguard cellular homeostasis. Activation of Toll-like receptors (TLRs) leads to a complex cellular response, orchestrating a diverse range of inflammatory events that need to be tightly controlled. Here, we identified the GPI-anchored Sphingomyelin Phosphodiesterase, Acid-Like 3B (SMPDL3B) in a mass spectrometry screening campaign for membrane proteins co-purifying with TLRs. Deficiency of Smpdl3b in macrophages enhanced responsiveness to TLR stimulation and profoundly changed the cellular lipid composition and membrane fluidity. Increased cellular responses could be reverted by re-introducing affected ceramides, functionally linking membrane lipid composition and innate immune signaling. Finally, Smpdl3b-deficient mice displayed an intensified inflammatory response in TLR-dependent peritonitis models, establishing its negative regulatory role in vivo. Taken together, our results identify the membrane-modulating enzyme SMPDL3B as a negative regulator of TLR signaling that functions at the interface of membrane biology and innate immunity. PMID:26095358

  2. XIST repression in the absence of DNMT1 and DNMT3B.

    PubMed

    Vasques, Luciana R; Stabellini, Raquel; Xue, Fei; Tian, X Cindy; Soukoyan, Marina; Pereira, Lygia V

    2005-01-01

    X chromosome inactivation (XCI) in human and mice involves XIST/Xist gene expression from the inactive X (Xi) and repression from the active X (Xa). Repression of the XIST/Xist gene on the Xa has been associated with methylation of its 5' region. In mice, Dnmt1 has been shown to be involved in the methylation and transcriptional repression of Xist on Xa. We examined maintenance of XIST gene repression on Xa in HCT116 cell lines knockout for either DNMT1 or DNMT3B and for DNMT1 and DNMT3B simultaneously. Methylation of the XIST promoter and XIST transcriptional repression is sustained in DNMT1-, DNMT3B- and DNMT1/DNMT3B knockout cells. Despite global DNA demethylation, the double knockout cells present only partial demethylation of the XIST promoter, which is not sufficient for gene reactivation. In contrast, global DNA demethylation with 5-aza-2'-deoxycytidine leads to XIST expression. Therefore, in these human cells maintenance of XIST methylation is controlled differently than global genomic methylation and in the absence of both DNMT1 and DNMT3B.

  3. Crystallization and preliminary diffraction studies of CBM3b of cellobiohydrolase 9A from Clostridium thermocellum

    SciTech Connect

    Jindou, Sadanari; Petkun, Svetlana; Shimon, Linda; Bayer, Edward A.; Lamed, Raphael; Frolow, Felix

    2007-12-01

    The cloning, expression, purification and crystallization of the CBM3b module of cellobiohydrolase 9A from C. thermocellum is described. The crystals diffract to 2.68 Å. Family 3 carbohydrate-binding modules (CBM3s) are associated with the scaffoldin subunit of the multi-enzyme cellulosome complex and with the family 9 glycoside hydrolases, which are multimodular enzymes that act on plant cell-wall polysaccharides, notably cellulose. Here, the crystallization of CBM3b from cellobiohydrolase 9A is reported. The crystals are tetragonal and belong to space group P4{sub 1} or P4{sub 3}. X-ray diffraction data for CBM3b have been collected to 2.68 Å resolution on beamline ID14-4 at the ESRF.

  4. Rare SF3B1 R625 mutations in cutaneous melanoma.

    PubMed

    Kong, Yong; Krauthammer, Michael; Halaban, Ruth

    2014-08-01

    RNA splicing is the cellular process that has only recently been found to be an important target for various cancers. Among the spliceosome genes that are involved in cancers, SF3B1 is most frequently mutated. Recurrent mutation in codon 625 has been found in uveal melanoma, but this mutation has not been identified in cutaneous melanoma. We used whole-exome sequencing to explore the mutational landscape of 295 melanoma samples, 231 of which are cutaneous melanoma. Among these cutaneous melanoma samples, we found two samples with R625 mutation in SF3B1 gene. The results were validated by Sanger sequencing. We conclude that SF3B1 R625 mutation does occur in cutaneous melanoma, although with a low frequency (∼1%).

  5. Extinction coefficient of H2CC(3B2) at 137 nm

    NASA Technical Reports Server (NTRS)

    Fahr, A.; Laufer, A. H.

    1985-01-01

    In spite of the conduction of numerous studies regarding the vinylidene free radical, its role and importance as a reactive intermediate is not well characterized. Laufer (1980, 1983) has reported the absorption spectrum of metastable H2CC(3B2), the lowest excited state, in the vacuum ultraviolet and has measured several aspects of its quenching properties. The present study provides a measurement of the extinction coefficient of H2CC(3B2). Knowledge of the vinylidene concentration is required to convert readily available absorption data into an extinction coefficient or cross section. In the current work, the H2CC(3B2) concentration was determined in an investigation of the photodissociation of vinyl chloride.

  6. 77 FR 41795 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-16

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and ] Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended.... Implementation of this determination will be made by U.S. Citizenship and Immigration Services (USCIS),...

  7. 76 FR 2130 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as... Immigration Services (USCIS), in consultation with U.S. Immigration and Customs Enforcement (ICE), or by...

  8. 76 FR 2131 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as.... Implementation of this determination will be made by U.S. Citizenship and Immigration Services (USCIS),...

  9. 76 FR 14418 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as... determination will be made by U.S. Citizenship and Immigration Services (USCIS), in consultation with...

  10. 76 FR 14419 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as.... Citizenship and Immigration Services (USCIS), in consultation with U.S. Immigration and Customs...

  11. Downregulation of KDM4A Suppresses the Survival of Glioma Cells by Promoting Autophagy.

    PubMed

    Wang, Bo; Fan, Xinxin; Ma, Chong; Lei, Hui; Long, Qianfa; Chai, Yuan

    2016-10-01

    Glioma is the most common type of primary intracranial tumor and has a poor prognosis. It has been reported that lysine-specific demethylase 4A (KDM4A) can promote tumor progression; however, its role in human glioma remains unclear. Western blot and qRT-PCR analyses showed that KDM4A was highly expressed in U87MG and T98G cells. 48 h after transfection with siKDM4A, the protein level of KDM4A was significantly downregulated. The silenced expression of KDM4A in T98G or U87MG cells inhibited cell viability and invasion, and aggravated cell apoptosis. We found that the siKDM4A led to a significant increase in acidic vesicular organelles (AVOs) and upregulated the expression of autophagy-related proteins, including LC3B-phosphatidylethanolamine conjugate, a cytosolic form of LC3B (LC3B-II/LC3B-I) and Beclin 1 in T98G and U87MG cells. Further studies demonstrated that after pretreatment with 3-MA (3 mmol/L) for 48 h, siKDM4A-transfected cells showed a prominent decrease in LC3B-II/LC3B-I and Beclin 1, accompanied by increased viability and invasion and decreased apoptosis. Our results suggest that the inhibition of KDM4A expression might efficiently suppress glioma cell survival by promoting autophagy, providing a promising agent for treating malignant gliomas. PMID:27514525

  12. Pyrano-[2,3b]-pyridines as potassium channel antagonists.

    PubMed

    Finlay, Heather J; Lloyd, John; Nyman, Michael; Conder, Mary Lee; West, Tonya; Levesque, Paul; Atwal, Karnail

    2008-04-15

    The design and synthesis of a series of highly functionalized pyrano-[2,3b]-pyridines is described. These compounds were assayed for their ability to block the I(Kur) channel encoded by the gene hKV1.5 in patch-clamped L-929 cells. Six of the compounds in this series showed sub-micromolar activity, the most potent being 4-(4-ethyl-benzenesulfonylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3b]-pyridine-6-carboxylic acid ethyl-phenyl-amide with an IC(50) of 378 nM.

  13. Analyzing the Effects of Nitrogen Deficiency on the PHB Production of Methylosinus trichosporium OB3b

    NASA Astrophysics Data System (ADS)

    Kyauk, E.

    2011-12-01

    Polyhydroxybutyrate (PHB) is a biodegradable thermoplastic that is produced by various microorganisms. Because of its potential to replace conventional plastics, it has been closely researched in the past few years. Methanotrophic bacteria, bacteria that consume methane, produce this bioplastic when it lacks certain nutrients. The utilization of methane to produce PHB shows much promise as methane is a cheap, plentiful gas. In this study, we observed the methanotroph, Methylosinus trichosporium OB3b , and its yield of PHB in the absence of nitrogen. The optical density of Methylosinus trichosporium OB3b was measured in order to observe cell growth and PHB production patterns over a 48 hour period.

  14. Use of fluorescence-activated flow cytometry to determine membrane lipid peroxidation during hypothermic liquid storage and freeze-thawing of viable boar sperm loaded with 4, 4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid.

    PubMed

    Guthrie, H D; Welch, G R

    2007-06-01

    Part of the reduction in boar sperm motility and fertility associated with hypothermic liquid storage and cryopreservation may be due to membrane lipid peroxidation. Lipid peroxidation was monitored by the shift from red to green fluorescence emission of the lipophilic probe 4, 4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid, C(11)BODIPY(581/591) (BODIPY), as measured by fluorescence-activated flow cytometry in live sperm (negative for propidium iodide). Experiments were conducted with Percoll-washed sperm to determine the specificity of BODIPY oxidation in the presence of different reactive oxygen species generators and metal chelators. Compared with no FeSO(4) and Na ascorbate, the combination of FeSO(4) and Na ascorbate (FeAc) increased (P < 0.01) the percentage of sperm containing oxidized BODIPY from 70% and increased (P < 0.05) BOD-IPY fluorescence intensity/cell by 5- to 10-fold after a 30-min incubation. Motility was depressed (P < 0.05) after exposure to FeAc, but viability was not affected. Of the reactive oxygen species generators tested, BODIPY oxidation was specific for FeAc, because menadione and H(2)O(2) had little or no effect. The oxidization of hydroethidine to ethidium was specific for menadione and H(2)O(2); FeAc had no effect. The presence of the metal chelators EDTA or deferoxamine mesylate at 3 and 9 muM inhibited FeAc-induced BODIPY oxidation and maintained motility. Experiments were conducted to determine the effect of liquid storage at 17 degrees C for 1 and 5 d and the effect of freeze-thawing on basal and FeAc-induced BODIPY oxidation. Basal BODIPY oxidation (no FeAc) was low in liquid stored and thawed viable sperm (1.3 and 3.4%, respectively). Although the incidence of basal or spontaneous membrane lipid peroxidation was low during liquid storage and after freeze-thawing, viable boar sperm were susceptible to FeAc-induced lipid peroxidation. PMID:17296775

  15. Uptake and effect of rare earth elements on gene expression in Methylosinus trichosporium OB3b.

    PubMed

    Gu, Wenyu; Farhan Ul Haque, Muhammad; DiSpirito, Alan A; Semrau, Jeremy D

    2016-07-01

    It is well known that Methylosinus trichosporium OB3b has two forms of methane monooxygenase (MMO) responsible for the initial conversion of methane to methanol, a cytoplasmic (soluble) methane monooxygenase and a membrane-associated (particulate) methane monooxygenase, and that copper strongly regulates expression of these alternative forms of MMO. More recently, it has been discovered that M. trichosporium OB3b has multiple types of the methanol dehydrogenase (MeDH), i.e. the Mxa-type MeDH (Mxa-MeDH) and Xox-type MeDH (Xox-MeDH), and the expression of these two forms is regulated by the availability of the rare earth element (REE), cerium. Here, we extend these studies and show that lanthanum, praseodymium, neodymium and samarium also regulate expression of alternative forms of MeDH. The effect of these REEs on MeDH expression, however, was only observed in the absence of copper. Further, a mutant of M. trichosporium OB3b, where the Mxa-MeDH was knocked out, was able to grow in the presence of lanthanum, praseodymium and neodymium, but was not able to grow in the presence of samarium. Collectively, these data suggest that multiple levels of gene regulation by metals exist in M. trichosporium OB3b, but that copper overrides the effect of other metals by an as yet unknown mechanism. PMID:27190151

  16. The 46359CT polymorphism of DNMT3B is associated with the risk of cervical cancer.

    PubMed

    Hernández-Sotelo, Daniel; García-Aguilar, Rubén; Castro-Coronel, Yaneth; Magaña, Jonathan J; Leyva-Vazquez, Marco Antonio; Alarcón-Romero, Luz del Carmen; López-Bayghen, Esther; Illades-Aguiar, Berenice

    2013-07-01

    Abnormal methylation is related to cancer development. Since DNMT3B is an enzyme that modulates genomic methylation, we hypothesized that genetic variants of the promoter DNMT3B may be associated with an increased risk of developing cervical cancer. Our aim was to investigate the association between -579GT and 46359CT polymorphisms of DNMT3B and cervical cancer, high-grade squamous intraepithelial lesions (HSIL), and low-grade squamous intraepithelial lesions (LSIL). Samples from 200 healthy women and 130 women with squamous intraepithelial lesions (70 with cervical cancer, 30 with HSIL, and 30 with LSIL) were analyzed. Polymorphism genotyping was performed using PCR and restriction fragment length polymorphism. The -579GT polymorphism was not associated with cervical cancer, HSIL, or LSIL. The CT genotype of 46359CT polymorphism was significantly associated with cervical cancer risk (OR 8.75, CI 1.27-374.1), whereas the TT genotype was associated with a significantly decreased risk of HSIL (OR 0.66, CI 0.01-0.32) and LSIL (OR 0.11, CI 0.026-0.45). Our results suggest that genotyping the 46359CT polymorphism in DNMT3B may help identify women who are genetically susceptible to cervical cancer development. Additional studies with larger sample sizes are necessary to confirm our findings.

  17. Blocked versus randomized presentation modes differentially modulate feedback-related negativity and P3b amplitudes

    PubMed Central

    Pfabigan, Daniela M.; Zeiler, Michael; Lamm, Claus; Sailer, Uta

    2014-01-01

    Objective Electrophysiological studies on feedback processing typically use a wide range of feedback stimuli which might not always be comparable. The current study investigated whether two indicators of feedback processing – feedback-related negativity (FRN) and P3b – differ for feedback stimuli with explicit (facial expressions) or assigned valence information (symbols). In addition, we assessed whether presenting feedback in either a trial-by-trial or a block-wise fashion affected these ERPs. Methods EEG was recorded in three experiments while participants performed a time estimation task and received two different types of performance feedback. Results Only P3b amplitudes varied consistently in response to feedback type for both presentation types. Moreover, the blocked feedback type presentation yielded more distinct FRN peaks, higher effect sizes, and a significant relation between FRN amplitudes and behavioral task performance measures. Conclusion Both stimulus type and presentation mode may provoke systematic changes in feedback-related ERPs. The current findings point at important potential confounds that need to be controlled for when designing FRN or P3b studies. Significance Studies investigating P3b amplitudes using mixed types of stimuli have to be interpreted with caution. Furthermore, we suggest implementing a blocked presentation format when presenting different feedback types within the same experiment. PMID:24144779

  18. Online / Offline reconstruction of trigger-less readout in the R3B experiment at FAIR

    NASA Astrophysics Data System (ADS)

    Kresan, Dmytro; Al-Turany, Mohammad; Uhlig, Florian

    2015-12-01

    The R3B (Reactions with Rare Radioactive Beams) experiment is one of the planned experiments at the future FAIR facility at GSI Darmstadt. R3B will cover experimental reaction studies with exotic nuclei far off stability, thus enabling a broad physics program with rare-isotope beams with emphasis on nuclear structure and dynamics. Several different detection subsystems as well as sophisticated DAQ system and data-analysis software are being developed for this purpose. The data analysis software for R3B is based on FairRoot framework and called R3BRoot. R3BRoot is being used for simulation and detector design studies for the last few years. Recently, it was successfully used directly with the data acquisition and for the analysis of the R3B test beam-time in April 2014. For the future beam times the framework has to deal with the free streaming readout of the detectors. The implementation within R3BRoot to fulfil this trigger-less run mode will be discussed in this paper, as well as the set of tools developed for the online reconstruction and quality assurance of the data during the run.

  19. Uptake and effect of rare earth elements on gene expression in Methylosinus trichosporium OB3b.

    PubMed

    Gu, Wenyu; Farhan Ul Haque, Muhammad; DiSpirito, Alan A; Semrau, Jeremy D

    2016-07-01

    It is well known that Methylosinus trichosporium OB3b has two forms of methane monooxygenase (MMO) responsible for the initial conversion of methane to methanol, a cytoplasmic (soluble) methane monooxygenase and a membrane-associated (particulate) methane monooxygenase, and that copper strongly regulates expression of these alternative forms of MMO. More recently, it has been discovered that M. trichosporium OB3b has multiple types of the methanol dehydrogenase (MeDH), i.e. the Mxa-type MeDH (Mxa-MeDH) and Xox-type MeDH (Xox-MeDH), and the expression of these two forms is regulated by the availability of the rare earth element (REE), cerium. Here, we extend these studies and show that lanthanum, praseodymium, neodymium and samarium also regulate expression of alternative forms of MeDH. The effect of these REEs on MeDH expression, however, was only observed in the absence of copper. Further, a mutant of M. trichosporium OB3b, where the Mxa-MeDH was knocked out, was able to grow in the presence of lanthanum, praseodymium and neodymium, but was not able to grow in the presence of samarium. Collectively, these data suggest that multiple levels of gene regulation by metals exist in M. trichosporium OB3b, but that copper overrides the effect of other metals by an as yet unknown mechanism.

  20. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal) of...: carbon, 0.55; phosphorus, 0.045; sulphur, 0.050. (c) Identification of material. Material must be... by water-jacket, or other suitable method, operated so as to obtain accurate data. The pressure...

  1. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal) of...: carbon, 0.55; phosphorus, 0.045; sulphur, 0.050. (c) Identification of material. Material must be... by water-jacket, or other suitable method, operated so as to obtain accurate data. The pressure...

  2. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal) of...: carbon, 0.55; phosphorus, 0.045; sulphur, 0.050. (c) Identification of material. Material must be... by water-jacket, or other suitable method, operated so as to obtain accurate data. The pressure...

  3. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal) of...: carbon, 0.55; phosphorus, 0.045; sulphur, 0.050. (c) Identification of material. Material must be... by water-jacket, or other suitable method, operated so as to obtain accurate data. The pressure...

  4. 12 CFR 563d.3b-6 - Liability for certain statements by savings associations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... savings associations. This section replaces adherence to 17 CFR 240.3b-6 and applies as follows: (a) A... registration statement filed with the Office under the Act on Form 10 (17 CFR 249.210); in part I of a quarterly report filed with the Office on Form 10-Q (17 CFR 241.308a); in an annual report to...

  5. 12 CFR 563d.3b-6 - Liability for certain statements by savings associations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... savings associations. This section replaces adherence to 17 CFR 240.3b-6 and applies as follows: (a) A... registration statement filed with the Office under the Act on Form 10 (17 CFR 249.210); in part I of a quarterly report filed with the Office on Form 10-Q (17 CFR 241.308a); in an annual report to...

  6. 17 CFR 240.3b-12 - Definition of OTC derivatives dealer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Definition of OTC derivatives... Securities Exchange Act of 1934 Definitions § 240.3b-12 Definition of OTC derivatives dealer. The term OTC derivatives dealer means any dealer that is affiliated with a registered broker or dealer (other than an...

  7. 17 CFR 240.3b-12 - Definition of OTC derivatives dealer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of OTC derivatives... Securities Exchange Act of 1934 Definitions § 240.3b-12 Definition of OTC derivatives dealer. The term OTC derivatives dealer means any dealer that is affiliated with a registered broker or dealer (other than an...

  8. 12 CFR 563d.3b-6 - Liability for certain statements by savings associations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... savings associations. This section replaces adherence to 17 CFR 240.3b-6 and applies as follows: (a) A... registration statement filed with the Office under the Act on Form 10 (17 CFR 249.210); in part I of a quarterly report filed with the Office on Form 10-Q (17 CFR 241.308a); in an annual report to...

  9. Polymorphism in Serotonin Receptor 3B Is Associated with Pain Catastrophizing

    PubMed Central

    Horjales-Araujo, Emilia; Demontis, Ditte; Lund, Ellen Kielland; Finnerup, Nanna Brix; Børglum, Anders D.; Jensen, Troels Staehelin; Svensson, Peter; Vase, Lene

    2013-01-01

    Pain catastrophizing, a coping style characterized by excessively negative thoughts and emotions in relation to pain, is one of the psychological factors that most markedly predicts variability in the perception of pain; however, only little is known about the underlying neurobiology. The aim of this study was to test for associations between psychological variables, such as pain catastrophizing, anxiety and depression, and selected polymorphisms in genes related to monoaminergic neurotransmission, in particular serotonin pathway genes. Three hundred seventy-nine healthy participants completed a set of psychological questionnaires: the Pain Catastrophizing Scale (PCS), the State-Trait Anxiety Inventory and Beck’s Depression Inventory, and were genotyped for 15 single nucleotide polymorphisms (SNPs) in nine genes. The SNP rs1176744 located in the serotonin receptor 3B gene (5-HTR3B) was found to be associated with pain catastrophizing scores: both the global score and the subscales of magnification and helplessness. This is the first study to show an association between 5-HTR3B and PCS scores, thus suggesting a role of the serotonin pathway in pain catastrophizing. Since 5-HTR3B has previously been associated with descending pain modulation pathways, future studies will be of great interest to elucidate the molecular pathways involved in the relation between serotonin, its receptors and pain catastrophizing. PMID:24244382

  10. ARID3B: a Novel Regulator of the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle

    PubMed Central

    Wood, Jennifer J.; Boyne, James R.; Paulus, Christina; Jackson, Brian R.; Nevels, Michael M.

    2016-01-01

    ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of commonly fatal malignancies of immunocompromised individuals, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is their biphasic life cycle—viral latency and the productive lytic cycle—and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein replication and transcription activator (RTA) is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B [ARID3B]) whose expression was enhanced by RTA and that relocalized to replication compartments upon lytic reactivation. We also show that small interfering RNA (siRNA) knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of fatal malignancies of

  11. Physicochemical characterization of C3b receptors isolated from human erythrocytes by immunoprecipitation.

    PubMed Central

    Gerdes, J; Stein, H

    1980-01-01

    A high yield of active C3b receptors was obtained by solubilizing human erythrocyte membranes with 2 M KBr, whereas other solubilization agents yielded no, or significantly less activity. Gel filtration of the KBr lysates revealed that the apparent molecular wieght of biologically active C3b receptor molecules was greater than 1 x 10(6). Immunoprecipitates prepared with radio-iodinated KBr lysates and anti-C3 receptor sera (AC3RS) were subjected to sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) or sodium dodecyl gel filtration. Unreduced SDS-PAGE and gel filtration profiles showed three predominant peaks with apparent mol. wts of 1--1.3 x 10(6), 80,000 and 60,000. Whereas the high mol. wt component decreased only slightly after reduction, the 80,000 and 60,000 mol. wt components disappeared and two new peaks with apparent mol. wts of 38,000 and 18,000 appeared in SDS-PAGE profiles. Although the high mol. wt component present in reduced SDS-PAGE profiles was detectable in some of the control experiments, none of the other peaks could be precipitated with control sera, and these components could be demonstrated only when KBr lysates of C3b receptor-positive erythrocytes and AC3RS that were able to inhibit ligand binding of the C3b receptors were used for precipitation. These findings suggest that (a) the C3b receptor of human erythrocytes in its biologically active state is a macromolecule with an apparent mol. wt higher than 1 x 10(6) and (b) the protein moiety consists predominantly of non-covalently linked protein molecules with apparent mol wts of 80,000 and 60,000. These protein molecules are composed of disulphide-bridged polypeptide chains with apparent mol. wts of 38,000 and 18,000. PMID:7461716

  12. Antibody-mediated complement C3b/iC3b binding to group B Streptococcus in paired mother and baby serum samples in a refugee population on the Thailand-Myanmar border.

    PubMed

    Herbert, Jenny; Thomas, Stephen; Brookes, Charlotte; Turner, Claudia; Turner, Paul; Nosten, Francois; Le Doare, Kirsty; Hudson, Michael; Heath, Paul T; Gorringe, Andrew; Taylor, Stephen

    2015-03-01

    Streptococcus agalactiae (group B streptococcus [GBS]) is the leading cause of neonatal sepsis and meningitis. In this study, we determined antibody-mediated deposition of complement C3b/iC3b onto the bacterial cell surface of GBS serotypes Ia, Ib, II, III, and V. This was determined for 520 mother and umbilical cord serum sample pairs obtained at the time of birth from a population on the Thailand-Myanmar border. Antibody-mediated deposition of complement C3b/iC3b was detected to at least one serotype in 91% of mothers, despite a known carriage rate in this population of only 12%. Antibody-mediated C3b/iC3b deposition corresponded to known carriage rates, with the highest levels of complement deposition observed onto the most prevalent serotype (serotype II) followed by serotypes Ia, III, V, and Ib. Finally, neonates born to mothers carrying serotype II GBS at the time of birth showed higher antibody-mediated C3b/iC3b deposition against serotype II GBS than neonates born to mothers with no serotype II carriage. Assessment of antibody-mediated C3b/iC3b deposition against GBS may provide insights into the seroepidemiology of anti-GBS antibodies in mothers and infants in different populations. PMID:25589553

  13. Antibody-Mediated Complement C3b/iC3b Binding to Group B Streptococcus in Paired Mother and Baby Serum Samples in a Refugee Population on the Thailand-Myanmar Border

    PubMed Central

    Herbert, Jenny; Thomas, Stephen; Brookes, Charlotte; Turner, Claudia; Turner, Paul; Nosten, Francois; Le Doare, Kirsty; Hudson, Michael; Heath, Paul T.; Gorringe, Andrew

    2015-01-01

    Streptococcus agalactiae (group B streptococcus [GBS]) is the leading cause of neonatal sepsis and meningitis. In this study, we determined antibody-mediated deposition of complement C3b/iC3b onto the bacterial cell surface of GBS serotypes Ia, Ib, II, III, and V. This was determined for 520 mother and umbilical cord serum sample pairs obtained at the time of birth from a population on the Thailand-Myanmar border. Antibody-mediated deposition of complement C3b/iC3b was detected to at least one serotype in 91% of mothers, despite a known carriage rate in this population of only 12%. Antibody-mediated C3b/iC3b deposition corresponded to known carriage rates, with the highest levels of complement deposition observed onto the most prevalent serotype (serotype II) followed by serotypes Ia, III, V, and Ib. Finally, neonates born to mothers carrying serotype II GBS at the time of birth showed higher antibody-mediated C3b/iC3b deposition against serotype II GBS than neonates born to mothers with no serotype II carriage. Assessment of antibody-mediated C3b/iC3b deposition against GBS may provide insights into the seroepidemiology of anti-GBS antibodies in mothers and infants in different populations. PMID:25589553

  14. Effects of Lu-Do-Huang Extract (LDHE) on Apoptosis Induction in Human Hep3B Cells.

    PubMed

    Huang, Hui-Yu; Chen, Li-Han; Liu, Chen-Wei; Chien, Ting-Yi; Yu, Yu-Ping; Kao, Yu-Yu; Yang, Jo-Hsuan; Tsai, Ying-Chieh

    2015-06-30

    Lu-Do-Huang (Pracparatum mungo) is a fermented mung bean [corrected] (Vigna radiata) and has long been used as a traditional and functional food in Traditional Chinese Medicine, especially for treating a variety of liver disorders. The present study aimed to evaluate the apoptotic effects of Lu-Do-Huang ethanol extract (LDHE) on Hep3B cells, a human hepatoma cell line. A variety of cellular assays, flow cytometry and immunoblotting were used. Our results showed that LDHE significantly inhibited Hep3B cells growth. Additionally, the cell cycle assay showed that LDHE prevented Hep3B cell entry into S phase and led to an arrest of Hep3B cells in the G₀/G₁ phase. LDHE induced Hep3B cells to undergo apoptosis as determined through Hep3B cell morphology changes, increase of apoptotic bodies, apoptotic cells, DNA fragmentations and caspase activity. We further examined the protein expression of TRADD, FADD, and Bax to verify the possible apoptotic pathways. The results indicated that LDHE-induced apoptosis in Hep3B cells might be mediated [corrected] by an extrinsic signaling pathway leading to an induction of apoptosis in Hep3B cells. In conclusion, LDHE induced apoptosis and cell cycle arrest in Hep3B cells. Our data provide the evidences regarding the anti-hepatoma potential of LDHE in Hep3B cells.

  15. THERMAL EMISSION AND TIDAL HEATING OF THE HEAVY AND ECCENTRIC PLANET XO-3b

    SciTech Connect

    Machalek, Pavel; Greene, Tom; McCullough, Peter R.; Burrows, Adam; Burke, Christopher J.; Hora, Joseph L.; Johns-Krull, Christopher M.; Deming, Drake L.

    2010-03-01

    We determined the flux ratios of the heavy and eccentric planet XO-3b to its parent star in the four Infrared Array Camera bands of the Spitzer Space Telescope: 0.101% +- 0.004% at 3.6 {mu}m; 0.143% +- 0.006% at 4.5 {mu}m; 0.134% +- 0.049% at 5.8 {mu}m; and 0.150% +- 0.036% at 8.0 {mu}m. The flux ratios are within [-2.2, 0.3, -0.8, and -1.7]sigma of the model of XO-3b with a thermally inverted stratosphere in the 3.6 {mu}m, 4.5 {mu}m, 5.8 {mu}m, and 8.0 {mu}m channels, respectively. XO-3b has a high illumination from its parent star (F{sub p} {approx} (1.9-4.2) x 10{sup 9} erg cm{sup -2} s{sup -1}) and is thus expected to have a thermal inversion, which we indeed observe. When combined with existing data for other planets, the correlation between the presence of an atmospheric temperature inversion and the substellar flux is insufficient to explain why some high insolation planets like TrES-3 do not have stratospheric inversions and some low insolation planets like XO-1b do have inversions. Secondary factors such as sulfur chemistry, atmospheric metallicity, amounts of macroscopic mixing in the stratosphere, or even dynamical weather effects likely play a role. Using the secondary eclipse timing centroids, we determined the orbital eccentricity of XO-3b as e = 0.277 +- 0.009. The model radius-age trajectories for XO-3b imply that at least some amount of tidal heating is required to inflate the radius of XO-3b, and the tidal heating parameter of the planet is constrained to Q{sub p} {approx}< 10{sup 6}.

  16. The new silver borate Ag{sub 3}B{sub 5}O{sub 9}

    SciTech Connect

    Sohr, Gerhard; Falkowski, Viktoria; Huppertz, Hubert

    2015-05-15

    Single crystals of Ag{sub 3}B{sub 5}O{sub 9} were obtained via high-pressure synthesis at 3 GPa and 600 °C, using a Walker-type multianvil high-pressure device. Ag{sub 3}B{sub 5}O{sub 9} crystalizes with a=674.7(2), b=943.5(2), c=1103.5(2) pm, V=0.7025(2) nm{sup 3}, and Z=4 in the noncentrosymmetric space group P2{sub 1}2{sub 1}2{sub 1} (no. 19). The orthorhombic structure was refined from 3740 independent reflections with R1=0.0496 and wR2=0.587 (all data). It is built up from infinite corner-sharing chains of BO{sub 4} tetrahedra along the a axis, which are interconnected by BO{sub 3} groups to form a network. In the structure, three crystallographically independent sites are occupied with Ag{sup +} cations exhibiting argentophillic interactions. The synthetic conditions as well as the results of the single crystal structure analysis are presented. - Graphical abstract: Noncentrosymmetric silver borate: During investigations in the system Ag–B–O, a new noncentrosymmetric silver borate Ag{sub 3}B{sub 5}O{sub 9} was discovered. The new structure type is built up from corner-sharing BO{sub 3} and BO{sub 4} groups, forming a network. Argentophillic interactions are clearly indicated by the Ag{sup +}⋯Ag{sup +} distances present in the structure. - Highlights: • A noncentrosymmetric borate Ag{sub 3}B{sub 5}O{sub 9} is accessible via high-pressure synthesis. • Ag{sub 3}B{sub 5}O{sub 9} is the second high-pressure silver borate. • Ag{sup +}⋯Ag{sup +} distances in Ag3B5O9 clearly indicate the presence of argentophillic interactions.

  17. Synthesis and photoluminescence properties of Ca3B2O6:Tb3+ nanophosphors

    NASA Astrophysics Data System (ADS)

    Manhas, Mohit; Kumar, Vinay; Ntwaeaborwa, O. M.; Swart, H. C.

    2014-04-01

    The green light emitting Tb3+ doped Ca3B2O6 nanophosphors have been synthesized by combustion method at 600°C, and their luminescent properties have been studied. The formation of phosphors has been confirmed by X-ray diffraction (XRD). The photoluminescence (PL) spectra show four emission peaks at 491 nm, 544 nm, 587 and 621 nm. It exhibited a strong green emission located at 544 nm. The effect of different dopant concentrations on emission intensity has also been studied. The maximum photo emission intensity of the Ca3B2O6:Tb3+ was obtained at a dopant concentration of 1.5 mol% of Tb3+.

  18. Evaluation of T3B fingerprinting for identification of clinical and environmental Sporothrix species.

    PubMed

    Oliveira, Manoel Marques Evangelista; Franco-Duarte, Ricardo; Romeo, Orazio; Pais, Célia; Criseo, Giuseppe; Sampaio, Paula; Zancope-Oliveira, Rosely Maria

    2015-03-01

    In this study, PCR fingerprinting using the universal primer T3B was applied to distinguish among clinical and environmental species of the Sporothrix complex, Sporothrix brasiliensis, S. globosa, S. mexicana, S. pallida, S. luriei and S. schenckii sensu stricto. The T3B fingerprinting generated clearly distinct banding patterns, allowing the correct identification of all 43 clinical and environmental isolates at the species level, what was confirmed by partial calmodulin gene sequence analyses. This technique is reproducible and provides the identification of all species of the Sporothrix complex with sufficient accuracy to be applied in clinical mycology laboratories as well as in epidemiological studies in order to obtain a better understanding of the epidemiology of sporotrichosis.

  19. Investigation on the decolorizing mechanism of Pseudomonas sp. R1 on reactive red X-3B.

    PubMed

    Zeng, Xinping; Zhang, Min; Li, Weihao; Li, Chang; Tang, Wenwei

    2014-01-01

    A strain of Pseudomonas aeruginosa (Pseudomonas sp. R1), which can efficiently decolorize reactive red X-3B, was isolated from activated sludge in a dye plant, and the decolorizing mechanism was explored in this paper. The result shows that Pseudomonas sp. R1 has very good capability for decolorization of reactive red X-3B and the decolorization rate is increased by 9.1% after optimization of the experimental parameters, which means that 89.6% of the reactive red can be removed. Investigation on decolorization mechanism showed that the decolorizing capability of Pseudomonassp. R1 was significantly affected after plasmids in Pseudomonassp. R1 were eliminated by acridine orange (AO). Meanwhile, E. coli DH5a could gain decolorizing capability after transformed with the plasmids. Plasmid elimination and transformation tests proved that the decolorizing gene in Pseudomonas sp. R1 exists in the plasmid.

  20. Batch conversion of methane to methanol using Methylosinus trichosporium OB3b as biocatalyst.

    PubMed

    Hwang, In Yeub; Hur, Dong Hoon; Lee, Jae Hoon; Park, Chang-Ho; Chang, In Seop; Lee, Jin Won; Lee, Eun Yeol

    2015-03-01

    Recently, methane has attracted much attention as an alternative carbon feedstock since it is the major component of abundant shale and natural gas. In this work, we produced methanol from methane using whole cells of Methylosinus trichosporium OB3b as the biocatalyst. M. trichosporium OB3b was cultured on NMS medium with a supply of 7:3 air/methane ratio at 30°C. The optimal concentrations of various methanol dehydrogenase inhibitors such as potassium phosphate and EDTA were determined to be 100 and 0.5 mM, respectively, for an efficient production of methanol. Sodium formate (40 mM) as a reducing power source was added to enhance the conversion efficiency. A productivity of 49.0 mg/l·h, titer of 0.393 g methanol/l, and conversion of 73.8% (mol methanol/mol methane) were obtained under the optimized batch condition. PMID:25563419

  1. Sorption of wastewater containing reactive red X-3B on inorgano-organo pillared bentonite.

    PubMed

    Zeng, Xiu-qiong

    2006-04-01

    Bentonite is a kind of natural clay with good exchanging ability. By exchanging its interlamellar cations with various soluble cations, such as quaternary ammonium cations and inorganic metal ions, the properties of natural bentonite can be greatly improved. In this study, hexadecyltrimethylammonium bromide (HDTMA), CaCl(2), MgCl(2), FeCl(3), AlCl(3) were used as organic and inorganic pillared materials respectively to produce several kinds of Ca-, Mg-, Fe-, Al-organo pillared bentonites. Sorption of reactive red X-3B on them was studied to determine their potential application as sorbents in wastewater treatment. The results showed that these pillared bentonites had much improved sorption properties, and that the dye solutions' pH value had some effect on the performance of these inorgano-organo pillared bentonites. Isotherms of reactive X-3B on these pillared bentonites suggested a Langmuir-type sorption mechanism. PMID:16532535

  2. Crystal structure of DPF3b in complex with an acetylated histone peptide.

    PubMed

    Li, Weiguo; Zhao, Anthony; Tempel, Wolfram; Loppnau, Peter; Liu, Yanli

    2016-09-01

    Histone acetylation plays an important role in chromatin dynamics and is associated with active gene transcription. This modification is written by acetyltransferases, erased by histone deacetylases and read out by bromodomain containing proteins, and others such as tandem PHD fingers of DPF3b. Here we report the high resolution crystal structure of the tandem PHD fingers of DPF3b in complex with an H3K14ac peptide. In the complex structure, the histone peptide adopts an α-helical conformation, unlike previously observed by NMR, but similar to a previously reported MOZ-H3K14ac complex structure. Our crystal structure adds to existing evidence that points to the α-helix as a natural conformation of histone tails as they interact with histone-associated proteins. PMID:27402533

  3. RL10A-3-3B high mixture ratio qualification program

    NASA Technical Reports Server (NTRS)

    Vogel, T.; Varella, D.; Smith, C.

    1987-01-01

    The results of the high mixture ratio qualification testing of the RL10 engine for the Shuttle/Centaur program are presented. The objective of the engine qualification test was to demonstrate the suitability of the RL10A-3-3B engine for space vehicle flight by subjecting it to the testing specified in RL10A-3-3B Model Specification Number 2295 dated February 1986. The applicable section of the specification is presented. Due to payload volume advantages which can be achieved by increasing the operating mixture ratio of the RL10, a decision was made to qualify the engine to run at a higher mixture ratio. A program was created to qualify the RL10 engine for operation at 15,000 pounds thrust and a nominal 6.0 to 1 mixture ratio. This model of the engine was designated the RL10A-3-3B. The qualification program included three test series as follows: (1) hardware durability and limits test in which the engine completed 23 firings and 4605.7 seconds with 1588.7 seconds at less than 6.6 mixture ratio; (2) preliminary qualification test in which the engine completed 26 firings and 5750 seconds; and (3) qualification test in which the engine completed 26 hot firings and 5693.4 seconds with 905.9 seconds at 6.7 mixture ratio. Several changes in engine hardware were required for operation of the RL10A-3-3B engine in the Space Shuttle which include a duel pressure switch ignition, an oxidizer flow control, and helium plumbing changes.

  4. The standards process: Technical committee X3B5 digital magnetic tape

    NASA Technical Reports Server (NTRS)

    Cheatham, Sam

    1993-01-01

    The definition of X3B5, where it fits in the national and international standards development process, and how it interfaces and influences the world community of standards developers are provided. Details concerning the focus of the committee, how it operates, and what the group sees as the future trends in the area of interchange standards utilizing the multifaceted, ubiquitous magnetic tape are presented.

  5. MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b

    PubMed Central

    Roscigno, Giuseppina; Quintavalle, Cristina; Donnarumma, Elvira; Puoti, Ilaria; Diaz-Lagares, Angel; Iaboni, Margherita; Fiore, Danilo; Russo, Valentina; Todaro, Matilde; Romano, Giulia; Thomas, Renato; Cortino, Giuseppina; Gaggianesi, Miriam; Esteller, Manel; Croce, Carlo M.; Condorelli, Gerolama

    2016-01-01

    Cancer stem cells (CSCs) are a small part of the heterogeneous tumor cell population possessing self-renewal and multilineage differentiation potential as well as a great ability to sustain tumorigenesis. The molecular pathways underlying CSC phenotype are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that play a powerful role in biological processes. Early studies have linked miRs to the control of self-renewal and differentiation in normal and cancer stem cells. We aimed to study the functional role of miRs in human breast cancer stem cells (BCSCs), also named mammospheres. We found that miR-221 was upregulated in BCSCs compared to their differentiated counterpart. Similarly, mammospheres from T47D cells had an increased level of miR-221 compared to differentiated cells. Transfection of miR-221 in T47D cells increased the number of mammospheres and the expression of stem cell markers. Among miR-221's targets, we identified DNMT3b. Furthermore, in BCSCs we found that DNMT3b repressed the expression of various stemness genes, such as Nanog and Oct 3/4, acting on the methylation of their promoters, partially reverting the effect of miR-221 on stemness. We hypothesize that miR-221 contributes to breast cancer tumorigenicity by regulating stemness, at least in part through the control of DNMT3b expression. PMID:26556862

  6. Photoluminescence and thermoluminescence characteristics of Sr3 B2 O6 :Eu(2+) yellow phosphor.

    PubMed

    Ho Van, Tuyen; Nguyen Manh, Son; Vu Xuan, Quang; Bounyavong, Sengthong

    2016-08-01

    Sr3 B2 O6 :Eu(2+) yellow phosphor was prepared by the combustion method. The crystalline structure, photoluminescence and thermoluminescence properties of Sr3 B2 O6 :Eu(2+) were investigated extensively. The X-ray diffraction result indicates that the Sr3 B2 O6 :Eu(2+) phosphor exhibited a rhombohedral crystal structure. The emission spectra under a 435 nm excited wavelength showed an intense broad band peaking at 574 nm, which corresponds to the 4f(6) 5d(1) → 4f(7) transition of Eu(2+) ion. There were two different sites of Sr replaced by Eu in host lattice. The concentration quenching process between Eu(2+) ions is determined and the corresponding concentration quenching mechanism was verified as dipole-quadrupole interaction. The glow curve under 3 Gy β- ray irradiation had the glow peak at 160°C and the average activation energy was defined as about 0.98 eV. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Chemical synthesis of Nd2Fe14B/Fe3B nanocomposites

    NASA Astrophysics Data System (ADS)

    Yu, L. Q.; Zhang, Y. P.; Yang, Z.; He, J. D.; Dong, K. T.; Hou, Y.

    2016-06-01

    High exchange-coupled Nd2Fe14B/Fe3B nanocomposites were synthesized by an integrative procedure of thermal decomposition and reductive annealing processes. The molar ratio of the resulting products of Nd/Fe/B can be tuned by adjusting the raw material proportion. The as-prepared nanocomposites exhibited an exchanged coupled effect with a large coercivity of 11 100 Gs, enhanced remanence Mr of 42.0 emu g-1, and Mr/M3T of 0.59.High exchange-coupled Nd2Fe14B/Fe3B nanocomposites were synthesized by an integrative procedure of thermal decomposition and reductive annealing processes. The molar ratio of the resulting products of Nd/Fe/B can be tuned by adjusting the raw material proportion. The as-prepared nanocomposites exhibited an exchanged coupled effect with a large coercivity of 11 100 Gs, enhanced remanence Mr of 42.0 emu g-1, and Mr/M3T of 0.59. Electronic supplementary information (ESI) available: Experimental details, XPS spectra of α-Fe@Fe3B nanoalloys and SEM images and EDS for nanocomposites. See DOI: 10.1039/c6nr03172b

  8. Thermoluminescent responses of Li3B7O12:Cu to proton beam.

    PubMed

    Koba, Y; Shinsho, K; Tamatsu, S; Fukuda, S; Wakabayashi, G

    2014-10-01

    A thermoluminescent (TL) phosphor Li3B7O12:Cu was irradiated by a proton beam at NIRS-HIMAC in Japan. Irradiation was performed at different water-equivalent depths using range shifters made of polymethyl methacrylate. The thermoluminescent responses of Li3B7O12:Cu were analysed, focusing on the TL efficiency and glow curve. The irradiated samples were heated from room temperature to 200°C at 0.16°C s(-1). The high-temperature area of the glow curve under proton irradiation changed in comparison with that under (60)Co gamma-ray irradiation. The relative TL efficiency of the main peak slightly varied between 0.8 and 1.1. The relationship between the relative TL efficiency of the main peak and the high-temperature area ratio (HTR) value, the relative TL ratio of the main peak to the high-temperature area, showed approximate linearity for proton dosimetry. Using correction based on the HTR method, the TL phosphor Li3B7O12:Cu can become a useful dosimetric tool for therapeutic proton beams. PMID:24759914

  9. APOBEC3B: pathological consequences of an innate immune DNA mutator.

    PubMed

    Burns, Michael B; Leonard, Brandon; Harris, Reuben S

    2015-01-01

    Cancer is a disease that results from alterations in the cellular genome. Several recent studies have identified mutational signatures that implicate a variety of mutagenic processes in cancer, a major one of which is explained by the enzymatic activity of the DNA cytosine deaminase, APOBEC3B. As a deaminase, APOBEC3B converts cytosines to uracils in single-stranded DNA. Failure to properly repair these uracil lesions can result in a diverse array of mutations. For instance, DNA uracils can template the insertion of complementary adenines leading to C-to-T transition mutations. DNA uracils can also be converted into abasic sites that, depending upon the DNA polymerase recruited to bypass this lesion in the template strand, can lead to adenine insertion and C-to-T mutations as well as cytosine insertion and C-to-G transversion mutations. Finally, DNA uracils can also be converted into DNA breaks that may precipitate some types of larger chromosomal aberrations observed in cancer. These studies cumulatively demonstrate that APOBEC3B is a major source of genetic heterogeneity in several human cancers and, as such, this enzyme may prove to be a critical diagnostic and therapeutic target.

  10. Copper-responsive gene expression in the methanotroph Methylosinus trichosporium OB3b.

    PubMed

    Kenney, Grace E; Sadek, Monica; Rosenzweig, Amy C

    2016-09-01

    Methanotrophic bacteria convert methane to methanol using methane monooxygenase (MMO) enzymes. In many strains, either an iron-containing soluble (sMMO) or a copper-containing particulate (pMMO) enzyme can be produced depending on copper availability; the mechanism of this copper switch has not been elucidated. A key player in methanotroph copper homeostasis is methanobactin (Mbn), a ribosomally produced, post-translationally modified natural product with a high affinity for copper. The Mbn precursor peptide is encoded within an operon that contains a range of putative transporters, regulators, and biosynthetic proteins, but the involvement of these genes in Mbn-related processes remains unclear. Extensive time-dependent qRT-PCR studies of Methylosinus trichosporium OB3b and the constitutive sMMO-producing mutant M. trichosporium OB3b PP358 show that the Mbn operon is indeed copper-regulated, providing experimental support for its bioinformatics-based identification. Moreover, the Mbn operon is co-regulated with the sMMO operon and reciprocally regulated with the pMMO operon. Within the Mbn and sMMO operons, a subset of regulatory genes exhibits a distinct and shared pattern of expression, consistent with their proposed functions as internal regulators. In addition, genome sequencing of the M. trichosporium OB3b PP358 mutant provides new evidence for the involvement of genes adjacent to the pMMO operon in methanotroph copper homeostasis.

  11. Photoluminescence and thermoluminescence characteristics of Sr3 B2 O6 :Eu(2+) yellow phosphor.

    PubMed

    Ho Van, Tuyen; Nguyen Manh, Son; Vu Xuan, Quang; Bounyavong, Sengthong

    2016-08-01

    Sr3 B2 O6 :Eu(2+) yellow phosphor was prepared by the combustion method. The crystalline structure, photoluminescence and thermoluminescence properties of Sr3 B2 O6 :Eu(2+) were investigated extensively. The X-ray diffraction result indicates that the Sr3 B2 O6 :Eu(2+) phosphor exhibited a rhombohedral crystal structure. The emission spectra under a 435 nm excited wavelength showed an intense broad band peaking at 574 nm, which corresponds to the 4f(6) 5d(1) → 4f(7) transition of Eu(2+) ion. There were two different sites of Sr replaced by Eu in host lattice. The concentration quenching process between Eu(2+) ions is determined and the corresponding concentration quenching mechanism was verified as dipole-quadrupole interaction. The glow curve under 3 Gy β- ray irradiation had the glow peak at 160°C and the average activation energy was defined as about 0.98 eV. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26669720

  12. Zebrafish Tshz3b negatively regulates Hox function in the developing hindbrain.

    PubMed

    Erickson, Timothy; Pillay, Laura M; Waskiewicz, Andrew J

    2011-09-01

    In flies, the zinc-finger protein Teashirt promotes trunk segmental identities, in part, by repressing the expression and function of anterior hox paralog group (PG) 1-4 genes that specify head fates. Anterior-posterior patterning of the vertebrate hindbrain also requires Hox PG 1-4 function, but the role of vertebrate teashirt-related genes in this process has not been investigated. In this work, we use overexpression and structure-function analyses to show that zebrafish tshz3b antagonizes Hox-dependent hindbrain segmentation. Ectopic Tshz3b perturbs the specification of rhombomere identities and leads to the caudal expansion of r1, the only rhombomere whose identity is specified independently of Hox function. This overexpression phenotype does not require the homeodomain and C-terminal zinc fingers that are unique to vertebrate Teashirt-related proteins, but does require that Tshz3b function as a repressor. Together, these results argue that the negative regulation of Hox PG 1-4 function is a conserved characteristic of Teashirt-related proteins.

  13. Copper-responsive gene expression in the methanotroph Methylosinus trichosporium OB3b.

    PubMed

    Kenney, Grace E; Sadek, Monica; Rosenzweig, Amy C

    2016-09-01

    Methanotrophic bacteria convert methane to methanol using methane monooxygenase (MMO) enzymes. In many strains, either an iron-containing soluble (sMMO) or a copper-containing particulate (pMMO) enzyme can be produced depending on copper availability; the mechanism of this copper switch has not been elucidated. A key player in methanotroph copper homeostasis is methanobactin (Mbn), a ribosomally produced, post-translationally modified natural product with a high affinity for copper. The Mbn precursor peptide is encoded within an operon that contains a range of putative transporters, regulators, and biosynthetic proteins, but the involvement of these genes in Mbn-related processes remains unclear. Extensive time-dependent qRT-PCR studies of Methylosinus trichosporium OB3b and the constitutive sMMO-producing mutant M. trichosporium OB3b PP358 show that the Mbn operon is indeed copper-regulated, providing experimental support for its bioinformatics-based identification. Moreover, the Mbn operon is co-regulated with the sMMO operon and reciprocally regulated with the pMMO operon. Within the Mbn and sMMO operons, a subset of regulatory genes exhibits a distinct and shared pattern of expression, consistent with their proposed functions as internal regulators. In addition, genome sequencing of the M. trichosporium OB3b PP358 mutant provides new evidence for the involvement of genes adjacent to the pMMO operon in methanotroph copper homeostasis. PMID:27087171

  14. Punctate LC3B expression is a common feature of solid tumors and associated with proliferation, metastasis and poor outcome

    PubMed Central

    Lazova, Rossitza; Camp, Robert L.; Klump, Vincent; Siddiqui, Summar F.; Amaravadi, Ravi K.; Pawelek, John M.

    2014-01-01

    Purpose Measurement of autophagy in cancer and correlation with histopathologic grading or clinical outcomes has been limited. Accordingly, we investigated LC3B as an autophagosome marker by analyzing nearly 1400 tumors from 20 types of cancer, focussing on correlations with clinical outcomes in melanoma and breast cancer. Experimental Design Staining protocols were developed for automated quantitative analysis (AQUA) using antibodies vs LC3 isoform B (LC3B) and Ki-67. Clinically annotated breast and melanoma TMA’s and a multitumor array were employed. An AQUA program was developed to quantitate LC3B distribution in punctate and diffuse compartments of the cell. Results LC3B staining was moderate to high in the large majority of tumors. The % area occupied by punctate LC3B was elevated 3–5 fold at high LC3B intensities. In breast cancer and melanoma TMAs, LC3B and Ki-67 showed strong correlations (p < 0.0001) and in multitumor TMAs mitotic figures were most often seen in tumors with highest LC3B expression (p < 0.002). In breast cancer, LC3B expression was elevated in node-positive vs node-negative primaries and associated with increased nuclear grade and shortened survival. In a melanoma TMA with no survival data, LC3B levels were highest in nodal, visceral and cutaneous metastases. Conclusions The results reveal a common expression of LC3B in malignancy and support emerging evidence that autophagy plays a significant role in cancer progression. High LC3B was associated proliferation, invasion and metastasis, high nuclear grade and worse outcome. Thus autophagy presents a key target of therapeutic vulnerability in solid tumors. PMID:22080440

  15. LC3B is indispensable for selective autophagy of p62 but not basal autophagy

    SciTech Connect

    Maruyama, Yoko; Sou, Yu-Shin; Kageyama, Shun; Takahashi, Takao; Ueno, Takashi; Tanaka, Keiji; Komatsu, Masaaki; Ichimura, Yoshinobu

    2014-03-28

    Highlights: • Knockdown of LC3 or GABARAP families did not affect the basal autophagy. • LC3B has a higher affinity for the autophagy-specific substrate, p62, than GABARAPs. • siRNA-mediated knockdown of LC3B, but not that of GABARAPs, resulted in significant accumulation of p62. - Abstract: Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs.

  16. Comparative proteomic analysis of drug sodium iron chlorophyllin addition to Hep 3B cell line.

    PubMed

    Zhang, Jun; Wang, Wenhai; Yang, Fengying; Zhou, Xinwen; Jin, Hong; Yang, Peng-yuan

    2012-09-21

    The human hepatoma 3B cell line was chosen as an experimental model for in vitro test of drug screening. The drugs included chlorophyllin and its derivatives such as fluo-chlorophyllin, sodium copper chlorophyllin, and sodium iron chlorophyllin. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method was used in this study to obtain the primary screening results. The results showed that sodium iron chlorophyllin had the best LC(50) value. Proteomic analysis was then performed for further investigation of the effect of sodium iron chlorophyllin addition to the Hep 3B cell line. The proteins identified from a total protein extract of Hep 3B before and after the drug addition were compared by two-dimensional-gel-electrophoresis. Then 32 three-fold differentially expressed proteins were successfully identified by MALDI-TOF-TOF-MS. There are 29 unique proteins among those identified proteins. These proteins include proliferating cell nuclear antigen (PCNA), T-complex protein, heterogeneous nuclear protein, nucleophosmin, heat shock protein A5 (HspA5) and peroxiredoxin. HspA5 is one of the proteins which are involved in protecting cancer cells against stress-induced apoptosis in cultured cells, protecting them against apoptosis through various mechanisms. Peroxiredoxin has anti-oxidant function and is related to cell proliferation, and signal transduction. It can protect the oxidation of other proteins. Peroxiredoxin has a close relationship with cancer and can eventually become a disease biomarker. This might help to develop a novel treatment method for carcinoma cancer.

  17. Birefringence Bragg Binary (3B) grating, quasi-Bragg grating and immersion gratings

    NASA Astrophysics Data System (ADS)

    Ebizuka, Noboru; Morita, Shin-ya; Yamagata, Yutaka; Sasaki, Minoru; Bianco, Andorea; Tanabe, Ayano; Hashimoto, Nobuyuki; Hirahara, Yasuhiro; Aoki, Wako

    2014-07-01

    A volume phase holographic (VPH) grating achieves high angular dispersion and very high diffraction efficiency for the first diffraction order and for S or P polarization. However the VPH grating could not achieve high diffraction efficiency for non-polarized light at a large diffraction angle because properties of diffraction efficiencies for S and P polarizations are different. Furthermore diffraction efficiency of the VPH grating extinguishes toward a higher diffraction order. A birefringence binary Bragg (3B) grating is a thick transmission grating with optically anisotropic material such as lithium niobate or liquid crystal. The 3B grating achieves diffraction efficiency up to 100% for non-polarized light by tuning of refractive indices for S and P polarizations, even in higher diffraction orders. We fabricated 3B grating with liquid crystal and evaluated the performance of the liquid crystal grating. A quasi-Bragg (QB) grating, which consists long rectangle mirrors aligned in parallel precisely such as a window shade, also achieves high diffraction efficiency toward higher orders. We fabricated QB grating by laminating of silica glass substrates and glued by pressure fusion of gold films. A quasi-Bragg immersion (QBI) grating has smooth mirror hypotenuse and reflector array inside the hypotenuse, instead of step-like grooves of a conventional immersion grating. An incident beam of the QBI grating reflects obliquely at a reflector, then reflects vertically at the mirror surface and reflects again at the same reflector. We are going to fabricate QBI gratings by laminating of mirror plates as similar to fabrication of the QB grating. We will also fabricate silicon and germanium immersion gratings with conventional step-like grooves by means of the latest diamond machining methods. We introduce characteristics and performance of these gratings.

  18. SPITZER IMAGING OF THE NEARBY RICH YOUNG CLUSTER, Cep OB3b

    SciTech Connect

    Allen, Thomas S.; Kryukova, Erin; Thomas Megeath, S.; Gutermuth, Robert A.; Pipher, Judith L.; Naylor, Tim; Jeffries, R. D.; Wolk, Scott J.; Spitzbart, Brad; Muzerolle, James

    2012-05-10

    We map the full extent of a rich massive young cluster in the Cep OB3b association with the Infrared Array Camera and Multi-band Imaging Photometer System instruments aboard the Spitzer Space Telescope and the ACIS instrument aboard the Chandra X-Ray Observatory. At 700 pc, it is revealed to be the second nearest large (>1000 member), young (<5 Myr) cluster known. In contrast to the nearest large cluster, the Orion Nebula Cluster, Cep OB3b is only lightly obscured and is mostly located in a large cavity carved out of the surrounding molecular cloud. Our infrared and X-ray data sets, as well as visible photometry from the literature, are used to take a census of the young stars in Cep OB3b. We find that the young stars within the cluster are concentrated in two sub-clusters; an eastern sub-cluster, near the Cep B molecular clump, and a western sub-cluster, near the Cep F molecular clump. Using our census of young stars, we examine the fraction of young stars with infrared excesses indicative of circumstellar disks. We create a map of the disk fraction throughout the cluster and find that it is spatially variable. Due to these spatial variations, the two sub-clusters exhibit substantially different average disk fractions from each other: 32% {+-} 4% and 50% {+-} 6%. We discuss whether the discrepant disk fractions are due to the photodestruction of disks by the high mass members of the cluster or whether they result from differences in the ages of the sub-clusters. We conclude that the discrepant disk fractions are most likely due to differences in the ages.

  19. Stimulus-Rate Sensitivity Discerns Area 3b of the Human Primary Somatosensory Cortex

    PubMed Central

    Hlushchuk, Yevhen; Simões-Franklin, Cristina; Nangini, Cathy; Hari, Riitta

    2015-01-01

    Previous studies have shown that the hemodynamic response of the primary somatosensory cortex (SI) to electrical median nerve stimulation doubles in strength when the stimulus rate (SR) increases from 1 to 5 Hz. Here we investigated whether such sensitivity to SR is homogenous within the functionally different subareas of the SI cortex, and whether SR sensitivity would help discern area 3b among the other SI subareas. We acquired 3-tesla functional magnetic resonance imaging (fMRI) data from nine healthy adults who received pneumotactile stimuli in 25-s blocks to three right-hand fingers, either at 1, 4, or 10 Hz. The main contrast (all stimulations pooled vs. baseline), applied to the whole brain, first limited the search to the whole SI cortex. The conjunction of SR-sensitive contrasts [4 Hz − 1 Hz] > 0 and [10 Hz − 1 Hz] > 0 ([4Hz − 1Hz] + [10Hz − 1Hz] > 0), applied to the SI cluster, then revealed an anterior-ventral subcluster that reacted more strongly to both 10-Hz and 4-Hz stimuli than to the 1-Hz stimuli. No other SR-sensitive clusters were found at the group-level in the whole-brain analysis. The site of the SR-sensitive SI subcluster corresponds to the canonical position of area 3b; such differentiation was also possible at the individual level in 5 out of 9 subjects. Thus the SR sensitivity of the BOLD response appears to discern area 3b among other subareas of the human SI cortex. PMID:26020639

  20. Purification and physical-chemical properties of methanobactin: a chalkophore from Methylosinus trichosporium OB3b.

    PubMed

    Kim, Hyung J; Galeva, Nadezhda; Larive, Cynthia K; Alterman, Michail; Graham, David W

    2005-04-01

    Methanobactin is an extracellular, copper-binding chromopeptide from the methane-oxidizing bacterium, Methylosinus trichosporium OB3b, believed to be involved in copper detoxification, sequestration, and uptake. Although small (1217.2 Da), methanobactin possesses a complex three-dimensional macrocyclic structure with several unusual moieties. The molecule binds one copper and has the N-2-isopropylester-(4-thionyl-5-hydroxyimidazolate)-Gly(1)-Ser(2)-Cys(3)-Tyr(4)-pyrrolidine-(4-hydroxy-5-thionylimidazolate)-Ser(5)-Cys(6)-Met(7) sequence [Kim, H. J., et al. (2004) Science 305, 1612-1615]. We report methods for purifying methanobactin from M. trichosporium OB3b and present initial evidence of its physiological function. MALDI-TOF MS was used to systematically monitor samples for optimizing purification conditions, and for detecting and analyzing specific metal-methanobactin complexes. Purification was performed by first stabilizing the extracted compound with copper followed by separation using reversed-phase HPLC in neutral pH buffers. Purified methanobactin exhibited UV-visible maxima at 342 nm, a shoulder at 388 nm, and a broad peak at 282 nm. These features were lost upon CuCl(2) titration with appearance of new features at 335, 356, 290, and 255 nm. Furthermore, methanobactin contains two fluorescent moieties, which exhibit broad emissions at 440-460 nm (lambda(max)(ex) at 388 nm) and 390-430 nm (lambda(max)(ex) = 342 nm), respectively. Finally, methanobactin eliminates the growth lag in M. trichosporium OB3b and substantially increases growth rates when cultures are exposed to elevated copper levels. PMID:15794651

  1. DNMT3B7 Expression Promotes Tumor Progression to a More Aggressive Phenotype in Breast Cancer Cells

    PubMed Central

    Brambert, Patrick R.; Kelpsch, Daniel J.; Hameed, Rabia; Desai, Charmi V.; Calafiore, Gianfranco; Godley, Lucy A.; Raimondi, Stacey L.

    2015-01-01

    Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics. PMID:25607950

  2. Methane and Trichloroethylene Degradation by Methylosinus trichosporium OB3b Expressing Particulate Methane Monooxygenase

    PubMed Central

    Lontoh, Sonny; Semrau, Jeremy D.

    1998-01-01

    Whole-cell assays of methane and trichloroethylene (TCE) consumption have been performed on Methylosinus trichosporium OB3b expressing particulate methane monooxygenase (pMMO). From these assays it is apparent that varying the growth concentration of copper causes a change in the kinetics of methane and TCE degradation. For M. trichosporium OB3b, increasing the copper growth concentration from 2.5 to 20 μM caused the maximal degradation rate of methane (Vmax) to decrease from 300 to 82 nmol of methane/min/mg of protein. The methane concentration at half the maximal degradation rate (Ks) also decreased from 62 to 8.3 μM. The pseudo-first-order rate constant for methane, Vmax/Ks, doubled from 4.9 × 10−3 to 9.9 × 10−3 liters/min/mg of protein, however, as the growth concentration of copper increased from 2.5 to 20 μM. TCE degradation by M. trichosporium OB3b was also examined with varying copper and formate concentrations. M. trichosporium OB3b grown with 2.5 μM copper was unable to degrade TCE in both the absence and presence of an exogenous source of reducing equivalents in the form of formate. Cells grown with 20 μM copper, however, were able to degrade TCE regardless of whether formate was provided. Without formate the Vmax for TCE was 2.5 nmol/min/mg of protein, while providing formate increased the Vmax to 4.1 nmol/min/mg of protein. The affinity for TCE also increased with increasing copper, as seen by a change in Ks from 36 to 7.9 μM. Vmax/Ks for TCE degradation by pMMO also increased from 6.9 × 10−5 to 5.2 × 10−4 liters/min/mg of protein with the addition of formate. From these whole-cell studies it is apparent that the amount of copper available is critical in determining the oxidation of substrates in methanotrophs that are expressing only pMMO. PMID:16349516

  3. Comparison of aerosol behavior during sodium fires in CSTF with the HAA-3B code. [LMFBR

    SciTech Connect

    Postma, A.K.; Owen, R.K.

    1980-03-01

    Four large-scale tests using sodium fire aerosol sources have been carried out in the Containment System Test Facility (CSTF). Two of the tests employed pool fires and two used spray fires as the aerosol source. Because the CSTF containment vessel is approximately half-scale (20.3 m in height) of a typical reactor building, the CSTF results have provided a large-scale proof test of the HAA-3B Code. For the two pool fire tests, the measured and predicted airborne concentrations were in good agreement when the aerosol source term was based on post-test measurements of aerosol formation, accounting for water vapor uptake.

  4. A full CI treatment of the 1A1-3B1 separation in methylene

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Taylor, Peter R.

    1986-01-01

    The accuracy of recent theoretical computations of the total energies and the adiabatic separation of the 1A1 and 3B1 states of CH2 is investigated on the basis of complete CI calculations using the double-zeta basis sets of Dunning (1970). The results are presented in a table and characterized in detail. The errors in the separation values are found to range from less than 0.01 kcal/mol for a CASSCF/MRSDCI calculation, to 0.38 kcal/mol for a Davidson-corrected SCF/SDCI calculation, to 14.17 kcal/mol for an uncorrected SCF calculation.

  5. The research of remote sensing duststorm with FY-3B three infrared channels

    NASA Astrophysics Data System (ADS)

    Xu, Hui; Yu, Tao; Cheng, Tianhai; Li, Jiaguo; Lai, Jibao; Liu, Qian

    2012-12-01

    April 8, 2012, the east region of Inner Mongolia out broke a strong sandstorm. Based on the analysis of the spectral characteristics of dust, cloud and surface, this paper propose a duststorm mask algorithm for the identification of dust coverage region by using three infrared channels of FY-3B. By utilizing diurnal variation of brightness temperature of dust aerosol, the bi-temporal thermal dust index was established to represent the intensity of duststorm. Through the analysis we found that BTDI has a high negative correlation with aerosol optical depth which can be used as an effective means to monitor the duststorm.

  6. Occupational dermatitis from Synacril Red 3b liquid (CI Basic Red 22).

    PubMed

    Sadhra, S; Duhra, P; Foulds, I S

    1989-11-01

    A carpet factory worker, exposed to a number of different dyes, developed a severe hand dermatitis. The handling of warm, wet and freshly-dyed yarn with unprotected hands was thought to have caused the onset of dermatitis. Patch testing indicated that the patient was sensitive to only one of the dyes handled, namely Synacril Red 3B liquid, which is based on the single dyestuff Basic Red 22 (CI 11055). Chemical analysis revealed the dyestuff to be of high purity (greater than 95%), suggesting that sensitization was caused by the Basic Red 22 dyestuff itself and not by an avoidable impurity.

  7. Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin.

    PubMed

    Ravindra, Kodihalli C; Selvi, B Ruthrotha; Arif, Mohammed; Reddy, B A Ashok; Thanuja, Gali R; Agrawal, Shipra; Pradhan, Suman Kalyan; Nagashayana, Natesh; Dasgupta, Dipak; Kundu, Tapas K

    2009-09-01

    Lysine acetyltransferases (KATs), p300 (KAT3B), and its close homologue CREB-binding protein (KAT3A) are probably the most widely studied KATs with well documented roles in various cellular processes. Hence, the dysfunction of p300 may result in the dysregulation of gene expression leading to the manifestation of many disorders. The acetyltransferase activity of p300/CREB-binding protein is therefore considered as a target for new generation therapeutics. We describe here a natural compound, plumbagin (RTK1), isolated from Plumbago rosea root extract, that inhibits histone acetyltransferase activity potently in vivo. Interestingly, RTK1 specifically inhibits the p300-mediated acetylation of p53 but not the acetylation by another acetyltransferase, p300/CREB-binding protein -associated factor, PCAF, in vivo. RTK1 inhibits p300 histone acetyltransferase activity in a noncompetitive manner. Docking studies and site-directed mutagenesis of the p300 histone acetyltransferase domain suggest that a single hydroxyl group of RTK1 makes a hydrogen bond with the lysine 1358 residue of this domain. In agreement with this, we found that indeed the hydroxyl group-substituted plumbagin derivatives lost the acetyltransferase inhibitory activity. This study describes for the first time the chemical entity (hydroxyl group) required for the inhibition of acetyltransferase activity.

  8. Optimization and characterization of biosurfactant production from marine Vibrio sp. strain 3B-2

    PubMed Central

    Hu, Xiaoke; Wang, Caixia; Wang, Peng

    2015-01-01

    A biosurfactant-producing bacterium, designated 3B-2, was isolated from marine sediment and identified as Vibrio sp. by 16S rRNA gene sequencing. The culture medium composition was optimized to increase the capability of 3B-2 for producing biosurfactant. The produced biosurfactant was characterized in terms of protein concentration, surface tension, and oil-displacement efficiency. The optimal medium for biosurfactant production contained: 0.5% lactose, 1.1% yeast extract, 2% sodium chloride, and 0.1% disodium hydrogen phosphate. Under optimal conditions (28°C), the surface tension of crude biosurfactant could be reduced to 41 from 71.5 mN/m (water), while its protein concentration was increased to up to 6.5 g/L and the oil displacement efficiency was improved dramatically at 6.5 cm. Two glycoprotein fractions with the molecular masses of 22 and 40 kDa were purified from the biosurfactant, which held great potential for applications in microbial enhanced oil recovery and bioremediation. PMID:26441908

  9. A spin-orbit alignment for the hot Jupiter HATS-3b

    SciTech Connect

    Addison, B. C.; Tinney, C. G.; Wright, D. J.; Bayliss, D.

    2014-09-10

    We have measured the alignment between the orbit of HATS-3b (a recently discovered, slightly inflated Hot Jupiter) and the spin axis of its host star. Data were obtained using the CYCLOPS2 optical-fiber bundle and its simultaneous calibration system feeding the UCLES spectrograph on the Anglo-Australian Telescope. The sky-projected spin-orbit angle of λ = 3° ± 25° was determined from spectroscopic measurements of the Rossiter-McLaughlin effect. This is the first exoplanet discovered through the HATSouth transit survey to have its spin-orbit angle measured. Our results indicate that the orbital plane of HATS-3b is consistent with being aligned to the spin axis of its host star. The low obliquity of the HATS-3 system, which has a relatively hot mid F-type host star, agrees with the general trend observed for Hot Jupiter host stars with effective temperatures >6250 K to have randomly distributed spin-orbit angles.

  10. Physical aging effects on the compressive linear viscoelastic creep of IM7/K3B composite

    NASA Technical Reports Server (NTRS)

    Veazie, David R.; Gates, Thomas S.

    1995-01-01

    An experimental study was undertaken to establish the viscoelastic behavior of 1M7/K3B composite in compression at elevated temperature. Creep compliance, strain recovery and the effects of physical aging on the time dependent response was measured for uniaxial loading at several isothermal conditions below the glass transition temperature (T(g)). The IM7/K3B composite is a graphite reinforced thermoplastic polyimide with a T(g) of approximately 240 C. In a composite, the two matrix dominated compliance terms associated with time dependent behavior occur in the transverse and shear directions. Linear viscoelasticity was used to characterize the creep/recovery behavior and superposition techniques were used to establish the physical aging related material constants. Creep strain was converted to compliance and measured as a function of test time and aging time. Results included creep compliance master curves, physical aging shift factors and shift rates. The description of the unique experimental techniques required for compressive testing is also given.

  11. Trichloroethylene degradation using recombinant bacteria expressing the soluble methane monooxygenase from methylosinus trichosporium OB3b

    SciTech Connect

    Jahng, D.; Kim, C.; Wood, T.K.

    1995-12-01

    Soluble methane monooxygenase (sMMO) from M. trichosporium OB3b has the ability to degrade many halogenated aliphatic compounds that are found in contaminated soil and groundwater. For efficient trichloroethylene (TCE) degradation in a foreign host, efforts are being made to improve inconsistent and low sMMO activity of the recombinant strain constructed previously (Pseudomonas putida F1/pSMMO20). Additional smmo-containing recombinant strains have been constructed including various Pseudomonas, Agrobacterium, and Rhizobium strains. Recombinant facultative methylotrophs containing the smmo locus were also constructed through electroporation and tri-parental mating using a new plasmid pSMMO50. TCE degradation by these recombinant strains was examined. The effect of metal ions on in vitro sMMO activity was also discerned to optimize the expression medium. Among the metal ions examined, Cu(I), Cu(II), Ni(II), and Zn(II) inhibited sMMO purified from trichosporium OB3b, and the effect of the metal ions on each of the components of sMMO will also be discussed. In addition, the post-segregational killing locus (hok/sok) from E. coli plasmid R1 was inserted downstream of the smmo locus to stabilize the recombinant plasmid in these host cells, and chemostat cultures were used to optimize expression of active sMMO by varying the growth rate.

  12. HATS-3b: AN INFLATED HOT JUPITER TRANSITING AN F-TYPE STAR

    SciTech Connect

    Bayliss, D.; Zhou, G.; Schmidt, B.; Penev, K.; Bakos, G. Á.; Hartman, J. D.; Csubry, Z.; Jordán, A.; Suc, V.; Rabus, M.; Brahm, R.; Espinoza, N.; Mancini, L.; Mohler-Fischer, M.; Henning, T.; Nikolov, N.; Csák, B.; Béky, B.; Noyes, R. W.; Buchhave, L.; and others

    2013-11-01

    We report the discovery by the HATSouth survey of HATS-3b, a transiting extrasolar planet orbiting a V = 12.4 F dwarf star. HATS-3b has a period of P = 3.5479 days, mass of M{sub p} = 1.07 M {sub J}, and radius of R{sub p} = 1.38 R {sub J}. Given the radius of the planet, the brightness of the host star, and the stellar rotational velocity (vsin i = 9.0 km s{sup –1}), this system will make an interesting target for future observations to measure the Rossiter-McLaughlin effect and determine its spin-orbit alignment. We detail the low-/medium-resolution reconnaissance spectroscopy that we are now using to deal with large numbers of transiting planet candidates produced by the HATSouth survey. We show that this important step in discovering planets produces log g and T {sub eff} parameters at a precision suitable for efficient candidate vetting, as well as efficiently identifying stellar mass eclipsing binaries with radial velocity semi-amplitudes as low as 1 km s{sup –1}.

  13. CALIFA, a Dedicated Calorimeter for the R{sup 3}B/FAIR

    SciTech Connect

    Cortina-Gil, D.; Alvarez-Pol, H.; Aumann, T.; Avdeichikov, V.; Bendel, M.; Benlliure, J.; Bertini, D.; Bezbakh, A.; Bloch, T.; Böhmer, M.; Borge, M.J.G.; Briz, J.A.; Cabanelas, P.; Casarejos, E.; Carmona Gallardo, M.; Cederkäll, J.; Chulkov, L.; Dierigl, M.; Di Julio, D.; Durán, I.; and others

    2014-06-15

    The R{sup 3}B experiment (Reactions with Relativistic Radioactive Beams) at FAIR (Facility for Antiproton and Ion Research) is a versatile setup dedicated to the study of reactions induced by high-energy radioactive beams. It will provide kinematically complete measurements with high efficiency, acceptance and resolution, making possible a broad physics program with rare-isotopes. CALIFA (CALorimeter for In-Flight detection of gamma-rays and high energy charged pArticles), is a complex detector based on scintillation crystals, that will surround the target of the R{sup 3}B experiment. CALIFA will act as a total absorption gamma-calorimeter and spectrometer, as well as identifier of charged particles from target residues. This versatility is its most challenging requirement, demanding a huge dynamic range, to cover from low energy gamma-rays up to 300 MeV protons. This fact, along with the high-energy of the beams determine the conceptual design of the detector, presented in this paper, together with the technical solutions proposed for its construction.

  14. Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo.

    PubMed

    Lou, Xin; Deshwar, Ashish R; Crump, J Gage; Scott, Ian C

    2011-08-01

    Development of the heart requires recruitment of cardiovascular progenitor cells (CPCs) to the future heart-forming region. CPCs are the building blocks of the heart, and have the potential to form all the major cardiac lineages. However, little is known regarding what regulates CPC fate and behavior. Activity of GATA4, SMARCD3 and TBX5 - the `cardiac BAF' (cBAF) complex, can promote myocardial differentiation in embryonic mouse mesoderm. Here, we exploit the advantages of the zebrafish embryo to gain mechanistic understanding of cBAF activity. Overexpression of smarcd3b and gata5 in zebrafish results in an enlarged heart, whereas combinatorial loss of cBAF components inhibits cardiac differentiation. In transplantation experiments, cBAF acts cell autonomously to promote cardiac fate. Remarkably, cells overexpressing cBAF migrate to the developing heart and differentiate as cardiomyocytes, endocardium and smooth muscle. This is observed even in host embryos that lack endoderm or cardiac mesoderm. Our results reveal an evolutionarily conserved role for cBAF activity in cardiac differentiation. Importantly, they demonstrate that Smarcd3b and Gata5 can induce a primitive, CPC-like state. PMID:21715426

  15. Theoretical Rotation-Vibration Energies of X3B1NH 2+

    NASA Astrophysics Data System (ADS)

    Jensen, Per

    1997-01-01

    The present work reports rotation-vibration energies for the electronic ground state X3B1of the amidogen ion, NH 2+, predicted by means of the MORBID Hamiltonian and computer program (see P. Jensen in"Molecules in the Stellar Environment" (U. G. Jørgensen, Ed.), Lecture Notes in Physics, No. 428. Springer-Verlag, Berlin, 1994, and references therein). The predictions are based on a potential energy function obtained by Barclay et al.( J. Chem. Phys.99,9709-9719 (1993)) in a least-squares fit to the available high-resolution rotation-vibration data for X3B1NH 2+(M. Okumura, B. D. Rehfuss, B. M. Dinelli, M. G. Bawendi, and T. Oka, J. Chem. Phys.90,5918-5923 (1989); Y. Kabbadj, T. R. Huet, D. Uy, and T. Oka, J. Mol. Spectrosc.175,277-288 (1996)). We hope that the predicted energies will facilitate the assignment of further rotation-vibration transitions of this interesting, extremely floppy molecule. Further, we give a detailed discussion of the correlation between the linear-molecule and the bent-molecule quantum numbers which have been used in the literature to label the energy levels of the quasilinear NH 2+ion.

  16. Communal action of microbial cultures for Red HE3B degradation.

    PubMed

    Patil, P S; Phugare, S S; Jadhav, S B; Jadhav, J P

    2010-09-15

    The consortium PMB11 consisting of three bacterial species, originally isolated from dye contaminated soil was identified as Bacillus odysseyi SUK3, Morganella morganii SUK5 and Proteus sp. SUK7. The consortium possessed the ability to decolorize various textile dyes as well as mixtures of dyes. PMB11 could decolorize Red HE3B (50 mg l(-1)) with 99% of decolorization within 12 h in nutrient broth, while in mineral medium it could decolorize up to 97% within 24h. Induction in the activities of various oxidative and reductive enzymes indicates the involvement of these enzymes in decolorization. Biodegradation of the dye was monitored using UV-vis spectroscopy, HPLC and FTIR analysis. The Red HE3B degradation pathway was proposed by GC-MS analysis. Various metabolites formed after the degradation were identified as 2,5-diaminobenzene 6-aminotriazine, aniline 2-sulfate, aniline 3-sulfate, 2-amino 5-chlorotriazine and naphthalene. Phytotoxicity studies revealed that metabolites formed after degradation were significantly less toxic in nature.

  17. Certification procedures for sirius red F3B (CI 35780, Direct red 80).

    PubMed

    Dapson, R W; Fagan, C; Kiernan, J A; Wickersham, T W

    2011-06-01

    Sirius red F3B (CI 35780, Direct red 80) is a polyazo dye used principally in staining methods for collagen and amyloid. For certification by the Biological Stain Commission, a sample of the dye must exhibit an absorption spectrum of characteristic shape with a maximum at 528-529 nm, a small shoulder near 500 nm and narrow peaks at 372, 281-282 and 230-235 nm. Spot tests (color changes with addition of concentrated H(2)SO(4) or HCl and subsequent dilution or neutralization) also are applied. The dye must perform satisfactorily in the picro-sirius red method for collagen by providing red staining of all types of collagen with yellow and green birefringence of fibers. Llewellyn's alkaline sirius red method applied to tissue known to contain amyloid must show red coloration of the products with green birefringence. Dye content, which does not influence significantly the staining properties of sirius red F3B, is not assayed. PMID:21417582

  18. KELT-3b: A HOT JUPITER TRANSITING A V = 9.8 LATE-F STAR

    SciTech Connect

    Pepper, Joshua; Siverd, Robert J.; Stassun, Keivan G.; Cargile, Phillip A.; Dhital, Saurav; Beatty, Thomas G.; Gaudi, B. Scott; Eastman, Jason; Fulton, Benjamin J.; Collins, Karen; Latham, David W.; Bieryla, Allyson; Calkins, Michael L.; Esquerdo, Gilbert A.; Berlind, Perry; Buchhave, Lars A.; Jensen, Eric L. N.; Manner, Mark; Penev, Kaloyan; Crepp, Justin R.; and others

    2013-08-10

    We report the discovery of KELT-3b, a moderately inflated transiting hot Jupiter with a mass of 1.477{sub -0.067}{sup +0.066} M{sub J}, radius of 1.345 {+-} 0.072 R{sub J}, and an orbital period of 2.7033904 {+-} 0.000010 days. The host star, KELT-3, is a V = 9.8 late F star with M{sub *} = 1.278{sub -0.061}{sup +0.063} M{sub sun}, R{sub *} = 1.472{sub -0.067}{sup +0.065} R{sub sun}, T{sub eff}= 6306{sub -49}{sup +50} K, log (g) = 4.209{sub -0.031}{sup +0.033}, and [Fe/H] = 0.044{sub -0.082}{sup +0.080}, and has a likely proper motion companion. KELT-3b is the third transiting exoplanet discovered by the KELT survey, and is orbiting one of the 20 brightest known transiting planet host stars, making it a promising candidate for detailed characterization studies. Although we infer that KELT-3 is significantly evolved, a preliminary analysis of the stellar and orbital evolution of the system suggests that the planet has likely always received a level of incident flux above the empirically identified threshold for radius inflation suggested by Demory and Seager.

  19. On the last explosions of carbonatite pipe G3b, Gross Brukkaros, Namibia

    NASA Astrophysics Data System (ADS)

    Lorenz, Volker; Kurszlaukis, Stephan

    Pipe G3b is part of the Upper Cretaceous carbonatitic Gross Brukkaros Volcanic Field in southern Namibia. The pipe represents the root zone of a diatreme and is located 2800m west of the rim of Gross Brukkaros, a downsag caldera. The pipe is exposed approximately 550m below the original Upper Cretaceous land surface. It cuts down into its own feeder dyke, 0.3m thick. The pipe coalesced from two small pipes and in plan view is 19m long and 12m wide. It consists of fragmented Cambrian Nama quartzites and shales of the Fish River subgroup. Despite intensive brecciation, the stratigraphic sequence of the country rocks is almost preserved in the pipe. In addition, the feeder dyke became fragmented too and can be traced in a 2- to 3-m-wide zone full of carbonatite blocks along the southern margin of the pipe. The void space of the breccia is 30-50% in volume. Finally, after the disruption of country rocks and feeder dyke, a little carbonatite magma intruded some of the void space. The breccia of pipe G3b is considered to represent a root zone at the transition from the feeder dyke into a diatreme above. Formation of the breccia required a shock wave thought to have been associated with a last explosion of the diatreme immediately above the present level of exposure. The explosion can be shown to have been phreatomagmatic in origin.

  20. Douglas OA-4A Dolphin

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Douglas OA-4A Dolphin: This twin-engine Douglas OA-4A Dolphin was unusual in comparison with other OA-4s in that it employed a nose wheel instead of a tail wheel during its NACA testing at Langley. Here is is seen in the NACA hangar in September 1938.

  1. a Bayesian Approach for Calibration of Trmm 3B42 Over North Amazonia

    NASA Astrophysics Data System (ADS)

    Linguet, L.; Marie-Joseph, I.; Becker, M.; Seyler, F.

    2013-12-01

    Northern Amazonian regions experience extremes conditions like floods and droughts. These regions are also characterized by the limited spatial coverage of ground based rain gauges, and unavailability of real-time rainfall data. Satellite-based rainfall estimates (SRE) may be one of the best and appropriate approaches in detecting rainfall distribution. However SRE data need specific calibration and validation for use in flood and drought monitoring activities. This study aimed to calibrate of TRMM 3B42 RT rainfall products over northern Amazonia with a Bayesian filtering approach [1] [2]. The study area is located north of the Amazon River and includes the three Guianas and northern states of Brazil. A set of daily satellite rainfall products with spatial resolution of 0.25°x0.25° (TRMM 3B42 RT) from the year 2000 to 2010 has been selected. Ground reference data are located in French Guiana (27 ground stations from French national meteorological agency) and in the northern Brazilian states (70 ground stations from Brazilian Agência Nacional de Aguas). A lot of bias-adjustment methods rely on computing the difference between satellite and gauge-based precipitation [3] [4]. In this study we defend the idea that an inverse approach based on sequential Monte Carlo filtering helps to calibrate of TRMM 3B42 RT rainfall products. The developed method combines a model of the rainfall process at rain gauge locations with a stochastic observation model based on the joint distribution between ground reference data of the state variable (rainfall data) and the observed satellite data. 50% of the total ground based rainfall measurements were used for the joint distribution and the remaining 50% were used for validation purposes. Validation of the method has been done by comparing the corrected satellite data against independent observed data from rain gauges using the standard verification techniques: mean bias error, root mean square error, and correlation coefficient

  2. 75 FR 1017 - Airworthiness Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-08

    ... service certain part number (P/N) and serial number (S/N) fan blades within compliance times specified in the AD, inspecting the fan blade abradable rub strip on certain engines for wear, inspecting the fan... corrects the effectivity for certain fan blades requiring corrective actions and changes the effective...

  3. Soil moisture from the recent AMSR2 and FY3B multi-frequency passive microwave sensors

    NASA Astrophysics Data System (ADS)

    Parinussa, Robert; Wang, Guojie; de Jeu, Richard

    2014-05-01

    Over the years several different multi-frequency passive microwave sensors were used to estimate surface soil moisture. An historical multi-frequency passive microwave database from these satellite platforms was already used to generate a long term (32 years) surface soil moisture dataset. The Land Parameter Retrieval Algorithm (LPRM) was applied to this historical multi-frequency passive microwave database, including the Advanced Microwave Scanning Radiometer - Earth Observing System (AMSR-E), that plays a dominant role in the 2002-2011 period. The Advanced Microwave Scanning Radiometer 2 (AMSR2) shares a similar design with its predecessor, it was improved based on general technical development as well as the valuable heritage that AMSR-E left behind. Most recently, the Japanese Aerospace Exploration Agency (JAXA) started offering brightness temperature observations from the AMSR2 radiometer. In the recent years, China's National Satellite Meteorological Center (NSMC) developed meteorological satellites. The NSMC has polar orbiting sun-synchronized meteorological satellites in operation since 1988 in the so-called FengYun (FY) satellite series. FY3 is China's 2nd generation polar orbiting satellite series, its design was based on the previous polar orbiting satellite series and FY3 will ultimately become series of four satellites (FY3A to FY3D). The FY3B satellite is the 2nd satellite of the FY3 series and it's the 1st in the series to carry a microwave imager (MWRI) onboard observing the Earth's surface in 10 microwave channels. Brightness temperature observations of these recently developed sensors were compared to the existing database. An inter-calibration step was performed in order to overcome small difference in brightness temperature observations as a result of the different sensor calibration procedures. The LPRM was applied to observations made by the FY3B and AMSR2 sensors resulting in global soil moisture products. After the implementation of the

  4. Stress-mediated Sin3B activation leads to negative regulation of subset of p53 target genes.

    PubMed

    Kadamb, Rama; Mittal, Shilpi; Bansal, Nidhi; Saluja, Daman

    2015-01-01

    The multiprotein SWI-independent 3 (Sin3)-HDAC (histone deacetylase) corepressor complex mediates gene repression through its interaction with DNA-binding factors and recruitment of chromatin-modifying proteins on to the promoters of target gene. Previously, an increased expression of Sin3B and tumour suppressor protein, p53 has been established upon adriamycin treatment. We, now provide evidence that Sin3B expression is significantly up-regulated under variety of stress conditions and this response is not stress-type specific. We observed that Sin3B expression is significantly up-regulated both at transcript and at protein level upon DNA damage induced by bleomycin drug, a radiomimetic agent. This increase in Sin3B expression upon stress is found to be p53-dependent and is associated with enhanced interaction of Sin3B with Ser(15) phosphorylated p53. Binding of Sin3-HDAC repressor complex on to the promoters of p53 target genes influences gene regulation by altering histone modifications (H3K9me3 and H3K27me3) at target genes. Furthermore, knockdown of Sin3B by shRNA severely compromises p53-mediated gene repression under stress conditions. Taken together, these results suggest that stress-induced Sin3B activation is p53-dependent and is essential for p53-mediated repression of its selective target genes. The present study has an implication in understanding the transrepression mechanism of p53 under DNA damaging conditions.

  5. Precipitation comparison for the CFSR, MERRA, TRMM3B42 and Combined Scheme datasets in Bolivia

    NASA Astrophysics Data System (ADS)

    Blacutt, Luis A.; Herdies, Dirceu L.; de Gonçalves, Luis Gustavo G.; Vila, Daniel A.; Andrade, Marcos

    2015-09-01

    An overwhelming number of applications depend on reliable precipitation estimations. However, over complex terrain in regions such as the Andes or the southwestern Amazon, the spatial coverage of rain gauges is scarce. Two reanalysis datasets, a satellite algorithm and a scheme that combines surface observations with satellite estimations were selected for studying rainfall in the following areas of Bolivia: the central Andes, Altiplano, southwestern Amazonia, and Chaco. These Bolivian regions can be divided into three main basins: the Altiplano, La Plata, and Amazon. The selected reanalyses were the Modern-Era Retrospective Analysis for Research and Applications, which has a horizontal resolution (~ 50 km) conducive for studying rainfall in relatively small precipitation systems, and the Climate Forecast System Reanalysis and Reforecast, which features an improved horizontal resolution (~ 38 km). The third dataset was the seventh version of the Tropical Rainfall Measurement Mission 3B42 algorithm, which is conducive for studying rainfall at an ~ 25 km horizontal resolution. The fourth dataset utilizes a new technique known as the Combined Scheme, which successfully removes satellite bias. All four of these datasets were aggregated to a coarser resolution. Additionally, the daily totals were calculated to match the cumulative daily values of the ground observations. This research aimed to describe and compare precipitations in the two reanalysis datasets, the satellite-algorithm dataset, and the Combined Scheme with ground observations. Two seasons were selected for studying the precipitation estimates: the rainy season (December-February) and the dry season (June-August). The average, bias, standard deviation, correlation coefficient, and root mean square error were calculated. Moreover, a contingency table was generated to calculate the accuracy, bias frequency, probability of detection, false alarm ratio, and equitable threat score. All four datasets correctly

  6. The origin of hyper-ferroelectricity in Li BO3 (B=V, Nb, Ta, Os)

    NASA Astrophysics Data System (ADS)

    He, Lixin; Li, Pengfei; Ren, Xinguo; Guo, G.-C.

    The electronic and structural properties of Li BO3 (B=V, Nb, Ta, Os) are investigated via first-principles methods. We show that Li BO3 are belong to the recently proposed hyperferroelectrics, i.e., they all have unstable longitudinal optical phonon modes. Especially, the ferroelectric-like instability in the metal LiOsO3 is a limiting case of a hyperferroelectrics, whose optical dielectric constant goes to infinity. We further show via an effective Hamiltonian that in contrast to normal proper ferroelectricity, in which the ferroelectric instability usually comes from long range coulomb interactions, the hyperferroelectric instability is due to the structure instability driven by the short range interactions. This could happen in systems with large ion size mismatches, which therefore provides a useful guidance in searching for novel hyperferroelectrics.

  7. Dynamic Wind-Tunnel Testing of a Sub-Scale Iced S-3B Viking

    NASA Technical Reports Server (NTRS)

    Lee, Sam; Barnhart, Billy; Ratvasky, Thomas P.

    2012-01-01

    The effect of ice accretion on a 1/12-scale complete aircraft model of S-3B Viking was studied in a rotary-balance wind tunnel. Two types of ice accretions were considered: ice protection system failure shape and runback shapes that form downstream of the thermal ice protection system. The results showed that the ice shapes altered the stall characteristics of the aircraft. The ice shapes also reduced the control surface effectiveness, but mostly near the stall angle of attack. There were some discrepancies with the data with the flaps deflected that were attributed to the low Reynolds number of the test. Rotational and forced-oscillation studies showed that the effects of ice were mostly in the longitudinal forces, and the effects on the lateral forces were relatively minor.

  8. Non-Abelian quasigapless modes localized on mass vortices in superfluid He3-B

    NASA Astrophysics Data System (ADS)

    Nitta, Muneto; Shifman, Mikhail; Vinci, Walter

    2013-04-01

    Kelvin waves, or Kelvons, have been known for a long time as gapless excitations propagating along superfluid vortices. These modes can be interpreted as the Nambu-Goldstone excitations arising from the spontaneous breaking of the translational symmetry. Recently a different type of gapless excitation localized on strings—the so-called non-Abelian mode—attracted much attention in high-energy physics. We discuss their relevance in condensed matter physics. Non-Abelian rotational quasigapless excitations could appear on the mass vortices in the B phase of the superfluid He3, due to the fact that the order parameter in He3-B is tensorial. While the U(1) rotational excitations are well established in vortices with asymmetric cores, the non-Abelian rotational excitations belonging to the same family were not considered.

  9. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation.

    PubMed

    Shen, Weijun; Taylor, Brandon; Jin, Qihui; Nguyen-Tran, Van; Meeusen, Shelly; Zhang, You-Qing; Kamireddy, Anwesh; Swafford, Austin; Powers, Andrew F; Walker, John; Lamb, John; Bursalaya, Badry; DiDonato, Michael; Harb, George; Qiu, Minhua; Filippi, Christophe M; Deaton, Lisa; Turk, Carolina N; Suarez-Pinzon, Wilma L; Liu, Yahu; Hao, Xueshi; Mo, Tingting; Yan, Shanshan; Li, Jing; Herman, Ann E; Hering, Bernhard J; Wu, Tom; Martin Seidel, H; McNamara, Peter; Glynne, Richard; Laffitte, Bryan

    2015-01-01

    Insufficient pancreatic β-cell mass or function results in diabetes mellitus. While significant progress has been made in regulating insulin secretion from β-cells in diabetic patients, no pharmacological agents have been described that increase β-cell replication in humans. Here we report aminopyrazine compounds that stimulate robust β-cell proliferation in adult primary islets, most likely as a result of combined inhibition of DYRK1A and GSK3B. Aminopyrazine-treated human islets retain functionality in vitro and after transplantation into diabetic mice. Oral dosing of these compounds in diabetic mice induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control. Biochemical, genetic and cell biology data point to Dyrk1a as the key molecular target. This study supports the feasibility of treating diabetes with an oral therapy to restore β-cell mass, and highlights a tractable pathway for future drug discovery efforts. PMID:26496802

  10. [Transporting models of reactive X-3B red dye in water-soil-crop continuums].

    PubMed

    Zhou, Qixing

    2002-02-01

    Reactive X-3B red dye entering into environment is a typical persistent organic pollutant(POPs). Transport of the dye from water to soil and from soil to crop compartment is a continuous ecological process. According to the cognitionm, the quantitative depiction of the process using mathematical models was theoretically discussed. Some of the mathematical models were also verified using burozem-soybean, cinnamon soil-wheat, krasnozem-radish, aquorizem-rice systems. In particular, transference of the dye from water compartment to soil compartment by way of adsorbent mechanisms was accorded with the Langmuir model, and movement of the dye from soil compartment to crop compartment on the basis of root-absorbing mechanisms could be expressed using logarithmic crop-soil accumulation factor(CSAF) models. PMID:11993110

  11. Selenium regulation of glutathione peroxidase in human hepatoma cell line Hep3B.

    PubMed

    Baker, R D; Baker, S S; LaRosa, K; Whitney, C; Newburger, P E

    1993-07-01

    Glutathione peroxidase is an important enzyme in cellular antioxidant defense systems, detoxifying peroxides and hydroperoxides. As a component of the glutathione cycle, it protects the liver from reactive oxygen metabolites. Selenocysteine is present at the catalytic site of glutathione peroxidase, and selenium availability regulates glutathione peroxidase enzyme activity. Hep3B cells, a well-differentiated human hepatoma-derived cell line, exhibited time-dependent decrease in glutathione peroxidase activity (nmol NADPH oxidized/min/mg protein, mean +/- SE) when incubated in selenium-free medium for 10 days (Day 0, 21.8 +/- 7.3; Day 2, 10.9 +/- 1.2; Day 4, 7.9 +/- 0.8; Day 6, 4.0 +/- 0.7; Day 8, 4.5 +/- 0.6; Day 10, 1.6 +/- 0.4). With the reintroduction of selenium, glutathione peroxidase activity returned. A second human hepatoma cell line, HepG2, demonstrated a similar pattern when depleted of and then repleted with selenium. To assess protein synthesis, glutathione peroxidase activity was measured in deficient and replete Hep3B cells incubated with and without selenium and with and without cycloheximide. Deficient cells (mean +/- SE) (4.9 +/- 0.2) showed an increase in glutathione peroxidase activity after 24 h in selenium-containing medium (11.6 +/- 0.2), but not when cycloheximide was included in the medium (6.9 +/- 0.5) or when cycloheximide and no selenium was included (5.3 +/- 0.8). Replete Hep3B cells (40.1 +/- 1.1) demonstrated decreased glutathione peroxidase after 24 h in medium without selenium (34.0 +/- 1.4), medium with both cycloheximide and selenium (34.0 +/- 2.6), and medium without selenium and containing cycloheximide (37.6 +/- 1.3). These data suggest that protein synthesis is needed for selenium repletion to exert control on glutathione peroxidase activity. Using a cDNA for human glutathione peroxidase (GPx1), selenium-deficient and replete Hep3B cell RNA was analyzed by Northern blot. mRNA for GPx was quantified by densitometry. The steady

  12. Preparation of integrated multifunction Pb3B10O16[OH]4 whisker by solvothermal method

    NASA Astrophysics Data System (ADS)

    Sun, Qing; Zhang, Quan-Ping; Zheng, Jian; Zhou, Dong; Li, Yin-Tao; Zhou, Yuan-Lin

    2016-03-01

    Elaborate design of multifunction materials is of great scientific and technological significance; but it is a great challenge. Here, a lead borate is successfully prepared via a facile solvothermal method. The results of XRD, SEM and TEM show the product is a kind of whiskers with uniform structure and high length-diameter ratio, which is represented as Pb3B10O16[OH]4. The whisker is capable of attenuating both γ-rays and neutrons and shows a little difference with that of the equal molar mass of Pb and B in mixture. In addition, the whisker displays good photoluminescence properties, especially for luminescent intensity. These significant results indicate an integrated multifunction whisker that will stimulate new application research.

  13. Intermediate type excitons in Schottky barriers of A3B6 layer semiconductors and UV photodetectors

    NASA Astrophysics Data System (ADS)

    Alekperov, O. Z.; Guseinov, N. M.; Nadjafov, A. I.

    2006-09-01

    Photoelectric and photovoltaic spectra of Schottky barrier (SB) structures of InSe, GaSe and GaS layered semiconductors (LS) are investigated at quantum energies from the band edge excitons of corresponding materials up to 6.5eV. Spectral dependences of photoconductivity (PC) of photo resistors and barrier structures are strongly different at the quantum energies corresponding to the intermediate type excitons (ITE) observed in these semiconductors. It was suggested that high UV photoconductivity of A3B6 LS is due to existence of high mobility light carriers in the depth of the band structure. It is shown that SB of semitransparent Au-InSe is high sensitive photo detector in UV region of spectra.

  14. RAMONA-3B calculations for Browns Ferry ATWS (Anticipated Transient Without Scram) study

    SciTech Connect

    Saha, P; Slovik, G C; Neymotin, L Y

    1987-02-01

    Several aspects of the Anticipated Transient Without Scram (ATWS) initiated by an inadvertent closure of all Main Steam Isolation Valves (MSIV) in a typical BWR/4 are analyzed in the report. The analysis is performed using the Brookhaven National Laboratory code, RAMONA-3B, which employs a three-dimensional neutron kinetics model coupled with a parallel-channel thermal hydraulics in representing a Boiling Water Reactor (BWR) Core. Four different transient scenarios have been investigated: (a) downcomer water level and reactor pressure control, (b) manual control rod insertion transient, (c) high pressure boil-off, and (d) recirculation pump trip failure. Results of these calculations should provide better understanding of mitigative effects of operator actions during ATWS, thus helping in the development of adequate Emergency Procedure Guidelines (EPG) required for the BWR plant safety. A few unresolved questions subject to future investigations are also discussed.

  15. Proinsulin C-peptide inhibits lipolysis in diabetic rat adipose tissue through phosphodiestrase-3B enzyme.

    PubMed

    Ghorbani, A; Omrani, G R; Hadjzadeh, M A; Varedi, M

    2013-03-01

    We have previously reported that C-peptide modulates insulin-mediated inhibition of lipolysis and glucose consumption but has no significant effects per se on adipose tissue of normal rats. It has been repeatedly observed that certain actions of C-peptide are restricted to the diabetic states. In the present study, therefore, we examined whether C-peptide alters lipolysis in adipose tissue of diabetic rats. Rats were rendered diabetic by streptozotocin and divided into 2 groups; insulin treated and untreated. Retroperitoneal adipose tissue was excised aseptically, subjected to organ culture and incubated with rat C-peptide, insulin, or a combination of both peptides in the presence or absence of isoproterenol. Tissue lipolysis was assessed by the rate of glycerol release into the culture media. The cultures were pretreated with cilostamide, a phosphodiesterase-3B enzyme inhibitor, when the role of this enzyme was to be examined. C-Peptide on its own, like insulin, significantly inhibited isoproterenol-stimulated lipolysis in the adipose tissue of untreated diabetic rats. The effect was enhanced by a combination of C-peptide and insulin. Notably, the C-peptide's effect was totally blocked in the presence of cilostamide. In the adipose tissue of insulin treated rats, however, C-peptide failed to show any significant antilipolytic effects. These data show that C-peptide has the potential to act, conditionally, as an antilipolytic hormone by activating phosphodiesterase-3B and suggest that the action may contribute to the C-peptide's beneficial effects on diabetes-induced complications. PMID:22990990

  16. Cerium Regulates Expression of Alternative Methanol Dehydrogenases in Methylosinus trichosporium OB3b

    PubMed Central

    Farhan Ul Haque, Muhammad; Kalidass, Bhagyalakshmi; Bandow, Nathan; Turpin, Erick A.; DiSpirito, Alan A.

    2015-01-01

    Methanotrophs have multiple methane monooxygenases that are well known to be regulated by copper, i.e., a “copper switch.” At low copper/biomass ratios the soluble methane monooxygenase (sMMO) is expressed while expression and activity of the particulate methane monooxygenase (pMMO) increases with increasing availability of copper. In many methanotrophs there are also multiple methanol dehydrogenases (MeDHs), one based on Mxa and another based on Xox. Mxa-MeDH is known to have calcium in its active site, while Xox-MeDHs have been shown to have rare earth elements in their active site. We show here that the expression levels of Mxa-MeDH and Xox-MeDH in Methylosinus trichosporium OB3b significantly decreased and increased, respectively, when grown in the presence of cerium but the absence of copper compared to the absence of both metals. Expression of sMMO and pMMO was not affected. In the presence of copper, the effect of cerium on gene expression was less significant, i.e., expression of Mxa-MeDH in the presence of copper and cerium was slightly lower than in the presence of copper alone, but Xox-MeDH was again found to increase significantly. As expected, the addition of copper caused sMMO and pMMO expression levels to significantly decrease and increase, respectively, but the simultaneous addition of cerium had no discernible effect on MMO expression. As a result, it appears Mxa-MeDH can be uncoupled from methane oxidation by sMMO in M. trichosporium OB3b but not from pMMO. PMID:26296730

  17. The Arctic Boundary Layer Expedition (ABLE-3B): July-August 1990

    NASA Astrophysics Data System (ADS)

    Harriss, R. C.; Wofsy, S. C.; Hoell, J. M.; Bendura, R. J.; Drewry, J. W.; McNeal, R. J.; Pierce, D.; Rabine, V.; Snell, R. L.

    1994-01-01

    The Arctic Boundary Layer Expedition (ABLE) 3B used data from ground-based, aircraft, and satellite platforms to characterize the chemistry and dynamics of the troposphere in subarctic and Arctic regions of midcontinent and eastern Canada during July-August 1990. This paper reports the experimental design for ABLE 3B and a brief overview of results. The detailed results are presented in a series of papers in this issue. The chemical composition of the atmospheric mixed layer over remote tundra, boreal wetland, and forested environments was influenced by emissions of CH4 and nonmethane hydrocarbons from biogenic sources, emissions of gases and aerosols from local biomass burning, and transport of pollutants into the study areas from urban/industrial sources. Minimum concentrations of both trace gas and aerosol species in boundary layer air were associated with Arctic source areas. In the free troposphere the biospheric influence was undetectable, and major sources of chemical variability were related to long-range transport of pollutants into the study areas from biomass burning and industrial sources in Alaska and the Great Lakes regions, respectively. Minimum concentrations of both trace gas and aerosol species in the free troposphere were associated with a persistent, widespread air mass which both chemistry and air mass trajectory analyses suggested had originated in the tropical Pacific. Subsidence of air from the upper troposphere and lower stratosphere frequently enhanced ozone and influenced other trace gas and aerosol species at midtropospheric altitudes. The North American Arctic is a complex dynamical and chemical environment with considerable spatial and temporal variability in aerosol and trace gas concentrations. The use of atmospheric chemical indicators for climate change detection will require a much more comprehensive Arctic monitoring program than currently exists.

  18. Study on the Retrieval of Snow Depth from FY3B/MWRI in the Atctic

    NASA Astrophysics Data System (ADS)

    Li, Lele; Chen, Haihua; Guan, Lei

    2016-06-01

    temperatures. Given the high albedo and low thermal conductivity, snow is regarded as one of the key reasons for the amplification of the warming in polar regions. The distributions of sea ice and snow depth are essential to the whole thermal conduction in the Arctic. This study focused on the retrieval of snow depth on sea ice from brightness temperatures of the MicroWave Radiometer Imager (MWRI) onboard the FengYun (FY)-3B satellite during the period from December 1, 2010 to April 30, 2011. After cross calibrated to the Advanced Microwave Scanning Radiometer-EOS (AMSR-E) Level 2A data, the MWRI brightness temperatures were applied to calculate the sea ice concentrations based on the Arctic Radiation and Turbulence Interaction Study Sea Ice (ASI) algorithm. According to the proportional relationship between the snow depth and the surface scattering in 18.7 and 36.5 GHz, the snow depths were derived. In order to eliminate the influence of uncertainties in grain sizes of snow as well as sporadic weather effects, the seven-day averaged snow depths were calculated. Then the results were compared with the snow depths from the AMSR-E Level 3 Sea Ice products. The bias of differences between the MWRI and the AMSR-E Level 3 products are ranged between -1.09 and -0.32 cm while the standard deviations and the correlation coefficients are ranged from 2.47 to 2.88 cm and from 0.78 to 0.90 for different months. As a result, it could be summarized that FY3B/MWRI showed a promising prospect in retrieving snow depth on sea ice.

  19. Cerium regulates expression of alternative methanol dehydrogenases in Methylosinus trichosporium OB3b.

    PubMed

    Farhan Ul Haque, Muhammad; Kalidass, Bhagyalakshmi; Bandow, Nathan; Turpin, Erick A; DiSpirito, Alan A; Semrau, Jeremy D

    2015-11-01

    Methanotrophs have multiple methane monooxygenases that are well known to be regulated by copper, i.e., a "copper switch." At low copper/biomass ratios the soluble methane monooxygenase (sMMO) is expressed while expression and activity of the particulate methane monooxygenase (pMMO) increases with increasing availability of copper. In many methanotrophs there are also multiple methanol dehydrogenases (MeDHs), one based on Mxa and another based on Xox. Mxa-MeDH is known to have calcium in its active site, while Xox-MeDHs have been shown to have rare earth elements in their active site. We show here that the expression levels of Mxa-MeDH and Xox-MeDH in Methylosinus trichosporium OB3b significantly decreased and increased, respectively, when grown in the presence of cerium but the absence of copper compared to the absence of both metals. Expression of sMMO and pMMO was not affected. In the presence of copper, the effect of cerium on gene expression was less significant, i.e., expression of Mxa-MeDH in the presence of copper and cerium was slightly lower than in the presence of copper alone, but Xox-MeDH was again found to increase significantly. As expected, the addition of copper caused sMMO and pMMO expression levels to significantly decrease and increase, respectively, but the simultaneous addition of cerium had no discernible effect on MMO expression. As a result, it appears Mxa-MeDH can be uncoupled from methane oxidation by sMMO in M. trichosporium OB3b but not from pMMO. PMID:26296730

  20. HATS-3b: An Inflated Hot Jupiter Transiting an F-type Star

    NASA Astrophysics Data System (ADS)

    Bayliss, D.; Zhou, G.; Penev, K.; Bakos, G. Á.; Hartman, J. D.; Jordán, A.; Mancini, L.; Mohler-Fischer, M.; Suc, V.; Rabus, M.; Béky, B.; Csubry, Z.; Buchhave, L.; Henning, T.; Nikolov, N.; Csák, B.; Brahm, R.; Espinoza, N.; Noyes, R. W.; Schmidt, B.; Conroy, P.; Wright, D. J.; Tinney, C. G.; Addison, B. C.; Sackett, P. D.; Sasselov, D. D.; Lázár, J.; Papp, I.; Sári, P.

    2013-11-01

    We report the discovery by the HATSouth survey of HATS-3b, a transiting extrasolar planet orbiting a V = 12.4 F dwarf star. HATS-3b has a period of P = 3.5479 days, mass of Mp = 1.07 M J, and radius of Rp = 1.38 R J. Given the radius of the planet, the brightness of the host star, and the stellar rotational velocity (vsin i = 9.0 km s-1), this system will make an interesting target for future observations to measure the Rossiter-McLaughlin effect and determine its spin-orbit alignment. We detail the low-/medium-resolution reconnaissance spectroscopy that we are now using to deal with large numbers of transiting planet candidates produced by the HATSouth survey. We show that this important step in discovering planets produces log g and T eff parameters at a precision suitable for efficient candidate vetting, as well as efficiently identifying stellar mass eclipsing binaries with radial velocity semi-amplitudes as low as 1 km s-1. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), and the Australian National University (ANU). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with collaborators at the Pontificia Universidad Católica de Chile (PUC), the station at the High Energy Spectroscopic Survey (HESS) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU.

  1. The ‘de novo’ DNA methyltransferase Dnmt3b compensates the Dnmt1-deficient intestinal epithelium

    PubMed Central

    Elliott, Ellen N; Sheaffer, Karyn L; Kaestner, Klaus H

    2016-01-01

    Dnmt1 is critical for immediate postnatal intestinal development, but is not required for the survival of the adult intestinal epithelium, the only rapidly dividing somatic tissue for which this has been shown. Acute Dnmt1 deletion elicits dramatic hypomethylation and genomic instability. Recovery of DNA methylation state and intestinal health is dependent on the de novo methyltransferase Dnmt3b. Ablation of both Dnmt1 and Dnmt3b in the intestinal epithelium is lethal, while deletion of either Dnmt1 or Dnmt3b has no effect on survival. These results demonstrate that Dnmt1 and Dnmt3b cooperate to maintain DNA methylation and genomic integrity in the intestinal epithelium. DOI: http://dx.doi.org/10.7554/eLife.12975.001 PMID:26808831

  2. Synthesis, structure and properties of Li{sub 2}Rh{sub 3}B{sub 2}

    SciTech Connect

    Bailey, Mark S. Lobkovsky, Emil B.; Hinks, David G.; Claus, Helmut; Hor, Yew San; Schlueter, John A.; Mitchell, John F.

    2007-04-15

    Li{sub 2}Rh{sub 3}B{sub 2} has been synthesized at 1000 deg. C from a stoichiometric mix of rhodium and boron and an excess of lithium. Li{sub 2}Rh{sub 3}B{sub 2} crystallizes in the orthorhombic space group Pbam (no. 55, Z=2) with room temperature lattice constants a=5.7712(1) A, b=9.4377(2) A, c=2.8301(1) A and cell volume 154.149(6) A{sup 3}. The structure was solved from single crystal X-ray diffraction yielding the final R indices (all data) R1=2.8% and wR2=4.7%. The structure is a distortion of the CeCo{sub 3}B{sub 2} structure type, containing a network of Rh{sub 6}B trigonal prisms and short Li-Li contacts of 2.28(2) A. Li{sub 2}Rh{sub 3}B{sub 2} is a diamagnetic metal with a room temperature resistivity of 19 {mu}{omega} cm, as determined by magnetic susceptibility and single crystal transport measurements. The measured diamagnetism and electronic structure calculations show that Li{sub 2}Rh{sub 3}B{sub 2} contains rhodium in a d {sup 10} configuration. - Graphical abstract: Li{sub 2}Rh{sub 3}B{sub 2}, a diamagnetic metal, has been synthesized from a lithium flux. It adopts a distortion of the CeCo{sub 3}B{sub 2} structure type and is closely related to the 3 K superconductor, LaRh{sub 3}B{sub 2}. Pairs of lithium ions (white) fill the channels formed by rhodium-boron trigonal prisms (gray)

  3. Measurement of OH, H2SO4, MSA, and HNO3 Aboard the P-3B Aircraft

    NASA Technical Reports Server (NTRS)

    Eisele, F. L.

    2003-01-01

    This paper addresses the measurement of OH, H2SO4, MSA, and HNO3 aboard the P-3B aircraft under the following headings: 1) Performance Report; 2) Highlights of OH, H2SO4, and MSA Measurements Made Aboard the NASA P-3B During TRACE-P; 3) Development and characteristics of an airborne-based instrument used to measure nitric acid during the NASA TRACE-P field experiment.

  4. Crystal structure of a 3B3 variant - A broadly neutralizing HIV-1 scFv antibody

    SciTech Connect

    Clark, K. Reed; Walsh, Scott T.R.

    2009-12-10

    We present the crystal structure determination of an anti-HIV-1 gp120 single-chain variable fragment antibody variant, 3B3, at 2.5 {angstrom} resolution. This 3B3 variant was derived from the b12 antibody, using phage display and site-directed mutagenesis of the variable heavy chain (V{sub H}) complementary-determining regions (CDRs). 3B3 exhibits enhanced binding affinity and neutralization activity against several cross-clade primary isolates of HIV-1 by interaction with the recessed CD4-binding site on the gp120 envelope protein. Comparison with the structures of the unbound and bound forms of b12, the 3B3 structure closely resembles these structures with minimal differences with two notable exceptions. First, there is a reorientation of the CDR-H3 of the V{sub H} domain where the primary sequences evolved from b12 to 3B3. The structural changes in CDR-H3 of 3B3, in light of the b12-gp120 complex structure, allow for positioning an additional Trp side chain in the binding interface with gp120. Finally, the second region of structural change involves two peptide bond flips in CDR-L3 of the variable light (VL) domain triggered by a point mutation in CDR-H3 of Q100eY resulting in changes in the intramolecular hydrogen bonding patterning between the VL and VH domains. Thus, the enhanced binding affinities and neutralization capabilities of 3B3 relative to b12 probably result from higher hydrophobic driving potential by burying more aromatic residues at the 3B3-gp120 interface and by indirect stabilization of intramolecular contacts of the core framework residues between the VL and VH domains possibly through more favorable entropic effect through the expulsion of water.

  5. 6H-Indolo[2,3-b]quinoxalines: DNA and protein interacting scaffold for pharmacological activities.

    PubMed

    Moorthy, N S Hari Narayana; Manivannan, E; Karthikeyan, C; Trivedi, Piyush

    2013-08-01

    6H-Indolo[2,3-b]quinoxaline, a planar fused heterocyclic compound exhibits a wide variety of pharmacological activities. The mechanism of pharmacological action exerted by these compounds is predominantly DNA intercalation. The thermal stability of the intercalated complex (DNA and 6H-indolo[2,3-b]quinoxaline derivatives) is an important parameter for the elucidation of anticancer, antiviral and other activities. This thermal stability of the 6H-indolo[2,3- b]quinoxaline-DNA complex depends on the type of substituents and side chains attached to the 6H-indolo[2,3- b]quinoxaline nucleus and also the orientation of the side chain towards the GC rich minor groove of the DNA. Highly active 6H-indolo[2,3-b]quinoxaline derivatives such as NCA0424, B-220 and 9-OH-B-220 have shown good binding affinity to DNA as evident from high thermal stability of compound-DNA complex. Interestingly, these compounds possessed poor inhibitory activity on topoisomerase II enzyme but have significant MDR modulating activity. This review establishes '6H-indolo[2,3-b]quinoxaline' as a valuable template for design and development of novel molecules with different biological activities.

  6. The Rab GTPase RabG3b functions in autophagy and contributes to tracheary element differentiation in Arabidopsis.

    PubMed

    Kwon, Soon Il; Cho, Hong Joo; Jung, Jin Hee; Yoshimoto, Kohki; Shirasu, Ken; Park, Ohkmae K

    2010-10-01

    The tracheary elements (TEs) of the xylem serve as the water-conducting vessels of the plant vascular system. To achieve this, TEs undergo secondary cell wall thickening and cell death, during which the cell contents are completely removed. Cell death of TEs is a typical example of developmental programmed cell death that has been suggested to be autophagic. However, little evidence of autophagy in TE differentiation has been provided. The present study demonstrates that the small GTP binding protein RabG3b plays a role in TE differentiation through its function in autophagy. Differentiating wild type TE cells were found to undergo autophagy in an Arabidopsis culture system. Both autophagy and TE formation were significantly stimulated by overexpression of a constitutively active mutant (RabG3bCA), and were inhibited in transgenic plants overexpressing a dominant negative mutant (RabG3bDN) or RabG3b RNAi (RabG3bRNAi), a brassinosteroid insensitive mutant bri1-301, and an autophagy mutant atg5-1. Taken together, our results suggest that autophagy occurs during TE differentiation, and that RabG3b, as a component of autophagy, regulates TE differentiation.

  7. A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors.

    PubMed

    Qiu, Feng; Jiang, Haisong; Xiang, Mengqing

    2008-03-26

    The retinal ganglion cells (RGCs) are the sole output neurons in the retina that form the optic nerve and convey light signals detected by photoreceptors to the higher visual system. Their degeneration and damage caused by glaucoma and injury can lead to blindness. During retinogenesis, RGCs are specified from a population of multipotential precursors capable of generating RGC, amacrine, horizontal, and cone cells. How the RGC fate is selected from these multiple neuron fates is unknown at present. Here we show that the previously unsuspected POU domain transcription factor Brn3b (brain-specific homeobox/POU domain protein 3b) plays such a critical role. Loss of Brn3b function in mice leads to misspecification of early RGC precursors as late-born RGC, amacrine, and horizontal cells, whereas misexpressed Brn3b suppresses non-RGC cell fates but promotes the RGC fate. Microarray profiling and other molecular analyses reveal that, in RGC precursors, Brn3b normally represses the expression of a network of retinogenic factor genes involved in fate commitment and differentiation of late-born RGC, amacrine, horizontal, and cone cells. Our data suggest that Brn3b specifies the RGC fate from multipotential precursors not only by promoting RGC differentiation but also by suppressing non-RGC differentiation programs as a safeguard mechanism. PMID:18367606

  8. Cancer-relevant Splicing Factor CAPERα Engages the Essential Splicing Factor SF3b155 in a Specific Ternary Complex*

    PubMed Central

    Loerch, Sarah; Maucuer, Alexandre; Manceau, Valérie; Green, Michael R.; Kielkopf, Clara L.

    2014-01-01

    U2AF homology motifs (UHMs) mediate protein-protein interactions with U2AF ligand motifs (ULMs) of pre-mRNA splicing factors. The UHM-containing alternative splicing factor CAPERα regulates splicing of tumor-promoting VEGF isoforms, yet the molecular target of the CAPERα UHM is unknown. Here we present structures of the CAPERα UHM bound to a representative SF3b155 ULM at 1.7 Å resolution and, for comparison, in the absence of ligand at 2.2 Å resolution. The prototypical UHM/ULM interactions authenticate CAPERα as a bona fide member of the UHM family of proteins. We identify SF3b155 as the relevant ULM-containing partner of full-length CAPERα in human cell extracts. Isothermal titration calorimetry comparisons of the purified CAPERα UHM binding known ULM-containing proteins demonstrate that high affinity interactions depend on the presence of an intact, intrinsically unstructured SF3b155 domain containing seven ULM-like motifs. The interplay among bound CAPERα molecules gives rise to the appearance of two high affinity sites in the SF3b155 ULM-containing domain. In conjunction with the previously identified, UHM/ULM-mediated complexes of U2AF65 and SPF45 with SF3b155, this work demonstrates the capacity of SF3b155 to offer a platform for coordinated recruitment of UHM-containing splicing factors. PMID:24795046

  9. Negative autoregulation of BMP dependent transcription by SIN3B splicing reveals a role for RBM39

    PubMed Central

    Faherty, Noel; Benson, Matthew; Sharma, Eshita; Lee, Angela; Howarth, Alison; Lockstone, Helen; Ebner, Daniel; Bhattacharya, Shoumo

    2016-01-01

    BMP signalling is negatively autoregulated by several genes including SMAD6, Noggin and Gremlin, and autoregulators are possible targets for enhancing BMP signalling in disorders such as fibrosis and pulmonary hypertension. To identify novel negative regulators of BMP signalling, we used siRNA screening in mouse C2C12 cells with a BMP-responsive luciferase reporter. Knockdown of several splicing factors increased BMP4-dependent transcription and target gene expression. Knockdown of RBM39 produced the greatest enhancement in BMP activity. Transcriptome-wide RNA sequencing identified a change in Sin3b exon usage after RBM39 knockdown. SIN3B targets histone deacetylases to chromatin to repress transcription. In mouse, Sin3b produces long and short isoforms, with the short isoform lacking the ability to recruit HDACs. BMP4 induced a shift in SIN3B expression to the long isoform, and this change in isoform ratio was prevented by RBM39 knockdown. Knockdown of long isoform SIN3B enhanced BMP4-dependent transcription, whereas knockdown of the short isoform did not. We propose that BMP4-dependent transcription is negatively autoregulated in part by SIN3B alternative splicing, and that RBM39 plays a role in this process. PMID:27324164

  10. Summertime Tropospheric Nonmethane Hydrocarbon and Halocarbon Concentrations Over Central and Eastern Canada during ABLE-3B.

    NASA Astrophysics Data System (ADS)

    Smith, Tyrrel Wayne, Jr.

    Global tropospheric change is now a reality and a focus of international scientific and policy concern. An attempt to understand this tropospheric change was initiated at UCI with the development of a trace gas apparatus to analyze simultaneously nonmethane hydrocarbon (NMHC) and chlorocarbon trace gas species with atmospheric lifetimes ranging from minutes to tens and even hundreds of years. The experimental design of the equipment used to collect, transfer, and analyze ambient air samples is described in detail, and the data obtained show the usefulness of such a system. Approximately 1400 whole air samples were collected on the NASA Electra aircraft and at ground locations and were assayed for selected C_2-C _{10} hydrocarbons and seven halocarbons during the five-week Arctic Boundary Layer Experiment (ABLE-3B) conducted in the eastern Canadian Wetlands. Urban plumes, enhanced in many NMHCs, were identified by their high correlation with elevated levels of perchloroethene (C_2Cl_4). Meteorological isentropic back-trajectories were used in conjunction with NMHC and halocarbon chemical tracers to confirm that the identity of a clean air mass transported to the Canadian Wetlands was attributed to tropical marine air. In more than half of the 46 vertical profiles flown, enhanced NMHC concentrations attributable to plumes from Canadian forest fires were observed. Emission factors relative to ethane were determined for 22 hydrocarbons released from circumpolar biomass burning. Using these data for rm C_2H_6, C_2H _2, C_3H_8, and n- rm C_4H_{10} and CO enhancement estimates from the literature, emissions from biomass burning were calculated to be significant on a global scale. Because of its very short atmospheric lifetime and its below detection background mixing ratio, 1,3-butadiene is an excellent indicator of recent combustion. No statistically significant emissions of N_2O, isoprene (rm C_5H_8), CCl_2F _2 (CFC-12) or any other halocarbon were observed in the

  11. A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a craniofacial disorder associated with limb defects.

    PubMed

    Favaro, Francine P; Alvizi, Lucas; Zechi-Ceide, Roseli M; Bertola, Debora; Felix, Temis M; de Souza, Josiane; Raskin, Salmo; Twigg, Stephen R F; Weiner, Andrea M J; Armas, Pablo; Margarit, Ezequiel; Calcaterra, Nora B; Andersen, Gregers R; McGowan, Simon J; Wilkie, Andrew O M; Richieri-Costa, Antonio; de Almeida, Maria L G; Passos-Bueno, Maria Rita

    2014-01-01

    Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5' untranslated region (5' UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis. PMID:24360810

  12. A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a craniofacial disorder associated with limb defects.

    PubMed

    Favaro, Francine P; Alvizi, Lucas; Zechi-Ceide, Roseli M; Bertola, Debora; Felix, Temis M; de Souza, Josiane; Raskin, Salmo; Twigg, Stephen R F; Weiner, Andrea M J; Armas, Pablo; Margarit, Ezequiel; Calcaterra, Nora B; Andersen, Gregers R; McGowan, Simon J; Wilkie, Andrew O M; Richieri-Costa, Antonio; de Almeida, Maria L G; Passos-Bueno, Maria Rita

    2014-01-01

    Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5' untranslated region (5' UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis.

  13. Binding of the repressor complex REST-mSIN3b by small molecules restores neuronal gene transcription in Huntington's disease models.

    PubMed

    Conforti, Paola; Zuccato, Chiara; Gaudenzi, Germano; Ieraci, Alessandro; Camnasio, Stefano; Buckley, Noel J; Mutti, Cesare; Cotelli, Franco; Contini, Alessandro; Cattaneo, Elena

    2013-10-01

    Transcriptional dysregulation is a hallmark of Huntington's disease (HD) and one cause of this dysregulation is enhanced activity of the REST-mSIN3a-mSIN3b-CoREST-HDAC repressor complex, which silences transcription through REST binding to the RE1/NRSE silencer. Normally, huntingtin (HTT) prevents this binding, allowing expressing of REST target genes. Here, we aimed to identify HTT mimetics that disrupt REST complex formation in HD. From a structure-based virtual screening of 7 million molecules, we selected 94 compounds predicted to interfere with REST complex formation by targeting the PAH1 domain of mSIN3b. Primary screening using DiaNRSELuc8 cells revealed two classes of compounds causing a greater than two-fold increase in luciferase. In particular, quinolone-like compound 91 (C91) at a non-toxic nanomolar concentration reduced mSIN3b nuclear entry and occupancy at the RE1/NRSE within the Bdnf locus, and restored brain-derived neurotrophic factor (BDNF) protein levels in HD cells. The mRNA levels of other RE1/NRSE-regulated genes were similarly increased while non-REST-regulated genes were unaffected. C91 stimulated REST-regulated gene expression in HTT-knockdown Zebrafish and increased BDNF mRNA in the presence of mutant HTT. Thus, a combination of virtual screening and biological approaches can lead to compounds reducing REST complex formation, which may be useful in HD and in other pathological conditions. PMID:23800350

  14. The Angular Power Spectrum of BATSE 3B Gamma-Ray Bursts

    NASA Technical Reports Server (NTRS)

    Tegmark, Max; Hartmann, Dieter H.; Briggs, Michael S.; Meegan, Charles A.

    1996-01-01

    We compute the angular power spectrum C(sub l) from the BATSE 3B catalog of 1122 gamma-ray bursts and find no evidence for clustering on any scale. These constraints bridge the entire range from small scales (which probe source clustering and burst repetition) to the largest scales (which constrain possible anisotropics from the Galactic halo or from nearby cosmological large-scale structures). We develop an analysis technique that takes the angular position errors into account. For specific clustering or repetition models, strong upper limits can be obtained down to scales l approx. equal to 30, corresponding to a couple of degrees on the sky. The minimum-variance burst weighting that we employ is visualized graphically as an all-sky map in which each burst is smeared out by an amount corresponding to its position uncertainty. We also present separate bandpass-filtered sky maps for the quadrupole term and for the multipole ranges l = 3-10 and l = 11-30, so that the fluctuations on different angular scales can be inspected separately for visual features such as localized 'hot spots' or structures aligned with the Galactic plane. These filtered maps reveal no apparent deviations from isotropy.

  15. Rotating eruption of an untwisting filament triggered by the 3B flare of 25 April, 1984

    NASA Astrophysics Data System (ADS)

    Kurokawa, Hiroki; Hanaoka, Yoichiro; Shibata, Kazunari; Uchida, Yutaka

    1987-09-01

    A great 3B flare, whose X-ray class was X13, occurred over a delta-sunspot at 00:01 UT on April 25, 1984. Before the flare, a strong magnetic shear was found to be formed along the neutral line in the delta-sunspot with shear motions of umbrae. The shear motions of the umbrae were caused by the successive emergence of a magnetic flux rope. Before the flare, several groups of sheared H-alpha threads and filaments were found to merge into an elongated filament along the neutral line through the delta-sunspot. In the merging process the helical twists were formed in the filament by the reconnection as in Pneuman's (1983) model. At the post-maximum phase of the flare, the helically twisted filament spouted out with an untwisting rotation. Examining the morphological and dynamical features of the filament eruption, it is concluded that it has some typical features of the flare spray, and that it seems to be accelerated by the sweeping-magnetic-twist mechanism proposed by Shibata and Uchida (1986).

  16. Mindfulness (Vipassana) meditation: effects on P3b event-related potential and heart rate variability.

    PubMed

    Delgado-Pastor, Luis Carlos; Perakakis, Pandelis; Subramanya, Pailoor; Telles, Shirley; Vila, Jaime

    2013-11-01

    The concept of mindfulness is based on Vipassana, a Buddhist meditation technique. The present study examines the physiological indices of attention and autonomic regulation in experienced Vipassana meditators to test the claim that mindfulness is an effective therapeutic tool due to its effects on increasing awareness of present experience and emotional self-regulation. Ten male experienced Vipassana meditators underwent two assessment sessions, one where they practiced Vipassana meditation and another where they rested with no meditation (random thinking). Each meditation/no-meditation session lasted 30 min and was preceded and followed by an auditory oddball task with two tones (standard and target). Event-related potentials to the tones were recorded at the Fz, Cz, and Pz locations. Heart rate variability, derived from an EKG, was recorded continuously during the meditation/no-meditation sessions and during a 5-minute baseline before the task. The Vipassana experts showed greater P3b amplitudes to the target tone after meditation than they did both before meditation and after the no-meditation session. They also showed a larger LF/HF ratio increase during specific Vipassana meditation. These results suggest that expert Vipassana meditators showed increased attentional engagement after meditation and increased autonomic regulation during meditation supporting, at least partially, the two claims concerning the clinical effectiveness of mindfulness. PMID:23892096

  17. Water Resources Data, Florida, Water Year 2001, Volume 3B. Southwest Florida Ground Water

    USGS Publications Warehouse

    Stoker, Y.E.; Kane, R.L.; Fletcher, W.L.

    2002-01-01

    Water resources data for the 2001 water year in Florida consist of continuous or daily discharges for 406 streams, periodic discharge for 12 streams, continuous daily stage for 142 streams, periodic stage for 12 streams, peak stage and discharge for 37 streams, continuous or daily elevations for 11 lakes, periodic elevations for 30 lakes; continuous ground-water levels for 424 wells, periodic ground-water levels for 1,426 wells, and quality-of-water data for 80 surface-water sites and 245 wells. The data for Southwest Florida include records of stage, discharge, and water quality of streams; stage, contents, water quality of lakes and reservoirs, and water levels and water quality of ground-water wells. Volume 3B contains records for continuous ground-water elevations for 128 wells; periodic ground-water elevations at 33 wells; miscellaneous ground-water elevations at 347 wells; and water quality at 25 ground-water sites. These data represent the national Water Data System records collected by the U.S. Geological Survey and cooperating local, state, and federal agencies in Florida.

  18. Simultaneous separation, seaming, and sealing using brazing (S3B) for sample containerization and planetary protection

    NASA Astrophysics Data System (ADS)

    Bar-Cohen, Yoseph; Wu, Jiunnjenq; Olorunsola, Ayoola K.; Rivellini, Tommaso P.; Bley, Susan; Wincentsen, James; Gershman, Robert

    2005-05-01

    Any future NASA mission would require protection of our planet from the risk of possibly returning uncontrolled biological materials. For this purpose, it is necessary to contain the acquired samples and destroy any potential biological materials that may contaminate the external surface of the container while protecting the sample itself for further analysis. A novel method that allows simultaneous separation, seaming and sealing using brazing (S3B) process for sample containerization and planetary protection has been conceived and demonstrated. A double wall container is used with clean inner-walls allowing brazing the container base (containing the sample) to its lid while separating it from the support mount and assuring its seal. The use of brazing materials that melt at temperatures that are higher than 500°C assures sterilization of the exposed areas that can potentially be contaminated by biological materials from Mars and other planets. The results of this study and the issues that were identified to require attention will be described and discussed.

  19. Rhodamine 3B + ClO 4- electronic transitions: reaction field and vibrational structure

    NASA Astrophysics Data System (ADS)

    Ferreira, José A. B.; Costa, Sílvia M. B.

    2001-11-01

    The electronic absorption and emission in the visible region of the spectrum of a xanthene dye, Rhodamine 3B perchlorate, have been studied as a function of solvent and temperature. The spectral shifts correlate well with the function f( n2)=( n2-1)/(2 n2+1) (Ooshika, Bayliss and McRae theory) and are essentially due to dispersion and induced electronic polarization. A further energy lowering occurs due to orientation polarization giving an estimation of μe- μg=1.7 D. The broadenings in absorption reveal the contribution from orbital expansion whilst in emission provide evidence for the opposite effect. The contribution of an electrostriction effect is inferred from the good correlation obtained between a vibronic function containing the elongation of molecular coordinates and the temperature. The double configuration coordinate model describes well the effect of temperature on both the S 1↔S 0 transitions Stokes shift and broadening at the vibronic 0↔0 bands.

  20. Evaluation of BWR emergency procedure guidelines for BWR ATWS using RAMONA-3B code

    SciTech Connect

    Neymotin, L.; Slovik, G.; Cazzoli, E.; Saha, P.

    1985-01-01

    An MSIV Closure ATWS calculation for a typical BWR/4 (Browns Ferry, Unit 1) was performed using the RAMONA-3B code which is a BWR systems transient code combining three-dimensional neutronic core representation with multi-channel one-dimensional thermal hydraulics. The main objective of the study was to perform a best-estimate evaluation of the recently proposed Emergency Procedure Guidelines for Anticipated Transients Without Scram (ATWS). Emphasis was placed on evaluating the effects of lowering the downcomer water level to the Top of Active Fuel (TAF) and vessel depressurization. The calculation was run up to approximately 1200 seconds. Both actions, namely, lowering the water level and vessel depressurization, lowered the reactor power to some extent. However, the pressure suppression pool water temperature still reached approximately 90/sup 0/C (potential High Pressure Coolant Injection (HPCI) pump seal failure temperature) in twenty minutes. Thus, other actions such as boron injection and/or manual control rod insertion are necessary to mitigate a BWR/4 Main Steam Isolation Valve (MSIV) closure ATWS. 19 refs., 14 figs., 3 tabs.

  1. Isolation and Purification of Cu-free Methanobactin from Methylosinus trichosporium OB3b

    SciTech Connect

    M Pesch; I Christl; K Barmettler; S Kraemer; R Kretzschmar

    2011-12-31

    The isolation of highly pure copper-free methanobactin is a prerequisite for the investigation of the biogeochemical functions of this chalkophore molecule produced by methane oxidizing bacteria. Here, we report a purification method for methanobactin from Methylosinus trichosporium OB3b cultures based on reversed-phase HPLC fractionation used in combination with a previously reported resin extraction. HPLC eluent fractions of the resin extracted product were collected and characterized with UV-vis, FT-IR, and C-1s NEXAFS spectroscopy, as well as with elemental analysis and ESI-MS. The results showed that numerous compounds other than methanobactin were present in the isolate obtained with resin extraction. Molar C/N ratios, mass spectrometry measurements, and UV-vis spectra indicated that methanobactin was only present in one of the HPLC fractions. On a mass basis, methanobactin carbon contributed only 32% to the total organic carbon isolated with resin extraction. Our spectroscopic results implied that besides methanobactin, the organic compounds in the resin extract comprised breakdown products of methanobactin as well as polysaccharide-like substances. Our results demonstrate that a purification step is indispensable in addition to resin extraction in order to obtain pure methanobactin. The proposed HPLC purification procedure is suitable for semi-preparative work and provides copper-free methanobactin.

  2. BOREAS RSS-16 AIRSAR CM Images: Integrated Processor Version 6.1 Level-3b

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Saatchi, Susan; Newcomer, Jeffrey A.; Strub, Richard; Irani, Fred

    2000-01-01

    The BOREAS RSS-16 team used satellite and aircraft SAR data in conjunction with various ground measurements to determine the moisture regime of the boreal forest. RSS-16 assisted with the acquisition and ordering of NASA JPL AIRSAR data collected from the NASA DC-8 aircraft. The NASA JPL AIRSAR is a side-looking imaging radar system that utilizes the SAR principle to obtain high resolution images that represent the radar backscatter of the imaged surface at different frequencies and polarizations. The information contained in each pixel of the AIRSAR data represents the radar backscatter for all possible combinations of horizontal and vertical transmit and receive polarizations (i.e., HH, HV, VH, and VV). Geographically, the data cover portions of the BOREAS SSA and NSA. Temporally, the data were acquired from 12-Aug-1993 to 31-Jul-1995. The level-3b AIRSAR CM data are in compressed Stokes matrix format, which has 10 bytes per pixel. From this data format, it is possible to synthesize a number of different radar backscatter measurements. The data are stored in binary image-format files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  3. BOREAS RSS-16 Level-3b DC-8 AIRSAR SY Images

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Saatchi, Sasan; Newcomer, Jeffrey A.; Strub, Richard; Irani, Fred

    2000-01-01

    The BOREAS RSS-16 team used satellite and aircraft SAR data in conjunction with various ground measurements to determine the moisture regime of the boreal forest. RSS-16 assisted with the acquisition and ordering of NASA JPL AIRSAR data collected from the NASA DC-8 aircraft. The NASA JPL AIRSAR is a side-looking imaging radar system that utilizes the SAR principle to obtain high-resolution images that represent the radar backscatter of the imaged surface at different frequencies and polarizations. The information contained in each pixel of the AIRSAR data represents the radar backscatter for all possible combinations of horizontal and vertical transmit and receive polarizations (i.e., HH, HV, VH, and VV). Geographically, the data cover portions of the BOREAS SSA and NSA. Temporally, the data were acquired from 12-Aug-1993 to 31-Jul-1995. The level-3b AIRSAR SY data are the JPL synoptic product and contain 3 of the 12 total frequency and polarization combinations that are possible. The data are stored in binary image format files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  4. Water resources data, Florida, water year 2005. Volume 3B: Southwest Florida ground water

    USGS Publications Warehouse

    Kane, Richard L.

    2005-01-01

    Water resources data for the 2005 water year in Florida consist of continuous or daily discharges for 429 streams, periodic discharge for 9 streams, continuous or daily stage for 218 streams, periodic stage for 5 streams, peak stage for 28 streams and peak discharge for 28 streams, continuous or daily elevations for 15 lakes, periodic elevations for 23 lakes; continuous ground-water levels for 401 wells, periodic ground-water levels for 1,098 wells, and quality-of-water data for 211 surface-water sites and 208 wells. The data for Southwest Florida include records of stage, discharge, and water quality of streams; stage, contents, water quality of lakes and reservoirs, and water levels and water quality of ground-water wells. Volume 3B contains records for continuous ground-water elevations for 108 wells; periodic ground-water elevations at 24 wells; miscellaneous ground-water elevations at 354 wells; and water quality at 2 ground-water sites. These data represent the national Water Data System records collected by the U.S. Geological Survey and cooperating local, state, and federal agencies in Florida.

  5. Water resources data Florida, water year 2004: Volume 3B: southwest Florida ground water

    USGS Publications Warehouse

    Kane, Richard L.

    2004-01-01

    Water resources data for the 2004 water year in Florida consist of continuous or daily discharges for 405 streams, periodic discharge for 12 streams, continuous or daily stage for 159 streams, periodic stage for 19 streams, peak stage for 30 streams and peak discharge for 30 streams, continuous or daily elevations for 14 lakes, periodic elevations for 23 lakes; continuous ground-water levels for 408 wells, periodic ground-water levels for 1,188 wells, and quality-of-water data for 140 surface-water sites and 240 wells. The data for Southwest Florida include records of stage, discharge, and water quality of streams; stage, contents, water quality of lakes and reservoirs, and water levels and water quality of ground-water wells. Volume 3B contains records for continuous ground-water elevations for 98 wells; periodic ground-water elevations at 56 wells; miscellaneous ground-water elevations at 374 wells; and water quality at 25 ground-water sites. These data represent the national Water Data System records collected by the U.S. Geological Survey and cooperating local, state, and federal agencies in Florida.

  6. Water Resources Data, Florida, Water Year 2002, Volume 3B. Southwest Florida Ground Water

    USGS Publications Warehouse

    Kane, R.L.; Fletcher, W.L.

    2003-01-01

    Water resources data for the 2002 water year in Florida consist of continuous or daily discharges for 392 streams, periodic discharge for 15 streams, continuous daily stage for 191 streams, periodic stage for 13 streams, peak stage for 33 streams and peak discharge for 33 streams, continuous or daily elevations for 14 lakes, periodic elevations for 49 lakes; continuous ground-water levels for 418 wells, periodic ground-water levels for 1,287 wells, and quality-of-water data for 116 surface-water sites and 291 wells. The data for Southwest Florida include records of stage, discharge, and water quality of streams; stage, contents, water quality of lakes and reservoirs, and water levels and water quality of ground-water wells. Volume 3B contains records for continuous ground-water elevations for 125 wells; periodic ground-water elevations at 31 wells; miscellaneous ground-water elevations at 377 wells; and water quality at 46 ground-water sites. These data represent the national Water Data System records collected by the U.S. Geological Survey and cooperating local, state, and federal agencies in Florida.

  7. Water Resources Data, Florida, Water Year 2003, Volume 3B: Southwest Florida Ground Water

    USGS Publications Warehouse

    Kane, Richard L.; Fletcher, William L.; Lane, Susan L.

    2004-01-01

    Water resources data for the 2003 water year in Florida consist of continuous or daily discharges for 385 streams, periodic discharge for 13 streams, continuous daily stage for 255 streams, periodic stage for 13 streams, peak stage for 36 streams and peak discharge for 36 streams, continuous or daily elevations for 13 lakes, periodic elevations for 46 lakes; continuous ground-water levels for 441 wells, periodic ground-water levels for 1,227 wells, and quality-of-water data for 133 surface-water sites and 308 wells. The data for Southwest Florida include records of stage, discharge, and water quality of streams; stage, contents, water quality of lakes and reservoirs, and water levels and water quality of ground-water wells. Volume 3B contains records for continuous ground-water elevations for 128 wells; periodic ground-water elevations at 31 wells; miscellaneous ground-water elevations at 405 wells; and water quality at 32 ground-water sites. These data represent the national Water Data System records collected by the U.S. Geological Survey and cooperating local, state, and federal agencies in Florida.

  8. Stress-mediated Sin3B activation leads to negative regulation of subset of p53 target genes

    PubMed Central

    Kadamb, Rama; Mittal, Shilpi; Bansal, Nidhi; Saluja, Daman

    2015-01-01

    The multiprotein SWI-independent 3 (Sin3)–HDAC (histone deacetylase) corepressor complex mediates gene repression through its interaction with DNA-binding factors and recruitment of chromatin-modifying proteins on to the promoters of target gene. Previously, an increased expression of Sin3B and tumour suppressor protein, p53 has been established upon adriamycin treatment. We, now provide evidence that Sin3B expression is significantly up-regulated under variety of stress conditions and this response is not stress-type specific. We observed that Sin3B expression is significantly up-regulated both at transcript and at protein level upon DNA damage induced by bleomycin drug, a radiomimetic agent. This increase in Sin3B expression upon stress is found to be p53-dependent and is associated with enhanced interaction of Sin3B with Ser15 phosphorylated p53. Binding of Sin3–HDAC repressor complex on to the promoters of p53 target genes influences gene regulation by altering histone modifications (H3K9me3 and H3K27me3) at target genes. Furthermore, knockdown of Sin3B by shRNA severely compromises p53-mediated gene repression under stress conditions. Taken together, these results suggest that stress-induced Sin3B activation is p53-dependent and is essential for p53-mediated repression of its selective target genes. The present study has an implication in understanding the transrepression mechanism of p53 under DNA damaging conditions. PMID:26181367

  9. Sf3b4-depleted Xenopus embryos: A model to study the pathogenesis of craniofacial defects in Nager syndrome.

    PubMed

    Devotta, Arun; Juraver-Geslin, Hugo; Gonzalez, Jose Antonio; Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

    2016-07-15

    Mandibulofacial dysostosis (MFD) is a human developmental disorder characterized by defects of the facial bones. It is the second most frequent craniofacial malformation after cleft lip and palate. Nager syndrome combines many features of MFD with a variety of limb defects. Mutations in SF3B4 (splicing factor 3b, subunit 4) gene, which encodes a component of the pre-mRNA spliceosomal complex, were recently identified as a cause of Nager syndrome, accounting for 60% of affected individuals. Nothing is known about the cellular pathogenesis underlying Nager type MFD. Here we describe the first animal model for Nager syndrome, generated by knocking down Sf3b4 function in Xenopus laevis embryos, using morpholino antisense oligonucleotides. Our results indicate that Sf3b4-depleted embryos show reduced expression of the neural crest genes sox10, snail2 and twist at the neural plate border, associated with a broadening of the neural plate. This phenotype can be rescued by injection of wild-type human SF3B4 mRNA but not by mRNAs carrying mutations that cause Nager syndrome. At the tailbud stage, morphant embryos had decreased sox10 and tfap2a expression in the pharyngeal arches, indicative of a reduced number of neural crest cells. Later in development, Sf3b4-depleted tadpoles exhibited hypoplasia of neural crest-derived craniofacial cartilages, phenocopying aspects of the craniofacial skeletal defects seen in Nager syndrome patients. With this animal model we are now poised to gain important insights into the etiology and pathogenesis of Nager type MFD, and to identify the molecular targets of Sf3b4. PMID:26874011

  10. Targeted disruption of glycogen synthase kinase 3A (GSK3A) in mice affects sperm motility resulting in male infertility.

    PubMed

    Bhattacharjee, Rahul; Goswami, Suranjana; Dudiki, Tejasvi; Popkie, Anthony P; Phiel, Christopher J; Kline, Douglas; Vijayaraghavan, Srinivasan

    2015-03-01

    The signaling enzyme glycogen synthase kinase 3 (GSK3) exists as two isoforms-GSK3A and GSK3B. Protein phosphorylation by GSK3 has important signaling roles in several cells. In our past work, we found that both isoforms of GSK3 are present in mouse sperm and that catalytic GSK3 activity correlates with motility of sperm from several species. Here, we examined the role of Gsk3a in male fertility using a targeted gene knockout (KO) approach. The mutant mice are viable, but have a male infertility phenotype, while female fertility is unaffected. Testis weights of Gsk3a(-/-) mice are normal and sperm are produced in normal numbers. Although spermatogenesis is apparently unimpaired, sperm motility parameters in vitro are impaired. In addition, the flagellar waveform appears abnormal, characterized by low amplitude of flagellar beat. Sperm ATP levels were lower in Gsk3a(-/-) mice compared to wild-type animals. Protein phosphatase PP1 gamma2 protein levels were unaltered, but its catalytic activity was elevated in KO sperm. Remarkably, tyrosine phosphorylation of hexokinase and capacitation-associated changes in tyrosine phosphorylation of proteins are absent or significantly lower in Gsk3a(-/-) sperm. The GSK3B isoform was present and unaltered in testis and sperm of Gsk3a(-/-) mice, showing the inability of GSK3B to substitute for GSK3A in this context. Our studies show that sperm GSK3A is essential for male fertility. In addition, the GSK3A isoform, with its highly conserved glycine-rich N terminus in mammals, may have an isoform-specific role in its requirement for normal sperm motility and fertility.

  11. Hispolon induces apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK phosphorylation.

    PubMed

    Huang, Guan-Jhong; Deng, Jeng-Shyan; Huang, Shyh-Shyun; Hu, Miao-Lin

    2011-07-13

    Hispolon is an active phenolic compound of Phellinus igniarius , a mushroom that has recently been shown to have antioxidant, anti-inflammatory, and anticancer activities. This study investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma Hep3B cells by using the MTT assay, DNA fragmentation, DAPI (4,6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analyses. Hispolon inhibited cellular growth of Hep3B cells in a time-dependent and dose-dependent manner, through the induction of cell cycle arrest at S phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Hispolon-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A and E and cyclin-dependent kinase (CDK) 2, with concomitant induction of p21waf1/Cip1 and p27Kip1. Exposure of Hep3B cells to hispolon resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. Hispolon treatment also activated JNK, p38 MAPK, and ERK expression. Inhibitors of ERK (PB98095), but not those of JNK (SP600125) and p38 MAPK (SB203580), suppressed hispolon-induced S-phase arrest and apoptosis in Hep3B cells. These findings establish a mechanistic link between the MAPK pathway and hispolon-induced cell cycle arrest and apoptosis in Hep3B cells. PMID:21630638

  12. Changes in P3b Latency and Amplitude Reflect Expertise Acquisition in a Football Visuomotor Learning Task

    PubMed Central

    Morgan, Kyle K.; Luu, Phan; Tucker, Don M.

    2016-01-01

    Learning is not a unitary phenomenon. Rather, learning progresses through stages, with the stages reflecting different challenges that require the support of specific cognitive processes that reflect the functions of different brain networks. A theory of general learning proposes that learning can be divided into early and late stages controlled by corticolimbic networks located in frontal and posterior brain regions, respectively. Recent human studies using dense-array EEG (dEEG) support these results by showing progressive increases in P3b amplitude (an Event Related Potential with estimated sources in posterior cingulate cortex and hippocampus) as participants acquire a new visuomotor skill. In the present study, the P3b was used to track the learning and performance of participants as they identify defensive football formations and make an appropriate response. Participants acquired the task over three days, and P3b latency and amplitude significantly changed when participants learned the task. As participants demonstrated further proficiency with extensive training, amplitude and latency changes in the P3b continued to closely mirror performance improvements. Source localization results across all days suggest that an important source generator of the P3b is located in the posterior cingulate cortex. Results from the study support prior findings and further suggest that the careful analysis of covert learning mechanisms and their underlying electrical signatures are a robust index of task competency. PMID:27111898

  13. The Rab GTPase RabG3b positively regulates autophagy and immunity-associated hypersensitive cell death in Arabidopsis.

    PubMed

    Kwon, Soon Il; Cho, Hong Joo; Kim, Sung Ryul; Park, Ohkmae K

    2013-04-01

    A central component of the plant defense response to pathogens is the hypersensitive response (HR), a form of programmed cell death (PCD). Rapid and localized induction of HR PCD ensures that pathogen invasion is prevented. Autophagy has been implicated in the regulation of HR cell death, but the functional relationship between autophagy and HR PCD and the regulation of these processes during the plant immune response remain controversial. Here, we show that a small GTP-binding protein, RabG3b, plays a positive role in autophagy and promotes HR cell death in response to avirulent bacterial pathogens in Arabidopsis (Arabidopsis thaliana). Transgenic plants overexpressing a constitutively active RabG3b (RabG3bCA) displayed accelerated, unrestricted HR PCD within 1 d of infection, in contrast to the autophagy-defective atg5-1 mutant, which gradually developed chlorotic cell death through uninfected sites over several days. Microscopic analyses showed the accumulation of autophagic structures during HR cell death in RabG3bCA cells. Our results suggest that RabG3b contributes to HR cell death via the activation of autophagy, which plays a positive role in plant immunity-triggered HR PCD.

  14. MAP1LC3B overexpression protects against Hermansky-Pudlak syndrome type-1-induced defective autophagy in vitro.

    PubMed

    Ahuja, Saket; Knudsen, Lars; Chillappagari, Shashi; Henneke, Ingrid; Ruppert, Clemens; Korfei, Martina; Gochuico, Bernadette R; Bellusci, Saverio; Seeger, Werner; Ochs, Matthias; Guenther, Andreas; Mahavadi, Poornima

    2016-03-15

    Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, and some patients with HPS develop pulmonary fibrosis, known as HPS-associated interstitial pneumonia (HPSIP). We have previously reported that HPSIP is associated with severe surfactant accumulation, lysosomal stress, and alveolar epithelial cell type II (AECII) apoptosis. Here, we hypothesized that defective autophagy might result in excessive lysosomal stress in HPSIP. Key autophagy proteins, including LC3B lipidation and p62, were increased in HPS1/2 mice lungs. Electron microscopy demonstrated a preferable binding of LC3B to the interior of lamellar bodies in the AECII of HPS1/2 mice, whereas in wild-type mice it was present on the limiting membrane in addition to the interior of the lamellar bodies. Similar observations were noted in human HPS1 lung sections. In vitro knockdown of HPS1 revealed increased LC3B lipidation and p62 accumulation, associated with an increase in proapoptotic caspases. Overexpression of LC3B decreased the HPS1 knockdown-induced p62 accumulation, whereas rapamycin treatment did not show the same effect. We conclude that loss of HPS1 protein results in impaired autophagy that is restored by exogenous LC3B and that defective autophagy might therefore play a critical role in the development and progression of HPSIP. PMID:26719147

  15. Constraints on the atmospheric circulation and variability of the eccentric hot Jupiter XO-3b

    SciTech Connect

    Wong, Ian; Knutson, Heather A.; Cowan, Nicolas B.; Lewis, Nikole K.; Agol, Eric; Burrows, Adam; Deming, Drake; Fortney, Jonathan J.; Laughlin, Gregory; Fulton, Benjamin J.; Langton, Jonathan; Showman, Adam P.

    2014-10-20

    We report secondary eclipse photometry of the hot Jupiter XO-3b in the 4.5 μm band taken with the Infrared Array Camera on the Spitzer Space Telescope. We measure individual eclipse depths and center of eclipse times for a total of 12 secondary eclipses. We fit these data simultaneously with two transits observed in the same band in order to obtain a global best-fit secondary eclipse depth of 0.1580% ± 0.0036% and a center of eclipse phase of 0.67004 ± 0.00013. We assess the relative magnitude of variations in the dayside brightness of the planet by measuring the size of the residuals during ingress and egress from fitting the combined eclipse light curve with a uniform disk model and place an upper limit of 0.05%. The new secondary eclipse observations extend the total baseline from one and a half years to nearly three years, allowing us to place an upper limit on the periastron precession rate of 2.9 × 10{sup –3} deg day{sup –1}— the tightest constraint to date on the periastron precession rate of a hot Jupiter. We use the new transit observations to calculate improved estimates for the system properties, including an updated orbital ephemeris. We also use the large number of secondary eclipses to obtain the most stringent limits to date on the orbit-to-orbit variability of an eccentric hot Jupiter and demonstrate the consistency of multiple-epoch Spitzer observations.

  16. DETECTION OF K{sub S} -BAND THERMAL EMISSION FROM WASP-3b

    SciTech Connect

    Zhao Ming; Wright, Jason; Milburn, Jennifer; Hinkley, Sasha; Barman, Travis; Swain, Mark R.; Monnier, John D.

    2012-03-20

    We report the detection of thermal emission from the hot Jupiter WASP-3b in the K{sub S} band, using a newly developed guiding scheme for the WIRC instrument at the Palomar Hale 200 inch telescope. Our new guiding scheme has improved the telescope guiding precision by a factor of {approx}5-7, significantly reducing the correlated systematics in the measured light curves. This results in the detection of a secondary eclipse with depth of 0.181% {+-} 0.020% (9{sigma})-a significant improvement in WIRC's photometric precision and a demonstration of the capability of Palomar/WIRC to produce high-quality measurements of exoplanetary atmospheres. Our measured eclipse depth cannot be explained by model atmospheres with heat redistribution but favors a pure radiative equilibrium case with no redistribution across the surface of the planet. Our measurement also gives an eclipse phase center of 0.5045 {+-} 0.0020, corresponding to an ecos {omega} of 0.0070 {+-} 0.0032. This result is consistent with a circular orbit, although it also suggests that the planet's orbit might be slightly eccentric. The possible non-zero eccentricity provides insight into the tidal circularization process of the star-planet system, but might also have been caused by a second low-mass planet in the system, as suggested by a previous transit timing variation study. More secondary eclipse observations, especially at multiple wavelengths, are necessary to determine the temperature-pressure profile of the planet's atmosphere and shed light on its orbital eccentricity.

  17. Constraints on the Atmospheric Circulation and Variability of the Eccentric Hot Jupiter XO-3b

    NASA Astrophysics Data System (ADS)

    Wong, Ian; Knutson, Heather A.; Cowan, Nicolas B.; Lewis, Nikole K.; Agol, Eric; Burrows, Adam; Deming, Drake; Fortney, Jonathan J.; Fulton, Benjamin J.; Langton, Jonathan; Laughlin, Gregory; Showman, Adam P.

    2014-10-01

    We report secondary eclipse photometry of the hot Jupiter XO-3b in the 4.5 μm band taken with the Infrared Array Camera on the Spitzer Space Telescope. We measure individual eclipse depths and center of eclipse times for a total of 12 secondary eclipses. We fit these data simultaneously with two transits observed in the same band in order to obtain a global best-fit secondary eclipse depth of 0.1580% ± 0.0036% and a center of eclipse phase of 0.67004 ± 0.00013. We assess the relative magnitude of variations in the dayside brightness of the planet by measuring the size of the residuals during ingress and egress from fitting the combined eclipse light curve with a uniform disk model and place an upper limit of 0.05%. The new secondary eclipse observations extend the total baseline from one and a half years to nearly three years, allowing us to place an upper limit on the periastron precession rate of 2.9 × 10-3 deg day-1— the tightest constraint to date on the periastron precession rate of a hot Jupiter. We use the new transit observations to calculate improved estimates for the system properties, including an updated orbital ephemeris. We also use the large number of secondary eclipses to obtain the most stringent limits to date on the orbit-to-orbit variability of an eccentric hot Jupiter and demonstrate the consistency of multiple-epoch Spitzer observations.

  18. Reduced iC3b-mediated phagocytotic capacity of pulmonary neutrophils in cystic fibrosis

    PubMed Central

    Morris, MR; Doull, IJM; Dewitt, S; Hallett, MB

    2005-01-01

    Cystic fibrosis (CF) is characterized by a neutrophil-dominated chronic inflammation of the airways with persistent infections. In order to investigate whether neutrophils contribute to an inadequacy in the pulmonary defence mechanism, the phagocytic activity of pulmonary and peripheral blood neutrophils from CF and non-CF respiratory patients were compared. Neutrophils were isolated from both the blood and bronchoalveolar lavage fluid of 21 patients with CF (12 male, 9 female; mean age 7·5 years, range 0·25–16·4 years) and 17 non-CF subjects (9 male, 8 female; mean age 5·4 years, range 0·2–13·1 years). The ex vivo phagocytic rate of normal pulmonary neutrophils to internalize zymosan particles opsonized with iC3b was faster than that of circulating neutrophils (P < 0·05), but the maximum capacity (9 particles/cell) was similar. In contrast, pulmonary neutrophils from patients with CF had a lower phagocytic capacity than circulating neutrophils either from the same patients or from normal subjects. This deficiency could not be attributed to (i) the cell surface density of CR3 (CD18/CD11b) receptors, which were not significantly different between the other groups (ii) the signalling ability of the CR3 receptors, using cytosolic free Ca2+ signalling as the receptor activity read-out or (iii) a decrease in cellular ATP concentration. As CFTR was not detectable on neutrophils from any source by either histochemistry or Western blotting, it was concluded that the reduced phagocytic capacity was not the direct result of a CFTR mutation, but was attributed to a failure of neutrophil phagocytic priming during translocation into the CF lung. PMID:16178858

  19. Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing.

    PubMed

    Ly, Diane; Taylor, Jude M; Tsatsaronis, James A; Monteleone, Mercedes M; Skora, Amanda S; Donald, Cortny A; Maddocks, Tracy; Nizet, Victor; West, Nicholas P; Ranson, Marie; Walker, Mark J; McArthur, Jason D; Sanderson-Smith, Martina L

    2014-01-01

    The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates directly with a decrease in C3b opsonization, neutrophil phagocytosis, and increased bacterial survival in a humanized plasminogen mouse model of infection. These findings demonstrate that localized plasmin(ogen) plays an important role in facilitating GAS escape from the host innate immune response and increases bacterial virulence in the early stages of infection.

  20. A role for phosphodiesterase 3B in acquisition of brown fat characteristics by white adipose tissue in male mice.

    PubMed

    Guirguis, Emilia; Hockman, Steven; Chung, Youn Wook; Ahmad, Faiyaz; Gavrilova, Oksana; Raghavachari, Nalini; Yang, Yanqin; Niu, Gang; Chen, Xiaoyuan; Yu, Zu Xi; Liu, Shiwei; Degerman, Eva; Manganiello, Vincent

    2013-09-01

    Obesity is linked to various diseases, including insulin resistance, diabetes, and cardiovascular disorders. The idea of inducing white adipose tissue (WAT) to assume characteristics of brown adipose tissue (BAT), and thus gearing it to fat burning instead of storage, is receiving serious consideration as potential treatment for obesity and related disorders. Phosphodiesterase 3B (PDE3B) links insulin- and cAMP-signaling networks in tissues associated with energy metabolism, including WAT. We used C57BL/6 PDE3B knockout (KO) mice to elucidate mechanisms involved in the formation of BAT in epididymal WAT (EWAT) depots. Examination of gene expression profiles in PDE3B KO EWAT revealed increased expression of several genes that block white and promote brown adipogenesis, such as C-terminal binding protein, bone morphogenetic protein 7, and PR domain containing 16, but a clear BAT-like phenotype was not completely induced. However, acute treatment of PDE3B KO mice with the β3-adrenergic agonist, CL316243, markedly increased the expression of cyclooxygenase-2, which catalyzes prostaglandin synthesis and is thought to be important in the formation of BAT in WAT and the elongation of very long-chain fatty acids 3, which is linked to BAT recruitment upon cold exposure, causing a clear shift toward fat burning and the induction of BAT in KO EWAT. These data provide insight into the mechanisms of BAT formation in mouse EWAT, suggesting that, in a C57BL/6 background, an increase in cAMP, caused by ablation of PDE3B and administration of CL316243, may promote differentiation of prostaglandin-responsive progenitor cells in the EWAT stromal vascular fraction into functional brown adipocytes.

  1. Domain disruptions of individual 3B proteins for foot-and-mouth disease virus do not alter growth in cell culture nor virulence in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Picornavirus RNA replication is initiated by a small viral protein primer, 3B (also known as VPg), that is covalently linked to the 5’RNA of the viral genome. In contrast to other picornaviruses that encode a single copy of 3B, foot-and-mouth disease virus (FMDV) encodes three copies of 3B that are ...

  2. Verifying FY-3B Level 2 Rain Rate Retrievals Using Gauge Measurements of Minute-Rainfall over Eastern China

    NASA Astrophysics Data System (ADS)

    Xu, Bin; Xie, Pingping; Jiang, Lipeng; Shi, Chunxiang; You, Ran

    2014-05-01

    Despite their critical importance to the technology development and products applications, evaluating the performance for and quantifying the error in the satellite-based passive microwave (PMW) level 2 rain rate retrievals have been a challenging task, largely due to the lack of reliable ground truth matching the time / space scales of the target satellite retrievals. In this paper, we report a new approach to verify the level 2 rain rate retrievals from the Microwave Imager aboard the Chinese FengYun (FY) 3B satellite using gauge measurements of minute-rainfall over a dense network over the eastern China. As a first step, analyses of minute-rainfall are constructed on a 0.05olat/lon grid over eastern China for the warm seasons (May - September) of 2012 and 2013 through interpolation of quality controlled gauge reports from over 30,000 stations. At the meantime, parallax correction is performed to correct the displacement of the satellite field of view (FOV) position caused by the assumption of zero cloud height. Ground truth for the FY-3B level 2 retrievals of instantaneous rain rate is then defined as the 5-minute mean rate centering at the corresponding FOV observation time and over the 0.05olat/lon grid boxes falling into the target FY-3B FOV of ~25km diameter. Quantitative examinations of the FY-3B level 2 retrievals are finally conducted through comparisons against the gauge-based analyses of 5-minute rainfall for the 2012-2013 warm seasons. Only gauge analyses with three or more reporting gauges inside an FOV are used as the ground truth to ensure reasonable quality. Our preliminary results showed the following: 1) Parallax correction is crucial to ensure accurate evaluation of the level 2 satellite retrievals. The spatial displacement caused by parallax is about the same as the cloud top height, or half of the FY-3B FOV size, greatly compromising the accuracy of the performance evaluation; 2) The current version of the FY-3B level 2 retrievals tend to

  3. Dipolar Dyes with a Pyrrolo[2,3-b]quinoxaline Skeleton Containing a Cyano Group and a Bridged Tertiary Amino Group: Synthesis, Solvatofluorochromism, and Bioimaging.

    PubMed

    Łukasiewicz, Łukasz G; Deperasińska, Irena; Poronik, Yevgen M; Jun, Yong Woong; Banasiewicz, Marzena; Kozankiewicz, Bolesław; Ahn, Kyo Han; Gryko, Daniel T

    2016-06-01

    Two strongly polarized dipolar chromophores possessing a cyclic tertiary amino group at one terminus of the molecule and a CN group at the opposite terminus were designed and synthesized. Their rigid skeleton contains the rarely studied pyrrolo[2,3-b]quinoxaline ring system. The photophysical properties of these regioisomeric dyes were different owing to differing π conjugation between the CN group and the electron-donor moiety. These dipolar molecules showed very intense emission, strong solvatofluorochromism, and sufficient two-photon brightness for bioimaging. One of these regioisomeric dyes, namely, 11-carbonitrile-2,3,4,5,6,7-hexahydro-1H-3a,8,13,13b-tetraazabenzo[b]cyclohepta[1,2,3-jk]fluorene, was successfully utilized in two-photon imaging of mouse organ tissues and showed distinct tissue morphology with high resolution.

  4. 17 CFR 240.3b-5 - Non-exempt securities issued under governmental obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... be used, under a lease, sale, or loan arrangement, by or for industrial or commercial enterprise, shall be deemed to be a separate “security” within the meaning of section 3(a)(10) of the Act, issued by... a separate “security” as defined in paragraph (a) of this section if, (1) the obligation is...

  5. Summertime partitioning and budget of NO{sub y} compounds in the troposphere over Alaska and Canada: ABLE 3B

    SciTech Connect

    Sandholm, S.; Olson, J.; Bradshaw, J.; Talbot, R.; Singh, H.; Gregory, G.; Anderson, B.; Sachse, G.; Barrick, J.; Blake, D.

    1994-01-20

    As part of NASA`s Arctic Boundary Layer Expedition 3A and 3B field measurement programs, measurements of NO{sub x}, HNO{sub 3}, PAN, PPN, and NO{sub y} were made in the middle to lower troposphere over Alaska and Canada during the summers of 1988 and 1990. These measurements are used to assess the degree of closure within the reactive odd nitrogen (N{sub x}O{sub y}) budget through the comparison of the values of NO{sub y} measured with a catalytic convertor to the sum of individually measured NO{sub y}(i) compounds (i.e., {Sigma}NO{sub y}(i) = NO{sub x} + HNO{sub 3} + PAN + PPN). In the lower 6 km of the troposphere over Alaska and the Hudson Bay lowlands of Canada a significant fraction of the NO{sub y} budget (30 to 60%) could not be accounted for by the measured {Sigma}NO{sub y}(i). This deficit in the NO{sub y} budget is about 100 to 200 parts per trillion by volume (pptv) in the lower troposphere (0.15 to 3 km) and about 200 to 400 pptv in the middle free troposphere (3 to 6.2 km). Conversely, the NO{sub y} budget in the northern Labrador and Quebec regions of Canada is almost totally accounted for within the combined measurement uncertainties of NO{sub y} and the various NO{sub y}(i) compounds. A substantial portion of the NO{sub y} budget`s {open_quotes}missing compounds{close_quotes} appears to be coupled to the photochemical and/or dynamical parameters influencing the tropospheric oxidative potential over these regions. A combination of factors are suggested as the causes for the variability observed in the NO{sub y} budget. In addition, the apparent stability of compounds represented by the NO{sub y} budget deficit in the lower-altitude range questions the ability of these compounds to participate as reversible reservoirs for {open_quotes}active{close_quotes} odd nitrogen and suggest that some portion of the NO{sub y} budget may consist of relatively unreactive nitrogen-containing compounds. 56 refs., 16 figs., 4 tabs.

  6. In{sub 3}Ir{sub 3}B, In{sub 3}Rh{sub 3}B and In{sub 5}Ir{sub 9}B{sub 4}, the first indium platinum metal borides

    SciTech Connect

    Kluenter, Wilhelm; Jung, Walter . E-mail: walter.jung@uni-koeln.de

    2006-09-15

    The first indium platinum metal borides have been synthesized and structurally characterized by single crystal X-ray diffraction data. In{sub 3}Ir{sub 3}B and In{sub 3}Rh{sub 3}B are isotypic. They crystallize with the hexagonal space group P6-bar 2m and Z=1. The lattice constants are a=685.78(1)pm, c=287.30(1)pm for In{sub 3}Ir{sub 3}B and a=678.47(3)pm, c=288.61(6)pm for In{sub 3}Rh{sub 3}B. The structure which is derived from the Fe{sub 2}P type is characterized by columns of boron centered triangular platinum metal prisms inserted in a three-dimensional indium matrix. The indium atoms are on split positions. In{sub 5}Ir{sub 9}B{sub 4} (hexagonal, space group P6-bar 2m, a=559.0(2)pm, c=1032.6(3)pm, Z=1) crystallizes with a structure derived from the CeCo{sub 3}B{sub 2} type. The structure can be interpreted as a layer as well as a channel structure. In part the indium atoms are arranged at the vertices of a honeycomb net (Schlaefli symbol 6{sup 3}) separating slabs consisting of double layers of triangular Ir{sub 6}B prisms, and in part they form a linear chain in a hexagonal channel formed by iridium prisms and indium atoms of the honeycomb lattice.

  7. Association of HSD17B3 and HSD3B1 polymorphisms with acne vulgaris in Southwestern Han Chinese.

    PubMed

    Yang, Xiao-Yan; Wu, Wen-Juan; Yang, Cheng; Yang, Ting; He, Jun-Dong; Yang, Zhi; He, Li

    2013-01-01

    Acne vulgaris is a very common skin disorder. Previous studies have indicated that genetic background factors play key roles in the onset of acne. Our previous investigation implicated several genes in the androgen metabolism pathway with acne vulgaris in the Han Chinese population. Thus, we further investigated genes and genetic variants that play important roles in this pathway for their relationship with the pathology of acne. In this study, a total of 610 subjects, including 403 acne patients and 207 healthy controls, were genotyped for 15 single-nucleotide polymorphisms in HSD3B1 and HSD17B3 genes. This study shows that rs6428829 in HSD3B1 was associated with acne vulgaris in Han patients from Southwest China, even after adjusting for age and sex. The GG genotype was associated with an increased risk of acne vulgaris (p < 0.05) and G allele carriers were associated with an increased risk of acne vulgaris (p < 0.05). In addition, the haplotype AAT in HSD3B1 significantly increased the risk of acne vulgaris in the case-control study (p < 0.05). Furthermore, for another gene in this pathway, HSD17B3, the haplotype H8 was significantly associated with an increased risk of acne vulgaris. Based on these analyses, our study indicates that the cutaneous androgen metabolism-regulated genes HSD3B1 and HSD17B3 increase the susceptibility to acne vulgaris in Han Chinese from Southwest China.

  8. SF3B1 mutant MDS-initiating cells may arise from the haematopoietic stem cell compartment

    PubMed Central

    Mian, Syed A.; Rouault-Pierre, Kevin; Smith, Alexander E.; Seidl, Thomas; Pizzitola, Irene; Kizilors, Aytug; Kulasekararaj, Austin G.; Bonnet, Dominique; Mufti, Ghulam J.

    2015-01-01

    Despite the recent evidence of the existence of myelodysplastic syndrome (MDS) stem cells in 5q-MDS patients, it is unclear whether haematopoietic stem cells (HSCs) could also be the initiating cells in other MDS subgroups. Here we demonstrate that SF3B1 mutation(s) in our cohort of MDS patients with ring sideroblasts can arise from CD34+CD38−CD45RA−CD90+CD49f+ HSCs and is an initiating event in disease pathogenesis. Xenotransplantation of SF3B1 mutant HSCs leads to persistent long-term engraftment restricted to myeloid lineage. Moreover, genetically diverse evolving subclones of mutant SF3B1 exist in mice, indicating a branching multi-clonal as well as ancestral evolutionary paradigm. Subclonal evolution in mice is also seen in the clinical evolution in patients. Sequential sample analysis shows clonal evolution and selection of the malignant driving clone leading to AML transformation. In conclusion, our data show SF3B1 mutations can propagate from HSCs to myeloid progeny, therefore providing a therapeutic target. PMID:26643973

  9. A novel europium (III) nitridoborate Eu3[B3N6]: Synthesis, crystal structure, magnetic properties, and Raman spectra

    NASA Astrophysics Data System (ADS)

    Aydemir, Umut; Kokal, Ilkin; Prots, Yurii; Förster, Tobias; Sichelschmidt, Jörg; Schappacher, Falko M.; Pöttgen, Rainer; Ormeci, Alim; Somer, Mehmet

    2016-07-01

    A novel europium (III) nitridoborate, Eu3[B3N6], was successfully synthesized by oxidation of Eu3II[BN2]2 with Br2 at 1073 K. The compound crystallizes in the trigonal space group R 3 barc (No:167) with a=11.9370(4) Å, c=6.8073(4) Å, and Z=6. The crystal structure of Eu3[B3N6] consists of isolated, planar cyclic [B3N6]9- units which are charge-balanced by Eu3+ cations. The oxidation state of Eu was investigated by Mössbauer spectroscopy, electron spin resonance (ESR) spectroscopy, and quantum chemical calculations. The 151Eu Mössbauer spectroscopic measurement at 77 K reveals that the main signal at δ=0.93(7) mm/s is originating from trivalent Europium. Eu3[B3N6] showed no ESR signal in accordance with a non-magnetic (J=0) 7F0 ground state of the 4f6 configuration. Quantum chemical calculations find six electrons in the 4f subshell (4f6) of Eu indicating an oxidation state of +3. We present for the first time the vibrational spectra of a compound with cyclic trimer [B3N6]9- moieties. The Raman spectrum of Eu3[B3N6] is in good agreement with the predicted number of modes for the spectroscopically relevant cyclic [B3N6]9- group with D3h symmetry.

  10. Unique Features of Human Protein Arginine Methyltransferase 9 (PRMT9) and Its Substrate RNA Splicing Factor SF3B2*

    PubMed Central

    Hadjikyriacou, Andrea; Yang, Yanzhong; Espejo, Alexsandra; Bedford, Mark T.; Clarke, Steven G.

    2015-01-01

    Human protein arginine methyltransferase (PRMT) 9 symmetrically dimethylates arginine residues on splicing factor SF3B2 (SAP145) and has been functionally linked to the regulation of alternative splicing of pre-mRNA. Site-directed mutagenesis studies on this enzyme and its substrate had revealed essential unique residues in the double E loop and the importance of the C-terminal duplicated methyltransferase domain. In contrast to what had been observed with other PRMTs and their physiological substrates, a peptide containing the methylatable Arg-508 of SF3B2 was not recognized by PRMT9 in vitro. Although amino acid substitutions of residues surrounding Arg-508 had no great effect on PRMT9 recognition of SF3B2, moving the arginine residue within this sequence abolished methylation. PRMT9 and PRMT5 are the only known mammalian enzymes capable of forming symmetric dimethylarginine (SDMA) residues as type II PRMTs. We demonstrate here that the specificity of these enzymes for their substrates is distinct and not redundant. The loss of PRMT5 activity in mouse embryo fibroblasts results in almost complete loss of SDMA, suggesting that PRMT5 is the primary SDMA-forming enzyme in these cells. PRMT9, with its duplicated methyltransferase domain and conserved sequence in the double E loop, appears to have a unique structure and specificity among PRMTs for methylating SF3B2 and potentially other polypeptides. PMID:25979344

  11. Genome Sequence of "Thalassospira australica" NP3b2T Isolated from St. Kilda Beach, Tasman Sea.

    PubMed

    López-Pérez, Mario; Rodriguez-Valera, Francisco; Webb, Hayden K; Crawford, Russell J; Ivanova, Elena P

    2014-01-01

    Here, we present the draft genome of "Thalassospira australica" NP3b2(T), a potential poly(ethylene terephthalate) (PET) plastic biodegrader. This genomic information will enhance information on the genetic basis of metabolic pathways for the degradation of PET plastic. PMID:25395631

  12. Genome Sequence of "Thalassospira australica" NP3b2T Isolated from St. Kilda Beach, Tasman Sea.

    PubMed

    López-Pérez, Mario; Rodriguez-Valera, Francisco; Webb, Hayden K; Crawford, Russell J; Ivanova, Elena P

    2014-11-13

    Here, we present the draft genome of "Thalassospira australica" NP3b2(T), a potential poly(ethylene terephthalate) (PET) plastic biodegrader. This genomic information will enhance information on the genetic basis of metabolic pathways for the degradation of PET plastic.

  13. Genome Sequence of “Thalassospira australica” NP3b2T Isolated from St. Kilda Beach, Tasman Sea

    PubMed Central

    López-Pérez, Mario; Webb, Hayden K.; Crawford, Russell J.

    2014-01-01

    Here, we present the draft genome of “Thalassospira australica” NP3b2T, a potential poly(ethylene terephthalate) (PET) plastic biodegrader. This genomic information will enhance information on the genetic basis of metabolic pathways for the degradation of PET plastic. PMID:25395631

  14. SF3B1 mutant MDS-initiating cells may arise from the haematopoietic stem cell compartment.

    PubMed

    Mian, Syed A; Rouault-Pierre, Kevin; Smith, Alexander E; Seidl, Thomas; Pizzitola, Irene; Kizilors, Aytug; Kulasekararaj, Austin G; Bonnet, Dominique; Mufti, Ghulam J

    2015-12-08

    Despite the recent evidence of the existence of myelodysplastic syndrome (MDS) stem cells in 5q-MDS patients, it is unclear whether haematopoietic stem cells (HSCs) could also be the initiating cells in other MDS subgroups. Here we demonstrate that SF3B1 mutation(s) in our cohort of MDS patients with ring sideroblasts can arise from CD34(+)CD38(-)CD45RA(-)CD90(+)CD49f(+) HSCs and is an initiating event in disease pathogenesis. Xenotransplantation of SF3B1 mutant HSCs leads to persistent long-term engraftment restricted to myeloid lineage. Moreover, genetically diverse evolving subclones of mutant SF3B1 exist in mice, indicating a branching multi-clonal as well as ancestral evolutionary paradigm. Subclonal evolution in mice is also seen in the clinical evolution in patients. Sequential sample analysis shows clonal evolution and selection of the malignant driving clone leading to AML transformation. In conclusion, our data show SF3B1 mutations can propagate from HSCs to myeloid progeny, therefore providing a therapeutic target.

  15. 49 CFR 545.7 - Reporting requirements for vehicles listed in § 541.3(b)(2).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 6 2011-10-01 2011-10-01 false Reporting requirements for vehicles listed in § 541.3(b)(2). 545.7 Section 545.7 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR VEHICLE THEFT PREVENTION STANDARD PHASE-IN...

  16. A highly fluorescent DNA toolkit: synthesis and properties of oligonucleotides containing new Cy3, Cy5 and Cy3B monomers.

    PubMed

    Hall, Lucy M; Gerowska, Marta; Brown, Tom

    2012-08-01

    Cy3B is an extremely bright and stable fluorescent dye, which is only available for coupling to nucleic acids post-synthetically. This severely limits its use in the fields of genomics, biology and nanotechnology. We have optimized the synthesis of Cy3B, and for the first time produced a diverse range of Cy3B monomers for use in solid-phase oligonucleotide synthesis. This molecular toolkit includes phosphoramidite monomers with Cy3B linked to deoxyribose, to the 5-position of thymine, and to a hexynyl linker, in addition to an oligonucleotide synthesis resin in which Cy3B is linked to deoxyribose. These monomers have been used to incorporate single and multiple Cy3B units into oligonucleotides internally and at both termini. Cy3B Taqman probes, Scorpions and HyBeacons have been synthesized and used successfully in mutation detection, and a dual Cy3B Molecular Beacon was synthesized and found to be superior to the corresponding Cy3B/DABCYL Beacon. Attachment of Cy3, Cy3B and Cy5 to the 5-position of thymidine by an ethynyl linker enabled the synthesis of an oligonucleotide FRET system. The rigid linker between the dye and nucleobase minimizes dye-dye and dye-DNA interactions and reduces fluorescence quenching. These reagents open up new future applications of Cy3B, including more sensitive single-molecule and cell-imaging studies.

  17. Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma

    PubMed Central

    Liu, J-L; Chen, F-F; Lung, J; Lo, C-H; Lee, F-H; Lu, Y-C; Hung, C-H

    2014-01-01

    Background: Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs. Methods: We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated. Results: We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied

  18. SYNTHESIS AND CYTOTOXIC ACTIVITY OF NEW 5H-INDOLO[2,3-B]QUINOLINE O-AMINOGLYCOSIDES.

    PubMed

    Badowska-Rosłonek, Katarzyna; Ciesielska, Agnieszka; Switalska, Marta; Piskozub, Małgorzata; Peczyńska-Czoch, Wanda; Wietrzyk, Joanna; Kaczmarek, Łukasz

    2016-01-01

    Novel 5H-indolo[2,3-b]quinoline O-aminoglycosides were synthesized in order to check the hypothesis that the construction of hybrids composed of the active 5H-indolo[2,3-b]quinoline chromophore and daunosaminyl or acosaminyl moiety may result in the cytotoxic activity of the obtained derivatives that is much higher than the one of the parent DIMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline) and 6H-indoloquinoline analogs. Actually, 5H-indolo[2,3-b]indoloquinoline O-aminoglycosides showed the anti-proliferative activity in vitro against human lung adenocarcinoma A549, breast cancer MCF-7, melanoma Hs294T, promyelocytic leukemia HL-60, uterine sarcoma MES-SA and colon cancer LoVo cell lines, which was 10 times higher than that of the 6H-analogs and comparable to the one of the referential DIMIQ. Unexpectedly, it appeared that except for HL-60/MX2 (P-gp-independent and topoisomerase II-dependent resistance), other MDR tumor cell lines (LoVo/DX. P-gp-dependent, MRP-, LRP-dependent multidrug resistance) and MES-SA/DX5 (P-gp-dependent resistance to doxorubicin) are also resistant to the 5H-indolo[2,3-b]indoloquinoline O-aminoglycosides tested. This is surprising because 6H-analogs, in general, 10 times less active against non-MDR tumor cell lines, as well as the DIMIQ itself, are able to overcome drug resistance in all MDR cell lines examined. The cytotoxicity of the tested compounds against tumor cell lines and against normal cells (mice fibroblasts BALB/3T3) was comparable. PMID:27476287

  19. Complotype affects the extent of down-regulation by Factor I of the C3b feedback cycle in vitro.

    PubMed

    Lay, E; Nutland, S; Smith, J E; Hiles, I; Smith, R A G; Seilly, D J; Buchberger, A; Schwaeble, W; Lachmann, P J

    2015-08-01

    Sera from a large panel of normal subjects were typed for three common polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H), that influence predisposition to age-related macular degeneration and to some forms of kidney disease. Three groups of sera were tested; those that were homozygous for the three risk alleles; those that were heterozygous for all three; and those homozygous for the low-risk alleles. These groups vary in their response to the addition of exogenous Factor I when the alternative complement pathway is activated by zymosan. Both the reduction in the maximum amount of iC3b formed and the rate at which the iC3b is converted to C3dg are affected. For both reactions the at-risk complotype requires higher doses of Factor I to produce similar down-regulation. Because iC3b reacting with the complement receptor CR3 is a major mechanism by which complement activation gives rise to inflammation, the breakdown of iC3b to C3dg can be seen to have major significance for reducing complement-induced inflammation. These findings demonstrate for the first time that sera from subjects with different complement alleles behave as predicted in an in-vitro assay of the down-regulation of the alternative complement pathway by increasing the concentration of Factor I. These results support the hypothesis that exogenous Factor I may be a valuable therapeutic aid for down-regulating hyperactivity of the C3b feedback cycle, thereby providing a treatment for age-related macular degeneration and other inflammatory diseases of later life. PMID:25124117

  20. GSK3B and MAPT Polymorphisms Are Associated with Grey Matter and Intracranial Volume in Healthy Individuals

    PubMed Central

    Dobson-Stone, Carol; Polly, Patsie; Korgaonkar, Mayuresh S.; Williams, Leanne M.; Gordon, Evian; Schofield, Peter R.; Mather, Karen; Armstrong, Nicola J.; Wen, Wei; Sachdev, Perminder S.; Kwok, John B. J.

    2013-01-01

    The microtubule-associated protein tau gene (MAPT) codes for a protein that plays an integral role in stabilisation of microtubules and axonal transport in neurons. As well as its role in susceptibility to neurodegeneration, previous studies have found an association between the MAPT haplotype and intracranial volume and regional grey matter volumes in healthy adults. The glycogen synthase kinase-3β gene (GSK3B) codes for a serine/threonine kinase that phosphorylates various proteins, including tau, and has also been associated with risk for neurodegenerative disorders and schizophrenia. We examined the effects of MAPT and two functional promoter polymorphisms in GSK3B (rs3755557 and rs334558) on total grey matter and intracranial volume in three independent cohorts totaling 776 neurologically healthy individuals. In vitro analyses revealed a significant effect of rs3755557 on gene expression, and altered binding of at least two transcription factors, Octamer transcription factor 1 (Oct-1) and Pre-B-cell leukemia transcription factor 1 (Pbx-1), to the GSK3B promoter. Meta-analysis across the three cohorts revealed a significant effect of rs3755557 on total grey matter volume (summary B = 0.082, 95% confidence interval = 0.037–0.128) and intracranial volume (summary B = 0.113, 95% confidence interval = 0.082–0.144). No significant effect was observed for MAPT H1/H2 diplotype or GSK3B rs334558 on total grey matter or intracranial volume. Our genetic and biochemical analyses have identified a role for GSK3B in brain development, which could have important aetiological implications for neurodegenerative and neurodevelopmental disorders. PMID:23951236

  1. Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B.

    PubMed

    Heemskerk, Mattijs M; van den Berg, Sjoerd A A; Pronk, Amanda C M; van Klinken, Jan-Bert; Boon, Mariëtte R; Havekes, Louis M; Rensen, Patrick C N; van Dijk, Ko Willems; van Harmelen, Vanessa

    2014-04-01

    The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the underlying mechanisms are poorly understood. The current study addressed the effects of long-term niacin treatment on insulin-mediated inhibition of adipocyte lipolysis and focused on the regulation of cAMP levels. APOE*3-Leiden.CETP transgenic mice treated with niacin for 15 wk were subjected to an insulin tolerance test and showed whole body insulin resistance. Similarly, adipocytes isolated from niacin-treated mice were insulin resistant and, interestingly, exhibited an increased response to cAMP stimulation by 8Br-cAMP, β1- and β2-adrenergic stimulation. Gene expression analysis of the insulin and β-adrenergic pathways in adipose tissue indicated that all genes were downregulated, including the gene encoding the cAMP-degrading enzyme phosphodiesterase 3B (PDE3B). In line with this, we showed that insulin induced a lower PDE3B response in adipocytes isolated from niacin-treated mice. Inhibiting PDE3B with cilostazol increased lipolytic responsiveness to cAMP stimulation in adipocytes. These data show that long-term niacin treatment leads to a downregulation of PDE3B in adipocytes, which could explain part of the observed insulin resistance and the increased responsiveness to cAMP stimulation.

  2. Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)

    PubMed Central

    REILLY, B D; MOLD, C

    1997-01-01

    Complement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CR1 binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd ≍ 1.4 10−7M) than C4Bb2 (Kd ≍ 4–8 10−7M), indicating a preferential binding of CR1 for C4A. PMID:9367418

  3. Synthesis and biological assessment of diversely substituted furo[2,3-b]quinolin-4-amine and pyrrolo[2,3-b]quinolin-4-amine derivatives, as novel tacrine analogues.

    PubMed

    Martins, Carla; Carreiras, M Carmo; León, Rafael; de los Ríos, Cristóbal; Bartolini, Manuela; Andrisano, Vincenza; Iriepa, Isabel; Moraleda, Ignacio; Gálvez, Enrique; García, Manuela; Egea, Javier; Samadi, Abdelouhaid; Chioua, Mourad; Marco-Contelles, José

    2011-12-01

    The synthesis and pharmacological analyses of a number of furo[2,3-b]quinolin-4-amine, and pyrrolo[2,3-b]quinolin-4-amine derivatives are reported. Thus, we synthesized diversely substituted tacrine analogues 1-11 and 12-16 by Friedländer-type reaction of readily available o-amino(furano/pyrrolo)nitriles with suitable and selected cycloalkanones. The biological evaluation of furanotacrines1-11 and pyrrolotacrine13 showed that these are good, in the micromolar range, and highly selective inhibitors of BuChE. In the furanotacrine group, the most interesting inhibitor was 2-(p-tolyl)-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (3) [IC(50) (eqBuChE)=2.9 ± 0.4 μM; IC(50) (hBuChE)=119 ± 15 μM]. Conversely, pyrrolotacrines 12 and 14 proved moderately equipotent for both cholinesterases, being 1,2-diphenyl-5,6,7,8-tetrahydro-1H-pyrrolo[2,3-b]quinolin-4-amine (12) the most potent for the inhibition of both enzymes [IC(50) (EeAChE)=0.61 ± 0.04 μM; IC(50) (eqBuChE)=0.074 ± 0.009 μM]. Moreover, pyrrolotacrine 12, at concentrations as low as 300 nM can afford significant neuroprotective effects against Aβ-induced toxicity. Docking studies show that compounds 3 and 12 bind in the middle of the AChE active site gorge, but are buried deeper inside BuChE active site gorge, as a consequence of larger BuChE gorge void. All these data suggest that these new tacrine analogues could be used for the potential treatment of Alzheimer's disease. PMID:22000936

  4. Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation.

    PubMed

    Obeng, Esther A; Chappell, Ryan J; Seiler, Michael; Chen, Michelle C; Campagna, Dean R; Schmidt, Paul J; Schneider, Rebekka K; Lord, Allegra M; Wang, Lili; Gambe, Rutendo G; McConkey, Marie E; Ali, Abdullah M; Raza, Azra; Yu, Lihua; Buonamici, Silvia; Smith, Peter G; Mullally, Ann; Wu, Catherine J; Fleming, Mark D; Ebert, Benjamin L

    2016-09-12

    More than 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a conditional knockin mouse model of the most common SF3B1 mutation, Sf3b1(K700E). Sf3b1(K700E) mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Sf3b1(K700E) myeloid progenitors and SF3B1-mutant MDS patient samples demonstrate aberrant 3' splice-site selection associated with increased nonsense-mediated decay. Tet2 loss cooperates with Sf3b1(K700E) to cause a more severe erythroid and LT-HSC phenotype. Furthermore, the spliceosome modulator, E7017, selectively kills SF3B1(K700E)-expressing cells. Thus, SF3B1(K700E) expression reflects the phenotype of the mutation in MDS and may be a therapeutic target in MDS. PMID:27622333

  5. Demonstration in human plasma of a form of C3 that has the conformation of "C3b-like C3".

    PubMed

    Hack, C E; Paardekooper, J; Van Milligen, F

    1990-06-01

    Disruption of the thioester in native C3 yields a C3 molecule that functionally resembles C3b. It has been proposed that this C3 molecule (iC3) plays a key role in initiation of the alternative pathway of the C system. However, its presence in plasma has never been demonstrated. We investigated the presence of iC3 in plasma, using mAb that recognize iC3 as well as C3 activation products but not native C3. One of these mAb, anti-C3-5, which binds iC3 via its C3a moiety, was used together with polyclonal 125I-anti-C3c to develop a RIA for iC3. Plasma incubated with methylamine yielded a strong response in this RIA, whereas neither fresh plasma nor serum in which the C system had been activated by incubation with aggregated IgG, did show this strong response. The specificity of this RIA was further demonstrated by additional experiments including experiments with purified preparations of the various forms of C3. Mean level of iC3 in freshly obtained plasma samples from 10 normal donors was 27 nmol/liter, which is 0.49% of total C3. Analysis by SDS-PAGE of C3 species that had been immunoprecipitated by mAb antiC3-5, revealed that some iC3 consisted of C3 molecules with an intact alpha-chain whereas another part consisted of iC3 molecules with an alpha-chain that had been cleaved by factor I. Thus, this study shows that fresh human plasma contains a C3 species with the conformation of "C3b-like C3" (iC3).

  6. Nucleation of (He-3)-B from the A phase - A cosmic-ray effect?

    NASA Technical Reports Server (NTRS)

    Leggett, A. J.

    1984-01-01

    When He-3 is liquified and subsequently cooled, it undergoes, at a temperature of approximately 2.0-2.5 mK, a second-order transition into the so-called A phase. On further cooling, a first-order transition occurs, and the liquid passes into the B phase. Supercooling occurs with respect to the second transition, and the problem of nucleation arises. In connection with the experimental interest in studying metastable (He-3)-A down to the lowest temperatures in weak magnetic fields, the understanding of the mechanism of this transition and the feasibility of its inhibition is of some importance. The present investigation is concerned with the possibility that the transition is nucleated by the passage of a cosmic ray through the sample cell.

  7. Discovery and synthesis of novel allylthioaralkylthiopyridazines: their antiproliferative activity against MCF-7 and Hep3B cells.

    PubMed

    Park, Hae-Sun; Kim, Chaewon; Park, Myung-Sook

    2015-01-01

    A new series of 6-allylthio-3-aralkylthio-4,5-dimethylpyridazines 5a-5k and 1-allylthio-4-alkylthio-5,6,7,8-tetrahydrophthalazine 6a-6j was synthesized from maleic anhydride derivatives for development of new anticancer agents. The process involves the formation of pyridazine and phthalazine rings, dichlorination, allylthiolation, and aralkylthiolation. These new compounds showed antiproliferative activities against breast cancer (MCF-7) and hepatocarcinoma (Hep3B) cells in CCK-8 assays, and could be promising candidates for chemotherapy of carcinomas. Among 21 synthesized compounds, five compounds (5a, 5b, 6b, 6d, and 6f) showed higher potency than 5-FU for inhibiting the growth of cell line. The results indicated that compound 6f had the highest activity towards MCF-7 and Hep3B cells. These results suggest the potential anticancer activity of compounds 5a, 5b, 6b, 6d, and 6f.

  8. Synthesis and biological activity of 7H-benzo[4,5]indolo[2,3-b]-quinoxaline derivatives.

    PubMed

    Shibinskaya, Marina O; Karpenko, Alexander S; Lyakhov, Sergey A; Andronati, Sergey A; Zholobak, Nadezhda M; Spivak, Nikolay Ya; Samochina, Natalia A; Shafran, Lev M; Zubritsky, Mykhail Ju; Galat, Valerij F

    2011-02-01

    New 7-(2-aminoethyl)-7H-benzo[4,5]indolo[2,3-b]quinoxalines (13-20) were synthesized with high yields starting from 3H-benzo[e]indole-1,2-dione. These compounds were screened for the cytotoxicity, anti-viral activity, interferon inducing ability and DNA affinity compared with the corresponding 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxaline derivatives (1-12). It was shown, that compounds 13-20 bind to DNA stronger (lg Кa=6.23-6.87) than compounds 1-12 (lg Кa=5.57-5.89). Anti-viral activity is significantly reduced with annulations of benzene ring in Indoloquinoxaline moiety 13-20.

  9. Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b

    PubMed Central

    Wingert, Rebecca A.; Davidson, Alan J.

    2013-01-01

    Kidney nephrons are comprised of proximal and distal tubule segments that perform unique roles in excretion. The developmental pathways that establish nephron segment identities from renal progenitors are poorly understood. Here, we used the zebrafish pronephros to study nephron segmentation. We found that zebrafish nephron progenitors undergo elaborate spatiotemporal expression changes of many genes before adopting a segment fate. Initially, two domains of nephron progenitors are established, then are subdivided and demarcate individual nephron segments. Using genetic and chemical genetic models of retinoic acid (RA) deficiency, we discovered that RA modulates rostral progenitor formation. To delineate downstream pathways, we knocked down the irx3b transcription factor and found it regulates proximal tubule segment size and distal segment differentiation. Our results suggest a model whereby RA patterns the early field of nephron progenitors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs. PMID:21761484

  10. GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway.

    PubMed

    Ying, Ying; Zhu, Huazhang; Liang, Zhen; Ma, Xiaosong; Li, Shiwei

    2015-12-01

    Activation of apoptosis in cardiomyocytes by saturated palmitic acids contributes to cardiac dysfunction in diabetic cardiomyopathy. Beta-catenin (b-catenin) is a transcriptional regulator of several genes involved in survival/anti-apoptosis. However, its role in palmitate-induced cardiomyocyte apoptosis remains unclear. Glucagon-like peptide 1 (GLP1) has been shown to exhibit potential cardioprotective properties. This study was designed to evaluate the role of b-catenin signalling in palmitate-induced cardiomyocyte apoptosis and the molecular mechanism underlying the protective effects of GLP1 on palmitate-stressed cardiomyocytes. Exposure of neonatal rat cardiomyocytes to palmitate increased the fatty acid transporter CD36-mediated intracellular lipid accumulation and cardiomyocyte apoptosis, decreased accumulation and nuclear translocation of active b-catenin, and reduced expression of b-catenin target protein survivin and BCL2. These detrimental effects of palmitate were significantly attenuated by GLP1 co-treatment. However, the anti-apoptotic effects of GLP1 were markedly abolished when b-catenin was silenced with a specific short hairpin RNA. Furthermore, analysis of the upstream molecules and mechanisms responsible for GLP1-associated cardiac protection revealed that GLP1 restored the decreased phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3b (GSK3b) in palmitate-stimulated cardiomyocytes. In contrast, inhibition of Akt with an Akt-specific inhibitor MK2206 or blockade of GLP1 receptor (GLP1R) with a competitive antagonist exendin-(9-39) significantly abrogated the GLP1-mediated activation of GSK3b/b-catenin signalling, leading to increased apoptosis in palmitate-stressed cardiomyocytes. Collectively, our results demonstrated for the first time that the attenuated b-catenin signalling may contribute to palmitate-induced cardiomyocyte apoptosis, while GLP1 can protect cardiomyocytes from palmitate-induced apoptosis through

  11. Spectral energy distribution simulations of a possible ring structure around the young, red brown dwarf G 196-3 B

    NASA Astrophysics Data System (ADS)

    Zakhozhay, Olga V.; Zapatero Osorio, María Rosa; Béjar, Víctor J. S.; Boehler, Yann

    2016-09-01

    The origin of the very red optical and infrared colours of intermediate-age (˜10-500 Myr) L-type dwarfs remains unknown. It has been suggested that low-gravity atmospheres containing large amounts of dust may account for the observed reddish nature. We explored an alternative scenario by simulating protoplanetary and debris discs around G 196-3 B, which is an L3 young brown dwarf with a mass of ˜15 MJup and an age in the interval 20-300 Myr. The best-fit solution to G 196-3 B's photometric spectral energy distribution from optical wavelengths through 24 μm corresponds to the combination of an unreddened L3 atmosphere (Teff ≈ 1870 K) and a warm (≈ 1280 K), narrow (≈ 0.07-0.11 R⊙) debris disc located at very close distances (≈ 0.12-0.20 R⊙) from the central brown dwarf. This putative, optically thick, dusty belt, whose presence is compatible with the relatively young system age, would have a mass ≥7 × 10-10 M⊕ comprised of sub-micron/micron characteristic dusty particles with temperatures close to the sublimation threshold of silicates. Considering the derived global properties of the belt and the disc-to-brown dwarf mass ratio, the dusty ring around G 196-3 B may resemble the rings of Neptune and Jupiter, except for its high temperature and thick vertical height (≈6 × 103 km). Our inferred debris disc model is able to reproduce G 196-3 B's spectral energy distribution to a satisfactory level of achievement.

  12. Measurement of OH, H2SO4, MSA, NH3 and DMSO Aboard the NASA P-3B Aircraft

    NASA Technical Reports Server (NTRS)

    Eisele, Fred

    2001-01-01

    This project involved the installation of a downsized multichannel mass spectrometer instrument on the NASA P-3B aircraft and its subsequent use on the PEM-Tropics B mission. The new instrument performed well, measuring a number of difficult-to-measure compounds and providing much new photochemical and sulfur data as well as possibly uncovering a new nighttime DMSO source. The details of this effort are discussed.

  13. High Resolution Fabry-Perot Spectroscopy Of Comet Fragments 73P/ Schwassmann-Wachmann 3-B,C

    NASA Astrophysics Data System (ADS)

    Oliversen, Ronald J.; Mierkiewicz, E. J.; Morgenthaler, J. P.; Harris, W. M.; Kokorowski, M.; Kidder, A.; Schnackenberg, T.; Carpena Nunez, J.; Hall, T.; Haffner, L.

    2006-09-01

    In May 2006, comet 73P/Schwassmann-Wachmann 3 (SW3) made a spectacular close approach to the Earth. During its 1995 apparition, the comet fragmented into several pieces. One of the brighter components, SW3-B, fragmented into dozens of pieces during the 2006 apparition while another bright fragment, SW3-C did not. Understanding the difference between these two fragments will contribute significantly to our understanding of cometary interiors. We performed observations of SW3-B and SW3-C from Kitt Peak using the Fabry-Perot spectrometers at the McMath-Pierce (MMP) telescope from April 29 - May 10 and at the Wisconsin Hydrogen Alpha Mapper (WHαM) from May 1 - 6, 2006. This period is significant due to its proximity to perigee, overlap with complementary observations, and coincidence with the onset and decline-phase of a major outburst/fragmentation event from SW3-B. The MMP and WHAM Fabry-Perot spectrometers made high resolution measurements of [O I] and NH2 emissions near 6300 Å at δV = 5 km/s and 12 km/s with 4.5 arcmin and 1 degree fields of view, respectively. Many of the spectra separate the cometary and terrestrial [O I] lines and allow determination of water production rates. We report the preliminary analysis of these data, including discussion of the radial distribution of emissions, a comparison activity levels between the two fragments, and a comparison with complementary production rate measurements made over the same period. In addition, following the SW3-B May 9 outburst, H20+ measurements near 6200 Å were made to map the acceleration of water ions near the head and down the tail.

  14. GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway

    PubMed Central

    Ying, Ying; Zhu, Huazhang; Liang, Zhen; Ma, Xiaosong; Li, Shiwei

    2015-01-01

    Activation of apoptosis in cardiomyocytes by saturated palmitic acids contributes to cardiac dysfunction in diabetic cardiomyopathy. Beta-catenin (b-catenin) is a transcriptional regulator of several genes involved in survival/anti-apoptosis. However, its role in palmitate-induced cardiomyocyte apoptosis remains unclear. Glucagon-like peptide 1 (GLP1) has been shown to exhibit potential cardioprotective properties. This study was designed to evaluate the role of b-catenin signalling in palmitate-induced cardiomyocyte apoptosis and the molecular mechanism underlying the protective effects of GLP1 on palmitate-stressed cardiomyocytes. Exposure of neonatal rat cardiomyocytes to palmitate increased the fatty acid transporter CD36-mediated intracellular lipid accumulation and cardiomyocyte apoptosis, decreased accumulation and nuclear translocation of active b-catenin, and reduced expression of b-catenin target protein survivin and BCL2. These detrimental effects of palmitate were significantly attenuated by GLP1 co-treatment. However, the anti-apoptotic effects of GLP1 were markedly abolished when b-catenin was silenced with a specific short hairpin RNA. Furthermore, analysis of the upstream molecules and mechanisms responsible for GLP1-associated cardiac protection revealed that GLP1 restored the decreased phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3b (GSK3b) in palmitate-stimulated cardiomyocytes. In contrast, inhibition of Akt with an Akt-specific inhibitor MK2206 or blockade of GLP1 receptor (GLP1R) with a competitive antagonist exendin-(9–39) significantly abrogated the GLP1-mediated activation of GSK3b/b-catenin signalling, leading to increased apoptosis in palmitate-stressed cardiomyocytes. Collectively, our results demonstrated for the first time that the attenuated b-catenin signalling may contribute to palmitate-induced cardiomyocyte apoptosis, while GLP1 can protect cardiomyocytes from palmitate-induced apoptosis through

  15. Investigation of Somatic GNAQ, GNA11, BAP1 and SF3B1 Mutations in Ophthalmic Melanocytomas

    PubMed Central

    Francis, Jasmine H.; Wiesner, Thomas; Milman, Tatyana; Won, Helen H.; Lin, Amy; Lee, Vivian; Albert, Daniel M.; Folberg, Robert; Berger, Michael F.; Char, Devron H.; Marr, Brian; Abramson, David H.

    2016-01-01

    Purpose The aim of this study was to use massively parallel DNA sequencing to identify GNAQ/11, BAP1 and SF3B1 mutations in ophthalmic melanocytoma. Procedures Six ophthalmic melanocytoma specimens (1 iridociliary and 5 optic nerve) were profiled for genomic alterations in GNAQ/11, BAP1 and SF3B1 using a custom deep sequencing assay. This assay uses solution phase hybridization-based exon capture and deep-coverage massively parallel DNA sequencing to interrogate all protein-coding exons and select introns. Results The only iridociliary melanocytoma showed a mutation in GNAQ but not in BAP1. Of the 2 optic-nerve melanocytomas that developed into melanoma, one had a GNAQ mutation and both a BAP1 mutation and monosomy 3. The remaining 3 optic-nerve melanocytomas did not reveal mutations in GNAQ/11 or BAP1. SF3B1 mutations were not detected in any specimen. Conclusions The presence of GNAQ mutation in some iridociliary and optic-nerve melanocytomas suggests a possible relationship between ophthalmic melanocytoma and other ophthalmic melanocytic neoplasms. BAP1 mutation may accompany the transformation of ophthalmic melanocytoma to melanoma. PMID:27239460

  16. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    SciTech Connect

    Tsukahara, Tamotsu; Matsuda, Yoshikazu; Usui, Yuki; Haniu, Hisao

    2013-10-18

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

  17. Fibronectin and serum amyloid P component stimulate C3b- and C3bi- mediated phagocytosis in cultured human monocytes

    PubMed Central

    1983-01-01

    Fibronectin (FN) and serum amyloid P component (SAP) markedly enhance phagocytosis mediated by the C3b and C3bi receptors of cultured human monocytes but not of granulocytes. (The C3b and C3bi receptors of granulocytes can be activated by treatment of these phagocytes with PMA.) Activation of monocyte C3 receptors by FN is developmentally regulated: Freshly explanted monocytes respond to FN with a small increase in C3 receptor-mediated phagocytosis while monocytes matured in culture exhibit a much greater response. The mechanism of action of FN on C3 receptors of cultured monocytes is unique in two respects. First, while substrate-bound FN or SAP activate monocyte C3 receptors, soluble FN does not. Second, stimulation of the basal surface of monocyte plasma membranes by substrate-bound FN activates C3b and C3bi receptors on the apical surface of the plasma membrane, i.e., at sites remote from the segments of membrane in contact with the FN or SAP. PMID:6225825

  18. Procion red MX-3B-derived poly(HEMA/EGDMA) microspheres for removal of cadmium ions

    SciTech Connect

    Denizli, A.; Bueyuektuncel, E.; Genc, O.; Piskin, E.

    1998-12-01

    The heavy metal pollution is becoming more and more serious an environmental problem throughout the world due to rapid industrialization. Heavy metals such as cadmium and mercury exhibit human toxicity at extremely low concentrations. Poly(hydroxyethyl methacrylate/ethylene glycol dimethacrylate) [poly(HEMA/EGDMA)]-Procion Red MX-3B microspheres were used for removal of Cd(II) ions from aqueous solutions containing different amounts of Cd(II) ions (5--60 ppm). Dye-derived microbeads carrying 8.95 {micro}mol Procion Red MX-3B/g polymer were used in the adsorption-desorption of Cd(II) ions. High adsorption rates were observed at the beginning of adsorption and then equilibrium was achieved in about 5--10 min. The maximum adsorption of Cd(II) ions onto the Procion Red MX-3B-derived microspheres (i.e., by chelate formation of Cd(II) ions with dye molecules) was about 4.2 mg Cd(II) ions/g polymer, which was observed at pH 7.0. While non-specific adsorption onto the underived microspheres was 0.93 mg Cd(II) ions/g polymer. More than 96% of the adsorbed Cd(II) ions was desorbed in 15 min by using 0.1 M HNO{sub 3} as an desorption agent. The regenerability of the dye-derived atmospheres was also sufficient.

  19. An anomalous extinction law in the Cep OB3b young cluster: Evidence for dust processing during gas dispersal

    SciTech Connect

    Allen, Thomas S.; Prchlik, Jakub J.; Megeath, S. Thomas; Gutermuth, Robert A.; Pipher, Judith L.; Naylor, Tim; Jeffries, R. D.

    2014-05-10

    We determine the extinction law through Cep OB3b, a young cluster of 3000 stars undergoing gas dispersal. The extinction is measured toward 76 background K giants identified with MMT/Hectospec spectra. Color excess ratios were determined toward each of the giants using V and R photometry from the literature, g, r, i, and z photometry from the Sloan Digital Sky Survey and J, H, and K{sub s} photometry from the Two Micron All Sky Survey. These color excess ratios were then used to construct the extinction law through the dusty material associated with Cep OB3b. The extinction law through Cep OB3b is intermediate between the R{sub V} = 3.1 and R{sub V} = 5 laws commonly used for the diffuse atomic interstellar medium and dense molecular clouds, respectively. The dependence of the extinction law on line-of-sight A{sub V} is investigated and we find the extinction law becomes shallower for regions with A{sub V} > 2.5 mag. We speculate that the intermediate dust law results from dust processing during the dispersal of the molecular cloud by the cluster.

  20. The Ap3b1 gene regulates the ocular melanosome biogenesis and tyrosinase distribution differently from the Hps1 gene.

    PubMed

    Jing, Renwei; Dong, Xuan; Li, Kailin; Yan, Jie; Chen, Xiangyuan; Feng, Lijun

    2014-11-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. The pearl (pe) mouse, a mouse model for the human HPS-2, bears a mutation in Ap3b1 gene. Here we investigated the pigmentation in eyes of pearl (pe) mice, and compared it with our previously published data in pale ear (ep) mice. We revealed that the hypopigmentation in eyes of pearl mice was more severe than pale ear mice, especially in the neural crest-derived tissues. However, the total tyrosinase activity in eyes of pearl mice was stronger than pale ear mice, suggesting that the degradation of aberrantly transported tyrosinase in eyes of pearl mice was weaker than that of pale ear mice. Furthermore, the pigmentation in eyes of mice doubly heterozygous for Hps1 and Ap3b1 genes was similar to the wild-type, while the hypopigmentation in iris of double mutant mice was more severe than either single mutant. Besides, we found several previously reported characters in pale ear mice, including macromelanosomes in the neural crest-derived melanocytes and increased accumulation of lipofuscin in the RPE, were absent in pearl mice. Our study indicates that Ap3b1 gene play distinct roles in melanin production and tyrosinase distribution compared with Hps1 gene. PMID:25160823

  1. Variation in PTCHD2, CRISP3, NAP1L4, FSCB, and AP3B2 associated with spherical equivalent

    PubMed Central

    Chen, Fei; Duggal, Priya; Klein, Barbara E.K.; Lee, Kristine E.; Truitt, Barbara; Klein, Ronald; Iyengar, Sudha K.

    2016-01-01

    Purpose Ocular refraction is measured in spherical equivalent as the power of the external lens required to focus images on the retina. Myopia (nearsightedness) and hyperopia (farsightedness) are the most common refractive errors, and the leading causes of visual impairment and blindness in the world. The goal of this study is to identify rare and low-frequency variants that influence spherical equivalent. Methods We conducted variant-level and gene-level quantitative trait association analyses for mean spherical equivalent, using data from 1,560 individuals in the Beaver Dam Eye Study. Genotyping was conducted using the Illumina exome array. We analyzed 34,976 single nucleotide variants and 11,571 autosomal genes across the genome, using single-variant tests as well as gene-based tests. Results Spherical equivalent was significantly associated with five genes in gene-based analysis: PTCHD2 at 1p36.22 (p = 3.6 × 10−7), CRISP3 at 6p12.3 (p = 4.3 × 10−6), NAP1L4 at 11p15.5 (p = 3.6 × 10−6), FSCB at 14q21.2 (p = 1.5 × 10−7), and AP3B2 at 15q25.2 (p = 1.6 × 10−7). The variant-based tests identified evidence suggestive of association with two novel variants in linkage disequilibrium (pairwise r2 = 0.80) in the TCTE1 gene region at 6p21.1 (rs2297336, minor allele frequency (MAF) = 14.1%, β = –0.62 p = 3.7 × 10−6; rs324146, MAF = 16.9%, β = –0.55, p = 1.4 × 10−5). In addition to these novel findings, we successfully replicated a previously reported association with rs634990 near GJD2 at 15q14 (MAF = 47%, β = –0.29, p=1.8 × 10−3). We also found evidence of association with spherical equivalent on 2q37.1 in PRSS56 at rs1550094 (MAF = 31%, β = –0.33, p = 1.7 × 10−3), a region previously associated with myopia. Conclusions We identified several novel candidate genes that may play a role in the control of spherical equivalent. However, further studies are needed to replicate these findings. In addition, our results contribute to the

  2. Hubble Space Telescope Observations of the Nucleus Fragment 73P/Schwassmann-Wachmann 3-B

    NASA Astrophysics Data System (ADS)

    Toth, I.; Lamy, P. L.; Weaver, H. A.

    2003-05-01

    The nucleus of 73P/Schwassmann-Wachmann 3 (73P/SW3), a Jupiter-Family comet, has non-tidally broken into at least three components A, B and C, in autumn 1995. Fragment B was detected with the Planetary Camera 2 of the Hubble Space Telescope on 26 November 2001. i.e., after the comet's perihelion passage on 27.9 January 2001, when it was at 3.25 AU from the Sun, 2.33 AU from the Earth, and at a solar phase angle of 7.4o. The high spatial resolution of the PC2 allowed to separate the signal of the faint nucleus fragment from that of its active coma, and we measured its R magnitude from our images taken with the F675W filter. Assuming a spherical body whose geometric albedo is 0.04 and a linear phase coefficient of 0.04 mag/deg for the R band, we derived an effective radius of 0.68+/-0.04 km. The short time span of our HST observations did not allow to determine its shape but the lower limit of its axial ratio a/b (assuming a prolate spheroid) is ˜1.16. From the pre-breakup radius of the original nucleus of 1.3 km determined by Boehnhardt et al. (2002: EMPl 90, 131), we found that the fractional volume of fragment B is about 14%. Its size of a few hundred meters, typical of fragments of other split comets, is probably too large for a primordial building block and indicate that it still is a conglomerate; further disintegration of this fragment remains possible. Its level of activity is remarkably high in spite of a heliocentric distance of ˜3.2 AU, just beyond the limit for sublimation of water ice (2.8 AU). We measured an Afρ of 19.6-23.2 cm but the determination of a dust production rate is precluded by the absence of gas production rates at the time of our observation. Ground-based observations performed in 2001 by Boehnhardt et al. (2002: EMPl 90, 131) indicate that another fragment (E) has already disappeared, and we conclude that this may well be short-term fate of fragment B as it may not survive its next perihelion passage in 2006. The tau-Herculids meteor

  3. Promotion on the differentiation of retinal Müller cells into retinal ganglion cells by Brn-3b

    PubMed Central

    Wu, Zhen-Kai; Cao, Lan; Zhang, Xue-Yong; Song, Wei-Tao; Xia, Xiao-Bo

    2016-01-01

    AIM To investigate the role of Brn-3b in differentiation process of stem cells derived from retinal Müller cells into the ganglion cell. METHODS The passage culture method of Müller cells from retina of newborn Sprague Dawley rats was carried out by repeated incomplete pancreatic enzyme digestion method. The cells were detected by fluorescence-activated cell sorter (FACS), immunohistochemistry technology and reverse transcription-polymerase chain reaction (RT-PCR) to determine the purity. The third passage of cells was induced in the serum-free dedifferentiation medium. The expression of the specific markers Ki-67 and nestin of retinal stem cells was measured by RT-PCR and Western blot. The cell proliferation of retinal stem cells was detected by 5-ethynyl-2′-deoxyuridine (Edu) staining. The cells were randomly divided into 5 groups as follows: group A: Brn-3bsiRNA group; group B: Brn-3b control siRNA group; group C: pGC-Brn-3b-green fluorescent protein (GFP) group; group D: pGC-GFP group; group E: control group (without any handling). The purified Müller cells were cultured for 3-7d, then, the percentage of ganglion cells was counted by immunofluorescence staining. RESULTS FACS demonstrated the purity of retinal Müller cells was more 97.44%. A few spherical cell spheres appeared. Immunofluorescence staining showed that stem cells within the spheres were positive for retinal stem cell-specific markers nestin (red fluorescence, 92.94%±6.48%) and Ki-67 (green fluorescence, 85.96%±6.04%). Meanwhile, RT-PCR analysis showed cell spheres in the culture to have expressed a battery of transcripts characteristic of stem cells such as nestin and Ki-67, which were absent in the Müller cells. Western blot analysis further confirmed the expression of nestin and Ki-67 in the cell spheres but not in the Müller cells. Edu staining showed most of the nuclei within the cell spheres were stained red (82.80%±6.65%), suggesting the new cell spheres had the capacity for

  4. Embryonic type Na+ channel β-subunit, SCN3B masks the disease phenotype of Brugada syndrome

    PubMed Central

    Okata, Shinichiro; Yuasa, Shinsuke; Suzuki, Tomoyuki; Ito, Shogo; Makita, Naomasa; Yoshida, Tetsu; Li, Min; Kurokawa, Junko; Seki, Tomohisa; Egashira, Toru; Aizawa, Yoshiyasu; Kodaira, Masaki; Motoda, Chikaaki; Yozu, Gakuto; Shimojima, Masaya; Hayashiji, Nozomi; Hashimoto, Hisayuki; Kuroda, Yusuke; Tanaka, Atsushi; Murata, Mitsushige; Aiba, Takeshi; Shimizu, Wataru; Horie, Minoru; Kamiya, Kaichiro; Furukawa, Tetsushi; Fukuda, Keiichi

    2016-01-01

    SCN5A is abundant in heart and has a major role in INa. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation. Here we show that electrophysiological analysis revealed that LQTS3/BrS iPSC-derived cardiomyocytes recapitulate the phenotype of LQTS3 but not BrS. Each β-subunit of the sodium channel is differentially expressed in embryonic and adult hearts. SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. A heterologous expression system revealed that INa of mutated SCN5A is decreased and SCN3B augmented INa of mutated SCN5A. Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes successfully unmasked the phenotype of BrS. Isogenic control of LQTS3/BrS (corrected-LQTS3/BrS) iPSC-derived cardiomyocytes gained the normal electrophysiological properties. PMID:27677334

  5. Unique features of Erwinia chrysanthemi (Dickeya dadantii) RA3B genes involved in the blue indigoidine production.

    PubMed

    Chu, Mu-Kuei; Lin, Lee-Fong; Twu, Chung-Shing; Lin, Rong-Hwa; Lin, Yuan-Chuen; Hsu, Shih-Tien; Tzeng, Kuo-Ching; Huang, Hsiou-Chen

    2010-08-20

    Erwinia chrysanthemi (Ech) RA3B produces a large amount of blue indigoidine. Using Tn5-induced mutagenesis, three indigoidine-deficient mutants were generated. Followed by library screening, a 5.8kb fragment complemented mutants for indigoidine synthesis was cloned. This fragment contains four complete open-reading frames (ORFs), pecS, pecM, idgA, and idgB, and two partial ORFs, argG, and idgC. These genes are nearly identical to those in strain Ech3937. Primer extension assays demonstrated a clear transcriptional start site prior to idgA, while no promoter preceding idgB and idgC was detected, suggesting that idgA, idgB, and idgC are organized as one transcription unit. In contrast, indAB is separated from indC in Ech3937. Interestingly, an ERIC sequence was present between idgB and idgC in place of the promoter region of the homolog indC, which may contribute to the loss of promoter activity in RA3B. Futhermore, idgB mutant displayed much lighter blue color, while indB mutant appeared white on media. Overexpression of pecS in RA3B resulted in significantly reduced indigoidine production and idgC transcript. Moreover, gel shift and luxAB reporter assays revealed that PecS specifically binds to the sequence preceding idgA and inhibits gene expression, which is consistent with the results observed in Ech3937.

  6. Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game.

    PubMed

    Riepl, Korbinian; Mussel, Patrick; Osinsky, Roman; Hewig, Johannes

    2016-01-01

    The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants' behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task) via short movie clips and measured trait affect (longer-lasting emotional dispositions) via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states) led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on depression and

  7. Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game.

    PubMed

    Riepl, Korbinian; Mussel, Patrick; Osinsky, Roman; Hewig, Johannes

    2016-01-01

    The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants' behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task) via short movie clips and measured trait affect (longer-lasting emotional dispositions) via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states) led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on depression and

  8. An antarctic psychrotrophic bacterium Halomonas sp. ANT-3b, growing on n-hexadecane, produces a new emulsyfying glycolipid.

    PubMed

    Pepi, Milva; Cesàro, Attilio; Liut, Gianfranco; Baldi, Franco

    2005-06-01

    A bacterial strain ANT-3b was isolated at the sea-ice seawater interface from Terra Nova Bay station, Ross Sea, Antarctica. It was isolated on mineral medium supplemented with 2% diesel fuel as a sole carbon and energy source and grown routinely on 2% n-hexadecane. Analysis of 16S rRNA gene sequence indicates that the strain has 99.8% sequence similarity with Halomonas neptunia. The strain ANT-3b was grown in mineral medium supplemented with n-hexadecane between 4 and 20 degrees C, but not at 30 degrees C. The maximum degradation rate of the n-alkane was measured at 15 degrees C, with 5.6+/-1.7 mg O2 microg(-1) protein d(-1). The strain ANT-3b produced emulsifying compounds when grown on n-hexadecane, but not on mineral medium supplemented with D-fructose. A preliminary characterisation of the emulsifier was carried out. The lipid moiety contained a mixture of fatty acids with a following composition in molar ratio: caprylic acid 18.85, myristic acid 1.0, palmitic acid 9.68, palmitoleic acid 5.69 and oleic acid 1.26. The polysaccharide moiety also contained a mixture of sugars with the following molar ratio: mannose 1.71, galactose 1.00 and glucose 2.96. The molecular weight of the glycolipid component determined by gel permeation chromatography was in the 18 kDa range and contained smaller fragments, possibly oligomeric contaminants. Transmission electron microscopy showed contact between the glycolipid secreted by the strain and n-hexadecane broken down to nanodroplets at the water interface, to form a material with mesophase (liquid crystal) organisation.

  9. Complement component C3b and immunoglobulin Fc receptors on neutrophils from calves with leukocyte adhesion deficiency.

    PubMed

    Worku, M; Paape, M J; Di Carlo, A; Kehrli, M E; Marquardt, W W

    1995-04-01

    Receptors for opsonins, such as complement component C3b (CR1) and immunoglobulins, Fc receptors, interact with adhesion glycoproteins in mediating immune functions. Defects in expression of the adhesion glycoproteins CD11/CD18 results in severely hampered in vitro and in vivo adherence-related functions of leukocytes. Little is known regarding the effect of leukocyte adhesion deficiency (LAD) on ligand binding and receptor expression. We investigated the binding and expression of CR1 and Fc receptors by bovine neutrophils isolated from dairy calves suffering from LAD, compared with clinically normal (hereafter referred to as normal) age-matched calves. Neutrophils were also assayed for endogenously bound IgG and IgM and for exogenous binding of C3b, IgG1, IgG2, IgM, and aggregated IgG (aIgG), using flow cytometry. Luminol-enhanced chemiluminescence (CL) production in response to IgG2 opsonized zymosan was studied, and specific inhibition of CL was used to determine the specificity of IgG2 binding. Activation of protein kinase C with phorbol myristate acetate was used to determine the effect of cellular activation on expression of CR1. A greater percentage of neutrophils from normal calves bound C3b than did neutrophils from LAD-affected calves. Receptor expression was similar. Activation with phorbol myristate acetate resulted in increased expression of CR1 on neutrophils from normal and LAD-affected calves, but expression was almost twofold greater on neutrophils from normal calves. There was no difference between LAD-affected and normal calves in percentage of neutrophils that bound endogenous IgG and IgM. A greater percentage of neutrophils from normal calves bound exogenous IgM than did neutrophils from LAD-affected calves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7785817

  10. An antarctic psychrotrophic bacterium Halomonas sp. ANT-3b, growing on n-hexadecane, produces a new emulsyfying glycolipid.

    PubMed

    Pepi, Milva; Cesàro, Attilio; Liut, Gianfranco; Baldi, Franco

    2005-06-01

    A bacterial strain ANT-3b was isolated at the sea-ice seawater interface from Terra Nova Bay station, Ross Sea, Antarctica. It was isolated on mineral medium supplemented with 2% diesel fuel as a sole carbon and energy source and grown routinely on 2% n-hexadecane. Analysis of 16S rRNA gene sequence indicates that the strain has 99.8% sequence similarity with Halomonas neptunia. The strain ANT-3b was grown in mineral medium supplemented with n-hexadecane between 4 and 20 degrees C, but not at 30 degrees C. The maximum degradation rate of the n-alkane was measured at 15 degrees C, with 5.6+/-1.7 mg O2 microg(-1) protein d(-1). The strain ANT-3b produced emulsifying compounds when grown on n-hexadecane, but not on mineral medium supplemented with D-fructose. A preliminary characterisation of the emulsifier was carried out. The lipid moiety contained a mixture of fatty acids with a following composition in molar ratio: caprylic acid 18.85, myristic acid 1.0, palmitic acid 9.68, palmitoleic acid 5.69 and oleic acid 1.26. The polysaccharide moiety also contained a mixture of sugars with the following molar ratio: mannose 1.71, galactose 1.00 and glucose 2.96. The molecular weight of the glycolipid component determined by gel permeation chromatography was in the 18 kDa range and contained smaller fragments, possibly oligomeric contaminants. Transmission electron microscopy showed contact between the glycolipid secreted by the strain and n-hexadecane broken down to nanodroplets at the water interface, to form a material with mesophase (liquid crystal) organisation. PMID:16329937

  11. A TonB-Dependent Transporter Is Responsible for Methanobactin Uptake by Methylosinus trichosporium OB3b

    PubMed Central

    Gu, Wenyu; Farhan Ul Haque, Muhammad; Baral, Bipin S.; Turpin, Erick A.; Bandow, Nathan L.; Kremmer, Elisabeth; Flatley, Andrew; Zischka, Hans; DiSpirito, Alan A.

    2016-01-01

    Methanobactin, a small modified polypeptide synthesized by methanotrophs for copper uptake, has been found to be chromosomally encoded. The gene encoding the polypeptide precursor of methanobactin, mbnA, is part of a gene cluster that also includes several genes encoding proteins of unknown function (but speculated to be involved in methanobactin formation) as well as mbnT, which encodes a TonB-dependent transporter hypothesized to be responsible for methanobactin uptake. To determine if mbnT is truly responsible for methanobactin uptake, a knockout was constructed in Methylosinus trichosporium OB3b using marker exchange mutagenesis. The resulting M. trichosporium mbnT::Gmr mutant was found to be able to produce methanobactin but was unable to internalize it. Further, if this mutant was grown in the presence of copper and exogenous methanobactin, copper uptake was significantly reduced. Expression of mmoX and pmoA, encoding polypeptides of the soluble methane monooxygenase (sMMO) and particulate methane monooxygenase (pMMO), respectively, also changed significantly when methanobactin was added, which indicates that the mutant was unable to collect copper under these conditions. Copper uptake and gene expression, however, were not affected in wild-type M. trichosporium OB3b, indicating that the TonB-dependent transporter encoded by mbnT is responsible for methanobactin uptake and that methanobactin is a key mechanism used by methanotrophs for copper uptake. When the mbnT::Gmr mutant was grown under a range of copper concentrations in the absence of methanobactin, however, the phenotype of the mutant was indistinguishable from that of wild-type M. trichosporium OB3b, indicating that this methanotroph has multiple mechanisms for copper uptake. PMID:26773085

  12. Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game

    PubMed Central

    Riepl, Korbinian; Mussel, Patrick; Osinsky, Roman; Hewig, Johannes

    2016-01-01

    The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants’ behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task) via short movie clips and measured trait affect (longer-lasting emotional dispositions) via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states) led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on depression and

  13. Validation of Satellite Precipitation (trmm 3B43) in Ecuadorian Coastal Plains, Andean Highlands and Amazonian Rainforest

    NASA Astrophysics Data System (ADS)

    Ballari, D.; Castro, E.; Campozano, L.

    2016-06-01

    Precipitation monitoring is of utmost importance for water resource management. However, in regions of complex terrain such as Ecuador, the high spatio-temporal precipitation variability and the scarcity of rain gauges, make difficult to obtain accurate estimations of precipitation. Remotely sensed estimated precipitation, such as the Multi-satellite Precipitation Analysis TRMM, can cope with this problem after a validation process, which must be representative in space and time. In this work we validate monthly estimates from TRMM 3B43 satellite precipitation (0.25° x 0.25° resolution), by using ground data from 14 rain gauges in Ecuador. The stations are located in the 3 most differentiated regions of the country: the Pacific coastal plains, the Andean highlands, and the Amazon rainforest. Time series, between 1998 - 2010, of imagery and rain gauges were compared using statistical error metrics such as bias, root mean square error, and Pearson correlation; and with detection indexes such as probability of detection, equitable threat score, false alarm rate and frequency bias index. The results showed that precipitation seasonality is well represented and TRMM 3B43 acceptably estimates the monthly precipitation in the three regions of the country. According to both, statistical error metrics and detection indexes, the coastal and Amazon regions are better estimated quantitatively than the Andean highlands. Additionally, it was found that there are better estimations for light precipitation rates. The present validation of TRMM 3B43 provides important results to support further studies on calibration and bias correction of precipitation in ungagged watershed basins.

  14. Ribosomal P3 protein AtP3B of Arabidopsis acts as both protein and RNA chaperone to increase tolerance of heat and cold stresses.

    PubMed

    Kang, Chang Ho; Lee, Young Mee; Park, Joung Hun; Nawkar, Ganesh M; Oh, Hun Taek; Kim, Min Gab; Lee, Soo In; Kim, Woe Yeon; Yun, Dae-Jin; Lee, Sang Yeol

    2016-07-01

    The P3 proteins are plant-specific ribosomal P-proteins; however, their molecular functions have not been characterized. In a screen for components of heat-stable high-molecular weight (HMW) complexes, we isolated the P3 protein AtP3B from heat-treated Arabidopsis suspension cultures. By size-exclusion chromatography (SEC), SDS-PAGE and native PAGE followed by immunoblotting with anti-AtP3B antibody, we showed that AtP3B was stably retained in HMW complexes following heat shock. The level of AtP3B mRNA increased in response to both high- and low-temperature stresses. Bacterially expressed recombinant AtP3B protein exhibited both protein and RNA chaperone activities. Knockdown of AtP3B by RNAi made plants sensitive to both high- and low-temperature stresses, whereas overexpression of AtP3B increased tolerance of both conditions. Together, our results suggest that AtP3B protects cells against both high- and low-temperature stresses. These findings provide novel insight into the molecular functions and in vivo roles of acidic ribosomal P-proteins, thereby expanding our knowledge of the protein production machinery. PMID:27004478

  15. A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects

    PubMed Central

    Favaro, Francine P.; Alvizi, Lucas; Zechi-Ceide, Roseli M.; Bertola, Debora; Felix, Temis M.; de Souza, Josiane; Raskin, Salmo; Twigg, Stephen R.F.; Weiner, Andrea M.J.; Armas, Pablo; Margarit, Ezequiel; Calcaterra, Nora B.; Andersen, Gregers R.; McGowan, Simon J.; Wilkie, Andrew O.M.; Richieri-Costa, Antonio; de Almeida, Maria L.G.; Passos-Bueno, Maria Rita

    2014-01-01

    Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5′ untranslated region (5′ UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis. PMID:24360810

  16. Effect of copper speciation on whole-cell soluble methane monooxygenase activity in Methylosinus trichosporium OB3b.

    PubMed

    Morton, J D; Hayes, K F; Semrau, J D

    2000-04-01

    Soluble methane monooxygenase (sMMO) activity in Methylosinus trichosporium OB3b was found to be more strongly affected as copper-to-biomass ratios changed in a newly developed medium, M2M, which uses pyrophosphate for metal chelation, than in nitrate mineral salts (NMS), which uses EDTA. When M2M medium was amended with EDTA, sMMO activity was similar to that in NMS medium, indicating that EDTA-bound copper had lower bioavailability than pyrophosphate-bound copper. EDTA did not limit the association of copper with the cells; rather, copper was sequestered in a form which did not affect sMMO activity.

  17. Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: Lead optimization.

    PubMed

    Nógrádi, Katalin; Wágner, Gábor; Domány, György; Bobok, Amrita; Magdó, Ildikó; Kolok, Sándor; Mikó-Bakk, Mónika L; Vastag, Mónika; Sághy, Katalin; Gyertyán, István; Kóti, János; Gál, Krisztina; Farkas, Sándor; Keserű, György M; Greiner, István; Szombathelyi, Zsolt

    2015-04-15

    An HTS campaign of our corporate compound library, and hit-to lead development resulted in thieno[2,3-b]pyridine derivative leads with mGluR5 negative allosteric modulator effects. During the lead optimization process, our objective was to improve affinity and metabolic stability. Modification of the first two targeted regions resulted in compounds with nanomolar affinity, then optimal substitution of the third region improved metabolic stability. One of the most promising compounds showed excellent in vivo efficacy and is a potential development candidate.

  18. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  19. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  20. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  1. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  2. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  3. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  4. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  5. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  6. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  7. Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer.

    PubMed

    Ladoire, Sylvain; Penault-Llorca, Frédérique; Senovilla, Laura; Dalban, Cécile; Enot, David; Locher, Clara; Prada, Nicole; Poirier-Colame, Vichnou; Chaba, Kariman; Arnould, Laurent; Ghiringhelli, François; Fumoleau, Pierre; Spielmann, Marc; Delaloge, Suzette; Poillot, Marie Laure; Arveux, Patrick; Goubar, Aicha; Andre, Fabrice; Zitvogel, Laurence; Kroemer, Guido

    2015-01-01

    In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B(+) puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B(+) puncta reflects increased autophagic flux. After setting optimal thresholds in the test cohort, cytoplasmic LC3B(+) puncta and nuclear HMGB1 were scored as positive in 27.2% and 28.6% of the tumors, respectively, in the validation cohort, while 8.7% were considered as double positive. LC3B(+) puncta or HMGB1 expression alone did not constitute independent prognostic factors for metastasis-free survival (MFS) in multivariate analyses. However, the combined positivity for LC3B(+) puncta and nuclear HMGB1 constituted an independent prognostic factor significantly associated with prolonged MFS (hazard ratio: 0.49 95% confidence interval [0.26-0.89]; P = 0.02), and improved breast cancer specific survival (hazard ratio: 0.21 95% confidence interval [0.05-0.85]; P = 0.029). Subgroup analyses revealed that within patients with poor-prognosis BC, HMGB1(+) LC3B(+) double-positive tumors had a better prognosis than BC that lacked one or both of these markers. Altogether, these results suggest that the combined positivity for LC3B(+) puncta and nuclear HMGB1 is a positive predictor for longer BC survival.

  8. Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer

    PubMed Central

    Ladoire, Sylvain; Penault-Llorca, Frédérique; Senovilla, Laura; Dalban, Cécile; Enot, David; Locher, Clara; Prada, Nicole; Poirier-Colame, Vichnou; Chaba, Kariman; Arnould, Laurent; Ghiringhelli, François; Fumoleau, Pierre; Spielmann, Marc; Delaloge, Suzette; Poillot, Marie Laure; Arveux, Patrick; Goubar, Aicha; Andre, Fabrice; Zitvogel, Laurence; Kroemer, Guido

    2015-01-01

    In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B+ puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B+ puncta reflects increased autophagic flux. After setting optimal thresholds in the test cohort, cytoplasmic LC3B+ puncta and nuclear HMGB1 were scored as positive in 27.2% and 28.6% of the tumors, respectively, in the validation cohort, while 8.7% were considered as double positive. LC3B+ puncta or HMGB1 expression alone did not constitute independent prognostic factors for metastasis-free survival (MFS) in multivariate analyses. However, the combined positivity for LC3B+ puncta and nuclear HMGB1 constituted an independent prognostic factor significantly associated with prolonged MFS (hazard ratio: 0.49 95% confidence interval [0.26–0.89]; P = 0.02), and improved breast cancer specific survival (hazard ratio: 0.21 95% confidence interval [0.05–0.85]; P = 0.029). Subgroup analyses revealed that within patients with poor-prognosis BC, HMGB1+ LC3B+ double-positive tumors had a better prognosis than BC that lacked one or both of these markers. Altogether, these results suggest that the combined positivity for LC3B+ puncta and nuclear HMGB1 is a positive predictor for longer BC survival. PMID:26506894

  9. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients.

    PubMed

    Jeromin, S; Weissmann, S; Haferlach, C; Dicker, F; Bayer, K; Grossmann, V; Alpermann, T; Roller, A; Kohlmann, A; Haferlach, T; Kern, W; Schnittger, S

    2014-01-01

    We analyzed a large cohort of 1160 untreated CLL patients for novel genetic markers (SF3B1, NOTCH1, FBXW7, MYD88, XPO1) in the context of molecular, immunophenotypic and cytogenetic data. NOTCH1 mutations (mut) (12.3%), SF3B1mut (9.0%) and TP53mut (7.1%) were more frequent than XPO1mut (3.4%), FBXW7mut (2.5%) and MYD88mut (1.5%). SF3B1mut, NOTCH1mut, TP53mut and XPO1mut were highly correlated to unmutated, whereas MYD88mut were associated with mutated IGHV status. Associations of diverse cytogenetic aberrations and mutations emerged: (1) SF3B1mut with del(11q), (2) NOTCH1mut and FBXW7mut with trisomy 12 and nearly exclusiveness of SF3B1mut, (3) MYD88mut with del(13q) sole and low frequencies of SF3B1mut, NOTCH1mut and FBXW7mut. In patients with normal karyotype only SF3B1mut were frequent, whereas NOTCH1mut rarely occurred. An adverse prognostic impact on time to treatment (TTT) and overall survival (OS) was observed for SF3B1mut, NOTCH1mut and TP53 disruption. In multivariate analyses SF3B1mut, IGHV mutational status and del(11q) were the only independent genetic markers for TTT, whereas for OS SF3B1mut, IGHV mutational status and TP53 disruption presented with significant impact. Finally, our data suggest that analysis of gene mutations refines the risk stratification of cytogenetic prognostic subgroups and confirms data of a recently proposed model integrating molecular and cytogenetic data. PMID:24113472

  10. Age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis.

    PubMed

    Broséus, J; Alpermann, T; Wulfert, M; Florensa Brichs, L; Jeromin, S; Lippert, E; Rozman, M; Lifermann, F; Grossmann, V; Haferlach, T; Germing, U; Luño, E; Girodon, F; Schnittger, S

    2013-09-01

    Refractory anaemia with ring sideroblasts (RARS) and marked thrombocytosis (RARS-T) is a provisional entity in the World Health Organisation 2008 classification and has previously been shown to have a high proportion of JAK2(V617F) (Janus Kinase 2) and SF3B1 (Splicing Factor 3B subunit 1) mutations. The purpose of the present study was to analyse the frequency of SF3B1 mutations in a large cohort of 111 patients with RARS-T and 33 patients with RARS and to explore the prognostic impact of SF3B1 mutational status on RARS-T. The frequency of SF3B1 mutations in RARS-T (96/111, 86.5%) and RARS (28/33, 84.8%) was similar. In RARS-T, median survival was better in SF3B1-mutated patients than in SF3B1-non-mutated patients (6.9 and 3.3 years, respectively, P=0.003). RARS can be differentiated from RARS-T by the frequency of JAK2(V617F) (0% vs 48.6%). In RARS-T patients, SF3B1 (P=0.021) and JAK2 mutations (P=0.016) were independent factors for a better prognosis. Altogether, our results confirm that RARS-T is an independent entity that should be recognised by the next World Health Organisation classification. The assessment of SF3B1 mutations is of prognostic interest in RARS-T patients. Younger age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in RARS-T. PMID:23594705

  11. Results of the recent precipitation static flight test program on the Navy P-3B antisubmarine aircraft

    NASA Technical Reports Server (NTRS)

    Whitaker, Mike

    1991-01-01

    Severe precipitation static problems affecting the communication equipment onboard the P-3B aircraft were recently studied. The study was conducted after precipitation static created potential safety-of-flight problems on Naval Reserve aircraft. A specially designed flight test program was conducted in order to measure, record, analyze, and characterize potential precipitation static problem areas. The test program successfully characterized the precipitation static interference problems while the P-3B was flown in moderate to extreme precipitation conditions. Data up to 400 MHz were collected on the effects of engine charging, precipitation static, and extreme cross fields. These data were collected using a computer controlled acquisition system consisting of a signal generator, RF spectrum and audio analyzers, data recorders, and instrumented static dischargers. The test program is outlined and the computer controlled data acquisition system is described in detail which was used during flight and ground testing. The correlation of test results is also discussed which were recorded during the flight test program and those measured during ground testing.

  12. The activation of the C3b feedback cycle with human complement components. I. Through the classical pathway.

    PubMed

    Mak, L W; Lachmann, P J; Majewski, J

    1977-11-01

    Reaction between the fourth, the oxidized second and the activated first components of human complement generated the stable enzyme C4oxy2 capable of cleaving the third component and depleting total complement in human serum. This enzyme was shown further to activate the C3b feedback cycle as shown by its ability to consume factor B in serum and the reduction in the extent of complement consumption in the presence of EDTA. OxyC2 on its own gave rise to C3 cleavage in normal human serum by a pathway needing classical pathway components. This unexpected finding suggests that there may be a 'C-1 tickover' in serum analogous to the 'C3b tickover'; the presence of oxyC2 allowing the 'capture' of the trivial amounts of C42 normally formed. In preliminary experiments in the rat, C4oxy2 was successfully formed in vivo, where it gave rise to cleavage of C3, consumption of C5, depletion of cobra venom factor cofactors and a biphasic change in the neutrophil count.

  13. The Rossiter-McLaughlin effect of CoRoT-3b and HD 189733b

    NASA Astrophysics Data System (ADS)

    Triaud, A. H. M. J.; Queloz, D.; Bouchy, F.; Moutou, C.; Collier Cameron, A.; Claret, A.; Barge, P.; Benz, W.; Deleuil, M.; Guillot, T.; Hébrard, G.; Lecavelier Des Étangs, A.; Lovis, C.; Mayor, M.; Pepe, F.; Udry, S.

    2009-10-01

    We present radial-velocity sequences acquired during three transits of the exoplanet HD 189733b and one transit of CoRoT-3b. We applied a combined Markov-chain Monte-Carlo analysis of spectroscopic and photometric data on these stars, to determine a full set of system parameters including the projected spin-orbit misalignment angle of HD 189733b to an unprecedented precision via the Rossiter-McLaughlin effect: β = 0.85 circ + 0.32 ~- 0.28. This small but non-zero inclination of the planetary orbit is important to understand the origin of the system. On CoRoT-3b, results seem to point towards a non-zero inclination as well with β=37.6circ + 10.0 ~-22.3, but this remains marginal. Systematic effects due to non-Gaussian cross-correlation functions appear to be the main cause of significant residuals that prevent an accurate determination of the projected stellar rotation velocity V sin(I) for both stars. Using observations with the Harps spectrograph from the ESO 3.6 m installed at La Silla, Chile, under the allocated programmes 072.C-0488(E) and 079.C-0828(A). The data is publicly available in electronic form at the CDS. Tables 3 and 4 are only available in electronic form at http://www.aanda.org

  14. On the transferability of electron density in binary vanadium borides VB, V3B4 and VB2.

    PubMed

    Terlan, Bürgehan; Akselrud, Lev; Baranov, Alexey I; Borrmann, Horst; Grin, Yuri

    2015-12-01

    Binary vanadium borides are suitable model systems for a systematic analysis of the transferability concept in intermetallic compounds due to chemical intergrowth in their crystal structures. In order to underline this structural relationship, topological properties of the electron density in VB, V3B4 and VB2 reconstructed from high-resolution single-crystal X-ray diffraction data as well as derived from quantum chemical calculations, are analysed in terms of Bader's Quantum Theory of Atoms in Molecules [Bader (1990). Atoms in Molecules: A Quantum Theory, 1st ed. Oxford: Clarendon Press]. The compounds VB, V3B4 and VB2 are characterized by a charge transfer from the metal to boron together with two predominant atomic interactions, the shared covalent B-B interactions and the polar covalent B-M interactions. The resembling features of the crystal structures are well reflected by the respective B-B interatomic distances as well as by ρ(r) values at the B-B bond critical points. The latter decrease with an increase in the corresponding interatomic distances. The B-B bonds show transferable electron density properties at bond critical points depending on the respective bond distances. PMID:26634735

  15. Measurement of OH, H2SO4, MSA, DMSO, DMSO2 on the NASA P-3B Aircraft

    NASA Technical Reports Server (NTRS)

    Eisele, F. L.

    1998-01-01

    This project involves the deployment of a variety of unique aircraft measurements for the PEM-Tropics program. These measurements were all to be accomplished on a near simultaneous basis using a two channel selected ion chemical ionization mass spectrometer instrument. The first year of this project consisted of four components; improve and perform additional testing of the OH, H2SO4, and MSA instrument which had only flown on one previous mission (ACE-I); develop and test the vacuum and electronic hardware and software which would allow two independent mass spectrometer systems to be operated from a single instrument (one vacuum/pumping system); construct an aircraft compatible DMSO/DMS02 ion source and calibration system; and operate the above system on the NASA P-3B during PEM-Tropics. The first two of the components were to be accomplished at NCAR. The third component was to be completed at Georgia Tech and the fourth was to be conducted by researchers from both institutions on the NASA P-3B.

  16. Biotransformation of various saccharides and production of exopolymeric substances by cloud-borne Bacillus sp. 3B6.

    PubMed

    Matulová, Mária; Husárová, Slavomíra; Capek, Peter; Sancelme, Martine; Delort, Anne-Marie

    2014-12-16

    The ability of Bacillus sp. 3B6, a bacterial strain isolated from cloudwaters, to biotransform saccharides present in the atmosphere was evaluated using in situ 1D and 2D NMR spectroscopy. Bacillus is one of the genera most frequently described in the air and in atmospheric waters. Sugars present in these environments have a biogenic origin; they include alditols, monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Bacillus sp. 3B6 was able to efficiently metabolize sugars, which could thus provide sources of energy for this bacterium and allow it to live and to be metabolically active in warm clouds. In addition, a number of these saccharides (L-arabitol, D-fructose, sucrose, D-glucose, cellotetraose, cellulose, and starch) were transformed to EPSs (exopolymeric substances). We have clearly identified the structure of two EPSs as 1,6-α-galactan and partially acetylated polyethylene glycol. 1,6-α-Galactan is a newly described polymer. The production of EPSs might protect this bacterium under hostile cloud environment conditions, including low nutrient availability, cold temperature and freeze-thaw processes, UV and radical exposure, and evaporation-condensation processes and thus desiccation and osmolarity changes. EPSs could also have a potential role in atmospheric processes because they can be considered as secondary organic aerosols and efficient cloud condensation nuclei.

  17. NADH-Regulated metabolic model for growth of Methylosinus trichosporium OB3b. Model presentation, parameter estimation, and model validation.

    PubMed

    Sipkema, E M; de Koning, W; Ganzeveld, K J; Janssen, D B; Beenackers, A A

    2000-01-01

    A biochemical model is presented that describes growth of Methylosinus trichosporium OB3b on methane. The model, which was developed to compare strategies to alleviate NADH limitation resulting from cometabolic contaminant conversion, includes (1) catabolism of methane via methanol, formaldehyde, and formate to carbon dioxide; (2) growth as formaldehyde assimilation; and (3) storage material (poly-beta-hydroxybutyric acid, PHB) metabolism. To integrate the three processes, the cofactor NADH is used as central intermediate and controlling factor-instead of the commonly applied energy carrier ATP. This way a stable and well-regulated growth model is obtained that gives a realistic description of a variety of steady-state and transient-state experimental data. An analysis of the cells' physiological properties is given to illustrate the applicability of the model. Steady-state model calculations showed that in strain OB3b flux control is located primarily at the first enzyme of the metabolic pathway. Since no adaptation in V(MAX) values is necessary to describe growth at different dilution rates, the organism seems to have a "rigid enzyme system", the activity of which is not regulated in response to continued growth at low rates. During transient periods of excess carbon and energy source availability, PHB is found to accumulate, serving as a sink for transiently available excess reducing power. PMID:10753442

  18. Synthesis, crystal structure and magnetic properties of Li0.44Eu3[B3N6

    NASA Astrophysics Data System (ADS)

    Kokal, I.; Aydemir, U.; Prots, Yu.; Förster, T.; Sichelschmidt, J.; Yahyaoglu, M.; Auffermann, G.; Schnelle, W.; Schappacher, F.; Pöttgen, R.; Somer, M.

    2014-02-01

    Li0.44Eu3[B3N6] was synthesized from the metathesis reaction of Li3[BN2] and EuCl3 at 850 °C. Li0.44Eu3[B3N6] crystallizes in the trigonal space group R3barc (No. 167) with a=12.0225(2) Å, c=6.8556(2) Å and Z=6. In the crystal structure, isolated, planar cyclic [B3N6]9- units are charge-balanced by the mixed-valence Eu3+/Eu2+ and Li+ cations. Li+ occupies partially (44%) the Wyckoff site 6b and is sandwiched between the [B3N6]9- anions. Mössbauer spectroscopy results show the resonance lines of Eu2+ and Eu3+, respectively, indicating the heterogeneous mixed valency of the Eu atoms. X-Band ESR investigations between 5 and 300 K reveal an intense signal over the whole temperature range originating from Eu2+. Magnetic susceptibility measurements indicate a Curie-Weiss behavior with an experimental effective magnetic moment of μeff=8.28 μB per formula unit.

  19. Discovery of Novel N-alkyl 4-anilinofuro[2,3-b]quinoline Derivatives (CIL-102 Derivatives) Against Castration-resistant Human Prostate Cancers.

    PubMed

    Lo, We-Fen; Chou, Yu-Wei; Tseng, Chih-Hua; Shiu, Yia-Huei; Chen, Yu-Wen; Yang, Shyh-Chyun; Chen, Yeh-Long; Lin, Ming-Fong; Tzeng, Cherng-Chyi

    2015-01-01

    A number of N-alkylated 4-anilinofuro[2,3-b]quinoline derivatives were synthesized and evaluated in vitro against PC-3, A549, and MCF-7 cancer cells and M-10 normal human mammary epithelial cells. The known antimitotic CIL-102 was moderately active against the growth of PC-3 prostate cancer cells with an IC50 value of 2.69 μM while it was more potent against the growth of A549, MCF-7 and M-10 cells with IC50 values of 0.61, 0.31 and 0.95 μM, respectively. However, the cytotoxic profiles of its N-alkylated derivatives, 6a - 6c, were reversed and strongly inhibited PC-3 cell growth with IC50 values of less than 1.0 μM but only weakly against the growth of A549, MCF-7 and M-10 cells. These results indicated that N-alkylation of CIL-102 increased not only selectivity but also the antiproliferative potency against PC-3 cell growth. Among these derivatives synthesized, N-(4-acetylphenyl)-N-(furo[2,3-b]quinolin- 4-yl)methylamine (6a) and its N-ethyl counterpart 6b are the two most active CIL-102 derivatives against PC-3 cell growth with IC50 value of 0.22 and 0.20 μM, respectively. Compound 6a is less cytotoxic to normal human M-10 cells than 6b and therefore was selected for further mechanism studies. The flow cytometry studies clearly indicated that compound 6a induced cell accumulation in G2/M phase in a dose-dependent manner after 24 h-treatment. While the proliferation of LNCaP C-81 prostate cancer cells was also strongly suppressed by compound 6a; compound 11a exhibited better selective activity toward LNCaP C-81 prostate cancer cells over RWPE-1 non-cancerous prostate epithelia. Thus, this group of compounds has a potential of serving as therapeutic agents toward advanced castration-resistant prostate cancers.

  20. Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.

    PubMed

    Dolatshad, H; Pellagatti, A; Fernandez-Mercado, M; Yip, B H; Malcovati, L; Attwood, M; Przychodzen, B; Sahgal, N; Kanapin, A A; Lockstone, H; Scifo, L; Vandenberghe, P; Papaemmanuil, E; Smith, C W J; Campbell, P J; Ogawa, S; Maciejewski, J P; Cazzola, M; Savage, K I; Boultwood, J

    2015-05-01

    The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

  1. Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells

    PubMed Central

    Dolatshad, H; Pellagatti, A; Fernandez-Mercado, M; Yip, B H; Malcovati, L; Attwood, M; Przychodzen, B; Sahgal, N; Kanapin, A A; Lockstone, H; Scifo, L; Vandenberghe, P; Papaemmanuil, E; Smith, C W J; Campbell, P J; Ogawa, S; Maciejewski, J P; Cazzola, M; Savage, K I; Boultwood, J

    2015-01-01

    The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1–BCLAF1–SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34+ cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link. PMID:25428262

  2. Ras-Related Nuclear Protein Ran3B Gene Is Involved in Hormone Responses in the Embryogenic Callus of Dimocarpus longan Lour.

    PubMed Central

    Tian, Qilin; Lin, Yuling; Zhang, Dongmin; Lai, Ruilian; Lai, Zhongxiong

    2016-01-01

    Ras-related guanosine triphosphate (GTP)-binding nuclear protein (Ran) GTPases function as molecular switches and regulate diverse cellular events in eukaryotes. Our previous work suggested that DlRan3B is active during longan (Dimocarpus longan Lour.) somatic embryogenesis (SE) processes. Herein, subcellular localization of DlRan3B was found to be localized in the nucleus and expression profiling of DlRan3B was performed during longan SE and after exposure to plant hormones (indoleacetic acid (IAA), gibberellin A3 (GA3), salicylic acid (SA), methyl jasmonte (MeJA), and abscisic acid (ABA)). We cloned and sequenced 1569 bp of 5′-flanking sequence of DlRan3B (GenBank: JQ279697). Bioinformatic analysis indicated that the promoter contained plant hormone-related regulatory elements. Deletion analysis and responses to hormones identified stimulative and repressive regulatory elements in the DlRan3B promoter. The key elements included those responding to auxin, gibberellin, SA, MeJA, and ABA. DlRan3B was located in the nucleus and accumulated in the late stage of longan SE. The expression of DlRan3B was significantly induced by IAA, GA3, and ABA, but suppressed by SA and MeJA. Promoter transcription was induced by IAA and GA3, but suppressed by SA. Thus, DlRan3B might participate in auxin, gibberellin, and ABA responses during longan late SE, and DlRan3B is involved in phytohormone responsiveness. PMID:27271605

  3. E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor

    SciTech Connect

    Jenei, Veronika; Andersson, Tommy; Jakus, Judit; Dib, Karim . E-mail: k.dib@qub.ac.uk

    2005-11-01

    E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21{sup Ras} and Rac. E3b1 is a regulator of Rac because it can form a complex with Sos-1 and eps8, and such a Sos-1-e3B1-eps8 complex serves as a guanine nucleotide exchange factor for Rac. In the present study, we found that overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21{sup Ras}. Remarkably, we found that EGF-induced activation of the p21{sup Ras}-related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells. Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF-induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells. We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF-induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl. However, EGF-induced tyrosine phosphorylation of the Rap GEF C3G occurred regardless of whether e3B1 was overexpressed or not, and this did not involve Src tyrosine kinases. Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF-induced activation of Rap1 and inhibition of cell proliferation.

  4. Implementation of an optimal stomatal conductance scheme in the Australian Community Climate Earth Systems Simulator (ACCESS1.3b)

    NASA Astrophysics Data System (ADS)

    Kala, J.; De Kauwe, M. G.; Pitman, A. J.; Lorenz, R.; Medlyn, B. E.; Wang, Y.-P.; Lin, Y.-S.; Abramowitz, G.

    2015-12-01

    We implement a new stomatal conductance scheme, based on the optimality approach, within the Community Atmosphere Biosphere Land Exchange (CABLEv2.0.1) land surface model. Coupled land-atmosphere simulations are then performed using CABLEv2.0.1 within the Australian Community Climate and Earth Systems Simulator (ACCESSv1.3b) with prescribed sea surface temperatures. As in most land surface models, the default stomatal conductance scheme only accounts for differences in model parameters in relation to the photosynthetic pathway but not in relation to plant functional types. The new scheme allows model parameters to vary by plant functional type, based on a global synthesis of observations of stomatal conductance under different climate regimes over a wide range of species. We show that the new scheme reduces the latent heat flux from the land surface over the boreal forests during the Northern Hemisphere summer by 0.5-1.0 mm day-1. This leads to warmer daily maximum and minimum temperatures by up to 1.0 °C and warmer extreme maximum temperatures by up to 1.5 °C. These changes generally improve the climate model's climatology of warm extremes and improve existing biases by 10-20 %. The bias in minimum temperatures is however degraded but, overall, this is outweighed by the improvement in maximum temperatures as there is a net improvement in the diurnal temperature range in this region. In other regions such as parts of South and North America where ACCESSv1.3b has known large positive biases in both maximum and minimum temperatures (~ 5 to 10 °C), the new scheme degrades this bias by up to 1 °C. We conclude that, although several large biases remain in ACCESSv1.3b for temperature extremes, the improvements in the global climate model over large parts of the boreal forests during the Northern Hemisphere summer which result from the new stomatal scheme, constrained by a global synthesis of experimental data, provide a valuable advance in the long-term development

  5. Association of DNMT3B -283 T > C and -579 G > T polymorphisms with decreased cancer risk: evidence from a meta-analysis

    PubMed Central

    Zhang, Yang; Xu, Haisheng; Shen, Yi; Gong, Zhimin; Xiao, Tianlin

    2015-01-01

    Numerous studies have explored the association of polymorphisms in the DNA methyltransferase 3b (DNMT3B) gene with the risk of different types of cancer, but yielded controversial results. Therefore, we performed a meta-analysis to derive a more precise estimation of the association between three widely-studied DNMT3B polymorphisms and overall cancer susceptibility. Totally, 4 studies with 1234 cases and 1337 controls were eligible for DNMT3B -283 T > C (rs6087990), 19 studies with 5332 cases and 7407 controls for DNMT3B -149 C > T (rs2424913), and 14 studies with 3933 cases and 4436 controls for DNMT3B -579 G > T (rs1569686). Overall, DNMT3B -283 T > C was associated with a significantly reduced risk of overall cancer (T vs. C: OR = 0.84, 95% CI = 0.71-0.99, P = 0.039). Likewise, the association of DNMT3B -579 G > T with a decreased overall cancer risk was also observed (heterozygous: OR = 0.77, 95% CI = 0.65-0.91, P = 0.003 and dominant: OR = 0.80, 95% CI = 0.66-0.98, P = 0.029); in the subgroup analysis, the protective association was found for lung and colorectal cancer, but not for head and neck cancer. Finally, the pooled analysis showed no significant association between DNMT3B -149 C > T and overall cancer susceptibility, but stratification analysis indicated that this polymorphism decreased the risk of developing head and neck cancer (heterozygous: OR = 0.73, 95% CI = 0.59-0.90, P = 0.003 and dominant: OR = 0.76, 95% CI = 0.61-0.93, P = 0.009). In conclusion, our results suggested that DNMT3B -283 T > C and DNMT3B -579 G > T but DNMT3B -149 C > T might confer protection against overall cancer risk. In the future, large and well-designed case-control studies are needed to validate our findings. PMID:26550225

  6. Evidence suggesting phosphodiesterase-3B regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons.

    PubMed

    Anamthathmakula, Prashanth; Sahu, Maitrayee; Sahu, Abhiram

    2015-09-14

    Hypothalamic neurons expressing neuropeptide Y (NPY) and agouti related-protein (AgRP) are critical regulators of feeding behavior and body weight, and transduce the action of many peripheral signals including leptin and insulin. However, intracellular signaling molecules involved in regulating NPY/AgRP neuronal activity are incompletely understood. Since phosphodiesterase-3B (PDE3B) mediates the hypothalamic action of leptin and insulin on feeding, and is expressed in NPY/AgRP neurons, PDE3B could play a significant role in regulating NPY/AgRP neuronal activity. To investigate the direct regulation of NPY/AgRP neuronal activity by PDE3B, we examined the effects of gain-of-function or reduced function of PDE3B on NPY/AgRP gene expression in a clonal hypothalamic neuronal cell line, mHypoE-46, which endogenously express NPY, AgRP and PDE3B. Overexpression of PDE3B in mHypoE-46 cells with transfection of pcDNA-3.1-PDE3B expression plasmid significantly decreased NPY and AgRP mRNA levels and p-CREB levels as compared to the control plasmid. For the PDE3B knockdown study, mHypoE-46 cells transfected with lentiviral PDE3BshRNAmir plasmid or non-silencing lentiviral shRNAmir control plasmid were selected with puromycin, and stably transfected cells were grown in culture for 48h. Results showed that PDE3BshRNAmir mediated knockdown of PDE3B mRNA and protein levels (∼60-70%) caused an increase in both NPY and AgRP gene expression and in p-CREB levels. Together, these results demonstrate a reciprocal change in NPY and AgRP gene expression following overexpression and knockdown of PDE3B, and suggest a significant role for PDE3B in the regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons.

  7. Research Update: Magnetic phase diagram of EuTi1-xBxO3 (B = Zr, Nb)

    DOE PAGES

    Li, Ling; Zhou, Haidong; Yan, Jiaqiang; Mandrus, David; Keppens, Veerle

    2014-11-21

    Herein, we report the magnetic phase diagram of EuTi1-xBxO3 (B = Zr, Nb), determined from magnetization and heat capacity measurements. Upon Zr-doping, the antiferromagnetic ordering temperature TN of EuTi1-xZrxO3 gradually decreases from 5.6 K (x = 0) to 4.1 K (x = 1). Whereas a similar decrease in TN is observed for small amounts of Nb doping (x ≤ 0.05), ferromagnetism is induced in EuTi1-xNbxO3 with x > 0.05. Lastly, the ferromagnetic interaction between localized Eu 4f spins mediated by itinerant electrons introduced by Nb doping results in the ferromagnetism in EuTi1-xNbxO3.

  8. Magnetic ordering and spin-reorientation transitions in TbCo{sub 3}B{sub 2}

    SciTech Connect

    Dubman, Moshe; Caspi, El'ad N.; Ettedgui, Hanania; Keller, Lukas; Melamud, Mordechai; Shaked, Hagai

    2005-07-01

    The magnetic structure of the compound TbCo{sub 3}B{sub 2} has been studied in the temperature range 1.5 K{<=}T{<=}300 K by means of neutron powder diffraction, magnetization, magnetic ac susceptibility, and heat capacity measurements. The compound is of hexagonal symmetry and is paramagnetic at 300 K, undergoes a magnetic Co-Co ordering transition at {approx}170 K, and a second magnetic Tb-Tb ordering transition at {approx}30 K. The latter induces a spin-reorientation transition, in which the magnetic axis rotates from the c axis toward the basal plane. Below this transition a symmetry decrease ({gamma} magnetostriction) sets in, leading to an orthorhombic distortion of the crystal lattice. The crystal and magnetic structures and interactions and their evolution with temperature are discussed using a microscopic physical model.

  9. Crystal structure and magnetization of a Co{sub 3}B{sub 2}O{sub 6} single crystal

    SciTech Connect

    Kazak, N. V.; Platunov, M. S.; Ivanova, N. B.; Knyazev, Yu. V.; Bezmaternykh, L. N.; Eremin, E. V.; Vasil'ev, A. D.; Bayukov, O. A.; Ovchinnikov, S. G.; Velikanov, D. A.; Zubavichus, Ya. V.

    2013-07-15

    The crystal structure and magnetic properties of Co{sub 3}B{sub 2}O{sub 6} single crystals are studied. Orthorhombic symmetry with space group Pnnm is detected at room temperature. The measurements of static magnetization and dynamic magnetic susceptibility reveal two magnetic anomalies at T{sub 1} = 33 K and T{sub 2} = 10 K and an easy-axis magnetic anisotropy. The effective magnetic moment indicates a high-spin state of the Co{sup 2+} ion. A spin-flop transition is found at low temperatures and H{sub sf} = 23 kOe. EXAFS spectra of the K-edge absorption of Co are recorded at various temperatures, the temperature-induced changes in the parameters of the local environment of cobalt are analyzed, and the effective Co-Co and Co-O distances are determined. The magnetic interactions in the crystal are analyzed in terms of an indirect coupling model.

  10. The effects of physical aging at elevated temperatures on the viscoelastic creep on IM7/K3B

    NASA Technical Reports Server (NTRS)

    Gates, Thomas S.; Feldman, Mark

    1994-01-01

    Physical aging at elevated temperature of the advanced composite IM7/K3B was investigated through the use of creep compliance tests. Testing consisted of short term isothermal, creep/recovery with the creep segments performed at constant load. The matrix dominated transverse tensile and in-plane shear behavior were measured at temperatures ranging from 200 to 230 C. Through the use of time based shifting procedures, the aging shift factors, shift rates and momentary master curve parameters were found at each temperature. These material parameters were used as input to a predictive methodology, which was based upon effective time theory and linear viscoelasticity combined with classical lamination theory. Long term creep compliance test data was compared to predictions to verify the method. The model was then used to predict the long term creep behavior for several general laminates.

  11. Sequential electrophilic trifluoromethanesulfanylation-cyclization of tryptamine derivatives: synthesis of C(3)-trifluoromethanesulfanylated hexahydropyrrolo[2,3-b]indoles.

    PubMed

    Yang, Yi; Jiang, Xueliang; Qing, Feng-Ling

    2012-09-01

    A practical and efficient synthesis of C(3)-trifluoromethanesulfanylated hexahydropyrrolo[2,3-b]indoles 5 from tryptamine derivatives was described. The features of this synthesis included electrophilic activation of C(3) of tryptamine derivatives with "CF(3)S(+)" and cascade ring cyclization by carbamate nucleophile attacking at C(2). Surprisingly, when Lewis acid (BF(3)·OEt(2)) was used as activator instead of proton acid (TsOH·H(2)O) for the electrophilic trifluoromethanesulfanylation of tryptamine derivatives, the uncyclized product 6 was formed preferentially. This sequential trifluoromethanesulfanylation-cyclization protocol was used to synthesize several pyrrolidinoindolinic alkaloid analogues. The cytotoxicity activities of these trifluoromethanesulfanylated alkaloid analogues were evaluated against three cancer cell lines (K562, HeLa, L929). PMID:22889233

  12. Bioprinting is coming of age: Report from the International Conference on Bioprinting and Biofabrication in Bordeaux (3B'09).

    PubMed

    Guillemot, Fabien; Mironov, Vladimir; Nakamura, Makoto

    2010-03-01

    The International Conference on Bioprinting and Biofabrication in Bordeaux (3B'09) demonstrated that the field of bioprinting and biofabrication continues to evolve. The increasing number and broadening geography of participants, the emergence of new exciting bioprinting technologies, and the attraction of young investigators indicates the strong growth potential of this emerging field. Bioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies. The use of bioprinting technology for biofabrication of in vitro assay has been shown to be a realistic short-term application. At the same time, the principal feasibility of bioprinting vascularized human organs as well as in vivo bioprinting has been demonstrated. The bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications. It was decided that the 5th International Conference on Bioprinting and Biofabrication would be held in Philadelphia, USA in October 2010. The specially appointed 'Eploratory Committee' will consider the possibility of turning the growing bioprinting community into a more organized entity by creating a new bioprinting and biofabrication society. The new journal Biofabrication was also presented at 3B'09. This is an important milestone per se which provides additional objective evidence that the bioprinting and biofabrication field is consolidating and maturing. Thus, it is safe to state that bioprinting technology is coming of age.

  13. Detection of norovirus genotype I.3b and II.4 in bioaccumulated blue mussels using different virus recovery methods.

    PubMed

    Comelli, Heidi Lange; Rimstad, Espen; Larsen, Stig; Myrmel, Mette

    2008-09-30

    Noroviruses (NoVs) are the most common non bacterial human pathogens associated with shellfish borne gastroenteritis. Norovirus detection is based on molecular procedures such as reverse transcriptase (RT)-PCR. A variety of methods have been developed to extract viral RNA from complex shellfish matrixes and to reduce the level of RT-PCR inhibitors. The present study had three objectives: 1) Determine the most appropriate sample treatment protocol for detection of NoVs in mussels, 2) Examine whether there is a variation of the binding affinity between a NoV GI and a GII strain to mussel digestive tissue and how this influences the detection sensitivity, 3) Establish an internal control for sample processing and virus detection. Three RNA extraction methods were evaluated on extracts from blue mussels (Mytilus edulis) spiked with NoV GII.4. The most efficient RNA extraction method was subsequently used for evaluation of three virus recovery methods of blue mussels bio accumulated with NoV GI.3b and GII.4. Mengovirus was evaluated as an internal process control and TaqMan RT-PCRs were used for virus detection. Elution of the two viruses from shellfish tissue differed, indicating a difference in binding affinities. Only a method based upon Proteinase K digestion followed by NucliSenseasyMAG was able to detect both NoV GI.3b and GII.4 (3.0% and 3.5% recovery respectively). The results show that the processing method influences the possibility to detect different variants of NoV.

  14. Discovery of antitumor anthra[2,3-b]furan-3-carboxamides: Optimization of synthesis and evaluation of antitumor properties.

    PubMed

    Shchekotikhin, Andrey E; Dezhenkova, Lyubov G; Tsvetkov, Vladimir B; Luzikov, Yuri N; Volodina, Yulia L; Tatarskiy, Victor V; Kalinina, Anastasia A; Treshalin, Michael I; Treshalina, Helen M; Romanenko, Vladimir I; Kaluzhny, Dmitry N; Kubbutat, Michael; Schols, Dominique; Pommier, Yves; Shtil, Alexander A; Preobrazhenskaya, Maria N

    2016-04-13

    Anthraquinones and their analogues, in particular heteroarene-fused anthracendiones, are prospective scaffolds for new compounds with improved antitumor characteristics. We herein report the use of a 'scaffold hopping' approach for the replacement of the core structure in the previously discovered hit compound naphtho[2,3-f]indole-5,10-dione 2 with an alternative anthra[2,3-b]furan-5,10-dione scaffold. Among 13 newly synthesized derivatives the majority of 4,11-dihydroxy-2-methyl-5,10-dioxoanthra[2,3-b]furan-3-carboxamides demonstrated a high antiproliferative potency against a panel of wild type and drug resistant tumor cell lines, a property superior over the reference drug doxorubicin or lead naphtho[2,3-f]indole-5,10-dione 2. At low micromolar concentrations the selected derivative of (R)-3-aminopyrrolidine 3c and its stereoisomer (S)-3-aminopyrrolidine 3d caused an apoptotic cell death preceded by an arrest in the G2/M phase. Studies of intracellular targets showed that 3c and 3d formed stable intercalative complexes with the duplex DNA as determined by spectral analysis and molecular docking. Both 3c and 3d attenuated topoisomerase 1 and 2 mediated unwinding of the supercoiled DNA via a mechanism different from conventional DNA-enzyme tertiary complex formation. Furthermore, 3d decreased the activity of selected human protein kinases in vitro, indicating multiple targeting by the new chemotype. Finally, 3d demonstrated an antitumor activity in a model of murine intraperitoneally transplanted P388 leukemia, achieving the increase of animal life span up to 262% at tolerable doses. Altogether, the 'scaffold hopping' demonstrated its productivity for obtaining new perspective antitumor drug candidates.

  15. Tactile orientation perception: an ideal observer analysis of human psychophysical performance in relation to macaque area 3b receptive fields.

    PubMed

    Peters, Ryan M; Staibano, Phillip; Goldreich, Daniel

    2015-12-01

    The ability to resolve the orientation of edges is crucial to daily tactile and sensorimotor function, yet the means by which edge perception occurs is not well understood. Primate cortical area 3b neurons have diverse receptive field (RF) spatial structures that may participate in edge orientation perception. We evaluated five candidate RF models for macaque area 3b neurons, previously recorded while an oriented bar contacted the monkey's fingertip. We used a Bayesian classifier to assign each neuron a best-fit RF structure. We generated predictions for human performance by implementing an ideal observer that optimally decoded stimulus-evoked spike counts in the model neurons. The ideal observer predicted a saturating reduction in bar orientation discrimination threshold with increasing bar length. We tested 24 humans on an automated, precision-controlled bar orientation discrimination task and observed performance consistent with that predicted. We next queried the ideal observer to discover the RF structure and number of cortical neurons that best matched each participant's performance. Human perception was matched with a median of 24 model neurons firing throughout a 1-s period. The 10 lowest-performing participants were fit with RFs lacking inhibitory sidebands, whereas 12 of the 14 higher-performing participants were fit with RFs containing inhibitory sidebands. Participants whose discrimination improved as bar length increased to 10 mm were fit with longer RFs; those who performed well on the 2-mm bar, with narrower RFs. These results suggest plausible RF features and computational strategies underlying tactile spatial perception and may have implications for perceptual learning.

  16. Detection of norovirus genotype I.3b and II.4 in bioaccumulated blue mussels using different virus recovery methods.

    PubMed

    Comelli, Heidi Lange; Rimstad, Espen; Larsen, Stig; Myrmel, Mette

    2008-09-30

    Noroviruses (NoVs) are the most common non bacterial human pathogens associated with shellfish borne gastroenteritis. Norovirus detection is based on molecular procedures such as reverse transcriptase (RT)-PCR. A variety of methods have been developed to extract viral RNA from complex shellfish matrixes and to reduce the level of RT-PCR inhibitors. The present study had three objectives: 1) Determine the most appropriate sample treatment protocol for detection of NoVs in mussels, 2) Examine whether there is a variation of the binding affinity between a NoV GI and a GII strain to mussel digestive tissue and how this influences the detection sensitivity, 3) Establish an internal control for sample processing and virus detection. Three RNA extraction methods were evaluated on extracts from blue mussels (Mytilus edulis) spiked with NoV GII.4. The most efficient RNA extraction method was subsequently used for evaluation of three virus recovery methods of blue mussels bio accumulated with NoV GI.3b and GII.4. Mengovirus was evaluated as an internal process control and TaqMan RT-PCRs were used for virus detection. Elution of the two viruses from shellfish tissue differed, indicating a difference in binding affinities. Only a method based upon Proteinase K digestion followed by NucliSenseasyMAG was able to detect both NoV GI.3b and GII.4 (3.0% and 3.5% recovery respectively). The results show that the processing method influences the possibility to detect different variants of NoV. PMID:18640736

  17. Selective role for DNMT3a in learning and memory

    PubMed Central

    Morris, Michael J; Adachi, Megumi; Na, Elisa S; Monteggia, Lisa M

    2014-01-01

    Methylation of cytosine nucleotides is governed by DNA methyltransferases (DNMTs) that establish de novo DNA methylation patterns in early embryonic development (e.g., DNMT3a and DNMT3b) or maintain those patterns on hemimethylated DNA in dividing cells (e.g., DNMT1). DNMTs continue to be expressed at high levels in mature neurons, however their impact on neuronal function and behavior are unclear. To address this issue we examined DNMT1 and DNMT3a expression following associative learning. We also generated forebrain specific conditional Dnmt1 or Dnmt3a knockout mice and characterized them in learning and memory paradigms as well as for alterations in long-term potentiation (LTP) and synaptic plasticity. Here, we report that experience in an associative learning task impacts expression of Dnmt3a, but not Dnmt1, in brain areas that mediate learning of this task. We also found that Dnmt3a knockout mice, and not Dnmt1 knockouts have synaptic alterations as well as learning deficits on several associative and episodic memory tasks. These findings indicate that the de novo DNA methylating enzyme DNMT3a in postmitotic neurons is necessary for normal memory formation and its function cannot be substituted by the maintenance DNA methylating enzyme DNMT1. PMID:24937014

  18. Distinct pattern of P3a event-related potential in borderline personality disorder.

    PubMed

    Meares, Russell; Melkonian, Dmitriy; Gordon, Evian; Williams, Leanne

    2005-02-28

    P3a and P3b event-related brain potentials to auditory stimuli were recorded for 17 unmedicated patients with borderline personality disorder, 17 matched healthy controls and 100 healthy control participants spanning five decades. Using high-resolution fragmentary decomposition for single-trial event-related potential analysis, distinctive disturbances in P3a in borderline personality disorder patients were found: abnormally enhanced amplitude, failure to habituate and a loss of temporal locking with P3b. Normative age dependencies from 100 controls suggest that natural age-related decline in P3a amplitude is reduced in borderline personality disorder patients and is likely to indicate failure of frontal maturation. On the basis of the theories of Hughlings Jackson, this conceptualization of borderline personality disorder is consistent with an aetiological model of borderline personality disorder. PMID:15706238

  19. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION... E.O. 12958. The levels established by E.O. 12958 (Top Secret, Secret, and Confidential) are the...

  20. Epstein-Barr virus nuclear antigen 3A promotes cellular proliferation by repression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1.

    PubMed

    Tursiella, Melissa L; Bowman, Emily R; Wanzeck, Keith C; Throm, Robert E; Liao, Jason; Zhu, Junjia; Sample, Clare E

    2014-10-01

    Latent infection by Epstein-Barr virus (EBV) is highly associated with the endemic form of Burkitt lymphoma (eBL), which typically limits expression of EBV proteins to EBNA-1 (Latency I). Interestingly, a subset of eBLs maintain a variant program of EBV latency - Wp-restricted latency (Wp-R) - that includes expression of the EBNA-3 proteins (3A, 3B and 3C), in addition to EBNA-1. In xenograft assays, Wp-R BL cell lines were notably more tumorigenic than their counterparts that maintain Latency I, suggesting that the additional latency-associated proteins expressed in Wp-R influence cell proliferation and/or survival. Here, we evaluated the contribution of EBNA-3A. Consistent with the enhanced tumorigenic potential of Wp-R BLs, knockdown of EBNA-3A expression resulted in abrupt cell-cycle arrest in G0/G1 that was concomitant with conversion of retinoblastoma protein (Rb) to its hypophosphorylated state, followed by a loss of Rb protein. Comparable results were seen in EBV-immortalized B lymphoblastoid cell lines (LCLs), consistent with the previous observation that EBNA-3A is essential for sustained growth of these cells. In agreement with the known ability of EBNA-3A and EBNA-3C to cooperatively repress p14(ARF) and p16(INK4a) expression, knockdown of EBNA-3A in LCLs resulted in rapid elevation of p14(ARF) and p16I(NK4a). By contrast, p16(INK4a) was not detectably expressed in Wp-R BL and the low-level expression of p14(ARF) was unchanged by EBNA-3A knockdown. Amongst other G1/S regulatory proteins, only p21(WAF1/CIP1), a potent inducer of G1 arrest, was upregulated following knockdown of EBNA-3A in Wp-R BL Sal cells and LCLs, coincident with hypophosphorylation and destabilization of Rb and growth arrest. Furthermore, knockdown of p21(WAF1/CIP1) expression in Wp-R BL correlated with an increase in cellular proliferation. This novel function of EBNA-3A is distinct from the functions previously described that are shared with EBNA-3C, and likely contributes to the