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Sample records for 3a 3b 4a

  1. Broadcasting Satellite-3A and -3B (BS-3A and 3B)

    NASA Technical Reports Server (NTRS)

    Horii, M.; Funakawa, K.

    1991-01-01

    The BS-3A and -3B will provide direct color TV broadcasting to the Japanese mainland and remote islands. The satellites will be launched from Tanegashima Space Center by a type H-1 launch vehicle. The coverage will consist of the 26-m antenna and the 34-m antenna as a backup support for the transfer and drift orbits. Maximum support will consist of one 8-hour track per station for a seven day period, plus 23 days of contingency support from all complexes. Information is given in tabular form for Deep Space Network support, frequency assignments, telemetry, command, and tracking support responsibility.

  2. 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

    ... 7, 2010 (75 FR 910), we published a final rule AD, FR Doc, E9-30471, in the Federal Register. That... (GE) CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1 turbofan engines. The GE alert service bulletin...

  3. Evidence of CH{sub 2}O (a-tilde{sup 3}A{sub 2}) and C{sub 2}H{sub 4} (a-tilde{sup 3}B{sub 1u}) produced from photodissociation of 1,3-trimethylene oxide at 193 nm

    SciTech Connect

    Lee, S.-H.; Ong, C.-S.; Lee, Yuan T.

    2006-02-21

    We investigated the dissociative ionization of formaldehyde (CH{sub 2}O) and ethene (C{sub 2}H{sub 4}) produced from photolysis of 1,3-trimethylene oxide at 193 nm using a molecular-beam apparatus and vacuum-ultraviolet radiation from an undulator for direct ionization. The CH{sub 2}O (C{sub 2}H{sub 4}) product suffers from severe dissociative ionization to HCO{sup +} (C{sub 2}H{sub 3}{sup +} and C{sub 2}H{sub 2}{sup +}) even though photoionization energy is as small as 9.8 eV. Branching ratios of fragmentation of CH{sub 2}O and C{sub 2}H{sub 4} following ionization are revealed as a function of kinetic energy of products using ionizing photons from 9.8 to 14.8 eV. Except several exceptions, branching ratios of daughter ions increase with increasing photon energy but decrease with increasing kinetic energy. The title reaction produces CH{sub 2}O and C{sub 2}H{sub 4} mostly on electronic ground states but a few likely on triplet states; C{sub 2}H{sub 4} (a-tilde{sup 3}B{sub 1u}) seems to have a yield greater than CH{sub 2}O (a-tilde{sup 3}A{sub 2}). The distinct features observed at small kinetic energies of daughter ions are attributed to dissociative ionization of photoproducts CH{sub 2}O (a-tilde{sup 3}A{sub 2}) and C{sub 2}H{sub 4} (a-tilde{sup 3}B{sub 1u}). The observation of triplet products indicates that intersystem crossing occurs prior to fragmentation of 1,3-trimethylene oxide.

  4. 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

  5. Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem cells.

    PubMed

    Challen, Grant A; Sun, Deqiang; Mayle, Allison; Jeong, Mira; Luo, Min; Rodriguez, Benjamin; Mallaney, Cates; Celik, Hamza; Yang, Liubin; Xia, Zheng; Cullen, Sean; Berg, Jonathan; Zheng, Yayun; Darlington, Gretchen J; Li, Wei; Goodell, Margaret A

    2014-09-01

    Epigenetic regulation of hematopoietic stem cells (HSCs) ensures lifelong production of blood and bone marrow. Recently, we reported that loss of de novo DNA methyltransferase Dnmt3a results in HSC expansion and impaired differentiation. Here, we report conditional inactivation of Dnmt3b in HSCs either alone or combined with Dnmt3a deletion. Combined loss of Dnmt3a and Dnmt3b was synergistic, resulting in enhanced HSC self-renewal and a more severe block in differentiation than in Dnmt3a-null cells, whereas loss of Dnmt3b resulted in a mild phenotype. Although the predominant Dnmt3b isoform in adult HSCs is catalytically inactive, its residual activity in Dnmt3a-null HSCs can drive some differentiation and generates paradoxical hypermethylation of CpG islands. Dnmt3a/Dnmt3b-null HSCs displayed activated β-catenin signaling, partly accounting for the differentiation block. These data demonstrate distinct roles for Dnmt3b in HSC differentiation and provide insights into complementary de novo methylation patterns governing regulation of HSC fate decisions. PMID:25130491

  6. 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

    ...-07R1, Amendment 39-15179 (72 FR 49183, August 28, 2007) and AD 2007-05-16, Amendment 39-14977 (72 FR... FR 17799). That action proposed to require: Replacing certain fan disks installed on regional jets... instructions related to operators who fly a regional jet (RJ) with the CF34-3A1 engine as a business jet...

  7. FCGR3A and FCGR3B copy number variations are risk factors for sarcoidosis.

    PubMed

    Wu, Jianming; Li, Yunfang; Guan, Weihua; Viken, Kevin; Perlman, David M; Bhargava, Maneesh

    2016-07-01

    Sarcoidosis is a multisystem granulomatous disorder that causes significant morbidity. Genetic factors contribute to sarcoidosis risks. In this study, we investigated whether copy number variations (CNVs) of FCGR3A (coding for FcγRIIIA) and FCGR3B (coding for FcγRIIIB) genes are associated with sarcoidosis susceptibility and whether the expressions of FcγRIIIA on NK cells and FcγRIIIB on neutrophils are altered in sarcoidosis patients. TaqMan real-time PCR assays were used to analyze the CNV of FCGR3A and FCGR3B genes. FCGR3A and FCGR3B CNV genotypes were compared between 671 biopsy-proven sarcoidosis patients and the same number of healthy controls matched with age, sex, race, and geographic area from the ACCESS (A Case Control Etiologic Study of Sarcoidosis) cohort. Flow cytometry analyses were used to determine expressions of FcγRIIIA on NK cells and FcγRIIIB on neutrophils in phenotype analyses. We found that FCGR3A CNVs were significantly associated with sarcoidosis in females (CN = 1 vs. CN = 2 logistic regression adjusted for sex and race, OR 4.0156, SE = 2.2784, P = 0.0143; CN = 3 vs. CN = 2 logistic regression adjusted for sex and race, OR 2.8044, SE = 1.1065, P = 0.0090), suggesting that FCGR3A gene abnormality influences sarcoidosis development in a gender-specific manner. Furthermore, FcγRIIIA expressions were significantly decreased on NK cells from sarcoidosis patients compared to those from healthy controls (P = 0.0007). Additionally, low FCGR3B CN was associated with sarcoidosis (CN <2 vs. CN = 2 logistic regression adjusted for sex and race, OR 1.5025, SE = 0.2682, P = 0.0226), indicating that the functions of FCGR3B gene may also contribute to the pathogenesis of sarcoidosis. We conclude that FCGR3A CNVs are a major risk factor for female sarcoidosis and FCGR3B CNVs may also affect the development of sarcoidosis. PMID:27059607

  8. APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication

    PubMed Central

    Mertz, Tony; Malc, Ewa P.; Mieczkowski, Piotr A.; Roberts, Steven A.

    2016-01-01

    Summary APOBEC family cytidine deaminases have been recently implicated as powerful mutators of cancer genomes. How APOBECs, which are ssDNA specific enzymes, gain access to chromosomal DNA is unclear. To ascertain the chromosomal ssDNA substrates of the APOBECs, we expressed APOBEC3A and APOBEC3B, the two most probable APOBECs mediating cancer mutagenesis, in a yeast model system. We demonstrate, using mutation reporters and whole genome sequencing, that APOBEC3A- and APOBEC3B-induced mutagenesis primarily results from the deamination of the lagging strand template during DNA replication. Moreover, our results indicate that both genetic deficiencies in replication fork-stabilizing proteins and chemical induction of replication stress greatly augment the mutagenesis of APOBEC3A and 3B. Taken together, these results strongly indicate that ssDNA formed during DNA lagging strand synthesis is a major substrate for APOBECs and may be the principal substrate in human cancers experiencing replication stress. PMID:26832400

  9. 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

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

    PubMed

    Lammi, Johanna; Rajalin, Ann-Marie; Huppunen, Johanna; Aarnisalo, Piia

    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. PMID:17543277

  11. Are serotonin 3A and 3B receptor genes associated with suicidal behavior in schizophrenia subjects?

    PubMed

    Souza, Renan P; De Luca, Vincenzo; Manchia, Mirko; Kennedy, James L

    2011-02-11

    Suicide is a major contributor to the morbidity and mortality of schizophrenia, accounting for approximately 10% of deaths in these patients. Genetic factors have been reported to modulate the risk for suicide, although the precise mechanism and magnitude of the genetic contribution are unknown. Further, suicide attempters present abnormalities in the serotonergic system. We evaluated whether genetic variants in the serotonin receptors HTR3A (rs897692, rs1150226, rs1176724, rs2276302, rs3737457, rs897687 and rs1176713) and HTR3B (rs3758987, rs10502180, rs11606194, rs17116121, rs1176744, rs17116138, rs2276307, rs3782025 and rs1176761) were susceptibility components for suicidal behavior in 154 Caucasians schizophrenia subjects (20.1% of suicide attempters). In a second step, we compared haplotype and gene-gene interaction approaches because both genes are located in the chromosome 11q23 approximately 28Kbp apart. We did not observe allelic or genotypic associations. Six haplotypes were nominally significant associated with suicide. Gene-gene interaction using Helix Tree software showed two nominally significant interactions reproduced by haplotype association. Likewise, haplotypes composed by the markers included in the best multidimensional reduction three-locus model were nominally significant. Our results suggest that HTR3A and HTR3B polymorphisms may not play a major role in the susceptibility for suicidal behavior in schizophrenia subjects. Moreover, gene-gene interaction and haplotype association may have consistent results for genes located in the same chromosome. PMID:21184810

  12. 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

  13. Association of DNA Methyltransferases 3A and 3B Polymorphisms, and Plasma Folate Levels with the Risk of Urothelial Carcinoma

    PubMed Central

    Chung, Chi-Jung; Chang, Chao-Hsiang; Liu, Chiu-Shong; Huang, Chi-Ping; Chang, Yi-Huei; Chien, Ssu-Ning; Tsai, Ping-Huan; Hsieh, Hui-An

    2014-01-01

    Background Interindividual genetic variations of human DNA methyltransferases (DNMTs), which involve the methyl donor from the folate-related one-carbon metabolism pathway, are hypothesized as a risk factor for urothelial carcinoma (UC). Therefore, we evaluated the role of gene-environment interaction in UC carcinogenesis. Methods A hospital-based case-control study was conducted by recruiting 192 patients with UC and 381 controls. Their plasma folate levels were measured using a competitive immunoassay kit. In addition, DNMT3A −448A>G and DNMT3B −579G>T genotyping was evaluated using a polymerase chain reaction-restriction fragment length polymorphism technique. Multivariate logistic regression and 95% confidence intervals (CIs) were applied to estimate the UC risk. Results We observed that patients with UC exhibited a higher prevalence rate of folate insufficiency (folate levels ≤6 ng/mL) compared with the controls (35.94% and 18.37%, respectively). Furthermore, folate levels were higher in the prevalent UC patients than in the incident UC patients. However, folate insufficiency was similarly associated with a nearly two-fold increase in the risk of UC regardless of the UC patient group. In addition, the frequencies of the variant alleles for DNMT3A and DNMT3B were 0.80 and 0.92, respectively, and no association was observed with UC risk. However, participants with a variant homozygous genotype of DNMT3B −579G>T and folate insufficiency or with high cumulative cigarette smoking exhibited an increased risk of UC. Conclusion Overall, environmental factors may contribute more significantly to UC carcinogenesis compared with genetic susceptibility. Future studies should investigate other polymorphisms of DNMT3A and DNMT3B to determine genetic susceptibility. PMID:25126948

  14. 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

  15. Trajectories and single-particle tracking data of intracellular vesicles loaded with either SNAP-Crb3A or SNAP-Crb3B.

    PubMed

    Siebrasse, Jan Peter; Djuric, Ivona; Schulze, Ulf; Schlüter, Marc A; Pavenstädt, Hermann; Weide, Thomas; Kubitscheck, Ulrich

    2016-06-01

    Using a combined approach of pulse chase labeling and single-particle tracking of Crb3A or 3B loaded vesicles we collected trajectories of different vesicle population in living podocyte cells and evaluated statistically their different mobility patterns. Differences in their intracellular mobility and in their directed transport correspond well to the role of Crb3A and 3B in renal plasma membrane sorting (Djuric et al., 2016) [1]. PMID:27222870

  16. Auditory P3a and P3b neural generators in schizophrenia: An adaptive sLORETA P300 localization approach.

    PubMed

    Bachiller, Alejandro; Romero, Sergio; Molina, Vicente; Alonso, Joan F; Mañanas, Miguel A; Poza, Jesús; Hornero, Roberto

    2015-12-01

    The present study investigates the neural substrates underlying cognitive processing in schizophrenia (Sz) patients. To this end, an auditory 3-stimulus oddball paradigm was used to identify P3a and P3b components, elicited by rare-distractor and rare-target tones, respectively. Event-related potentials (ERP) were recorded from 31 Sz patients and 38 healthy controls. The P3a and P3b brain-source generators were identified by time-averaging of low-resolution brain electromagnetic tomography (LORETA) current density images. In contrast with the commonly used fixed window of interest (WOI), we proposed to apply an adaptive WOI, which takes into account subjects' P300 latency variability. Our results showed different P3a and P3b source activation patterns in both groups. P3b sources included frontal, parietal and limbic lobes, whereas P3a response generators were localized over bilateral frontal and superior temporal regions. These areas have been related to the discrimination of auditory stimulus and to the inhibition (P3a) or the initiation (P3b) of motor response in a cognitive task. In addition, differences in source localization between Sz and control groups were observed. Sz patients showed lower P3b source activity in bilateral frontal structures and the cingulate. P3a generators were less widespread for Sz patients than for controls in right superior, medial and middle frontal gyrus. Our findings suggest that target and distractor processing involves distinct attentional subsystems, both being altered in Sz. Hence, the study of neuroelectric brain information can provide further insights to understand cognitive processes and underlying mechanisms in Sz. PMID:26481687

  17. 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

  18. Association study of copy number variants in FCGR3A and FCGR3B gene with risk of ankylosing spondylitis in a Chinese population.

    PubMed

    Wang, Li; Yang, Xiao; Cai, Guoqi; Xin, Lihong; Xia, Qing; Zhang, Xu; Li, Xiaona; Wang, Mengmeng; Wang, Kang; Xia, Guo; Xu, Shengqian; Xu, Jianhua; Zou, Yanfeng; Pan, Faming

    2016-03-01

    Ankylosing spondylitis (AS) is a common inherited autoimmune disease. Copy number variation (CNV) of DNA segments has been found to be an important part of genetic variation, and the FCGR3A and FCGR3B gene CNVs have been associated with various autoimmune disorders. The aim of the study was to determine whether CNVs of FCGR3A and FCGR3B were also associated with the susceptibility of AS. A total of 801 individuals including 402 AS patients and 399 healthy controls were enrolled in this study. The copy numbers of FCGR3 gene (two fragments, included FCGR3A and FCGR3B) were measured by AccuCopy™ methods. Chi-square test and logistic regression model were used to evaluate association between FCGR3 gene CNVs and AS susceptibility. P values, odds ratio, and 95 % confidence intervals (CIs) were used to estimate the effects of risk. Significantly, difference in the frequencies of FCGR3A and FCGR3B gene CNVs was founded between the patients with AS and controls. For the FCGR3A gene, a low (≤3) copy number was significantly associated with AS [for ≤3 copies versus 4 copies, (OR 2.17, 95 % CI (1.41, 3.34), P < 0.001, adjusted OR 2.22, 95 % CI (1.44, 3.43), P < 0.001)]. A low FCGR3B copy number was also significantly associated with increasing risk of AS [for ≤3 copies versus 4 copies, (OR 1.87, 95 % CI (1.25, 2.79), P = 0.002, adjusted OR 1.94, 95 % CI (1.29, 2.91), P = 0.001)]; however, both the high FCGR3A and FCGR3B copy numbers (≥5) were not significantly associated with the risk of AS (≥5 copies versus 4 copies). The lower copy numbers (≤3) of FCGR3A and FCGR3B genes confer a risk factor for AS susceptibility. PMID:26494566

  19. 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.

  20. Structural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B.

    PubMed

    Rondelet, Grégoire; Dal Maso, Thomas; Willems, Luc; Wouters, Johan

    2016-06-01

    DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone modification patterns. In particular, trimethylation of Lys36 on histone H3 tail (H3K36me3) is associated with DNA methylation and elongation phase of transcription. PWWP domains of the de novo DNA methyltransferases DNMT3A and DNMT3B read this epigenetic mark to guide DNA methylation. Here we report the first crystal structure of the DNMT3B PWWP domain-H3K36me3 complex. Based on this structure, we propose a model of the DNMT3A PWWP domain-H3K36me3 complex and build a model of DNMT3A (PWWP-ADD-CD) in a nucleosomal context. The trimethylated side chain of Lys36 (H3K36me3) is inserted into an aromatic cage similar to the "Royal" superfamily domains known to bind methylated histones. A key interaction between trimethylated Lys36 and a conserved water molecule stabilized by Ser270 explains the lack of affinity of mutated DNMT3B (S270P) for the H3K36me3 epigenetic mark in the ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome. The model of the DNMT3A-DNMT3L heterotetramer in complex with a dinucleosome highlights the mechanism for recognition of nucleosome by DNMT3s and explains the periodicity of de novo DNA methylation. PMID:26993463

  1. Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease.

    PubMed

    Cai, Tian-Tian; Zhang, Jian; Wang, Xuan; Song, Rong-Hua; Qin, Qiu; Muhali, Fatuma-Said; Zhou, Jiao-Zhen; Xu, Jian; Zhang, Jin-An

    2016-07-30

    The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD. PMID:27237591

  2. A Comparison of Assays for Accurate Copy Number Measurement of the Low-Affinity Fc Gamma Receptor Genes FCGR3A and FCGR3B

    PubMed Central

    Haridan, Umi Shakina; Mokhtar, Umairah; Machado, Lee R.; Abdul Aziz, Abu Thalhah; Shueb, Rafidah Hanim; Zaid, Masliza; Sim, Benedict; Mustafa, Mahiran; Nik Yusof, Nik Khairudin; Lee, Christopher K. C.; Abu Bakar, Suhaili; AbuBakar, Sazaly; Hollox, Edward J.; Boon Peng, Hoh

    2015-01-01

    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method’s performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs. PMID:25594501

  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. DNMT1, DNMT3A and DNMT3B gene variants in relation to ovarian cancer risk in the Polish population.

    PubMed

    Mostowska, Adrianna; Sajdak, Stefan; Pawlik, Piotr; Lianeri, Margarita; Jagodzinski, Paweł P

    2013-08-01

    Studies have demonstrated that changes in DNA methylation of cancer related genes can be an elementary process accounting for ovarian tumorigenesis. Therefore, we evaluated the possible association of single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) genes, including DNMT1, DNMT3B, and DNMT3A, with ovarian cancer development in the Polish population. Using PCR-RFLP and HRM analyses, we studied the prevalence of the DNMT1 rs8101626, rs2228611 and rs759920, DNMT3A rs2289195, 7590760, rs13401241, rs749131 and rs1550117, and DNMT3B rs1569686, rs2424913 and rs2424932 SNPs in patients with ovarian cancer (n=159) and controls (n=180). The lowest p values of the trend test were observed for the DNMT1 rs2228611 and rs759920 SNPs in patients with ovarian cancer (p trend=0.0118 and p trend=0.0173, respectively). Moreover, we observed, in the recessive inheritance model, that the DNMT1 rs2228611 and rs759920 SNPs are associated with an increased risk of ovarian cancer development [OR 1.836 (1.143-2.949), p=0.0114, p corr=0.0342, and OR 1.932 (1.185-3.152), p=0.0078, p cor=0.0234, respectively]. However, none of other nine studied SNPs displayed significant contribution to the development of ovarian cancer. Furthermore, haplotype and multifactor dimensionality reduction analysis of the studied DNMT1, DNMT3B, and DNMT3A polymorphisms did not reveal either SNP combinations or gene interactions to be associated with the risk of ovarian cancer development. Our results may suggest that DNMT1 variants may be risk factors of ovarian cancer. PMID:23666104

  5. A novel orange-red phosphor Ca3B2O6:Sm3+, A+(A = Li, Na, K) for white light emitting diodes

    NASA Astrophysics Data System (ADS)

    Liu, Qingbo; Liu, Yufeng; Yang, Fu; Han, Bing; Feng, Hao; Yu, Quanmao

    2014-03-01

    A novel orange-red phosphor Ca3B2O6:Sm3+, A+(A = Li, Na, K) has been synthesized by solid-state reaction at 950°C. The phase purity and photoluminescence (PL) behavior of the phosphor are studied in detail using the powder X-ray diffraction (XRD) technique and PL measurements. Ca3B2O6:Sm3+ phosphor can be efficiently excited by near ultraviolet (n-UV) and blue light, and the emission spectrum consists of four emission peaks at 563, 599, 646 and 709 nm, generating bright orange-red light. When a cation A+ is introduced into Ca3B2O6:Sm3+ as charge compensator, the emission intensity of Ca3B2O6:Sm3+ is evidently enhanced, but the PL spectral profile is unchanged. The integral intensity of the emission spectrum of Ca2.96Sm0.02Na0.02B2O6 excited at 401 nm is about 1.2 times than that of Y2O2S:Eu3+ commercial red phosphor. The CIE chromaticity coordinates of Ca2.96Sm0.02Na0.02B2O6 phosphor were (0.608, 0.365), which are close to that of the commercial red phosphors Y2O3:Eu3+ (0.655, 0.345), Y2O2S:Eu3+ (0.622, 0.351) and Sr2Si5N8:Eu2+ (0.620, 0.370).

  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. 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.

  8. Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis.

    PubMed

    Song, Gwan Gyu; Lee, Young Ho

    2013-08-01

    The aim of this study was to determine whether the Fcγ receptors (FCGRs) polymorphisms confer susceptibility to periodontitis in ethnically different populations. We did a literature search using PubMed and Embase, and conducted a meta-analysis on the associations between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and periodontitis using allele contrast, the recessive model, the dominant model, and the homozygote contrast. A total of 17 separate comparisons with 1,421 patients with periodontitis and 1,454 controls, involving six Caucasian, six East Asian, two African and one South Asian population were considered in the meta-analysis. Meta-analysis of the FCGR2A H131R polymorphism showed no association between periodontitis and the FCGR2A R allele (OR=0.987, 95% CI=0.881-1.107, p=0.827). Stratification by ethnicity revealed an association between the RR+RH genotype with periodontitis in Caucasian population (OR=0.624, 95% CI=0.479-0.813, p=4.7×10(-5)), but not in East Asian, and African populations. Meta-analysis of the FCGR3A F158V polymorphism revealed an association between the FCGR3A V allele and periodontitis is in Caucasians (OR=1.457, 95% CI=1.014-2.092, p=0.042), but not in East Asians and Africans. In addition, analysis using the dominant model and homozygote contrast showed the same pattern for the FCGR3A V allele. Meta-analysis of the FCGR3B NA1/NA2 polymorphism using the recessive model revealed a significant association between the NA2/NA2 genotype and periodontitis in aggressive periodontitis (OR=2.853, 95% CI=1.673-4.863, 1.1×10(-5)). This meta-analysis demonstrates that the FCGR2A, and FCGR3A polymorphisms may confer susceptibility to periodontitis in Caucasians, and that the FCGR3B polymorphism may be associated with susceptibility to aggressive periodontitis. PMID:23649770

  9. 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.

  10. Deoxyribonucleic acid methyl transferases 3a and 3b associate with the nuclear orphan receptor COUP-TFI during gene activation.

    PubMed

    Gallais, Rozenn; Demay, Florence; Barath, Peter; Finot, Laurence; Jurkowska, Renata; Le Guével, Rémy; Gay, Frédérique; Jeltsch, Albert; Métivier, Raphaël; Salbert, Gilles

    2007-09-01

    Transcriptional activation of silent genes can require the erasure of epigenetic marks such as DNA methylation at CpGs (cytosine-guanine dinucleotide). Active demethylation events have been observed, and associated processes are repeatedly suspected to involve DNA glycosylases such as mCpG binding domain protein 4, thymine DNA glycosylase (TDG), Demeter, and repressor of silencing 1. A complete characterization of the molecular mechanisms occurring in metazoan is nonetheless awaited. Here, we report that activation of the endogenous vitronectin gene in P19 cells by the nuclear receptor chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) is observed in parallel with the recruitment of TDG and p68 RNA helicase, two components of a putative demethylation complex. Interestingly, when activated, the vitronectin gene was loaded with DNA methyltransferases 3a and 3b (Dnmt3a/b), and a strand-biased decrease in CpG methylation was detected. Dnmt3a was further found to associate with COUP-TFI and TDG in vivo, and cotransfection experiments demonstrated that Dnmt3a/b can enhance COUP-TFI-mediated activation of a methylated reporter gene. These results suggest that Dnmt3a/b could cooperate with the orphan receptor COUP-TFI to regulate transcription of the vitronectin gene. PMID:17579209

  11. Autophagosome Proteins LC3A, LC3B and LC3C Have Distinct Subcellular Distribution Kinetics and Expression in Cancer Cell Lines

    PubMed Central

    Koukourakis, Michael I.; Kalamida, Dimitra; Giatromanolaki, Alexandra; Zois, Christos E.; Sivridis, Efthimios; Pouliliou, Stamatia; Mitrakas, Achilleas; Gatter, Kevin C.; Harris, Adrian L.

    2015-01-01

    LC3s (MAP1-LC3A, B and C) are structural proteins of autophagosomal membranes, widely used as biomarkers of autophagy. Whether these three LC3 proteins have a similar biological role in autophagy remains obscure. We examine in parallel the subcellular expression patterns of the three LC3 proteins in a panel of human cancer cell lines, as well as in normal MRC5 fibroblasts and HUVEC, using confocal microscopy and western blot analysis of cell fractions. In the cytoplasm, there was a minimal co-localization between LC3A, B and C staining, suggesting that the relevant autophagosomes are formed by only one out of the three LC3 proteins. LC3A showed a perinuclear and nuclear localization, while LC3B was equally distributed throughout the cytoplasm and localized in the nucleolar regions. LC3C was located in the cytoplasm and strongly in the nuclei (excluding nucleoli), where it extensively co-localized with the LC3A and the Beclin-1 autophagy initiating protein. Beclin 1 is known to contain a nuclear trafficking signal. Blocking nuclear export function by Leptomycin B resulted in nuclear accumulation of all LC3 and Beclin-1 proteins, while Ivermectin that blocks nuclear import showed reduction of accumulation, but not in all cell lines. Since endogenous LC3 proteins are used as major markers of autophagy in clinical studies and cell lines, it is essential to check the specificity of the antibodies used, as the kinetics of these molecules are not identical and may have distinct biological roles. The distinct subcellular expression patterns of LC3s provide a basis for further studies. PMID:26378792

  12. 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

  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

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

    2014-08-01

    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 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

  15. X-ray-induced specific-locus mutations in the ad-3 region of two-component heterokaryons of Neurospora crassa. X. Heterozygous effects of multilocus deletion mutations of genotype ad-3A or ad-3B.

    PubMed

    de Serres, F J; Overton, L K; Sadler, B M

    1992-05-01

    Previous studies on X-ray-induced irreparable adenine-3 mutations (designated [ad-3]IR), induced in heterokaryon 12 of Neurospora crassa, demonstrated that they were not recessive and exhibited heterozygous effects in terms of markedly reduced linear growth rates (de Serres, 1965). Complementation tests with a series of tester strains carrying multilocus deletion mutations in the ad-3 and immediately adjacent genetic regions demonstrated that X-ray-induced irreparable mutations map, in the main part, as a series of overlapping multilocus deletion mutations that extend both proximally and distally into the immediately adjacent genetic regions, as well as into the 'X' region (a region of unknown, but essential function) between ad-3A and ad-3B (de Serres, 1968, 1989). Further studies (de Serres and Miller, 1988) have shown that the heterozygous effects of multilocus deletion mutations in the ad-3 region can be modified genetically and biochemically. In the present paper, the heterozygous effects of X-ray-induced multilocus deletion mutations of genotype ad-3A or ad-3B, induced in heterokaryon 12 (Webber and de Serres, 1965; de Serres, 1988, 1989), have been determined. These data show that 57.7% (15/26) of X-ray-induced multilocus deletion mutations covering the ad-3A locus have heterozygous effects, in terms of reduced linear growth rates, in forced dikaryons with a gene/point mutant at the ad-3B locus and 80.0% (20/25) in forced dikaryons with a multilocus deletion mutation covering the ad-3B locus. In addition, 35.1% (20/57) of X-ray-induced multilocus deletion mutations covering the ad-3B locus have heterozygous effects in forced dikaryons with a gene/point mutant at the ad-3A locus, and 100.0% (35/35) in forced dikaryons with a multilocus deletion mutation covering the ad-3A locus. These results demonstrate that the dominant or recessive characteristics of X-ray-induced specific-locus mutations resulting from multilocus deletion mutations are allele specific

  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

    ...-7756; fax: (781) 238-7199. SUPPLEMENTARY INFORMATION: On January 8, 2010 (75 FR 1017), we published a final rule AD, FR Doc. E9-31274, in the Federal Register. That AD applies to GE CF34-1A, CF34-3A, and...; AD 2010-01-04] RIN 2120-AA64 Airworthiness Directives; General Electric Company (GE) CF34-1A,...

  17. 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

  18. mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, KIF5, and cytoplasmic dynein during axonal regeneration.

    PubMed

    Takemura, R; Nakata, T; Okada, Y; Yamazaki, H; Zhang, Z; Hirokawa, N

    1996-01-01

    Mouse brain expresses multiple kinesin superfamily proteins (KIFs), which are involved in vesicle transport. The expression of KIFs is developmentally regulated, and both the mRNA and proteins of KIF2 and KIF4 are expressed abundantly in the juvenile brain. To elucidate the role of individual kinesin superfamily motor proteins during regenerative outgrowth of axons, we examined the mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, and KIF5 in adult mouse dorsal root ganglion cells after sciatic nerve crush. Seven to fourteen days after the nerve crush, the mRNA expression pattern of neurofilament and beta-tubulin isotypes suggested that the regenerative outgrowth of axons was active. At these stages, levels of mRNA for KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, and KIF5 were 50.80% of control. The levels of mRNA for KIF4, which are detected in juvenile brain but not in the adult, were under the detection limit in both control and regenerating dorsal root ganglion cells. Because mRNA of neither KIF2 nor KIF4 increased significantly, the results suggest that the gene expression of KIFs during regeneration does not recapitulate the embryonic development and support the hypothesis that different series of events take place during the regenerative and embryonic outgrowths of axons. In contrast, mRNA for cytoplasmic dynein was slightly increased, up to 140%. This is consistent with the hypothesis that retrograde transport plays critical roles in regeneration such as the transport of neurotrophic factors. PMID:8613797

  19. Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish.

    PubMed

    Hadrys, Thorsten; Punnamoottil, Beena; Pieper, Mareike; Kikuta, Hiroshi; Pezeron, Guillaume; Becker, Thomas S; Prince, Victoria; Baker, Robert; Rinkwitz, Silke

    2006-09-01

    The expression of zebrafish hoxb3a and hoxb4a has been found to be mediated through five transcripts, hoxb3a transcripts I-III and hoxb4a transcripts I-II, driven by four promoters. A "master" promoter, located about 2 kb downstream of hoxb5a, controls transcription of a pre-mRNA comprising exon sequences of both genes. This unique gene structure is proposed to provide a novel mechanism to ensure overlapping, tissue-specific expression of both genes in the posterior hindbrain and spinal cord. Transgenic approaches were used to analyze the functions of zebrafish hoxb3a/hoxb4a promoters and enhancer sequences containing regions of homology that were previously identified by comparative genomics. Two neural enhancers were shown to establish specific anterior expression borders within the hindbrain and mediate expression in defined neuronal populations derived from hindbrain rhombomeres (r) 5 to 8, suggesting a late role of the genes in neuronal cell lineage specification. Species comparison showed that the zebrafish hoxb3a r5 and r6 enhancer corresponded to a sequence within the mouse HoxA cluster controlling activity of Hoxa3 in r5 and r6, whereas a homologous region within the HoxB cluster activated Hoxb3 expression but limited to r5. We conclude that the similarity of hoxb3a/Hoxa3 regulatory mechanisms reflect the shared descent of both genes from a single ancestral paralog group 3 gene. PMID:16860306

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. A first detection of singlet to triplet conversion from the 1 1B u- to the 1 3A g state and triplet internal conversion from the 1 3A g to the 1 3B u state in carotenoids: dependence on the conjugation length

    NASA Astrophysics Data System (ADS)

    Rondonuwu, Ferdy S.; Watanabe, Yasutaka; Fujii, Ritsuko; Koyama, Yasushi

    2003-07-01

    Subpicosecond time-resolved absorption spectra were recorded in the visible region for a set of photosynthetic carotenoids having different numbers of conjugated double bonds ( n), which include neurosporene ( n=9), spheroidene ( n=10), lycopene ( n=11), anhydrorhodovibrin ( n=12) and spirilloxanthin ( n=13). Singular-value decomposition and global fitting of the spectral-data matrices lead us to a branched relaxation scheme including both (1) the singlet internal conversion in the sequence of 1 1B u+ → 1 1B u- → 2 1A g- → 1 1A g-(ground), and (2) the singlet-to-triplet conversion of 1 1B u- → 1 3A g followed by triplet internal conversion of 1 3A g → 1 3B u.

  5. Correlation between mutations in the core and NS5A genes of hepatitis C virus genotypes 1a, 1b, 3a, 3b, 6f and the response to pegylated interferon and ribavirin combination therapy.

    PubMed

    Kumthip, K; Pantip, C; Chusri, P; Thongsawat, S; O'Brien, A; Nelson, K E; Maneekarn, N

    2011-04-01

    Several studies have reported correlation between mutations in core and NS5A proteins of hepatitis C virus (HCV) and response to interferon (IFN) therapy. In particular, mutations in NS5A protein have been shown to correlate with responsiveness to IFN treatment of HCV-1b in Japanese patients. This study investigated whether amino acid (aa) mutations in the core and NS5A proteins of HCV-1a, 1b, 3a, 3b and 6f correlated with the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in Thai patients. The entire sequences of core and NS5A of HCV from 76 HCV-infected patients were analysed in comparison with corresponding reference sequences. The data revealed that the number of aa mutations in full-length NS5A, its C-terminus, IFN sensitivity-determining region, variable region 3 (V3) and V3 plus flanking region of HCV-1b NS5A protein were significantly higher in responders than in the treatment failure group (P = 0.010, 0.031, 0.046, 0.020 and 0.006, respectively). Similar results were found in a putative protein kinase R binding domain region in HCV-6f NS5A protein (P = 0.022). Moreover, specific aa substitutions in NS5A that appeared to be associated with responders or the treatment failure group were observed at positions 78 and 305 for HCV-1b (P = 0.028), 64 and 52 for HCV-1a (P = 0.033) and 6f (P = 0.045). Nevertheless, analysis of aa sequences of core protein revealed highly conserved sequences among HCV genotypes and no significant differences between the viruses from responders and the treatment failure group. Our findings indicate that mutations in aa residues of NS5A of HCV-1a, 1b and 6f correlated well with responsiveness to Peg-IFN and RBV combination therapy. PMID:20955493

  6. 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.

  7. 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

  8. Tissue C3b receptors.

    PubMed Central

    Schrieber, L; Penny, R

    1979-01-01

    Using fluorescein-labelled S. typhi coated with C3b (FBC) the presence of a receptor for C3b in normal human glomeruli has been confirmed. A quantitative system, counting the number of FBC bound per unit area of glomerulus, has been developed. Experimental variables have been studied to determine optimal conditions for FBC binding. Glomerular FBC binding has been shown to be dependent on FBC concentration, temperature and time of tissue incubation. A standardized procedure has been adopted. Using this technique we have examined a number of target tissues, including synovium, skin, lung, choroid plexus and uveal tract, which are frequently affected in systemic immune complex diseases. No evidence of this receptor has been found in these tissues. These results suggest a mechanism different from the C3b receptor operating to localise immune complexes in these non-renal sites. Images FIG. 2 PMID:527266

  9. 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

  10. 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

  11. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: 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...

  13. 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. PMID:26474391

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 17 CFR 240.3b-6 - Liability for certain statements by issuers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b... security holders meeting the requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) under the Act (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b) of this chapter) and that relates to: (i) The...

  19. 17 CFR 240.3b-6 - Liability for certain statements by issuers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b... security holders meeting the requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) under the Act (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b) of this chapter) and that relates to: (i) The...

  20. 17 CFR 240.3b-6 - Liability for certain statements by issuers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b... security holders meeting the requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) under the Act (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b) of this chapter) and that relates to: (i) The...

  1. 17 CFR 240.3b-6 - Liability for certain statements by issuers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b... security holders meeting the requirements of Rules 14a-3(b) and (c) or 14c-3(a) and (b) under the Act (§ 240.14a-3(b) and (c) or § 240.14c-3(a) and (b) of this chapter) and that relates to: (i) The...

  2. 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.

  3. 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 PERSONAL INFORMATION Rules for Disclosure of Records...

  4. 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 PERSONAL INFORMATION Rules for Disclosure of Records...

  5. 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 OF IDENTIFIABLE PERSONAL INFORMATION Rules...

  6. 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 OF IDENTIFIABLE PERSONAL INFORMATION Rules...

  7. 18 CFR 3b.222 - Identification 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 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 OF IDENTIFIABLE PERSONAL INFORMATION Rules...

  8. 18 CFR 3b.222 - Identification requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 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 OF IDENTIFIABLE PERSONAL INFORMATION Rules...

  9. 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, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF...

  10. 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...

  11. 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...

  12. 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...

  13. 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... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or...

  14. 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... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or...

  15. 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

  16. 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.

  17. 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.

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

    PubMed

    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

  19. 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

  20. 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.

  1. 12 CFR 563d.3b-6 - Liability for certain statements by savings associations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 17 CFR 240.14a-3 (b) and (c) or 17 CFR 240.14c-3 (a) and (b) under the Act: Provided, That such... 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...

  2. 12 CFR 563d.3b-6 - Liability for certain statements by savings associations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 17 CFR 240.14a-3 (b) and (c) or 17 CFR 240.14c-3 (a) and (b) under the Act: Provided, That such... 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 17 CFR 240.14a-3 (b) and (c) or 17 CFR 240.14c-3 (a) and (b) under the Act: Provided, That such... 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 17 CFR 240.14a-3 (b) and (c) or 17 CFR 240.14c-3 (a) and (b) under the Act: Provided, That such... 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...

  5. A Revised Mechanism for the Activation of Complement C3 to C3b

    PubMed Central

    Rodriguez, Elizabeth; Nan, Ruodan; Li, Keying; Gor, Jayesh; Perkins, Stephen J.

    2015-01-01

    The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allotype with Arg102. In 50 mm NaCl buffer, atomistic scattering modeling showed that both C3b and C3u adopted a compact structure, similar to the C3b crystal structure in which its TED and macroglobulin 1 (MG1) domains were connected through the Arg102–Glu1032 salt bridge. In physiological 137 mm NaCl, scattering modeling showed that C3b and C3u were both extended in structure, with the TED and MG1 domains now separated by up to 6 nm. The importance of the Arg102–Glu1032 salt bridge was determined using surface plasmon resonance to monitor the binding of wild-type C3d(E1032) and mutant C3d(A1032) to immobilized C3c. The mutant did not bind, whereas the wild-type form did. The high conformational variability of TED in C3b in physiological buffer showed that C3b is more reactive than previously thought. Because the Arg102-Glu1032 salt bridge is essential for the C3b-Factor H complex during the regulatory control of C3b, the known clinical associations of the major C3S (Arg102) and disease-linked C3F (Gly102) allotypes of C3b were experimentally explained for the first time. PMID:25488663

  6. Selective inhibition of human cytochrome P450 3A4 by N-[2(R)-hydroxy-1(S)-indanyl]-5-[2(S)-(1, 1-dimethylethylaminocarbonyl)-4-[(furo[2, 3-b]pyridin-5-yl)methyl]piperazin-1-yl]-4(S)-hydroxy-2(R)-phenylmethy lpentanamide and P-glycoprotein by valspodar in gene transfectant systems.

    PubMed

    Kawahara, I; Kato, Y; Suzuki, H; Achira, M; Ito, K; Crespi, C L; Sugiyama, Y

    2000-10-01

    Our previous report showed that L754.394 and valspodar (PSC833) are potent inhibitors of midazolam hydroxylation in human jejunum microsomes and vectorial transport of vinblastine in Caco-2 cells, respectively. In the present study, to directly examine the interactions of these compounds as well as other substrates with CYP3A4 and P-glycoprotein (P-gp), we performed in vitro inhibition studies using recombinant CYP3A4-expressed microsomes and an MDR1-transfected cell line, LLC-MDR1, respectively. In CYP3A4-expressed microsomes, both L754.394 and ketoconazole, at a concentration less than 0.5 microM, are the most potent inhibitors of the formation of 1'-hydroxymidazolam, a major metabolite of midazolam formed by CYP3A4. The greatest inhibitory effect on the transcellular transport of digoxin in LLC-MDR1 cells was observed in the presence of valspodar (<0.1 microM), followed by verapamil. From a comparison of the IC(50) values, it was shown that L754.394 and valspodar exhibited the highest selectivity for CYP3A4 and P-gp, respectively. To demonstrate such specificity, both midazolam hydroxylation and digoxin transport were observed in CYP3A4 transfected Caco-2 cells, which coexpress both P-gp and CYP3A4, in the presence or absence of L754.394 (0.5 microM) and valspodar (1.0 microM). L754.394 almost completely inhibited midazolam hydroxylation, but not digoxin transport, whereas almost complete inhibition of digoxin transport was observed in the presence of valspodar, but inhibition of the hydroxylation was minimal. Thus, the present study has demonstrated that L754.394 has a specific inhibitory effect on CYP3A4, whereas valspodar is specific for P-gp. PMID:10997946

  7. Immunization with a Recombinant Expression Vector Encoding NS3/NS4A of Hepatitis C Virus Genotype 3a Elicits Cell-Mediated Immune Responses in C57BL/6 Mice.

    PubMed

    Behzadi, Mohammad Amin; Alborzi, Abdolvahab; Kalani, Mehdi; Pouladfar, Gholamreza; Dianatpour, Mehdi; Ziyaeyan, Mazyar

    2016-04-01

    Today, hepatitis C virus (HCV) infection is considered as one of the most significant international health concerns. Although novel therapeutic regimens against the infection have shown satisfactory results, no approved vaccine exists yet. This study aimed to evaluate the immunogenicity of a DNA vaccine candidate for HCV-3a, based on nonstructural proteins NS3/NS4A, in C57BL/6 mice. Immunogenicity effect of pDisplay-NS3/NS4A was analyzed through immunization with 100 and 200 μg concentrations of the construct with complete Freund's adjuvant, monophosphoryl lipid A (MPL), or without adjuvant. The frequencies of different splenic mononuclear cells were measured using the Mouse Th1/Th2/Th17 Phenotyping Kit. Moreover, the number of T-CD8(+) cells was determined using conjugated anti-CD8a and anti-CD3e antibodies by flow cytometry. As observed, the frequencies of Th1, T-CD8(+), and Th2 cells increased in all the experimental groups, compared with the controls. The highest levels of the respective cells were seen in the group immunized with 200 μg of the construct with MPL. Also, there were positive correlations between the frequency of Th1 cells and those of Th2 and T-CD8(+) cells in all the immunized groups, but were significant in those receiving adjuvants. The frequency of Th17 cells did not statistically change among the groups. Taken together, our findings revealed that the constructed DNA vaccine encoding HCV-3a NS3/NS4A gene induces the cell-mediated immune responses significantly. However, its coadministration with adjuvants exhibits more efficient results than the recombinant plasmid alone. Further study is currently underway to evaluate the specific immune responses and recognize the responsible antigenic epitopes. PMID:26909520

  8. 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

    NASA Astrophysics Data System (ADS)

    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 -1 s with a 3 σ 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.

  9. Novel Infectious cDNA Clones of Hepatitis C Virus Genotype 3a (Strain S52) and 4a (Strain ED43): Genetic Analyses and In Vivo Pathogenesis Studies ▿ †

    PubMed Central

    Gottwein, Judith M.; Scheel, Troels K. H.; Callendret, Benoit; Li, Yi-Ping; Eccleston, Heather B.; Engle, Ronald E.; Govindarajan, Sugantha; Satterfield, William; Purcell, Robert H.; Walker, Christopher M.; Bukh, Jens

    2010-01-01

    Previously, RNA transcripts of cDNA clones of hepatitis C virus (HCV) genotypes 1a (strains H77, HCV-1, and HC-TN), 1b (HC-J4, Con1, and HCV-N), and 2a (HC-J6 and JFH1) were found to be infectious in chimpanzees. However, only JFH1 was infectious in human hepatoma Huh7 cells. We performed genetic analysis of HCV genotype 3a (strain S52) and 4a (strain ED43) prototype strains and generated full-length consensus cDNA clones (pS52 and pED43). Transfection of Huh7.5 cells with RNA transcripts of these clones did not yield cells expressing HCV Core. However, intrahepatic transfection of chimpanzees resulted in robust infection with peak HCV RNA titers of ∼5.5 log10 international units (IU)/ml. Genomic consensus sequences recovered from serum at the times of peak viral titers were identical to the sequences of the parental plasmids. Both chimpanzees developed acute hepatitis with elevated liver enzymes and significant necroinflammatory liver changes coinciding with detection of gamma interferon-secreting, intrahepatic T cells. However, the onset and broadness of intrahepatic T-cell responses varied greatly in the two animals, with an early (week 4) multispecific response in the ED43-infected animal (3 weeks before the first evidence of viral control) and a late (week 11) response with limited breadth in the S52-infected animal (without evidence of viral control). Autologous serum neutralizing antibodies were not detected during the acute infection in either animal. Both animals became persistently infected. In conclusion, we generated fully functional infectious cDNA clones of HCV genotypes 3a and 4a. Proof of functionality of all genes might further the development of recombinant cell culture systems for these important genotypes. PMID:20200247

  10. 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

  11. 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

    2015-01-01

    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. PMID:26045207

  12. 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

  13. 27 CFR 21.36 - Formula No. 3-B.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula No. 3-B. 21.36... OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.36 Formula No. 3-B. (a) Formula. To every 100 gallons of alcohol add:...

  14. 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 IDENTIFIABLE PERSONAL INFORMATION Standards...

  15. 18 CFR 3b.225 - Written consent for disclosure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... disclosure. 3b.225 Section 3b.225 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF..., on a matter within its jurisdiction; (10) To the Comptroller General, or any of his...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Content of records. 3b.201 Section 3b.201 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL INFORMATION Standards...

  17. 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.

  18. Expert system verification and validation study. Delivery 3A and 3B: Trip summaries

    NASA Technical Reports Server (NTRS)

    French, Scott

    1991-01-01

    Key results are documented from attending the 4th workshop on verification, validation, and testing. The most interesting part of the workshop was when representatives from the U.S., Japan, and Europe presented surveys of VV&T within their respective regions. Another interesting part focused on current efforts to define industry standards for artificial intelligence and how that might affect approaches to VV&T of expert systems. The next part of the workshop focused on VV&T methods of applying mathematical techniques to verification of rule bases and techniques for capturing information relating to the process of developing software. The final part focused on software tools. A summary is also presented of the EPRI conference on 'Methodologies, Tools, and Standards for Cost Effective Reliable Software Verification and Validation. The conference was divided into discussion sessions on the following issues: development process, automated tools, software reliability, methods, standards, and cost/benefit considerations.

  19. 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...

  20. PROCEEDINGS: 1990 SO2 CONTROL SYMPOSIUM - VOLUME 1: SESSIONS 1, 2, 3A, AND 3B

    EPA Science Inventory

    The proceedings document 110 papers presented at the Symposium held in New Orleans, LA, May 8-11, 1990. opics included SO2 control economics, furnace sorbent injection, byproduct utilization, spray dryer technology, wet flue gas desulfurization (FGD) and combined SOx/NOx control ...

  1. 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. PMID:26356988

  2. First highly efficient and photostable E and C derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as dye lasers in the liquid phase, thin films, and solid-state rods.

    PubMed

    Duran-Sampedro, Gonzalo; Esnal, Ixone; Agarrabeitia, Antonia R; Bañuelos Prieto, Jorge; Cerdán, Luis; García-Moreno, Inmaculada; Costela, Angel; Lopez-Arbeloa, Iñigo; Ortiz, María J

    2014-02-24

    A new library of E- and C-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives has been synthesized through a straightforward protocol from commercially available BODIPY complexes, and a systematic study of the photophysical properties and laser behavior related to the electronic properties of the B-substituent group (alkynyl, cyano, vinyl, aryl, and alkyl) has been carried out. The replacement of fluorine atoms by electron-withdrawing groups enhances the fluorescence response of the dye, whereas electron-donor groups diminish the fluorescence efficiency. As a consequence, these compounds exhibit enhanced laser action with respect to their parent dyes, both in liquid solution and in the solid phase, with lasing efficiencies under transversal pumping up to 73 % in liquid solution and 53 % in a solid matrix. The new dyes also showed enhanced photostability. In a solid matrix, the derivative of commercial dye PM597 that incorporated cyano groups at the boron center exhibited a very high lasing stability, with the laser emission remaining at the initial level after 100 000 pump pulses in the same position of the sample at a 10 Hz repetition rate. Distributed feedback laser emission was demonstrated with organic films that incorporated parent dye PM597 and its cyano derivative. The films were deposited onto quartz substrates engraved with appropriate periodical structures. The C derivative exhibited a laser threshold lower than that of the parent dye as well as lasing intensities up to three orders of magnitude higher. PMID:24453119

  3. 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

  4. Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation.

    PubMed

    David, Gregory; Grandinetti, Kathryn B; Finnerty, Patricia M; Simpson, Natalie; Chu, Gerald C; Depinho, Ronald A

    2008-03-18

    The Sin3-histone deacetylase (HDAC) corepressor complex is conserved from yeast to humans. Mammals possess two highly related Sin3 proteins, mSin3A and mSin3B, which serve as scaffolds tethering HDAC enzymatic activity, and numerous sequence-specific transcription factors to enable local chromatin regulation at specific gene targets. Despite broad overlapping expression of mSin3A and mSin3B, mSin3A is cell-essential and vital for early embryonic development. Here, genetic disruption of mSin3B reveals a very different phenotype characterized by the survival of cultured cells and lethality at late stages of embryonic development with defective differentiation of multiple lineages-phenotypes that are strikingly reminiscent of those associated with loss of retinoblastoma family members or E2F transcriptional repressors. Additionally, we observe that, whereas mSin3B(-/-) cells cycle normally under standard growth conditions, they show an impaired ability to exit the cell cycle with limiting growth factors. Correspondingly, mSin3B interacts physically with the promoters of known E2F target genes, and its deficiency is associated with derepression of these gene targets in vivo. Together, these results reveal a critical role for mSin3B in the control of cell cycle exit and terminal differentiation in mammals and establish contrasting roles for the mSin3 proteins in the growth and development of specific lineages. PMID:18332431

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

    PubMed

    DiMauro, T; Cantor, D J; Bainor, A J; David, G

    2015-07-23

    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

  6. 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

  7. Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

    PubMed Central

    Wei, Qiang; Wang, Ya-Yi; Du, Yu-Liu

    2013-01-01

    Summary A chiral phosphoric acid-catalyzed selenofunctionalization of tryptamine derivatives provides access to 3a-(phenylselenyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole derivatives in high yields and with synthetically useful levels of enantioselectivity (up to 89% ee). PMID:23946855

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. FLASH_SSF_Aqua-FM3_V3B

    Atmospheric Science Data Center

    2016-07-20

    ... FLASH_SSF_Aqua-FM3_V3B Project Title:  CERES Discipline:  Clouds Radiation Budget ...   Reverb Tutorial Subset/Visualization Tool:  CERES Order Tool CERES Search and Subset Tool (HDF4 & netCDF) ...

  13. FLASH_SSF_Terra-FM1_V3B

    Atmospheric Science Data Center

    2016-07-22

    ... FLASH_SSF_Terra-FM1_V3B Project Title:  CERES Discipline:  Clouds Radiation Budget ...   Reverb Tutorial Subset/Visualization Tool:  CERES Order Tool CERES Search and Subset Tool (HDF4 & netCDF) ...

  14. 18 CFR 3b.226 - Accounting of disclosures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... IDENTIFIABLE PERSONAL INFORMATION Rules for Disclosure of Records § 3b.226 Accounting of disclosures. (a) The... this section for at least five years from the date of disclosure for which the accounting is made, or... be maintained for disclosure of the accounting of disclosures....

  15. 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... 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)...

  16. 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... 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)...

  17. 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)...

  18. 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... 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)...

  19. Biodegradation of trichloroethylene by Methylosinus trichosporium OB3b.

    PubMed Central

    Tsien, H C; Brusseau, G A; Hanson, R S; Waclett, L P

    1989-01-01

    The methanotroph Methylosinus trichosporium OB3b, a type II methanotroph, degraded trichloroethylene at rates exceeding 1.2 mmol/h per g (dry weight) following the appearance of soluble methane monooxygenase in continuous and batch cultures. Cells capable oxidizing trichloroethylene contained components of soluble methane monooxygenase as demonstrated by Western blot (immunoblot) analysis with antibodies prepared against the purified enzyme. Growth of cultures in a medium containing 0.25 microM or less copper sulfate caused derepression of the synthesis of soluble methane monooxygenase. In these cultures, the specific rates of methane and methanol oxidation did not change during growth, while trichloroethylene oxidation increased with the appearance of soluble methane monooxygenase. M. trichosporium OB3b cells that contained soluble methane monooxygenase also degraded vinyl chloride, 1,1-dichloroethylene, cis-1,2-dichloroethylene, and trans-1,2-dichloroethylene. Images PMID:2515801

  20. The new silver borate Ag3B5O9

    NASA Astrophysics Data System (ADS)

    Sohr, Gerhard; Falkowski, Viktoria; Huppertz, Hubert

    2015-05-01

    Single crystals of Ag3B5O9 were obtained via high-pressure synthesis at 3 GPa and 600 °C, using a Walker-type multianvil high-pressure device. Ag3B5O9 crystalizes with a=674.7(2), b=943.5(2), c=1103.5(2) pm, V=0.7025(2) nm3, and Z=4 in the noncentrosymmetric space group P212121 (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 BO4 tetrahedra along the a axis, which are interconnected by BO3 groups to form a network. In the structure, three crystallographically independent sites are occupied with Ag+ cations exhibiting argentophillic interactions. The synthetic conditions as well as the results of the single crystal structure analysis are presented.

  1. 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.

  2. Carbides with Filled Re 3B-Type Structure

    NASA Astrophysics Data System (ADS)

    Witte, Anne M.; Jeitschko, Wolfgang

    1994-10-01

    The new compounds AFe2SiC (A = Y, Sm, Gd, Tb, Ho, Er, Tm, Lu, Th, U) were prepared by arc-melting cold-pressed pellets of the elemental components. They are isotypic with the orthorhombic DyFe2SiC-type structure, which was refined from single-crystal X-ray data of ThFe2SiC: Cmcm, a = 386.32(6) pm, b = 1080.6(1) pm, c = 695.0(1) pm, Z = 4, R = 0.020 for 559 structure factors and 17 variable parameters. The polyanionic iron-silicon-carbon network is three-dimensionally infinite. The carbon atoms are situated in octahedral voids formed by four thorium and two iron atoms. The hydrolysis of ErFe2SiC with diluted hydrochloric acid yields mainly methane besides C2 and C3 hydro-carbons. A large number of compounds can be classified to crystallize with a filled-up version of the Re3B-type structure. They are isotypic with V3AsC, where the positions of the vanadium and arsenic atoms correspond to the atomic positions of Re3B and the carbon atoms fill octahedral voids formed by the vanadium atoms. The DyFe2SiC-type structure also can be described as a filled-up Re3B structure; however, the carbon atoms of DyFe2SiC occupy different octahedral voids.

  3. 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

  4. 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

  5. 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...

  6. 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

  7. Cleavage of Complement C3b to iC3b on the Surface of Staphylococcus aureus Is Mediated by Serum Complement Factor I

    PubMed Central

    Cunnion, K. M.; Hair, P. S.; Buescher, E. S.

    2004-01-01

    Complement-mediated opsonization of Staphylococcus aureus bearing the dominant capsule serotypes, serotypes 5 and 8, remains incompletely understood. We have previously shown that complement plays a vital role in the efficient phagocytosis of a serotype 5 S. aureus strain and that the opsonic fragments of the central complement protein C3, C3b and iC3b, were present on the bacterial surface after incubation in human serum. In the present studies, C3b and iC3b were found on several serotype 5 and 8 S. aureus strains after incubation in human serum. Using purified classical activation pathway complement proteins and the Western blot assay, we showed that when C3b was generated on the S. aureus surface no iC3b fragments were found, suggesting that other serum proteins may be required for cleaving C3b to iC3b. When C3b-coated S. aureus was incubated with serum factor I, a complement regulatory protein, iC3b was generated. Purified factor H, a serum protein cofactor for factor I, did not enhance factor I-mediated cleavage of C3b. These findings suggest that C3b cleavage to iC3b on S. aureus is mediated by serum factor I and does not require factor H. PMID:15102797

  8. 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

  9. Investigating the age-related “anterior shift” in the scalp distribution of the P3b component using principal component analysis

    PubMed Central

    Alperin, Brittany R.; Mott, Katherine K.; Rentz, Dorene M.; Holcomb, Phillip J.; Daffner, Kirk R.

    2015-01-01

    An age-related "anterior shift" in the distribution of the P3b is often reported. Temporospatial principal component analysis (PCA) was used to investigate the basis of this observation. ERPs were measured in young and old adults during a visual oddball task. PCA revealed two spatially distinct factors in both age groups, identified as the posterior P3b and anterior P3a. Young subjects generated a smaller P3a than P3b, while old subjects generated a P3a that did not differ in amplitude from their P3b. Rather than having a more anteriorly distributed P3b, old subjects produced a large, temporally overlapping P3a. The pattern of the age-related "anterior shift" in the P3 was similar for target and standard stimuli. The increase in the P3a in elderly adults may not represent a failure to habituate the novelty response, but may reflect greater reliance on executive control operations (P3a) to carry out the categorization/updating process (P3b). PMID:24660980

  10. Fluorine-containing heterocycles: synthesis and some reactions of new 3-amino-2-functionalized-6-(2'-thienyl)-4-trifluoromethylthieno [2,3-b]pyridines.

    PubMed

    Abdel-Monem, M I; Mohamed, O S; Bakhite, E A

    2001-01-01

    3-Cyano-6-(2'-thienyl)-4-trifluoromethylpyridine-2(1H)-thione (2) was prepared and reacted with chloroacetone or phenacyl bromide to yield the 2-acetyl or benzoyl-3-amino-6-(2'-thienyl)-4-trifluoromethylthieno[2,3-b]pyridines (3a, b). In contrast, the reaction of 2 with chloroacetamide or its N-aryl derivatives gave the corresponding 2-carbamoylmethyl thiopyridines 4a-c. Upon treatment of these educts with K2CO3 or C2H5ONa in ethanol, they underwent intramolecular Thorpe-Ziegler cyclization to afford 3-amino-2-carbamoyl-6-(2'-thienyl)-4-trifluoromethyl-thieno[2,3-b]pyridine (5a) and its N-aryl analogs 5b, c. Compounds 5a-c underwent some reactions to yield new pyrido[3',2':4,5]thieno[3,2-d]pyrimidines and pyrido[3',2':4,5]thieno[3,2-d][1,2,3] triazines. PMID:11210666

  11. Analysis of methane biodegradation by Methylosinus trichosporium OB3b

    PubMed Central

    Rodrigues, Andréa dos Santos; Salgado, Belkis Valdman e Andréa Medeiros

    2009-01-01

    The microbial oxidation of methane in the atmosphere is performed by methanotrophic bacteria that use methane as a unique source of carbon and energy. The objective of this work consisted of the investigation of the best conditions of methane biodegradation by methanotrophic bacteria Methylosinus trichosporium OB3b that oxidize it to carbon dioxide, and the use of these microorganisms in monitoring methods for methane. The results showed that M. trichosporium OB3b was capable to degrade methane in a more effective way with an initial microorganism concentration of 0.0700 g.L-1, temperature of 30ºC, pH 6.5 and using 1.79 mmol of methane. In these same conditions, there was no bacterial growth when 2.69 mmol of methane was used. The specific rate of microorganism growth, the conversion factor, the efficiency and the volumetric productivity, for the optimized conditions of biodegradation were, respectively, 0.0324 h-1, 0.6830 gcells/gCH4, 73.73% and 2.7732.10-3 gcells/L.h. The final product of methane microbiological degradation, carbon dioxide, was quantified through the use of a commercial electrode, and, through this, the grade of methane conversion in carbon dioxide was calculated. PMID:24031362

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Corticocortical projections to representations of the teeth, tongue, and face in somatosensory area 3b of macaque monkeys

    PubMed Central

    Cerkevich, Christina M.; Qi, Hui-Xin; Kaas, Jon H.

    2013-01-01

    We placed injections of anatomical tracers into representations of the tongue, teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys. Our injections revealed strong projections to representations of the tongue and teeth from other parts of the oral cavity responsive region in 3b. The 3b face also provided input to the representations of the intra-oral structures. The primary representation of the face showed a pattern of intrinsic connections similar to that of the mouth. The area 3b hand representation provided little to no input to either the mouth or face representations. The mouth and face representations of area 3b received projections from the presumptive oral cavity and face regions of other somatosensory areas in the anterior parietal cortex and the lateral sulcus including areas 3a, 1, 2, the second somatosensory area (S2), the parietal ventral area (PV), and cortex that may include the parietal rostral (PR) and ventral somatosensory (VS) areas. Additional inputs came from primary motor (M1) and ventral premotor (PMv) areas. This areal pattern of projections is similar to the well-studied pattern revealed by tracer injections in regions of 3b representing the hand. The tongue representation appeared to be unique in area 3b in that it also received inputs from areas in the anterior upper bank of the lateral sulcus and anterior insula that may include the primary gustatory area (area G) and other cortical taste processing areas, as well as a region of lateral prefrontal cortex (LPFC) lining the principal sulcus. PMID:23853118

  18. Nonequilibrium dynamics in amorphous Si3B3N7.

    PubMed

    Hannemann, A; Schön, J C; Jansen, M; Sibani, P

    2005-06-16

    We present extensive numerical investigations of the structural relaxation dynamics of a realistic model of the amorphous high-temperature ceramic a-Si3B3N7, probing the mean-square displacement of the atoms, the bond survival probability, the average energy, the specific heat, and the two-point energy average. Combining the information from these different sources, we identify a transition temperature Tc approximately 2000 K below which the system is no longer ergodic and physical quantities observed over a time t(obs) show a systematic parametric dependence on the waiting time t(w), or age, elapsed after the quench. The aging dynamics "stiffens" as the system becomes older, which is similar to the behavior of highly idealized models such as Ising spin glasses and Lennard-Jones glasses. PMID:16852445

  19. 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

  20. 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.

  1. 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

  2. Two Zebrafish hsd3b Genes Are Distinct in Function, Expression, and Evolution.

    PubMed

    Lin, Jen-Chieh; Hu, Shing; Ho, Pei-Hung; Hsu, Hwei-Jan; Postlethwait, John H; Chung, Bon-chu

    2015-08-01

    HSD3B catalyzes the synthesis of δ4 steroids such as progesterone in the adrenals and gonads. Individuals lacking HSD3B2 activity experience congenital adrenal hyperplasia with imbalanced steroid synthesis. To develop a zebrafish model of HSD3B deficiency, we characterized 2 zebrafish hsd3b genes. Our phylogenetic and conserved synteny analyses showed that the tandemly duplicated human HSD3B1 and HSD3B2 genes are coorthologs of zebrafish hsd3b1 on chromosome 9 (Dre9), whereas the gene called hsd3b2 resides on Dre20 in an ancestral chromosome segment, from which its ortholog was lost in the tetrapod lineage. Zebrafish hsd3b1(Dre 9) was expressed in adult gonads and headkidney, which contains interrenal glands, the zebrafish counterpart of the tetrapod adrenal. Knockdown of hsd3b1(Dre 9) caused the interrenal and anterior pituitary to expand and pigmentation to increase, resembling human HSD3B2 deficiency. The zebrafish hsd3b2(Dre 20) gene was expressed in zebrafish early embryos as maternal transcripts that disappeared 1 day after fertilization. Morpholino inactivation of hsd3b2(Dre 20) led to embryo elongation, which was rescued by the injection of hsd3b2 mRNA. Thus, zebrafish hsd3b2(Dre 20) evolved independently of hsd3b1(Dre 9) with a morphogenetic function during early embryogenesis. Zebrafish hsd3b1(Dre 9), on the contrary, functions like mammalian HSD3B2, whose deficiency leads to congenital adrenal hyperplasia. PMID:25974401

  3. 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)

    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 comparisons and e...

  4. Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression

    SciTech Connect

    Kim, Sung-Hak; Park, Jinah; Choi, Moon-Chang; Kim, Hwang-Phill; Park, Jung-Hyun; Jung, Yeonjoo; Lee, Ju-Hee; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You; E-mail: kimty@snu.ac.kr

    2007-04-06

    DNA methyltransferases (DNMT) 3B is a de novo DNMT that represses transcription independent of DNMT activity. In order to gain a better insight into DNMT3B-mediated transcriptional repression, we performed a yeast two-hybrid analysis using DNMT3B as a bait. Of the various binding candidates, ZHX1, a member of zinc-finger and homeobox protein, was found to interact with DNMT3B in vivo and in vitro. N-terminal PWWP domain of DNMT3B was required for its interaction with homeobox motifs of ZHX1. ZHX1 contains nuclear localization signal at C-terminal homeobox motif, and both ZHX1 and DNMT3B were co-localized in nucleus. Furthermore, we found that ZHX1 enhanced the transcriptional repression mediated by DNMT3B when DNMT3B is directly targeted to DNA. These results showed for First the direct linkage between DNMT and zinc-fingers homeoboxes protein, leading to enhanced gene silencing by DNMT3B.

  5. A promising birefringent crystal Ba2Na3(B3O6)2F

    NASA Astrophysics Data System (ADS)

    Wang, Xing; Xia, Mingjun; Li, R. K.

    2014-12-01

    Bulk crystals of Ba2Na3(B3O6)2F (BNBF) have been successfully grown by top-seeded solution growth (TSSG) technique. Its transmittance spectra show a wide transparency range from 186 nm to 3000 nm. The refractive indices in 13 wavelengths were measured with high accuracy and the Sellmeier equations were obtained, which demonstrated that the title crystal displayed a birefringence (Δn = 0.1030 at 588 nm) comparable to that of the commercial birefringent crystal α-BBO (the high temperature form of BaB2O4). A prototype Glan-Taylor polarizer made of BNBF prisms was fabricated, which showed high transparency and large optical extinction ratio similar to the commercial polarizer made of α-BBO. In addition, BNBF crystal is less moisture sensitive than that of α-BBO, thus BNBF can be a potential new birefringent crystal.

  6. 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

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

    PubMed

    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

    2016-05-01

    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

  8. 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...

  9. 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...

  10. 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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, 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...

  13. 12 CFR 563d.3b-6 - Liability for certain statements by savings associations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Liability for certain statements by savings associations. 563d.3b-6 Section 563d.3b-6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OF SAVINGS ASSOCIATIONS Regulations § 563d.3b-6 Liability for certain statements by savings associations. This...

  14. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 3B seamless steel cylinders. 178.38... PACKAGINGS Specifications for Cylinders § 178.38 Specification 3B seamless steel cylinders. (a) Type, size, and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal)...

  15. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 3B seamless steel cylinders. 178.38... PACKAGINGS Specifications for Cylinders § 178.38 Specification 3B seamless steel cylinders. (a) Type, size, and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal)...

  16. 49 CFR 178.38 - Specification 3B seamless steel cylinders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Specification 3B seamless steel cylinders. 178.38... PACKAGINGS Specifications for Cylinders § 178.38 Specification 3B seamless steel cylinders. (a) Type, size, and service pressure. A DOT 3B cylinder is seamless steel cylinder with a water capacity (nominal)...

  17. 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...

  18. 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...

  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, 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...

  1. 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...

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

    PubMed Central

    Shrimal, Shiteshu; Trueman, Steven F.

    2013-01-01

    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. PMID:23530066

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

    PubMed Central

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

    2016-01-01

    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. PMID:27121154

  4. Isolation and characterization of avian paramyxovirus type 3b from farmed Namibian ostriches (Struthio camelus f. dom.).

    PubMed

    Kaleta, Erhard F; Werner, Ortrud; Hemberger, Yvonne

    2010-01-01

    Meat and skin from farmed ostriches are valuable products for European consumers. The EU regulations require that ostrich products deamed for export need to come from ostriches that are free of antibodies against Newcastle disease virus (avian paramxovirus type 1, aPMV-1). After the detection of antibodies against aPMV-1 in one of five ostrich farms in Namibia, attempts were made to isolate the causative virus. No aPMV-1 but an avian paramyxovirus type 3 (aPMV-3) was isolated from five pharyngeal/cloacal swabs of clinically healthy farmed Namibian ostriches. Subtype determination proved that all isolates are members of the subtype aPMV-3 of psittacine bird origin and were designated as aPMV-3b. In the haemagglutination inhibition test, the aPMV-3b isolates cross-reacted with aPMV-1. This allows the conclusion that the antibodies originally detected in sera of the ostriches are due to the cross-reaction with aPMV-3b, rather than to an infection with aPMV-1.To our knowledge, this is the first description of the occurrence of aPMV-3b in farmed ostriches. PMID:20329642

  5. Identification and characterization of Noc2 as a potential Rab3B effector protein in epithelial cells.

    PubMed

    Manabe, Shinji; Nishimura, Noriyuki; Yamamoto, Yasuyo; Kitamura, Hiroko; Morimoto, Shinya; Imai, Mayu; Nagahiro, Shinji; Seino, Susumu; Sasaki, Takuya

    2004-03-26

    The Rab3 family small G proteins (Rab3A-D) are involved in the regulated secretory pathway of brain and secretory tissues. Among Rab3-interacting proteins, Rabphilin-3, Rim, and Noc2, all of which contain a conserved Rab3-binding domain (RBD3), are generally recognized Rab3 effector proteins in neurons and secretory cells. Although Rab3B was also detected in epithelial cells, its function remained unknown. We isolated cDNA sequences from human epithelial Caco2-cell mRNA by degenerate RT-PCR based on the conserved amino acid sequence of RBD3. Multiple cDNA clones were identified as encoding Noc2. Northern blot analysis revealed that Noc2 mRNA was expressed not only in secretory tissues but also in epithelial tissues and cell lines. A pull-down assay demonstrated that Noc2 bound to Rab3B in a GTP-dependent manner. When Noc2 was co-expressed with the GTP-bound form of Rab3B, it was recruited from the cytosol to perinuclear membranes. Furthermore, overexpression of Noc2 inhibited the cell-surface transport of basolateral vesicular stomatitis virus glycoprotein. These results suggest that Noc2 functions as a potential Rab3B effector protein in epithelial cells. PMID:15003533

  6. The 5-HT3B subunit affects high-potency inhibition of 5-HT3 receptors by morphine

    PubMed Central

    Baptista-Hon, Daniel T; Deeb, Tarek Z; Othman, Nidaa A; Sharp, Douglas; Hales, Tim G

    2012-01-01

    BACKGROUND AND PURPOSE Morphine is an antagonist at 5-HT3A receptors. 5-HT3 and opioid receptors are expressed in many of the same neuronal pathways where they modulate gut motility, pain and reinforcement. There is increasing interest in the 5-HT3B subunit, which confers altered pharmacology to 5-HT3 receptors. We investigated the mechanisms of inhibition by morphine of 5-HT3 receptors and the influence of the 5-HT3B subunit. EXPERIMENTAL APPROACH 5-HT-evoked currents were recorded from voltage-clamped HEK293 cells expressing human 5-HT3A subunits alone or in combination with 5-HT3B subunits. The affinity of morphine for the orthosteric site of 5-HT3A or 5-HT3AB receptors was assessed using radioligand binding with the antagonist [3H]GR65630. KEY RESULTS When pre-applied, morphine potently inhibited 5-HT-evoked currents mediated by 5-HT3A receptors. The 5-HT3B subunit reduced the potency of morphine fourfold and increased the rates of inhibition and recovery. Inhibition by pre-applied morphine was insurmountable by 5-HT, was voltage-independent and occurred through a site outside the second membrane-spanning domain. When applied simultaneously with 5-HT, morphine caused a lower potency, surmountable inhibition of 5-HT3A and 5-HT3AB receptors. Morphine also fully displaced [3H]GR65630 from 5-HT3A and 5-HT3AB receptors with similar potency. CONCLUSIONS AND IMPLICATIONS These findings suggest that morphine has two sites of action, a low-affinity, competitive site and a high-affinity, non-competitive site that is not available when the channel is activated. The affinity of morphine for the latter is reduced by the 5-HT3B subunit. Our results reveal that morphine causes a high-affinity, insurmountable and subunit-dependent inhibition of human 5-HT3 receptors. PMID:21740409

  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. 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.

  9. 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

  10. Regulation of the Expression of Heparan Sulfate 3-O-Sulfotransferase 3B (HS3ST3B) by Inflammatory Stimuli in Human Monocytes.

    PubMed

    Sikora, Anne-Sophie; Delos, Maxime; Martinez, Pierre; Carpentier, Mathieu; Allain, Fabrice; Denys, Agnès

    2016-07-01

    Heparan sulfate (HS) is recognized as an important player in a wide range of dynamic steps of inflammatory reactions. Thereby, structural HS remodeling is likely to play an important role in the regulation of inflammatory and immune responses; however, little is known about underlying mechanism. In this study, we analyzed the regulation of expression of HS 3-O-sulfotransferases (HS3STs) in response to inflammatory stimuli. We found that among the seven HS3ST isoenzymes, only the expression of HS3ST3B was markedly up-regulated in human primary monocytes and the related cell line THP1 after exposure to TLR agonists. TNF-α was also efficient, to a lesser extent, to increase HS3ST3B expression, while IL-6, IL-4, and IFN-γ were poor inducers. We then analyzed the molecular mechanisms that regulate the high expression of HS3ST3B in response to LPS. Based on the expression of HS3ST3B transcripts and on the response of a reporter gene containing the HS3ST3B1 promoter, we provide evidence that LPS induces a rapid and strong transcription of HS3ST3B1 gene, which was mainly dependent on the activation of NF-κB and JNK signaling pathways. Additionally, active p38 MAPK and de novo synthesized proteins are involved in post-transcriptional mechanisms to maintain a high level of HS3ST3B mRNA to a steady state. Altogether, our findings indicate that HS3ST3B1 gene behaves as a primary response gene, suggesting that it may play an important role in making 3-O-sulfated HS with specific functions in the regulation of inflammatory and immune responses. J. Cell. Biochem. 117: 1529-1542, 2016. © 2015 Wiley Periodicals, Inc. PMID:26575945

  11. Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine.

    PubMed

    Blair, J B; Marona-Lewicka, D; Kanthasamy, A; Lucaites, V L; Nelson, D L; Nichols, D E

    1999-03-25

    The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b substituted for LSD or DOI up to doses of 50 micromol/kg. By comparison, 1a fully substituted in LSD-trained rats. However, 3a and 3b fully substituted for the 5-HT1A agonist LY293284 ((-)-(4R)-6-acetyl-4-(di-n-propylamino)-1,3,4, 5-tetrahydrobenz[c,d]indole). Both 3a and 3b induced a brief "serotonin syndrome" and salivation, an indication of 5-HT1A receptor activation. At the cloned human 5-HT2A receptor 3b had about twice the affinity of 3a. At the cloned human 5-HT2B and 5-HT2C receptors, however, 3a had about twice the affinity of 3b. Therefore, thiophene lacks equivalence as a replacement for the phenyl ring in the indole nucleus of tryptamines that bind to 5-HT2 receptor subtypes and possess LSD-like behavioral effects. Whereas both of the thienopyrroles had lower affinity than the corresponding 1a at 5-HT2 receptors, 3a and 3b had significantly greater affinity than 1a at the 5-HT1A receptor. Thus, thienopyrrole does appear to serve as a potent bioisostere for the indole nucleus in compounds that bind to the serotonin 5-HT1A receptor. These differences in biological activity suggest that serotonin receptor isoforms are very sensitive to subtle changes in the electronic character of the aromatic systems of indole compounds. PMID:10090793

  12. 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

  13. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma

    PubMed Central

    Harbour, J. William; Roberson, Elisha D. O.; Anbunathan, Hima; Onken, Michael D.; Worley, Lori A.; Bowcock, Anne M.

    2013-01-01

    Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at arginine-625 in splicing factor 3B subunit 1 (SF3B1) in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutation, and these mutations denote a distinct molecular subset of uveal melanomas. PMID:23313955

  14. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma.

    PubMed

    Harbour, J William; Roberson, Elisha D O; Anbunathan, Hima; Onken, Michael D; Worley, Lori A; Bowcock, Anne M

    2013-02-01

    Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas. PMID:23313955

  15. 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

  16. Dnmt3b is a haploinsufficient tumor suppressor gene in Myc-induced lymphomagenesis

    PubMed Central

    Vasanthakumar, Aparna; Lepore, Janet B.; Zegarek, Matthew H.; Kocherginsky, Masha; Singh, Mahi; Davis, Elizabeth M.; Link, Petra A.; Anastasi, John; Le Beau, Michelle M.; Karpf, Adam R.

    2013-01-01

    The drivers of abnormal DNA methylation in human cancers include widespread aberrant splicing of the DNMT3B gene, producing abnormal transcripts that encode truncated proteins that may act as dominant negative isoforms. To test whether reduced Dnmt3b dosage can alter tumorigenesis, we bred Dnmt3b+/− mice to Eµ-Myc mice, a mouse model susceptible to B-cell lymphomas. Eµ-Myc/Dnmt3b+/− mice showed a dramatic acceleration of lymphomagenesis, greater even than that observed in Eµ-Myc mice that express a truncated DNMT3B isoform found in human tumors, DNMT3B7. This finding indicates that Dnmt3b can act as a haploinsufficient tumor suppressor gene. Although reduction in both Dnmt3b dosage and expression of DNMT3B7 within the Eµ-Myc system had similar effects on tumorigenesis and DNA hypermethylation, different molecular mechanisms appear to underlie these changes. This study offers insight into how de novo DNA methyltransferases function as tumor suppressors and the sensitivity of Myc-induced lymphomas to DNA methylation. PMID:23315164

  17. 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.

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

    PubMed Central

    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.

    2012-01-01

    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. PMID:22826563

  19. 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

  20. Predominance of G3B and G14 equine group A rotaviruses of a single VP4 serotype in Japan.

    PubMed

    Tsunemitsu, H; Imagawa, H; Togo, M; Shouji, T; Kawashima, K; Horino, R; Imai, K; Nishimori, T; Takagi, M; Higuchi, T

    2001-10-01

    A total of 65 equine group A rotaviruses (GAR) isolated from diarrheal foals at 48 farms in Hokkaido, Japan, between 1996 (29 isolates) and 1997 (36 isolates) were characterized for their VP7 and VP4 serotypes by PCR, nucleotide sequencing, and virus neutralization (VN) tests. By PCR VP7 typing, all isolates were classified as G3 or G 14, and the predominant serotype in each year was G3 (86%) in 1996 and G14 (53%) in 1997. VN tests with these 20 isolates randomly selected confirmed the specificity of PCR on the bases of complete agreement of the results in these methods (9 G3 and 11 G14), and revealed that all 9 G3 isolates were subtype G3B. There were five differing amino acid residues in three VP7 antigenic regions between subtypes G3A and G3B. Antiserum to a baculovirus recombinant that expressed P[12] VP4 neutralized all isolates and P[12] reference strains. These results suggest that genotype P[12] GAR belong to a single VP4 serotype, and that one VP4 and two VP7 serotypes (G3B and G14) of GAR were predominant in the equine population in Japan. PMID:11722016

  1. (NH{sub 3}CH{sub 2}CH{sub 2}NH{sub 3})B{sub 6}O{sub 9}(OH){sub 2}: Synthesis and crystal structure of a novel layered borate templated by ethylenediamine

    SciTech Connect

    Li Min; Chang Jiazhong; Wang Zhenling; Shi Hengzhen . E-mail: hzshi@zknu.edu.cn

    2006-11-15

    A novel intercalated borate compound (NH{sub 3}CH{sub 2}CH{sub 2}NH{sub 3})B{sub 6}O{sub 9}(OH){sub 2}, has been solvothermally synthesized, and structurally characterized by single crystal X-ray diffraction. Compound crystallizes in the monoclinic, space group P2(1)/c, a=8.6200(17)A, b=15.656(3)A, c=8.8386(18)A, {beta}=93.32(3){sup o}, V=1190.8(4)A{sup 3}, Z=4. Its oxoborate structure is built up from 1-D polyborate chains with 3, 11-membered boron rings bonded diamine molecules through electrostatic attraction and hydrogen bond interactions to construct 2-D layered compound. Other characterizations by IR, element analysis, thermal analysis and specific surface area are also discussed.

  2. 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.

  3. 17 CFR 240.3b-15 - Definition of ancillary portfolio management securities activities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of incidental trading activities for portfolio management purposes; and (3) Are limited to risk... governing body of the dealer and included in the internal risk management control system for the dealer... portfolio management securities activities. 240.3b-15 Section 240.3b-15 Commodity and Securities...

  4. 17 CFR 240.3b-15 - Definition of ancillary portfolio management securities activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of incidental trading activities for portfolio management purposes; and (3) Are limited to risk... governing body of the dealer and included in the internal risk management control system for the dealer... portfolio management securities activities. 240.3b-15 Section 240.3b-15 Commodity and Securities...

  5. 17 CFR 240.3b-15 - Definition of ancillary portfolio management securities activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of incidental trading activities for portfolio management purposes; and (3) Are limited to risk... governing body of the dealer and included in the internal risk management control system for the dealer... portfolio management securities activities. 240.3b-15 Section 240.3b-15 Commodity and Securities...

  6. 17 CFR 240.3b-13 - Definition of eligible OTC derivative instrument.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal Reserve System, 12 CFR Part 221), such contract either: (1) Provides for the purchase or sale of... Reserve System, 12 CFR part 220, set forth in § 240.36a1-1. ... derivative instrument. 240.3b-13 Section 240.3b-13 Commodity and Securities Exchanges SECURITIES AND...

  7. 17 CFR 240.3b-13 - Definition of eligible OTC derivative instrument.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Federal Reserve System, 12 CFR Part 221), such contract either: (1) Provides for the purchase or sale of... Reserve System, 12 CFR part 220, set forth in § 240.36a1-1. ... derivative instrument. 240.3b-13 Section 240.3b-13 Commodity and Securities Exchanges SECURITIES AND...

  8. 17 CFR 240.3b-13 - Definition of eligible OTC derivative instrument.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Federal Reserve System, 12 CFR Part 221), such contract either: (1) Provides for the purchase or sale of... Reserve System, 12 CFR part 220, set forth in § 240.36a1-1. ... derivative instrument. 240.3b-13 Section 240.3b-13 Commodity and Securities Exchanges SECURITIES AND...

  9. 17 CFR 240.3b-13 - Definition of eligible OTC derivative instrument.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Federal Reserve System, 12 CFR Part 221), such contract either: (1) Provides for the purchase or sale of... Reserve System, 12 CFR part 220, set forth in § 240.36a1-1. ... derivative instrument. 240.3b-13 Section 240.3b-13 Commodity and Securities Exchanges SECURITIES AND...

  10. 17 CFR 240.3b-13 - Definition of eligible OTC derivative instrument.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Definition of eligible OTC derivative instrument. 240.3b-13 Section 240.3b-13 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange...

  11. 17 CFR 240.3b-15 - Definition of ancillary portfolio management securities activities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of incidental trading activities for portfolio management purposes; and (3) Are limited to risk... governing body of the dealer and included in the internal risk management control system for the dealer... portfolio management securities activities. 240.3b-15 Section 240.3b-15 Commodity and Securities...

  12. 17 CFR 240.3b-15 - Definition of ancillary portfolio management securities activities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of incidental trading activities for portfolio management purposes; and (3) Are limited to risk... governing body of the dealer and included in the internal risk management control system for the dealer... portfolio management securities activities. 240.3b-15 Section 240.3b-15 Commodity and Securities...

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

    PubMed

    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

    2015-10-01

    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

  14. Pressure induced variation of second harmonic efficiency of K3B6O10Cl

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Kong, Lingyao; Zhao, Xiaoyan; Lv, Zhenlong; Li, Tongwei; Ju, Wei Wei; You, Jinghan; Bai, Ying

    2013-09-01

    K3B6O10Cl is a perovskite-like nonlinear optical (NLO) crystal, which exhibits large second harmonic generation (SHG) response. Based on density-functional theory, we investigate the influence of pressure on SHG tensor of K3B6O10Cl. At zero pressure, the non-centrosymmetric distortion of K3B6O10Cl from BO4 tetrahedron results in the similar SHG tensor to β-BaB2O4 (BBO). At 50 GPa, the ClK6 octahedron distortion of K3B6O10Cl becomes the main source of SHG and give similar SHG tensor to LiNbO3. Therefore, pressure induces K3B6O10Cl from a BBO-like NLO material to a LiNbO3-like NLO material.

  15. RAMONA-3B/MINET composite representation of BWR thermal-hydraulic systems

    SciTech Connect

    Van Tuyle, G.J.; Slovik, G.; Cazzoli, E.G.; Nepsee, T.C.; Guppy, J.G.

    1985-01-01

    The modification and interfacing of two computer codes, RAMONA-3B and MINET, for the thermal hydraulic transient analysis of a Boiling Water Reactor nuclear steam supply system, is described. The RAMONA-3B code provides for multi-channel thermal hydraulics and three-dimensional (or one-dimensional) neutron kinetics analysis of a boiling water reactor core. The RAMONA-3B system representation terminates at the end of the steam line and at the junction of the feedwater line at the vessel inlet. By interfacing RAMONA-3B with MINET, a generic balance-of-plant systems analysis code, a complete BWR systems code with detailed core modeling was obtained. The result is a code of particular importance to the analysis of transients such as ATWS. A comparison between the 3-D and 1-D neutronics representation is provided, along with a test case utilizing the composite RAMONA-3B/MINET code.

  16. Spliceosomal component Sf3b1 is essential for hematopoietic differentiation in zebrafish.

    PubMed

    De La Garza, Adriana; Cameron, Rosannah C; Nik, Sara; Payne, Sara G; Bowman, Teresa V

    2016-09-01

    SF3B1 (Splicing factor 3b, subunit 1) is one of the most commonly mutated factors in myelodysplastic syndrome (MDS). Although the genetic correlation between SF3B1 mutations and MDS etiology are quite strong, no in vivo model currently exists to explore how SF3B1 loss alters blood cell development. Using zebrafish mutants, we show here that proper function of Sf3b1 is required for all hematopoietic lineages. As in MDS patients, zebrafish sf3b1 mutants develop a macrocytic-anemia-like phenotype due to a block in maturation at a late progenitor stage. The mutant embryos also develop neutropenia, because their primitive myeloid cells fail to mature and turn on differentiation markers such as l-plastin and myeloperoxidase. In contrast, production of definitive hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelial cells within the dorsal aorta is greatly diminished, whereas arterial endothelial cells are correctly fated. Notch signaling, imperative for the endothelial-to-hematopoietic transition, is also normal, indicating that HSPC induction is blocked in sf3b1 mutants downstream or independent of Notch signaling. The data demonstrate that Sf3b1 function is necessary during key differentiation fate decisions in multiple blood cell types. Zebrafish sf3b1 mutants offer a novel animal model with which to explore the role of splicing in hematopoietic development and provide an excellent in vivo system with which to delve into the question of why and how Sf3b1 dysfunction is detrimental to hematopoietic differentiation, which could improve MDS diagnosis and treatment. PMID:27260753

  17. 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

  18. SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

    PubMed Central

    Varshney, Bhavna; Agnihotram, Sudhakar; Tan, Yee-Joo; Baric, Ralph; Lal, Sunil K.

    2012-01-01

    Background The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. Methodology/Principal Findings In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. Conclusions/Significance These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection. PMID:22253733

  19. 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

  20. DNMT3b modulates melanoma growth by controlling levels of mTORC2 component RICTOR

    PubMed Central

    Micevic, Goran; Muthusamy, Viswanathan; Damsky, William; Theodosakis, Nicholas; Liu, Xiaoni; Meeth, Katrina; Wingrove, Emily; Santhanakrishnan, Manjula; Bosenberg, Marcus

    2016-01-01

    SUMMARY DNA methyltransferase DNMT3B is frequently overexpressed in tumor cells and plays important roles during the formation and progression of several cancer types. However, the specific signaling pathways controlled by DNMT3B in cancers, including melanoma, are poorly understood. Here, we report that DNMT3B plays a pro-tumorigenic role in human melanoma and that DNMT3B loss dramatically suppresses melanoma formation in the Braf/Pten mouse melanoma model. Loss of DNMT3B results in hypomethylation of the miR-196b promoter and increased miR-196b expression, which directly targets the mTORC2 component Rictor. Loss of RICTOR in turn prevents mTORC2 activation, which is critical for melanoma formation and growth. These findings establish Dnmt3b as a regulator of melanoma formation through its effect on mTORC2 signaling. Based on these results, DNMT3B is a potential therapeutic target in melanoma. PMID:26923591

  1. Modulation of human B cell immunoglobulin secretion by the C3b component of complement.

    PubMed

    Tsokos, G C; Berger, M; Balow, J E

    1984-02-01

    The human C3b component of complement was found to inhibit the differentiation of human B lymphocytes into immunoglobulin-secreting cells in vitro. Pokeweed mitogen (PWM)-induced plaque-forming cell (PFC) responses were inhibited by C3-coated zymosan particles and by purified human C3b. C3b inhibited the PWM-driven responses in a dose-dependent fashion, and it was necessary for C3b to be present in the early phases of the cultures. C3b acted directly on B cells rather than on helper T cells because it inhibited the PFC responses of MNC depleted of T cells and subsequently stimulated with a T cell-independent Epstein Barr virus mitogen. Furthermore, C3b failed to stimulate the generation of suppressor lymphocytes and/or monocytes that might have been responsible for the inhibition of B cell responses. Our results indicate that C3b or its fragments exert negative modulatory effects on human B lymphocyte responses. PMID:6228593

  2. 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

  3. Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

    PubMed Central

    Ostler, KR; Davis, EM; Payne, SL; Gosalia, BB; Expósito-Céspedes, J; Le Beau, MM; Godley, LA

    2008-01-01

    Cancer cells display an altered distribution of DNA methylation relative to normal cells. Certain tumor suppressor gene promoters are hypermethylated and transcriptionally inactivated, whereas repetitive DNA is hypomethylated and transcriptionally active. Little is understood about how the abnormal DNA methylation patterns of cancer cells are established and maintained. Here, we identify over 20 DNMT3B transcripts from many cancer cell lines and primary acute leukemia cells that contain aberrant splicing at the 5′ end of the gene, encoding truncated proteins lacking the C-terminal catalytic domain. Many of these aberrant transcripts retain intron sequences. Although the aberrant transcripts represent a minority of the DNMT3B transcripts present, Western blot analysis demonstrates truncated DNMT3B isoforms in the nuclear protein extracts of cancer cells. To test if expression of a truncated DNMT3B protein could alter the DNA methylation patterns within cells, we expressed DNMT3B7, the most frequently expressed aberrant transcript, in 293 cells. DNMT3B7-expressing 293 cells have altered gene expression as identified by microarray analysis. Some of these changes in gene expression correlate with altered DNA methylation of corresponding CpG islands. These results suggest that truncated DNMT3B proteins could play a role in the abnormal distribution of DNA methylation found in cancer cells. PMID:17353906

  4. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts

    PubMed Central

    Karimi, Mohsen; Papaemmanuil, Elli; Ambaglio, Ilaria; Jädersten, Martin; Jansson, Monika; Elena, Chiara; Gallì, Anna; Walldin, Gunilla; Della Porta, Matteo G.; Raaschou-Jensen, Klas; Travaglino, Erica; Kallenbach, Klaus; Pietra, Daniela; Ljungström, Viktor; Conte, Simona; Boveri, Emanuela; Invernizzi, Rosangela; Rosenquist, Richard; Campbell, Peter J.; Cazzola, Mario; Hellström Lindberg, Eva

    2015-01-01

    Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions. To identify mutation patterns that affect disease phenotype and clinical outcome, we performed a comprehensive mutation analysis in 293 patients with myeloid neoplasm and 1% or more ring sideroblasts. SF3B1 mutations were detected in 129 of 159 cases (81%) of RARS or RCMD-RS. Among other patients with ring sideroblasts, lower prevalence of SF3B1 mutations and higher prevalence of mutations in other splicing factor genes were observed (P < .001). In multivariable analyses, patients with SF3B1 mutations showed significantly better overall survival (hazard ratio [HR], .37; P = .003) and lower cumulative incidence of disease progression (HR = 0.31; P = .018) compared with SF3B1-unmutated cases. The independent prognostic value of SF3B1 mutation was retained in MDS without excess blasts, as well as in sideroblastic categories (RARS and RCMD-RS). Among SF3B1-mutated patients, coexisting mutations in DNA methylation genes were associated with multilineage dysplasia (P = .015) but had no effect on clinical outcome. TP53 mutations were frequently detected in patients without SF3B1 mutation, and were associated with poor outcome. Thus, SF3B1 mutation identifies a distinct MDS subtype that is unlikely to develop detrimental subclonal mutations and is characterized by indolent clinical course and favorable outcome. PMID:25957392

  5. Chronic myelocytic leukaemia: HLA association and decreased erythrocyte C3b receptor expression.

    PubMed Central

    Ruuska, P; Silvennoinen-Kassinen, S; Timonen, T; Tiilikainen, A

    1985-01-01

    A series of 27 adult patients with chronic myelocytic leukaemia (CML) were examined for erythrocyte C3b receptor (EC3bR) expression. Twenty-five patients were successfully HLA typed and there was a positive association of CML with HLA-B40 (P less than 0.01). Only 10 (37%) of the patients were EC3bR positive (P less than 0.00001) compared to 223 healthy controls of whom 198 (89%) were EC3bR positive. The positivity of EC3bR and HLA-B40 occurred simultaneously in six patients (P less than 0.05). HLA-B40 positivity and EC3bR expression were correlated with the following variables: age at the time of CML diagnoses, duration of CML (until death or the end of follow-up period 1 July 1983), the stage of CML and simultaneous medication. EC3bR positive patients were significantly more often in remission (P less than 0.05) and also had shorter duration of the disease (P less than 0.005) then did EC3bR negative ones. No significant correlation existed between EC3bR status and the other parameters. The presence of HLA-B40 did not associate with any of the listed variables. These findings may indicate the loss of the receptor in the course of CML with increasing immaturity of cells released from bone marrow. PMID:3156701

  6. Neuroprotective Effects of Transcription Factor Brn3b in an Ocular Hypertension Rat Model of Glaucoma

    PubMed Central

    Stankowska, Dorota L.; Minton, Alena Z.; Rutledge, Margaret A.; Mueller, Brett H.; Phatak, Nitasha R.; He, Shaoqing; Ma, Hai-Ying; Forster, Michael J.; Yorio, Thomas; Krishnamoorthy, Raghu R.

    2015-01-01

    Purpose. Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss, and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC development, axon outgrowth, and pathfinding. Previous studies suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The goal of this study was to determine if adeno-associated virus (AAV)-directed overexpression of the Brn3b protein could have neuroprotective effects following elevated IOP-mediated neurodegeneration. Methods. Intraocular pressure was elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the IOP-elevated eyes were intravitreally injected with AAV constructs encoding either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV-hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity markers and neuroprotection was assessed by RGC counts and visual acuity tests. Results. Adeno-associated virus–mediated expression of the Brn3b protein in IOP-elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP-43), actin binding LIM protein (abLIM) and acetylated α-tubulin (ac-Tuba) both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b–injected rats compared with those of the IOP-elevated rAAV-hsyn-GFP– injected rats. Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored the visual optomotor response in IOP-elevated rat eyes. Conclusions. Adeno-associated virus–mediated Brn3b protein expression may be a suitable approach for promoting neuroprotection in animal models of glaucoma. PMID:25587060

  7. Sulfotransferase 4A1.

    PubMed

    Minchin, Rodney F; Lewis, Aaron; Mitchell, Deanne; Kadlubar, Fred F; McManus, Michael E

    2008-01-01

    In this review, we highlight the physical and enzymatic properties of the novel human sulfotransferase, SULT4A1. The gene is most highly expressed in selective regions of the brain, although work to date has failed to identify any specific endogenous substrate for the enzyme. SULT4A1 shares low homology with other human sulfotransferases. Nevertheless, it is highly conserved between species. Despite the low homology, it is structurally very similar to other cytosolic sulfotransferases with a conserved substrate binding domain, dimerization site and partial cofactor binding sites. However, the catalytic cavity is much smaller, and it has been suggested that the cofactor may not be accommodated within it. A recent link between variability in the 5'UTR of the SULT4A1 gene and schizophrenia has heightened interest in the endogenous function of the enzyme and its possible role in human disease. PMID:18248844

  8. Synthesis, transformations and biological properties of furo[2,3-b]pyridines

    NASA Astrophysics Data System (ADS)

    Sirakanyan, S. N.; Hovakimyan, A. A.; Noravyan, A. S.

    2015-04-01

    Data on furo[2,3-b]pyridines published in the last 15 years are integrated and analyzed for the first time. Information on the methods of synthesis, chemical transformations and biological action of these systems is described systematically. Particular attention is paid to the preparation and study of properties of polycondensed derivatives as the most promising and rapidly developing line of research of furo[2,3-b]pyridine chemistry. The biological properties of this class of compounds are discussed, and examples of furo[2,3-b]pyridines that exhibit high biological activities are given. The bibliography includes 88 references.

  9. 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

  10. ∆ DNMT3B4-del Contributes to Aberrant DNA Methylation Patterns in Lung Tumorigenesis

    PubMed Central

    Ma, Mark Z.; Lin, Ruxian; Carrillo, José; Bhutani, Manisha; Pathak, Ashutosh; Ren, Hening; Li, Yaokun; Song, Jiuzhou; Mao, Li

    2015-01-01

    Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. We have previously shown that ∆DNMT3B is the predominantly expressed form of DNMT3B. In this study, we found that most of the lung cancer cell lines tested predominantly expressed DNMT3B isoforms without exons 21, 22 or both 21 and 22 (a region corresponding to the enzymatic domain of DNMT3B) termed DNMT3B/∆DNMT3B-del. In normal bronchial epithelial cells, DNMT3B/ΔDNMT3B and DNMT3B/∆DNMT3B-del displayed equal levels of expression. In contrast, in patients with non-small cell lung cancer NSCLC), 111 (93%) of the 119 tumors predominantly expressed DNMT3B/ΔDNMT3B-del, including 47 (39%) tumors with no detectable DNMT3B/∆DNMT3B. Using a transgenic mouse model, we further demonstrated the biological impact of ∆DNMT3B4-del, the ∆DNMT3B-del isoform most abundantly expressed in NSCLC, in global DNA methylation patterns and lung tumorigenesis. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation patterns during lung tumorigenesis and suggest that ∆DNMT3B4-del may be a target for lung cancer prevention. PMID:26629529

  11. Genome Sequence of the Obligate Methanotroph Methylosinus trichosporium Strain OB3b

    SciTech Connect

    Stein, Lisa Y.; Yoon, Sukhwan; Semrau, Jeremy D.; DiSpiritto, Alan A.; Crombie, Andrew; Murrell, J.; Vuilleumier, Stephane; Kalyuzhnaya, Marina G.; Den Camp, Huub J. M. Op; Bringel, Francoise O.; Bruce, David; Cheng, Jan-Fang; Copeland, A; Goodwin, Lynne A.; Han, Cliff; Hauser, Loren John; Jetten, MSM; Lajus, Aurelie; Lapidus, Alla L.; Lucas, Susan; Medigue, Claudine; Woyke, Tanja; Zeytun, Ahmet; Klotz, Martin G

    2010-01-01

    Methylosinus trichosporium OB3b (for "oddball" strain 3b) is an obligate aerobic methane-oxidizing alphaproteobacterium that was originally isolated in 1970 by Roger Whittenbury and colleagues. This strain has since been used extensively to elucidate the structure and function of several key enzymes of methane oxidation, including both particulate and soluble methane monooxygenase (sMMO) and the extracellular copper chelator methanobactin. In particular, the catalytic properties of soluble methane monooxygenase from M. trichosporium OB3b have been well characterized in context with biodegradation of recalcitrant hydrocarbons, such as trichloroethylene. The sequence of the M. trichosporium OB3b genome is the first reported from a member of the Methylocystaceae family in the order Rhizobiales.

  12. Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause.

    PubMed

    Petit, F; Escande, F; Jourdain, A S; Porchet, N; Amiel, J; Doray, B; Delrue, M A; Flori, E; Kim, C A; Marlin, S; Robertson, S P; Manouvrier-Hanu, S; Holder-Espinasse, M

    2014-09-01

    Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss-of-function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype-phenotype correlations. Most mutation-negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity. PMID:24003905

  13. Increased APOBEC3B Predicts Worse Outcomes in Lung Cancer: A Comprehensive Retrospective Study

    PubMed Central

    Yan, Shumei; He, Fan; Gao, Bei; Wu, Huini; Li, Mei; Huang, Liyun; Liang, Jianzhong; Wu, Qiuliang; Li, Yong

    2016-01-01

    Lung cancer ranks as the most common and lethal malignancy in America and worldwide. APOBEC3B is a newly identified DNA cytosine deaminase, which is supposed to function as a major source of DNA mutation in many different tumors. In this study, we combine the data of online databases and two hundred and twenty-one primary non-small-cell lung carcinoma (NSCLC) specimens from Sun Yat-sen University Cancer Center to investigate, for the first time, the clinical role of APOBEC3B in lung cancer. We found that the APOBEC3 expression was commonly elevated in NSCLC tissues and overexpression of APOBEC3B was correlated with unfavorable prognosis of the patients with NSCLC. Furthermore, APOBEC3B expression was associated with nodal status, TNM staging and adjuvant chemotherapy of the patients with NSCLC. Further research is warranted. PMID:27076842

  14. Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression.

    PubMed

    Chung, Chee Yeun; Koprich, James B; Hallett, Penelope J; Isacson, Ole

    2009-12-29

    In Parkinson's disease (PD), dopaminergic (DA) neurons in the substantia nigra (SN, A9) are particularly vulnerable, compared to adjacent DA neurons within the ventral tegmental area (VTA, A10). Here, we show that in rat and human, one RAB3 isoform, RAB3B, has higher expression levels in A10 compared to A9 neurons. RAB3 is a monomeric GTPase protein that is highly enriched in synaptic vesicles and is involved in synaptic vesicle trafficking and synaptic transmission, disturbances of which have been implicated in several neurodegenerative diseases, including PD. These findings prompted us to further investigate the biology and neuroprotective capacity of RAB3B both in vitro and in vivo. RAB3B overexpression in human dopaminergic BE (2)-M17 cells increased neurotransmitter content, [(3)H] dopamine uptake, and levels of presynaptic proteins. AAV-mediated RAB3B overexpression in A9 DA neurons of the rat SN increased striatal dopamine content, number and size of synaptic vesicles, and levels of the presynaptic proteins, confirming in vitro findings. Measurement of extracellular DOPAC, a dopamine metabolite, following l-DOPA injection supported a role for RAB3B in enhancing the dopamine storage capacity of synaptic terminals. RAB3B overexpression in BE (2)-M17 cells was protective against toxins that simulate aspects of PD in vitro, including an oxidative stressor 6-hydroxydopamine (6-OHDA) and a proteasome inhibitor MG-132. Furthermore, RAB3B overexpression in rat SN both protected A9 DA neurons and resulted in behavioral improvement in a 6-OHDA retrograde lesion model of PD. These results suggest that RAB3B improves dopamine handling and storage capacity at presynaptic terminals, and confers protection to vulnerable DA neurons. PMID:20007772

  15. 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

  16. Synthesis & photoluminescence study of UV emitting borate phosphor Ca3B2O6:Pb2+

    NASA Astrophysics Data System (ADS)

    Gawande, A. B.; Sonekar, R. P.; Omanwar, S. K.

    2013-06-01

    The powder sample of Ca3B2O6:Pb2+ has been prepared by a novel method which is slight variation of solution Combustion Synthesis. The synthesis is based on the exothermic reaction between the fuel (Urea) and Oxidizer (Ammonium nitrate). The structure of Ca3B2O6:Pb2+ has been confirmed by comparing the powder XRD pattern of the samples with the standard ICDD data files. The photoluminescent properties of Ca3B2O6:Pb2+ materials were investigated using F-7000 FL spectrophotometer at room temperature. The emission and excitation bands of Ca3B2O6:Pb2+ were observed at 335 and 270 nm, respectively. The Stoke shifts of phosphors Ca3B2O6:Pb2+ were calculated to be 7186 cm-1. The dependence of the emission intensity on the Pb2+ concentration was studied in detail. It has observed that, the phosphor Ca3B2O6:Pb2+ exhibits optimum emission intensity for 0.5 % concentration of Pb2+.

  17. 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

  18. 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. PMID:27216270

  19. Germline recombination in a novel Cre transgenic line, Prl3b1-Cre mouse.

    PubMed

    Al-Soudy, Al-Sayed; Nakanishi, Tsuyoshi; Mizuno, Seiya; Hasegawa, Yoshikazu; Shawki, Hossam H; Katoh, Megumi C; Basha, Walaa A; Ibrahim, Abdelaziz E; El-Shemy, Hany A; Iseki, Hiroyoshi; Yoshiki, Atsushi; Hiromori, Youhei; Nagase, Hisamitsu; Takahashi, Satoru; Oishi, Hisashi; Sugiyama, Fumihiro

    2016-07-01

    Spermatogenesis is a complex and highly regulated process by which spermatogonial stem cells differentiate into spermatozoa. To better understand the molecular mechanisms of the process, the Cre/loxP system has been widely utilized for conditional gene knockout in mice. In this study, we generated a transgenic mouse line that expresses Cre recombinase under the control of the 2.5 kbp of the Prolactin family 3, subfamily b, member 1 (Prl3b1) gene promoter (Prl3b1-cre). Prl3b1 was initially reported to code for placental lactogen 2 (PL-2) protein in placenta along with increased expression toward the end of pregnancy. PL-2 was found to be expressed in germ cells in the testis, especially in spermatocytes. To analyze the specificity and efficiency of Cre recombinase activity in Prl3b1-cre mice, the mice were mated with reporter R26GRR mice, which express GFP ubiquitously before and tdsRed exclusively after Cre recombination. The systemic examination of Prl3b1-cre;R26GRR mice revealed that tdsRed-positive cells were detected only in the testis and epididymis. Fluorescence imaging of Prl3b1-cre;R26GRR testes suggested that Cre-mediated recombination took place in the germ cells with approximately 74% efficiency determined by in vitro fertilization. In conclusion, our results suggest that the Prl3b1-cre mice line provides a unique resource to understand testicular germ-cell development. genesis 54:389-397, 2016. © 2016 Wiley Periodicals, Inc. PMID:27124574

  20. Superconductivity and spin fluctuations in the actinoid-platinum metal borides {Th ,U } Pt3B

    NASA Astrophysics Data System (ADS)

    Bauer, E.; Royanian, E.; Michor, H.; Sologub, O.; Scheidt, E.-W.; Gonçalves, A. P.; Bursik, J.; Wolf, W.; Reith, D.; Blaas-Schenner, C.; Moser, R.; Podloucky, R.; Rogl, P.

    2015-07-01

    Investigating the phase relations of the system {Th ,U } -Pt-B at 900 °C the formation of two compounds has been observed: cubic ThPt3B with P m 3 ¯m structure as a representative of the perovskites, and tetragonal UPt3B with P 4 m m structure being isotypic to the noncentrosymmetric structure of CePt3B . The crystal structures of the two compounds are defined by combined x-ray diffraction and transmission electron microscopy. Characterization of physical properties for ThPt3B reveals a superconducting transition at 0.75 K and an upper critical field at T =0 exceeding 0.4 T. For nonsuperconducting UPt3B a metallic resistivity behavior was found in the entire temperature range; at very low temperatures spin fluctuations become evident and the resistivity ρ (T ) follows non-Fermi liquid characteristics, ρ =ρ0+A T n with n =1.6 . Density functional theory (DFT) calculations were performed for both compounds for both types of structures. They predict that the experimentally claimed cubic structure of ThPt3B is thermodynamically not stable in comparison to a tetragonal phase, with a very large enthalpy difference of 25 kJ/mol, which cannot be explained by the formation energy of B vacancies. However, the presence of random boron vacancies possibly stabilizes the cubic structure via a local strain compensation mechanism during the growth of the crystal. For UPt3B the DFT results agree well with the experimental findings.

  1. APOBEC3B expression in drug resistant MCF-7 breast cancer cell lines.

    PubMed

    Onguru, Onder; Yalcin, Serap; Rosemblit, Cinthia; Zhang, Paul J; Kilic, Selim; Gunduz, Ufuk

    2016-04-01

    APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compared expression levels with drug sensitive MCF-7 cell line. After RNAscope staining, slides were scanned and saved as digital images using Aperio scanner and software. Quantitative scoring utilizing the number of punctate dots present within each cell boundary was performed for the parameters including positive cell percentage and signal intensity per positive cell. In Doxorubicin and Etoposide resistant MCF-7 cell lines, APOBEC3B expression was approximately five-fold increased (23% and 24% respectively) with higher signal intensity (1.92 and 1.44 signal/cell, respectively) compared to drug sensitive MCF-7 cell line (5%, 1.00 signal/cell) with statistical significance. The increase of APOBEC3B expression in Docataxel resitant and Paclitaxel resistant MCF-7 cell lines was not very high. In conclusion, APOBEC3B expression was increased in some population of tumor cells of drug resistant cell lines. At least for some drugs, APOBEC3B expression may be related to drug resistance, subjecting to some tumor cells to frequent mutation. PMID:27044816

  2. Polymorphism of FCGR2A, FCGR2C, and FCGR3B Genes in the Pathogenesis of Sarcoidosis.

    PubMed

    Typiak, M; Rębała, K; Dudziak, M; Słomiński, J M; Dubaniewicz, A

    2016-01-01

    We have previously presented evidence that the polymorphism of the FCGR3A gene, encoding the receptor for Fc fragment of immunoglobulin G IIIa (FcγRIIIa) plays a role in the enhancement of circulating immune complexes (CIs) with the occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis (SA). The immunocomplexemia might be caused by decreased affinity of CIs to Fcγ receptors, with the subsequently decreased receptor clearance by immune cells. In the present study we examined whether the polymorphisms of other related genes (FCGR2A, FCGR2C, FCGR3B) encoding other activatory Fcγ receptors, could have a similar effect. To this end, we genotyped 124 patients with sarcoidosis and 148 healthy volunteers using polymerase chain reaction with sequence-specific primers. We revealed a significant decrease in the percentage of the FCGR2A and FCGR2C variants that ensure effective CIs clearance, with a concomitant increase of less functional variants of these genes in Stages I/II, compared with Stages III/IV of SA. There was no aberration in FCGR3B allele/genotype frequencies. We conclude that the FCGR2A and FCGR2C polymorphisms may also contribute to immunocomplexemia present in SA. The assessment of FCGR genes could become a tool in presaging a clinical course of sarcoidosis and in its personalized therapy. PMID:26801149

  3. Cytotoxicity and cell cycle effects of novel indolo[2,3-b]quinoline derivatives.

    PubMed

    Humeniuk, Rita; Kaczmarek, Lukasz; Peczyńska-Czoch, Wanda; Marcinkowska, Ewa

    2003-01-01

    Cellular effects of novel indolo[2,3-b]quinoline derivatives were studied. These compounds are synthetic analogs of plant alkaloid neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) present in extracts from Cryptolepis sanguinolenta. They are traditionally used in natural medicine in Central and West Africa. Previous molecular and computational studies indicated that these compounds were DNA intercalators and inhibitors of topoisomerase II. We have extended our studies on their mode of action to the cellular level. Past experiments have shown that these compounds were active in vitro against cell lines derived from solid tumors, so for the present studies we selected leukemic cell lines. Jurkat acute T cell, CCRF-CEM T lymphoblastoid, THP-1 acute monocytic, HL-60 acute promyelocytic leukemias, and HL-60/MX2 subline with reduced expression of topoisomerase II were used. We evaluated the cytotoxicity and cell cycle effects of the indolo[2,3-b]quinoline compounds. We also tested if these compounds were able to induce apoptosis in the cells. Our studies revealed that novel indolo[2,3-b]quinoline derivatives were more cytotoxic to all cell lines than etoposide (used as a reference topoisomerase II inhibitor), and that their cytotoxicity depended on the substituents introduced to the indolo[2,3-b]quinoline core. Surprisingly, our studies have shown that HL-60/MX2 cell line and also THP-1 cell line, resistant to etoposide, were susceptible to methyl- and methoxy-substituted indolo[2,3-b]quinoline derivatives. In parallel to the evaluation of cytotoxicity we studied cell cycle effects of these compounds. Treatment of HL-60 cells with etoposide in subcytotoxic concentrations resulted in a massive accumulation of the cells in the G2/M phase of the cell cycle. When we used subcytotoxic concentrations of our novel indolo[2,3-b]quinoline derivatives the cell cycle progression of HL-60 cells was not affected. Moreover, the cell cycle of HL-60/MX2 cells was not influenced by

  4. Genetic and epigenetic variation in the DNMT3B and MTHFR genes and colorectal adenoma risk.

    PubMed

    Ho, Vikki; Ashbury, Janet E; Taylor, Sherryl; Vanner, Stephen; King, Will D

    2016-05-01

    Polymorphisms in DNMT3B and MTHFR have been implicated in cancer etiology; however, it is increasingly clear that gene-specific DNA methylation also affects gene expression. A cross-sectional study (N = 272) investigated the main and joint effects of polymorphisms and DNA methylation in DNMT3B and MTHFR on colorectal adenoma risk. Polymorphisms examined included DNMT3B c.-6-1045G > T, and MTHFR c.665C > T and c.1286A > C. DNA methylation of 66 and 28 CpG sites in DNMT3B and MTHFR, respectively, was quantified in blood leukocytes using Sequenom EpiTYPER®. DNA methylation was conceptualized using two approaches: (1) average methylation and (2) unsupervised principal component analysis to identify variables that represented methylation around the transcription start site and the gene coding area of both genes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with the main and joint effects of polymorphisms and DNA methylation. DNA methyltransferase 3B (DNMT3B) TT versus GG/GT genotypes was associated with increased colorectal adenoma risk (OR = 2.12; 95% CI: 1.03-4.34). In addition, increasing DNA methylation in the gene-coding area of DNMT3B was associated with higher risk of colorectal adenomas (OR = 1.34; 95% CI: 1.01-1.79 per SD). In joint effect analyses, synergistic effects were observed among those with both the DNMT3B TT genotype and higher DNMT3B methylation levels compared to those with GT/GG genotypes and lower methylation levels (OR = 4.19; 95% CI: 1.45-12.13 for average methylation; OR = 4.26; 95%CI: 1.31-13.87 for methylation in the transcription start site). This research provides novel evidence that genetic and epigenetic variations contribute to colorectal adenoma risk, precursor to the majority of colorectal cancer (CRC). Environ. Mol. Mutagen. 57:261-268, 2016. © 2016 Wiley Periodicals, Inc. PMID:27062459

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

    PubMed

    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

    2015-06-30

    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

  6. 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

  7. Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis.

    PubMed

    Arbeille, Elise; Reynaud, Florie; Sanyas, Isabelle; Bozon, Muriel; Kindbeiter, Karine; Causeret, Frédéric; Pierani, Alessandra; Falk, Julien; Moret, Frédéric; Castellani, Valérie

    2015-01-01

    The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones. PMID:25721514

  8. QTug.sau-3B Is a Major Quantitative Trait Locus for Wheat Hexaploidization

    PubMed Central

    Hao, Ming; Luo, Jiangtao; Zeng, Deying; Zhang, Li; Ning, Shunzong; Yuan, Zhongwei; Yan, Zehong; Zhang, Huaigang; Zheng, Youliang; Feuillet, Catherine; Choulet, Frédéric; Yen, Yang; Zhang, Lianquan; Liu, Dengcai

    2014-01-01

    Meiotic nonreduction resulting in unreduced gametes is thought to be the predominant mechanism underlying allopolyploid formation in plants. Until now, however, its genetic base was largely unknown. The allohexaploid crop common wheat (Triticum aestivum L.), which originated from hybrids of T. turgidum L. with Aegilops tauschii Cosson, provides a model to address this issue. Our observations of meiosis in pollen mother cells from T. turgidum×Ae. tauschii hybrids indicated that first division restitution, which exhibited prolonged cell division during meiosis I, was responsible for unreduced gamete formation. A major quantitative trait locus (QTL) for this trait, named QTug.sau-3B, was detected on chromosome 3B in two T. turgidum×Ae. tauschii haploid populations. This QTL is situated between markers Xgwm285 and Xcfp1012 and covered a genetic distance of 1 cM in one population. QTug.sau-3B is a haploid-dependent QTL because it was not detected in doubled haploid populations. Comparative genome analysis indicated that this QTL was close to Ttam-3B, a collinear homolog of tam in wheat. Although the relationship between QTug.sau-3B and Ttam requires further study, high frequencies of unreduced gametes may be related to reduced expression of Ttam in wheat. PMID:25128436

  9. 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. PMID:16769694

  10. 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.

  11. Dual functional activity of semaphorin 3B is required for positioning the anterior commissure.

    PubMed

    Falk, Julien; Julien, Falk; Bechara, Ahmad; Fiore, Roberto; Nawabi, Homaira; Zhou, Heather; Hoyo-Becerra, Carolina; Bozon, Muriel; Rougon, Geneviève; Grumet, Martin; Püschel, Andreas W; Sanes, Joshua R; Castellani, Valérie

    2005-10-01

    Chemorepulsion by semaphorins plays a critical role during the development of neuronal projections. Although semaphorin-induced chemoattraction has been reported in vitro, the contribution of this activity to axon pathfinding is still unclear. Using genetic and culture models, we provide evidence that both attraction and repulsion by Sema3B, a secreted semaphorin, are critical for the positioning of a major brain commissural projection, the anterior commissure (AC). NrCAM, an immunoglobulin superfamily adhesion molecule of the L1 subfamily, associates with neuropilin-2 and is a component of a receptor complex for Sema3B and Sema3F. Finally, we show that activation of the FAK/Src signaling cascade distinguishes Sema3B-mediated attractive from repulsive axonal responses of neurons forming the AC, revealing a mechanism underlying the dual activity of this guidance cue. PMID:16202709

  12. Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

    PubMed Central

    Yoo, Tae-Hyun; Pedigo, Christopher E.; Guzman, Johanna; Correa-Medina, Mayrin; Wei, Changli; Villarreal, Rodrigo; Mitrofanova, Alla; Leclercq, Farah; Faul, Christian; Li, Jing; Kretzler, Matthias; Nelson, Robert G.; Lehto, Markku; Forsblom, Carol; Groop, Per-Henrik; Reiser, Jochen; Burke, George William

    2015-01-01

    Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ3 integrin-dependent migration in vitro. Furthermore, αVβ3 integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ3 integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ3 integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target. PMID:24925721

  13. Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease.

    PubMed

    Yoo, Tae-Hyun; Pedigo, Christopher E; Guzman, Johanna; Correa-Medina, Mayrin; Wei, Changli; Villarreal, Rodrigo; Mitrofanova, Alla; Leclercq, Farah; Faul, Christian; Li, Jing; Kretzler, Matthias; Nelson, Robert G; Lehto, Markku; Forsblom, Carol; Groop, Per-Henrik; Reiser, Jochen; Burke, George William; Fornoni, Alessia; Merscher, Sandra

    2015-01-01

    Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ3 integrin-dependent migration in vitro. Furthermore, αVβ3 integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ3 integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ3 integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target. PMID:24925721

  14. LRRN4 and UPK3B Are Markers of Primary Mesothelial Cells

    PubMed Central

    Kanamori-Katayama, Mutsumi; Kaiho, Ai; Ishizu, Yuri; Okamura-Oho, Yuko; Hino, Okio; Abe, Masaaki; Kishimoto, Takumi; Sekihara, Hisahiko; Nakamura, Yukio; Suzuki, Harukazu; Forrest, Alistair R. R.; Hayashizaki, Yoshihide

    2011-01-01

    Background Mesothelioma is a highly malignant tumor that is primarily caused by occupational or environmental exposure to asbestos fibers. Despite worldwide restrictions on asbestos usage, further cases are expected as diagnosis is typically 20–40 years after exposure. Once diagnosed there is a very poor prognosis with a median survival rate of 9 months. Considering this the development of early pre clinical diagnostic markers may help improve clinical outcomes. Methodology Microarray expression arrays on mesothelium and other tissues dissected from mice were used to identify candidate mesothelial lineage markers. Candidates were further tested by qRTPCR and in-situ hybridization across a mouse tissue panel. Two candidate biomarkers with the potential for secretion, uroplakin 3B (UPK3B), and leucine rich repeat neuronal 4 (LRRN4) and one commercialized mesothelioma marker, mesothelin (MSLN) were then chosen for validation across a panel of normal human primary cells, 16 established mesothelioma cell lines, 10 lung cancer lines, and a further set of 8 unrelated cancer cell lines. Conclusions Within the primary cell panel, LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. MSLN was detected in bronchial epithelial cells and alveolar epithelial cells and UPK3B was detected in retinal pigment epithelial cells and urothelial cells. Testing the cell line panel, MSLN was detected in 15 of the 16 mesothelioma cells lines, whereas LRRN4 was only detected in 8 and UPK3B in 6. Interestingly MSLN levels appear to be upregulated in the mesothelioma lines compared to the primary mesothelial cells, while LRRN4 and UPK3B, are either lost or down-regulated. Despite the higher fraction of mesothelioma lines positive for MSLN, it was also detected at high levels in 2 lung cancer lines and 3 other unrelated cancer lines derived from papillotubular adenocarcinoma, signet ring carcinoma and transitional cell carcinoma. PMID

  15. 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.

  16. 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

  17. Mechanism and Regulation of Acetylated Histone Binding by the Tandem PHD Finger of DPF3b

    PubMed Central

    Zeng, Lei; Zhang, Qiang; Li, SiDe; Plotnikov, Alexander N.; Walsh, Martin J.; Zhou, Ming-Ming

    2010-01-01

    Histone lysine acetylation and methylation are important during gene transcription in a chromatin context1,2. Our knowledge about the types of protein modules that can interact with acetyl-lysine has so far been limited to bromodomains1. Recently, a tandem PHD (plant homeodomain) finger3 (PHD12) of human DPF3b, which functions in association with the BAF chromatin remodelling complex to initiate transcription in the heart and muscle development, was reported to bind histones H3 and H4 in an acetylation sensitive manner4, making it a first alternative to bromodomains for acetyl-lysine binding5. Here, we report the structural mechanism of acetylated histone binding by the double PHD fingers of DPF3b. Our three-dimensional solution structures and biochemical analysis of DPF3b illuminate the molecular basis of the integrated tandem PHD finger, which acts as one functional unit in the sequence-specific recognition of lysine 14-acetylated histone H3 (H3K14ac). Whereas the interaction with H3 is promoted by acetylation at lysine 14, it is inhibited by methylation at lysine 4, and these opposing influences are important during transcriptional activation of DPF3b target genes Pitx2 and Jmjd1c. Binding of this tandem protein module to chromatin can thus be regulated by different histone modifications during the initiation of gene transcription. PMID:20613843

  18. Structural model of the p14/SF3b155·branch duplex complex

    PubMed Central

    Schellenberg, Matthew J.; Dul, Erin L.; MacMillan, Andrew M.

    2011-01-01

    Human p14 (SF3b14), a component of the spliceosomal U2 snRNP, interacts directly with the pre-mRNA branch adenosine within the context of the bulged duplex formed between the pre-mRNA branch region and U2 snRNA. This association occurs early in spliceosome assembly and persists within the fully assembled spliceosome. Analysis of the crystal structure of a complex containing p14 and a peptide derived from p14-associated SF3b155 combined with the results of cross-linking studies has suggested that the branch nucleotide interacts with a pocket on a non-canonical RNA binding surface formed by the complex. Here we report a structural model of the p14•bulged duplex interaction based on a combination of X-ray crystallography of an adenine p14/SF3b155 peptide complex, biochemical comparison of a panel of disulfide cross-linked protein–RNA complexes, and small-angle X-ray scattering (SAXS). These studies reveal specific recognition of the branch adenosine within the p14 pocket and establish the orientation of the bulged duplex RNA bound on the protein surface. The intimate association of one surface of the bulged duplex with the p14/SF3b155 peptide complex described by this model buries the branch nucleotide at the interface and suggests that p14•duplex interaction must be disrupted before the first step of splicing. PMID:21062891

  19. A summary of staphylococcal C-terminal SH3b_5 cell wall binding domains.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Staphylococcal peptidoglycan hydrolases are a potential new source of antimicrobials. A large subset of these proteins contain a C-terminal SH3b_5 cell wall binding domain that has been shown for some to be essential for accurate cell wall recognition and subsequent staphylolytic activity, propert...

  20. 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.

  1. 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

  2. 17 CFR 240.3b-6 - Liability for certain statements by issuers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Liability for certain... Under the Securities Exchange Act of 1934 Definitions § 240.3b-6 Liability for certain statements by... proved oil and gas reserves as set forth in paragraphs 30-34 of Statement of Financial...

  3. 16 CFR 1500.14 - Products requiring special labeling under section 3(b) of the act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Products requiring special labeling under section 3(b) of the act. 1500.14 Section 1500.14 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS § 1500.14...

  4. [Modulation of Fcgamma and C3b receptor expression by marine bioglycans in mouse splenocytes].

    PubMed

    Zaporozhets, T S

    2003-01-01

    Investigation of polysacharide immunomodulators of marine origin was performed--mitilane, alpha-1,4;1,6-D-glucane, isolated from midia Crenomytilus grayanus, and translam--beta-1,3;1,6-D-glucane isolated from marine algae Laminaria cichorioides were compared. Mechanisms of phagocytes cells activation were investigated. Dose-dependent ability of investigated bioglycanes to facilitate Fc gamma R [symbol: see text] C3bR expression at mice splenocytes was demonstrated in vivo and in vitro. The effect depended on immunomodulator type, incubation conditions, dose, period of incubation in vitro and by splenocytes population used for Fc gamma R and C3bR identification. It was shown that C3bR expression was more enhanced by immunomodulators than Fc gamma R expression. For Fc gamma R induction on lymphocytes membranes the presence of phagocytes cell (macrophages and neutrophils) is obligatory. Mitilane, containing alpha-1,4;1,6-D-glucane and some amount of protein is more effective in stimulation of membrane receptors expression than translam--beta-1,3;1,6-D-glucane. The results of investigation demonstrates the possibility to use marine bioglicanes as activators of Fc gamma R and C3bR activity, that is the base for control of pathological processes, related to immune system. PMID:12914116

  5. 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

  6. Complement Evasion by Borrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

    PubMed Central

    Alitalo, Antti; Meri, Taru; Rämö, Lasse; Jokiranta, T. Sakari; Heikkilä, Tero; Seppälä, Ilkka J. T.; Oksi, Jarmo; Viljanen, Matti; Meri, Seppo

    2001-01-01

    The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation. PMID:11349031

  7. The Metal Centers of Particulate Methane Monooxygenase from Methylosinus trichosporium OB3b

    SciTech Connect

    Hakemian,A.; Kondapalli, K.; Telser, J.; Hoffman, B.; Stemmler, T.; Rosenzweig, A.

    2008-01-01

    Particulate methane monooxygenase (pMMO) is a membrane-bound metalloenzyme that oxidizes methane to methanol in methanotrophic bacteria. The nature of the pMMO active site and the overall metal content are controversial, with spectroscopic and crystallographic data suggesting the presence of a mononuclear copper center, a dinuclear copper center, a trinuclear center, and a diiron center or combinations thereof. Most studies have focused on pMMO from Methylococcus capsulatus (Bath). pMMO from a second organism, Methylosinus trichosporium OB3b, has been purified and characterized by spectroscopic and crystallographic methods. Purified M. trichosporium OB3b pMMO contains 2 copper ions per 100 kDa protomer. Electron paramagnetic resonance (EPR) spectroscopic parameters indicate that type 2 Cu(II) is present as two distinct species. Extended X-ray absorption fine structure (EXAFS) data are best fit with oxygen/nitrogen ligands and reveal a Cu-Cu interaction at 2.52 Angstroms. Correspondingly, X-ray crystallography of M. trichosporium OB3b pMMO shows a dinuclear copper center, similar to that observed previously in the crystal structure of M. capsulatus (Bath) pMMO. There are, however, significant differences between the pMMO structures from the two organisms. A mononuclear copper center present in M. capsulatus (Bath) pMMO is absent in M. trichosporium OB3b pMMO, whereas a metal center occupied by zinc in the M. capsulatus (Bath) pMMO structure is occupied by copper in M. trichosporium OB3b pMMO. These findings extend previous work on pMMO from M. capsulatus (Bath) and provide new insight into the functional importance of the different metal centers.

  8. The metal centers of particulate methane monooxygenase from Methylosinus trichosporium OB3b.

    PubMed

    Hakemian, Amanda S; Kondapalli, Kalyan C; Telser, Joshua; Hoffman, Brian M; Stemmler, Timothy L; Rosenzweig, Amy C

    2008-07-01

    Particulate methane monooxygenase (pMMO) is a membrane-bound metalloenzyme that oxidizes methane to methanol in methanotrophic bacteria. The nature of the pMMO active site and the overall metal content are controversial, with spectroscopic and crystallographic data suggesting the presence of a mononuclear copper center, a dinuclear copper center, a trinuclear center, and a diiron center or combinations thereof. Most studies have focused on pMMO from Methylococcus capsulatus (Bath). pMMO from a second organism, Methylosinus trichosporium OB3b, has been purified and characterized by spectroscopic and crystallographic methods. Purified M. trichosporium OB3b pMMO contains approximately 2 copper ions per 100 kDa protomer. Electron paramagnetic resonance (EPR) spectroscopic parameters indicate that type 2 Cu(II) is present as two distinct species. Extended X-ray absorption fine structure (EXAFS) data are best fit with oxygen/nitrogen ligands and reveal a Cu-Cu interaction at 2.52 A. Correspondingly, X-ray crystallography of M. trichosporium OB3b pMMO shows a dinuclear copper center, similar to that observed previously in the crystal structure of M. capsulatus (Bath) pMMO. There are, however, significant differences between the pMMO structures from the two organisms. A mononuclear copper center present in M. capsulatus (Bath) pMMO is absent in M. trichosporium OB3b pMMO, whereas a metal center occupied by zinc in the M. capsulatus (Bath) pMMO structure is occupied by copper in M. trichosporium OB3b pMMO. These findings extend previous work on pMMO from M. capsulatus (Bath) and provide new insight into the functional importance of the different metal centers. PMID:18540635

  9. CXCR3A contributes to the invasion and metastasis of gastric cancer cells.

    PubMed

    Yang, Chenggang; Zheng, Wanlei; Du, Wenfeng

    2016-09-01

    CXCR3, belonging to CXC chemokine receptors, has been identified to be overexpressed in various kinds of tumors. There are three mRNA variants of CXCR3 (CXCR3A, CXCR3B and CXCR3alt) in human cells. The functions of major CXCR3 isoforms (CXCR3A, CXCR3B) have been reported in some tumors including prostate and breast cancer. However, the effects of CXCR3A and CXCR3B on gastric cancer cell progression remain unknown. The present investigation found that CXCR3A mRNA level was upregulated but CXCR3B mRNA level was downregulated in gastric cancer cells and tissues. In vitro growth analysis showed that CXCR3A acted as a positive mediator in regulating cell growth, whereas CXCR3B exerted the opposite effect. In vitro invasion and migration assays showed that CXCL10 promoted gastric cancer cell invasion and migration via CXCR3A, but not CXCR3B. Moreover, knockdown of CXCR3A inhibited cell growth and metastasis in vivo. Additionally, CXCR3A knockdown attenuated matrix metalloproteinase (MMP)‑13 and IL‑6 expression, and reduced ERK1/2 activation. Together, these data suggest that CXCR3A contributes to the growth, invasion and metastasis of gastric cancer cells in vitro and in vivo, and thus may be a key mediator of gastric cancer progression. PMID:27461521

  10. 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.

  11. 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}.

  12. HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power—an intermediate phenotype for alcoholism and co-morbid behaviors

    PubMed Central

    Ducci, Francesca; Enoch, Mary-Anne; Yuan, Qiaoping; Shen, Pei-Hong; White, Kenneth V.; Hodgkinson, Colin; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2009-01-01

    Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, Plains American Indians (PI), has shown a suggestive linkage peak for alpha power at the 5-HT3R locus. We tested whether genetic variation within the HTR3A and HTR3B genes influences vulnerability to AUD with comorbid ASPD (AUD + ASPD) and moderates alpha power. Our study included three samples: 284 criminal alcoholic Finnish Caucasians and 234 controls; two independent community-ascertained samples with resting EEG recordings: a predominantly Caucasian sample of 191 individuals (Bethesda) and 306 PI. In the Finns, an intronic HTR3B SNP rs3782025 was associated with AUD + ASPD (P = .004). In the Bethesda sample, the same allele predicted lower alpha power (P = 7.37e-5). Associations between alpha power and two other HTR3B SNPs were also observed among PI (P = .03). One haplotype in the haplotype block at the 3′ region of the gene that included rs3782025 was associated with AUD + ASPD in the Finns (P = .02) and with reduced alpha power in the Bethesda population (P = .00009). Another haplotype in this block was associated with alpha power among PI (P = .03). No associations were found for HTR3A. Genetic variation within HTR3B may influence vulnerability to develop AUD with comorbid ASPD. 5-HT3R might contribute to the imbalance between excitation and inhibition that characterize the brain of alcoholics. PMID:19185213

  13. HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power--an intermediate phenotype for alcoholism and co-morbid behaviors.

    PubMed

    Ducci, Francesca; Enoch, Mary-Anne; Yuan, Qiaoping; Shen, Pei-Hong; White, Kenneth V; Hodgkinson, Colin; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2009-02-01

    Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, Plains American Indians (PI), has shown a suggestive linkage peak for alpha power at the 5-HT3R locus. We tested whether genetic variation within the HTR3A and HTR3B genes influences vulnerability to AUD with comorbid ASPD (AUD+ASPD) and moderates alpha power. Our study included three samples: 284 criminal alcoholic Finnish Caucasians and 234 controls; two independent community-ascertained samples with resting EEG recordings: a predominantly Caucasian sample of 191 individuals (Bethesda) and 306 PI. In the Finns, an intronic HTR3B SNP rs3782025 was associated with AUD+ASPD (P=.004). In the Bethesda sample, the same allele predicted lower alpha power (P=7.37e(-5)). Associations between alpha power and two other HTR3B SNPs were also observed among PI (P=.03). One haplotype in the haplotype block at the 3' region of the gene that included rs3782025 was associated with AUD+ASPD in the Finns (P=.02) and with reduced alpha power in the Bethesda population (P=.00009). Another haplotype in this block was associated with alpha power among PI (P=.03). No associations were found for HTR3A. Genetic variation within HTR3B may influence vulnerability to develop AUD with comorbid ASPD. 5-HT3R might contribute to the imbalance between excitation and inhibition that characterize the brain of alcoholics. PMID:19185213

  14. 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

  15. Dieckol, isolated from Ecklonia stolonifera, induces apoptosis in human hepatocellular carcinoma Hep3B cells.

    PubMed

    Yoon, Jin-Soo; Kasin Yadunandam, Anandam; Kim, Soon-Jin; Woo, Hee-Chul; Kim, Hyeung-Rak; Kim, Gun-Do

    2013-07-01

    Phlorotannins have been reported to demonstrate several biological properties, including antioxidant activity, and activities useful in the treatment of diabetic complications and in chemoprevention of several vascular diseases. In this study, we focused on the apoptosis induced by dieckol, a marine algal phlorotannin isolated from Ecklonia stolonifera, on human hepatocellular carcinoma (HCC) Hep3B cells. Dieckol reduced the numbers of viable cells and increased the numbers of apoptotic cells in a dose-dependent manner. Immunoblotting analysis revealed that dieckol increased the expression levels of cleaved caspases-3, 7, 8, and 9, and cleaved poly(ADP-ribose) polymerase. Dieckol increased the permeability of mitochondrial membranes and the release of cytochrome c from mitochondria into the cytosol with apoptosis-inducing factor. In addition, dieckol induced increased expression of truncated Bid and Bim. The results indicate that dieckol induces apoptosis via the activation of both death receptor and mitochondrial-dependent pathways in HCC Hep3B cells. PMID:23054486

  16. A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

    PubMed Central

    Karmatsky, Arseny A; Rusinov, Gennady L; Charushin, Valery N

    2015-01-01

    Summary A short and robust approach for the synthesis of 2-(hetero)aryl substituted thieno[2,3-b]indoles from easily available 1-alkylisatins and acetylated (hetero)arenes has been advanced. The two-step procedure includes the “aldol-crotonic” type of condensation of the starting materials, followed by treatment of the intermediate 3-(2-oxo-2-(hetero)arylethylidene)indolin-2-ones with Lawesson’s reagent. The latter process involves two sequential reactions, namely reduction of the C=C ethylidene double bond of the intermediate indolin-2-ones followed by the Paal–Knorr cyclization, thus affording tricyclic thieno[2,3-b]indoles. PMID:26199654

  17. 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

  18. Rodriguez syndrome with SF3B4 mutation: a severe form of Nager syndrome?

    PubMed

    McPherson, Elizabeth; Zaleski, Christina; Ye, Zhan; Lin, Simon

    2014-07-01

    We report on the findings of a novel heterozygous de novo SF3B4 mutation in a long-surviving patient with clinical features of Rodriguez syndrome including severe acrofacial dysostosis, phocomelia with pre- and post-axial limb defects, fibular agenesis, rib, and shoulder girdle anomalies. Since SF3B4 mutations have been recently associated with Nager syndrome, this suggests that at least some cases of Rodriguez syndrome are either allelic to or represent unusually severe manifestations of Nager syndrome. Although clinical overlap is obvious, this is somewhat surprising given the presumed autosomal recessive inheritance of Rodriguez syndrome. Investigation of other Rodriguez syndrome patients is needed to clarify the genetic mechanism and possible heterogeneity in patients with clinical features of Rodriguez syndrome. PMID:24715698

  19. 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.

  20. 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.

  1. Hepatitis E Virus Genotype 3 Diversity: Phylogenetic Analysis and Presence of Subtype 3b in Wild Boar in Europe

    PubMed Central

    Vina-Rodriguez, Ariel; Schlosser, Josephine; Becher, Dietmar; Kaden, Volker; Groschup, Martin H.; Eiden, Martin

    2015-01-01

    An increasing number of indigenous cases of hepatitis E caused by genotype 3 viruses (HEV-3) have been diagnosed all around the word, particularly in industrialized countries. Hepatitis E is a zoonotic disease and accumulating evidence indicates that domestic pigs and wild boars are the main reservoirs of HEV-3. A detailed analysis of HEV-3 subtypes could help to determine the interplay of human activity, the role of animals as reservoirs and cross species transmission. Although complete genome sequences are most appropriate for HEV subtype determination, in most cases only partial genomic sequences are available. We therefore carried out a subtype classification analysis, which uses regions from all three open reading frames of the genome. Using this approach, more than 1000 published HEV-3 isolates were subtyped. Newly recovered HEV partial sequences from hunted German wild boars were also included in this study. These sequences were assigned to genotype 3 and clustered within subtype 3a, 3i and, unexpectedly, one of them within the subtype 3b, a first non-human report of this subtype in Europe. PMID:26008708

  2. 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

  3. gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance.

    PubMed

    Charoy, Camille; Nawabi, Homaira; Reynaud, Florie; Derrington, Edmund; Bozon, Muriel; Wright, Kevin; Falk, Julien; Helmbacher, Françoise; Kindbeiter, Karine; Castellani, Valérie

    2012-09-20

    The Neurotrophic factor gdnf plays diverse developmental roles, supporting survival and also acting as a chemoattractant for axon and cell migration. We report that in the developing spinal cord, a focal source of gdnf is present in the floor plate (FP) where commissural axons cross the midline. Gdnf has no direct guidance properties but switches on the responsiveness of crossing commissural growth cones to the midline repellent Semaphorin3B by suppressing calpain-mediated processing of the Sema3B signaling coreceptor Plexin-A1. Analysis of single and double mutant mouse models indicates that although gdnf is the principal trigger of Sema3B midline repulsion, it acts with another FP cue, NrCAM. Finally, genetic and in vitro experiments provide evidence that this gdnf effect is RET independent and mediated by NCAM/GFRα1 signaling. This study identifies a regulator of midline crossing and reveals interplays between Semaphorin and gdnf signaling during axon guidance. PMID:22998873

  4. Inner shell excitation spectroscopy of transient molecules: HBS, HBO, and H3B3O3

    NASA Astrophysics Data System (ADS)

    Ennis, L. E.; Hitchcock, A. P.

    1999-08-01

    Inner shell electron energy spectroscopy (ISEELS) was used to study HBS, HBO, and H3B3O3, reactive, transient species generated in situ. The reaction of H2S with crystalline boron in a quartz tube was used to produce thioborine (HBS) at ˜1100 °C, and borine (HBO) at ˜1200 °C. The reaction of H2O vapor with crystalline boron in a quartz tube at ˜1200 °C was used to produce boroxine (H3B3O3). These species were identified from their inner shell excitation spectra and mass spectrometry. The B 1s, S 2s, and S 2p ISEEL spectra of HBS, and the B 1s and O 1s spectra of HBO and H3B3O3 are reported and analyzed with the help of GSCF3 ab initio calculations. A reaction scheme is proposed for the generation of HBO from the reaction of H2S and boron in a heated quartz tube.

  5. 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

  6. Energy transfer between rhodamine 3B and oxazine 4 in synthetic-saponite dispersions and films.

    PubMed

    Czímerová, A; Iyi, N; Bujdák, J

    2007-02-15

    The objective of this study was the investigation of energy transfer between the laser dyes rhodamine 3B (R3B) and oxazine 4 (Ox4) adsorbed on the surface of synthetic Sumecton saponite (Sum). The process of energy transfer was studied for both saponite dispersions and oriented solid films. The electronic properties, luminescence, and the energy transfer process were described by UV-vis absorption and fluorescence spectroscopy. For the efficiency of the energy transfer process, the concentrations of energy donor and acceptor components on a clay mineral surface were found to be essential. A side reaction of the molecular assembly formation reduced both the luminescence and energy-transfer yields, mainly due to fluorescence quenching. The quenching was more problematic for the solid film specimens, where an appropriate modification of the inorganic host with hydrophobic alkylammonium cations was used to achieve a higher luminescence. Due to the higher tendency of Ox4 to form nonluminescent aggregates at higher concentrations, the lowering of the Ox4 concentration further improved the luminescent properties of the films. In this case, the energy transfer occurring in the solid film from R3B to Ox4 was clearly proven. PMID:17118384

  7. A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation

    PubMed Central

    Fujimori, Hiroaki; Sato, Akira; Kikuhara, Sota; Wang, Junhui; Hirai, Takahisa; Sasaki, Yuka; Murakami, Yasufumi; Okayasu, Ryuichi; Masutani, Mitsuko

    2015-01-01

    A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both γ-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by γ-irradiation, including HP1β-, γH2AX- and Rad51-foci formation. DNMT3B RNAi impaired damage-dependent H2AX accumulation and showed a reduced level of γH2AX induction after γ-irradiation. DNMT3B interacted with HP1β in non-irradiated conditions, whereas irradiation abrogated the DNMT3B/HP1β complex but induced interaction between DNMT3B and H2AX. Consistent with radiosensitization, TP63, BAX, PUMA and NOXA expression was induced after γ-irradiation in DNMT3B knockdown cells. Together with the observation that H2AX overexpression canceled radiosensitization by DNMT3B RNAi, these results suggest that DNMT3B RNAi induced radiosensitization through impairment of damage-dependent HP1β foci formation and efficient γH2AX-induction mechanisms including H2AX accumulation. Enhanced radiosensitivity by DNMT3B RNAi was also observed in a tumor xenograft model. Taken together, the current study implies that comprehensive screening accompanied by a cluster analysis enabled the identification of radiosensitization targets. Downregulation of DNMT3B, one of the targets identified using this method, radiosensitizes cancer cells by disturbing multiple DNA damage responses. PMID:26667181

  8. A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation.

    PubMed

    Fujimori, Hiroaki; Sato, Akira; Kikuhara, Sota; Wang, Junhui; Hirai, Takahisa; Sasaki, Yuka; Murakami, Yasufumi; Okayasu, Ryuichi; Masutani, Mitsuko

    2015-01-01

    A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both γ-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by γ-irradiation, including HP1β-, γH2AX- and Rad51-foci formation. DNMT3B RNAi impaired damage-dependent H2AX accumulation and showed a reduced level of γH2AX induction after γ-irradiation. DNMT3B interacted with HP1β in non-irradiated conditions, whereas irradiation abrogated the DNMT3B/HP1β complex but induced interaction between DNMT3B and H2AX. Consistent with radiosensitization, TP63, BAX, PUMA and NOXA expression was induced after γ-irradiation in DNMT3B knockdown cells. Together with the observation that H2AX overexpression canceled radiosensitization by DNMT3B RNAi, these results suggest that DNMT3B RNAi induced radiosensitization through impairment of damage-dependent HP1β foci formation and efficient γH2AX-induction mechanisms including H2AX accumulation. Enhanced radiosensitivity by DNMT3B RNAi was also observed in a tumor xenograft model. Taken together, the current study implies that comprehensive screening accompanied by a cluster analysis enabled the identification of radiosensitization targets. Downregulation of DNMT3B, one of the targets identified using this method, radiosensitizes cancer cells by disturbing multiple DNA damage responses. PMID:26667181

  9. Diastereodivergent Catalysis Using Modularly Designed Organocatalysts: Synthesis of both cis- and trans-Fused Pyrano[2,3-b]pyrans.

    PubMed

    Huang, Huicai; Konda, Swapna; Zhao, John C-G

    2016-02-01

    Both enantiomers of cis- and trans-fused 3,4,4a,8a-tetrahydro-2H,5H-pyrano[2,3-b]pyran-7-carboxylates have been obtained in high diastereoselectivities and enantioselectivities from the same starting materials using a tandem inverse-electron-demand hetero-Diels-Alder/oxa-Michael reaction catalyzed by modularly designed organocatalysts (MDOs). Diastereodivergence was achieved in these reactions through the direct control of the stereochemistry of the bridgehead atoms of the fused ring using new MDOs self-assembled from both enantiomers of proline and cinchona alkaloid thiourea derivatives. PMID:26754923

  10. Evaluation of the TRMM 3B43 gridded precipitation estimates over Greece

    NASA Astrophysics Data System (ADS)

    Nastos, P. T.; Kapsomenakis, J.; Philandras, K. M.

    2016-03-01

    The goal of this study is the assessment of the reliability of the V7 TRMM (Tropical Rainfall Measuring Mission) 3B43 gridded precipitation estimates over Greece. The validation was carried out using gridded monthly precipitation data derived from 96 meteorological stations over the wider region of Greece. The TRMM 3B43 gridded estimates are on a calendar month temporal resolution and 0.25° × 0.25° spatial resolution concerning the 11-year period 1998-2008. In order to compare directly the TRMM 3B43 products with the rain gauge data, the latter were interpolated at the same spatial resolution grid with that of TRMM 3B43 (0.25° × 0.25°) and a new Greek gridded precipitation database (GGPDB) was constructed, using Kriging spatial interpolation method, taking into account the altitude of the meteorological stations. Further, to ensure reliable ground truth, we performed the comparison using data only over the 0.25° grid box when/where at least one reporting gauge is available. The annual and seasonal spatial distribution of the differences between the two datasets along with the spatial distribution of the correlation coefficients are presented and analyzed. The findings of the analysis revealed that the correlations between the two examined gridded databases (satellite and ground based) in winter were very high (r > 0.90) for the entire Greek domain with small exceptions over sparse data continental mountainous regions and restricted areas over north and south Aegean Sea. Regarding the other seasons, small correlations occur in the northern high altitude areas (Olympus Mt.) and the central/south mountainous Peloponnese. Besides, it is worth noting the remarkable small correlations over the eastern Aegean Sea and the Cyclades complex, in summer and the Cyclades complex in autumn. The TRMM 3B43 gridded data overestimate the precipitation over the Aegean and Ionian Sea, the coastal areas of Asia Minor and western Greece, in winter (> 50 mm), spring (> 25 mm) and

  11. Indolylmethylene benzo[h]thiazolo[2,3-b]quinazolinones: synthesis, characterization and evaluation of anticancer and antimicrobial activities.

    PubMed

    Gali, Rajitha; Banothu, Janardhan; Porika, Mahendar; Velpula, Ravibabu; Hnamte, Sairengpuii; Bavantula, Rajitha; Abbagani, Sadanandam; Busi, Siddhardha

    2014-09-01

    A series of novel 10-((1H-indol-3-yl)methylene)-7-aryl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9(6H)-ones (8a-t) have been synthesized in good yields by the reaction of benzo[h]quinazoline-2(1H)-thiones (4a-f) with 2-chloro-N-phenylacetamide (5) followed by Knoevenagel condensation with various indole-3-carbaldehydes (7a-d) under conventional method. All the synthesized compounds were characterized by spectral studies and screened for their in vitro anticancer and antimicrobial activities. Compound 8c has exhibited excellent activity against MCF-7 (breast cancer cell line) than the standard drug Doxorubicin. Compound 8d against both the cancer cell lines, 8q against MCF-7 and 8c, 8h against HepG2 have also shown good activity. Remaining compounds have shown moderate activity against both the cell lines. Antimicrobial activity revealed that, the compound 8q and 8t against Staphylococcus aureus and 8i, 8k, 8l, 8q &8t against Klebsiella pneumoniae have shown equipotent activity on comparing with the standard drug Streptomycin. Remaining compounds have shown significant antibacterial and comparable antifungal activities against all the tested microorganisms. PMID:25096298

  12. Pan-Serotype Diagnostic for Foot-and-Mouth Disease Using the Consensus Antigen of Nonstructural Protein 3B

    PubMed Central

    Van Dreumel, Alyssa K.; Michalski, Wojtek P.; McNabb, Leanne M.; Shiell, Brian J.; Singanallur, Nagendrakumar B.

    2015-01-01

    An amino acid consensus sequence for the seven serotypes of foot-and-mouth disease virus (FMDV) nonstructural protein 3B, including all three contiguous repeats, and its use in the development of a pan-serotype diagnostic test for all seven FMDV serotypes are described. The amino acid consensus sequence of the 3B protein was determined from a multiple-sequence alignment of 125 sequences of 3B. The consensus 3B (c3B) protein was expressed as a soluble recombinant fusion protein with maltose-binding protein (MBP) using a bacterial expression system and was affinity purified using amylose resin. The MBP-c3B protein was used as the antigen in the development of a competition enzyme-linked immunosorbent assay (cELISA) for detection of anti-3B antibodies in bovine sera. The comparative diagnostic sensitivity and specificity at 47% inhibition were estimated to be 87.22% and 93.15%, respectively. Reactivity of c3B with bovine sera representing the seven FMDV serotypes demonstrated the pan-serotype diagnostic capability of this bioreagent. The consensus antigen and competition ELISA are described here as candidates for a pan-serotype diagnostic test for FMDV infection. PMID:25788546

  13. 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

  14. 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.

  15. 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.

  16. miR-125b targets ARID3B in breast cancer cells.

    PubMed

    Akhavantabasi, Shiva; Sapmaz, Aysegul; Tuna, Serkan; Erson-Bensan, Ayse Elif

    2012-01-01

    Mounting evidence suggests involvement of deregulated microRNA (miRNA) expression during the complex events of tumorigenesis. Among such deregulated miRNAs in cancer, miR-125b expression is reported to be consistently low in breast cancers. In this study, we screened a panel of breast cancer cell lines (BCCLs) for miR-125b expression and detected decreased expression in 14 of 19 BCCLs. Due to the heterogeneity of breast cancers, MCF7 cells were chosen as a model system for ERBB2 independent breast cancers to restore miR-125b expression (MCF7-125b) to investigate the phenotypical and related functional changes. Earlier, miR-125b was shown to regulate cell motility by targeting ERBB2 in ERBB2 overexpressing breast cancer cells. Here we showed decreased motility and migration in miR-125b expressing MCF7 cells, independent of ERBB2. MCF7-125b cells demonstrated profoundly decreased cytoplasmic protrusions detected by phalloidin staining of filamentous actin along with decreased motility and migration behaviors detected by in vitro wound closure and transwell migration assays compared to empty vector transfected cells (MCF7-EV). Among possible numerous targets of miR-125b, we showed ARID3B (AT-rich interactive domain 3B) to be a novel target with roles in cell motility in breast cancer cells. When ARID3B was transiently silenced, the decreased cell migration was also observed. In light of these findings, miR-125b continues to emerge as an interesting regulator of cancer related phenotypes. PMID:22307404

  17. Variant allele of HSD3B1 increases progression to castration-resistant prostate cancer

    PubMed Central

    Nastiuk, Kent L.; Li, Jinliang; Gu, Jun; Wu, Ming; Zhang, Qimin; Lin, Hanqing; Wu, Denglong

    2016-01-01

    BACKGROUND 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which is a rate-limiting enzyme that catalyzes the conversion of adrenal-derived steroid dehydroepiandrosterone to DHT, may be a promising target for treating castration-resistant prostate cancer (CRPC). METHODS From 2004 to 2011, a total of 103 consecutive patients presenting with advanced prostate cancer were included in this study. All patients were treated with surgical castration as androgen deprivation therapy (ADT). Germline DNA was extracted from archived tissue from each patient and sequenced. PSA half-time (representing rate to PSA nadir after ADT), the incidence of, and time to CRPC occurrence, and cause-specific mortality rates were determined during the 3-10 year follow-up. The perioperative data and postoperative outcomes are compared. The patients were retrospectively analyzed for survival time. RESULTS Of the 103 patient samples analyzed, 18 harbored a heterozygous variant (1245C) HSD3B1 gene, while 85 patients were homozygous wild-type (1245A) for HSD3B1. The two groups were homogenous for age, PSA, Gleason and metastases rate preoperatively. The incidence of CRPC observed in the variant group was significantly higher than that of wild-type group (100% vs 64.7%, respectively; p = 0.003). Despite this higher incidence of CRPC, there were no significant differences in time to develop CRPC, or in cause-specific mortality. Further, neither PSA half-time, nor time to biochemical recurrence (rising PSA is only one of the defining characteristics of CRPC) were different between the variant and wild-type groups. CONCLUSION Prostate cancer patients who harbored the heterozygous variant HSD3B1 (1245C) are more likely to develop to CRPC, but do not have shorter time to biochemical recurrence, shorter survival time or higher mortality risk. PMID:25731771

  18. Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

    PubMed Central

    Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

  19. 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

  20. 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.

  1. Coulomb excitation of exotic nuclei at the R3B-LAND setup

    NASA Astrophysics Data System (ADS)

    Rossi, D. M.; Adrich, P.; Aksouh, F.; Alvarez-Pol, H.; Aumann, T.; Benlliure, J.; Böhmer, M.; Boretzky, K.; Casarejos, E.; Chartier, M.; Chatillon, A.; Cortina-Gil, D.; Datta Pramanik, U.; Emling, H.; Ershova, O.; Fernandez-Dominguez, B.; Geissel, H.; Gorska, M.; Heil, M.; Johansson, H.; Junghans, A.; Kiselev, O.; Klimkiewicz, A.; Kratz, J. V.; Kurz, N.; Labiche, M.; Le Bleis, T.; Lemmon, R.; Litvinov, Yu A.; Mahata, K.; Maierbeck, P.; Movsesyan, A.; Nilsson, T.; Nociforo, C.; Palit, R.; Paschalis, S.; Plag, R.; Reifarth, R.; Simon, H.; Sümmerer, K.; Wagner, A.; Walus, W.; Weick, H.; Winkler, M.

    2013-03-01

    Exotic Ni isotopes have been measured at the R3B-LAND setup at GSI in Darmstadt, using Coulomb excitation in inverse kinematics at beam energies around 500 MeV/u. As the experimental setup allows kinematically complete measurements, the excitation energy was reconstructed using the invariant mass method. The GDR and additional low-lying strength have been observed in 68Ni, the latter exhausting 4.1(1.9)% of the E1 energy-weighted sum rule. Also, the branching ratio for the non-statistical decay of the excited 68Ni nuclei was measured and amounts to 24(4)%.

  2. Chemical synthesis of Nd2Fe14B/Fe3B nanocomposites.

    PubMed

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

    2016-07-14

    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. PMID:27314879

  3. 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.

  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. 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.

  6. Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient

    PubMed Central

    Heyn, Holger; Vidal, Enrique; Sayols, Sergi; Sanchez-Mut, Jose V.; Moran, Sebastian; Medina, Ignacio; Sandoval, Juan; Simó-Riudalbas, Laia; Szczesna, Karolina; Huertas, Dori; Gatto, Sole; Matarazzo, Maria R.; Dopazo, Joaquin; Esteller, Manel

    2012-01-01

    The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable to analyze single loci were applied to determine epigenetic alterations in ICF patients. In the current study, we performed whole-genome bisulphite sequencing to assess alteration in DNA methylation at base pair resolution. Genome-wide we detected a decrease of methylation level of 42%, with the most profound changes occurring in inactive heterochromatic regions, satellite repeats and transposons. Interestingly, transcriptional active loci and ribosomal RNA repeats escaped global hypomethylation. Despite a genome-wide loss of DNA methylation the epigenetic landscape and crucial regulatory structures were conserved. Remarkably, we revealed a mislocated activity of mutant DNMT3B to H3K4me1 loci resulting in hypermethylation of active promoters. Functionally, we could associate alterations in promoter methylation with the ICF syndrome immunodeficient phenotype by detecting changes in genes related to the B-cell receptor mediated maturation pathway. PMID:22595875

  7. 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.

  8. 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.

  9. 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}.

  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. 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.

  12. 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

  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. 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.

  15. T3B — an experiment to measure the time structure of hadronic showers

    NASA Astrophysics Data System (ADS)

    Simon, F.; Soldner, C.; Weuste, L.

    2013-12-01

    The goal of the T3B experiment is the measurement of the time structure of hadronic showers with nanosecond precision and high spatial resolution together with the CALICE hadron calorimeter prototypes, with a focus on the use of tungsten as absorber medium. The detector consists of a strip of 15 scintillator cells individually read out by silicon photomultipliers (SiPMs) and fast oscilloscopes with a PC-controlled data acquisition system. The data reconstruction uses an iterative subtraction technique which provides a determination of the arrival time of each photon on the light sensor with sub-nanosecond precision. The calibration is based on single photon-equivalent dark pulses constantly recorded during data taking, automatically eliminating the temperature dependence of the SiPM gain. In addition, a statistical correction for SiPM afterpulsing is demonstrated. To provide the tools for a comparison of T3B data with GEANT4 simulations, a digitization routine, which accounts for the detector response to energy deposits in the detector, has been implemented.

  16. 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

  17. 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

  18. Methanotrophs, Methylosinus trichosporium OB3b, sMMO, and their application to bioremediation.

    PubMed

    Sullivan, J P; Dickinson, D; Chase, H A

    1998-01-01

    One of the most problematic groups of the USEPA and EU priority pollutants are the halogenated organic compounds. These substances have a wide range of industrial applications, such as solvents and cleaners. Inadequate disposal techniques and accidental spillages have led to their detection in soil, groundwater, and river sediments. Persistence of these compounds in the environment has resulted from low levels of biodegradation due to chemical structural features that preclude or retard biological attack. Research has indicated the idea that treatment systems based on methanotrophic co-metabolic transformation may be a cost-effective and efficient alternative to physical methods because of the potential for high transformation rates, the possibility of complete compound degradation without the formation of toxic metabolites, applicability to a broad spectrum of compounds, and the use of a widely available and inexpensive growth substrate. A substantial amount of work concerning methanotrophic cometabolic transformations has been carried out using the soluble form of methane monooxygenase (sMMO) from the obligate methanotroph Methylosinus trichosporium OB3b. This NADH-dependent monooxygenase is derepressed when cells are grown under copper stress. sMMO has a wider specificity than the particulate form. sMMO has been shown to degrade trichloroethylene (TCE) at a rate of at least one order of magnitude faster than obtained with other mixed and pure cultures, suggesting it has a wider application to bioremediation. Furthermore, sMMO catalyzes an unusually wide range of oxidation reactions, including the hydroxylation of alkanes, epoxidation of alkenes, ethers, halogenated methanes, cyclic and aromatic compounds including compounds, that are resistant to degradation in the environment. However, the practical application of methantrophs and Methylosinus trichosporium OB3b to the treatment of chlorinated organics has met with mixed success. Although oxidation rates are

  19. 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.

  20. SEMA3B improves the survival of patients with esophageal squamous cell carcinoma by upregulating p53 and p21.

    PubMed

    Tang, Hong; Wu, Yufeng; Liu, Ming; Qin, Yanru; Wang, Haiying; Wang, Lili; Li, Shaomei; Zhu, Hui; He, Zheng; Luo, Junpeng; Wang, Hongyan; Wang, Qiming; Luo, Suxia

    2016-08-01

    As one of the most common malignancies, esophageal squamous cell carcinoma (ESCC) is ranked as the sixth leading cause of cancer-related death worldwide. In our previous study, by employing cDNA microarray analysis, semaphorin 3B (SEMA3B) was found to be significantly downregulated in ESCC. In the present study, SEMA3B downregulation at the mRNA level was found in 34 of 60 primary ESCCs (56.7%) and in 6 of 9 ESCC cell lines (66.7%) by transcription-polymerase chain reaction (RT-PCR). Moreover, immunohistochemical (IHC) staining of SEMA3B in a tissue microarray further indicated that downregulated expression of SEMA3B protein was found in 125 of 222 (56.3%) ESCC cases and downregulation of SEMA3B protein was significantly correlated with lymph node metastasis (P=0.000), advanced clinicopathological stage (P=0.001) and poor disease-specific survival (P=0.017) of ESCC patients. In addition, functional studies demonstrated that the SEMA3B gene could suppress the tumorigenic ability of ESCC cells and cell motility. Furthermore, it was found that by upregulating p53 and p21 expression and inhibiting Akt (Ser473) phosphorylation, SEMA3B could induce cell cycle arrest at G1/S phase. Taken together, our results suggest that SEMA3B may be an important tumor-suppressor gene in the malignant progression of ESCC, as well as a valuable prognostic marker for ESCC patients. PMID:27349960

  1. 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

    ... 2009-24-11, Amendment 39-16103 (74 FR 62481, November 30, 2009). That AD requires removing from service... Register published on April 11, 2000 (65 FR 19477-78). Examining the AD Docket You may examine the AD... Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant...

  2. 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

  3. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation

    PubMed Central

    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

  4. 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

  5. TDPAC Study of the Intermetallic Compound HfCo3B2

    NASA Astrophysics Data System (ADS)

    Yaar, I.; Halevy, I.; Salhov, S.; Caspi, E. N.; Dubman, M.; Kahane, S.; Berant, Z.

    2004-11-01

    The electronic properties of the intermetallic compound HfCo3B2 were investigated using combined TDPAC measurements and first principles LAPW calculations. The V zz value at the hafnium site is determined from dominant positive p p contribution, with less than 20%, negative s d and d d contributions. Based on the calculated density of state (DOS) at 0 K, a band contribution ( γ band) of 7.26 (mJ/mol/K2) to the value of the electronic specific heat coefficient ( γ) was obtained. This relatively low γ band value is attributed to the hybridization between hafnium d-states, boron 2 p-states and cobalt 3 d-states, formed at the energy interval below E Fermi. This hybridization, together with the dip in the DOS around E Fermi, implies a possible reduction of the low temperature magnetic moment in this compound.

  6. Degradation of Trichloroethylene by Methanol-Grown Cultures of Methylosinus trichosporium OB3b PP358

    PubMed Central

    Fitch, M. W.; Speitel, G. E.; Georgiou, G.

    1996-01-01

    A soluble methane monooxygenase-constitutive mutant strain of Methylosinus trichosporium OB3b, strain PP358, was grown with methanol as the carbon source, and the kinetics of trichloroethylene (TCE) degradation were determined. PP358 exhibited high TCE degradation rates under both oxygen- and carbon-limiting conditions. The optimal pseudo first-order rate constant for TCE was comparable to the values measured for cells grown with methane. We found that growth under oxygen-limiting conditions results in increased accumulation of polyhydroxybutyrate, which in turn correlates with higher transformation capacities for TCE. It was also shown that methanol inhibits TCE degradation only at high concentrations. Thus, methanol-grown cultures of PP358 represent an efficient system for the biodegradation of chlorinated hydrocarbons. PMID:16535263

  7. [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

  8. 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.

  9. 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.

  10. 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.

  11. A PROGRADE, LOW-INCLINATION ORBIT FOR THE VERY HOT JUPITER WASP-3b

    SciTech Connect

    Tripathi, Anjali; Winn, Joshua N.; De Kleer, Katherine R.; Carter, Joshua A.; Johnson, John Asher; Cabrera, Nicole E.; Howard, Andrew W.; Halverson, Sam; Marcy, Geoffrey W.; Holman, Matthew J.; Esquerdo, Gilbert A.; Everett, Mark E. E-mail: jwinn@mit.ed

    2010-05-20

    We present new spectroscopic and photometric observations of the transiting exoplanetary system WASP-3. Spectra obtained during two separate transits exhibit the Rossiter-McLaughlin (RM) effect and allow us to estimate the sky-projected angle between the planetary orbital axis and the stellar rotation axis, {lambda} = 3.3{sup +2.5}{sub -4.4} deg. This alignment between the axes suggests that WASP-3b has a low orbital inclination relative to the equatorial plane of its parent star. During our first night of spectroscopic measurements, we observed an unexpected redshift briefly exceeding the expected sum of the orbital and RM velocities by 140 m s{sup -1}. This anomaly could represent the occultation of material erupting from the stellar photosphere, although it is more likely to be an artifact caused by moonlight scattered into the spectrograph.

  12. A3B5 photodiode sensors for low-temperature pyrometry

    NASA Astrophysics Data System (ADS)

    Sotnikova, Galina Y.; Aleksandrov, Sergey E.; Gavrilov, Gennadiy A.

    2011-05-01

    Mid-infrared immersion lens photodiodes developed at the Ioffe Institute have high spectral selectivity (λmax/▵λ~0.1...0.15) at different wavelengths -2.9, 3.3, 4.2 and 4.7 microns, the response time (up to 10-9s) and detectivity (D* ~ 109-1011, (cm√Hz)/W) being significantly higher than those of currently known detectors of thermal radiation[1].The analysis of the transfer function of the temperature sensors based on A3B5 photodiodes has shown that they permit implementing the methods of color and two-color pyrometry providing a significant decrease of the methodical error in optical temperature measurements associated with unknown values of object surface emissivity and uncontrollable changes in the environment transmission.

  13. 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.

  14. 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

  15. 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

  16. The Arctic Boundary Layer Expedition (ABLE-3B): July - August 1990

    NASA Technical Reports Server (NTRS)

    Harriss, R. C.; Wofsy, S. C.; Hoell, J. M., Jr.; 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.

  17. 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.

  18. Disruption reduces accuracy and P3b amplitudes in the attentional blink.

    PubMed

    Pincham, Hannah L; Szücs, Dénes

    2014-10-01

    In everyday life, distracting stimuli often interfere with daily tasks, and disrupt successful task performance. The attentional blink paradigm (a deficit in reporting the second target (T2) in a rapid stream of visual stimuli) allows for an investigation of disruption by rapidly appearing stimuli. Specifically, the magnitude of the attentional blink deficit can be manipulated by positioning relevant stimuli at strategic locations within the visual stream. The current study therefore designed and tested a disruption paradigm that aimed to reduce T2 accuracy using a disruptor stimulus. Electroencephalography was used to reveal the neural correlates of the effect. To that end, targets were defined by task-set colours. The item immediately preceding T2 appeared in a task-set colour (disrupted trials) or a different colour (non-disrupted trials). The results revealed that T2 accuracy was reduced on disrupted trials, and disruption appeared to be worse when T2 appeared inside the attentional blink window. The behavioural data were paralleled by the neural results. On trials where T2 appeared within the AB window and was correctly reported, T2-P3b amplitude (a neural correlate of working memory consolidation) was significantly depressed on disrupted trials compared with non-disrupted trials. Single trial plots of P3b amplitude confirmed a weaker neural trace for T2 on disrupted trials. These data indicate that the magnitude and neural signature of the attentional blink deficit is malleable, and can be influenced by non-target, task-relevant stimuli. PMID:25139528

  19. Streptococcus pyogenes Employs Strain-dependent Mechanisms of C3b Inactivation to Inhibit Phagocytosis and Killing of Bacteria.

    PubMed

    Agrahari, Garima; Liang, Zhong; Glinton, Kristofor; Lee, Shaun W; Ploplis, Victoria A; Castellino, Francis J

    2016-04-22

    Evasion of complement-mediated opsonophagocytosis enables group A Streptococcus pyogenes (GAS) to establish infection. Different strain-dependent mechanisms are employed by the host to accomplish this goal. In general, GAS inhibits the amplification of the complement cascade on its cell surface by facilitating the degradation of C3b, an opsonin, to an inactive product, inactivated C3b (iC3b), in a step catalyzed by factor I (FI) and its cofactor, factor H (FH), with or without the participation of human host plasmin (hPm). GAS recruits FH to its cell surface via FH receptors, which are transcriptionally controlled by the two-component cluster of virulence responder-sensor system. The manner in which FI-FH and hPm function together on GAS cells is unknown. Using GAS strain AP53, which strongly binds host human plasminogen/plasmin (hPg/hPm) directly via an hPg/hPm surface receptor (PAM), we show that both FI-FH and hPm sequentially cleave C3b. Whereas FI-FH proteolytically cleaves C3b into iC3b, PAM-bound hPm catalyzes cleavage of iC3b into multiple smaller peptides. Unlike AP53, GAS strain M23ND weakly binds FH and recruits hPg/hPm to its cell surface indirectly via fibrinogen bound to M-protein, M23. In this case, FH-FI cleaves C3b into iC3b, with negligible degradation of iC3b by hPm that is bound to fibrinogen on the cells. AP53 and M23ND display similar resistance to human neutrophil-mediated phagocytosis, which results in a corresponding high lethality in mice after injection of these cells. These results suggest that GAS utilizes diverse mechanisms to degrade C3b and thus to protect bacterial cells from the complement response of the host. PMID:26945067

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins.

    PubMed

    Gentzsch, Martina; Cui, Liying; Mengos, April; Chang, Xiu-Bao; Chen, Jey-Hsin; Riordan, John R

    2003-02-21

    ClC chloride channels are widely distributed in organisms across the evolutionary spectrum, and members of the mammalian family play crucial roles in cellular function and are mutated in several human diseases (Jentsch, T. J., Stein, V., Weinreich, F., and Zdebik, A. A. (2002) Physiol. Rev. 82, 503-568). Within the ClC-3, -4, -5 branch of the family that are intracellular channels, two alternatively spliced ClC-3 isoforms were recognized recently (Ogura, T., Furukawa, T., Toyozaki, T., Yamada, K., Zheng, Y. J., Katayama, Y., Nakaya, H., and Inagaki, N. (2002) FASEB J. 16, 863-865). ClC-3A resides in late endosomes where it serves as an anion shunt during acidification. We show here that the ClC-3B PDZ-binding isoform resides in the Golgi where it co-localizes with a small amount of the other known PDZ-binding chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator). Both channel proteins bind the Golgi PDZ protein, GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein). Interestingly, however, when overexpressed, GOPC, which is thought to influence traffic in the endocytic/secretory pathway, causes a large reduction in the amounts of both channels, probably by leading them to the degradative end of this pathway. ClC-3B as well as CFTR also binds EBP50 (ERM-binding phosphoprotein 50) and PDZK1, which are concentrated at the plasma membrane. However, only PDZK1 was found to promote interaction between the two channels, perhaps because they were able to bind to two different PDZ domains in PDZK1. Thus while small portions of the populations of ClC-3B and CFTR may associate and co-localize, the bulk of the two populations reside in different organelles of cells where they are expressed heterologously or endogenously, and therefore their cellular functions are likely to be distinct and not primarily related. PMID:12471024

  5. Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1.

    PubMed

    Kang, E S; Park, C W; Chung, J H

    2001-12-14

    Dnmt3b, a DNA methyltransferase, is essential for mammalian development potentially through its transcription repression activity. To comprehend the underlying regulatory mechanism of Dnmt3b, we isolated small ubiquitin-like modifier 1 (SUMO-1) and Ubc9 as Dnmt3b-interacting proteins using yeast two-hybrid screens. Deletion analysis and colocalization experiment demonstrated that Dnmt3b interacts with SUMO-1 and Ubc9 at its N-terminal region. We also confirmed the modification of Dnmt3b by SUMO-1 in vivo. These results suggest that sumoylation may constitute a regulation mechanism of Dnmt3b in vivo. PMID:11735126

  6. 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

  7. p62 sequestosome 1/light chain 3b complex confers cytoprotection on lung epithelial cells after hyperoxia.

    PubMed

    Liang, Xiaoliang; Wei, Shu-Quan; Lee, Seon-Jin; Fung, James K; Zhang, Meng; Tanaka, Akihiko; Choi, Augustine M K; Jin, Yang

    2013-04-01

    Lung epithelial cell death is a prominent feature of hyperoxic lung injury, and has been considered a very important underlying mechanism of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Here we report on a novel mechanism involved in epithelial cytoprotection and homeostasis after oxidative stress. p62 (sequestosome 1; SQSTM1) is a ubiquitously expressed cellular protein. It interacts with ubiquitinated proteins and autophagic marker light chain 3b (LC3b), thus mediating the degradation of selective targets. In this study, we explored the role of p62 in mitochondria-mediated cell death after hyperoxia. Lung alveolar epithelial cells demonstrate abundant p62 expression, and p62 concentrations are up-regulated by oxidative stress at both the protein and mRNA levels. The p62/LC3b complex interacts with Fas and truncated BID (tBID) physically. These interactions abruptly diminish after hyperoxia. The deletion of p62 robustly increases tBID and cleaved caspase-3, implying an antiapoptotic effect. This antiapoptotic effect of p62 is further confirmed by measuring caspase activities, cleaved poly ADP ribose polymerase, and cell viability. The deletion of the p62 PBI domain or the ubiquitin-associated domain both lead to elevated tBID, cleaved caspase-3, and significantly more cell death after hyperoxia. Moreover, p62 traffics in an opposite direction with LC3b after hyperoxia, leading to the dissociation of the p62/Cav-1/LC3b/BID complex. Subsequently, the LC3b-mediated lysosomal degradation of tBID is eliminated. Taken together, our data suggest that the p62/LC3b complex regulates lung alveolar epithelial cell homeostasis and cytoprotection after hyperoxia. PMID:23333919

  8. 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

  9. 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.

  10. Structural disorder in the paraelectric phase of the Fe3B7O13Br boracite

    NASA Astrophysics Data System (ADS)

    Shuvaeva, V. A.; Lysenko, K. A.; Antipin, M. Yu.

    2011-04-01

    A structural model of the cubic paraelectric phase of a Fe3B7O13Br crystal belonging to the boracite family has been developed using the data obtained by single-crystal X-ray diffraction with due regard for the results of extended X-ray absorption fine structure (EXAFS) spectroscopy. It has been shown that the best agreement between the data obtained by these two methods is achieved within a model assuming a disorder in the arrangement of both the Fe and Br atoms and a high degree of correlation of their displacements. It has been found that, during the phase transition from the rhombohedral ferroelectric phase to the cubic paraelectric phase, no significant transformation of the structure is observed on a local level. In this case, a change in the macroscopic symmetry occurs predominantly as a result of the variation in the set of possible spatial orientations of stable structural fragments, which is characteristic of order-disorder phase transitions.

  11. Development of MMRPC prototype for the NeuLAND detector of the R3B collaboration

    NASA Astrophysics Data System (ADS)

    Pramanik, U. Datta; Chakraborty, S.; Basu, P.; Basu, J.; Banerjee, P.; Bemmerer, D.; Bose, S.; Chatterjee, S.; Elekes, Z.; Kempe, M.; Leifels, Y.; Panja, J.; Mukherjee, A.; Rahaman, A.; Roy, S.; Simon, H.; Sobiella, M.; Stach, D.; Wagner, A.; Yakorev, D.

    2012-01-01

    A prototype of Multi-strip Multi-gap Resistive Plate chamber (MMRPC) with active area 40cm×20cm has been developed at SINP, Kolkata as a new Time-Of-Flight (TOF) system with timing resolution σt<120ps and position resolution σx˜0.58cm. The intention is to use multilayers of this type together with converter materials as a high energy neutron (1GeV>En>200MeV) TOF system for the R3B collaboration at the FAIR facility. The design of the detector elements is as follows: a double stack MMRPC with float glass plates and two gas gaps of 0.3 mm per stack. The response of this MMRPC has been studied with cosmic muons and γ-rays from a standard radioactive source (60Co) in coincidence with fast inorganic scintillators at SINP laboratory. Recently, response of developed MMRPC has been studied using pulsed electron beam at ELBE, FZD. The details of the MMRPC construction , experimental set-up for investigation of its response and first results are presented.

  12. Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice.

    PubMed

    Peixoto, Rui T; Wang, Wengang; Croney, Donyell M; Kozorovitskiy, Yevgenia; Sabatini, Bernardo L

    2016-05-01

    Some autistic individuals exhibit abnormal development of the caudate nucleus and associative cortical areas, suggesting potential dysfunction of cortico-basal ganglia (BG) circuits. Using optogenetic and electrophysiological approaches in mice, we identified a narrow postnatal period that is characterized by extensive glutamatergic synaptogenesis in striatal spiny projection neurons (SPNs) and a concomitant increase in corticostriatal circuit activity. SPNs during early development have high intrinsic excitability and respond strongly to cortical afferents despite sparse excitatory inputs. As a result, striatum and corticostriatal connectivity are highly sensitive to acute and chronic changes in cortical activity, suggesting that early imbalances in cortical function alter BG development. Indeed, a mouse model of autism with deletions in Shank3 (Shank3B(-/-)) shows early cortical hyperactivity, which triggers increased SPN excitatory synapse and corticostriatal hyperconnectivity. These results indicate that there is a tight functional coupling between cortex and striatum during early postnatal development and suggest a potential common circuit dysfunction that is caused by cortical hyperactivity. PMID:26928064

  13. Biquadratic coupling between two ordering parameters in 1:3 B-site ordered spinels

    NASA Astrophysics Data System (ADS)

    Kremenović, A.; Antic, B.

    2004-04-01

    The Letter presents an analysis of the order-disorder phase transition mechanism, Fd3¯m↔ P4332 , in 1:3 B-site ordered spinels, Li 1.33 xCo 2-2 xTi 1+0.67 xO 4 and Li 1-0.5 xFe 2.5 xMn 2-2 xO 4, by using the Landau's theory of phase transitions. Two ordering parameters were used to describe cation distribution: Q1 for cation distribution between tetrahedral and octahedral sites, and Q2 for cation distribution between two octahedral sites. Analysis of the topology of the order parameter vector space indicates biquadratic coupling between Q1 and Q2. For the Li 1.33 xCo 2-2 xTi 1+0.67 xO 4 ( x=0.50) in the low-temperature ferroelastic phase both ordering parameters differ from zero and they both influence on the spontaneous strain scalar values.

  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. 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.

  16. Energy Localization in the Ordered Condensed Systems: A 3 B Alloys With L12 Superstructure

    NASA Astrophysics Data System (ADS)

    Medvedev, N. N.; Starostenkov, M. D.; Potekaev, A. I.; Zakharov, P. V.; Markidonov, A. V.; Eremin, A. M.

    2014-07-01

    Energy localization in the ordered condensed systems is analyzed using А3В alloys with L12 superstructure. Using molecular dynamics, possible localization of phonon vibration energy in the aluminum sublattice and generation of a localized mode oscillating at a frequency belonging to the phonon spectrum energy gap and not representing a breather is considered for the ordered Pt3Al and Ni3Al alloys with L12 superstructure, which possess translational symmetry. Manifestations of anharmonicity in the atomic interactions and the relevant features of energy redistribution between sublattices of the ordered alloys are investigated. It is found out that in the ordered alloys of an A3B stoichiometry with L12 superstructure, whose phonon spectrum has a forbidden energy gap, vibrational energy can localize on the sublattice of B atoms. The alloys, found in a state of thermodynamic equilibrium at a certain temperature, are characterized by a local effect of spontaneous energy localization (the effect of energy redistribution between the lattices).

  17. 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).

  18. 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).

  19. Photoluminescence and thermoluminescence investigations of Ca3B2O6: Sm3+ phosphor

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

    Sm3+ doped Ca3B2O6 phosphors have been synthesized by combustion method. X-ray diffraction (XRD), photoluminescence (PL), UV-Vis spectroscopy and thermoluminescence (TL) have been used to study the structural, luminescence and optical properties of the phosphors. Under 400 nm excitation, the phosphor shows characteristic emission for Sm3+ ion (4G5/2 → 6Hj/2, j = 5, 7, 9 and 11) with the main orange-red emission peak at 600 nm corresponding to the 4G5/2 → 6H7/2 transition state of the Sm3+ ion. The optimum molar concentration and maximum critical distance between the Sm3+- Sm3+ ions were found to be 3 mol.% and 20.098 Å, respectively. The phosphor can be efficiently excited by near UV chips for their potential use in solid state lighting. The calculated CIE coordinates (0.60, 0.40) were found to be in the orange-red spectrum region. The thermoluminescence studies were carried out after irradiating the phosphor by gamma rays in the dose range of 10-5000 Gy. The glow peak was deconvoluted by the TLAnal program and the kinetic parameters associated with the deconvoluted peaks were evaluated.

  20. 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.

  1. 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.

  2. 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.

  3. Kinetics of chlorinated hydrocarbon degradation by Methylosinus trichosporium OB3b and toxicity of trichloroethylene.

    PubMed Central

    Oldenhuis, R; Oedzes, J Y; van der Waarde, J J; Janssen, D B

    1991-01-01

    The kinetics of the degradation of trichloroethylene (TCE) and seven other chlorinated aliphatic hydrocarbons by Methylosinus trichosporium OB3b were studied. All experiments were performed with cells grown under copper stress and thus expressing soluble methane monooxygenase. Compounds that were readily degraded included chloroform, trans-1,2-dichloroethylene, and TCE, with Vmax values of 550, 330, and 290 nmol min-1 mg of cells-1, respectively. 1,1-Dichloroethylene was a very poor substrate. TCE was found to be toxic for the cells, and this phenomenon was studied in detail. Addition of activated carbon decreased the acute toxicity of high levels of TCE by adsorption, and slow desorption enabled the cells to partially degrade TCE. TCE was also toxic by inactivating the cells during its conversion. The degree of inactivation was proportional to the amount of TCE degraded; maximum degradation occurred at a concentration of 2 mumol of TCE mg of cells-1. During conversion of [14C]TCE, various proteins became radiolabeled, including the alpha-subunit of the hydroxylase component of soluble methane monooxygenase. This indicated that TCE-mediated inactivation of cells was caused by nonspecific covalent binding of degradation products to cellular proteins. Images PMID:2036023

  4. Synthesis of Thieno[2,3-b]thiophene Containing Bis-Heterocycles-Novel Pharmacophores

    PubMed Central

    Mabkhot, Yahia Nasser; Barakat, Assem; Al-Majid, Abdullah Mohammed; Choudhary, Muhammad Iqbal

    2013-01-01

    Thioenethiophene derivatives represent an important class of compounds with diverse biological activities. We describe here the synthesis of a new series of thieno[2,3-b]thiophene containing bis-heterocyclic compounds 3–7. All the compounds were evaluated for their in vitro antioxidant potential, α-glucosidase and β-glucuronidase inhibiton and anticancer activity against PC-3 cell lines. Compounds 2b (IC50 = 1.3 ± 0.2 μM), 5a (IC50 = 2.3 ± 0.4 μM) and 5b (IC50 = 8.7 ± 0.1 μM) showed a potent inhibition of β-glucuronidase enzyme, more active than the standard d-saccharic acid 1,4-lactone (IC50 = 45.8 ± 2.5 μM). Compounds 5a (IC50 = 22.0 ± 0.3 μM) and 5b (IC50 = 58.4 ± 1.2 μM) were also found to be potent α-glucosidase inhibitors as compared to standard drug (acarbose, IC50 = 841 ± 1.7 μM). PMID:23481634

  5. Validation of the TRMM Multi Satellite Rainfall Product 3B42 and estimation of scavenging coefficients for (131)I and (137)Cs using TRMM 3B42 rainfall data.

    PubMed

    Shrivastava, R; Dash, S K; Hegde, M N; Pradeepkumar, K S; Sharma, D N

    2014-12-01

    The TRMM rainfall product 3B42 is compared with rain gauge observations for Kaiga, India on monthly and seasonal time scales. This comparison is carried out for the years 2004-2007 spanning four monsoon seasons. A good correlation is obtained between the two data sets however; magnitude wise, the cumulative precipitation of the satellite product on monthly and seasonal time scales is deficient by almost 33-40% as compared to the rain gauge data. The satellite product is also compared with APHRODITE's Monsoon Asia data set on the same time scales. This comparison indicates a much better agreement since both these data sets represent an average precipitation over the same area. The scavenging coefficients for (131)I and (137)Cs are estimated using TRMM 3B42, rain gauge and APHRODITE data. The values obtained using TRMM 3B42 rainfall data compare very well with those obtained using rain gauge and APHRODITE data. PMID:25222937

  6. Deletion of the late cornified envelope (LCE) 3B and 3C genes as a susceptibility factor for psoriasis

    PubMed Central

    de Cid, Rafael; Riveira-Munoz, Eva; Zeeuwen, Patrick L.J.M.; Robarge, Jason; Liao, Wilson; Dannhauser, Emma N.; Giardina, Emiliano; Stuart, Philip E.; Nair, Rajan; Helms, Cynthia; Escaramís, Georgia; Ballana, Ester; Martín-Ezquerra, Gemma; den Heijer, Martin; Kamsteeg, Marijke; Joosten, Irma; Eichler, Evan E.; Lázaro, Conxi; Pujol, Ramón M.; Armengol, Lluís; Abecasis, Gonçalo; Elder, James T.; Novelli, Giuseppe; Armour, John A.L.; Kwok, Pui; Bowcock, Anne; Schalkwijk, Joost; Estivill, Xavier

    2011-01-01

    Psoriasis is a common inflammatory skin disease with a prevalence of 2% to 3% in Caucasians1. In a genome-wide search for copy number variants (CNV) using a sample pooling approach we have identified a deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster2. The absence of LCE3B and LCE3C (LCE3C-LCE3B-del) is significantly associated (p=1.38E-08) with risk of psoriasis in 2,831 samples from Spain, The Netherlands, Italy and the USA, and in a family-based study (p=5.4E-04). LCE3C-LCE3B-del is tagged by rs4112788 (r2=0.93), which is also strongly associated with psoriasis (p<6.6E-09). LCE3C-LCE3B-del shows epistatic effects with the HLA-Cw6 allele on the development of psoriasis in Dutch samples, and multiplicative effects in the other samples. LCE expression can be induced in normal epidermis by skin barrier disruption and is strongly expressed in psoriatic lesions, suggesting that compromised skin barrier function plays a role in psoriasis susceptibility. PMID:19169253

  7. Quantification of gene-specific methylation of DNMT3B and MTHFR using sequenom EpiTYPER®.

    PubMed

    Ho, Vikki; Ashbury, Janet E; Taylor, Sherryl; Vanner, Stephen; King, Will D

    2016-03-01

    Among 272 patients undergoing a screening colonoscopy, DNA methylation of DNMT3B and MTHFR, genes encoding enzymes critical to one-carbon metabolism, was quantified in blood leukocytes using Sequenom EpiTYPER®. DNA methylation was quantified in 66 and 28 CpG sites of DNMT3B and MTHFR respectively, and conceptualized using two approaches. First, measures representing average methylation across all CpG sites were created. Second, unsupervised principal component (PC) analysis was used as a pattern derivation and data-reduction approach, to develop two summary variables (PC1 and PC2). These two summary variables represented methylation around the transcription start site (PC1) and in the gene-coding area (PC2) for both DNMT3B and MTHFR. The data contained in this article presents the variation of methylation levels for individual CpG sites within the DNMT3B and MTHFR genes and possible correlations uncovered using PC analysis. The data are related to the research article "Gene-specific DNA methylation of DNMT3B and MTHFR and colorectal adenoma risk" in Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. PMID:26759827

  8. 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

  9. 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

  10. Raman diagnostics of new types of A3B2X9 layered crystals

    NASA Astrophysics Data System (ADS)

    Vakulenko, Olegh V.; Gubanov, Victor O.; Kun, Stepan V.; Motsnyi, Fedir V.; Peresh, Eugen Y.; Terekhov, Volodymyr A.

    1998-04-01

    Vibrational spectra of layered crystals Rb3Bi2Br9, Rb3Bi2I9, Cs3Bi2I9 were investigated by the method of Raman spectroscopy at 293 K and 100 K. The distribution of vibrational modes by symmetric type was considered for molecular ion [B2X9]3-, for layered packet and for the whole crystal. It is shown that the approximate vibrational forms of the molecule B2X9 and the ions [B2X9]3- can be obtained unambiguously using on the symmetry considerations only. The condition is imposed that the vibrational modes in addition to their classification by the symmetry types allow resolution to the quasivalent and quasideformational ones which differ significantly in frequencies. The forms of the normal vibrations of [B2X9]3- are consistent with the vibration forms of the layer packet, whereas the shape of the vibration forms of the given symmetry type for the whole crystal coincides with the shapes of the normal vibration forms of two adjacent elementary packets which have the same or contrary phases. The correlation diagram is built up allows to establish correspondence between the modes of the elementary layer packet and the fundamental vibration modes of the crystal lattice which are combined into the Davydov doublets. The analysis of the obtained experimental results for the A3B2X9 crystals was carried out. It was obtained that at the modification of the chemical composition of the compound by isovalent substitution, the slight change in the vibration forms does not actually effect the power constant, and the frequencies are modified only due to the atoms mass change.

  11. 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.

  12. Formate dehydrogenase from the methane oxidizer Methylosinus trichosporium OB3b.

    PubMed Central

    Yoch, D C; Chen, Y P; Hardin, M G

    1990-01-01

    Formate dehydrogenase (NAD+ dependent) was isolated from the obligate methanotroph Methylosinus trichosporium OB3b. When the enzyme was isolated anaerobically, two forms of the enzyme were seen on native polyacrylamide gels, DE-52 cellulose and Sephacryl S-300 columns; they were approximately 315,000 and 155,000 daltons. The enzyme showed two subunits on sodium dodecyl sulfate-polyacrylamide gels. The Mr of the alpha-subunit was 53,800 +/- 2,800, and that of the beta-subunit was 102,600 +/- 3,900. The enzyme (Mr 315,000) was composed of these subunits in an apparent alpha 2 beta 2 arrangement. Nonheme iron was present at a concentration ranging from 11 to 18 g-atoms per mol of enzyme (Mr 315,000). Similar levels of acid-labile sulfide were detected. No other metals were found in stoichiometric amounts. When the enzyme was isolated aerobically, there was no cofactor requirement for NAD reduction; however, when isolated anaerobically, activity was 80 to 90% dependent on the addition of flavin mononucleotide (FMN) to the reaction mixture. Furthermore, the addition of formate to an active, anoxic solution of formate dehydrogenase rapidly inactivated it in the absence of an electron acceptor; this activity could be reconstituted approximately 85% by 50 nM FMN. Flavin adenine dinucleotide could not replace FMN in reconstituting enzyme activity. The Kms of formate dehydrogenase for formate, NAD, and FMN were 146, 200, and 0.02 microM, respectively. "Pseudomonas oxalaticus" formate dehydrogenase, which has physical characteristics nearly identical to those of the M. trichosporium enzyme, was also shown to be inactivated under anoxic conditions by formate and reactivated by FMN. The evolutionary significance of this similarity is discussed. Images PMID:2376564

  13. The discovery of low-mass pre-main-sequence stars in Cepheus OB3b

    NASA Astrophysics Data System (ADS)

    Pozzo, M.; Naylor, T.; Jeffries, R. D.; Drew, J. E.

    2003-05-01

    We report the discovery of a low-mass pre-main-sequence (PMS) stellar population in the younger subgroup of the Cepheus OB3 association, Cep OB3b, using UBVI CCD photometry and follow-up spectroscopy. The optical survey covers approximately 1300 arcmin2 on the sky and gives a global photometric and astrometric catalogue for more than 7000 objects. The location of a PMS population is well defined in a V versus (V-I) colour-magnitude diagram. Multifibre spectroscopic results for optically selected PMS candidates confirm the T Tauri nature for 10 objects, with equal numbers of classical TTS (CTTS) and weak-line TTS (WTTS). There are six other objects that we classify as possible PMS stars. The newly discovered TTS stars have masses in the range ~0.9-3.0 Msolar and ages from <1 to nearly 10 Myr, based on the Siess, Dufour & Forestini isochrones. Their location close to the O and B stars of the association (especially the O7n star) demonstrates that low-mass star formation is indeed possible in such an apparently hostile environment dominated by early-type stars and that the latter must have been less effective in eroding the circumstellar discs of their lower-mass siblings compared with other OB associations (e.g. λ-Ori). We attribute this to the nature of the local environment, speculating that the bulk of molecular material, which shielded low-mass stars from the ionizing radiation of their early-type siblings, has only recently been removed.

  14. 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.

  15. Performance analysis for the CALIFA Barrel calorimeter of the R3B experiment

    NASA Astrophysics Data System (ADS)

    Alvarez-Pol, H.; Ashwood, N.; Aumann, T.; Bertini, D.; Cabanelas, P.; Casarejos, E.; Cederkall, J.; Cortina-Gil, D.; Díaz Fernández, P.; Duran, I.; Fiori, E.; Galaviz, D.; Labiche, M.; Nacher, E.; Pietras, B.; Savran, D.; Tengblad, O.; Teubig, P.

    2014-12-01

    The CALIFA calorimeter is an advanced detector for gamma rays and light charged particles, accordingly optimized for the demanding requirements of the physics programme proposed for the R3B facility at FAIR. The multipurpose character of CALIFA is required to fulfil challenging demands in energy resolution (5-6% at 1 MeV for gamma rays) and efficiency. Charged particles, e.g. protons of energies up to 320 MeV in the Barrel section, should also be identified with an energy resolution better to 1%. CALIFA is divided into two well-separated sections: a "Forward EndCap" and a cylindrical "Barrel" covering an angular range from 43.2° to 140.3°. The Barrel section, based on long CsI(Tl) pyramidal frustum crystals coupled to large area avalanche photodiodes (LAAPDs), attains the requested high efficiency for calorimetric purposes. The construction of the CALIFA Demonstrator, comprising 20% of the total detector, has already been initiated, and commissioning experiments are expected for 2014. The assessment of the capabilities and expected performance of the detector elements is a crucial step in their design, along with the prototypes evaluation. For this purpose, the Barrel geometry has been carefully implemented in the simulation package R3BRoot, including easily variable thicknesses of crystal wrapping and carbon fibre supports. A complete characterization of the calorimeter response (including efficiency, resolution, evaluation of energy and reconstruction losses) under different working conditions, with several physics cases selected to probe the detector performance over a wide range of applications, has been undertaken. Prototypes of different sections of the CALIFA Barrel have been modeled and their responses have been evaluated and compared with the experimental results. The present paper summarizes the outcome of the simulation campaign for the entire Barrel section and for the corresponding prototypes tested at different European installations.

  16. Thieno[2,3-b]indole-Based Small Push-Pull Chromophores: Synthesis, Structure, and Electronic Properties.

    PubMed

    Baert, François; Cabanetos, Clément; Allain, Magali; Silvestre, Virginie; Leriche, Philippe; Blanchard, Philippe

    2016-04-01

    Small push-pull molecules were synthesized in high yields by connecting a N-methyl or N-phenyl substituted thieno[2,3-b]indole electron-donating block directly to a 2,2-dicyanovinyl or (1-(dicyanomethylene)-3-oxo-1-inden-2-ylidene)methyl electron-withdrawing group. The effects of the N-substitution on thieno[2,3-b]indole and the nature of the electron-accepting group on the electrochemical, optical, and charge-transport properties were investigated by cyclic voltammetry, UV-vis spectroscopy, and the space-charge-limited current method, respectively. These results, together with the 1% power conversion efficiency of a bilayer solar cell prepared with the smallest compound of the series, show the potential of thieno[2,3-b]indole for organic electronics. PMID:27003243

  17. 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 ...

  18. A Role for Phosphodiesterase 3B in Acquisition of Brown Fat Characteristics by White Adipose Tissue in Male Mice

    PubMed Central

    Hockman, Steven; Chung, Youn Wook; Ahmad, Faiyaz; Gavrilova, Oksana; Raghavachari, Nalini; Yang, Yanqin; Niu, Gang; Chen, Xiaoyuan; Yu, Zu Xi; Liu, Shiwei; Degerman, Eva

    2013-01-01

    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. PMID:23766131

  19. 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. PMID:27027726

  20. Synthesis, reactions and antimicrobial activity of new cyclopenta[e]thieno[2,3-b]pyridines and related heterocyclic systems.

    PubMed

    Bakhite, E A; Abdel-Rahman, A E; Mohamed, O S; Thabet, E A

    2000-08-01

    Reaction of the arylidene cyanothioacetamides 1a, b with cyclopentanone was proved to give a mixture of 4-aryl-3-cyanocyclopenta[b]pyridine-2(1H)-thiones 2a, b and the corresponding 7-arylidene derivatives 3a, b. Compounds 2a, b were reacted with ethyl chloroacetate or chloroacetamide to give the promising S-substituted thiopyridines 6a-d. On treatment of the latter compounds with sodium ethoxide in boiling ethanol, they underwent intramolecular Thorpe-Ziegler cyclization to yield the corresponding 3-amino-4-aryl-2-functionalized-cyclopenta[e]thieno[2,3-b]pyridines (7a-d). Most of these thienopyridines were reacted with a variety of reagents to produce other new cyclopentathienopyridines as well as numerous of their condensed heterocyclic derivatives. Some of the compounds synthesized were tested in vitro for their antibacterial and antifungal activity. PMID:10989834

  1. 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.

  2. Summertime partitioning and budget of NO(y) compounds in the troposphere over Alaska and Canada: ABLE 3B

    NASA Technical Reports Server (NTRS)

    Sandholm, S.; Olson, J.; Bradshaw, J.; Talbot, R.; Singh, H.; Gregory, G.; Blake, D.; Anderson, B.; Sachse, G.; Barrick, J.

    1994-01-01

    As part of NASA's Arctic Boundary Layer Expedition 3A and 3B field measurement programs, measurements of NO(x), HNO3, PAN, PPN, and NO(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(x)O(y)) budget through the comparison of the values of NO(y) measured with a catalytic convertor to the sum of individually measured NO(y) (i) compounds (i.e., sigmaNO(y)(i) = NO(x) + HNO3 + PAN + PPN). Significant differences were observed between the various study regions. In the lower 6 km of the troposphere over Alaska and the Hudson Bay lowlands of Canada a significant fraction of the NO(y) budget (30 to 60%) could not be accounted for by the measured sigmaNO(y)i. This deficit in the NO(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(y) budget in the northern Labrador and Quebec regions of Canada is almost totally accounted for within the combined measurement uncertainties of NO(y) and the various NO(y)(i) compounds. A substantial portion of the NO(y) budget's 'missing compounds' 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(y) budget. In addition, the apparent stability of compounds represented by the NO(y) budget deficit in the lower-altitude range questions the ability of these compounds to participate as reversible reservoirs for 'active' odd nitrogen and suggest that some portion of the NO(y) budget may consist of relatively unreactive nitrogen-containing compounds.

  3. 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.

  4. Enhanced photocatalytic-electrolytic degradation of Reactive Brilliant Red X-3B in the presence of water jet cavitation.

    PubMed

    Wang, Xiaoning; Jia, Jinping; Wang, Yalin

    2015-03-01

    Photocatalysis, electrolysis, water jet cavitation (WJC), alone and in combinations were applied to degrade an azo dye, Reactive Brilliant Red X-3B (X-3B). Experiments were conducted in a 4.0 L aqueous solution with different initial dye concentrations, TiO₂ dose, and solution pH. WJC substantially increased the photocatalytic, electrolytic and photocatalytic-electrolytic rates of the dye removal. The observed first-order rate of X-3B decolorization in the process of combined photocatalysis and electrolysis coupled with WJC was 1.6-2.9 times of that in the process of combined photocatalysis and electrolysis coupled with mechanical stirring. The rate enhancements may be attributed primarily to the reduced diffusion layer thickness on the electrodes and the deagglomeration of photocatalyst particles due to the chemical and physical effects of WJC. Under the conditions of 80 mg/L X-3B solution, 100 mg/L TiO₂ dose and solution pH 6.3, 97% and 71% of color and chemical oxygen demand (CODCr) were removed, respectively, within 90-min photocatalytic-electrolytic treatment coupled with WJC. During this process, azo groups and naphthalene, benzene and triazine structures of the dye can be destroyed. Industrial textile effluent was also investigated, and a positive synergistic effect between photocatalytic-electrolytic system and WJC was observed considering color removal. PMID:25453209

  5. 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

  6. 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... meets each of the criteria set forth above. This exercise of authority may be revoked as a matter of... determination made under this exercise of authority as set out above can inform but shall not control a...

  7. 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... meets each of the criteria set forth above. This exercise of authority may be revoked as a matter of... determination made under this exercise of authority as set out above can inform but shall not control a...

  8. 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... the particular applicant meets each of the criteria set forth above. This exercise of authority may be... subject to it. Any determination made under this exercise of authority as set out above can inform...

  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... exercise of authority may be revoked as a matter of discretion and without notice at any time with respect to any and all persons subject to it. Any determination made under this exercise of authority as...

  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... any other relevant factor. This exercise of authority may be revoked as a matter of discretion and... this exercise of authority as set out above can inform but shall not control a decision regarding...

  11. 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

  12. Methanol suppression of trichloroethylene degradation by Methylosinus trichosporium (OB3b) and methane-oxidizing mixed cultures

    SciTech Connect

    Eng, W.; Palumbo, A.V.; Strandberg, G.W.; Sriharan, S.

    1991-12-31

    The effect of methanol on trichloroethylene (TCE) degradation by mixed and pure methylotrophic cultures was examined in batch culture experiments. Methanol was found to relieve growth inhibition of Methylosinus trichosporium (OB3b) at high (14 mg/L) TCE concentrations. Degradation of TCE was determined by both radiolabeling and gas chromatography techniques. When cultures were grown on methanol over 10 to 14 d with 0.3 mg/L TCE, OB3b degraded 16.89 {+-} 0.82% (mean {+-} SD) of the TCE, and a mixed culture (DT type II) degraded 4.55 {+-} 0.11%. Mixed culture (JS type I) degraded 4.34 {+-} 0.06% of the TCE. When grown on methane with 0.3 mg/L TCE, 32.93 {+-} 2.01% of the TCE was degraded by OB3b, whereas the JS culture degraded 24.3 {+-} 1.38% of the TCE, and the DT culture degraded 34.3 {+-} 2.97% of the TCE. The addition of methanol to cultures grown on methane reduced TCE degradation to 16.21 {+-} 1.17% for OB3b and to 5.08 {+-} 0.56% for JS. Although methanol reduces the toxicity of TCE to the cultures, biodegradation of TCE cannot be sustained in methanol-grown cultures. Since high TCE concentrations appear to inhibit methane uptake and growth, we suggest the primary toxicity of TCE is directed towards the methane monooxygenase.

  13. Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter

    PubMed Central

    Hamada, Katsuyuki; Shirakawa, Toshiro; Terao, Shuji; Gotoh, Akinobu; Tani, Kenzaburo; Huang, Wenlin

    2014-01-01

    The use of carrier cells infected with oncolytic viruses in cancer gene therapy is an attractive method because it can overcome viral immunogenicity and induce tumor immunity and significant antitumor activity. To enable human clinical trials of this treatment, acute and chronic toxicity tests must first be performed to ensure safety. IAI.3B promoter, oncolytic adenovirus AdE3-IAI.3B introduced by IAI.3B promoter, and A549 carrier cells infected with AdE3-IAI.3B were highly active in cancer cells but not in normal cells. Freeze-thawing increased the antitumor effect of A549 carrier cells by promoting the translocation of oncolytic adenovirus particles from the nucleus to the cytoplasm following the rupture of the nuclear membranes. No deaths or abnormal blood test data resulted from acute toxicity tests conducted in nude mice after a single dose. In chronic toxicity tests in rabbits, there were no serious side effects after eight doses of 1.25 × 107 cells/kg or less for 4 weeks; a significant immune response is known to elicit increased numbers of antiadenovirus antibodies and enlarge the spleen. From these results, it could be concluded that cancer gene therapy of recurrent solid tumors using carrier cells can be safely trialed in humans. PMID:26015963

  14. SH3b Cell wall binding domains can enhance anti-staphylococcal activity of endolysin lytic domains.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteriophage endolysins are peptidoglycan hydrolases and a potential new source of antimicrobials. A large subset of these proteins contain a C-terminal SH3b_5 cell wall binding domain that has been shown [for some] to be essential for accurate cell wall recognition and subsequent staphylolytic ac...

  15. 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

  16. 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

  17. 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...

  18. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness

    PubMed Central

    Rossi, Davide; Bruscaggin, Alessio; Spina, Valeria; Rasi, Silvia; Khiabanian, Hossein; Messina, Monica; Fangazio, Marco; Vaisitti, Tiziana; Monti, Sara; Chiaretti, Sabina; Guarini, Anna; Del Giudice, Ilaria; Cerri, Michaela; Cresta, Stefania; Deambrogi, Clara; Gargiulo, Ernesto; Gattei, Valter; Forconi, Francesco; Bertoni, Francesco; Deaglio, Silvia; Rabadan, Raul; Pasqualucci, Laura; Foà, Robin

    2011-01-01

    The genetic lesions identified in chronic lymphocytic leukemia (CLL) do not entirely recapitulate the disease pathogenesis and the development of serious complications, such as chemorefractoriness. While investigating the coding genome of fludarabine-refractory CLL, we observed that mutations of SF3B1, encoding a splicing factor and representing a critical component of the cell spliceosome, were recurrent in 10 of 59 (17%) fludarabine-refractory cases, with a frequency significantly greater than that observed in a consecutive CLL cohort sampled at diagnosis (17/301, 5%; P = .002). Mutations were somatically acquired, were generally represented by missense nucleotide changes, clustered in selected HEAT repeats of the SF3B1 protein, recurrently targeted 3 hotspots (codons 662, 666, and 700), and were predictive of a poor prognosis. In fludarabine-refractory CLL, SF3B1 mutations and TP53 disruption distributed in a mutually exclusive fashion (P = .046). The identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in CLL. PMID:22039264

  19. Theory and practice: bulk synthesis of C3B and its H2- and Li-storage capacity.

    PubMed

    King, Timothy C; Matthews, Peter D; Glass, Hugh; Cormack, Jonathan A; Holgado, Juan Pedro; Leskes, Michal; Griffin, John M; Scherman, Oren A; Barker, Paul D; Grey, Clare P; Dutton, Siân E; Lambert, Richard M; Tustin, Gary; Alavi, Ali; Wright, Dominic S

    2015-05-11

    Previous theoretical studies of C3B have suggested that boron-doped graphite is a promising H2- and Li-storage material, with large maximum capacities. These characteristics could lead to exciting applications as a lightweight H2-storage material for automotive engines and as an anode in a new generation of batteries. However, for these applications to be realized a synthetic route to bulk C3B must be developed. Here we show the thermolysis of a single-source precursor (1,3-(BBr2)2C6H4) to produce graphitic C3B, thus allowing the characteristics of this elusive material to be tested for the first time. C3B was found to be compositionally uniform but turbostratically disordered. Contrary to theoretical expectations, the H2- and Li-storage capacities are lower than anticipated, results that can partially be explained by the disordered nature of the material. This work suggests that to model the properties of graphitic materials more realistically, the possibility of disorder must be considered. PMID:25810151

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO

    PubMed Central

    Goyama, Susumu; Schibler, Janet; Gasilina, Anjelika; Shrestha, Mahesh; Lin, Shan; Link, Kevin A.; Chen, Jianjun; Whitman, Susan P.; Bloomfield, Clara D.; Nicolet, Deedra; Assi, Salam; Ptasinska, Anetta; Heidenreich, Olaf; Bonifer, Constanze; Kitamura, Toshio; Nassar, Nicolas N.; Mulloy, James C.

    2015-01-01

    The t(8;21) rearrangement, which creates the AML1-ETO fusion protein, represents the most common chromosomal translocation in acute myeloid leukemia (AML). Clinical data suggest that CBL mutations are a frequent event in t(8;21) AML, but the role of CBL in AML1-ETO-induced leukemia has not been investigated. In this study, we demonstrate that CBL mutations collaborate with AML1-ETO to expand human CD34+ cells both in vitro and in a xenograft model. CBL depletion by shRNA also promotes the growth of AML1-ETO cells, demonstrating the inhibitory function of endogenous CBL in t(8;21) AML. Mechanistically, loss of CBL function confers hyper-responsiveness to thrombopoietin and enhances STAT5/AKT/ERK/Src signaling in AML1-ETO cells. Interestingly, we found the protein tyrosine phosphatase UBASH3B/Sts-1, which is known to inhibit CBL function, is upregulated by AML1-ETO through transcriptional and miR-9-mediated regulation. UBASH3B/Sts-1 depletion induces an aberrant pattern of CBL phosphorylation and impairs proliferation in AML1-ETO cells. The growth-inhibition caused by UBASH3B/Sts-1 depletion can be rescued by ectopic expression of CBL mutants, suggesting that UBASH3B/Sts-1 supports the growth of AML1-ETO cells partly through modulation of CBL function. Our study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETO-induced leukemia, and identifies UBASH3B/Sts-1 as a potential target for pharmaceutical intervention. PMID:26449661

  6. Methanobactin from Methylocystis sp. Strain SB2 Affects Gene Expression and Methane Monooxygenase Activity in Methylosinus trichosporium OB3b

    PubMed Central

    Farhan Ul-Haque, Muhammad; Kalidass, Bhagyalakshmi; Vorobev, Alexey; Baral, Bipin S.; DiSpirito, Alan A.

    2015-01-01

    Methanotrophs can express a cytoplasmic (soluble) methane monooxygenase (sMMO) or membrane-bound (particulate) methane monooxygenase (pMMO). Expression of these MMOs is strongly regulated by the availability of copper. Many methanotrophs have been found to synthesize a novel compound, methanobactin (Mb), that is responsible for the uptake of copper, and methanobactin produced by Methylosinus trichosporium OB3b plays a key role in controlling expression of MMO genes in this strain. As all known forms of methanobactin are structurally similar, it was hypothesized that methanobactin from one methanotroph may alter gene expression in another. When Methylosinus trichosporium OB3b was grown in the presence of 1 μM CuCl2, expression of mmoX, encoding a subunit of the hydroxylase component of sMMO, was very low. mmoX expression increased, however, when methanobactin from Methylocystis sp. strain SB2 (SB2-Mb) was added, as did whole-cell sMMO activity, but there was no significant change in the amount of copper associated with M. trichosporium OB3b. If M. trichosporium OB3b was grown in the absence of CuCl2, the mmoX expression level was high but decreased by several orders of magnitude if copper prebound to SB2-Mb (Cu-SB2-Mb) was added, and biomass-associated copper was increased. Exposure of Methylosinus trichosporium OB3b to SB2-Mb had no effect on expression of mbnA, encoding the polypeptide precursor of methanobactin in either the presence or absence of CuCl2. mbnA expression, however, was reduced when Cu-SB2-Mb was added in both the absence and presence of CuCl2. These data suggest that methanobactin acts as a general signaling molecule in methanotrophs and that methanobactin “piracy” may be commonplace. PMID:25616801

  7. Methanobactin from Methylocystis sp. strain SB2 affects gene expression and methane monooxygenase activity in Methylosinus trichosporium OB3b.

    PubMed

    Farhan Ul-Haque, Muhammad; Kalidass, Bhagyalakshmi; Vorobev, Alexey; Baral, Bipin S; DiSpirito, Alan A; Semrau, Jeremy D

    2015-04-01

    Methanotrophs can express a cytoplasmic (soluble) methane monooxygenase (sMMO) or membrane-bound (particulate) methane monooxygenase (pMMO). Expression of these MMOs is strongly regulated by the availability of copper. Many methanotrophs have been found to synthesize a novel compound, methanobactin (Mb), that is responsible for the uptake of copper, and methanobactin produced by Methylosinus trichosporium OB3b plays a key role in controlling expression of MMO genes in this strain. As all known forms of methanobactin are structurally similar, it was hypothesized that methanobactin from one methanotroph may alter gene expression in another. When Methylosinus trichosporium OB3b was grown in the presence of 1 μM CuCl2, expression of mmoX, encoding a subunit of the hydroxylase component of sMMO, was very low. mmoX expression increased, however, when methanobactin from Methylocystis sp. strain SB2 (SB2-Mb) was added, as did whole-cell sMMO activity, but there was no significant change in the amount of copper associated with M. trichosporium OB3b. If M. trichosporium OB3b was grown in the absence of CuCl2, the mmoX expression level was high but decreased by several orders of magnitude if copper prebound to SB2-Mb (Cu-SB2-Mb) was added, and biomass-associated copper was increased. Exposure of Methylosinus trichosporium OB3b to SB2-Mb had no effect on expression of mbnA, encoding the polypeptide precursor of methanobactin in either the presence or absence of CuCl2. mbnA expression, however, was reduced when Cu-SB2-Mb was added in both the absence and presence of CuCl2. These data suggest that methanobactin acts as a general signaling molecule in methanotrophs and that methanobactin "piracy" may be commonplace. PMID:25616801

  8. Differential effects of phorbol ester on growth and protein kinase C isoenzyme regulation in human hepatoma Hep3B cells.

    PubMed Central

    Hsu, S L; Chou, Y H; Yin, S C; Liu, J Y

    1998-01-01

    PMA has both mitogenic and antiproliferative effects on human hepatoma Hep3B cells. In response to low PMA concentration (10 nM), Hep3B cells displayed an increasing proliferation potentiation. At high PMA concentration (1 microM) Hep3B cells exhibited modest cytostatic effects. Determinations of protein kinase C (PKC) activity in PMA-treated cells revealed that alterations in PKC activity are associated with proliferative capacity. The decrease in PKC activity mediated by a high dose of PMA was accompanied by cell growth inhibition. Increases in PKC activity mediated by a low dose of PMA were consistent with proliferation stimulation. Immunoblot analysis showed that there are at least six PKC isoenzymes: alpha, delta, epsilon, mu, zeta and iota/lambda, constitutively expressed in Hep3B cells. Cellular fractionation and immunocytochemical staining results demonstrated that both 10 nM and 1 microM PMA treatments induced a marked translocation of PKC-alpha from cytosol to membrane or nuclear fraction within 5-30 min. At the same time PKC-delta and epsilon were translocated from the membrane to nuclear fraction. In addition, prolonged treatment with 1 microM PMA, but not with 10 nM PMA, selectively mediated the down-regulation of these three PKC isoenzymes. The distinct effects of different concentrations of PMA on cell proliferation and PKC-alpha, delta and epsilon isoenzyme modulation support the involvement of these three PKC isotypes in the mechanism of action of Hep3B cells in cell growth events. PMID:9639562

  9. 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

  10. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells

    PubMed Central

    Sohn, Jeong-Hyeon; Bora, Puran S.; Suk, Hye-Jung; Molina, Hector; Kaplan, Henry J.; Bora, Nalini S.

    2007-01-01

    Systemic tolerance can be induced by the introduction of antigen into an immune-privileged site. Here we investigated the role of complement in the induction of tolerance after intraocular injection. We found that the development of antigen-specific tolerance is dependent on a complement activation product. The ligation of the complement C3 activation product iC3b to complement receptor type 3 (the iC3b receptor) on antigen-presenting cells resulted in the sequential production of transforming growth factor-β2 and interleukin-10, which is essential for the induction of tolerance. These observations may extend to the development of both neonatal tolerance and other forms of acquired tolerance. PMID:12514742

  11. DNA replication is altered in Immunodeficiency Centromeric instability Facial anomalies (ICF) cells carrying DNMT3B mutations

    PubMed Central

    Lana, Erica; Mégarbané, André; Tourrière, Hélène; Sarda, Pierre; Lefranc, Gérard; Claustres, Mireille; De Sario, Albertina

    2012-01-01

    ICF syndrome is a rare autosomal recessive disorder that is characterized by Immunodeficiency, Centromeric instability, and Facial anomalies. In all, 60% of ICF patients have mutations in the DNMT3B (DNA methyltransferase 3B) gene, encoding a de novo DNA methyltransferase. In ICF cells, constitutive heterochromatin is hypomethylated and decondensed, metaphase chromosomes undergo rearrangements (mainly involving juxtacentromeric regions), and more than 700 genes are aberrantly expressed. This work shows that DNA replication is also altered in ICF cells: (i) heterochromatic genes replicate earlier in the S-phase; (ii) global replication fork speed is higher; and (iii) S-phase is shorter. These replication defects may result from chromatin changes that modify DNA accessibility to the replication machinery and/or from changes in the expression level of genes involved in DNA replication. This work highlights the interest of using ICF cells as a model to investigate how DNA methylation regulates DNA replication in humans. PMID:22378288

  12. Synthesis, structures and magnetic properties of Pr-lean Pr2Fe14B/Fe3B nanocomposite alloys

    NASA Astrophysics Data System (ADS)

    Mingxiang, Pan; Pengyue, Zhang; Hongliang, Ge; Hangfu, Yang; Qiong, Wu

    2012-09-01

    The lean rare-earth Pr4.5Fe77-xTixB18.5 (x=0, 1, 4, 5) nanocomposite alloys were prepared by melt spinning method and subsequent thermal annealing. The effect of Ti content and annealing temperature on the magnetic properties and the microstructure of these magnets were investigated. The enhancing coercivity Hc from 211.4 to 338.2 kA/m has been observed at the optimal annealing temperature of 700 °C by the addition of 5 at% Ti in Pr2Fe14B/Fe3B alloys. It was also found that increasing Ti content leads to marked grain refinement in the annealed alloys, resulting in strong exchange-coupling interaction between the hard and the soft phases in these ribbons. In addition, the magnetization reversal behaviors of Pr2Fe14B/Fe3B nanocomposites were discussed in detail.

  13. Human C3b- and C4b-regulatory proteins: a new multi-gene family.

    PubMed

    Holers, V M; Cole, J L; Lublin, D M; Seya, T; Atkinson, J P

    1985-06-01

    The complement cascade is regulated to prevent inappropriate activation. This regulation is targeted not only at the initiation of the cascade but also at the amplification andjunctional (C3) steps. Five glycoproteins with both complement regulatory activity and binding affinity for C3b/C4b have been characterized. In plasma these molecules are factor H(H) and C4-binding protein (C4-bp) and, on cells, they are the C3b/C4b receptor (CR1), decay-accelerating factor (DAF), and gp45-70. Here Michael Holers and his colleagues review structural, functional and genetic studies of these proteins and discuss the evidence for a new multi-gene family with a common ancestral protein. PMID:25289982

  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. Association of 5-HT3B Receptor Gene Polymorphisms with the Efficacy of Ondansetron for Postoperative Nausea and Vomiting

    PubMed Central

    Kim, Min-Soo; Lee, Jeong-Rim; Choi, Eun-Mi; Kim, Eun Ho

    2015-01-01

    Purpose Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have significantly reduced PONV, over 35% of patients treated with ondansetron can experience PONV. In this study, we investigated whether the Y129S and -100_-102AAG deletion polymorphisms of the 5-HT3B receptor gene affect the efficacy of ondansetron in preventing PONV. Materials and Methods Two hundred and forty-five adult patients who underwent laparoscopic cholecystectomy were enrolled. Ondansetron 0.1 mg/kg was intravenously administered 30 minutes before the end of surgery. Genomic DNA was prepared from blood samples using a nucleic acid isolation device. Both the Y129S variant and the -100_-102AAG deletion variant were screened for using a single base primer extension assay and a DNA direct sequencing method, respectively. The relationship between genetic polymorphisms and clinical outcomes of ondansetron treatment was investigated. Results Among the 5-HT3B AAG deletion genotypes, the incidence of PONV was higher in patients with the homomutant than with other genotypes during the first 2 hours after surgery (p=0.02). There were no significant differences in the incidence of PONV among genotypes at 2-24 hours after surgery. In the Y129S variants of the 5-HT3B receptor gene, there were no significant differences in the incidence of PONV among genotypes during the first 2 hours and at 2-24 hours after surgery. Conclusion The response to ondansetron for PONV was significantly influenced by the -100_-102AAG deletion polymorphisms of the 5-HT3B gene. Thus, the -100_-102AAG deletion variants may be a pharmacogenetic predictor for responsiveness to ondansetron for PONV. PMID:26256989

  16. Sonic boom results for a nominal mission 3B. Space Shuttle engineering and operations support, engineering systems analysis

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The results obtained in the analysis of the effects of sonic boom overpressures at ground level for a nominal Mission 3B with the current baseline guidance are reported. These results are in the form of ground level overpressures generated along the groundtrack out to lateral cutoff from Mach 3.0-1.10 at 0.10 (tenth) Mach intervals. Preliminary trajectory constraints which will reduce excess sonic boom overpressures to approximately 2.0 PSF are included.

  17. 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.

  18. 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

  19. 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.

  20. HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease

    PubMed Central

    Grimm, Fiona; Sarre, Alexandre; Hörl, Manuel; Kayikci, Melis; Fankhauser, Niklaus; Christinat, Yann; Cortijo, Cédric; Feehan, Owen; Vukolic, Ana; Sossalla, Samuel; Stehr, Sebastian N.; Ule, Jernej; Zamboni, Nicola; Pedrazzini, Thierry; Krek, Wilhelm

    2016-01-01

    Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs. KHK-C displays superior affinity for fructose compared with KHK-A and is produced primarily in the liver, thus restricting fructose metabolism almost exclusively to this organ. Here we show that myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1α (HIF1α) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C. Heart-specific depletion of SF3B1 orgenetic ablation of Khk, but not Khk-A alone, in mice, suppresses pathological stress-induced fructose metabolism, growth and contractile dysfunction, thus defining signalling components and molecular underpinnings of a fructose metabolism regulatory system crucial for pathological growth. PMID:26083752

  1. Selection and application of endophytic bacterium Achromobacter xylosoxidans strain F3B for improving phytoremediation of phenolic pollutants.

    PubMed

    Ho, Ying-Ning; Mathew, Dony Chacko; Hsiao, Shu-Chuan; Shih, Chun-Hao; Chien, Mei-Fang; Chiang, Hsing-Mei; Huang, Chieh-Chen

    2012-06-15

    While phytoremediation has been considered as an in situ bioprocess to remediate environmental contaminants, the application of functional endophytic bacteria within plants remains a potential strategy that could enhance the plants' efficiency in phytoremediation. In this study, 219 endophytes were isolated from plants that are predominantly located in a constructed wetland, including reed (Phragmites australis) and water spinach (Ipomoea aquatica). Twenty-five strains of the isolated endophytes utilize aromatic compounds as sole carbon source; Achromobacter xylosoxidans strain F3B was chosen for the in planta studies using the model plant Arabidopsis thaliana. Phylogenetic analysis indicated that those endophytic isolates of A. xylosoxidans formed a cluster within its species, and a specific real-time PCR detection method was developed for confirming the stability of the isolates in plants. In the presence of either catechol or phenol, inoculation of A. thaliana with F3B could extend into the root lengths and fresh weights to promote pollutants removal rates. These results demonstrate the potential of the endophytic F3B strain for helping plants to tolerate stress from aromatic compounds and to improve phytoremediation of phenolic pollutants. PMID:22497718

  2. 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.

  3. Isolation and characterization of a serine proteinase specific to human C3b from human erythrocyte membranes

    SciTech Connect

    Charriaut, C.; Krikorian, L.; Barel, M.; Frade, R.

    1986-03-05

    In a previous report, they have shown that human C3b bound through CR1 to human erythrocytes is cleaved by a membrane proteinase activity. Following the molecular analysis of this proteinase activity, they have purified it by a four step procedure: ammonium sulfate precipitation, biogel filtration, fluid phase electrophoresis and hydroxylapatite chromatography. The highly purified proteinase was labeled by /sup 125/I iodine or /sup 3/H-DFP and analyzed by gel electrophoresis: a single band membrane component was characterized by its apparent molecular weight of 57 K or 60 K, under non reducing or reducing conditions respectively and was called p 57. Its reactivity with /sup 3/H-DFP and the inhibition by PMSF of the proteinase activity indicate that p 57 is a serine proteinase. Moreover, it is sensitive to aprotinin and ..gamma..1-antitrypsin. This membrane proteinase presents a higher activity in the presence of detergent and cleaves both alpha and beta chains of human C3b. Polyclonal antibody prepared against this purified proteinase inhibits its activity. On the basis of its structure and its functions, i.e. molecular weight, antigenic properties, proteinase properties and proteinases inhibitors sensitivity, p57 is not related to CR1 or DAF, two others membrane components which react with human C3b and identified by others on human erythrocytes. These specific antibodies allow to analyze the presence of p57 on human cells.

  4. 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.

  5. Immune evasion of Enterococcus faecalis by an extracellular gelatinase that cleaves C3 and iC3b.

    PubMed

    Park, Shin Yong; Shin, Yong Pyo; Kim, Chong Han; Park, Ho Jin; Seong, Yeon Sun; Kim, Byung Sam; Seo, Sook Jae; Lee, In Hee

    2008-11-01

    Enterococcus faecalis (Ef) accounts for most cases of enterococcal bacteremia, which is one of the principal causes of nosocomial bloodstream infections (BSI). Among several virulence factors associated with the pathogenesis of Ef, an extracellular gelatinase (GelE) has been known to be the most common factor, although its virulence mechanisms, especially in association with human BSI, have yet to be demonstrated. In this study, we describe the complement resistance mechanism of Ef mediated by GelE. Using purified GelE, we determined that it cleaved the C3 occurring in human serum into a C3b-like molecule, which was inactivated rapidly via reaction with water. This C3 convertase-like activity of GelE was shown to result in a consumption of C3 and thus inhibited the activation of the complement system. Also, GelE was confirmed to degrade an iC3b that was deposited on the Ag surfaces without affecting the bound C3b. This proteolytic effect of GelE against the major complement opsonin resulted in a substantial reduction in Ef phagocytosis by human polymorphonuclear leukocytes. In addition, we verified that the action of GelE against C3, which is a central component of the complement cascade, was human specific. Taken together, it was suggested that GelE may represent a promising molecule for targeting human BSI associated with Ef. PMID:18941224

  6. Degradation of Active Brilliant Red X-3B by a microwave discharge electrodeless lamp in the presence of activated carbon.

    PubMed

    Fu, Jie; Wen, Teng; Wang, Qing; Zhang, Xue-Wei; Zeng, Qing-Fu; An, Shu-Qing; Zhu, Hai-Liang

    2010-06-01

    Degradation of Active Brilliant Red X-3B (X-3B) in aqueous solution by a microwave discharge electrodeless lamp (MDEL) in the presence of activated carbon was investigated. The preliminary results proved this method could effectively degrade X-3B in aqueous solution. The removal percentages of colour and chemical oxygen demand were up to approximately 99% and 66%, respectively, at the conditions of 0.8 g/L dye concentration, 20 g/L activated carbon, pH 7.0 and 8 min microwave irradiation time. The degradation basically belonged to first-order reaction kinetics and its rate constant was 0.42 min(-1). No aromatic organics were detected in the final treated solution, indicating that the mineralization was relatively complete. By studying the change in solution properties, it could be concluded that MDEL-assisted oxidation was the dominant reaction mechanism. In addition, the influence of operational parameters and reuse of activated carbon were also discussed. PMID:20586239

  7. 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

  8. Ras-Related Nuclear Protein Ran3B Gene Is Involved in Hormone Responses in the Embryogenic Callus of Dimocarpus longan Lour.

    PubMed

    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

  9. Translation initiation factor eIF3b expression in human cancer and its role in tumor growth and lung colonization

    PubMed Central

    Wang, Hong; Ru, Yuanbin; Sanchez-Carbayo, Marta; Wang, Xuejiao; Kieft, Jeffrey S.; Theodorescu, Dan

    2013-01-01

    Purpose Discovery transcriptomic analyses suggest eukaryotic initiation factor 3b (eIF3b) is elevated in human bladder and prostate cancer, yet its role as a prognostic factor or its requirement in the maintenance or progression of human cancer is not established. Here we determine the therapeutic potential of eIF3b by examining the clinical relevance of its expression in human cancer tissues and its role in experimental tumor models. Experimental Design We examined mRNA expression of eIF3b in bladder (N=317) and prostate (N=566) tissue samples and protein expression by immunohistochemistry in 143 bladder tumor samples as a function of clinicopathologic features. The impact of eIF3b depletion by siRNA in human cancer lines was evaluated in regards to in vitro cell growth, cell cycle, migration, in vivo subcutaneous tumor growth and lung colonization. Results eIF3b mRNA expression correlated to tumor grade, stage and survival in human bladder and prostate cancer. eIF3b protein expression stratified survival in human bladder cancer. eIF3b depletion reduced in vitro cancer cell growth; inhibited G1/S cell cycle transition by changing protein but not RNA expression of Cyclin A, E, Rb and p27Kip1; inhibited migration and disrupted actin cytoskeleton and focal adhesions. These changes were associated with decreased protein expression of integrin α5. Integrin α5 depletion phenocopied effects observed with eIF3b. eIF3b depleted bladder cancer cells formed fewer subcutaneous tumors that grew more slowly and had reduced lung colonization. Conclusion eIF3b expression relates to human bladder and prostate cancer prognosis, is required for tumor growth and thus a candidate therapeutic target. PMID:23575475

  10. 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

  11. Synthesis and antimicrobial evaluation of new pyrano[4,3-b]pyran and Pyrano[3,2-c]chromene derivatives bearing a 2-thiophenoxyquinoline nucleus.

    PubMed

    Makawana, Jigar A; Patel, Manish P; Patel, Ranjan G

    2012-04-01

    A new series of pyrano[4,3-b]pyran 4a-i and pyrano[3,2-c]chromene 6a-r derivatives bearing a 2-thiophenoxyquinoline nucleus were synthesized by reaction of 2-(4-(un)-substituted thiophenoxy)quinoline-3-carbaldehydes 2a-i with 6-methyl-4-hydroxypyran-2-one 3 and 4-hydroxy-6-(un)-substituted-2H-chromen-2-one 5a-b respectively and malononitrile at room temperature in the presence of KOH as a basic catalyst. All the compounds were screened against three Gram-positive bacteria (Streptococcus pneumoniae, Bacillus subtilis, Clostridium tetani), three Gram-negative bacteria (Salmonella typhi, Escherichia coli, Vibrio cholerae) and two fungi (Candida albicans, Aspergillus fumigatus) using the broth microdilution MIC (minimum inhibitory concentration) method. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Bacillus subtilis, Clostridium tetani and Candida albicans as compared to standard drugs. PMID:22105795

  12. 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

  13. 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

  14. 8 CFR 208.16 - Withholding of removal under section 241(b)(3)(B) of the Act and withholding of removal under the...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...)(3)(B) of the Act and withholding of removal under the Convention Against Torture. 208.16 Section 208... section 241(b)(3)(B) of the Act and withholding of removal under the Convention Against Torture. (a... withholding of removal under the Convention Against Torture. (1) For purposes of regulations under Title II...

  15. 8 CFR 208.16 - Withholding of removal under section 241(b)(3)(B) of the Act and withholding of removal under the...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...)(3)(B) of the Act and withholding of removal under the Convention Against Torture. 208.16 Section 208... section 241(b)(3)(B) of the Act and withholding of removal under the Convention Against Torture. (a... withholding of removal under the Convention Against Torture. (1) For purposes of regulations under Title II...

  16. 8 CFR 208.16 - Withholding of removal under section 241(b)(3)(B) of the Act and withholding of removal under the...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...)(3)(B) of the Act and withholding of removal under the Convention Against Torture. 208.16 Section 208... section 241(b)(3)(B) of the Act and withholding of removal under the Convention Against Torture. (a... withholding of removal under the Convention Against Torture. (1) For purposes of regulations under Title II...

  17. 8 CFR 208.16 - Withholding of removal under section 241(b)(3)(B) of the Act and withholding of removal under the...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...)(3)(B) of the Act and withholding of removal under the Convention Against Torture. 208.16 Section 208... section 241(b)(3)(B) of the Act and withholding of removal under the Convention Against Torture. (a... withholding of removal under the Convention Against Torture. (1) For purposes of regulations under Title II...

  18. 8 CFR 208.16 - Withholding of removal under section 241(b)(3)(B) of the Act and withholding of removal under the...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...)(3)(B) of the Act and withholding of removal under the Convention Against Torture. 208.16 Section 208... section 241(b)(3)(B) of the Act and withholding of removal under the Convention Against Torture. (a... withholding of removal under the Convention Against Torture. (1) For purposes of regulations under Title II...

  19. Intracortical connections are altered after long-standing deprivation of dorsal column inputs in the hand region of area 3b in squirrel monkeys.

    PubMed

    Liao, Chia-Chi; Reed, Jamie L; Kaas, Jon H; Qi, Hui-Xin

    2016-05-01

    A complete unilateral lesion of the dorsal column somatosensory pathway in the upper cervical spinal cord deactivates neurons in the hand region in contralateral somatosensory cortex (areas 3b and 1). Over weeks to months of recovery, parts of the hand region become reactivated by touch on the hand or face. To determine whether changes in cortical connections potentially contribute to this reactivation, we injected tracers into electrophysiologically identified locations in cortex of area 3b representing the reactivated hand and normally activated face in adult squirrel monkeys. Our results indicated that even when only partially reactivated, most of the expected connections of area 3b remained intact. These intact connections include the majority of intrinsic connections within area 3b; feedback connections from area 1, secondary somatosensory cortex (S2), parietal ventral area (PV), and other cortical areas; and thalamic inputs from the ventroposterior lateral nucleus (VPL). In addition, tracer injections in the reactivated hand region of area 3b labeled more neurons in the face and shoulder regions of area 3b than in normal monkeys, and injections in the face region of area 3b labeled more neurons in the hand region. Unexpectedly, the intrinsic connections within area 3b hand cortex were more widespread after incomplete dorsal column lesions (DCLs) than after a complete DCL. Although these additional connections were limited, these changes in connections may contribute to the reactivation process after injuries. J. Comp. Neurol. 524:1494-1526, 2016. © 2015 Wiley Periodicals, Inc. PMID:26519356

  20. 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

  1. A TonB-Dependent Transporter Is Responsible for Methanobactin Uptake by Methylosinus trichosporium OB3b.

    PubMed

    Gu, Wenyu; Farhan Ul Haque, Muhammad; Baral, Bipin S; Turpin, Erick A; Bandow, Nathan L; Kremmer, Elisabeth; Flatley, Andrew; Zischka, Hans; DiSpirito, Alan A; Semrau, Jeremy D

    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::Gm(r) 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::Gm(r) 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Phonon anomaly and anisotropic superconducting gap in noncentrosymmetric Li2(Pd1-xPtx)3B

    NASA Astrophysics Data System (ADS)

    Eguchi, G.; Peets, D. C.; Kriener, M.; Yonezawa, S.; Bao, G.; Harada, S.; Inada, Y.; Zheng, G.-q.; Maeno, Y.

    2013-04-01

    We report the systematic investigation of the specific heat of the noncentrosymmetric superconductor Li2(Pd1-xPtx)3B as a function of x. There is a large deviation of the phononic specific heat from the conventional Debye specific heat for Pt-rich samples. In contrast with the fully gapped conventional behavior for small x, a power-law temperature dependence of the electronic specific heat is observed even at x=0.5. These results manifest a strongly anisotropic or nodal superconducting gap even at x=0.5 and a nodal superconducting gap for x≳0.9.

  7. Investigation of the Dipole Response in Exotic Nuclei --- Experiments at the LAND-R^3B Setup

    NASA Astrophysics Data System (ADS)

    Rossi, D.; Adrich, P.; Aksouh, F.; Alvarez-Pol, H.; Aumann, T.; Benlliure, J.; Böhmer, M.; Boretzky, K.; Casarejos, E.; Chartier, M.; Chatillon, A.; Cortina-Gil, D.; Pramanik, U. D.; Emling, H.; Ershova, O.; Fernando-Dominguez, B.; Geissel, H.; Gorska, M.; Heil, M.; Johansson, H. k.; Junghans, A.; Kiselev, O.; Klimkiewicz, A.; Kratz, J.; Kurz, N.; Labiche, M.; Bleis, T. L.; Lemmon, R.; Litvinov, Y.; Mahata, K.; Maierbeck, P.; Movsesyan, A.; Nilsson, T.; Nociforo, C.; Palit, R.; Paschalis, S.; Plag, R.; Reifarth, R.; Simon, H.; Sümmerer, K.; Wagner, A.; Walus, W.; Weick, H.; Winkler, M.

    We present experimental results on the electromagneticexcitation of neutron-rich nickel isotopes, making use of the R^{3}B-LAND setup at GSI. Exotic beams were produced at approximately 500 MeV/u and their reactions were studied in inverse kinematics. Integral cross sections for ^{58}Ni are discussed and compared to previous data, providing a validation of our experimental method. The E1 excitation-energy distribution of the unstable ^{68}Ni is presented as well, showing an excess in cross section in the 1n decay channel when compared only with a typical Giant Dipole Resonance.

  8. The mechanical design of the BARREL section of the detector CALIFA for R3B-FAIR.

    NASA Astrophysics Data System (ADS)

    Casarejos, E.; Alvarez-Pol, H.; Cortina-Gil, D.; Durán, I.; Izquierdo, P.; Yañez, P.; Vilán, J. A.

    2014-03-01

    In this work we present the mechanical concept proposed for one of the sections of the detector CALIFA of the R3B experiment for FAIR. The use of an alveolar structure made of carbon-fiber composites allows for a light and robust solution to hold the active elements with an extreme mass ratio below 0.7%. The active core is supported by structural elements designed to make a fully operational assembly, taking care of different configurations and functionality. All the design has been developed using intensive calculation based in finite elements models and physical simulations.

  9. Reduced losses in rolled Fe73.5Si15.5Nb3B7Cu1 nanocrystalline ribbon

    NASA Astrophysics Data System (ADS)

    Kernion, S. J.; Lucas, M. S.; Horwath, J.; Turgut, Z.; Michel, E.; Keylin, V.; Huth, J. F.; Leary, A. M.; Shen, S.; McHenry, M. E.

    2013-05-01

    Eddy currents in magnetic components undergoing high frequency switching can be mitigated by reducing the thickness of the component. Planar flow cast Fe73.5Si15.5Nb3B7Cu1 ribbon was plastically deformed by cold rolling, resulting in a thickness reduction of 38%. Shear band formation was seen and the coercivity was dramatically higher in the rolled ribbon. After crystallization, the hysteresis loop of the rolled ribbon was nearly identical to a non-rolled ribbon and losses were lower in the rolled ribbon above 25 kHz. Reductions in thickness by this method can lead to increases in operating frequency for power conversion applications.

  10. New family of pectinase genes PGU1b-PGU3b of the pectinolytic yeast Saccharomyces bayanus var. uvarum.

    PubMed

    Naumov, G I; Shalamitskiy, M Yu; Naumova, E S

    2016-03-01

    Using yeast genome databases and literature data, we have conducted a phylogenetic analysis of pectinase PGU genes from Saccharomyces strains assigned to the biological species S. arboricola, S. bayanus (var. uvarum), S. cariocanus, S. cerevisiae, S. kudriavzevii, S. mikatae, S. paradoxus, and hybrid taxon S. pastorianus (syn. S. carlsbergensis). Single PGU genes were observed in all Saccharomyces species, except S. bayanus. The superfamily of divergent PGU genes has been documented in S. bayanus var. uvarum for the first time. Chromosomal localization of new PGU1b, PGU2b, and PGU3b genes in the yeast S. bayanus var. uvarum has been determined by molecular karyotyping and Southern hybridization. PMID:27193705

  11. C3b inactivator in the rheumatic diseases. Measurement by radial immunodiffusion and by inhibition of formation of properdin pathway C3 convertase.

    PubMed Central

    Whaley, K; Schur, P H; Ruddy, S

    1976-01-01

    C3b inactivator (C3bINA) has been measured in biologic fluids by radial immunodiffusion using a monospecific antiserum prepared in rabbits, and by a hemolytic assay which measures the reduction in the capacity of EAC43 cells bearing limited C3b sites to form C3B, the alternative pathway C3 convertase. The radial immunodiffusion and hemolytic assays show a good correlation (r = 0.86 P less than 0.001). Measurement of C3bINA concentrations in the sera of patients with systemic lupus erythematosus showed that during exacerbations of disease activity C3bINA concentrations tended to be lower, usually in association with reductions in C4, C3, factor B, and properdin, and sometimes with reductions of the alternative pathway proteins, factor B, and properdin alone. Supranormal values for C3bINA were found in the sera of 14 of 20 patients with seropositive rheumatoid arthritis and 3 of 9 seronegative patients, but none of 7 patients with degenerative joint disease. Synovial fluid concentrations of C3bINA, after correction for total synovial fluid protein and serum concentration of the enzyme, were significantly reduced in patients with rheumatoid arthritis compared to patients with degenerative joint disease (P less than 0.05). In both serum and synovial fluid from patients with rheumatoid arthritis, there was a good correlation between the concentrations of C3bINA and those of C3, factor B, and properdin, but not that of C4, suggesting that levels of C3bINA may serve to modulate recruitment of the properdin amplification loop in this disease. PMID:819459

  12. 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

  13. Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes.

    PubMed

    Bitsi, Stavroula; Ali, Houda; Maskell, Lauren; Ounzain, Samir; Mohamed-Ali, Vidya; Budhram-Mahadeo, Vishwanie S

    2016-03-01

    The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type 2 diabetes (T2D), whereas Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential gene expression in skeletal muscle from Brn-3b KO mice showed changes in genes that are implicated in T2D such as increased glycogen synthase kinase-3β and reduced GLUT4 glucose transporter. The GLUT4 gene promoter contains multiple Brn-3b binding sites and is directly transactivated by this transcription factor in cotransfection assays, whereas chromatin immunoprecipitation assays confirm that Brn-3b binds to this promoter in vivo. In addition, correlation between GLUT4 and Brn-3b in KO tissues or in C2C12 cells strongly supports a close association between Brn-3b levels and GLUT4 expression. Since Brn-3b is regulated by metabolites and insulin, this may provide a mechanism for controlling key genes that are required for normal metabolic processes in insulin-responsive tissues and its loss may contribute to abnormal glucose uptake. PMID:26670484

  14. Synthesis and structure of a 1,6-hexyldiamine heptaborate, [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}][B{sub 7}O{sub 10}(OH){sub 3}

    SciTech Connect

    Yang Sihai; Li Guobao Tian Shujian; Liao Fuhui; Xiong Ming; Lin Jianhua

    2007-08-15

    A new 1,6-hexyldiamine heptaborate, [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}][B{sub 7}O{sub 10}(OH){sub 3}] (1), has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, FTIR, elemental analysis, and thermogravimetric analysis. Compound 1 crystallizes in monoclinic system, space group P2{sub 1}/n with a=8.042(2) A, b=20.004(4) A, c=10.103(2) A, and {beta}=90.42(3) deg. The anionic [B{sub 7}O{sub 10}(OH){sub 3}]{sub n}{sup 2n-} layers are interlinked via hydrogen bonding to form a 3D supramolecular network containing large channels, in which the templated [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}]{sup 2+} cations are located. - Graphical abstract: A layered 1,6-hexyldiamine heptaborate, [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}][B{sub 7}O{sub 10}(OH){sub 3}], was solvothermally synthesized at 150 deg. C. It is a layer borate and crystallized in monoclinic space group P2{sub 1}/n with a=8.042(2) A, b=20.004(4) A, c=10.103(2) A, {beta}=90.42(3) deg.

  15. 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 may be classified as national security...

  16. 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 to originally classify information as Secret...

  17. 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...

  18. The Aspergillus fumigatus Dihydroxyacid Dehydratase Ilv3A/IlvC Is Required for Full Virulence

    PubMed Central

    Oliver, Jason D.; Kaye, Sarah J.; Tuckwell, Danny; Johns, Anna E.; Macdonald, Darel A.; Livermore, Joanne; Warn, Peter A.; Birch, Mike; Bromley, Michael J.

    2012-01-01

    Dihydroxyacid dehydratase (DHAD) is a key enzyme in the branched-chain amino acid biosynthetic pathway that exists in a variety of organisms, including fungi, plants and bacteria, but not humans. In this study we identified four putative DHAD genes from the filamentous fungus Aspergillus fumigatus by homology to Saccharomyces cerevisiae ILV3. Two of these genes, AFUA_2G14210 and AFUA_1G03550, initially designated AfIlv3A and AfIlv3B for this study, clustered in the same group as S. cerevisiae ILV3 following phylogenetic analysis. To investigate the functions of these genes, AfIlv3A and AfIlv3B were knocked out in A. fumigatus. Deletion of AfIlv3B gave no apparent phenotype whereas the Δilv3A strain required supplementation with isoleucine and valine for growth. Thus, AfIlv3A is required for branched-chain amino acid synthesis in A. fumigatus. A recombinant AfIlv3A protein derived from AFUA_2G14210 was shown to have DHAD activity in an in vitro assay, confirming that AfIlv3A is a DHAD. In addition we show that mutants lacking AfIlv3A and ilv3B exhibit reduced levels of virulence in murine infection models, emphasising the importance of branched-chain amino acid biosynthesis in fungal infections, and hence the potential of targeting this pathway with antifungal agents. Here we propose that AfIlv3A/AFUA_2G2410 be named ilvC. PMID:23028460

  19. 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.

  20. 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

  1. 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. PMID:25390890

  2. 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

  3. Typical BWR/4 MSIV closure ATWS analysis using RAMONA-3B code with space-time neutron kinetics

    SciTech Connect

    Neymotin, L.; Saha, P.

    1984-01-01

    A best-estimate analysis of a typical BWR/4 MSIV closure ATWS has been performed using the RAMONA-3B code with three-dimensional neutron kinetics. All safety features, namely, the safety and relief valves, recirculation pump trip, high pressure safety injections and the standby liquid control system (boron injection), were assumed to work as designed. No other operator action was assumed. The results show a strong spatial dependence of reactor power during the transient. After the initial peak of pressure and reactor power, the reactor vessel pressure oscillated between the relief valve set points, and the reactor power oscillated between 20 to 50% of the steady state power until the hot shutdown condition was reached at approximately 1400 seconds. The suppression pool bulk water temperature at this time was predicted to be approx. 96/sup 0/C (205/sup 0/F). In view of code performance and reasonable computer running time, the RAMONA-3B code is recommended for further best-estimate analyses of ATWS-type events in BWRs.

  4. 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.

  5. Preliminary Results for the Radiation Environment Observed by RD3-B3 Radiometerdosimeter Inside Bion-M # 1 Spacecraft

    NASA Astrophysics Data System (ADS)

    Dachev, Tsvetan; Tomov, Borislav; Matviichuk, Yury; Dimitrov, Plamen; Bankov, Nikolay; Petrov, Vladisloav; Shurshakov, Viacheslav; Ivanova, Olga; Häder, Donat-Peter; Lebert, Michael; Schuster, Martin; Reitz, Günter; Horneck, Gerda; Ploc, Ondrej

    2013-12-01

    Space radiation has been monitored using the P#xd0bb;3-킑3 (further is used the Latin transcription RD3-B3) spectrometer-dosimeter on board a recent space flight on the Russian recoverable satellite 킑킍OH-M No.1 (further is used the Latin transcription BIONM No. 1). The instrument was mounted inside of the satellite in pressurized volume together with biological objects and samples. RD3-B3 instrument is a battery operated version of the spare model of the R3D-B3 instrument developed and built for the ESA BIOPAN-6 facility on Foton M3 satellite flown in September 2007. Cosmic ionizing radiation has been monitored and separated in 256 deposited energy spectra, which were further used for determination of the absorbed dose rate and flux. The report summarizes the first results for the Earth radiation environment at the altitude (253-585 km) of the BION-M No.1 spacecraft.

  6. Performance of the correlation consistent composite approach for transition states: A comparison to G3B theory

    SciTech Connect

    Grimes, Thomas V.; Wilson, Angela K.; DeYonker, Nathan J.; Cundari, Thomas R.

    2007-10-21

    The correlation consistent composite approach (ccCA) was applied to the prediction of reaction barrier heights (i.e., transition state energy relative to reactants and products) for a standard benchmark set of reactions comprised of both hydrogen transfer reactions and nonhydrogen transfer reactions (i.e., heavy-atom transfer, S{sub N}2, and unimolecular reactions). The ccCA method was compared against G3B for the same set of reactions. Error metrics indicate that ccCA achieves 'chemical accuracy' with a mean unsigned error (MUE) of 0.89 kcal/mol with respect to the benchmark data for barrier heights; G3B has a mean unsigned error of 1.94 kcal/mol. Further, the greater accuracy of ccCA for predicted reaction barriers is compared to other benchmarked literature methods, including density functional (BB1K, MUE=1.16 kcal/mol) and wavefunction-based [QCISD(T), MUE=1.10 kcal/mol] methods.

  7. Micromagnetic finite element simulation of nanocrystalline α-Fe/Nd2Fe14B/Fe3B magnets

    NASA Astrophysics Data System (ADS)

    Saiden, N. M.; Schrefl, T.; Davies, H. A.; Hrkac, G.

    2014-09-01

    Nanocomposite Nd2Fe14B permanent magnets with Fe3B and α-Fe as the soft phase have been simulated using micromagnetic modelling. This paper reviews extensively the results from the simulation point of view. The magnetization configuration along the hysteresis loop is discussed in details. It was clear that the grain size and phase distribution play important roles in determining the magnetic properties. By changing the size of the grain and the volume fraction of the hard and soft phase, the magnetic properties change and the relationship between microstructure and properties is investigated. The remanence, Jr increases with decreasing of grain size, but oppositely for coercivity, Hc. The highest Jr, 1.46 T was obtained with a grain size 10 nm, and volume fraction of α-Fe, 40%. Whereas, the highest Hc with combination Nd2Fe14B 80% and 20% Fe3B, 947 kA/m. On the other hand, if Nd2Fe14B alone, the Hc able to reach up to 1000 kA/m. From this study, micromagnetic modelling contributes to a better understanding how microstructure and phase distribution influences the magnetic properties.

  8. The STT3a Subunit Isoform of the Arabidopsis Oligosaccharyltransferase Controls Adaptive Responses to Salt/Osmotic Stress

    PubMed Central

    Koiwa, Hisashi; Li, Fang; McCully, Michael G.; Mendoza, Imelda; Koizumi, Nozomu; Manabe, Yuzuki; Nakagawa, Yuko; Zhu, Jianhua; Rus, Ana; Pardo, José M.; Bressan, Ray A.; Hasegawa, Paul M.

    2003-01-01

    Arabidopsis stt3a-1 and stt3a-2 mutations cause NaCl/osmotic sensitivity that is characterized by reduced cell division in the root meristem. Sequence comparison of the STT3a gene identified a yeast ortholog, STT3, which encodes an essential subunit of the oligosaccharyltransferase complex that is involved in protein N-glycosylation. NaCl induces the unfolded protein response in the endoplasmic reticulum (ER) and cell cycle arrest in root tip cells of stt3a seedlings, as determined by expression profiling of ER stress–responsive chaperone (BiP-GUS) and cell division (CycB1;1-GUS) genes, respectively. Together, these results indicate that plant salt stress adaptation involves ER stress signal regulation of cell cycle progression. Interestingly, a mutation (stt3b-1) in another Arabidopsis STT3 isogene (STT3b) does not cause NaCl sensitivity. However, the stt3a-1 stt3b-1 double mutation is gametophytic lethal. Apparently, STT3a and STT3b have overlapping and essential functions in plant growth and developmental processes, but the pivotal and specific protein glycosylation that is a necessary for recovery from the unfolded protein response and for cell cycle progression during salt/osmotic stress recovery is associated uniquely with the function of the STT3a isoform. PMID:12972670

  9. 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. PMID:25612680

  10. Comprehensive precipitation evaluation of TRMM 3B42 with dense rain gauge networks in a mid-latitude basin, northeast, China

    NASA Astrophysics Data System (ADS)

    Cai, Yancong; Jin, Changjie; Wang, Anzhi; Guan, Dexin; Wu, Jiabing; Yuan, Fenghui; Xu, Leilei

    2015-08-01

    Knowledge on understanding quality of The Tropical Rainfall Measuring Mission (TRMM) 3B42 V7 dataset over mid-high latitudes regions is limited, which restricts its potential application in climate and hydrology fields. This study focuses on giving a detailed evaluation of the accuracy of 3B42 with observation data obtained from a high density rain gauge network over the Hun-Tai Basin in Liaoning Province, northeast China during 1998-2006. Several accuracy statistics are used to evaluate it quantitatively in terms of error of precipitation amount and ability in detecting the occurrence of precipitation events. Comparative results for three timescales (daily, monthly, and annual scale) at the basin scale show that 3B42 is more suitable for analyzing precipitation at large timescale, especially monthly scale (strong correlation of 0.93) due to the use of monthly rain gauge observation for bias correction in producing 3B42. Yet, 3B42 generally overestimates precipitation at all three timescales, especially the most serious degree of overestimation at daily scale with the absolute bias of 123.94 % and light to moderate rain events (1-20 mm). Moreover, the performance is influenced by topography, and 3B42 has a larger error of precipitation amount but has a better detection of the occurrence of precipitation events over high-altitude region than those over low-altitude region. Also, accuracy of 3B42 decreases with precipitation intensity, it suggests that 3B42 is incapable of capturing heavy precipitation events with desirable accuracy for the study on extreme precipitation events. In following works, overestimation characteristic should be weaken by improving satellite-based precipitation estimations algorithms and developing more effective bias correction techniques, it is important for streamflow simulations using 3B42 as forcing data over ungauged regions.

  11. Genomic pathology of SLE-associated copy-number variation at the FCGR2C/FCGR3B/FCGR2B locus.

    PubMed

    Mueller, Michael; Barros, Paula; Witherden, Abigail S; Roberts, Amy L; Zhang, Zhou; Schaschl, Helmut; Yu, Chack-Yung; Hurles, Matthew E; Schaffner, Catherine; Floto, R Andres; Game, Laurence; Steinberg, Karyn Meltz; Wilson, Richard K; Graves, Tina A; Eichler, Evan E; Cook, H Terence; Vyse, Timothy J; Aitman, Timothy J

    2013-01-10

    Reduced FCGR3B copy number is associated with increased risk of systemic lupus erythematosus (SLE). The five FCGR2/FCGR3 genes are arranged across two highly paralogous genomic segments on chromosome 1q23. Previous studies have suggested mechanisms for structural rearrangements at the FCGR2/FCGR3 locus and have proposed mechanisms whereby altered FCGR3B copy number predisposes to autoimmunity, but the high degree of sequence similarity between paralogous segments has prevented precise definition of the molecular events and their functional consequences. To pursue the genomic pathology associated with FCGR3B copy-number variation, we integrated sequencing data from fosmid and bacterial artificial chromosome clones and sequence-captured DNA from FCGR3B-deleted genomes to establish a detailed map of allelic and paralogous sequence variation across the FCGR2/FCGR3 locus. This analysis identified two highly paralogous 24.5 kb blocks within the FCGR2C/FCGR3B/FCGR2B locus that are devoid of nonpolymorphic paralogous sequence variations and that define the limits of the genomic regions in which nonallelic homologous recombination leads to FCGR2C/FCGR3B copy-number variation. Further, the data showed evidence of swapping of haplotype blocks between these highly paralogous blocks that most likely arose from sequential ancestral recombination events across the region. Functionally, we found by flow cytometry, immunoblotting and cDNA sequencing that individuals with FCGR3B-deleted alleles show ectopic presence of FcγRIIb on natural killer (NK) cells. We conclude that FCGR3B deletion juxtaposes the 5'-regulatory sequences of FCGR2C with the coding sequence of FCGR2B, creating a chimeric gene that results in an ectopic accumulation of FcγRIIb on NK cells and provides an explanation for SLE risk associated with reduced FCGR3B gene copy number. PMID:23261299

  12. 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. PMID:25428262

  13. 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.

  14. 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

  15. 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

  16. 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

  17. PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia.

    PubMed

    Cole, Christopher B; Verdoni, Angela M; Ketkar, Shamika; Leight, Elizabeth R; Russler-Germain, David A; Lamprecht, Tamara L; Demeter, Ryan T; Magrini, Vincent; Ley, Timothy J

    2016-01-01

    The DNA methyltransferases DNMT3A and DNMT3B are primarily responsible for de novo methylation of specific cytosine residues in CpG dinucleotides during mammalian development. While loss-of-function mutations in DNMT3A are highly recurrent in acute myeloid leukemia (AML), DNMT3A mutations are almost never found in AML patients with translocations that create oncogenic fusion genes such as PML-RARA, RUNX1-RUNX1T1, and MLL-AF9. Here, we explored how DNMT3A is involved in the function of these fusion genes. We used retroviral vectors to express PML-RARA, RUNX1-RUNX1T1, or MLL-AF9 in bone marrow cells derived from WT or DNMT3A-deficient mice. Additionally, we examined the phenotypes of hematopoietic cells from Ctsg-PML-RARA mice, which express PML-RARA in early hematopoietic progenitors and myeloid precursors, with or without DNMT3A. We determined that the methyltransferase activity of DNMT3A, but not DNMT3B, is required for aberrant PML-RARA-driven self-renewal ex vivo and that DNMT3A is dispensable for RUNX1-RUNX1T1- and MLL-AF9-driven self-renewal. Furthermore, both the PML-RARA-driven competitive transplantation advantage and development of acute promyelocytic leukemia (APL) required DNMT3A. Together, these findings suggest that PML-RARA requires DNMT3A to initiate APL in mice. PMID:26595813

  18. 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

  19. Research Update: Magnetic phase diagram of EuTi1-xBxO3 (B = Zr, Nb)

    DOE PAGESBeta

    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.

  20. 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.

  1. Spectroscopic investigations of Er3+ :CdO-Bi2 O3-B2O3 glasses.

    PubMed

    Nageswara Raju, C; Adinarayana Reddy, C; Sailaja, S; Seo, Hyo Jin; Sudhakar Reddy, B

    2012-01-01

    This article reports on the optical properties of Er3+ ions doped CdO-Bi2O3-B2O3 (CdBiB) glasses. The materials were characterized by optical absorption and emission spectra. By using Judd-Ofelt theory, the intensity parameters Ω(λ) (λ = 2, 4, 6) and also oscillatory strengths were calculated from the absorption spectra. The results were used to compute the radiative properties of Er3+ :CdBiB glasses. The concentration quenching and energy transfer from Yb3+ -Er3+ were explained. The stimulated emission cross-section, full width at half maximum (FWHM) and FWHM × σpE values are also calculated for all the Er3+ CdBiB glasses. PMID:21932395

  2. Femtosecond time-resolved ionization spectroscopy of Na 3(B) and the question of the geometric phase

    NASA Astrophysics Data System (ADS)

    Schön, J.; Köppel, H.

    1994-12-01

    The femtosecond time-resolved ionization spectrum of the B-state of Na 3 has been studied theoretically, taking two nuclear degrees of freedom into account (bending mode and pseudorotation). Special emphasis is put on a comparison between different approaches to the pseudorotational dynamics of Na 3(B) proposed earlier in the literature: a Jahn-Teller treatment invoked in the original work versus a pseudo-Jahn-Teller treatment advanced in later studies. The time-dependent wave-packet dynamics is found to differ drastically in the two cases although it proceeds on (virtually) the same potential energy surface. This is interpreted as a consequence of the geometric phase which is nontrivial only in the Jahn-Teller case. A low-energy peak in the Fourier transform of the pump-probe spectrum of Baumert et al. (Chem. Phys. Letters 209 (1993) 29) is tentatively interpreted as evidence in favour of the pseudo-Jahn-Teller mechanism.

  3. 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.

  4. Cell Cycle Regulation in the Estrogen Receptor Beta (ESR2)-Overexpressing Hep3B Hepatocellular Carcinoma Cell Line.

    PubMed

    Liu, Yi-Sheng; Tsai, Ying-Lan; Yeh, Yu-Lan; Chung, Li-Chin; Wen, Su-Ying; Kuo, Chia-Hua; Lin, Yueh-Min; Padma, V Vijaya; Kumar, V Bharath; Huang, Chih-Yang

    2015-04-30

    Epidemiological studies and experimental data have shown that the incidences of hepatocellular carcinoma in men are more frequent than in women. Evidence suggests that imbalance of hormones, including estrogen, androgen, prolactin, and growth hormone, modifies liver tumorigenesis. In this present study, we investigated how estrogen and estrogen receptor 2 (ESR2), regulates the cell cycle mechanism in Hep3B hepatocellular carcinoma cell line. Our results showed that ESR2 overexpression in the presence of 10⁻⁸ M 17-β-estradiol downregulated c-myc and cyclin D1 expression and simultaneously upregulated p27 expression. However, flow cytometry and MTT assays showed only minor G₁ phase arrest without affecting cell viability. Taken together, these observations indicate that ESR2 is required to lower tumorigenesis in males by altering cell cycle proteins in a ligand-dependent manner. PMID:25858474

  5. 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

  6. Characterizing the composition and evolution of homoeologous genomes in hexaploid wheat through BAC-end sequencing on chromosome 3B.

    PubMed

    Paux, Etienne; Roger, Delphine; Badaeva, Ekatherina; Gay, Georges; Bernard, Michel; Sourdille, Pierre; Feuillet, Catherine

    2006-11-01

    Bread wheat (Triticum aestivum) is one of the most important crops worldwide. However, because of its large, hexaploid, highly repetitive genome it is a challenge to develop efficient means for molecular analysis and genetic improvement in wheat. To better understand the composition and molecular evolution of the hexaploid wheat homoeologous genomes and to evaluate the potential of BAC-end sequences (BES) for marker development, we have followed a chromosome-specific strategy and generated 11 Mb of random BES from chromosome 3B, the largest chromosome of bread wheat. The sequence consisted of about 86% of repetitive elements, 1.2% of coding regions, and 13% remained unknown. With 1.2% of the sequence length corresponding to coding sequences, 6000 genes were estimated for chromosome 3B. New repetitive sequences were identified, including a Triticineae-specific tandem repeat (Fat) that represents 0.6% of the B-genome and has been differentially amplified in the homoeologous genomes before polyploidization. About 10% of the BES contained junctions between nested transposable elements that were used to develop chromosome-specific markers for physical and genetic mapping. Finally, sequence comparison with 2.9 Mb of random sequences from the D-genome of Aegilops tauschii suggested that the larger size of the B-genome is due to a higher content in repetitive elements. It also indicated which families of transposable elements are mostly responsible for differential expansion of the homoeologous wheat genomes during evolution. Our data demonstrate that BAC-end sequencing from flow-sorted chromosomes is a powerful tool for analysing the structure and evolution of polyploid and highly repetitive genomes. PMID:17010109

  7. NADH-regulated metabolic model for growth of Methylosinus trichosporium OB3b. Model presentation, parameter estimation, and model validation

    SciTech Connect

    Sipkema, E.M.; Koning, W. de; Ganzeveld, K.J.; Janssen, D.B.; Beenackers, A.A.C.M.

    2000-04-01

    Chlorinated ethenes, such as the environmental pollutant trichloroethene, can be converted aerobically only via cometabolism. In this process, conversion results from the nonspecificity of oxygenating enzymes. Expression of these enzymes occurs during growth on compounds such as alkanes, aromatics, and ammonia. A biochemical model is presented that described 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}-hydroxy-butyric 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{sub 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.

  8. Crystal structures of methyl 3-(4-iso-propyl-phen-yl)-1-methyl-1,2,3,3a,4,9b-hexa-hydro-thio-chromeno[4,3-b]pyrrole-3a-carboxyl-ate, methyl 1-methyl-3-(o-tol-yl)-1,2,3,3a,4,9b-hexa-hydro-thio-chromeno[4,3-b]pyrrole-3a-carboxyl-ate and methyl 1-methyl-3-(o-tol-yl)-3,3a,4,9b-tetra-hydro-1H-thio-chromeno[4,3-c]isoxazole-3a-carboxyl-ate.

    PubMed

    Raja, R; Suresh, M; Raghunathan, R; SubbiahPandi, A

    2015-06-01

    In the title compounds, C23H27NO2S, (I), and C21H23NO2S, (II), the pyrrole rings have envelope conformations with the C atom substituted by the benzene ring as the flap. In the third title compound, C20H21NO3S, (III), the isoxazole ring has a twisted conformation on the C-C bond substituted by the benzene ring and the carboxyl-ate group. In all three compounds, the thio-pyran ring has a half-chair conformation. The mean plane of the pyrrole ring is inclined to the mean plane of the thio-pyran ring by 57.07 (9), 58.98 (9) and 60.34 (12)° in (I), (II) and (III), respectively. The benzene rings are inclined to one another by 73.26 (10)° in (I), 65.781)° in (II) and 63.37 (13)° in (III). In the crystals of all three compounds, there are no classical hydrogen bonds present. Only in the crystal of compound (I) are mol-ecules linked by a pair of C-H⋯π inter-actions, forming inversion dimers. The isopropyl group in compound (I) is disordered over two sets of sites and has a refined occupancy ratio of 0.586 (13):0.414 (13). PMID:26090125

  9. Lymphocyte receptors. I. Receptors for Fc of IgG and complement (C3b) on immunoglobulin-bearing, antigen-binding and antibody-secreting cells.

    PubMed Central

    McConnell, I; Hurd, C M

    1976-01-01

    Immunoglobulin (Ig) bearing, antigen-binding and antibody-secreting cells were investigated for the presence of membrane receptors for the Fc part of IgG and for C3b on their surface. Fc and C3b receptors were detected on the surface of most Ig-bearing and of most antigen-binding cells. Fc receptors were also detected on IgM antibody-secreting cells but not on IgG-secreting cells. C3b receptors were not detected on any antibody-secreting cells. These receptors are either lost from the B cell surface as they differentiate into antibody-secreting cells or are blocked in vivo by immune complexes or C3b. PMID:800392

  10. Construction of a plant-microbe phytoremediation system: combination of vetiver grass with a functional endophytic bacterium, Achromobacter xylosoxidans F3B, for aromatic pollutants removal.

    PubMed

    Ho, Ying-Ning; Hsieh, Ju-Liang; Huang, Chieh-Chen

    2013-10-01

    The endophytic bacterial strain Achromobacter xylosoxidans F3B, which was able to utilize aromatic compounds as a sole carbon source, was inoculated into vetiver grass in this study. A real-time PCR detection method has been developed for confirming the stability of F3B in plants and DGGE profiles were conducted for examining the diversity of endophytes during the remediation process. These results showed that the endophytic bacteria strain F3B could maintain a stable population in plant roots without largely interfering with the diversity of native endophytes. Furthermore, the strain F3B could protect plants against toluene stress and maintain chlorophyll content of leaves, and a 30% reduction of evapotranspiration through vetiver leaves was observed. Our results demonstrate the potential to improve phytoremediation of aromatic pollutants by inoculating functional endophytic bacterial strains. PMID:23591084

  11. Cyclical DNA Methyltransferase 3a Expression Is a Seasonal and Estrus Timer in Reproductive Tissues.

    PubMed

    Lynch, Eloise W J; Coyle, Chris S; Lorgen, Marlene; Campbell, Ewan M; Bowman, Alan S; Stevenson, Tyler J

    2016-06-01

    It is becoming clear that epigenetic modifications such as DNA methylation can be dynamic and, in many cases, reversible. Here we investigated the photoperiod and hormone regulation of DNA methylation in testes, ovaries, and uterine tissue across multiple time scales. We hypothesized that DNA methyltransferase 3a (dnmt3a) is driven by photoperiodic treatment and exhibits natural variation across the female reproductive cycle and that melatonin increases whereas estrogen reduces DNA methylation. We used Siberian hamsters (Phodopus sungorus) due to their robust changes in reproductive physiology across seasonal and estrus time scales. Our findings indicate that short-day (SD) winter-like conditions significantly increased global DNA methylation and dnmt3a expression in the testes. Using immunohistochemistry, we confirm that increased dnmt3a expression was primarily localized to spermatogonium. Conversely, the ovaries did not exhibit variation in DNA methylation or dnmt3a/3b expression. However, exposure to SD significantly increased uterine dnmt3a expression. We then determined that dnmt3a was significantly decreased during the estrus stage. Next, we ovariectomized females and subsequently identified that a single estrogen+progesterone injection was sufficient to rapidly inhibit dnmt3a and dnmt3b expression. Finally, we demonstrate that treatment of human embryonic kidney-293 cells with melatonin significantly increased both dnmt3a and dnmt3b expression, suggesting that long-duration nocturnal signaling in SD may be involved in the regulation of DNA methylation in both sexes. Overall, our data indicate that dnmt3a shows marked photoperiod and estrus plasticity that likely has broad downstream effects on the timing of the genomic control of reproductive function. PMID:27105384

  12. 17 CFR 240.3b-4 - Definition of “foreign government,” “foreign issuer” and “foreign private issuer”.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... government,â âforeign issuerâ and âforeign private issuerâ. 240.3b-4 Section 240.3b-4 Commodity and... Definition of “foreign government,” “foreign issuer” and “foreign private issuer”. (a) The term foreign... country. (c) The term foreign private issuer means any foreign issuer other than a foreign...

  13. Synthesis and Antimicrobial Studies of Some Novel Bis-[1,3,4]thiadiazole and Bis-thiazole Pendant to Thieno[2,3-b]thiophene Moiety

    PubMed Central

    Kheder, Nabila Abdelshafy; Mabkhot, Yahia Nasser

    2012-01-01

    The synthetic utility of 3,3′-(3,4-dimethylthieno[2,3-b]thiophene-2,5-diyl)bis (3-oxopropanenitrile) (1) in the synthesis of some novel bis-[1,3,4-thiadiazole] 6a–g and bis-thiazole 10 and 13 derivatives with thieno[2,3-b]thiophene moiety is reported. Antimicrobial evaluation of some selected examples from the synthesized products was carried out and showed promising results. PMID:22489174

  14. Molecular Basis for Complement Recognition and Inhibition Determined by Crystallographic Studies of the Staphylococcal Complement Inhibitor (SCIN) Bound to C3c and C3b

    SciTech Connect

    Garcia, Brandon L.; Ramyar, Kasra X.; Tzekou, Apostolia; Ricklin, Daniel; McWhorter, William J.; Lambris, John D.; Geisbrecht, Brian V.

    2010-10-22

    The human complement system plays an essential role in innate and adaptive immunity by marking and eliminating microbial intruders. Activation of complement on foreign surfaces results in proteolytic cleavage of complement component 3 (C3) into the potent opsonin C3b, which triggers a variety of immune responses and participates in a self-amplification loop mediated by a multi-protein assembly known as the C3 convertase. The human pathogen Staphylococcus aureus has evolved a sophisticated and potent complement evasion strategy, which is predicated upon an arsenal of potent inhibitory proteins. One of these, the staphylococcal complement inhibitor (SCIN), acts at the level of the C3 convertase (C3bBb) and impairs downstream complement function by trapping the convertase in a stable but inactive state. Previously, we have shown that SCIN binds C3b directly and competitively inhibits binding of human factor H and, to a lesser degree, that of factor B to C3b. Here, we report the co-crystal structures of SCIN bound to C3b and C3c at 7.5 and 3.5 {angstrom} limiting resolution, respectively, and show that SCIN binds a critical functional area on C3b. Most significantly, the SCIN binding site sterically occludes the binding sites of both factor H and factor B. Our results give insight into SCIN binding to activated derivatives of C3, explain how SCIN can recognize C3b in the absence of other complement components, and provide a structural basis for the competitive C3b-binding properties of SCIN. In the future, this may suggest templates for the design of novel complement inhibitors based upon the SCIN structure.

  15. 17 CFR 240.3b-4 - Definition of “foreign government,” “foreign issuer” and “foreign private issuer”.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... government,â âforeign issuerâ and âforeign private issuerâ. 240.3b-4 Section 240.3b-4 Commodity and... Definition of “foreign government,” “foreign issuer” and “foreign private issuer”. (a) The term foreign... country. (c) The term foreign private issuer means any foreign issuer other than a foreign...

  16. 17 CFR 240.3b-4 - Definition of “foreign government,” “foreign issuer” and “foreign private issuer”.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... government,â âforeign issuerâ and âforeign private issuerâ. 240.3b-4 Section 240.3b-4 Commodity and... Definition of “foreign government,” “foreign issuer” and “foreign private issuer”. (a) The term foreign... country. (c) The term foreign private issuer means any foreign issuer other than a foreign...

  17. 17 CFR 240.3b-4 - Definition of “foreign government,” “foreign issuer” and “foreign private issuer”.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... government,â âforeign issuerâ and âforeign private issuerâ. 240.3b-4 Section 240.3b-4 Commodity and... Definition of “foreign government,” “foreign issuer” and “foreign private issuer”. (a) The term foreign... country. (c) The term foreign private issuer means any foreign issuer other than a foreign...

  18. Unified Approach to the Spiro(pyrrolidinyl-oxindole) and Hexahydropyrrolo[2,3-b]indole Alkaloids: Total Syntheses of Pseudophrynamines 270 and 272A.

    PubMed

    De, Subhadip; Das, Mrinal Kanti; Bhunia, Subhajit; Bisai, Alakesh

    2015-12-01

    The first enantioselective total syntheses of architecturally interesting prenylated pyrroloindole alkaloids, (-)-pseudophrynamines 272A (3d) and 270 (3b), have been achieved starting from enantioenriched 2-oxindoles having all-carbon quaternary stereocenters. A common strategy involving a thio-urea catalyzed aldol reaction is employed for the total synthesis of both spiro(pyrrolidinyl-oxindole) and hexahydropyrrolo[2,3-b]indole alkaloids. PMID:26600374

  19. 17 CFR 240.3b-4 - Definition of “foreign government,” “foreign issuer” and “foreign private issuer”.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of âforeign government,â âforeign issuerâ and âforeign private issuerâ. 240.3b-4 Section 240.3b-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and...

  20. 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...

  1. Assimilation of Chinese Fengyun-3B Microwave Temperature Sounder radiances into the Global GRAPES system with an improved cloud detection threshold

    NASA Astrophysics Data System (ADS)

    Li, Juan; Liu, Guiqing

    2016-03-01

    Fengyun-3B (FY-3B) is the second polar-orbiting satellite in the new Fengyun-three series. This paper describes the assimilation of the FY-3B Microwave Temperature Sounder (MWTS) radiances in the Chinese Numerical Weather prediction system — the Global and Regional Assimilation and PrEdiction System (GRAPES). A quality control procedure for the assimilation of the FY-3B MWTS radiance was proposed. Extensive monitoring before assimilation shows that the observations of channel 4 are notably contaminated. Channels 2 and 3 are used in this research. A cloud detection algorithm with an improved cloud-detection threshold is determined and incorporated into the impact experiments. The clear field-of-view (FOV) percentage increased from 42% to 57% with the new threshold. In addition, the newly added FOVs are located in the clear region, as demonstrated by the cloud liquid water path data from NOAA-18. The impact of the MWTS radiances on the prediction of GRAPES was researched. The observation biases of FY-3B MWTS O-B (differences between satellite observations and model simulations) significantly decreased after an empirical bias correction procedure. After assimilation, the residual biases are small. The assimilation of the FY-3B MWTS radiances shows a positive impact in the Northern Hemisphere and a neutral impact in the Southern Hemisphere.

  2. KIF3C and KIF3A Form a Novel Neuronal Heteromeric Kinesin That Associates with Membrane Vesicles

    PubMed Central

    Muresan, Virgil; Abramson, Tatiana; Lyass, Asya; Winter, Dirk; Porro, Elena; Hong, Filbert; Chamberlin, Nancy L.; Schnapp, Bruce J.

    1998-01-01

    We have cloned from rat brain the cDNA encoding an 89,828-Da kinesin-related polypeptide KIF3C that is enriched in brain, retina, and lung. Immunocytochemistry of hippocampal neurons in culture shows that KIF3C is localized to cell bodies, dendrites, and, in lesser amounts, to axons. In subcellular fractionation experiments, KIF3C cofractionates with a distinct population of membrane vesicles. Native KIF3C binds to microtubules in a kinesin-like, nucleotide-dependent manner. KIF3C is most similar to mouse KIF3B and KIF3A, two closely related kinesins that are normally present as a heteromer. In sucrose density gradients, KIF3C sediments at two distinct densities, suggesting that it may be part of two different multimolecular complexes. Immunoprecipitation experiments show that KIF3C is in part associated with KIF3A, but not with KIF3B. Unlike KIF3B, a significant portion of KIF3C is not associated with KIF3A. Consistent with these biochemical properties, the distribution of KIF3C in the CNS has both similarities and differences compared with KIF3A and KIF3B. These results suggest that KIF3C is a vesicle-associated motor that functions both independently and in association with KIF3A. PMID:9487132

  3. Point Defects and Protonic Conduction in A(3)(B'B"(2))O(9) Perovskite-Type Compounds

    NASA Astrophysics Data System (ADS)

    Du, Yang

    The defect structure and protonic transport properties of a number of rm A_3(B^' Nb_2)O_9 perovskite-type oxides, with A and B^' cations being alkaline earth elements, are investigated. The oxygen vacancies, V_sp{rm o}{ ^ddot}, are generated by nonstoichiometry which replaces a fraction of Nb^{5+ } ions by B^{'2+ } ions. Protons are then incorporated into the structure through the exchange reaction,. rm H_2O + V_sp {rm o}{^ddot} to O_sp{o}{x} + 2H^{.} by annealing the materials in moistened atmosphere. The protons can be removed by high temperature annealing in vacuum or in dry atmospheres. Impedance analysis is employed to extract the bulk electrical conductivity, sigma. The conductivity, sigma_{rm H}, of proton charged samples is more than an order of magnitude higher than samples without protons. Among the compounds studied, the H^+ charged samples of rm Ba_3(Ca_{1+3x }Nb_{2-3x})O_{9-delta } and rm Sr_3(Ca_ {1+3x}Nb_{2-3x})O_{9 -delta} show activation energy, E _{rm H}, of 0.52 ~ 0.55 eV and 0.64 ~ 0.66 eV, respectively, with sigma_ {rm H} comparable to those of the well-studied Nd^{3+}-doped BaCeO_3 and Yb^{3+ }-doped SrCeO_3. Without protons, the materials studied here are oxygen ion conductors with activation energy and conductivity compatible to Y -stablized ZrO_2. The ionic character of the dry samples is stable in a range of P_{o_2} over 18 orders of magnitude. As the number ratio of B site cations, B ^'/Nb, increases from 1/2, 1-1 ordered domains with B^'/Nb ~ 1 are created. The size and volume fraction of 1-1 ordered domains increases as B ^'/Nb approaches unity. The domain regions are rich in B^' and require positive ions, e.g. H^+ and V_sp{o}{2+}, for compensation. Internal friction peaks related to protons are observed in Nd^{3+}-doped BaCeO_3 but not in rm A_3(B^' Nb_2)O_9 compounds. Then pair-wise association of H ^+ or V_sp{o}{2+ } to specific sites in rm A_3(B ^' Nb_2)O_9 should not be considered. All compounds, showing considerable enhancement of

  4. Precipitation in the Mediterranean basin as seen from the 2000-2010 TRMM-3B42-v6 database

    NASA Astrophysics Data System (ADS)

    Sarrand, B.; Dulac, F.; Baldi, M.; Bargaoui, Z.; Cindrić, K.; Ducrocq, V.; Labiadh, M.; Schiavone, J.; de Silvestri, L.; Somot, S.; Tovar-Sánchez, A.

    2012-04-01

    This work presents a detailed analysis of 11 yrs of the version 6 of the TRMM-3B42 multi-sensor precipitation product (3-h and 0.25° resolution) from March 2000 to February 2011 over the whole Mediterranean basin and surrounding areas including the Black Sea (25°N-50°N, 10°W-43°E). We first discuss some issues in the data set regarding spatial and temporal discontinuities in coastal areas, and further illustrate a critical underestimation of light rains at latitudes higher than 36-37° that somewhat improves from 2007 on and is associated to the absence of coverage by the Precipitation Radar. North of the radar field of view, it seems that the marine coastal band is subject to a significant under detection of precipitation, whereas, on the opposite, the terrestrial coastal band south of 35°N in North Africa and the Near East shows unrealistic over detection of precipitation. We then evaluate the product against rain gauges with a focus on the western Mediterranean basin and the Adriatic. Our reference rain gauge data set includes about 1 million daily rain reports from more than 260 Mediterranean surface stations from Croatia, France, Italy, Malta, Spain (including 2 stations on the northern coast of Africa) and Tunisia, and from 9 additional non-Mediterranean stations from a flat region in France. It includes stations from almost 20 small Mediterranean islands. The comparison shows a significant correlation between TRMM-3B42v6 and rain gauges but with an overall tendency to underestimation. The average ratio of daily rates between surface stations and TRMM product is ~0.63 with significant regional variations, Corsica showing the poorest results and Spain the best. Over the Mediterranean stations considered, the average rate of success on the occurrence of precipitation (~0.75) is enhanced by the high proportion of dry days in the Mediterranean climate (~4 over 5 on average in the rain gauge data set) and drops off when only days with precipitation recorded

  5. The targeted inhibition of mitochondrial Hsp90 overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis

    SciTech Connect

    Yan, Chunlan; Oh, Joon Seok; Yoo, Seung Hee; Lee, Jee Suk; Yoon, Young Geol; Oh, Yoo Jin; Jang, Min Seok; Lee, Sang Yeob; Yang, Jun; Lee, Sang Hwa; Kim, Hye Young; Yoo, Young Hyun

    2013-01-01

    Previous studies have reported that a Gamitrinib variant containing triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits its activity, thus inducing the apoptotic pathway in the cells. Accordingly, G-TPP shows a potential as a promising drug for the treatment of cancer. A cell can die from different types of cell death such as apoptosis, necrosis, necroptosis, and autophagic cell death. In this study, we further investigated the mechanisms and modes of cell death in the G-TPP-treated Hep3B and U937 cell lines. We discovered that G-TPP kills the U937 cells through the apoptotic pathway and the overexpression of Bcl-2 significantly inhibits U937 cell death to G-TPP. We further discovered that G-TPP kills the Hep3B cells by activating necroptosis in combination with the partial activation of caspase-dependent apoptosis. Importantly, G-TPP overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. We also observed that G-TPP induces compensatory autophagy in the Hep3B cell line. We further found that whereas there is a Bcl-2-Beclin 1 interaction in response to G-TPP, silencing the beclin 1 gene failed to block LC3-II accumulation in the Hep3B cells, indicating that G-TPP triggers Beclin 1-independent protective autophagy in Hep3B cells. Taken together, these data reveal that G-TPP induces cell death through a combination of death pathways, including necroptosis and apoptosis, and overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. These findings are important for the therapeutic exploitation of necroptosis as an alternative cell death program to bypass the resistance to apoptosis. Highlights: ► G-TPP binds to mitochondrial Hsp90. ► G-TPP induces apoptosis in U937 human leukemia cancer cells. ► G-TPP induces combination of death pathways in Hep3B cell. ► G-TPP overcomes the resistance conferred by Bcl-2 in Hep3B cells via necroptosis. ► G-TPP triggers Beclin 1-independent

  6. Inhibition of Osteoclast Bone Resorption by Disrupting Vacuolar H+-ATPase a3-B2 Subunit Interaction*

    PubMed Central

    Kartner, Norbert; Yao, Yeqi; Li, Keying; Crasto, Gazelle J.; Datti, Alessandro; Manolson, Morris F.

    2010-01-01

    Vacuolar H+-ATPases (V-ATPases) are highly expressed in ruffled borders of bone-resorbing osteoclasts, where they play a crucial role in skeletal remodeling. To discover protein-protein interactions with the a subunit in mammalian V-ATPases, a GAL4 activation domain fusion library was constructed from an in vitro osteoclast model, receptor activator of NF-κB ligand-differentiated RAW 264.7 cells. This library was screened with a bait construct consisting of a GAL4 binding domain fused to the N-terminal domain of V-ATPase a3 subunit (NTa3), the a subunit isoform that is highly expressed in osteoclasts (a1 and a2 are also expressed, to a lesser degree, whereas a4 is kidney-specific). One of the prey proteins identified was the V-ATPase B2 subunit, which is also highly expressed in osteoclasts (B1 is not expressed). Further characterization, using pulldown and solid-phase binding assays, revealed an interaction between NTa3 and the C-terminal domains of both B1 and B2 subunits. Dual B binding domains of equal affinity were observed in NTa, suggesting a possible model for interaction between these subunits in the V-ATPase complex. Furthermore, the a3-B2 interaction appeared to be moderately favored over a1, a2, and a4 interactions with B2, suggesting a mechanism for the specific subunit assembly of plasma membrane V-ATPase in osteoclasts. Solid-phase binding assays were subsequently used to screen a chemical library for inhibitors of the a3-B2 interaction. A small molecule benzohydrazide derivative was found to inhibit osteoclast resorption with an IC50 of ∼1.2 μm on both synthetic hydroxyapatite surfaces and dentin slices, without significantly affecting RAW 264.7 cell viability or receptor activator of NF-κB ligand-mediated osteoclast differentiation. Further understanding of these interactions and inhibitors may contribute to the design of novel therapeutics for bone loss disorders, such as osteoporosis and rheumatoid arthritis. PMID:20837476

  7. Rainfall in an experimental watershed: a comparison between observed and TRMM 3B42V7 dataset

    NASA Astrophysics Data System (ADS)

    Barbosa, L. R.; Freitas, E. S.; Almeide, C. N.; Melo, D. C. D.

    2015-04-01

    In 2003, a network for hydrology of the semiarid region (REHISA in Portuguese) was created in Brazil. Since then, experimental watersheds in this region has been providing hydrometeorological data collected in automatic stations. However, the spatial distribution of these gauges might be insufficient to thoroughly understand the hydrological processes occurring in the area. Remotely sensed hydrological variables presents a possible way to overcome such limitations as long as these estimates prove to have enough accuracy. This paper compares the monitored yearly and monthly rainfall in the Guaraira experimental watershed with data from the Tropical Rainfall Measuring Mission (TRMM) 3B42 Version-7 product. The study area has a drainage area of 5.84 km2 and is located in the coastal region of Paraiba State, where the mean annual rainfall is 1,700 mm. Two automatic stations provided rainfall data from 2004 to 2011 to assess the satellite estimates in annual and monthly basis. TRMM 3B42V7 performance was evaluated based on graphical analysis. In the annual analysis, relative error ranged from 3 to -51%, however due to the monthly variation, such errors seemed to be insufficient to draw any conclusion, regarding the monthly results. For instance, when the relative error was 3% (difference of 48.3 mm for year 2004), the monthly analysis showed that this was due to a compensation occurred during the year, this is, a month for which rainfall was significantly underestimated by TRMM was compensated by another one when the satellite rainfall was overestimated. On the opposite, in 2007 (relative error 51%, 855 mm of difference), the monthly data analysis showed that just 4 months presented observed data overestimation, but it was enough to result in such annual overestimation. The monthly analysis showed that 29% of the months presented difference between observed rainfall and TRMM data greater than 70 mm and less than 386 mm, which can be considered a relevant error. 72.4% of

  8. The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity

    PubMed Central

    de Winter, F.; Kwok, J. C. F.; Fawcett, J. W.; Vo, T. T.; Carulli, D.; Verhaagen, J.

    2016-01-01

    During postnatal development, closure of critical periods coincides with the appearance of extracellular matrix structures, called perineuronal nets (PNN), around various neuronal populations throughout the brain. The absence or presence of PNN strongly correlates with neuronal plasticity. It is not clear how PNN regulate plasticity. The repulsive axon guidance proteins Semaphorin (Sema) 3A and Sema3B are also prominently expressed in the postnatal and adult brain. In the neocortex, Sema3A accumulates in the PNN that form around parvalbumin positive inhibitory interneurons during the closure of critical periods. Sema3A interacts with high-affinity with chondroitin sulfate E, a component of PNN. The localization of Sema3A in PNN and its inhibitory effects on developing neurites are intriguing features and may clarify how PNN mediate structural neural plasticity. In the cerebellum, enhanced neuronal plasticity as a result of an enriched environment correlates with reduced Sema3A expression in PNN. Here, we first review the distribution of Sema3A and Sema3B expression in the rat brain and the biochemical interaction of Sema3A with PNN. Subsequently, we review what is known so far about functional correlates of changes in Sema3A expression in PNN. Finally, we propose a model of how Semaphorins in the PNN may influence local connectivity. PMID:27057361

  9. Identification of a conserved linear epitope using a monoclonal antibody against non-structural protein 3B of foot-and-mouth disease virus.

    PubMed

    Li, Chaosi; Liang, Weifeng; Liu, Wenming; Yang, Decheng; Wang, Haiwei; Ma, Wenge; Zhou, Guohui; Yu, Li

    2016-02-01

    Foot-and-mouth disease virus (FMDV) is a member of the family Picornaviridae that has caused severe economic losses in many countries of the world. Regular vaccinations have been effectively used to control foot-and-mouth disease (FMD) in countries where the disease is enzootic. Distinguishing between infected and vaccinated animals in herds after immunization is an important component of effective eradication strategies. Nonstructural protein (NSP) 3B of FMDV is part of a larger antigen that is used for this differential diagnosis. In this study, an FMDV serotype-independent monoclonal antibody (MAb) against NSP 3B, 5D12, was generated. Using western blot, it was revealed that MAb 5D12 binds to three fragments of 3B displaying the motifs G(1)PYAGPLERQKPLK(14), K(18)LPQQEGPYAGPMER(32) and V(45)KEGPYEGPVKKPVA(59). The motif G(1)PYAGPLERQKPLK(14) was chosen for further mapping. Different truncated motifs derived from the motif G(1)PYAGPLERQKPLK(14) were expressed as GST-fusion constructs for western blot analysis. The results showed that the 5-aa peptide P(2)YAGP(6) was the minimal epitope reactive to MAb 5D12. Subsequent alanine-scanning mutagenesis analysis revealed that Pro(2), Gly(5) and Pro(6) were crucial for MAb 5D12 binding to P(2)YAGP(6). Furthermore, through sequence alignment analysis, the epitope PxxGP recognized by 5D12 was found to be present not only in 3B-1 but also in 3B2 and 3B3 and was highly conserved in seven serotypes of FMDV strains. Western blot analysis also revealed that the peptide epitope could be recognized by sera from FMDV-infected pigs and cattle. Thus, the 5D12-recognized 3B epitope identified here provides theoretical support for the development of MAb 5D12 as a differential diagnosis reagent for FMDV infection. PMID:26563318

  10. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients.

    PubMed

    Talib, L L; Hototian, S R; Joaquim, H P G; Forlenza, O V; Gattaz, W F

    2015-12-01

    Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein. PMID:25920742

  11. Distinct Fine-Scale fMRI Activation Patterns of Contra- and Ipsilateral Somatosensory Areas 3b and 1 in Humans

    PubMed Central

    Stringer, Elizabeth Ann; Qiao, Peng-Gang; Friedman, Robert M.; Holroyd, Lauren; Newton, Allen T; Gore, John C; Chen, Li Min

    2014-01-01

    Inter-areal and ipsilateral cortical responses to tactile stimulation have not been well described in humans S1 cortex. By taking advantage of high signal-to-noise ratio at 7 T, we quantified blood oxygenation level dependent (BOLD) response patterns and time courses to tactile stimuli on individual distal finger pads at a fine spatial scale, and examined whether there are inter-areal (area 3b versus area 1) and inter-hemispheric response differences to unilateral tactile stimulation in healthy human subjects. We found that 2-Hz tactile stimulation of individual fingertips evoked detectable BOLD signal changes in both contralateral and ipsilateral area 3b and area 1. Contralateral digit activations were organized in an orderly somatotopic manner, and BOLD responses in area 3b were more digit selective than those in area 1. However, the area of cortex that was responsive to stimulation of a single digit (stimulus-response field) was similar across areas. In the ipsilateral hemisphere, response magnitudes in both area 3b and area 1 were significantly weaker than those of the contralateral hemisphere. Digit activations exhibited no clear somatotopic organizational pattern in either area 3b or area 1, yet digit-selectivity was retained in area 1 but not in area 3b. The observation of distinct digit-selective responses of contralateral area 3b versus area 1 supports a higher order function of contralateral area 1 in spatial integration. In contrast, ipsilateral cortices may play a less discriminative role in the perception of unilateral tactile sensation in humans. PMID:24692215

  12. Evaluation of TMPA 3B42 Precipitation Estimates during the Passage of Tropical Cyclones over New Caledonia

    NASA Astrophysics Data System (ADS)

    Deo, Anil; Walsh, Kevin J. E.; Peltier, Alexandre

    2016-04-01

    This study evaluates the Tropical Rainfall Measuring Mission (TRMM) Multi-Satellite Precipitation Analysis (TMPA) 3B42 version 7 (V7) estimates of tropical cyclone (TC) rainfall over New Caledonia using the island rain gauge observations as the ground-truth reference. Several statistical measures and techniques are utilised to characterise the difference and similarity between TMPA and the gauge observations. The results show that TMPA has skill in representing the observed rainfall during the passage of TCs. TMPA overestimates light rainfall events and underestimates moderate to higher rainfall events. The skill deteriorates with increasing elevation, as underestimation by TMPA is greater at higher altitudes. The ability of TMPA also varies with TC intensity and distance from the TC centre, whereby it is more skilful for less intense TCs (category 1-2) and near the TC centre than in the outer rainbands. The ability of TMPA varies from case to case but a better performance is shown for TCs with a higher average rainfall. Finally, case studies of TC Vania (2011), TC Innis (2009), and TC Erica (2003) show that TMPA has the ability to represent the spatial distribution of the observed rainfall, but it tends to underestimate the higher rainfall events.

  13. Isolation, characterization, and biological activity of ferredoxin-NAD+ reductase from the methane oxidizer Methylosinus trichosporium OB3b.

    PubMed Central

    Chen, Y P; Yoch, D C

    1989-01-01

    A ferredoxin-NAD+ oxidoreductase (EC 1.18.1.3) has been isolated from extracts of the obligate methanotroph Methylosinus trichosporium OB3b. This enzyme was shown to couple electron flow from formate dehydrogenase (NAD+ requiring) to ferredoxin. Ferredoxin-NAD+ reductase was purified to homogeneity by conventional chromatography techniques and was shown to be a flavoprotein with a molecular weight of 36,000 +/- 1,000. This ferredoxin reductase was specific for NADH (Km, 125 microM) and coupled electron flow to the native ferredoxin and to ferredoxins from spinach, Clostridium pasteurianum, and Rhodospirillum rubrum (ferredoxin II). M. trichosporium ferredoxin saturated the ferredoxin-NAD+ reductase at a concentration 2 orders of magnitude lower (3 nM) than did spinach ferredoxin (0.4 microM). Ferredoxin-NAD+ reductase also had transhydrogenase activity which transferred electrons and protons from NADH to thionicotinamide adenine dinucleotide phosphate (Km, 9 microM) and from NADPH to 3-acetylpyridine adenine dinucleotide (Km, 16 microM). Reconstitution of a soluble electron transport pathway that coupled formate oxidation to ferredoxin reduction required formate dehydrogenase, NAD+, and ferredoxin-NAD+ reductase. Images PMID:2768195

  14. X-ray and IR Surveys of the Orion Molecular Clouds and the Cepheus OB3b Cluster

    NASA Astrophysics Data System (ADS)

    Megeath, S. Thomas; Wolk, Scott J.; Pillitteri, Ignazio; Allen, Tom

    2014-08-01

    X-ray and IR surveys of molecular clouds between 400 and 700 pc provide complementary means to map the spatial distribution of young low mass stars associated with the clouds. We overview an XMM survey of the Orion Molecular Clouds, at a distance of 400 pc. By using the fraction of X-ray sources with disks as a proxy for age, this survey has revealed three older clusters rich in diskless X-ray sources. Two are smaller clusters found at the northern and southern edges of the Orion A molecular cloud. The third cluster surrounds the O-star Iota Ori (the point of Orion's sword) and is in the foreground to the Orion molecular cloud. In addition, we present a Chandra and Spitzer survey of the Cep OB3b cluster at 700 pc. These data show a spatially variable disk fraction indicative of age variations within the cluster. We discuss the implication of these results for understanding the spread of ages in young clusters and the star formation histories of molecular clouds.

  15. Entangled Uranyl Organic Frameworks with (10,3)-b Topology and Polythreading Network: Structure, Luminescence, and Computational Investigation.

    PubMed

    Liu, Chao; Gao, Chao-Ying; Yang, Weiting; Chen, Fang-Yuan; Pan, Qing-Jiang; Li, Jiyang; Sun, Zhong-Ming

    2016-06-01

    Two 3D uranyl organic frameworks (UOFs) with entangled structures, (HPhen)2[(UO2)2L2]·4.5H2O (1) and [(UO2)3(H2O)4L2]·6H2O (2), were synthesized using a rigid tripodal linker (4,4',4″-(phenylsilanetriyl)tribenzoic acid, H3L). Compound 1 represents a 2-fold interpenetrating UOF with the unique (10,3)-b topology. Compound 2 is composed of three interlocked sets of identical singlet networks and thus exhibits a rare 3D polythreading network with (3,4)-connected topology. These two compounds have been characterized by IR, UV-vis, and photoluminescent spectroscopy. A density functional theory (DFT) study on the model compounds of 1 and 2 shows good agreement of structural parameters and U═O stretching vibrational frequencies with experimental data. The experimentally measured absorption bands were well reproduced by the time-dependent DFT calculations. PMID:27171364

  16. Effects of Aging-Time Reference on the Long Term Behavior of the IM7/K3B Composite

    NASA Technical Reports Server (NTRS)

    Veazie, David R.; Gates, Thomas S.

    1998-01-01

    An analytical study was undertaken to investigate the effects of the time-based shift reference on the long term behavior of the graphite reinforced thermoplastic polyimide composite IM7/K3B at elevated temperature. Creep compliance 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(sub g). Two matrix dominated loading modes, shear and transverse, were investigated in tension and compression. The momentary sequenced creep/aging curves were collapsed through a horizontal (time) shift using the shortest, middle and longest aging time curve as the reference curve. Linear viscoelasticity was used to characterize the creep/recovery behavior and superposition techniques were used to establish the physical aging related material constants. The use of effective time expressions in a laminated plate model allowed for the prediction of long term creep compliance. The effect of using different reference curves with time/aging-time superposition was most sensitive to the physical aging shift rate at lower test temperatures. Depending on the loading mode, the reference curve used can result in a more accurate long term prediction, especially at lower test temperatures.

  17. Effects of Buthus martensii (Karsch) scorpion venom on sodium currents in rat anterior pituitary (GH3/B6) cells.

    PubMed

    Bauer, C K; Krylov, B; Zhou, P A; Schwarz, J R

    1992-01-01

    The effects of two fractions (II, containing anti-insect toxins, and III, containing eight anti-mammal toxins) isolated from the venom of the Old World scorpion Buthus martensii (Karsch) on Na+ currents of rat anterior pituitary cells (GH3/B6 cells) were investigated using the whole-cell configuration of the patch clamp technique. Fraction II induced a temporary, and fraction III a permanent increase of the Na+ current amplitude. Application of each of the venom fractions resulted in a flattening of the curve relating steady state Na+ inactivation to membrane potential. In addition, the two fractions had specific effects. Fraction II shifted the voltage dependence of Na+ current activation by -42 mV, and the voltage dependence of Na+ inactivation by -25 mV in the absence of a conditioning depolarizing pre-pulse. Slowing of Na+ inactivation was most prominent at negative membrane potentials, resulting in a steady Na+ inward current at the holding potential of -80 mV. Fraction III induced a pronounced slowing of Na+ inactivation leading to an increase of peak Na+ currents and to incomplete steady state Na+ inactivation even at positive membrane potentials. PMID:1325686

  18. Correlation among electronic polarizability, optical basicity and interaction parameter of Bi 2O 3-B 2O 3 glasses

    NASA Astrophysics Data System (ADS)

    Zhao, Xinyu; Wang, Xiaoli; Lin, Hai; Wang, Zhiqiang

    2007-03-01

    For optical basicity and electronic polarizability, the previous studies basically concentrate on the wavelength range of the visible light region. However, heavy metal oxides glasses have a reputation of being good materials for infrared region. In this study, new data of the average electronic polarizability of the oxide ion α, optical basicity Λ and Yamashita-Kurosawa's interaction parameter A of Bi 2O 3-B 2O 3 glasses have been calculated in a wavelength range from 404.66 to 1083.03 nm. The present investigation suggests that both α and Λ increase gradually with increasing wave number, and A decreases with increasing wave number. Furthermore, close correlations are studied among α, Λ, A and refractive index n in this paper. Particularly, it has been found that a quantitative relationship between electronic polarizability and optical basicity is observed in a wavelength range from 404.66 to 1083.03 nm. Our present study extends over a wide range of α, Λ and A values.

  19. Emulsifying Activity and Stability of a Non-Toxic Bioemulsifier Synthesized by Microbacterium sp. MC3B-10

    PubMed Central

    Camacho-Chab, Juan Carlos; Guézennec, Jean; Chan-Bacab, Manuel Jesús; Ríos-Leal, Elvira; Sinquin, Corinne; Muñiz-Salazar, Raquel; De la Rosa-García, Susana del C.; Reyes-Estebanez, Manuela; Ortega-Morales, Benjamín Otto

    2013-01-01

    A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan is a high molecular weight (700 kDa), non-ionic molecule. Gas chromatography of the lipid fraction revealed the presence of palmitic, stearic, and oleic acids; thus microbactan may be considered a glycolipoprotein. Microbactan emulsified aromatic hydrocarbons and oils to various extents; the highest emulsification index was recorded against motor oil (96%). The stability of the microbactan-motor oil emulsion model reached its highest level (94%) at 50 °C, pH 10 and 3.5% NaCl content. It was not toxic to Artemia salina nauplii. Microbactan is, therefore, a non-toxic and non-ionic bioemulsifier of high molecular weight with affinity for a range of oily substrates. Comparative phylogenetic assessment of the 16S rDNA gene of Microbacterium sp. MC3B-10 with genes derived from other marine Microbacterium species suggested that this genus is well represented in coastal zones. The chemical nature and stability of the bioemulsifier suggest its potential application in bioremediation of marine environments and in cosmetics. PMID:24065097

  20. Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2

    PubMed Central

    Jung, Johannes; Bohn, Georg; Allroth, Anna; Boztug, Kaan; Brandes, Gudrun; Sandrock, Inga; Schäffer, Alejandro A.; Rathinam, Chozhavendan; Köllner, Inga; Beger, Carmela; Schilke, Reinhard; Welte, Karl; Grimbacher, Bodo; Klein, Christoph

    2006-01-01

    We report on the molecular etiology of an unusual clinical phenotype associating congenital neutropenia, thrombocytopenia, developmental delay, and hypopigmentation. Using genetic linkage analysis and targeted gene sequencing, we defined a homozygous genomic deletion in AP3B1, the gene encoding the β chain of the adaptor protein-3 (AP-3) complex. The mutation leads to in-frame skipping of exon 15 and thus perturbs proper assembly of the heterotetrameric AP-3 complex. Consequently, trafficking of transmembrane lysosomal proteins is aberrant, as shown for CD63. In basal keratinocytes, the incorporated immature melanosomes were rapidly degraded in large phagolysosomes. Despite distinct ultramorphologic changes suggestive of aberrant vesicular maturation, no functional aberrations were detected in neutrophil granulocytes. However, a comprehensive immunologic assessment revealed that natural killer (NK) and NKT-cell numbers were reduced in AP-3-deficient patients. Our findings extend the clinical and molecular phenotype of human AP-3 deficiency (also known as Hermansky-Pudlak syndrome, type 2) and provide further insights into the role of the AP-3 complex for the innate immune system. (Blood. 2006;108:362-369) PMID:16537806