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Sample records for 6c reveals determinants

  1. Voltage-sensing phosphatase reveals temporal regulation of TRPC3/C6/C7 channels by membrane phosphoinositides.

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    Itsuki, Kyohei; Imai, Yuko; Okamura, Yasushi; Abe, Kihachiro; Inoue, Ryuji; Mori, Masayuki X

    2012-01-01

    TRPC3/C6/C7 channels, a subgroup of classical/canonical TRP channels, are activated by diacylglycerol produced via activation of phospholipase C (PLC)-coupled receptors. Recognition of the physiological importance of these channels has been steadily growing, but the mechanism by which they are regulated remains largely unknown. We recently used a membrane-resident danio rerio voltage-sensing phosphatase (DrVSP) to study TRPC3/C6/C7 regulation and found that the channel activity was controlled by PtdIns(4,5)P(2)-DAG signaling in a self-limiting manner (Imai Y et al., the Journal of Physiology, 2012). In this addendum, we present the advantages of using DrVSP as a molecular tool to study PtdIns(4,5)P(2) regulation. DrVSP should be readily applicable for studying phosphoinositide metabolism-linked channel regulation as well as lipid dynamics. Furthermore, in comparison to other modes of self-limiting ion channel regulation, the regulation of TRPC3/C6/C7 channels seems highly susceptible to activation signal strength, which could potentially affect both open duration and the time to peak activation and inactivation. Dysfunction of such self-limiting regulation may contribute to the pathology of the cardiovascular system, gastrointestinal tract and brain, as these channels are broadly distributed and affected by numerous neurohormonal agonists.

  2. Determination of the Chronic Mammalian Toxicological Effects of TNT (twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the B6C3F1 Hybrid Mouse). Volume 1

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    1984-12-01

    negative results. Serum antibody titer was determined for the following diseases: GD-VII virus , K virus , Mouse Adenovirus, Sendal virus , Reovirus 3...Pneumonia virus of mice, Lyrphocytic Chorlomeningitis, Polyoma vIrus , MInute vIrus of mice, Mouse Hepatitis and Ectomella. These antibody titers were...0I0 w l o N C I -I--a))CO-o 0)-000 ) ~ -~ -OWNOON 3 iN N. NN -N N -CN---.N(- N C V(NNNN NN (N- ( NCV (\\(N ( IN C () N ( N D C0 C N N -N N - - -I))( N U

  3. Proximity Labeling Reveals Molecular Determinants of FGFR4 Endosomal Transport.

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    Haugsten, Ellen Margrethe; Sørensen, Vigdis; Kunova Bosakova, Michaela; de Souza, Gustavo Antonio; Krejci, Pavel; Wiedlocha, Antoni; Wesche, Jørgen

    2016-10-07

    The fibroblast growth factor receptors (FGFRs) are important oncogenes promoting tumor progression in many types of cancer, such as breast, bladder, and lung cancer as well as multiple myeloma and rhabdomyosarcoma. However, little is known about how these receptors are internalized and down-regulated in cells. We have here applied proximity biotin labeling to identify proteins involved in FGFR4 signaling and trafficking. For this purpose we fused a mutated biotin ligase, BirA*, to the C-terminal tail of FGFR4 (FGFR4-BirA*) and the fusion protein was stably expressed in U2OS cells. Upon addition of biotin to these cells, proteins in proximity to the FGFR4-BirA* fusion protein became biotinylated and could be isolated and identified by quantitative mass spectrometry. We identified in total 291 proteins, including 80 proteins that were enriched in samples where the receptor was activated by the ligand (FGF1), among them several proteins previously found to be involved in FGFR signaling (e.g., FRS2, PLCγ, RSK2 and NCK2). Interestingly, many of the identified proteins were implicated in endosomal transport, and by precise annotation we were able to trace the intracellular pathways of activated FGFR4. Validating the data by confocal and three-dimensional structured illumination microscopy analysis, we concluded that FGFR4 uses clathrin-mediated endocytosis for internalization and is further sorted from early endosomes to the recycling compartment and the trans-Golgi network. Depletion of cells for clathrin heavy chain led to accumulation of FGFR4 at the cell surface and increased levels of active FGFR4 and PLCγ, while AKT and ERK signaling was diminished, demonstrating that functional clathrin-mediated endocytosis is required for proper FGFR4 signaling. Thus, this study reveals proteins and pathways involved in FGFR4 transport and signaling that provide possible targets and opportunities for therapeutic intervention in FGFR4 aberrant cancer.

  4. Pathogenicity determinants in smut fungi revealed by genome comparison.

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    Schirawski, Jan; Mannhaupt, Gertrud; Münch, Karin; Brefort, Thomas; Schipper, Kerstin; Doehlemann, Gunther; Di Stasio, Maurizio; Rössel, Nicole; Mendoza-Mendoza, Artemio; Pester, Doris; Müller, Olaf; Winterberg, Britta; Meyer, Elmar; Ghareeb, Hassan; Wollenberg, Theresa; Münsterkötter, Martin; Wong, Philip; Walter, Mathias; Stukenbrock, Eva; Güldener, Ulrich; Kahmann, Regine

    2010-12-10

    Biotrophic pathogens, such as the related maize pathogenic fungi Ustilago maydis and Sporisorium reilianum, establish an intimate relationship with their hosts by secreting protein effectors. Because secreted effectors interacting with plant proteins should rapidly evolve, we identified variable genomic regions by sequencing the genome of S. reilianum and comparing it with the U. maydis genome. We detected 43 regions of low sequence conservation in otherwise well-conserved syntenic genomes. These regions primarily encode secreted effectors and include previously identified virulence clusters. By deletion analysis in U. maydis, we demonstrate a role in virulence for four previously unknown diversity regions. This highlights the power of comparative genomics of closely related species for identification of virulence determinants.

  5. Low expression of SEMA6C accelerates the primordial follicle activation in the neonatal mouse ovary.

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    Zhou, Su; Yan, Wei; Shen, Wei; Cheng, Jing; Xi, Yueyue; Yuan, Suzhen; Fu, Fangfang; Ding, Ting; Luo, Aiyue; Wang, Shixuan

    2017-09-07

    The primordial follicle assembly, activation and the subsequent development are critical processes for female reproduction. A limited number of primordial follicles are activated to enter the growing follicle pool each wave, and the primordial follicle pool progressively diminishes over a woman's life-time. The number of remaining primordial follicles represents the ovarian reserve. Identification and functional investigation of the factors involved in follicular initial recruitment will be of great significance to the understanding of the female reproduction process and ovarian ageing. In this study, we aimed to study whether and how semaphorin 6C (Sema6c) regulated the primordial follicle activation in the neonatal mouse ovary. The attenuation of SEMA6C expression by SiRNA accelerated the primordial follicle activation in the in vitro ovary culture system. PI3K-AKT-rpS6 pathway was activated when SEMA6C expression was down-regulated. And the LY294002 could reverse the effect of low SEMA6C expression on primordial follicle activation. Our findings revealed that Sema6c was involved in the activation of primordial follicles, and the down-regulation of SEMA6C led to massive primordial follicle activation by interacting with the PI3K-AKT-rpS6 pathway, which might also provide valuable information for understanding premature ovarian failure and ovarian ageing. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Genetic mapping of sex determination in a wild strawberry, Fragaria virginiana, reveals earliest form of sex chromosome.

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    Spigler, R B; Lewers, K S; Main, D S; Ashman, T-L

    2008-12-01

    The evolution of separate sexes (dioecy) from hermaphroditism is one of the major evolutionary transitions in plants, and this transition can be accompanied by the development of sex chromosomes. Studies in species with intermediate sexual systems are providing unprecedented insight into the initial stages of sex chromosome evolution. Here, we describe the genetic mechanism of sex determination in the octoploid, subdioecious wild strawberry, Fragaria virginiana Mill., based on a whole-genome simple sequence repeat (SSR)-based genetic map and on mapping sex determination as two qualitative traits, male and female function. The resultant total map length is 2373 cM and includes 212 markers on 42 linkage groups (mean marker spacing: 14 cM). We estimated that approximately 70 and 90% of the total F. virginiana genetic map resides within 10 and 20 cM of a marker on this map, respectively. Both sex expression traits mapped to the same linkage group, separated by approximately 6 cM, along with two SSR markers. Together, our phenotypic and genetic mapping results support a model of gender determination in subdioecious F. virginiana with at least two linked loci (or gene regions) with major effects. Reconstruction of parental genotypes at these loci reveals that both female and hermaphrodite heterogamety exist in this species. Evidence of recombination between the sex-determining loci, an important hallmark of incipient sex chromosomes, suggest that F. virginiana is an example of the youngest sex chromosome in plants and thus a novel model system for the study of sex chromosome evolution.

  7. Interleukin-6 c.-174G>C Polymorphism and Periodontitis in a Brazilian Population.

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    Gabriela Teixeira, Fernanda; Mendonça, Samir Andrade; Menezes Oliveira, Kamilla; Barbosa Dos Santos, Djanilson; Miranda Marques, Lucas; Mendonça Amorim, Maise; de Souza Gestinari, Raquel

    2014-01-01

    Aim. Periodontitis is an inflammatory disease that affects the teeth supporting structures, triggered by periodontal pathogens, and is influenced by environmental and genetic factors. Genes encoding molecules related to the immune response, such as cytokine, are the main candidates for polymorphisms analysis and may be possibly associated with this pathology. A G/C promoter polymorphism on the IL6 gene has been shown to affect basal IL-6 levels. The aim of this study was to investigate the association between the IL6 c.-174G>C polymorphism and periodontitis in individuals from Vitória da Conquista, Bahia, Brazil. Material and Methods. Three hundred and thirty individuals (134 cases, 196 controls) were genotyped for the IL6 c.-174G>C by MS-PCR technique. Concentrations of salivary IL-6 were determined by ELISA method. Results. The IL6 c.-174G>C polymorphism was associated with periodontitis when comparing the distribution of genotypes between patients with periodontitis and control subjects. The GC genotype appeared as a protective factor for periodontitis. Results showed increased levels of salivary IL-6 in periodontitis patients. Nevertheless, there was no relationship between the concentrations of IL-6 and genotypes when comparing the case and control groups. Conclusions. Our data indicate an association between IL6 c.-174G>C polymorphism and periodontitis and showed that IL-6 may be considered an important marker for periodontitis.

  8. Interleukin-6 c.-174G>C Polymorphism and Periodontitis in a Brazilian Population

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    Fernanda Gabriela Teixeira

    2014-01-01

    Full Text Available Aim. Periodontitis is an inflammatory disease that affects the teeth supporting structures, triggered by periodontal pathogens, and is influenced by environmental and genetic factors. Genes encoding molecules related to the immune response, such as cytokine, are the main candidates for polymorphisms analysis and may be possibly associated with this pathology. A G/C promoter polymorphism on the IL6 gene has been shown to affect basal IL-6 levels. The aim of this study was to investigate the association between the IL6 c.-174G>C polymorphism and periodontitis in individuals from Vitória da Conquista, Bahia, Brazil. Material and Methods. Three hundred and thirty individuals (134 cases, 196 controls were genotyped for the IL6 c.-174G>C by MS-PCR technique. Concentrations of salivary IL-6 were determined by ELISA method. Results. The IL6 c.-174G>C polymorphism was associated with periodontitis when comparing the distribution of genotypes between patients with periodontitis and control subjects. The GC genotype appeared as a protective factor for periodontitis. Results showed increased levels of salivary IL-6 in periodontitis patients. Nevertheless, there was no relationship between the concentrations of IL-6 and genotypes when comparing the case and control groups. Conclusions. Our data indicate an association between IL6 c.-174G>C polymorphism and periodontitis and showed that IL-6 may be considered an important marker for periodontitis.

  9. Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders.

    NARCIS (Netherlands)

    Thiadens, A.A.H.J.; Hollander, A.I. den; Roosing, S.; Nabuurs, S.B.; Zekveld-Vroon, R.C.; Collin, R.W.J.; Baere, E. de; Koenekoop, R.K.; Schooneveld, M.J. van; Strom, T.M.; Lith-Verhoeven, J.J. van; Lotery, A.J.; Moll-Ramirez, N.G. van; Leroy, B.P.; Born, L.I. van den; Hoyng, C.B.; Cremers, F.P.M.; Klaver, C.C.

    2009-01-01

    Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of autosomal recessive (ar)CD are largely unknown. Our aim was to identify causative genes for these diso

  10. Homozygosity Mapping Reveals PDE6C Mutations in Patients with Early-Onset Cone Photoreceptor Disorders

    NARCIS (Netherlands)

    A.A.H.J. Thiadens (Alberta); A.I. Hollander (Anneke); S. Roosing (Susanne); S.B. Nabuurs (Sander); R.C. Zekveld-Vroon (Renate); R.W.J. Collin (Rob); E. de Baere (Elfride); R.K. Koenekoop (Robert); M.J. Schooneveld (Mary); T.M. Strom (Tim); J.J.C. van Lith-Verhoeven (Janneke); A.J. Lotery (Andrew); N. van Moll-Ramirez (Norka); B.P. Leroy (Bart); L.I. van den Born (Ingeborgh); C. Hoyng (Carel); F.P.M. Cremers (Frans); C.C.W. Klaver (Caroline)

    2009-01-01

    textabstractCone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of autosomal recessive (ar)CD are largely unknown. Our aim was to identify causative genes fo

  11. Multilocus Sex Determination Revealed in Two Populations of Gynodioecious Wild Strawberry, Fragaria vesca subsp. bracteata.

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    Ashman, Tia-Lynn; Tennessen, Jacob A; Dalton, Rebecca M; Govindarajulu, Rajanikanth; Koski, Matthew H; Liston, Aaron

    2015-10-19

    Gynodioecy, the coexistence of females and hermaphrodites, occurs in 20% of angiosperm families and often enables transitions between hermaphroditism and dioecy. Clarifying mechanisms of sex determination in gynodioecious species can thus illuminate sexual system evolution. Genetic determination of gynodioecy, however, can be complex and is not fully characterized in any wild species. We used targeted sequence capture to genetically map a novel nuclear contributor to male sterility in a self-pollinated hermaphrodite of Fragaria vesca subsp. bracteata from the southern portion of its range. To understand its interaction with another identified locus and possibly additional loci, we performed crosses within and between two populations separated by 2000 km, phenotyped the progeny and sequenced candidate markers at both sex-determining loci. The newly mapped locus contains a high density of pentatricopeptide repeat genes, a class commonly involved in restoration of fertility caused by cytoplasmic male sterility. Examination of all crosses revealed three unlinked epistatically interacting loci that determine sexual phenotype and vary in frequency between populations. Fragaria vesca subsp. bracteata represents the first wild gynodioecious species with genomic evidence of both cytoplasmic and nuclear genes in sex determination. We propose a model for the interactions between these loci and new hypotheses for the evolution of sex determining chromosomes in the subdioecious and dioecious Fragaria.

  12. Spondyloptosis of C6-C7: a rare case report

    Institute of Scientific and Technical Information of China (English)

    Manish Chadha; Ajay Pal Singh; Arun Pal Singh

    2010-01-01

    A 35 years old female presented to us after falling from a height. She complained of a neck pain and a complete quadriplegia and was diagnosed as having spondyloptosis of the C6-C7. Skeletal traction was performed on her. CT scan showed fractures of the C5, C6, and C7 vertebral body. The patient underwent anterior approach partial corpectomy with anterior cervical locking plate and strut grafting from ipsilateral iliac crest. Intraoperatively it was found that the disc was completely ruptured and there was a dural tear and cerebrospinal fluid leak. Her postoperative period was complicated by cerebrospinal fluid collection and posterior instrumentation was not performed due to the poor general condition. She had no neural recovery at the last follow-up. Spondyloptosis is a severe and highly unstable injury with a three column ligamentous disruption and may be complicated, as in our case, with a dural tear.Management of these cases is fraught with complications,and prognosis for neural recovery is dismal.

  13. Structure determination of archaea-specific ribosomal protein L46a reveals a novel protein fold

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    Feng, Yingang, E-mail: fengyg@qibebt.ac.cn [Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101 (China); Song, Xiaxia [Department of Biological Science and Engineering, School of Chemical and Biological Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Lin, Jinzhong [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Xuan, Jinsong [Department of Biological Science and Engineering, School of Chemical and Biological Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Cui, Qiu [Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101 (China); Wang, Jinfeng [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-07-18

    Highlights: • The archaea-specific ribosomal protein L46a has no homology to known proteins. • Three dimensional structure and backbone dynamics of L46a were determined by NMR. • The structure of L46a represents a novel protein fold. • A potential rRNA-binding surface on L46a was identified. • The potential position of L46a on the ribosome was proposed. - Abstract: Three archaea-specific ribosomal proteins recently identified show no sequence homology with other known proteins. Here we determined the structure of L46a, the most conserved one among the three proteins, from Sulfolobus solfataricus P2 using NMR spectroscopy. The structure presents a twisted β-sheet formed by the N-terminal part and two helices at the C-terminus. The L46a structure has a positively charged surface which is conserved in the L46a protein family and is the potential rRNA-binding site. Searching homologous structures in Protein Data Bank revealed that the structure of L46a represents a novel protein fold. The backbone dynamics identified by NMR relaxation experiments reveal significant flexibility at the rRNA binding surface. The potential position of L46a on the ribosome was proposed by fitting the structure into a previous electron microscopy map of the ribosomal 50S subunit, which indicated that L46a contacts to domain I of 23S rRNA near a multifunctional ribosomal protein L7ae.

  14. Ly6C- Monocytes Regulate Parasite-Induced Liver Inflammation by Inducing the Differentiation of Pathogenic Ly6C+ Monocytes into Macrophages.

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    Yannick Morias

    2015-05-01

    Full Text Available Monocytes consist of two well-defined subsets, the Ly6C+ and Ly6C- monocytes. Both CD11b+ myeloid cells populations have been proposed to infiltrate tissues during inflammation. While infiltration of Ly6C+ monocytes is an established pathogenic factor during hepatic inflammation, the role of Ly6C- monocytes remains elusive. Mice suffering experimental African trypanosome infection die from systemic inflammatory response syndrome (SIRS that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/necrosis of liver myeloid and parenchymal cells that reduces host survival. C57BL/6 mice are considered as trypanotolerant to Trypanosoma congolense infection. We have reported that in these animals, IL-10, produced among others by myeloid cells, limits the liver damage caused by pathogenic TNF-producing Ly6C+ monocytes, ensuring prolonged survival. Here, the heterogeneity and dynamics of liver myeloid cells in T. congolense-infected C57/BL6 mice was further dissected. Moreover, the contribution of Ly6C- monocytes to trypanotolerance was investigated. By using FACS analysis and adoptive transfer experiments, we found that the accumulation of Ly6C- monocytes and macrophages in the liver of infected mice coincided with a drop in the pool of Ly6C+ monocytes. Pathogenic TNF mainly originated from Ly6C+ monocytes while Ly6C- monocytes and macrophages were major and equipotent sources of IL-10 within myeloid cells. Moreover, Nr4a1 (Nur77 transcription factor-dependent Ly6C- monocytes exhibited IL-10-dependent and cell contact-dependent regulatory properties contributing to trypanotolerance by suppressing the production of TNF by Ly6C+ monocytes and by promoting the differentiation of the latter cells into macrophages. Thus, Ly6C- monocytes can dampen liver damage caused by an extensive Ly6C+ monocyte-associated inflammatory immune response in T. congolense trypanotolerant animals. In a more general context, Ly6C- or Ly6C

  15. Identification of Sex-Specific Markers Reveals Male Heterogametic Sex Determination in Pseudobagrus ussuriensis.

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    Pan, Zheng-Jun; Li, Xi-Yin; Zhou, Feng-Jian; Qiang, Xiao-Gang; Gui, Jian-Fang

    2015-08-01

    Comprehending sex determination mechanism is a first step for developing sex control breeding biotechnologies in fish. Pseudobagrus ussuriensis, one of bagrid catfishes in Bagridae, had been observed to have about threefold size dimorphism between males and females, but its sex determination mechanism had been unknown. In this study, we firstly used the amplified fragment length polymorphism (AFLP)-based screening approach to isolate a male-specific DNA fragment and thereby identified a 10,569 bp of male-specific sequence and a 10,365 bp of female-related sequence by genome walking in the bagrid catfish, in which a substantial genetic differentiation with 96.35 % nucleotide identity was revealed between them. Subsequently, a high differentiating region of 650 bp with only 70.26 % nucleotide identity was found from the corresponding two sequences, and three primer pairs of male-specific marker, male and female-shared marker with different length products in male and female genomes, and female-related marker were designed. Significantly, when these markers were used to identify genetic sex of the bagrid catfish, only male individuals was detected to amplify the male-specific marker fragment, and female-related marker was discovered to produce dosage association in females and in males. Our current data provide significant genetic evidence that P. ussuriensis has heterogametic XY sex chromosomes in males and homogametic XX sex chromosomes in females. Therefore, sex determination mechanism of P. ussuriensis is male heterogametic XX/XY system.

  16. Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors.

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    Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

    2015-05-19

    In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

  17. Epidemiology of pneumococcal serotype 6A and 6C among invasive and carriage isolates from Alaska, 1986–2009☆

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    Rudolph, Karen; Bruce, Michael; Bruden, Dana; Zulz, Tammy; Wenger, Jay; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas

    2015-01-01

    We investigated serotype 6A/6C invasive pneumococcal disease (IPD) incidence, genetic diversity, and carriage before and after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Alaska. IPD cases (1986–2009) were identified through population-based laboratory surveillance. Isolates were initially serotyped by conventional methods, and 6C isolates were differentiated from 6A by polymerase chain reaction. Among invasive and carriage isolates initially typed as 6A, 35% and 50% were identified as 6C, respectively. IPD rates caused by serotype 6A or 6C among children <5 years did not change from the pre- to post-PCV7 period (P = 0.71 and P = 0.09, respectively). Multilocus sequence typing of IPD isolates revealed 28 sequence types. The proportion of serotype 6A carriage isolates decreased from 7.4% pre-PCV7 to 1.8% (P < 0.001) during 2008–2009; the proportion of serotype 6C carriage isolates increased from 3.0% to 8.4% (P = 0.004) among children <5 years. Continued surveillance is warranted to monitor changes in serotype distribution and prevalence. PMID:23276772

  18. 6-C-methyl flavonoids isolated from Pinus densata inhibit the proliferation and promote the apoptosis of the HL-60 human promyelocytic leukaemia cell line.

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    Yue, Rongcai; Li, Bo; Shen, Yunheng; Zeng, Huawu; Li, Bo; Yuan, Hu; He, Yiren; Shan, Lei; Zhang, Weidong

    2013-08-01

    Three structurally related 6-C-methyl flavonoids isolated from Pinus densata, including 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (PD1), 5,7,4'-trihydroxy-3,8-dimethoxy-6-C-methylflavone (PD2), and 5,7,4'-trihydroxy-3-methoxy-6-C-methylflavone (PD3), were tested for their ability to inhibit the proliferation and promote the apoptosis of the HL-60 human leukaemia cell line. Cytotoxicity assays in the HL-60 human cancer cell line demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone exhibited the most potent cytotoxicity of the three structurally related 6-C-methyl flavonoids. 5,4'-Dihydroxy-3,7,8-trimethoxy-6-C-methylflavone inhibited the proliferation of HL-60 cells in a dose-dependent manner with an IC₅₀ of 7.91 µM (48 h treatment). Furthermore, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-induced apoptosis was associated with mitochondrial membrane disruption and cytochome c release. Flow cytometry analyses revealed an increase in the hypodiploid population in 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-treated HL-60 cells. Treatment with a concentration of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone that induced apoptosis activated caspase-3 but did not activate caspase-1. A caspase-3 inhibitor (Ac-DEVD-CHO), but not a caspase-1 inhibitor (Ac-YVAD-CHO), reversed the cytotoxic effects of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone in HL-60 cells. These data demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone effectively induced the apoptosis of HL-60 cells and exhibited significant anticancer activity via the mitochondrial caspase-3-dependent apoptosis pathway.

  19. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    Science.gov (United States)

    2010-04-01

    ... registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and Securities... 1940 § 270.6c-3 Exemptions for certain registered variable life insurance separate accounts. A separate account which meets the requirements of paragraph (a) of Rule 6e-2 (17 CFR 270.6e-2) or paragraph (a)...

  20. 40 CFR 721.2088 - Carboxylic acids, (C6-C9) branched and linear.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Carboxylic acids, (C6-C9) branched and... Specific Chemical Substances § 721.2088 Carboxylic acids, (C6-C9) branched and linear. (a) Chemical... as carboxylic acids, (C6-C9) branched and linear (PMNs P-93-313, 314, 315, and 316) are subject...

  1. Determinants of national fire plan fuels treatment expenditures: a revealed preference analysis for northern New Mexico.

    Science.gov (United States)

    Shepherd, Curt; Grimsrud, Kristine; Berrens, Robert P

    2009-10-01

    The accumulation of fire fuels in forests throughout the world contributes significantly to the severity of wildfires. To combat the threat of wildfire, especially in the wildland-urban interface (WUI), US federal land management agencies have implemented a number of forest restoration and wildfire risk reduction programs. In the spirit of revealed preference analyses, the objective of this study is to investigate the pattern and determinants of National Fire Plan (NFP) expenditures for fuel reduction treatments in northern New Mexico (USA). Estimation results from a set of Generalized Estimating Equations models are mixed with respect to risk reduction hypotheses, and also raise issues regarding how risk reduction should be defined for a region characterized by both pockets of urban sprawl into the WUI and large areas of chronic rural poverty. Program preferences for project funding under the federal Collaborative Forest Restoration Program in New Mexico are shown to be distinctly different (e.g., exhibiting greater concern for social equity) than for other NFP-funded projects.

  2. Determinants of National Fire Plan Fuels Treatment Expenditures: A Revealed Preference Analysis for Northern New Mexico

    Science.gov (United States)

    Shepherd, Curt; Grimsrud, Kristine; Berrens, Robert P.

    2009-10-01

    The accumulation of fire fuels in forests throughout the world contributes significantly to the severity of wildfires. To combat the threat of wildfire, especially in the wildland-urban interface (WUI), US federal land management agencies have implemented a number of forest restoration and wildfire risk reduction programs. In the spirit of revealed preference analyses, the objective of this study is to investigate the pattern and determinants of National Fire Plan (NFP) expenditures for fuel reduction treatments in northern New Mexico (USA). Estimation results from a set of Generalized Estimating Equations models are mixed with respect to risk reduction hypotheses, and also raise issues regarding how risk reduction should be defined for a region characterized by both pockets of urban sprawl into the WUI and large areas of chronic rural poverty. Program preferences for project funding under the federal Collaborative Forest Restoration Program in New Mexico are shown to be distinctly different (e.g., exhibiting greater concern for social equity) than for other NFP-funded projects.

  3. A compendium of nucleosome and transcript profiles reveals determinants of chromatin architecture and transcription.

    Science.gov (United States)

    van Bakel, Harm; Tsui, Kyle; Gebbia, Marinella; Mnaimneh, Sanie; Hughes, Timothy R; Nislow, Corey

    2013-05-01

    Nucleosomes in all eukaryotes examined to date adopt a characteristic architecture within genes and play fundamental roles in regulating transcription, yet the identity and precise roles of many of the trans-acting factors responsible for the establishment and maintenance of this organization remain to be identified. We profiled a compendium of 50 yeast strains carrying conditional alleles or complete deletions of genes involved in transcriptional regulation, histone biology, and chromatin remodeling, as well as compounds that target transcription and histone deacetylases, to assess their respective roles in nucleosome positioning and transcription. We find that nucleosome patterning in genes is affected by many factors, including the CAF-1 complex, Spt10, and Spt21, in addition to previously reported remodeler ATPases and histone chaperones. Disruption of these factors or reductions in histone levels led genic nucleosomes to assume positions more consistent with their intrinsic sequence preferences, with pronounced and specific shifts of the +1 nucleosome relative to the transcription start site. These shifts of +1 nucleosomes appear to have functional consequences, as several affected genes in Ino80 mutants exhibited altered expression responses. Our parallel expression profiling compendium revealed extensive transcription changes in intergenic and antisense regions, most of which occur in regions with altered nucleosome occupancy and positioning. We show that the nucleosome-excluding transcription factors Reb1, Abf1, Tbf1, and Rsc3 suppress cryptic transcripts at their target promoters, while a combined analysis of nucleosome and expression profiles identified 36 novel transcripts that are normally repressed by Tup1/Cyc8. Our data confirm and extend the roles of chromatin remodelers and chaperones as major determinants of genic nucleosome positioning, and these data provide a valuable resource for future studies.

  4. A compendium of nucleosome and transcript profiles reveals determinants of chromatin architecture and transcription.

    Directory of Open Access Journals (Sweden)

    Harm van Bakel

    2013-05-01

    Full Text Available Nucleosomes in all eukaryotes examined to date adopt a characteristic architecture within genes and play fundamental roles in regulating transcription, yet the identity and precise roles of many of the trans-acting factors responsible for the establishment and maintenance of this organization remain to be identified. We profiled a compendium of 50 yeast strains carrying conditional alleles or complete deletions of genes involved in transcriptional regulation, histone biology, and chromatin remodeling, as well as compounds that target transcription and histone deacetylases, to assess their respective roles in nucleosome positioning and transcription. We find that nucleosome patterning in genes is affected by many factors, including the CAF-1 complex, Spt10, and Spt21, in addition to previously reported remodeler ATPases and histone chaperones. Disruption of these factors or reductions in histone levels led genic nucleosomes to assume positions more consistent with their intrinsic sequence preferences, with pronounced and specific shifts of the +1 nucleosome relative to the transcription start site. These shifts of +1 nucleosomes appear to have functional consequences, as several affected genes in Ino80 mutants exhibited altered expression responses. Our parallel expression profiling compendium revealed extensive transcription changes in intergenic and antisense regions, most of which occur in regions with altered nucleosome occupancy and positioning. We show that the nucleosome-excluding transcription factors Reb1, Abf1, Tbf1, and Rsc3 suppress cryptic transcripts at their target promoters, while a combined analysis of nucleosome and expression profiles identified 36 novel transcripts that are normally repressed by Tup1/Cyc8. Our data confirm and extend the roles of chromatin remodelers and chaperones as major determinants of genic nucleosome positioning, and these data provide a valuable resource for future studies.

  5. Synthesis and Crystal Structure of Compound [ZnS6 (C12H8N2)

    Institute of Scientific and Technical Information of China (English)

    陈之荣; 李健晖; 李鸿钧; 苏卫平; 曹荣

    2000-01-01

    The title compound ZnS6(C12H8N2) was obtained by reaction of zinic powder with sulfur and 1,10-phenathtroline in DMF solvent, and its structure has been determined by single crystal X-ray diffraction analysis. The crystal data for the compound: triclinic, P-1, Z = 2, a = 8. 159(2), b = 9. 485(2), c = 11. 997(2)A , α =110. 00(3)°,β = 99.22(3)°, γ = 100.57(3)°, V = 832A3, Dc =1. 748g/cm3, μ(MoKa)=0. 2219 cm-1, F(000)=440. The structure was refined to R = 0. 0723 and Rw = 0. 0865 for 1427 independent observed reflections. The tilte crystal consists of a discrete molecules, in which the core of ZnS2N2 shows a distorted tetrahedral geometry.

  6. The small 6C RNA of Corynebacterium glutamicum is involved in the SOS response.

    Science.gov (United States)

    Pahlke, Jennifer; Dostálová, Hana; Holátko, Jiří; Degner, Ursula; Bott, Michael; Pátek, Miroslav; Polen, Tino

    2016-09-01

    The 6C RNA family is a class of small RNAs highly conserved in Actinobacteria, including the genera Mycobacterium, Streptomyces and Corynebacterium whose physiological function has not yet been elucidated. We found that strong transcription of the cgb_03605 gene, which encodes 6C RNA in C. glutamicum, was driven by the SigA- and SigB-dependent promoter Pcgb_03605. 6C RNA was detected at high level during exponential growth phase (180 to 240 molcules per cell) which even increased at the entry of the stationary phase. 6C RNA level did not decrease within 240 min after transcription had been stopped with rifampicin, which suggests high 6C RNA stability. The expression of cgb_03605 further increased approximately twofold in the presence of DNA-damaging mitomycin C (MMC) and nearly threefold in the absence of LexA. Deletion of the 6C RNA gene cgb_03605 resulted in a higher sensitivity of C. glutamicum toward MMC and UV radiation. These results indicate that 6C RNA is involved in the DNA damage response. Both 6C RNA level-dependent pausing of cell growth and branched cell morphology in response to MMC suggest that 6C RNA may also be involved in a control of cell division.

  7. Prevalence and molecular characterisation of Streptococcus pneumoniae serotype 6C in Queensland, Australia.

    Science.gov (United States)

    Staples, Megan; Jennison, Amy V; Ariotti, Lawrence; Hicks, Vicki; Graham, Rikki M A; Smith, Helen V

    2014-03-01

    Streptococcus pneumoniae serotype 6C was first identified in 2007, although retrospective studies have since identified serotype 6C among stored isolates dating back to 1962. We investigated the incidence and genetic diversity of serotype 6C strains isolated from Queensland patients between 2001 and 2011. Isolates were identified by Quellung reaction and antimicrobial susceptibility testing was performed. The incidence of serotype 6C among serogroup 6 Queensland invasive pneumococcal disease increased from 6.8% (2001-2004) to 39% (2005-2010) of serogroup 6 isolates (P = 0). Genetic diversity of Queensland 6C isolates was high, with molecular analysis identifying 19 sequence types by multi-locus sequence typing, and 35 types by multi-locus variable-number tandem repeat analysis.

  8. Anti-inflammatory activity of Arnica montana 6cH: preclinical study in animals.

    Science.gov (United States)

    Macêdo, S B; Ferreira, L R; Perazzo, F F; Carvalho, J C

    2004-04-01

    The anti-inflammatory effect of Arnica montana 6cH was evaluated using acute and chronic inflammation models. In the acute, model, carrageenin-induced rat paw oedema, the group treated with Arnica montana 6cH showed 30% inhibition compared to control (P < 0.05). Treatment with Arnica 6cH, 30 min prior to carrageenin, did not produce any inhibition of the inflammatory process. In the chronic model, Nystatin-induced oedema, the group treated 3 days previously with Arnica montana 6cH had reduced inflammation 6 h after the inflammatory agent was applied (P < 0.05). When treatment was given 6 h after Nystatin treatment, there was no significant inhibitory effect. In a model based on histamine-induced increase of vascular permeability, pretreatment with Arnica montana 6cH blocked the action of histamine in increasing vascular permeability.

  9. RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

    Science.gov (United States)

    Xiong, Hui Y; Alipanahi, Babak; Lee, Leo J; Bretschneider, Hannes; Merico, Daniele; Yuen, Ryan K C; Hua, Yimin; Gueroussov, Serge; Najafabadi, Hamed S; Hughes, Timothy R; Morris, Quaid; Barash, Yoseph; Krainer, Adrian R; Jojic, Nebojsa; Scherer, Stephen W; Blencowe, Benjamin J; Frey, Brendan J

    2015-01-01

    To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic and exonic variants revealed widespread patterns of mutation-driven aberrant splicing. Intronic disease mutations that are more than 30 nucleotides from any splice site alter splicing nine times as often as common variants, and missense exonic disease mutations that have the least impact on protein function are five times as likely as others to alter splicing. We detected tens of thousands of disease-causing mutations, including those involved in cancers and spinal muscular atrophy. Examination of intronic and exonic variants found using whole-genome sequencing of individuals with autism revealed misspliced genes with neurodevelopmental phenotypes. Our approach provides evidence for causal variants and should enable new discoveries in precision medicine.

  10. Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora.

    Science.gov (United States)

    Steige, Kim A; Laenen, Benjamin; Reimegård, Johan; Scofield, Douglas G; Slotte, Tanja

    2017-01-31

    Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.

  11. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

    Science.gov (United States)

    Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

    2015-01-01

    Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

  12. Seasonal determinations of algal virus decay rates reveal overwintering in a temperate freshwater pond.

    Science.gov (United States)

    Long, Andrew M; Short, Steven M

    2016-07-01

    To address questions about algal virus persistence (i.e., continued existence) in the environment, rates of decay of infectivity for two viruses that infect Chlorella-like algae, ATCV-1 and CVM-1, and a virus that infects the prymnesiophyte Chrysochromulina parva, CpV-BQ1, were estimated from in situ incubations in a temperate, seasonally frozen pond. A series of experiments were conducted to estimate rates of decay of infectivity in all four seasons with incubations lasting 21 days in spring, summer and autumn, and 126 days in winter. Decay rates observed across this study were relatively low compared with previous estimates obtained for other algal viruses, and ranged from 0.012 to 11% h(-1). Overall, the virus CpV-BQ1 decayed most rapidly whereas ATCV-1 decayed most slowly, but for all viruses the highest decay rates were observed during the summer and the lowest were observed during the winter. Furthermore, the winter incubations revealed the ability of each virus to overwinter under ice as ATCV-1, CVM-1 and CpV-BQ1 retained up to 48%, 19% and 9% of their infectivity after 126 days, respectively. The observed resilience of algal viruses in a seasonally frozen freshwater pond provides a mechanism that can support the maintenance of viral seed banks in nature. However, the high rates of decay observed in the summer demonstrate that virus survival and therefore environmental persistence can be subject to seasonal bottlenecks.

  13. VEGF Production by Ly6C+high Monocytes Contributes to Ventilator-Induced Lung Injury

    National Research Council Canada - National Science Library

    Shi, Chung-Sheng; Huang, Tzu-Hsiung; Lin, Chin-Kuo; Li, Jhy-Ming; Chen, Mei-Hsin; Tsai, Mei-Ling; Chang, Chih-Ching

    2016-01-01

      Background Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilator-induced lung injury (VILI). Ly6C...

  14. Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Denisa Liszeková

    Full Text Available BACKGROUND: Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH. While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE: The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions.

  15. Association Studies and Legume Synteny Reveal Haplotypes Determining Seed Size in Vigna unguiculata.

    Science.gov (United States)

    Lucas, Mitchell R; Huynh, Bao-Lam; da Silva Vinholes, Patricia; Cisse, Ndiaga; Drabo, Issa; Ehlers, Jeffrey D; Roberts, Philip A; Close, Timothy J

    2013-01-01

    Highly specific seed market classes for cowpea and other grain legumes exist because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large seeded lines. In this work we applied 1,536-plex SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker-based selection approaches to increase the frequency of progeny with large seed. For 804 individuals derived from eight bi-parental populations, QTL analysis was used to identify markers linked to 10 trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total 10 QTLs were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  16. Association studies and legume synteny reveal haplotypes determining seed size in Vigna unguiculata

    Directory of Open Access Journals (Sweden)

    Mitchell R Lucas

    2013-04-01

    Full Text Available Highly specific seed market classes for cowpea and other grain legumes exists because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large-seeded lines. In this work we applied SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker based selection approaches to increase the frequency of progeny with large seed. For ~800 samples derived from eight bi-parental populations, QTL analysis was used to identify markers linked to ten trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total ten QTL were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  17. Gene Regulatory Network Analysis Reveals Differences in Site-specific Cell Fate Determination in Mammalian Brain

    Directory of Open Access Journals (Sweden)

    Gokhan eErtaylan

    2014-12-01

    Full Text Available Neurogenesis - the generation of new neurons - is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ lining the walls of the lateral ventricles; and the subgranular zone (SGZ of the dentate gyrus of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a and Nr3c1.We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report thirty-one candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar - Pax6 in SVZ and Sox2 - Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact.Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis.

  18. Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

    Directory of Open Access Journals (Sweden)

    Claire Janoir

    Full Text Available In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7 lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003 to the PCV13 era (2010-2011, both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315, which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

  19. Synthetic CpG islands reveal DNA sequence determinants of chromatin structure

    Science.gov (United States)

    Wachter, Elisabeth; Quante, Timo; Merusi, Cara; Arczewska, Aleksandra; Stewart, Francis; Webb, Shaun; Bird, Adrian

    2014-01-01

    The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display ‘active’ histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a ‘bivalent’ chromatin state bearing simultaneous ‘active’ and ‘inactive’ chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G + C-rich DNA. A high CpG density alone is not sufficient for this effect, as A + T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G + C-richness are required for induction of signature chromatin structures at CGIs. DOI: http://dx.doi.org/10.7554/eLife.03397.001 PMID:25259796

  20. Natural resource landscapes of a marine bacterium reveal distinct fitness-determining genes across the genome.

    Science.gov (United States)

    Takemura, Alison F; Corzett, Christopher H; Hussain, Fatima; Arevalo, Philip; Datta, Manoshi; Yu, Xiaoqian; Le Roux, Frederique; Polz, Martin F

    2017-06-01

    Heterotrophic bacteria exploit diverse microhabitats in the ocean, from particles to transient gradients. Yet the degree to which genes and pathways can contribute to an organism's fitness on such complex and variable natural resource landscapes remains poorly understood. Here, we determine the gene-by-gene fitness of a generalist saprophytic marine bacterium (Vibrio sp. F13 9CS106) on complex resources derived from its natural habitats - copepods (Apocyclops royi) and brown algae (Fucus vesiculosus) - and as reference substrates, glucose and the polysaccharide alginate, derived from brown algal cell walls. We find that resource complexity strongly buffers fitness costs of mutations, and that anabolic rather than catabolic pathways are more stringently required, likely due to functional redundancy in the latter. Moreover, while carbohydrate-rich algae requires several synthesis pathways, protein-rich Apocyclops does not, suggesting this ancestral habitat for Vibrios is a replete medium with metabolically redundant substrates. We also identify a candidate fitness trade-off for algal colonization: deletion of mshA increases mutant fitness. Our results demonstrate that gene fitness depends on habitat composition, and suggest that this generalist uses distinct resources in different natural habitats. The results further indicate that substrate replete conditions may lead to relatively relaxed selection on catabolic genes. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  1. Cervical Sagittal Alignment in Extensive Fusions for Lenke 3C and 6C Scoliosis: The Effect of Upper Instrumented Vertebra.

    Science.gov (United States)

    Yanik, Hakan Serhat; Ketenci, Ismail Emre; Erdem, Sevki

    2017-03-15

    A retrospective analysis of cervical sagittal alignment (CSA) in Lenke 3C and 6C adolescent idiopathic scoliosis (AIS). The aim of this study was to evaluate CSA according to upper instrumented vertebra (UIV) level. Hypokyphotic effect of extensive fusions of Lenke 3C and 6C curves on thoracic spine leads to kyphotic changes in cervical region. No study has evaluated the CSA in these patients according to UIV level. A total of 55 Lenke 3C and 6C AIS patients who underwent posterior fusion with pedicle screw instrumentation were recruited in this study. Patients were divided into three groups according to UIV level, which was determined preoperatively on the basis of shoulder balance. There were 22, 19, and 14 patients in T2, T3, and T4 groups, respectively. Three groups were similar according to demographic and preoperative coronal and sagittal alignment parameters. Patients were compared at two-year follow-up according to radiographic changes in coronal and sagittal planes. Main sagittal parameters were C2-C7 cervical lordosis (CL), T1 slope, T1-T5, and T5-T12 kyphosis. Clinical outcomes were assessed using scoliosis research society (SRS)-22 and short form (SF)-36 questionnaires. In all patients, C2-C7 CL, T5-T12 kyphosis, and T1 slope significantly decreased postoperatively (P cervical kyphosis (CK). Thirteen of them had preoperative CL and 14 had CK. Twenty-eight of 41 patients with preoperative CL remained in lordotic CSA postoperatively. SRS-22 and SF-36 scores did not change significantly after the surgery. In Lenke 3C and 6C AIS, postoperative CSA is independent from UIV level. Decreased CL is mainly caused by T5-T12 and T1 slope decrease. In order to achieve level shoulders, fusion can be extended to appropriate upper level, without increased risk of CK. 4.

  2. The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq

    Directory of Open Access Journals (Sweden)

    Loren H. Rieseberg

    2012-10-01

    determinants of rates of protein evolution and the impact of selection on patterns of polymorphism and divergence.

  3. The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq.

    Science.gov (United States)

    Renaut, Sébastien; Grassa, Christopher J; Moyers, Brook T; Kane, Nolan C; Rieseberg, Loren H

    2012-10-25

    Few studies have investigated the causes of evolutionary rate variation among plant nuclear genes, especially in recently diverged species still capable of hybridizing in the wild. The recent advent of Next Generation Sequencing (NGS) permits investigation of genome wide rates of protein evolution and the role of selection in generating and maintaining divergence. Here, we use individual whole-transcriptome sequencing (RNAseq) to refine our understanding of the population genomics of wild species of sunflowers (Helianthus spp.) and the factors that affect rates of protein evolution. We aligned 35 GB of transcriptome sequencing data and identified 433,257 polymorphic sites (SNPs) in a reference transcriptome comprising 16,312 genes. Using SNP markers, we identified strong population clustering largely corresponding to the three species analyzed here (Helianthus annuus, H. petiolaris, H. debilis), with one distinct early generation hybrid. Then, we calculated the proportions of adaptive substitution fixed by selection (alpha) and identified gene ontology categories with elevated values of alpha. The "response to biotic stimulus" category had the highest mean alpha across the three interspecific comparisons, implying that natural selection imposed by other organisms plays an important role in driving protein evolution in wild sunflowers. Finally, we examined the relationship between protein evolution (dN/dS ratio) and several genomic factors predicted to co-vary with protein evolution (gene expression level, divergence and specificity, genetic divergence [FST], and nucleotide diversity pi). We find that variation in rates of protein divergence was correlated with gene expression level and specificity, consistent with results from a broad range of taxa and timescales. This would in turn imply that these factors govern protein evolution both at a microevolutionary and macroevolutionary timescale. Our results contribute to a general understanding of the determinants of

  4. PRINSIP 6C (CHARACTER, CAPACITY, CAPITAL, CONDITION OF ECONOMY, COLLATERAL DAN CONSTRAINT DALAM WIRAUSAHA MAHASISWA

    Directory of Open Access Journals (Sweden)

    Henny Sri Astuty

    2015-04-01

    Full Text Available Abstrak: Prinsip 6C (Character, Capacity, Capital, Condition of Economy, Collateral dan Constraint dalam Wirausaha Mahasiswa. Kegiatan wirausaha yang sekarang banyak dilakukan oleh mahasiswa memiliki sisi positif maupun negatif, dari yang berhasil kuliah dan wirausahanya hingga yang gagal semuanya. Untuk ini diperlukan pemahaman tentang prinsip enam C (character, capacity, capital, condition of economy, collateral and constraint yang akan membantu mahasiswa sebagai bekal dalam melakukan kegiatan usahanya. Banyak faktor yang diperoleh dalam prinsip ini yaitu aspek manajemen, pemasaran, produksi, dan keuangan. Kata Kunci: prinsip 6c, wirausaha, mahasiswa Abstract: 6C Principles (Character, Capacity, Capital, Condition of Economy, Collateral and Constraint in Entrepreneurial Students. Entrepreneurial activity that is widely performed by students has two different stories. Some of them are successful on the other hand, the rest of them are fail. Accordingly, it is required an understanding of the 6C principles of the six C (character, capacity, capital, condition of economy, collateral and constraints which will help the students as a preparation in conducting their business activities. Many factors obtained in this principle namely: management, marketing, production, and financial aspects. Keywords: 6C principles, entrepreneurs, students

  5. Cytogenetic Insights into the Evolution of Chromosomes and Sex Determination Reveal Striking Homology of Turtle Sex Chromosomes to Amphibian Autosomes.

    Science.gov (United States)

    Montiel, Eugenia E; Badenhorst, Daleen; Lee, Ling S; Literman, Robert; Trifonov, Vladimir; Valenzuela, Nicole

    2016-01-01

    Turtle karyotypes are highly conserved compared to other vertebrates; yet, variation in diploid number (2n = 26-68) reflects profound genomic reorganization, which correlates with evolutionary turnovers in sex determination. We evaluate the published literature and newly collected comparative cytogenetic data (G- and C-banding, 18S-NOR, and telomere-FISH mapping) from 13 species spanning 2n = 28-68 to revisit turtle genome evolution and sex determination. Interstitial telomeric sites were detected in multiple lineages that underwent diploid number and sex determination turnovers, suggesting chromosomal rearrangements. C-banding revealed potential interspecific variation in centromere composition and interstitial heterochromatin at secondary constrictions. 18S-NORs were detected in secondary constrictions in a single chromosomal pair per species, refuting previous reports of multiple NORs in turtles. 18S-NORs are linked to ZW chromosomes in Apalone and Pelodiscus and to X (not Y) in Staurotypus. Notably, comparative genomics across amniotes revealed that the sex chromosomes of several turtles, as well as mammals and some lizards, are homologous to components of Xenopus tropicalis XTR1 (carrying Dmrt1). Other turtle sex chromosomes are homologous to XTR4 (carrying Wt1). Interestingly, all known turtle sex chromosomes, except in Trionychidae, evolved via inversions around Dmrt1 or Wt1. Thus, XTR1 appears to represent an amniote proto-sex chromosome (perhaps linked ancestrally to XTR4) that gave rise to turtle and other amniote sex chromosomes.

  6. An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance.

    Science.gov (United States)

    Hansen, Scott B; Wang, Hai-Long; Taylor, Palmer; Sine, Steven M

    2008-12-26

    Neurotransmitter binding to Cys-loop receptors promotes a prodigious transmembrane flux of several million ions/s, but to date, structural determinants of ion flux have been identified flanking the membrane-spanning region. Using x-ray crystallography, sequence analysis, and single-channel recording, we identified a novel determinant of ion conductance near the point of entry of permeant ions. Co-crystallization of acetylcholine-binding protein with sulfate anions revealed coordination of SO4(2-) with a ring of lysines at a position equivalent to 24 A above the lipid membrane in homologous Cys-loop receptors. Analysis of multiple sequence alignments revealed that residues equivalent to the ring of lysines are negatively charged in cation-selective receptors but are positively charged in anion-selective receptors. Charge reversal of side chains at homologous positions in the nicotinic receptor from the motor end plate decreases unitary conductance up to 80%. Selectivity filters stemming from transmembrane alpha-helices have similar pore diameters and compositions of amino acids. These findings establish that when the channel opens under a physiological electrochemical gradient, permeant ions are initially stabilized within the extracellular vestibule of Cys-loop receptors, and this stabilization is a major determinant of ion conductance.

  7. Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes.

    Science.gov (United States)

    Tomcik, Kristyen A; Smiles, William J; Camera, Donny M; Hügel, Helmut M; Hawley, John A; Watts, Rani

    2017-04-01

    Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro. Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24 h with 0.5 mM creatine (CR), CR and 20 μg/mL fenugreek seed extract (CR + FEN), CR and 100 nM insulin (CR + INS), and CR + INS + FEN (n = 6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined. Compared to control (CON), CR + INS + FEN increased total creatine content after 4 h (P insulin signaling were demonstrated via increases in Akt(Thr308) phosphorylation, with CR + INS > CON and CR at 1 h (P  CON, CR, and CR + INS at 4 h (P insulin, modulates creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.

  8. Lowest instrumented vertebra selection in Lenke 3C and 6C scoliosis

    DEFF Research Database (Denmark)

    Wang, Yu; Bünger, Cody; Zhang, Yanqun

    2012-01-01

    PURPOSE: The aim of this study was to investigate whether or not post-op curve behaviour differs due to different choices of lowest instrumented vertebra (LIV) with reference to lumbar apical vertebra (LAV) in Lenke 3C and 6C scoliosis. METHODS: We reviewed all the AIS cases surgically treated...... in our institution from 2002 through 2008. Inclusion criteria were as follows: (1) patients with Lenke 3C or 6C scoliosis who were treated with posterior pedicle screw-only constructs; (2) 2-year radiographic follow-up. All the included patients were categorized into three groups based on the relative...... surgery. No significant differences were found in thoracic or lumbar correction rate, global coronal balance and incidence rate of trunk shift among the three groups. CONCLUSION: In conclusion, in Lenke 3C and 6C scoliosis, post-op lumbar curve behaviour differs due to different choices of LIV...

  9. Integrating total quality management principles with the requirements of DOE Order 5700.6C

    Energy Technology Data Exchange (ETDEWEB)

    Hedges, D. [Scientific Ecology Group, Inc. (United States)

    1993-03-01

    The Department of Energy has recently required its field offices, contractors, and subcontractors to implement DOE Order 5700.6C, ``Quality Assurance,`` for all work on waste management contracts. The order restructures the 18 criteria of NQA-1 and focuses on the role of management in achieving and assuring quality, performance of activities to achieve and assure quality, and management`s assessment of its performance for the purpose of identifying improvements to be made. The DOE order also introduces elements of the total quality management (TQM) philosophy, which were not present in DOE Order 5700.6B. The research community within DOE has recently issued a document entitled DOE Order 5700.6C Implementation Guide, which is more explicit about the integration of TQM principles with the implementation of DOE Order 5700.6C in research facilities. The Environmental Protection Agency is sponsoring a quality assurance standard (ANSI/ASQC E-4) to replace EPA`s QAMS 005/80. The new standard is consistent with DOE Order 5700.6C, and it also stresses the integration of TQM principles within the quality assurance process. This paper discusses the intent and philosophy of the 10 criteria of the new DOE order, the status of ANSI/ASQC E-4, and how to effectively integrate TQM principles into the quality assurance process as the conversion is made from NQA-1 to DOE Order 5700.6C. The purpose and value of DOE Order 5700.6C Implementation Guide for research will also be discussed.

  10. Denatured-state energy landscapes of a protein structural database reveal the energetic determinants of a framework model for folding.

    Science.gov (United States)

    Wang, Suwei; Gu, Jenny; Larson, Scott A; Whitten, Steven T; Hilser, Vincent J

    2008-09-19

    Position-specific denatured-state thermodynamics were determined for a database of human proteins by use of an ensemble-based model of protein structure. The results of modeling denatured protein in this manner reveal important sequence-dependent thermodynamic properties in the denatured ensembles as well as fundamental differences between the denatured and native ensembles in overall thermodynamic character. The generality and robustness of these results were validated by performing fold-recognition experiments, whereby sequences were matched with their respective folds based on amino acid propensities for the different energetic environments in the protein, as determined through cluster analysis. Correlation analysis between structure and energetic information revealed that sequence segments destined for beta-sheet in the final native fold are energetically more predisposed to a broader repertoire of states than are sequence segments destined for alpha-helix. These results suggest that within the subensemble of mostly unstructured states, the energy landscapes are dominated by states in which parts of helices adopt structure, whereas structure formation for sequences destined for beta-strand is far less probable. These results support a framework model of folding, which suggests that, in general, the denatured state has evolutionarily evolved to avoid low-energy conformations in sequences that ultimately adopt beta-strand. Instead, the denatured state evolved so that sequence segments that ultimately adopt alpha-helix and coil will have a high intrinsic structure formation capability, thus serving as potential nucleation sites.

  11. Distinct patterns of compartmentalization and proteolytic stability of PDE6C mutants linked to achromatopsia.

    Science.gov (United States)

    Cheguru, Pallavi; Majumder, Anurima; Artemyev, Nikolai O

    2015-01-01

    Phosphodiesterase-6 (PDE6) is an essential effector enzyme in vertebrate photoreceptor cells. Mutations in rod and cone PDE6 cause recessive retinitis pigmentosa and achromatopsia, respectively. The mechanisms of missense PDE6 mutations underlying severe visual disorders are poorly understood. To probe these mechanisms, we expressed seven known missense mutants of cone PDE6C in rods of transgenic Xenopus laevis and examined their stability and compartmentalization. PDE6C proteins with mutations in the catalytic domain, H602L and E790K, displayed modestly reduced proteolytic stability, but they were properly targeted to the outer segment of photoreceptor cells. Mutations in the regulatory GAF domains, R104W, Y323N, and P391L led to a proteolytic degradation of the proteins involving a cleavage in the GAFb domain. Lastly, the R29W and M455V mutations residing outside the conserved PDE6 domains produced a pattern of subcellular compartmentalization different from that of PDE6C. Thus, our results suggest a spectrum of mechanisms of missense PDE6C mutations in achromatopsia including catalytic defects, protein mislocalization, or a specific sequence of proteolytic degradation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Data of evolutionary structure change: 1IB6C-9LDTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1IB6C-9LDTA 1IB6 9LDT C A -------------------MKVAVLGAAGGIGQALALLL...GGGSATLSMGQAAARFGLSLVRALQGEQGVVECAYVEG----DGQYARFFSQPLLLGKNGVEERKSIGTLSAFEQNALEGMLDT...5 9LDT A 9LDTA LEU CA 482 ASP CA 492 ILE CA 464 9LDT... A 9LDTA RVIGSGCN

  13. Data of evolutionary structure change: 1IB6C-9LDTB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1IB6C-9LDTB 1IB6 9LDT C B -------------------MKVAVLGAAGGIGQALALLL...GGGSATLSMGQAAARFGLSLVRALQGEQGVVECAYVEG----DGQYARFFSQPLLLGKNGVEERKSIGTLSAFEQNALEGMLDT.../line> VAL CA 288 9LDT B 9LDT... 9 9LDT B... 9LDTB SDVVK-VTLTP - H

  14. 76 FR 56097 - Special Conditions: Pratt and Whitney Canada Model PT6C-67E Turboshaft Engine

    Science.gov (United States)

    2011-09-12

    ... the other model. Novel or Unusual Design Features The PWC model PT6C-67E turbo shaft engine will... These special conditions are applicable to PWC model PT6C-67E turbo shaft engines. If Pratt and Whitney... part of the type certification basis for PWC model PT6C-67E turbo shaft engines. 1. Part 1...

  15. 1,3,4,6,7,9-Hexamethylbenzo[1,2-c:3,4-c':5,6-c'']trithiophene: a twisted heteroarene.

    Science.gov (United States)

    Wu, Yao-Ting; Tai, Chia-Cheng; Lin, Wei-Chih; Baldridge, Kim K

    2009-07-01

    1,3,4,6,7,9-Hexamethylbenzo[1,2-c:3,4-c':5,6-c'']trithiophene (C-Me) was prepared by palladium-catalyzed methylations of the corresponding hexabromide C-Br. The twisted structure of C-Me has been confirmed by X-ray crystal analysis. The physical properties of twisted C-Me and planar benzo[1,2-c:3,4-c':5,6-c'']trithiophene (C-H) were studied and compared. Crystal structures are compared to computational structures determined using density functional theory, with both the M06-2X and B3PW91 functionals.

  16. Genome-Wide Association and Transcriptome Analyses Reveal Candidate Genes Underlying Yield-determining Traits in Brassica napus

    Science.gov (United States)

    Lu, Kun; Peng, Liu; Zhang, Chao; Lu, Junhua; Yang, Bo; Xiao, Zhongchun; Liang, Ying; Xu, Xingfu; Qu, Cunmin; Zhang, Kai; Liu, Liezhao; Zhu, Qinlong; Fu, Minglian; Yuan, Xiaoyan; Li, Jiana

    2017-01-01

    Yield is one of the most important yet complex crop traits. To improve our understanding of the genetic basis of yield establishment, and to identify candidate genes responsible for yield improvement in Brassica napus, we performed genome-wide association studies (GWAS) for seven yield-determining traits [main inflorescence pod number (MIPN), branch pod number (BPN), pod number per plant (PNP), seed number per pod (SPP), thousand seed weight, main inflorescence yield (MIY), and branch yield], using data from 520 diverse B. napus accessions from two different yield environments. In total, we detected 128 significant single nucleotide polymorphisms (SNPs), 93 of which were revealed as novel by integrative analysis. A combination of GWAS and transcriptome sequencing on 21 haplotype blocks from samples pooled by four extremely high-yielding or low-yielding accessions revealed the differential expression of 14 crucial candiate genes (such as Bna.MYB83, Bna.SPL5, and Bna.ROP3) associated with multiple traits or containing multiple SNPs associated with the same trait. Functional annotation and expression pattern analyses further demonstrated that these 14 candiate genes might be important in developmental processes and biomass accumulation, thus affecting the yield establishment of B. napus. These results provide valuable information for understanding the genetic mechanisms underlying the establishment of high yield in B. napus, and lay the foundation for developing high-yielding B. napus varieties. PMID:28261256

  17. Crystal structure of pentapeptide-independent chemotaxis receptor methyltransferase (CheR) reveals idiosyncratic structural determinants for receptor recognition.

    Science.gov (United States)

    Batra, Monu; Sharma, Rajesh; Malik, Anjali; Dhindwal, Sonali; Kumar, Pravindra; Tomar, Shailly

    2016-12-01

    Chemotactic methyltransferase, CheR catalyse methylation of specific glutamate residues in the cytoplasmic domain of methyl-accepting chemotactic protein receptors (MCPRs). The methylation of MCPRs is essential for the chemical sensing and chemotactic bacterial mobility towards favorable chemicals or away from unfavorable ones. In this study, crystal structure of B. subtilis CheR (BsCheR) in complex with S-adenosyl-l-homocysteine (SAH) has been determined to 1.8Å resolution. This is the first report of crystal structure belonging to the pentapeptide-independent CheR (PICheR) class. Till date, only one crystal structure of CheR from S. typhimurium (StCheR) belonging to pentapeptide-dependent CheR (PDCheR) class is available. Structural analysis of BsCheR reveals a helix-X-helix motif (HXH) with Asp53 as the linker residue in the N-terminal domain. The key structural features of the PDCheR β-subdomain involved in the formation of a tight complex with the pentapeptide binding motif in MCPRs were found to be absent in the structure of BsCheR. Additionally, isothermal titration calorimetry (ITC) experiments were performed to investigate S-adenosyl-(l)-methionine (SAM) binding affinity and KD was determined to be 0.32mM. The structure of BsCheR reveals that mostly residues of the large C-terminal domain contribute to SAH binding, with contributions of few residues from the linker region and the N-terminal domain. Structural investigations and sequence analysis carried out in this study provide critical insights into the distinct receptor recognition mechanism of the PDCheR and PICheR methyltransferase classes.

  18. Deep spectroscopy of z~1 6C radio galaxies - II. Breaking the redshift-radio power degeneracy

    CERN Document Server

    Inskip, K J; Röttgering, H J A; Rawlings, S; Cotter, G; Longair, M S

    2002-01-01

    The results of a spectroscopic analysis of 3CR and 6C radio galaxies at redshift z~1 are contrasted with the properties of lower redshift radio galaxies, chosen to be matched in radio luminosity to the 6C sources studied at z~1, thus enabling the P-z degeneracy to be broken. Partial rank correlations and principal component analysis have been used to determine which of z and P are the critical parameters underlying the observed variation of the ionization state andd kinematics of the emission line gas. [OII]/H-beta is shown to be a useful ionization mechanism diagnostic. Statistical analysis of the data shows that the ionization state of the emission line gas is strongly correlated with radio power, once the effects of other parameters are removed. No dependence of ionization state on z is observed, implying that the ionization state of the emission line gas is solely a function of the AGN properties rather than the hostt galaxy and/or environment. Statistical analysis of the kinematic properties of the emiss...

  19. An effective synthesis of isoorientin: the regioselective synthesis of a 6-C-glucosylflavone.

    Science.gov (United States)

    Kumazawa, T; Minatogawa, T; Matsuba, S; Sato, S; Onodera, J

    2000-11-17

    Isoorientin, a 6-C-beta-D-glucopyranosyl-3',4',5,7-tetrahydroxyflavone, was synthesized in a 15% overall yield, in ten steps, starting from the commercially available phloroacetophenone. The C-glucosyl phloroacetophenone derivative, a synthetic intermediate that contains a free hydroxyl group that is para to the glucosyl moiety, was obtained by hydrogenolysis by taking advantage of differences in the hydrogenolysis rates between a benzyl protecting group and a 2-methylbenzyl protecting group. Aldol condensation of the C-glucosyl phloroacetophenone derivative with 3,4-bis-benzyloxybenzaldehyde afforded the corresponding chalcone as a precursor of the 6-C-glucosyl flavone. Construction of the flavone system by application of I2-DMSO, followed by deprotection, yielded isoorientin.

  20. Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

    Directory of Open Access Journals (Sweden)

    Jatin Narula

    2010-05-01

    Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

  1. Specific depletion of Ly6C(hi inflammatory monocytes prevents immunopathology in experimental cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Beatrix Schumak

    Full Text Available Plasmodium berghei ANKA (PbA infection of C57BL/6 mice leads to experimental cerebral malaria (ECM that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb, we depleted in vivo Ly6C(hi inflammatory monocytes (by anti-CCR2, Ly6G+ neutrophils (by anti-Ly6G or both cell types (by anti-Gr1 during infection with Ovalbumin-transgenic PbA parasites (PbTg. Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6C(hi inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ+CD8+ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6C(hi inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C+ monocytes in ECM inflammatory processes.

  2. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice.

    Science.gov (United States)

    Yokose, Y; Uchida, K; Nakae, D; Shiraiwa, K; Yamamoto, K; Konishi, Y

    1987-01-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentrations of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice. PMID:3447900

  3. Developmental validation of the PowerPlex(®) Fusion 6C System.

    Science.gov (United States)

    Ensenberger, Martin G; Lenz, Kristy A; Matthies, Learden K; Hadinoto, Gregory M; Schienman, John E; Przech, Angela J; Morganti, Michael W; Renstrom, Daniel T; Baker, Victoria M; Gawrys, Kori M; Hoogendoorn, Marlijn; Steffen, Carolyn R; Martín, Pablo; Alonso, Antonio; Olson, Hope R; Sprecher, Cynthia J; Storts, Douglas R

    2016-03-01

    The PowerPlex(®) Fusion 6C System is a 27-locus, six-dye, multiplex that includes all markers in the expanded CODIS core loci and increases overlap with STR database standards throughout the world. Additionally, it contains two, rapidly mutating, Y-STRs and is capable of both casework and database workflows, including direct amplification. A multi-laboratory developmental validation study was performed on the PowerPlex(®) Fusion 6C System. Here, we report the results of that study which followed SWGDAM guidelines and includes data for: species specificity, sensitivity, stability, precision, reproducibility and repeatability, case-type samples, concordance, stutter, DNA mixtures, and PCR-based procedures. Where appropriate we report data from both extracted DNA samples and direct amplification samples from various substrates and collection devices. Samples from all studies were separated on both Applied Biosystems 3500 series and 6-dye capable 3130 series Genetic Analyzers and data is reported for each. Together, the data validate the design and demonstrate the performance of the PowerPlex(®) Fusion 6C System.

  4. The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

    Directory of Open Access Journals (Sweden)

    Matthias Stein

    Full Text Available BACKGROUND: Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics. CONCLUSIONS/SIGNIFICANCE: We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

  5. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice.

    OpenAIRE

    Yokose, Y; Uchida, K; Nakae, D; Shiraiwa, K; Yamamoto, K; Konishi, Y.

    1987-01-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentrations of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose)...

  6. Metabolism of methapyrilene by Fischer-344 rat and B6C3F1 mouse hepatocytes.

    Science.gov (United States)

    Kelly, D W; Holder, C L; Korfmacher, W A; Getek, T A; Lay, J O; Casciano, D A; Shaddock, J G; Duhart, H M; Slikker, W

    1992-12-01

    1. Suspension cultures of freshly isolated F344 rat and B6C3F1 mouse hepatocytes were compared for their ability to transform various concentrations of methapyrilene (MP). 2. MP metabolites were isolated and purified by h.p.l.c., and were identified by comparing their chromatographic and mass spectral properties with those of authentic standards. 3. Both rat and mouse hepatocytes transformed MP to tentatively identified 2-thiophenecarboxylic acid (I), and definitively identified mono-N-desmethyl methapyrilene glucuronide (II), methapyrilene glucuronide (III), methapyrilene N-oxide (V), and mono-N-desmethyl methapyrilene (VII).

  7. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  8. A Naturally-Derived Compound Schisandrin B Enhanced Light Sensation in the pde6c Zebrafish Model of Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    Liyun Zhang

    Full Text Available Retinal degeneration is often progressive. This feature has provided a therapeutic window for intervention that may extend functional vision in patients. Even though this approach is feasible, few promising drug candidates are available. The scarcity of new drugs has motivated research to discover novel compounds through different sources. One such example is Schisandrin B (SchB, an active component isolated from the five-flavor fruit (Fructus Schisandrae that is postulated in traditional Chinese medicines to exert prophylactic visual benefit. This SchB benefit was investigated in this study in pde6cw59, a zebrafish retinal-degeneration model. In this model, the pde6c gene (phosphodiesterase 6C, cGMP-specific, cone, alpha prime carried a mutation which caused cone degeneration. This altered the local environment and caused the bystander rods to degenerate too. To test SchB on the pde6cw59 mutants, a treatment concentration was first determined that would not cause morphological defects, and would initiate known physiological response. Then, the mutants were treated with the optimized SchB concentration before the appearance of retinal degeneration at 3 days postfertilization (dpf. The light sensation of animals was evaluated at 6 dpf by the visual motor response (VMR, a visual startle that could be initiated by drastic light onset and offset. The results show that the VMR of pde6cw59 mutants towards light onset was enhanced by the SchB treatment, and that the initial phase of the enhancement was primarily mediated through the mutants' eyes. Further immunostaining analysis indicates that the treatment specifically reduced the size of the abnormally large rods. These observations implicate an interesting hypothesis: that the morphologically-improved rods drive the observed VMR enhancement. Together, these investigations have identified a possible visual benefit of SchB on retinal degeneration, a benefit that can potentially be further developed to

  9. A Naturally-Derived Compound Schisandrin B Enhanced Light Sensation in the pde6c Zebrafish Model of Retinal Degeneration.

    Science.gov (United States)

    Zhang, Liyun; Xiang, Lue; Liu, Yiwen; Venkatraman, Prahatha; Chong, Leelyn; Cho, Jin; Bonilla, Sylvia; Jin, Zi-Bing; Pang, Chi Pui; Ko, Kam Ming; Ma, Ping; Zhang, Mingzhi; Leung, Yuk Fai

    2016-01-01

    Retinal degeneration is often progressive. This feature has provided a therapeutic window for intervention that may extend functional vision in patients. Even though this approach is feasible, few promising drug candidates are available. The scarcity of new drugs has motivated research to discover novel compounds through different sources. One such example is Schisandrin B (SchB), an active component isolated from the five-flavor fruit (Fructus Schisandrae) that is postulated in traditional Chinese medicines to exert prophylactic visual benefit. This SchB benefit was investigated in this study in pde6cw59, a zebrafish retinal-degeneration model. In this model, the pde6c gene (phosphodiesterase 6C, cGMP-specific, cone, alpha prime) carried a mutation which caused cone degeneration. This altered the local environment and caused the bystander rods to degenerate too. To test SchB on the pde6cw59 mutants, a treatment concentration was first determined that would not cause morphological defects, and would initiate known physiological response. Then, the mutants were treated with the optimized SchB concentration before the appearance of retinal degeneration at 3 days postfertilization (dpf). The light sensation of animals was evaluated at 6 dpf by the visual motor response (VMR), a visual startle that could be initiated by drastic light onset and offset. The results show that the VMR of pde6cw59 mutants towards light onset was enhanced by the SchB treatment, and that the initial phase of the enhancement was primarily mediated through the mutants' eyes. Further immunostaining analysis indicates that the treatment specifically reduced the size of the abnormally large rods. These observations implicate an interesting hypothesis: that the morphologically-improved rods drive the observed VMR enhancement. Together, these investigations have identified a possible visual benefit of SchB on retinal degeneration, a benefit that can potentially be further developed to extend

  10. Effects of bainitic transformation temperature on microstructure and tensile properties of 0.6C-Si-Mn steel; 0.6C-Si-Mn ko no bisai soshiki to hippari tokusei ni oyobosu benaito hentai ondo no eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Y. [University of Osaka Prefecture, Osaka (Japan). Faculty of Engineering

    1995-06-15

    To acquire excellent mechanical properties of Si-Mn steel by using an austempering treatment to have the steel undergo a bainitic transformation, it is important to identify the effect of its transformation temperature. This paper describes a transformation of 0.6% C-Si-Mn steel at temperatures ranging from 593 K to 673 K, and discussions on the effect of the transformation temperature on the microstructure and tensile properties. The following results were obtained: bainitic ferrite containing very little carbon is produced in layers at any transformation temperature, but a trend was shown that the bainitic ferrite is produced with its width grown larger and denser as the transformation temperature rises; the {gamma}R amount increases remarkably with increasing transformation temperature, and at the same time massive {gamma}R begins to remain in addition to thin film {gamma}R that exists between individual bainitic ferrites; and the result of this experiment revealed that when the transformation temperature is sufficiently high, the fracture elongation increases notably because of the transformation induced plasticity (TRIP) effect of the {gamma}R that occurs effectively during the transformation. 12 refs., 7 figs., 4 tabs.

  11. Carcinogenicity study of cochineal in B6C3F1 mice.

    Science.gov (United States)

    Mori, H; Iwata, H; Tanaka, T; Morishita, Y; Mori, Y; Kojima, T; Okumura, A

    1991-09-01

    The carcinogenicity of cochineal, a red colouring used in food and other products, was studied in a 2-yr bioassay in B6C3F1 mice. Groups of 50-55 mice of each sex were given 0, 3 or 6% cochineal in the diet for 2 yr. Mice of all groups developed tumours including hepatocellular adenomas or carcinomas, pulmonary adenomas or adenocarcinomas and lymphomas or lymphatic leukaemias, and the incidences of these tumours were not significantly different in treated and control groups. The results indicate that cochineal lacks carcinogenicity in mice and are consistent with those of in vitro short-term assays of cochineal and of carminic acid, an active principle of cochineal.

  12. Glycidol modulation of the immune responses in female B6C3F1 mice.

    Science.gov (United States)

    Guo, T L; McCay, J A; Brown, R D; Musgrove, D L; Butterworth, L; Munson, A E; Germolec, D R; White, K L

    2000-08-01

    The immunotoxic potential of glycidol was evaluated in female B6C3F1 mice using a battery of functional assays and three host resistance models. Glycidol was administered to the animals by oral gavage as a solution in sterile distilled water daily for 14 days at doses of 25, 125 and 250 mg/kg. In tier I, we observed that glycidol exposure produced a dose-related decrease in splenocyte IgM antibody-forming cell response to sheep red blood cells (sRBC); the spleen natural killer (NK) cell activity was also decreased. A decrease in B cell proliferative responses to anti-IgM F(ab')2 and/or interleukin-4 (IL-4) was observed while the splenocyte proliferative responses to T cell mitogen ConA and B cell mitogen LPS were not affected. The splenocyte proliferative response to allogeneic cells as evaluated in the mixed leukocyte reaction (MLR) to DBA/2 spleen cells was not affected. In tier II, we found that exposure to glycidol decreased the number and percentage of B cells and the absolute number of CD4+ T cells in the spleen while the number of total T cells, CD8+ T cells and CD4+CD8+ T cells was not affected. The cytotoxic T lymphocyte (CTL) response to mitomycin C-treated P815 mastocytoma was not affected; the cytotoxic activity of peritoneal macrophages was not suppressed. Moreover, the host resistance to Listeria monocytogenes was not affected although a slight increase in host resistance to Streptococcus pneumoniae was observed. However, exposure to glycidol decreased host resistance to the B16F10 melanoma tumor model with the maximal tumor formation in lung observed in the high dose group. Overall, these dada support the finding that glycidol is an immunosuppressive agent in female B6C3F1 mice.

  13. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    Science.gov (United States)

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6C3F1 mice for 2 years.

  14. Carcinogenicity of bisphenol-A in Fischer rats and B6C3F1 mice.

    Science.gov (United States)

    Huff, J

    2001-11-01

    Bisphenol-A (BP-A; 4,4'-isopropylidenediphenol) is a monomer of plastics commonly used in various consumer products, and is used as an intermediate in the manufacture of epoxy, polycarbonate, and polyester-styrene resins. A National Toxicology Program carcinogenesis bioassay of BP-A (>98% pure) was conducted by feeding diets containing 0, 1000, or 2000 ppm BP-A to groups of 50 male and 50 female Fischer (F)344 rats; 0, 1000, or 5000 ppm to groups of 50 male B6C3F1 mice; and 0, 5000, or 10,000 ppm to groups of 50 female B6C3F1 mice for 103 weeks. The mean body weights of the low- and high-dose rats and of female mice and high-dose male mice were lower than those of the controls throughout much of the study. Lower body weight gains in rats were likely caused by reduced food consumption. Survivals were comparable among groups. Regarding neoplasia, leukemias occurred at increased incidences in BP-A-dosed rats of both sexes: male, 13/50 controls vs 12/50 low-dose and 23/50 high-dose (P Toxicology Program concluded that there was no convincing evidence that BP-A was carcinogenic for rats or mice. However, the marginal increases in leukemias in male and female rats, along with increases in the combined incidence of lymphomas and leukemias in male mice, suggest that BP-A may be associated with increased cancers of the hematopoietic system. Increases in interstitial-cell tumors of the testes in rats were also evidence of carcinogenesis, as was the unusual occurrence of mammary gland fibroadenomas in male rats.

  15. Evaluation of the effect of different concentrations of Arsenicum album 6cH on intoxicated rats

    Directory of Open Access Journals (Sweden)

    Cíntia Maria Bertaglia Luizetto

    2009-09-01

    Full Text Available Aims: Homeopaths diverge on the concept of dose, i.e. the amount of drug that a patient must take to alter his or her state of disease. In order to stimulate reflections on this concept, this study sought to evaluate in vivo the effect of different concentrations of Arsenicum album 6cH prepared according to homeopathic pharmacotechnics. Methods: male Wistar rats were intoxicated with arsenic and then treated with Arsenicum album 6cH and Arsenicum album 6cH diluted at 1%, administered orally. The amount of arsenic retained in the animals’ organism and that eliminated by urine were measured through atomic absorption spectroscopy. Samples of urine were collected before and after intoxication and during treatment. The positive control group (intoxicated animals and the negative control group (non-intoxicated animals received only the vehicle used in the preparation of the medicine. Results: Groups treated with Arsenicum album 6cH and Arsenicum album 6cH diluted at 1% eliminated significant amounts of arsenic when compared to the control groups. The group treated with Arsenicum album 6cH eliminated significantly higher amounts of arsenic than the group treated with the diluted medicine at 1%. Conclusion: results suggest that Arsenicum album 6cH should not be diluted as not to compromise its effectiveness in the treatment of rats intoxicated with arsenic.

  16. Combat Support Forces (1C6C) Naval Surface Forces Requirements-based Budget Determination for Assault Craft Unit ONE

    Science.gov (United States)

    2009-06-01

    period of time. It is an instrument of planning, performance measurement, decision-making, and management control , as well as a statement of priorities...Dimmerling, 1997). In 1995, Fleming wrote of the importance of budgeting. She states that “budgeting is one of the important planning and control ...Landing Craft Air Cushioned (LCAC) hovercrafts out of its base at Marine Corps Base Camp Pendleton located in North San Diego County, California

  17. Characterization of the myelotoxicity of chloramphenicol succinate in the B6C3F1 mouse.

    Science.gov (United States)

    Turton, John A; Fagg, Rajni; Sones, William R; Williams, Thomas C; Andrews, C Michael

    2006-04-01

    Chloramphenicol (CAP) is haemotoxic in man, inducing two types of toxicity. First, a dose-related, reversible anaemia with reticulocytopenia, sometimes seen in conjunction with leucopenia and thrombocytopenia; this form of toxicity develops during drug treatment. The second haemotoxicity is aplastic anaemia (AA) which is evident in the blood as severe pancytopenia. AA development is not dose-related and occurs weeks or months after treatment. We wish, in the longer term, to investigate CAP-induced AA in the busulphan-pretreated mouse. However, as a prelude to that study, we wanted to characterize in detail the reversible haemotoxicity of CAP succinate (CAPS), administered at high dose levels in the mouse, and follow the recovery of the bone marrow in the post-dosing period. Female B6C3F1 mice were gavaged with CAPS at 0, 2500 and 3500 mg/kg, daily, for 5 days and sampled (n = 5) at 1, 7, 14 and 21 days post-dosing. Blood, bone marrow and spleen samples were analysed and clonogenic assays carried out. At day 1 post-dosing, at both CAPS dose levels, decreases were seen in erythrocytes and erythrocyte precursors; marrow erythroid cells were reduced. Reductions were also evident in splenic nucleated cell counts, blood high fluorescence ratio (HFR) reticulocyte counts and total reticulocyte counts; burst-forming units-erythroid and colony-forming units-erythroid showed decreases. At day 7 post-dosing (2500 mg/kg CAPS), there was regeneration of erythrocyte production, with marked splenic erythropoietic activity, and raised blood HFR reticulocytes. At day 7, at 3500 mg/kg CAPS, erythrocyte and reticulocyte parameters remained depressed. At 14 days post-dosing (2500 mg/kg CAPS), many erythrocyte parameters had returned to normal; at 3500 mg/kg CAPS, there was erythroid regeneration. By 21 days post-dosing, at both CAPS dose levels, most erythrocytic parameters were equivalent to control values. For leucocyte parameters, there was some depression at day 1 post-dosing (at

  18. Genomic analysis of the Pacific oyster (Crassostrea gigas) reveals possible conservation of vertebrate sex determination in a mollusc.

    Science.gov (United States)

    Zhang, Na; Xu, Fei; Guo, Ximing

    2014-09-11

    Despite the prevalence of sex in animal kingdom, we have only limited understanding of how sex is determined and evolved in many taxa. The mollusc Pacific oyster Crassostrea gigas exhibits complex modes of sexual reproduction that consists of protandric dioecy, sex change, and occasional hermaphroditism. This complex system is controlled by both environmental and genetic factors through unknown molecular mechanisms. In this study, we investigated genes related to sex-determining pathways in C. gigas through transcriptome sequencing and analysis of female and male gonads. Our analysis identified or confirmed novel homologs in the oyster of key sex-determining genes (SoxH or Sry-like and FoxL2) that were thought to be vertebrate-specific. Their expression profile in C. gigas is consistent with conserved roles in sex determination, under a proposed model where a novel testis-determining CgSoxH may serve as a primary regulator, directly or indirectly interacting with a testis-promoting CgDsx and an ovary-promoting CgFoxL2. Our findings plus previous results suggest that key vertebrate sex-determining genes such as Sry and FoxL2 may not be inventions of vertebrates. The presence of such genes in a mollusc with expression profiles consistent with expected roles in sex determination suggest that sex determination may be deeply conserved in animals, despite rapid evolution of the regulatory pathways that in C. gigas may involve both genetic and environmental factors.

  19. Carcinogenicity of glycidol in F344 rats and B6C3F1 mice.

    Science.gov (United States)

    Irwin, R D; Eustis, S L; Stefanski, S; Haseman, J K

    1996-01-01

    Glycidol, a simple aliphatic epoxide, was administered by gavage in water to groups of male and female F344/N rats and B6C3F1 mice. Rats received 0, 37.5 or 75 mg kg-1 and mice received 0, 25 or 50 mg kg-1 daily, 5 days per week for 2 years. Exposure to glycidol was associated with dose-related increases in the incidences of neoplasms in numerous tissues in both rats and mice. Survival of rats that received glycidol was markedly reduced compared to the control because of the early induction of neoplastic disease. In male rats, mesothelioma arising in the tunica vaginalis and frequently metastasizing to the peritoneum were considered the major cause of early death. Early deaths in female rats were associated with mammary gland neoplasms. Survival of female mice that received 50 mg kg-1 was lower than the control after week 101 due primarily to euthanasia of moribund animals with mammary gland neoplasms. Survival of male mice and female mice that received 25 mg kg-1 was comparable to the control. In mice, exposure to glycidol was associated with increased incidences of neoplasms of the harderian gland in males and females, the forestomach in males and the mammary gland in females.

  20. High-resolution Moho model for Greenland from EIGEN-6C4 gravity data

    DEFF Research Database (Denmark)

    Steffen, Rebekka; Strykowski, Gabriel; Lund, Björn

    2017-01-01

    are difficult to obtain. Here, we take advantage of the global gravity model EIGEN-6C4, together with the Parker-Oldenburg algorithm, to estimate the depth to the Moho beneath Greenland and surroundings. The available free-air gravity data are corrected for the topographic effect and the effect of sedimentary...... basins. We also correct for the effect on gravity due to the weight of the ice sheet and the accompanying deflection of the Earth's surface, which has not previously been taken into account in gravity studies of currently glaciated regions. Our final Moho depth model for Greenland has an associated...... uncertainty of ±4.5 km for areas with sedimentary basins and ±4 km for areas without sedimentary basins. The model shows maximum Moho depths below east Greenland of up to 55 km and values less than 20 km offshore east Greenland. There is a marked increase in Moho depth of 10–15 km from northern to central...

  1. Benzene-induced hematotoxicity and bone marrow compensation in B6C3F1 mice.

    Science.gov (United States)

    Farris, G M; Robinson, S N; Gaido, K W; Wong, B A; Wong, V A; Hahn, W P; Shah, R S

    1997-04-01

    Long-term inhalation exposure of benzene has been shown to cause hematotoxicity and an increased incidence of acute myelogenous leukemia in humans. The progression of benzene-induced hematotoxicity and the features of the toxicity that may play a major role in the leukemogenesis are not known. We report the hematological consequences of benzene inhalation in B6C3F1 mice exposed to 1, 5, 10, 100, and 200 ppm benzene for 6 hr/day, 5 days/week for 1, 2, 4, or 8 weeks and a recovery group. There were no significant effects on hematopoietic parameters from exposure to 10 ppm benzene or less. Exposure of mice to 100 and 200 ppm benzene reduced the number of total bone marrow cells, progenitor cells, differentiating hematopoietic cells, and most blood parameters. Replication of primitive progenitor cells in the bone marrow was increased during the exposure period as a compensation for the cytotoxicity induced by 100 and 200 ppm benzene. In mice exposed to 200 ppm benzene, the primitive progenitor cells maintained an increased percentage of cells in S-phase through 25 days of recovery compared with controls. The increased replication of primitive progenitor cells in concert with the reported genotoxicity induced by benzene provides the components necessary for producing an increased incidence of lymphoma in mice. Furthermore, we propose this mode of action as a biologically plausible mechanism for benzene-induced leukemia in humans exposed to high concentrations of benzene.

  2. Regeneration of roots from callus reveals stability of the developmental program for determinate root growth in Sonoran Desert Cactaceae.

    Science.gov (United States)

    Shishkova, Svetlana; García-Mendoza, Edith; Castillo-Díaz, Vicente; Moreno, Norma E; Arellano, Jesús; Dubrovsky, Joseph G

    2007-05-01

    In some Sonoran Desert Cactaceae the primary root has a determinate root growth: the cells of the root apical meristem undergo only a few cell division cycles and then differentiate. The determinate growth of primary roots in Cactaceae was found in plants cultivated under various growth conditions, and could not be reverted by any treatment tested. The mechanisms involved in root meristem maintenance and determinate root growth in plants remain poorly understood. In this study, we have shown that roots regenerated from the callus of two Cactaceae species, Stenocereus gummosus and Ferocactus peninsulae, have a determinate growth pattern, similar to that of the primary root. To demonstrate this, a protocol for root regeneration from callus was established. The determinate growth pattern of roots regenerated from callus suggests that the program of root development is very stable in these species. These findings will permit future analysis of the role of certain Cactaceae genes in the determinate pattern of root growth via the regeneration of transgenic roots from transformed calli.

  3. Absorption and metabolism of triclosan after application to the skin of B6C3F1 mice.

    Science.gov (United States)

    Fang, Jia-Long; Vanlandingham, Michelle; da Costa, Gonçalo Gamboa; Beland, Frederick A

    2016-05-01

    Triclosan is used as an antimicrobial agent in personal care products, household items, medical devices, and clinical settings. Humans can receive lifelong exposures to triclosan; however, data on the toxicity and carcinogenicity after topical application are lacking. This study determined the absorption, distribution, metabolism, and excretion of triclosan after application to the skin of B6C3F1 mice. [(14)C(U)]triclosan (10 or 100 mg triclosan/kg body weight) was administered topically to mice in two separate experiments: a vehicle selection experiment using propylene glycol, ethanol, and a generic cosmetic cream, and a toxicokinetic experiment. Mice were killed up to 72 h after triclosan administration, and excreta and tissues were analyzed for radioactivity. Ethanol had the best properties of the vehicles evaluated. Maximum absorption was obtained at approximately 12 h after dosing. Radioactivity appeared in the excreta and in all tissues examined, with the highest levels in the gall bladder and the lowest levels in the brain. Triclosan was metabolized to triclosan sulfate, triclosan glucuronide, 2,4-dichlorophenol, and hydroxytriclosan. The metabolite profile was tissue-dependent and the predominant route of excretion was fecal. The AUC(0-∞) and the Cmax of plasma and liver in females were greater than those in males. Slightly lower absorption was observed in mice with Elizabethan collars.

  4. Synthesis and Crystal Structure of [ Cp* Ru(η6- C6H5B Ph3)

    Institute of Scientific and Technical Information of China (English)

    YIN Jun; GUAN Jin-Tao; YU Guang-Ao; LIU Sheng-Hua

    2005-01-01

    The title complex [Cp*Ru(η6-C6H5BPh3)] has been synthesized by the reaction of [Cp*Ru(H2O)(NBD)]BF4 with H2 and NaBPh4, and its crystal structure was determined by singlecrystal X-ray diffraction analysis. It crystallizes in triclinic, space group P(1) with a = 11.0610(10), b = 11.2317(10), c = 12.3633(11) (A), α = 81.419(2), β = 67.8370(10), γ = 88.370(2)°, V= 1405.9(2) (A)3,Z= 2, C34H35BRu, Mr= 555.50, Dc = 1.312 g/cm3, F(000) = 576 and μ(MoKa) = 0.577 mm-1. The final R and wR are 0.0559 and 0.1483, respectively for 4365 observed reflections with I > 2σ(Ⅰ). In the title complex, the four phenyl rings bonded to the B atom are deposited in a tetrahedral geometry,and one of the phenyl rings is η6-bonded to ruthenium.

  5. Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant.

    Science.gov (United States)

    Amich, Jorge; Dümig, Michaela; O'Keeffe, Gráinne; Binder, Jasmin; Doyle, Sean; Beilhack, Andreas; Krappmann, Sven

    2016-04-01

    Fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. To date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. This is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. Here, we have investigated sulfur (S) utilization by the human-pathogenic mold Aspergillus fumigatus during invasive growth. Our data reveal that inorganic S compounds or taurine is unlikely to serve as an S source during invasive pulmonary aspergillosis since a sulfate transporter mutant strain and a sulfite reductase mutant strain are fully virulent. In contrast, the S-containing amino acid cysteine is limiting for fungal growth, as proven by the reduced virulence of a cysteine auxotroph. Moreover, phenotypic characterization of this strain further revealed the robustness of the subordinate glutathione redox system. Interestingly, we demonstrate that methionine synthase is essential for A. fumigatus virulence, defining the biosynthetic route of this proteinogenic amino acid as a potential antifungal target. In conclusion, we provide novel insights into the nutritional requirements ofA. fumigatus during pathogenesis, a prerequisite to understanding and fighting infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Comparison of the aggregation of homologous β2-microglobulin variants reveals protein solubility as a key determinant of amyloid formation.

    Science.gov (United States)

    Pashley, Clare L; Hewitt, Eric W; Radford, Sheena E

    2016-02-13

    The mouse and human β2-microglobulin protein orthologs are 70% identical in sequence and share 88% sequence similarity. These proteins are predicted by various algorithms to have similar aggregation and amyloid propensities. However, whilst human β2m (hβ2m) forms amyloid-like fibrils in denaturing conditions (e.g. pH2.5) in the absence of NaCl, mouse β2m (mβ2m) requires the addition of 0.3M NaCl to cause fibrillation. Here, the factors which give rise to this difference in amyloid propensity are investigated. We utilise structural and mutational analyses, fibril growth kinetics and solubility measurements under a range of pH and salt conditions, to determine why these two proteins have different amyloid propensities. The results show that, although other factors influence the fibril growth kinetics, a striking difference in the solubility of the proteins is a key determinant of the different amyloidogenicity of hβ2m and mβ2m. The relationship between protein solubility and lag time of amyloid formation is not captured by current aggregation or amyloid prediction algorithms, indicating a need to better understand the role of solubility on the lag time of amyloid formation. The results demonstrate the key contribution of protein solubility in determining amyloid propensity and lag time of amyloid formation, highlighting how small differences in protein sequence can have dramatic effects on amyloid formation.

  7. Genome editing reveals dmrt1 as an essential male sex-determining gene in Chinese tongue sole (Cynoglossus semilaevis)

    Science.gov (United States)

    Cui, Zhongkai; Liu, Yun; Wang, Wenwen; Wang, Qian; Zhang, Ning; Lin, Fan; Wang, Na; Shao, Changwei; Dong, Zhongdian; Li, Yangzhen; Yang, Yingming; Hu, Mengzhu; Li, Hailong; Gao, Fengtao; Wei, Zhanfei; Meng, Liang; Liu, Yang; Wei, Min; Zhu, Ying; Guo, Hua; Cheng, Christopher H. K.; Schartl, Manfred; Chen, Songlin

    2017-01-01

    Chinese tongue sole is a marine fish with ZW sex determination. Genome sequencing suggested that the Z-linked dmrt1 is a putative male determination gene, but direct genetic evidence is still lacking. Here we show that TALEN of dmrt1 efficiently induced mutations of this gene. The ZZ dmrt1 mutant fish developed ovary-like testis, and the spermatogenesis was disrupted. The female-related genes foxl2 and cyp19a1a were significantly increased in the gonad of the ZZ dmrt1 mutant. Conversely, the male-related genes Sox9a and Amh were significantly decreased. The dmrt1 deficient ZZ fish grew much faster than ZZ male control. Notably, we obtained an intersex ZW fish with a testis on one side and an ovary on the other side. This fish was chimeric for a dmrt1 mutation in the ovary, and wild-type dmrt1 in the testis. Our data provide the first functional evidence that dmrt1 is a male determining gene in tongue sole. PMID:28205594

  8. TNF-alpha-dependent regulation of acute pancreatitis severity by Ly-6C(hi) monocytes in mice.

    Science.gov (United States)

    Perides, George; Weiss, Eric R; Michael, Emily S; Laukkarinen, Johanna M; Duffield, Jeremy S; Steer, Michael L

    2011-04-15

    The roles of monocytes/macrophages and their mechanisms of action in the regulation of pancreatitis are poorly understood. To address these issues, we have employed genetically altered mouse strains that either express the human diphtheria toxin receptor (DTR) coupled to the CD11b promoter or have global deletion of TNF-α. Targeted, conditional depletion of monocytes/macrophages was achieved by administration of diphtheria toxin (DT) to CD11b-DTR mice. We show that in the absence of DT administration, pancreatitis is associated with an increase in pancreatic content of Ly-6C(hi) monocytes/macrophages but that this response is prevented by prior administration of DT to CD11b-DTR mice. DT administration also reduces pancreatic edema and acinar cell injury/necrosis in two dissimilar experimental models of acute pancreatitis (a secretagogue-induced model and a model elicited by retrograde pancreatic duct infusion of sodium taurocholate). In the secretagogue-elicited model, the DT-induced decrease in pancreatitis severity is reversed by adoptive transfer of purified Ly-6C(hi) monocytes harvested from non-DT-treated CD11b-DTR mice or by the transfer of purified Ly-6C(hi) monocytes harvested from TNF-α(+/+) donor mice, but it is not reversed by the transfer of Ly-6C(hi) monocytes harvested from TNF-α(-/-) donors. Our studies indicate that the Ly-6C(hi) monocyte subset regulates the severity of pancreatitis by promoting pancreatic edema and acinar cell injury/necrosis and that this phenomenon is dependent upon the expression of TNF-α by those cells. They suggest that therapies targeting Ly-6C(hi) monocytes and/or TNF-α expression by Ly-6C(hi) monocytes might prove beneficial in the prevention or treatment of acute pancreatitis.

  9. Single molecule force spectroscopy reveals critical roles of hydrophobic core packing in determining the mechanical stability of protein GB1.

    Science.gov (United States)

    Bu, Tianjia; Wang, Hui-Chuan Eileen; Li, Hongbin

    2012-08-21

    Understanding molecular determinants of protein mechanical stability is important not only for elucidating how elastomeric proteins are designed and functioning in biological systems but also for designing protein building blocks with defined nanomechanical properties for constructing novel biomaterials. GB1 is a small α/β protein and exhibits significant mechanical stability. It is thought that the shear topology of GB1 plays an important role in determining its mechanical stability. Here, we combine single molecule atomic force microscopy and protein engineering techniques to investigate the effect of side chain reduction and hydrophobic core packing on the mechanical stability of GB1. We engineered seven point mutants and carried out mechanical φ-value analysis of the mechanical unfolding of GB1. We found that three mutations, which are across the surfaces of two subdomains that are to be sheared by the applied stretching force, in the hydrophobic core (F30L, Y45L, and F52L) result in significant decrease in mechanical unfolding force of GB1. The mechanical unfolding force of these mutants drop by 50-90 pN compared with wild-type GB1, which unfolds at around 180 pN at a pulling speed of 400 nm/s. These results indicate that hydrophobic core packing plays an important role in determining the mechanical stability of GB1 and suggest that optimizing hydrophobic interactions across the surfaces that are to be sheared will likely be an efficient method to enhance the mechanical stability of GB1 and GB1 homologues.

  10. Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity

    Science.gov (United States)

    Ma, Siming; Upneja, Akhil; Galecki, Andrzej; Tsai, Yi-Miau; Burant, Charles F; Raskind, Sasha; Zhang, Quanwei; Zhang, Zhengdong D; Seluanov, Andrei; Gorbunova, Vera; Clish, Clary B; Miller, Richard A; Gladyshev, Vadim N

    2016-01-01

    Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences. DOI: http://dx.doi.org/10.7554/eLife.19130.001 PMID:27874830

  11. Genomic Insights and Its Comparative Analysis with Yersinia enterocolitica Reveals the Potential Virulence Determinants and Further Pathogenicity for Foodborne Outbreaks.

    Science.gov (United States)

    Gnanasekaran, Gopalsamy; Na, Eun Jung; Chung, Han Young; Kim, Suyeon; Kim, You-Tae; Kwak, Woori; Kim, Heebal; Ryu, Sangryeol; Choi, Sang Ho; Lee, Ju-Hoon

    2017-02-28

    Yersinia enterocolitica is a well-known foodborne pathogen causing gastrointestinal infections worldwide. The strain Y. enterocolitica FORC_002 was isolated from the gill of flatfish (plaice) and its genome was sequenced. The genomic DNA consists of 4,837,317 bp with a GC content of 47.1%, and is predicted to contain 4,221 open reading frames, 81 tRNA genes, and 26 rRNA genes. Interestingly, genomic analysis revealed pathogenesis and host immune evasion-associated genes encoding guanylate cyclase (Yst), invasin (Ail and Inv), outer membrane protein (Yops), autotransporter adhesin A (YadA), RTX-like toxins, and a type III secretion system. In particular, guanylate cyclase is a heat-stable enterotoxin causing Yersinia-associated diarrhea, and RTX-like toxins are responsible for attachment to integrin on the target cell for cytotoxic action. This genome can be used to identify virulence factors that can be applied for the development of novel biomarkers for the rapid detection of this pathogen in foods.

  12. Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant.

    Science.gov (United States)

    Yuchi, Zhiguang; Yuen, Siobhan M Wong King; Lau, Kelvin; Underhill, Ainsley Q; Cornea, Razvan L; Fessenden, James D; Van Petegem, Filip

    2015-08-06

    Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca(2+)-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

  13. TRA-1 ChIP-seq reveals regulators of sexual differentiation and multilevel feedback in nematode sex determination.

    Science.gov (United States)

    Berkseth, Matt; Ikegami, Kohta; Arur, Swathi; Lieb, Jason D; Zarkower, David

    2013-10-01

    How sexual regulators translate global sexual fate into appropriate local sexual differentiation events is perhaps the least understood aspect of sexual development. Here we have used ChIP followed by deep sequencing (ChIP-seq) to identify direct targets of the nematode global sexual regulator Transformer 1 (TRA-1), a transcription factor acting at the interface between organism-wide and cell-specific sexual regulation to control all sex-specific somatic differentiation events. We identified 184 TRA-1-binding sites in Caenorhabditis elegans, many with temporal- and/or tissue-specific TRA-1 association. We also identified 78 TRA-1-binding sites in the related nematode Caenorhabditis briggsae, 19 of which are conserved between the two species. Some DNA segments containing TRA-1-binding sites drive male-specific expression patterns, and RNAi depletion of some genes adjacent to TRA-1-binding sites results in defects in male sexual development. TRA-1 binds to sites adjacent to a number of heterochronic regulatory genes, some of which drive male-specific expression, suggesting that TRA-1 imposes sex specificity on developmental timing. We also found evidence for TRA-1 feedback regulation of the global sex-determination pathway: TRA-1 binds its own locus and those of multiple upstream masculinizing genes, and most of these associations are conserved in C. briggsae. Thus, TRA-1 coordinates sexual development by reinforcing the sex-determination decision and directing downstream sexual differentiation events.

  14. Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

    Science.gov (United States)

    Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

    2016-01-19

    The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

  15. ESA's Release 5 Gravity Field Model by the Direct Approach and its Part in the Combined Model EIGEN-6C4

    Science.gov (United States)

    Foerste, C.; Bruinsma, S.; Abrikosov, O.; Lemoine, J. M.; Marty, J. C.; Flechtner, F.; Dahle, C.; Neumayer, H.; Barthelmes, F.; König, R.; Balmino, G.; Biancale, R.

    2014-12-01

    GFZ Potsdam and GRGS Toulouse have a close cooperation in the field of global gravity field determination and both are members of the European GOCE Gravity Consortium and compute gravity fields on behalf of the European Space Agency. Here we present release 5 of the GOCE gravity field model by means of the Direct Approach (GOCE-DIR5), which was made with the GOCE data from the entire mission (Nov09 - Oct13) as well as with LAGEOS and GRACE data. Compared to release 4, GOCE data at the lower mission altitudes are included and the max d/o has been increased to 300. The 3-axes GOCE gradiometer gave gravity gradients that are measured with a high accuracy only within its measurement bandwidth of ~ 0.005 to 0.1 Hz. Thus, the gradient observation equations must be filtered which was done by a band pass filter of 8-120 sec. The GOCE GPS-SST data are only used to geolocate the gradients. The low-to-medium degree spherical harmonic coefficients of the gravity field are determined using GRACE as well as LAGEOS data from GRGS Release 3. All data are combined at normal equation level and a regularized solution is obtained by Cholesky decomposition. The GOCE-DIR5 data were used to make our latest combined model EIGEN-6C4. This is the 4th release of EIGEN-6C which was the very first combined gravity field model using GOCE data. EIGEN-6C4 is complete to d/o 2190 and was made from the GOCE-DIR5 data combined with DTU10 and EGM2008 surface gravity data. The combination of the different data types has been done on the basis of full normal equations up to d/o 370. In contrast to GOCE-DIR5 the satellite normal equation for EIGEN-6C4 contains 5 types of time variable parameters for each coefficient up to d/o 80. The coefficients beyond deg 370 were obtained from a block diagonal normal equation from the terrestrial data only. The comparison of test results (orbit computation, GPS leveling, geostrophic current speeds based on SVP buoy velocity data) of GOCE-DIR5 and EIGEN-6C4 with

  16. Meta-GWAS and Meta-Analysis of Exome Array Studies Do Not Reveal Genetic Determinants of Serum Hepcidin

    Science.gov (United States)

    Galesloot, Tessel E.; van Dijk, Freerk; Geurts-Moespot, Anneke J.; Girelli, Domenico; Kiemeney, Lambertus A. L. M.; Sweep, Fred C. G. J.; Swertz, Morris A.; van der Meer, Peter; Camaschella, Clara; Toniolo, Daniela; Vermeulen, Sita H.; van der Harst, Pim; Swinkels, Dorine W.

    2016-01-01

    Serum hepcidin concentration is regulated by iron status, inflammation, erythropoiesis and numerous other factors, but underlying processes are incompletely understood. We studied the association of common and rare single nucleotide variants (SNVs) with serum hepcidin in one Italian study and two large Dutch population-based studies. We genotyped common SNVs with genome-wide association study (GWAS) arrays and subsequently performed imputation using the 1000 Genomes reference panel. Cohort-specific GWAS were performed for log-transformed serum hepcidin, adjusted for age and gender, and results were combined in a fixed-effects meta-analysis (total N 6,096). Six top SNVs (p<5x10-6) were genotyped in 3,821 additional samples, but associations were not replicated. Furthermore, we meta-analyzed cohort-specific exome array association results of rare SNVs with serum hepcidin that were available for two of the three cohorts (total N 3,226), but no exome-wide significant signal (p<1.4x10-6) was identified. Gene-based meta-analyses revealed 19 genes that showed significant association with hepcidin. Our results suggest the absence of common SNVs and rare exonic SNVs explaining a large proportion of phenotypic variation in serum hepcidin. We recommend extension of our study once additional substantial cohorts with hepcidin measurements, GWAS and/or exome array data become available in order to increase power to identify variants that explain a smaller proportion of hepcidin variation. In addition, we encourage follow-up of the potentially interesting genes that resulted from the gene-based analysis of low-frequency and rare variants. PMID:27846281

  17. Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies.

    Science.gov (United States)

    Kaufmann, Kristian W; Dawson, Eric S; Henry, L Keith; Field, Julie R; Blakely, Randy D; Meiler, Jens

    2009-02-15

    To identify potential determinants of substrate selectivity in serotonin (5-HT) transporters (SERT), models of human and Drosophila serotonin transporters (hSERT, dSERT) were built based on the leucine transporter (LeuT(Aa)) structure reported by Yamashita et al. (Nature 2005;437:215-223), PBDID 2A65. Although the overall amino acid identity between SERTs and the LeuT(Aa) is only 17%, it increases to above 50% in the first shell of the putative 5-HT binding site, allowing de novo computational docking of tryptamine derivatives in atomic detail. Comparison of hSERT and dSERT complexed with substrates pinpoints likely structural determinants for substrate binding. Forgoing the use of experimental transport and binding data of tryptamine derivatives for construction of these models enables us to critically assess and validate their predictive power: A single 5-HT binding mode was identified that retains the amine placement observed in the LeuT(Aa) structure, matches site-directed mutagenesis and substituted cysteine accessibility method (SCAM) data, complies with support vector machine derived relations activity relations, and predicts computational binding energies for 5-HT analogs with a significant correlation coefficient (R = 0.72). This binding mode places 5-HT deep in the binding pocket of the SERT with the 5-position near residue hSERT A169/dSERT D164 in transmembrane helix 3, the indole nitrogen next to residue Y176/Y171, and the ethylamine tail under residues F335/F327 and S336/S328 within 4 A of residue D98. Our studies identify a number of potential contacts whose contribution to substrate binding and transport was previously unsuspected.

  18. Catalytic analysis of APOBEC3G involving real-time NMR spectroscopy reveals nucleic acid determinants for deamination.

    Directory of Open Access Journals (Sweden)

    Keisuke Kamba

    Full Text Available APOBEC3G (A3G is a single-stranded DNA-specific cytidine deaminase that preferentially converts cytidine to uridine at the third position of triplet cytosine (CCC hotspots. A3G restricts the infectivity of viruses, such as HIV-1, by targeting CCC hotspots scattered through minus DNA strands, reverse-transcribed from genomic RNA. Previously, we developed a real-time NMR method and elucidated the origin of the 3'→5' polarity of deamination of DNA by the C-terminal domain of A3G (CD2, which is a phenomenon by which a hotspot located closer to the 5'-end is deaminated more effectively than one less close to the 5'-end, through quantitative analysis involving nonspecific binding to and sliding along DNA. In the present study we applied the real-time NMR method to analyze the catalytic activity of CD2 toward DNA oligonucleotides containing a nucleotide analog at a single or multiple positions. Analyses revealed the importance of the sugar and base moieties throughout the consecutive 5 nucleotides, the CCC hotspot being positioned at the center. It was also shown that the sugar or base moieties of the nucleotides outside this 5 nucleotide recognition sequence are also relevant as to CD2's activity. Analyses involving DNA oligonucleotides having two CCC hotspots linked by a long sequence of either deoxyribonucleotides, ribonucleotides or abasic deoxyribonucleotides suggested that the phosphate backbone is required for CD2 to slide along the DNA strand and to exert the 3'→5' polarity. Examination of the effects of different salt concentrations on the 3'→5' polarity indicated that the higher the salt concentration, the less prominent the 3'→5' polarity. This is most likely the result of alleviation of sliding due to a decrease in the affinity of CD2 with the phosphate backbone at high salt concentrations. We also investigated the reactivity of substrates containing 5-methylcytidine (5mC or 5-hydroxymethylcytidine, and found that A3G exhibited low

  19. Determination of equilibrium structures of bromothymol blue revealed by using quantum chemistry with an aid of multivariate analysis of electronic absorption spectra.

    Science.gov (United States)

    Shimada, Toru; Hasegawa, Takeshi

    2017-10-05

    The pH dependent chemical structures of bromothymol blue (BTB), which have long been under controversy, are determined by employing a combined technique of multivariate analysis of electronic absorption spectra and quantum chemistry. Principle component analysis (PCA) of the pH dependent spectra apparently reveals that only two chemical species are adequate to fully account for the color changes, with which the spectral decomposition is readily performed by using augmented alternative least-squares (ALS) regression analysis. The quantity variation by the ALS analysis also reveals the practical acid dissociation constant, pKa'. The determination of pKa' is performed for various ionic strengths, which reveals the thermodynamic acid constant (pKa=7.5) and the number of charge on each chemical species; the yellow form is negatively charged species of -1 and the blue form that of -2. On this chemical information, the quantum chemical calculation is carried out to find that BTB molecules take the pure quinoid form in an acid solution and the quinoid-phenolate form in an alkaline solution. The time-dependent density functional theory (TD-DFT) calculations for the theoretically determined chemical structures account for the peak shift of the electronic spectra. In this manner, the structures of all the chemical species appeared in equilibrium have finally been confirmed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Determination of equilibrium structures of bromothymol blue revealed by using quantum chemistry with an aid of multivariate analysis of electronic absorption spectra

    Science.gov (United States)

    Shimada, Toru; Hasegawa, Takeshi

    2017-10-01

    The pH dependent chemical structures of bromothymol blue (BTB), which have long been under controversy, are determined by employing a combined technique of multivariate analysis of electronic absorption spectra and quantum chemistry. Principle component analysis (PCA) of the pH dependent spectra apparently reveals that only two chemical species are adequate to fully account for the color changes, with which the spectral decomposition is readily performed by using augmented alternative least-squares (ALS) regression analysis. The quantity variation by the ALS analysis also reveals the practical acid dissociation constant, pKa‧. The determination of pKa‧ is performed for various ionic strengths, which reveals the thermodynamic acid constant (pKa = 7.5) and the number of charge on each chemical species; the yellow form is negatively charged species of - 1 and the blue form that of - 2. On this chemical information, the quantum chemical calculation is carried out to find that BTB molecules take the pure quinoid form in an acid solution and the quinoid-phenolate form in an alkaline solution. The time-dependent density functional theory (TD-DFT) calculations for the theoretically determined chemical structures account for the peak shift of the electronic spectra. In this manner, the structures of all the chemical species appeared in equilibrium have finally been confirmed.

  1. Sex determination by SRY PCR and sequencing of Tasmanian devil facial tumour cell lines reveals non-allograft transmission.

    Science.gov (United States)

    Cui, Xianlan; Wang, Yunfeng; Hua, Bobby; Miller, Webb; Zhao, Yan; Cui, Hongyu; Kong, Xiangang

    2016-05-20

    Devil facial tumour disease (DFTD) is an infectious tumour disease and was hypothesised to be transmitted by allograft during biting based on two cytogenetic findings of DFTD tumours in 2006. It was then believed that DFTD tumours were originally from a female devil. In this study the devil sex-determining region Y (SRY) gene was PCR amplified and sequenced, and six pairs of devil SRY PCR primers were used for detection of devil SRY gene fragments in purified DFTD tumour cell lines. Using three pairs of devil SRY PCR primers, devil SRY gene sequence was detected by PCR and sequencing in genomic DNA of DFTD tumour cell lines from six male devils, but not from six female devils. Four out of six DFTD tumour cell lines from male devils contained nucleotides 288-482 of the devil SRY gene, and another two DFTD tumour cell lines contained nucleotides 381-577 and 493-708 of the gene, respectively. These results indicate that the different portions of the SRY gene in the DFTD tumours of the male devils were originally from the male hosts, rejecting the currently believed DFTD allograft transmission theory. The reasons why DFTD transmission was incorrectly defined as allograft are discussed.

  2. Stochastic kinetics reveal imperative role of anisotropic interfacial tension to determine morphology and evolution of nucleated droplets in nematogenic films

    Science.gov (United States)

    Bhattacharjee, Amit Kumar

    2017-01-01

    For isotropic fluids, classical nucleation theory predicts the nucleation rate, barrier height and critical droplet size by ac- counting for the competition between bulk energy and interfacial tension. The nucleation process in liquid crystals is less understood. We numerically investigate nucleation in monolayered nematogenic films using a mesoscopic framework, in par- ticular, we study the morphology and kinetic pathway in spontaneous formation and growth of droplets of the stable phase in the metastable background. The parameter κ that quantifies the anisotropic elastic energy plays a central role in determining the geometric structure of the droplets. Noncircular nematic droplets with homogeneous director orientation are nucleated in a background of supercooled isotropic phase for small κ. For large κ, noncircular droplets with integer topological charge, accompanied by a biaxial ring at the outer surface, are nucleated. The isotropic droplet shape in a superheated nematic background is found to depend on κ in a similar way. Identical growth laws are found in the two cases, although an unusual two-stage mechanism is observed in the nucleation of isotropic droplets. Temporal distributions of successive events indi- cate the relevance of long-ranged elasticity-mediated interactions within the isotropic domains. Implications for a theoretical description of nucleation in anisotropic fluids are discussed. PMID:28054600

  3. Stochastic kinetics reveal imperative role of anisotropic interfacial tension to determine morphology and evolution of nucleated droplets in nematogenic films

    Science.gov (United States)

    Bhattacharjee, Amit Kumar

    2017-01-01

    For isotropic fluids, classical nucleation theory predicts the nucleation rate, barrier height and critical droplet size by ac- counting for the competition between bulk energy and interfacial tension. The nucleation process in liquid crystals is less understood. We numerically investigate nucleation in monolayered nematogenic films using a mesoscopic framework, in par- ticular, we study the morphology and kinetic pathway in spontaneous formation and growth of droplets of the stable phase in the metastable background. The parameter κ that quantifies the anisotropic elastic energy plays a central role in determining the geometric structure of the droplets. Noncircular nematic droplets with homogeneous director orientation are nucleated in a background of supercooled isotropic phase for small κ. For large κ, noncircular droplets with integer topological charge, accompanied by a biaxial ring at the outer surface, are nucleated. The isotropic droplet shape in a superheated nematic background is found to depend on κ in a similar way. Identical growth laws are found in the two cases, although an unusual two-stage mechanism is observed in the nucleation of isotropic droplets. Temporal distributions of successive events indi- cate the relevance of long-ranged elasticity-mediated interactions within the isotropic domains. Implications for a theoretical description of nucleation in anisotropic fluids are discussed.

  4. Ly6C(high) Monocytes Oscillate in the Heart During Homeostasis and After Myocardial Infarction-Brief Report.

    Science.gov (United States)

    Schloss, Maximilian J; Hilby, Michael; Nitz, Katrin; Guillamat Prats, Raquel; Ferraro, Bartolo; Leoni, Giovanna; Soehnlein, Oliver; Kessler, Thorsten; He, Wenyan; Luckow, Bruno; Horckmans, Michael; Weber, Christian; Duchene, Johan; Steffens, Sabine

    2017-09-01

    Circadian regulation of neutrophil homeostasis affects myocardial infarction (MI) healing. It is unknown whether diurnal variations of monocyte counts exist in the heart and whether this affects their cardiac infiltration in response to MI. Murine blood and organs were harvested at distinct times of day and analyzed by flow cytometry. Ly6C(high) monocyte surface expression levels of chemokine receptors (CCR) were ≈2-fold higher at the beginning of the active phase, Zeitgeber Time (ZT) 13 compared with ZT5. This was because of enhanced receptor surface expression at ZT13, whereas no significant changes in total cellular protein levels were found. Most blood Ly6C(high) monocytes were CCR2(high), whereas only a minority was CCR1(high) and CCR5(high). We also found diurnal changes of classical monocyte blood counts in humans, being higher in the evening, while exhibiting enhanced CCR2 surface expression in the morning. In support of monocyte oscillations between blood and tissue, murine cardiac Ly6C(high) monocyte counts were highest at ZT13, accompanied by an upregulation of cardiac CC chemokine ligand 2 mRNA. Mice subjected to MI at ZT13 had an even higher upregulation of CCR2 surface expression on circulating monocytes compared with noninfarcted mice and more elevated cardiac CC chemokine ligand 2 protein expression and more pronounced Ly6C(high) monocyte infiltration compared with ZT5-infarcted mice. Concomitantly, CCR2 antagonism only inhibited the excessive cardiac Ly6C(high) monocyte infiltration after ZT13 MI but not ZT5 MI. CCR2 surface expression on Ly6C(high) monocytes changes in a time-of-day-dependent manner, which crucially affects cardiac monocyte recruitment after an acute ischemic event. © 2017 American Heart Association, Inc.

  5. Comparison of capsular genes of Streptococcus pneumoniae serotype 6A, 6B, 6C, and 6D isolates.

    Science.gov (United States)

    Song, Jae-Hoon; Baek, Jin Yang; Ko, Kwan Soo

    2011-05-01

    Recently, Streptococcus pneumoniae serotypes 6C and 6D have been identified. It is thought that they emerged by the replacement of wciN(β) in the capsular loci of serotypes 6A and 6B, respectively. However, their evolution has not been unveiled yet. To investigate the evolution of four serotypes of S. pneumoniae serogroup 6, four genes of the capsular polysaccharide synthesis (cps) locus, wchA, wciN, wciO, and wciP, of isolates of S. pneumoniae serotypes 6A, 6B, 6C, and 6D were sequenced. Multilocus sequence typing (MLST) was performed to investigate their genetic backgrounds. The wchA gene of serotype 6C and 6D isolates was distinct from that of serotype 6A and 6B isolates, which may suggest cotransfer of wchA with wciN(β). Otherwise, serotypes 6C and 6D displayed different genetic backgrounds from serotypes 6A and 6B, which was suggested by MLST analysis. In addition, serotype 6C isolates showed distinct wciP polymorphisms from other serotypes, which also indicated that serotype 6C had not recently originated from serotype 6A. Although serotype 6D shared the same amino acid polymorphisms of wciO with serotype 6B, wciP of serotype 6D differed from that of serotype 6B. The data indicate the implausibility of the scenario of a recent emergence of the cps locus of serotype 6D by genetic recombination between serotypes 6B and 6C. In addition, five serotype 6A and 6B isolates (6X group) displayed cps loci distinct from those of other isolates. The cps locus homogeneity and similar sequence types in MLST analysis suggest that most of the 6X group of isolates originated from the same ancestor and that the entire cps locus might have recently been transferred from an unknown origin. Serotype 6B isolates showed two or more cps locus subtypes, indicating a recombination-mediated mosaic structure of the cps locus of serotype 6B. The collective data favor the emergence of cps loci of serotypes 6A, 6B, 6C, and 6D by complicated recombination.

  6. Graphical linking of MO multicenter bond index and VB structures. II-5-c rings and 6-c heterocyclic rings

    CERN Document Server

    Bollini, C G; Giambiagi, M

    2001-01-01

    Through the graphical method proposed it is possible to set a link between an MO multicenter bond index and VB structures. The value of the index depends on the order of the atoms involved if they are more than three. For 5-c rings three basic structures are required; the eventually different values are 12. Unlike the 6-c case it may happen that different pairs of basic structures are used to build the same polygon. For the 6-c rings including heteroatoms the original degeneracy of benzene splits leading eventually to 60 different I sub r sub i sub n sub g values.

  7. Insight into the modulation of Shaw2 Kv channels by general anesthetics: structural and functional studies of S4-S5 linker and S6 C-terminal peptides in micelles by NMR.

    Science.gov (United States)

    Zhang, Jin; Qu, Xiaoguang; Covarrubias, Manuel; Germann, Markus W

    2013-02-01

    The modulation of the Drosophila Shaw2 Kv channel by 1-alkanols and inhaled anesthetics is correlated with the involvement of the S4-S5 linker and C-terminus of S6, and consistent with stabilization of the channel's closed state. Structural analysis of peptides from S4-S5 (L45) and S6 (S6c), by nuclear magnetic resonance and circular dichroism spectroscopy supports that an α-helical conformation was adopted by L45, while S6c was only in an unstable/dynamic partially folded α-helix in dodecylphosphocholine micelles. Solvent accessibility and paramagnetic probing of L45 revealed that L45 lies parallel to the surface of micelles with charged and polar residues pointing towards the solution while hydrophobic residues are buried inside the micelles. Chemical shift perturbation introduced by 1-butanol on residues Gln320, Thr321, Phe322 and Arg323 of L45, as well as Thr423 and Gln424 of S6c indicates possible anesthetic binding sites on these two important components in the channel activation apparatus. Diffusion measurements confirmed the association of L45, S6c and 1-butanol with micelles which suggests the capability of 1-butanol to influence a possible interaction of L45 and S6c in the micelle environment.

  8. Genome-wide mutagenesis of Xanthomonas axonopodis pv. citri reveals novel genetic determinants and regulation mechanisms of biofilm formation.

    Directory of Open Access Journals (Sweden)

    Jinyun Li

    determinants and regulatory mechanism of biofilm formation.

  9. The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance.

    Science.gov (United States)

    Saeed, Mohamed; Khalid, Hassan; Sugimoto, Yoshikazu; Efferth, Thomas

    2014-04-15

    (-)-Sesamin is a lignan present in sesam oil and a number of medicinal plants. It exerts various pharmacological effects, such as prevention of hyperlipidemia, hypertension, and carcinogenesis. Moreover, (-)-sesamin has chemopreventive and anticancer activity in vitro and in vivo. Multidrug resistance (MDR) of tumors leads to fatal treatment outcome in many patients and novel drugs able to kill multidrug-resistant cells are urgently needed. P-glycoprotein (MDR1/ABCB1) is the best known ATP-binding cassette (ABC) drug transporter mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. We found that the mRNA expressions of ABCB1 and ABCB5 were not related to the 50% inhibition concentrations (IC50) for (-)-sesamin in a panel of 55 cell lines of the National Cancer Institute, USA. Furthermore, (-)-sesamin inhibited ABCB1- or ABCB5-overexpressing cells with similar efficacy than their drug-sensitive parental counterparts. In addition to ABC transporter-mediated MDR, we attempted to identify other molecular determinants of (-)-sesamin resistance. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell panel. Twenty-three genes were identified, whose mRNA expression correlated with the IC50 values for (-)-sesamin. These genes code for proteins of different biological functions, i.e. ribosomal proteins, components of the mitochondrial respiratory chain, proteins involved in RNA metabolism, protein biosynthesis, or glucose and fatty acid metabolism. Subjecting this set of genes to cluster analysis showed that the cell lines were assembled in the resulting dendrogram according to their responsiveness to (-)-sesamin. In conclusion, (-)-sesamin is not involved in MDR mediated by ABCB1 or ABCB5 and may be valuable to bypass chemoresistance of refractory tumors. The microarray expression profile, which predicted sensitivity or resistance of tumor cells to (-)-sesamin

  10. Revealing the burden of maternal mortality: a probabilistic model for determining pregnancy-related causes of death from verbal autopsies

    Directory of Open Access Journals (Sweden)

    Desta Teklay

    2007-02-01

    Full Text Available Abstract Background Substantial reductions in maternal mortality are called for in Millennium Development Goal 5 (MDG-5, thus assuming that maternal mortality is measurable. A key difficulty is attributing causes of death for the many women who die unaided in developing countries. Verbal autopsy (VA can elicit circumstances of death, but data need to be interpreted reliably and consistently to serve as global indicators. Recent developments in probabilistic modelling of VA interpretation are adapted and assessed here for the specific circumstances of pregnancy-related death. Methods A preliminary version of the InterVA-M probabilistic VA interpretation model was developed and refined with adult female VA data from several sources, and then assessed against 258 additional VA interviews from Burkina Faso. Likely causes of death produced by the model were compared with causes previously determined by local physicians. Distinction was made between free-text and closed-question data in the VA interviews, to assess the added value of free-text material on the model's output. Results Following rationalisation between the model and physician interpretations, cause-specific mortality fractions were broadly similar. Case-by-case agreement between the model and any of the reviewing physicians reached approximately 60%, rising to approximately 80% when cases with a discrepancy were reviewed by an additional physician. Cardiovascular disease and malaria showed the largest differences between the methods, and the attribution of infections related to pregnancy also varied. The model estimated 30% of deaths to be pregnancy-related, of which half were due to direct causes. Data derived from free-text made no appreciable difference. Conclusion InterVA-M represents a potentially valuable new tool for measuring maternal mortality in an efficient, consistent and standardised way. Further development, refinement and validation are planned. It could become a routine

  11. Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

    Energy Technology Data Exchange (ETDEWEB)

    Ivičak-Kocjan, Karolina; Panter, Gabriela; Benčina, Mojca [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); Jerala, Roman, E-mail: roman.jerala@ki.si [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); The Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana (Slovenia)

    2013-05-24

    Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation.

  12. The Wright stuff: reimagining path analysis reveals novel components of the sex determination hierarchy in Drosophila melanogaster.

    Science.gov (United States)

    Fear, Justin M; Arbeitman, Michelle N; Salomon, Matthew P; Dalton, Justin E; Tower, John; Nuzhdin, Sergey V; McIntyre, Lauren M

    2015-09-04

    The Drosophila sex determination hierarchy is a classic example of a transcriptional regulatory hierarchy, with sex-specific isoforms regulating morphology and behavior. We use a structural equation modeling approach, leveraging natural genetic variation from two studies on Drosophila female head tissues--DSPR collection (596 F1-hybrids from crosses between DSPR sub-populations) and CEGS population (75 F1-hybrids from crosses between DGRP/Winters lines to a reference strain w1118)--to expand understanding of the sex hierarchy gene regulatory network (GRN). This approach is completely generalizable to any natural population, including humans. We expanded the sex hierarchy GRN adding novel links among genes, including a link from fruitless (fru) to Sex-lethal (Sxl) identified in both populations. This link is further supported by the presence of fru binding sites in the Sxl locus. 754 candidate genes were added to the pathway, including the splicing factors male-specific lethal 2 and Rm62 as downstream targets of Sxl which are well-supported links in males. Independent studies of doublesex and transformer mutants support many additions, including evidence for a link between the sex hierarchy and metabolism, via Insulin-like receptor. The genes added in the CEGS population were enriched for genes with sex-biased splicing and components of the spliceosome. A common goal of molecular biologists is to expand understanding about regulatory interactions among genes. Using natural alleles we can not only identify novel relationships, but using supervised approaches can order genes into a regulatory hierarchy. Combining these results with independent large effect mutation studies, allows clear candidates for detailed molecular follow-up to emerge.

  13. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia

    DEFF Research Database (Denmark)

    Grau, Tanja; Artemyev, Nikolai O; Rosenberg, Thomas

    2011-01-01

    characterization of six missense mutations applying the baculovirus system to express recombinant mutant and wildtype chimeric PDE6C/PDE5 proteins in Sf9 insect cells. Purified proteins were analyzed using Western blotting, phosphodiesterase (PDE) activity measurements as well as inhibition assays by zaprinast...

  14. Hypernuclear production cross section in the reaction of Li-6+C-12 at 2 A GeV

    NARCIS (Netherlands)

    Rappold, C.; Saito, T. R.; Bertini, O.; Bianchin, S.; Bozkurt, V.; Kim, E.; Kavatsyuk, M.; Ma, Y.; Maas, F.; Minami, S.; Nakajima, D.; Ozel-Tashenov, B.; Yoshida, K.; Achenbach, P.; Ajimura, S.; Aumann, T.; Gayoso, C. Ayerbe; Bhang, H. C.; Caesar, C.; Erturk, S.; Fukuda, T.; Goekuezuem, B.; Guliev, E.; Hoffmann, J.; Ickert, G.; Ketenci, Z. S.; Khaneft, D.; Kim, M.; Kim, S.; Koch, K.; Kurz, N.; Le Fevre, A.; Mizoi, Y.; Nungesser, L.; Ott, W.; Pochodzalla, J.; Sakaguchi, A.; Schmidt, C. J.; Sekimoto, M.; Simon, H.; Takahashi, T.; Tambave, G. J.; Tamura, H.; Trautmann, W.; Voltz, S.; Yoon, C. J.

    2015-01-01

    Hypernuclear production cross sections have been deduced for the first time with induced reaction of heavy ion beam on fixed target and by means of the invariant mass method by the HypHI Collaboration exploiting the reaction of Li-6 C-12 at 2 A GeV or root S-NN = 2.70 GeV. A production cross section

  15. Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

    Science.gov (United States)

    Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

    2015-07-01

    Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

  16. Crystal structure of a dimeric Ser49- PLA₂-like myotoxic component of the Vipera ammodytes meridionalis venomics reveals determinants of myotoxicity and membrane damaging activity.

    Science.gov (United States)

    Georgieva, Dessislava; Coronado, Monika; Oberthür, Dominik; Buck, Friedrich; Duhalov, Deyan; Arni, Raghuvir K; Betzel, Christian

    2012-04-01

    Myotoxicity and membrane damage play a central role in the life-threatening effects of the viper envenomation. Myotoxins are an important part of the viper venomics. A Ser49 PLA₂-like myotoxin from the venom of Vipera ammodytes meridionalis, the most venomous snake in Europe, was crystallized and its three-dimensional structure determined. The toxin is devoid of phospholipolytic activity. The structure demonstrates a formation of dimers. In the dimers functionally important peptide segments, located on the protein surface, point in the same direction which can strengthen the pharmacological effect. This supports the hypothesis about the physiological importance of the toxin oligomerization for the myotoxicity and membrane damage. The crystallographic model revealed that the structural determinants of myotoxicity (a positively charged C-terminal region and a hydrophobic knuckle) are fully exposed on the protein surface and accessible for interactions with target membranes. Distortion of the catalytic site region explains the absence of enzymatic activity. The structure reveals anion-binding sites which can be considered as possible sites of interactions of the toxin with a negatively charged membrane surface. The high structural similarity of the Ser49 myotoxin and Asp49 PLA₂ from the same venom suggests an evolutionary relationship: probably, the Ser49 myotoxin is a product of evolution of the catalytically active phospholipase A₂. The first toxin lost the enzymatic activity which is not necessary for the myotoxicity but preserved the cytotoxicity and membrane damaging activity as important components of the venom toxicity.

  17. Cellular responses to H(2)O(2) and bleomycin-induced oxidative stress in L6C5 rat myoblasts.

    Science.gov (United States)

    Caporossi, Daniela; Ciafrè, Silvia Anna; Pittaluga, Monica; Savini, Isabella; Farace, Maria Giulia

    2003-12-01

    In muscle cells, reactive oxygen species (ROS) are continually generated. It is believed that these molecules have a well-established role as physiological modulators of skeletal muscle functions, ranging from development to metabolism and from blood flow to contractile functions. Moreover, ROS may contribute to the development of muscle fatigue, inflammation, and degeneration, and may be implicated in many muscle diseases. The aim of the present study was to verify the role of short or prolonged exposure to oxidative stress, generated by different concentrations of H(2)O(2), on growth, chromosomal aberrations, and apoptosis induced in cultured L6C5 rat muscle cells used as model for myoblasts. Our results indicate that, in L6C5 cells, reactive oxygen intermediates (ROI) can activate distinct cell pathways leading to cell growth induction and development of resistant phenotype, or to chromosomal aberrations, cell cycle arrest, or cell death. The positive vs. negative effects of H(2)O(2)-altered redox potential in myoblasts are strictly related to the intensity of oxidative stress, likely depending on the types and number of cellular targets involved. Among these, DNA molecules appear to be very sensitive to breakage by H(2)O(2), although DNA damage is not directly responsible for ROI-induced apoptosis in L6C5 rat myoblasts.

  18. Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast.

    Directory of Open Access Journals (Sweden)

    Gábor Csárdi

    2015-05-01

    Full Text Available Cells respond to their environment by modulating protein levels through mRNA transcription and post-transcriptional control. Modest observed correlations between global steady-state mRNA and protein measurements have been interpreted as evidence that mRNA levels determine roughly 40% of the variation in protein levels, indicating dominant post-transcriptional effects. However, the techniques underlying these conclusions, such as correlation and regression, yield biased results when data are noisy, missing systematically, and collinear---properties of mRNA and protein measurements---which motivated us to revisit this subject. Noise-robust analyses of 24 studies of budding yeast reveal that mRNA levels explain more than 85% of the variation in steady-state protein levels. Protein levels are not proportional to mRNA levels, but rise much more rapidly. Regulation of translation suffices to explain this nonlinear effect, revealing post-transcriptional amplification of, rather than competition with, transcriptional signals. These results substantially revise widely credited models of protein-level regulation, and introduce multiple noise-aware approaches essential for proper analysis of many biological phenomena.

  19. Structure-Function Analysis of Friedreich's Ataxia Mutants Reveals Determinants of Frataxin Binding and Activation of the Fe-S Assembly Complex

    Energy Technology Data Exchange (ETDEWEB)

    Bridwell-Rabb, Jennifer; Winn, Andrew M; Barondeau, David P [TAM

    2012-08-01

    Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease associated with the loss of function of the protein frataxin (FXN) that results from low FXN levels due to a GAA triplet repeat expansion or, occasionally, from missense mutations in the FXN gene. Here biochemical and structural properties of FXN variants, including three FRDA missense mutations (N146K, Q148R, and R165C) and three related mutants (N146A, Q148G, and Q153A), were determined in an effort to understand the structural basis for the loss of function. In vitro assays revealed that although the three FRDA missense mutations exhibited similar losses of cysteine desulfurase and Fe-S cluster assembly activities, the causes for these activation defects were distinct. The R165C variant exhibited a kcat/KM higher than that of native FXN but weak binding to the NFS1, ISD11, and ISCU2 (SDU) complex, whereas the Q148R variant exhibited the lowest kcat/KM of the six tested FXN variants and only a modest binding deficiency. The order of the FXN binding affinities for the SDU Fe-S assembly complex was as follows: FXN > Q148R > N146A > Q148G > N146K > Q153A > R165C. Four different classes of FXN variants were identified on the basis of their biochemical properties. Together, these structure-function studies reveal determinants for the binding and allosteric activation of the Fe-S assembly complex and provide insight into how FRDA missense mutations are functionally compromised.

  20. Determining

    Directory of Open Access Journals (Sweden)

    Bahram Andarzian

    2015-06-01

    Full Text Available Wheat production in the south of Khuzestan, Iran is constrained by heat stress for late sowing dates. For optimization of yield, sowing at the appropriate time to fit the cultivar maturity length and growing season is critical. Crop models could be used to determine optimum sowing window for a locality. The objectives of this study were to evaluate the Cropping System Model (CSM-CERES-Wheat for its ability to simulate growth, development, grain yield of wheat in the tropical regions of Iran, and to study the impact of different sowing dates on wheat performance. The genetic coefficients of cultivar Chamran were calibrated for the CSM-CERES-Wheat model and crop model performance was evaluated with experimental data. Wheat cultivar Chamran was sown on different dates, ranging from 5 November to 9 January during 5 years of field experiments that were conducted in the Khuzestan province, Iran, under full and deficit irrigation conditions. The model was run for 8 sowing dates starting on 25 October and repeated every 10 days until 5 January using long-term historical weather data from the Ahvaz, Behbehan, Dezful and Izeh locations. The seasonal analysis program of DSSAT was used to determine the optimum sowing window for different locations as well. Evaluation with the experimental data showed that performance of the model was reasonable as indicated by fairly accurate simulation of crop phenology, biomass accumulation and grain yield against measured data. The normalized RMSE were 3%, 2%, 11.8%, and 3.4% for anthesis date, maturity date, grain yield and biomass, respectively. Optimum sowing window was different among locations. It was opened and closed on 5 November and 5 December for Ahvaz; 5 November and 15 December for Behbehan and Dezful;and 1 November and 15 December for Izeh, respectively. CERES-Wheat model could be used as a tool to evaluate the effect of sowing date on wheat performance in Khuzestan conditions. Further model evaluations

  1. The 6C Model

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille

    2016-01-01

    that knowledge production in the form of research into existing and future circumstances, looking at the situation from inside and from outside, combined with strong visualization skills are distinctive and invaluable as a driver for transformation processes across disciplines. They also enable the inclusion...

  2. Human SAS-6 C-Terminus Nucleates and Promotes Microtubule Assembly in Vitro by Binding to Microtubules.

    Science.gov (United States)

    Gupta, Hindol; Badarudeen, Binshad; George, Athira; Thomas, Geethu Emily; Gireesh, K K; Manna, Tapas K

    2015-10-20

    Centrioles are essential components of the animal centrosome and play crucial roles in the formation of cilia and flagella. They are cylindrical structures composed of nine triplet microtubules organized around a central cartwheel. Recent studies have identified spindle assembly abnormal protein SAS-6 as a critical component necessary for formation of the cartwheel. However, the molecular details of how the cartwheel participates in centriolar microtubule assembly have not been clearly understood. In this report, we show that the C-terminal tail (residues 470-657) of human SAS-6, HsSAS-6 C, the region that has been shown to extend toward the centriolar wall where the microtubule triplets are organized, nucleated and induced microtubule polymerization in vitro. The N-terminus (residues 1-166) of HsSAS-6, the domain known to be involved in formation of the central hub of the cartwheel, did not, however, exert any effect on microtubule polymerization. HsSAS-6 C bound to the microtubules and localized along the lengths of the microtubules in vitro. Microtubule pull-down and coimmunoprecipitation (Co-IP) experiments with S-phase synchronized HeLa cell lysates showed that the endogenous HsSAS-6 coprecipitated with the microtubules, and it mediated interaction with tubulin. Isothermal calorimetry titration and size exclusion chromatography showed that HsSAS-6 C bound to the αβ-tubulin dimer in vitro. The results demonstrate that HsSAS-6 possesses an intrinsic microtubule assembly promoting activity and further implicate that its outer exposed C-terminal tail may play critical roles in microtubule assembly and stabilizing microtubule attachment with the centriolar cartwheel.

  3. Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Division of Drug Safety Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993 (United States); Moland, Carrie L.; Branham, William S. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); George, Nysia I. [Division Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Information and Mathematics, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2013-01-01

    Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.

  4. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F sub 1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Huff, J.E.; Haseman, J.K.; Eustis, S.; Maronpot, R.R. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)); DeMarini, D.M. (Environmental Protection Agency, Research Triangle Park, NC (USA)); Peters, A.C.; Persing, R.L. (Battelle Columbus Division, OH (USA)); Chrisp, C.E. (Univ. of Michigan, Ann Arbor (USA)); Jacobs, A.C. (Carltech Associates, Rockville, MD (USA))

    1989-07-01

    Toxicology and carcinogenesis studies of benzene were conducted in groups of 60 F344/N rats and 60 B6C3F{sub 1} mice of each sex for each of three exposure doses and vehicle controls. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations, on clinical pathologic findings and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F{sub 1} mice, and female B6C3F{sub 1} mice. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F{sub 1} mice. These unequivocal observations show clearly that benzene is a trans-species, trans-sex, multisite potent carcinogen.

  5. A Black Cohosh Extract Causes Hematologic and Biochemical Changes Consistent with a Functional Cobalamin Deficiency in Female B6C3F1/N Mice.

    Science.gov (United States)

    Cora, Michelle C; Gwinn, William; Wilson, Ralph; King, Debra; Waidyanatha, Suramya; Kissling, Grace E; Brar, Sukhdev S; Olivera, Dorian; Blystone, Chad; Travlos, Greg

    2017-07-01

    Black cohosh rhizome, available as a dietary supplement, is most commonly marketed as a remedy for dysmenorrhea and menopausal symptoms. A previous subchronic toxicity study of black cohosh dried ethanolic extract (BCE) in female mice revealed a dose-dependent ineffective erythropoiesis with a macrocytosis consistent with the condition known as megaloblastic anemia. The purpose of this study was to investigate potential mechanisms by which BCE induces these particular hematological changes. B6C3F1/N female mice (32/group) were exposed by gavage to vehicle or 1,000 mg/kg BCE for 92 days. Blood samples were analyzed for hematology, renal and hepatic clinical chemistry, serum folate and cobalamin, red blood cell (RBC) folate, and plasma homocysteine and methylmalonic acid (MMA). Folate levels were measured in liver and kidney. Hematological changes included decreased RBC count; increased mean corpuscular volume; and decreased reticulocyte, white blood cell, neutrophil, and lymphocyte counts. Blood smear evaluation revealed increased Howell-Jolly bodies and occasional basophilic stippling in treated animals. Plasma homocysteine and MMA concentrations were increased in treated animals. Under the conditions of our study, BCE administration caused hematological and clinical chemistry changes consistent with a functional cobalamin, and possibly folate, deficiency. Further studies are needed to elucidate the mechanism by which BCE causes increases in homocysteine and MMA.

  6. Application of high-resolution continuum source flame atomic absorption spectrometry to reveal, evaluate and overcome certain spectral effects in Pb determination of unleaded gasoline

    Science.gov (United States)

    Kowalewska, Zofia; Laskowska, Hanna; Gzylewski, Michał

    2017-06-01

    scattering. For LS FAAS, the determination of Pb using the 283 nm line, a 0.1 nm bandpass and a fuel lean flame is strongly recommended. The analysis of certified reference materials, recovery studies and the analysis of real samples with low Pb content supported the satisfactory accuracy of Pb determination in automotive or aviation gasoline when the recommended analytical variants are applied. The studies in this work shed new light on spectral phenomena in air-acetylene flames. The structured background due to absorption by the OH molecules must be taken into account during Pb determination in other materials as well as in some other elemental determinations, especially at low absorbance levels. The usefulness of HR-CS FAAS for revealing and investigating a structured background was demonstrated. HR-CS FAAS does not reveal fully corrected spectral effects with a continuous character, which can be found in LS FAAS.

  7. The Crystal Structure of the Ivy delta4-16:0-ACP Desaturase Reveals Structural Details of the Oxidized Active Site and Potential Determinants of Regioselectivity

    Energy Technology Data Exchange (ETDEWEB)

    Guy,J.; Whittle, E.; Kumaran, D.; Lindqvist, Y.; Shanklin, J.

    2007-01-01

    The multifunctional acyl-acyl carrier protein (ACP) desaturase from Hedera helix (English ivy) catalyzes the {Delta}{sup 4} desaturation of 16:0-ACP and the{Delta}{sup 9} desaturation of 18:0-ACP and further desaturates{Delta}{sup 9}-16:1 or {Delta}{sup 9}-18:1 to the corresponding {Delta}{sup 4,9} dienes. The crystal structure of the enzyme has been solved to 1.95{angstrom} resolution, and both the iron-iron distance of 3.2{angstrom} and the presence of a {mu}-oxo bridge reveal this to be the only reported structure of a desaturase in the oxidized FeIII-FeIII form. Significant differences are seen between the oxidized active site and the reduced active site of the Ricinus communis (castor) desaturase; His{sup 227} coordination to Fe2 is lost, and the side chain of Glu{sup 224}, which bridges the two iron ions in the reduced structure, does not interact with either iron. Although carboxylate shifts have been observed on oxidation of other diiron proteins, this is the first example of the residue moving beyond the coordination range of both iron ions. Comparison of the ivy and castor structures reveal surface amino acids close to the annulus of the substrate-binding cavity and others lining the lower portion of the cavity that are potential determinants of their distinct substrate specificities. We propose a hypothesis that differences in side chain packing explains the apparent paradox that several residues lining the lower portion of the cavity in the ivy desaturase are bulkier than their equivalents in the castor enzyme despite the necessity for the ivy enzyme to accommodate three more carbons beyond the diiron site.

  8. A gene-rich linkage map in the dioecious species Actinidia chinensis (kiwifruit reveals putative X/Y sex-determining chromosomes

    Directory of Open Access Journals (Sweden)

    Gill Geoffrey P

    2009-03-01

    Full Text Available Abstract Background The genus Actinidia (kiwifruit consists of woody, scrambling vines, native to China, and only recently propagated as a commercial crop. All species described are dioecious, but the genetic mechanism for sex-determination is unknown, as is the genetic basis for many of the cluster of characteristics making up the unique fruit. It is, however, an important crop in the New Zealand economy, and a classical breeding program would benefit greatly by knowledge of the trait alleles carried by both female and male parents. The application of marker assisted selection (MAS in seedling populations would also aid the accurate and efficient development of novel fruit types for the market. Results Gene-rich female, male and consensus linkage maps of the diploid species A. chinensis have been constructed with 644 microsatellite markers. The maps consist of twenty-nine linkage groups corresponding to the haploid number n = 29. We found that sex-linked sequence characterized amplified region (SCAR markers and the 'Flower-sex' phenotype consistently mapped to a single linkage group, in a subtelomeric region, in a section of inconsistent marker order. The region also contained markers of expressed genes, some of unknown function. Recombination, assessed by allelic distribution and marker order stability, was, in the remainder of the linkage group, in accordance with other linkage groups. Fully informative markers to other genes in this linkage group identified the comparative linkage group in the female map, where recombination ratios determining marker order were similar to the autosomes. Conclusion We have created genetic linkage maps that define the 29 linkage groups of the haploid genome, and have revealed the position and extent of the sex-determining locus in A. chinensis. As all Actinidia species are dioecious, we suggest that the sex-determining loci of other Actinidia species will be similar to that region defined in our maps. As the

  9. Effect of the Gas6 c.834+7G>A polymorphism and the interaction of known risk factors on AMD pathogenesis in Hungarian patients.

    Directory of Open Access Journals (Sweden)

    Gergely Losonczy

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD. We searched for genetic interactions and for differences in dry and wet AMD etiology. We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested. No association was found between either the exudative or the dry form and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR = 0.50, 95%CI: 0.26-0.97, p = 0.04. Multiple regression models revealed an interesting genetic interaction in the dry AMD subgroup. In the absence of C3 risk allele, mutant genotypes of both CFH and HTRA1 behaved as strongly significant risk factors (OR = 7.96, 95%CI: 2.39 = 26.50, p = 0.0007, and OR = 36.02, 95%CI: 3.30-393.02, p = 0.0033, respectively, but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near-five-fold relative increase in the odds of dry type AMD (OR = 4.93, 95%CI: 1.98-12.25, p = 0.0006. Our results suggest a protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed between CFH, HTRA1 and C3 polymorphisms that might contribute to the

  10. Effect of the Gas6 c.834+7G>A polymorphism and the interaction of known risk factors on AMD pathogenesis in Hungarian patients.

    Science.gov (United States)

    Losonczy, Gergely; Vajas, Attila; Takács, Lili; Dzsudzsák, Erika; Fekete, Agnes; Márhoffer, Eva; Kardos, László; Ajzner, Eva; Hurtado, Begoña; de Frutos, Pablo Garcia; Berta, András; Balogh, István

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD. We searched for genetic interactions and for differences in dry and wet AMD etiology. We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested. No association was found between either the exudative or the dry form and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR = 0.50, 95%CI: 0.26-0.97, p = 0.04). Multiple regression models revealed an interesting genetic interaction in the dry AMD subgroup. In the absence of C3 risk allele, mutant genotypes of both CFH and HTRA1 behaved as strongly significant risk factors (OR = 7.96, 95%CI: 2.39 = 26.50, p = 0.0007, and OR = 36.02, 95%CI: 3.30-393.02, p = 0.0033, respectively), but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near-five-fold relative increase in the odds of dry type AMD (OR = 4.93, 95%CI: 1.98-12.25, p = 0.0006). Our results suggest a protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed between CFH, HTRA1 and C3 polymorphisms that might contribute to the pathogenesis of dry

  11. Magnetic Particle Spectroscopy Reveals Dynamic Changes in the Magnetic Behavior of Very Small Superparamagnetic Iron Oxide Nanoparticles During Cellular Uptake and Enables Determination of Cell-Labeling Efficacy.

    Science.gov (United States)

    Poller, Wolfram C; Löwa, Norbert; Wiekhorst, Frank; Taupitz, Matthias; Wagner, Susanne; Möller, Konstantin; Baumann, Gert; Stangl, Verena; Trahms, Lutz; Ludwig, Antje

    2016-02-01

    In vivo tracking of nanoparticle-labeled cells by magnetic resonance imaging (MRI) crucially depends on accurate determination of cell-labeling efficacy prior to transplantation. Here, we analyzed the feasibility and accuracy of magnetic particle spectroscopy (MPS) for estimation of cell-labeling efficacy in living THP-1 cells incubated with very small superparamagnetic iron oxide nanoparticles (VSOP). Cell viability and proliferation capacity were not affected by the MPS measurement procedure. In VSOP samples without cell contact, MPS enabled highly accurate quantification. In contrast, MPS constantly overestimated the amount of cell associated and internalized VSOP. Analyses of the MPS spectrum shape expressed as harmonic ratio A₅/A₃ revealed distinct changes in the magnetic behavior of VSOP in response to cellular uptake. These changes were proportional to the deviation between MPS and actual iron amount, therefore allowing for adjusted iron quantification. Transmission electron microscopy provided visual evidence that changes in the magnetic properties correlated with cell surface interaction of VSOP as well as with alterations of particle structure and arrangement during the phagocytic process. Altogether, A₅/A₃-adjusted MPS enables highly accurate, cell-preserving VSOP quantification and furthermore provides information on the magnetic characteristics of internalized VSOP.

  12. Crystal Structure of the Golgi-Associated Human Nα-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation.

    Science.gov (United States)

    Støve, Svein Isungset; Magin, Robert S; Foyn, Håvard; Haug, Bengt Erik; Marmorstein, Ronen; Arnesen, Thomas

    2016-07-06

    N-Terminal acetylation is a common and important protein modification catalyzed by N-terminal acetyltransferases (NATs). Six human NATs (NatA-NatF) contain one catalytic subunit each, Naa10 to Naa60, respectively. In contrast to the ribosome-associated NatA to NatE, NatF/Naa60 specifically associates with Golgi membranes and acetylates transmembrane proteins. To gain insight into the molecular basis for the function of Naa60, we developed an Naa60 bisubstrate CoA-peptide conjugate inhibitor, determined its X-ray structure when bound to CoA and inhibitor, and carried out biochemical experiments. We show that Naa60 adapts an overall fold similar to that of the catalytic subunits of ribosome-associated NATs, but with the addition of two novel elongated loops that play important roles in substrate-specific binding. One of these loops mediates a dimer to monomer transition upon substrate-specific binding. Naa60 employs a catalytic mechanism most similar to Naa50. Collectively, these data reveal the molecular basis for Naa60-specific acetyltransferase activity with implications for its Golgi-specific functions.

  13. Magnetic screw rod using dual state 0.6C-13Cr-Fe bulk magnetic material

    Science.gov (United States)

    Mita, Masahiro; Hirao, Noriyoshi; Kimura, Fumio

    2002-05-01

    A magnetic screw rod that can replace a mechanical ball screw has been successfully fabricated. This type of device provides linear motion from a rotating motor. The magnetic screw rod is made from dual state 0.6C-13Cr-Fe bulk magnetic rod stock. The material, originally soft magnetically, can be heat treated to obtain a nonmagnetic region which substitutes for the groove of a conventional magnetic screw rod. This method produces a magnetic screw rod with a smooth, round outer shape and a longer, cleaner operational life. This experiment successfully yielded a 300 mm long, 25 mm diameter magnetic rod with 10 mm pitch, 4 mm width, 4 mm depth spiral nonmagnetic region.

  14. Observation of the widetilde{A} - widetilde{X} Electronic Transition of C_6-C_{10} Peroxy Radicals

    Science.gov (United States)

    Kline, Neal D.; Miller, Terry A.

    2013-06-01

    The widetilde{A} - widetilde{X} electronic transition of straight chain C_6-C_{10} peroxy radicals and of the isooctyl peroxy radical have been observed and analyzed. These larger hydrocarbons are significant constituents of gasoline with heptane (octane rating of 0) and isooctane (2,2,4 trimethylpentane; octane rating of 100) being the two standards on which the octane rating scale is based. Spectra were obtained by abstraction of hydrogen atoms from the hydrocarbons using chlorine atoms. The origin and -OO stretch regions of the straight chain peroxy radicals are easily identifiable. It is relatively easy to uniquely identify hexyl peroxy, but differentiation among the spectra of the larger straight chain peroxy radicals has proven difficult. However, isooctyl peroxy is easily distinguished and the observation of the tertiary peroxy radical along with the primary and/or secondary peroxy radical(s) is discussed.

  15. Do vehicular emissions dominate the source of C6-C8 aromatics in the megacity Shanghai of eastern China?

    Science.gov (United States)

    Wang, Hongli; Wang, Qian; Chen, Jianmin; Chen, Changhong; Huang, Cheng; Qiao, Liping; Lou, Shengrong; Lu, Jun

    2015-01-01

    The characteristic ratios of volatile organic compounds (VOCs) to i-pentane, the indicator of vehicular emissions, were employed to apportion the vehicular and non-vehicular contributions to reactive species in urban Shanghai. Two kinds of tunnel experiments, one tunnel with more than 90% light duty gasoline vehicles and the other with more than 60% light duty diesel vehicles, were carried out to study the characteristic ratios of vehicle-related emissions from December 2009 to January 2010. Based on the experiments, the characteristic ratios of C6-C8 aromatics to i-pentane of vehicular emissions were 0.53 ± 0.08 (benzene), 0.70 ± 0.12 (toluene), 0.41 ± 0.09 (m,p-xylenes), 0.16 ± 0.04 (o-xylene), 0.023 ± 0.011 (styrene), and 0.15 ± 0.02 (ethylbenzene), respectively. The source apportionment results showed that around 23.3% of C6-C8 aromatics in urban Shanghai were from vehicular emissions, which meant that the non-vehicular emissions had more importance. These findings suggested that emission control of non-vehicular sources, i.e. industrial emissions, should also receive attention in addition to the control of vehicle-related emissions in Shanghai. The chemical removal of VOCs during the transport from emissions to the receptor site had a large impact on the apportionment results. Generally, the overestimation of vehicular contributions would occur when the VOC reaction rate constant with OH radicals (kOH) was larger than that of the vehicular indicator, while for species with smaller kOH than the vehicular indicator, the vehicular contribution would be underestimated by the method of characteristic ratios.

  16. Do vehicular emissions dominate the source of C6-C8 aromatics in the megacity Shanghai of eastern China?

    Institute of Scientific and Technical Information of China (English)

    Hongli Wang; Qian Wang; Jianmin Chen; Changhong Chen; Cheng Huang; Liping Qiao; Shengrong Lou

    2015-01-01

    The characteristic ratios of volatile organic compounds (VOCs) to i-pentane,the indicator of vehicular emissions,were employed to apportion the vehicular and non-vehicular contributions to reactive species in urban Shanghai.Two kinds of tunnel experiments,one tunnel with more than 90% light duty gasoline vehicles and the other with more than 60% light duty diesel vehicles,were carried out to study the characteristic ratios of vehicle-related emissions from December 2009 to January 2010.Based on the experiments,the characteristic ratios of C6-C8 aromatics to i-pentane of vehicular emissions were 0.53 ± 0.08 (benzene),0.70 ± 0.12 (toluene),0.41 ± 0.09 (m,p-xylenes),0.16 ± 0.04 (o-xylene),0.023 ± 0.011 (styrene),and 0.15 ± 0.02 (ethylbenzene),respectively.The source apportionment results showed that around 23.3% of C6-C8 aromatics in urban Shanghai were from vehicular emissions,which meant that the non-vehicular emissions had more importance.These findings suggested that emission control of non-vehicular sources,i.e.industrial emissions,should also receive attention in addition to the control of vehicle-related emissions in Shanghai.The chemical removal of VOCs during the transport from emissions to the receptor site had a large impact on the apportionment results.Generally,the overestimation of vehicular contributions would occur when the VOC reaction rate constant with OH radicals (kOH) was larger than that of the vehicular indicator,while for species with smaller kOH than the vehicular indicator,the vehicular contribution would be underestimated by the method of characteristic ratios.

  17. Microwave-assisted Synthesis of Arene Ru(Ⅱ) Complex [(η6-C6H6) Ru(H2iiP) Cl] Cl in SiC Vessel%SiC管中微波辅助芳烃钌(Ⅱ)化合物[(η6-C6H6)Ru(H2iiP)Cl]Cl的合成

    Institute of Scientific and Technical Information of China (English)

    吴琼; 梅文杰; 吴韦黎; 陈燕华; 曾玲莉; 郑文杰

    2013-01-01

    使用SiC管为反应容器,在微波辐射条件下以[(6-C6H6)RuCl2]2为原料与2-(吲哚基)咪唑[4,5-f]-[1,10]菲啰啉(H2iiP)反应,制得芳烃钌(Ⅱ)化合物[(η6-C6H6)Ru(H2iiP) C1]Cl(1),并对其进行了表征.采用正交实验法确定反应的最佳合成条件为:投料比n([(η6-C6 H6)RuCl2]2)∶n(H2iiP)=1∶2.2,反应温度90℃,微波辐射时间30 min.该反应的平均产率达到96.0%,反应产率的相对标准偏差(RSD)为1.28%,说明微波辐射条件下,在SiC管中能够高产率地制备芳烃钌化合物,并且反应具有良好的重现性.进一步采用MTT方法研究发现,芳烃钌(Ⅱ)化合物1能够选择性抑制MCF-7乳腺癌的生长.%Arene Ru(Ⅱ) complex [(η6-C6H6) Ru(H2iiP) Cl] Cl(1) was synthesized using [(η6-C6H6)·RuCl2] 2 and 2-indole-3-imidazole [4,5-f] [1,10] phenanthroline (H2 iiP) as raw material under microwave irradiation.The target compound was characterized by means of elemental analysis,ESI-MS,IR and NMR.The best craft condition determined by orthogonal test is that reactant molar ratio of 1.0 ∶ 2.2,the reaction temperature of 90 ℃ and the microwave irradiation time of 30 min.Then the average yield of 96.0% and RSD of 1.28% confirmed that microwave-assisted synthesis of arene Ru(Ⅱ) complex in SiC vessel gives a good stability and reiteration.The antitumor activity of arene Ru (Ⅱ) complex 1 was determined by MTT assay and the results showed that complex 1 could selectively inhibit the growth of MCF-7,indicating its potential utility in chemotherapy.

  18. Quercetin-6-C-β-D-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor.

    Science.gov (United States)

    Hamidullah; Kumar, Rajeev; Saini, Karan Singh; Kumar, Amit; Kumar, Sudhir; Ramakrishna, E; Maurya, Rakesh; Konwar, Rituraj; Chattopadhyay, Naibedya

    2015-12-01

    Pre-clinical studies suggest mitigating effect of dietary flavonoid quercetin against cancer and other diseases. However, quercetin suffers from poor metabolic stability, which appears to offset its pharmacological efficacy. Recently, we isolated quercetin-6-C-β-D-glucopyranoside (QCG) from Ulmus wallichiana planchon that has greater stability profile over quercetin. In the present study, the cytotoxic and apoptotic effects of QCG on prostate cancer cells were assessed. QCG inhibited prostate cancer cell proliferation by arresting cells at G0/G1 phase of cell cycle and induces apoptosis as evident from cytochrome c release, cleavage of caspase 3 and poly (ADP-ribose) polymerase. Mechanistic studies revealed that QCG inhibited reactive oxygen species (ROS) generation and Akt/mTOR cell survival pathways. Aryl hydrocarbon receptor (AhR) was a critical mediator of QCG action as knockdown of AhR attenuated QCG-induced cell cycle arrest, apoptosis and inhibition of Akt/mTOR pathway in prostate cancer cells. Taken together, our results suggest that QCG exhibits anti-cancer activity against prostate cancer cells via AhR-mediated down regulation of Akt/mTOR pathway in PC-3 cells. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  19. A zeolite-supported molecular ruthenium complex with eta6-C6H6 ligands: chemistry elucidated by using spectroscopy and density functional theory.

    Science.gov (United States)

    Ogino, Isao; Chen, Mingyang; Dyer, Jason; Kletnieks, Philip W; Haw, James F; Dixon, David A; Gates, Bruce C

    2010-07-05

    An essentially molecular ruthenium-benzene complex anchored at the aluminum sites of dealuminated zeolite Y was formed by treating a zeolite-supported mononuclear ruthenium complex, [Ru(acac)(eta(2)-C(2)H(4))(2)](+) (acac=acetylacetonate, C(5)H(7)O(2)(-)), with (13)C(6)H(6) at 413 K. IR, (13)C NMR, and extended X-ray absorption fine structure (EXAFS) spectra of the sample reveal the replacement of two ethene ligands and one acac ligand in the original complex with one (13)C(6)H(6) ligand and the formation of adsorbed protonated acac (Hacac). The EXAFS results indicate that the supported [Ru(eta(6)-C(6)H(6))](2+) incorporates an oxygen atom of the support to balance the charge, being bonded to the zeolite through three Ru-O bonds. The supported ruthenium-benzene complex is analogous to complexes with polyoxometalate ligands, consistent with the high structural uniformity of the zeolite-supported species, which led to good agreement between the spectra and calculations at the density functional theory level. The calculations show that the interaction of the zeolite with the Hacac formed on treatment of the original complex with (13)C(6)H(6) drives the reaction to form the ruthenium-benzene complex.

  20. Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.

    Directory of Open Access Journals (Sweden)

    Xiaomin Dong

    2015-12-01

    Full Text Available Long non-coding RNAs (lncRNAs (> 200 bp play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC differentiation from Neural Stem Cells (NSCs and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and

  1. Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection.

    Directory of Open Access Journals (Sweden)

    Aimee D Wilde

    2015-12-01

    Full Text Available Staphylococcus aureus is capable of infecting nearly every organ in the human body. In order to infiltrate and thrive in such diverse host tissues, staphylococci must possess remarkable flexibility in both metabolic and virulence programs. To investigate the genetic requirements for bacterial survival during invasive infection, we performed a transposon sequencing (TnSeq analysis of S. aureus during experimental osteomyelitis. TnSeq identified 65 genes essential for staphylococcal survival in infected bone and an additional 148 mutants with compromised fitness in vivo. Among the loci essential for in vivo survival was SrrAB, a staphylococcal two-component system previously reported to coordinate hypoxic and nitrosative stress responses in vitro. Healthy bone is intrinsically hypoxic, and intravital oxygen monitoring revealed further decreases in skeletal oxygen concentrations upon S. aureus infection. The fitness of an srrAB mutant during osteomyelitis was significantly increased by depletion of neutrophils, suggesting that neutrophils impose hypoxic and/or nitrosative stresses on invading bacteria. To more globally evaluate staphylococcal responses to changing oxygenation, we examined quorum sensing and virulence factor production in staphylococci grown under aerobic or hypoxic conditions. Hypoxic growth resulted in a profound increase in quorum sensing-dependent toxin production, and a concomitant increase in cytotoxicity toward mammalian cells. Moreover, aerobic growth limited quorum sensing and cytotoxicity in an SrrAB-dependent manner, suggesting a mechanism by which S. aureus modulates quorum sensing and toxin production in response to environmental oxygenation. Collectively, our results demonstrate that bacterial hypoxic responses are key determinants of the staphylococcal-host interaction.

  2. Local effect of enhancer of zeste-like reveals cooperation of epigenetic and cis-acting determinants for zygotic genome rearrangements.

    Directory of Open Access Journals (Sweden)

    Maoussi Lhuillier-Akakpo

    2014-09-01

    Full Text Available In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3 displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences.

  3. Local Effect of Enhancer of Zeste-Like Reveals Cooperation of Epigenetic and cis-Acting Determinants for Zygotic Genome Rearrangements

    Science.gov (United States)

    Denby Wilkes, Cyril; Matelot, Mélody; Vervoort, Michel; Sperling, Linda; Duharcourt, Sandra

    2014-01-01

    In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3) displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences. PMID:25254958

  4. On the biologic origin of C6-C10-dicarboxylic and C6-C10-omega-1-hydroxy monocarboxylic acids in human and rat with acyl-CoA dehydrogenation deficiencies: in vitro studies on the omega- and omega-1-oxidation of medium-chain (C6-C12) fatty acids in human and rat liver.

    Science.gov (United States)

    Gregersen, N; Mortensen, P B; Kølvraa, S

    1983-10-01

    C6-C10-dicarboxylic acid C6-C10-omega-1-hydroxy monocarboxylic acids were measured in postmitochondrial (10,000 g) fractions of rat liver after incubation with hexanoic, octanoic, and decanoic acids. In livers both from fed and starved rats, the proportion of decanoic acid converted to sebacic acid was high (approximately 25%) with only minor accumulation of the intermediate 10-hydroxy decanoic acid (1-2%). The conversion of octanoic and hexanoic acids to suberic and adipic acids, respectively, was low (less than 1%). The intermediate 8-hydroxy octanoic and 6-hydroxy hexanoic acids were also accumulated in very small amounts (less than 1%). It was concluded that cytochrome-P-450-mediated omega-hydroxylation was of decisive importance for the production rate of the dicarboxylic acids. Analysis of kinetic parameters of human and rat liver microsomal omega- and omega-1-hydroxylation of hexanoic, octanoic, decanoic, and dodecanoic acids gave the following results: in rats, the apparent Km values for the omega-hydroxylation for dodecanoic and decanoic acids are low, ie., 171 and 3.1 mumole/liter, respectively, whereas they are high for octanoic and hexanoic acids (8211 and 8822 mumole/liter, respectively). In two different humans, the corresponding Km values for dodecanoic, decanoic, octanoic, and hexanoic acids are 3.6-186, 522-247, 4861-3892, and 6825-10400 mumole/liter, respectively. Based on these results, it is argued that adipic and suberic acids found in urine from rats and humans with acyl-CoA dehydrogenation deficiencies are not biosynthesized by direct omega-oxidation of hexanoic and octanoic acids, but most probably by means of beta-oxidation of sebacic and dodecanedioic acids, produced by direct omega-oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR target gene Cyp2b10 in the liver of B6C3F1 mice.

    Directory of Open Access Journals (Sweden)

    Harri Lempiäinen

    Full Text Available Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.

  6. Phenobarbital Mediates an Epigenetic Switch at the Constitutive Androstane Receptor (CAR) Target Gene Cyp2b10 in the Liver of B6C3F1 Mice

    Science.gov (United States)

    Brasa, Sarah; Teo, Soon-Siong; Roloff, Tim-Christoph; Morawiec, Laurent; Zamurovic, Natasa; Vicart, Axel; Funhoff, Enrico; Couttet, Philippe; Schübeler, Dirk; Grenet, Olivier; Marlowe, Jennifer; Moggs, Jonathan; Terranova, Rémi

    2011-01-01

    Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis. PMID:21455306

  7. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

    DEFF Research Database (Denmark)

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K;

    2016-01-01

    of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions......A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment...

  8. NTP Toxicology and Carcinogenesis Studies of Isobutene (CAS No. 115-11-7) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-12-01

    Isobutene is produced during the fractionation of refinery gases or through the catalytic cracking of methyl-t-butyl ether. Isobutene is primarily used to produce diisobutylene, trimers, butyl rubber, and other polymers. In addition, it is used in the production of isooctane, high-octane aviation gasoline, methyl-t-butyl ether, and copolymer resins with butadiene and acrylonitrile. Isobutene was selected for evaluation because of the potential for human exposure due to its large production volume and the lack of adequate data on its carcinogenic potential. The toxicity and carcinogenicity of isobutene were determined in male and female F344/N rats and B6C3F1 mice exposed to isobutene (greater than 98% pure) by inhalation for 14 weeks or 2 years. The mutagenicity of isobutene was assessed in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed by inhalation for 14 weeks. 14-WEEK STUDIES: Groups of 10 male and 10 female F344/N rats and B6C3F1 mice were exposed to isobutene at concentrations of 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm 6 hours per day, 5 days per week, for 14 weeks. Concentrations greater than 8,000 ppm isobutene were not used because of the danger of explosion. All rats and mice survived to the end of the study. The final mean body weights and body weight gains of all exposed groups were similar to those of the chamber controls. No exposure-related gross lesions were observed in male or female rats or mice at necropsy. Microscopically, minimal hypertrophy of goblet cells lining the nasopharyngeal duct in the most caudal nose section was observed in some rats in each exposed group of males and females. 2-YEAR STUDIES: Based on the lack of significant exposure-related toxicologic effects in the 14-week rat and mouse studies, 8,000 ppm was selected as the highest exposure concentration in the 2-year studies. Concentrations of 0, 500, 2,000, and 8,000 ppm were selected for rats and mice with the

  9. Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

    Science.gov (United States)

    Saja, Maha F; Baudino, Lucie; Jackson, William D; Cook, H Terence; Malik, Talat H; Fossati-Jimack, Liliane; Ruseva, Marieta; Pickering, Matthew C; Woollard, Kevin J; Botto, Marina

    2015-09-22

    Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1(low) monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1(low) cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

  10. Study of internal permanent magnet rotor made of 0.6C-13Cr-Fe dual state magnetic material

    Science.gov (United States)

    Mita, Masahiro; Masuzawa, Masahiro; Hirao, Noriyoshi; Kimura, Fumio

    2003-05-01

    We have successfully developed an internal permanent magnet (IPM) rotor using dual state bulk magnetic material to increase usable magnetic flux dramatically. The most significant benefit of the IPM rotor is its mechanical reliability, because permanent magnets are inserted in slots of soft magnetic material. On the other hand, there is significant leakage flux between adjoining permanent magnets in the soft magnetic rotor core, reducing the usable magnetic flux flowing into the stator core. To solve this problem, we used a dual state magnetic material, 0.6C-13Cr-Fe alloy. This soft magnetic material could locally be changed into nonmagnetic material by localized heat treatment. By changing the material at leakage flux path into nonmagnetic, we can reduce the leakage flux, while keeping the rotor mechanically sound. By applying the dual state magnetic material to an experimental eight pole IPM rotor, the useful flux flowing in the stator core differs by 8% when compared to an all soft magnetic rotor core.

  11. Reduced Il17a expression distinguishes a Ly6c(lo)MHCII(hi) macrophage population promoting wound healing.

    Science.gov (United States)

    Rodero, Mathieu P; Hodgson, Samantha S; Hollier, Brett; Combadiere, Christophe; Khosrotehrani, Kiarash

    2013-03-01

    Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6c(lo)MHCII(hi) "noninflammatory" subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88-/- models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A-/- mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.

  12. Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1low Monocytes

    Directory of Open Access Journals (Sweden)

    Maha F. Saja

    2015-09-01

    Full Text Available Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1low monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1low monocytes at the endothelial interface and a marked accumulation of CD68+ macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1low monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1low cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

  13. Effects of IL6 C-634G polymorphism on tooth loss and their interaction with smoking habits.

    Science.gov (United States)

    Suma, S; Naito, M; Wakai, K; Sasakabe, T; Hattori, Y; Okada, R; Kawai, S; Hishida, A; Morita, E; Nakagawa, H; Tamura, T; Hamajima, N

    2015-09-01

    To examine the association between an IL6 (Interleukin-6) polymorphism (C-634G or rs1800796) and tooth loss, and an interaction between the polymorphism and smoking habits for the loss. Our subjects were 4917 check-up examinees ages 35-69. They reported tooth loss and lifestyle in a questionnaire. We regressed the number of teeth on the IL6 genotype, gender, age, smoking, drinking, diabetes, hypertension, physical activity, energy intake, education, and brushing. We further estimated multivariate-adjusted odds ratios (ORs) for having smoking and tooth loss was stronger among those with GG than among those with CC. In a multiple regression analysis, a significant interaction was found between GG genotype and current smoking in the prediction of tooth loss (P = 0.018). The IL6 C-634G polymorphism was significantly associated with tooth loss. Our results suggest greater effects of smoking on tooth loss in GG genotype individuals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Coherent Structure in Solar Wind C$^{6+}$/C$^{4+}$ Ionic Composition Data During the Quiet-Sun Conditions of 2008

    CERN Document Server

    Edmondson, J K; Lepri, S T; Zurbuchen, T H

    2013-01-01

    This analysis offers evidence of characteristic scale sizes in solar wind charge state data measured in-situ for thirteen quiet-sun Carrington rotations in 2008. Using a previously established novel methodology, we analyze the wavelet power spectrum of the charge state ratio C$^{6+}$/C$^{4+}$ measured in-situ by ACE/SWICS for 2-hour and 12-minute cadence. We construct a statistical significance level in the wavelet power spectrum to quantify the interference effects arising from filling missing data in the time series (Edmondson et al. 2013), allowing extraction of significant power from the measured data to a resolution of 24 mins. We analyze each wavelet power spectra for transient coherency, and global periodicities resulting from the superposition of repeating coherent structures. From the significant wavelet power spectra, we find evidence for a general upper-limit on individual transient coherency of $\\sim$10 days. We find evidence for a set of global periodicities between 4-5 hours and 35-45 days. We f...

  15. PowerPlex® Fusion 6C System: evaluation study for analysis of casework and database samples

    Science.gov (United States)

    Cisana, Selena; Cerri, Nicoletta; Bosetti, Alessandro; Verzeletti, Andrea; Cortellini, Venusia

    2017-01-01

    Aim To report on the successful analysis of amplicons obtained with PowerPlex® Fusion 6C System, a highly robust 27-plex genotyping kit developed for human identification laboratories, on the Applied Biosystems® 3500 Genetic Analyzer. Method We performed characterization and evaluation studies following the Scientific Working Group on DNA Analysis Methods (SWGDAM) validation guidelines, examining several critical areas of kit performance. We report the results of sensitivity, robustness, heterozygous peak height ratio, precision, concordance, caseworks, and mixture interpretations. We tested sensitivity, using serial dilutions of control DNA. Results The minimum amount of input DNA resulting in a full profile was 125 pg. Inhibition, inducted by urea, showed a progressively fragmentation of DNA and a full profile was obtained until 1M of inhibitor factor. To test the profile quality, casework samples were extracted with different extraction methods: Chelex®100, QIAmp DNA Micro Kit and Phenol-Chloroform extraction. The results demonstrated that extraction chemistries do not have affect on amplification performance. Concordance check was performed by typing some casework samples and comparing the typing results with those obtained with other available kits. Thus, concordance was expected and supported by the data. Conclusion Reliable DNA typing results can be obtained using this new kit, demonstrating its effectiveness and utility in forensic analysis. PMID:28252872

  16. Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Yen Ling Low

    2010-07-01

    Full Text Available Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (p(global = 0.034 and endometrial (p(global = 0.052 cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (p(global = 0.008 and endometrial cancer (p(global = 0.014. The sub-pathway association was validated in the Finnish sample of breast cancer (p(global = 0.015. Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (p(global = 0.0003. Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite

  17. Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis.

    Science.gov (United States)

    Möhle, Luisa; Mattei, Daniele; Heimesaat, Markus M; Bereswill, Stefan; Fischer, André; Alutis, Marie; French, Timothy; Hambardzumyan, Dolores; Matzinger, Polly; Dunay, Ildiko R; Wolf, Susanne A

    2016-05-31

    Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6C(hi) monocytes in the brain than antibiotic-treated mice. Elimination of Ly6C(hi) monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6C(hi) monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6C(hi) monocytes.

  18. Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice.

    Science.gov (United States)

    Denapoli, Priscila M A; Zanetti, Bianca F; Dos Santos, Adara A; de Moraes, Jane Z; Han, Sang W

    2017-03-01

    Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682. CEA2682 mice immunized with the scFv6.C4 expressing plasmid vector (uP/PS-scFv6.C4) by electroporation gave rise to the CEA-specific AB3 antibody after the third immunization. Sera from immunized mice reacted with CEA-expressing human colorectal cell lines CO112, HCT-8, and LISP-1, as well as with murine melanoma B16F10 cells expressing CEA (B16F10-CEA). Cytotoxic T lymphocytes (CTL) from uP/PS-scFv6.C4 immunized mice lysed B16F10-CEA (56.7%) and B16F10 expressing scFv6.C4 (B16F10-scFv6.C4) (46.7%) cells, against CTL from uP-immunized mice (10%). After the last immunization, 5 × 10(5) B16F10-CEA cells were injected into the left flank. All mice immunized with the uP empty vector died within 40 days, but uP/PS-scFv6.C4 vaccinated mice (40%) remained free of tumor for more than 100 days. Splenocytes obtained from uP/PS-scFv6.C4 vaccinated mice showed higher T-cell proliferative activity than those from uP vaccinated mice. Collectively, DNA vaccination with the uP-PS/scFv6.C4 plasmid vector was able to give rise to specific humoral and cellular responses, which were sufficient to retard growth and/or eliminate the injected B16F10-CEA cells.

  19. Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis

    Science.gov (United States)

    Tsuboi, Masaya; Watanabe, Manabu; Nibe, Kazumi; Yoshimi, Natsuko; Kato, Akihisa; Sakaguchi, Masahiro; Yamato, Osamu; Tanaka, Miyuu; Kuwamura, Mitsuru; Kushida, Kazuya; Harada, Tomoyuki; Chambers, James Kenn; Sugano, Sumio; Uchida, Kazuyuki; Nakayama, Hiroyuki

    2017-01-01

    Whole exome sequencing (WES) has become a common tool for identifying genetic causes of human inherited disorders, and it has also recently been applied to canine genome research. We conducted WES analysis of neuroaxonal dystrophy (NAD), a neurodegenerative disease that sporadically occurs worldwide in Papillon dogs. The disease is considered an autosomal recessive monogenic disease, which is histopathologically characterized by severe axonal swelling, known as “spheroids,” throughout the nervous system. By sequencing all eleven DNA samples from one NAD-affected Papillon dog and her parents, two unrelated NAD-affected Papillon dogs, and six unaffected control Papillon dogs, we identified 10 candidate mutations. Among them, three candidates were determined to be “deleterious” by in silico pathogenesis evaluation. By subsequent massive screening by TaqMan genotyping analysis, only the PLA2G6 c.1579G>A mutation had an association with the presence or absence of the disease, suggesting that it may be a causal mutation of canine NAD. As a human homologue of this gene is a causative gene for infantile neuroaxonal dystrophy, this canine phenotype may serve as a good animal model for human disease. The results of this study also indicate that WES analysis is a powerful tool for exploring canine hereditary diseases, especially in rare monogenic hereditary diseases. PMID:28107443

  20. Maternal plasma levels of interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane and oxidative status in women with preterm premature rupture of membranes.

    Science.gov (United States)

    Ilhan, Nevin; Celik, Ebru; Kumbak, Banu

    2015-02-01

    Preterm premature rupture of membranes (PPROM) is associated with significant maternal and perinatal morbidity. This study examined maternal oxidative stress in PPROM. This was a prospective cross-sectional study conducted in a university hospital. A total of 72 pregnant women were recruited into two groups, those with PPROM (38 cases) and those without PPROM (34 controls) matched for gestational age. Plasma interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane, total oxidant status (TOS) and antioxidant status (TAS) were determined for all study participants and the data were compared between the PPROM and control groups. Both case and control groups were comparably matched in age, parity, gestational age and smoking status. There was a significant association between low 8-isoprostane, low vitamin C and high total oxidant status and the occurrence of PPROM (p vitamin C and 8-isoprostane levels were lower and TOS higher in women with PPROM. Further research is needed to identify robust biological markers for the prevention and also prognosis of PPROM.

  1. Early metabolomics changes in heart and plasma during chronic doxorubicin treatment in B6C3F1 mice.

    Science.gov (United States)

    Schnackenberg, Laura K; Pence, Lisa; Vijay, Vikrant; Moland, Carrie L; George, Nysia; Cao, Zhijun; Yu, Li-Rong; Fuscoe, James C; Beger, Richard D; Desai, Varsha G

    2016-11-01

    The present study aimed to identify molecular markers of early stages of cardiotoxicity induced by a potent chemotherapeutic agent, doxorubicin (DOX). Male B6C3F1 mice were dosed with 3 mg kg(-1) DOX or saline via tail vein weekly for 2, 3, 4, 6 or 8 weeks (cumulative DOX doses of 6, 9, 12, 18 or 24 mg kg(-1) , respectively) and euthanized a week after the last dose. Mass spectrometry-based and nuclear magnetic resonance spectrometry-based metabolic profiling were employed to identify initial biomarkers of cardiotoxicity before myocardial injury and cardiac pathology, which were not noted until after the 18 and 24 mg kg(-1) cumulative doses, respectively. After a cumulative dose of 6 mg kg(-1) , 18 amino acids and four biogenic amines (acetylornithine, kynurenine, putrescine and serotonin) were significantly increased in cardiac tissue; 16 amino acids and two biogenic amines (acetylornithine and hydroxyproline) were significantly altered in plasma. In addition, 16 acylcarnitines were significantly increased in plasma and five were significantly decreased in cardiac tissue compared to saline-treated controls. Plasma lactate and succinate, involved in the Krebs cycle, were significantly altered after a cumulative dose of 6 mg kg(-1) . A few metabolites remained altered at higher cumulative DOX doses, which could partly indicate a transition from injury processes at 2 weeks to repair processes with additional injury happening concurrently before myocardial injury at 8 weeks. These altered metabolic profiles in mouse heart and plasma during the initial stages of injury progression due to DOX treatment may suggest these metabolites as candidate early biomarkers of cardiotoxicity. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  2. Trichloroethylene-induced gene expression and DNA methylation changes in B6C3F1 mouse liver.

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    Full Text Available Trichloroethylene (TCE, widely used as an organic solvent in the industry, is a common contaminant in air, soil, and water. Chronic TCE exposure induced hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE (0, 100, 500 and 1000 mg/kg b.w. per day for 5 days. After 5 days TCE treatment at a dose level of 1000 mg/kg b.w., a total of 431 differentially expressed genes were identified in mouse liver by microarray, of which 291 were up-regulated and 140 down-regulated. The expression changed genes were involved in key signal pathways including PPAR, proliferation, apoptosis and homologous recombination. Notably, the expression level of a number of vital genes involved in the regulation of DNA methylation, such as Utrf1, Tet2, DNMT1, DNMT3a and DNMT3b, were dysregulated. Although global DNA methylation change was not detected in the liver of mice exposed to TCE, the promoter regions of Cdkn1a and Ihh were found to be hypo- and hypermethylated respectively, which correlated negatively with their mRNA expression changes. Furthermore, the gene expression and DNA methylation changes induced by TCE were dose dependent. The overall data indicate that TCE exposure leads to aberrant DNA methylation changes, which might alter the expression of genes involved in the TCE-induced liver tumorgenesis.

  3. Trichloroethylene-induced gene expression and DNA methylation changes in B6C3F1 mouse liver.

    Science.gov (United States)

    Jiang, Yan; Chen, Jiahong; Tong, Jian; Chen, Tao

    2014-01-01

    Trichloroethylene (TCE), widely used as an organic solvent in the industry, is a common contaminant in air, soil, and water. Chronic TCE exposure induced hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s) for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE (0, 100, 500 and 1000 mg/kg b.w. per day) for 5 days. After 5 days TCE treatment at a dose level of 1000 mg/kg b.w., a total of 431 differentially expressed genes were identified in mouse liver by microarray, of which 291 were up-regulated and 140 down-regulated. The expression changed genes were involved in key signal pathways including PPAR, proliferation, apoptosis and homologous recombination. Notably, the expression level of a number of vital genes involved in the regulation of DNA methylation, such as Utrf1, Tet2, DNMT1, DNMT3a and DNMT3b, were dysregulated. Although global DNA methylation change was not detected in the liver of mice exposed to TCE, the promoter regions of Cdkn1a and Ihh were found to be hypo- and hypermethylated respectively, which correlated negatively with their mRNA expression changes. Furthermore, the gene expression and DNA methylation changes induced by TCE were dose dependent. The overall data indicate that TCE exposure leads to aberrant DNA methylation changes, which might alter the expression of genes involved in the TCE-induced liver tumorgenesis.

  4. Microstructural characterization of a Fe-20Mn-0.6C high Mn TRIP/TWIP steel%Fe-20Mn-0.6C 高锰 TRIP/TWIP 钢微观组织表征

    Institute of Scientific and Technical Information of China (English)

    邱从怀; 申勇峰; 薛文颖; 王沿东

    2013-01-01

      设计出一种 Fe-Mn-C 系 TRIP/TWIP 钢,通过静态拉伸测试热轧钢力学性能,并利用 EBSD、XRD、SEM 分析其拉伸变形后的微观组织变化.结果表明:Fe-20Mn-0.6C 钢板热轧后表现出优异的力学性能,真应变可达到0.59,抗拉强度为1631 MPa.热轧后组织为全奥氏体组织,晶粒尺寸较大并且伴有大量的退火孪晶,变形后出现孪生变形和马氏体相变;变形量较小时,马氏体相变并不明显,较大变形量时大量的马氏体在孪晶界和晶界附近弥散分布;并且随着应变量增大晶粒内出现二次孪生,并与一次孪生呈现多种交割方式.%  Tensile tests were carried out to explore the mechanical properties of a designed TRIP /TWIP steel, and the microstructures of the hot rolled steel before and after deformation have been investigated by using the electron -backscattering diffraction (EBSD), X-ray diffraction (XRD), and scanning electron micrograph (SEM).The re-sults indicated that the steel after hot rolling exhibited attractively mechanical properties , while the true strain rea-ches 0.59 and the true stress is 1631MPa.The microstructure of the hot-rolled steel mainly contains the austenitic matrix with large grain sizes and lots of annealing twins .Twins and martensitic plates are occurred after tensile de -formation.The martensite phase increases with increasing strain and occurs at the vicinity of twin boundaries and /or grain boundaries, and the second twinning systems have been observed with increasing strain ,which intersected with the first twinning systems by different styles .

  5. Determination of 5 '-leader sequences from radically disparate strains of porcine reproductive and respiratory syndrome virus reveals the presence of highly conserved sequence motifs

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Nielsen, Jens;

    1999-01-01

    We determined the untranslated 5'-leader sequence for three different isolates of porcine reproductive and respiratory syndrome virus (PRRSV): pathogenic European- and American-types, as well as an American-type vaccine strain. 5'-leader from European- and American-type PRRSV differed in length...... a priori knowledge for mutational identification of virulence determinants in the 5' nontranslated part of the PRRSV genome....

  6. Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and F344 rats.

    Science.gov (United States)

    Greenman, D L; Morrissey, R L; Blakemore, W; Crowell, J; Siitonen, P; Felton, P; Allen, R; Cronin, G

    1996-02-01

    Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a chelating agent used to treat Wilson's disease patients who are intolerant of the drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats. Mice and rats received trien-2HCl in the drinking water at concentrations of 0, 120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN-76A) diet, both containing nutritionally adequate levels of copper. An additional control group of rats and mice received a Cu-deficient AIN-76A diet. This low copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell proliferation, and increased heart weight, together with undetectable levels of plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels some-what (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation of the lung interstitium and liver periportal fatty infiltration were seen in both sexes, and hematopoietic cell proliferation was seen in the spleen of males. Kidney and body weights were reduced in males as was the incidence of renal cytoplasmic vacuolization. There were no signs of copper deficiency in mice exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31 diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm.

  7. MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action

    DEFF Research Database (Denmark)

    Wen, Jiayu; Parker, Brian J; Jacobsen, Anders

    2011-01-01

    the predictive effect of target flanking features. We observe distinct target determinants between expression-based and CLIP-based data. Target flanking features such as flanking region conservation are an important AGO-binding determinant-we hypothesize that CLIP experiments have a preference for strongly bound...... miRNP-target interactions involving adjacent RNA-binding proteins that increase the strength of cross-linking. In contrast, seed-related features are major determinants in expression-based studies, but less so for CLIP-seq studies, and increased miRNA concentrations typical of transfection studies...

  8. H,K-ATPase Protein Localization and Kir4.1 Function Reveal Concordance of 3 Axes During Early Determination of Left-Right Asymmetry

    OpenAIRE

    Aw, Sherry; Adams, Dany S.; Qiu, Dayong; Levin, Michael

    2007-01-01

    Consistent laterality is a fascinating problem, and study of the Xenopus embryo has led to molecular characterization of extremely early steps in left-right patterning: bioelectrical signals produced by ion pumps functioning upstream of asymmetric gene expression. Here, we reveal a number of novel aspects of the H+/K+-ATPase module in chick and frog embryos. Maternal H+/K+-ATPase subunits are asymmetrically localized along the left-right, dorso-ventral, and animal-vegetal axes during the firs...

  9. ALTERATION IN CONTRACTILE RESPONSE TO NORADRENALINE,5-HYDROXYTRYPTAMINE,SARAFOTOXIN 6c,AND ANGIOTENSINⅡIN RAT MESENTERIC ARTERY DURING ORGAN CULTURE

    Institute of Scientific and Technical Information of China (English)

    Cao Yongxiao(曹永孝); He Langchong(贺浪冲); Xu Cangbao(徐仓宝); EDVINSSON Lars

    2004-01-01

    Objective To compare the vasoconstrictive effects of 9 mediators on fresh and incubated mesenteric arteries of rats. Methods The superior mesenteric artery of rat was removed and the endothelium was denuded. The vessels were cut into 1 mm long cylindrical segments and subjected to organ culture for 24 hours. Fresh or incubated segments were immersed into tissue baths and the concentration-response curves were obtained by cumulative administration of the vasoconstrictors. Results In fresh mesenteric artery, endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), noradrenaline (NA), 5-carboxamidotryptamine (5-CT), and angiotensinⅡ (AngⅡ) induced potent and sustained constrictions in a concentration-dependent manner. The contraction induced by sarafotoxin 6c (S6c) was weak, while bradykinin (BK), des-Arg-bradykinin (DA-BK), and human urotensinⅡ (hUT-II) showed no detectable contraction. The concentraion-response curves in order of slopes was ET-1, NA, 5-HT, 5-CT, and AngⅡ. The order of the maximum contractions was ET-1>NA=5-HT=5-CT>AngⅡ>S6c. After organ culture, the concentration-response curves induced by S6c, NA, and 5-HT were significantly increased, while that induced by AngⅡ was decreased as comparing to fresh arteries. BK contracted the artery only weakly. Conclusion Organ culture changed the phenotypes towards an increased efficacy of NA, 5-HT, S6c, and a reduced efficacy of AngⅡ, which is in accordance with the results of pharmacological characterization in some human vascular disease.

  10. A computational study on some viable targets for gas-phase synthesis of metal complexes of the cyclic (B6C)-2 and their bonding pattern.

    Science.gov (United States)

    Shahbazian, Shant; Alizadeh, Shadi

    2008-10-16

    In this account, a detailed computational study is conducted to verify the geometric, energetic, and electronic properties of the planar cyclic (B 6C) (-2) (as the simplest carrier of hexacoordinate carbon) within some metal complexes. The [M(B 6C)] ((-)) (M = Li, Na, K) and [M(B 6C)] (M = Be, Mg, Ca) series are employed for this purpose. Relevant ab initio calculations at both DFT and post-HF levels vividly demonstrate that this dianion is stabilized considerably in the electric field generated by cations, whereas the geometrical and electronic properties of this ring remain almost intact in these complexes. The complementary topological analysis of charge densities confirms that cyclic (B 6C) (-2) within these complexes exhibits the same topological patterns as the naked dianion, thus confirming the presence of an unusual charge density distribution in this dianion. An electrostatic model is proposed that not only qualitatively but also quantitatively explains the observed computational trends in these complexes. This model successfully traces the polarization of the central carbon atom of the ring in the presence of a hard, multiply charged cation. To facilitate experimental detection, the photoelectron spectra of the [M(B 6C)] ((-)) (M = Li, Na, K) series are computed and the dominant features are extracted. Although considered species are not global minima on their potential energy hypersurfaces, their kinetic stabilities are verified and demonstrated unequivocally.

  11. Evaluation of gravity field model EIGEN-6C4 by means of various functions of gravity potential, and by GNSS/levelling

    Directory of Open Access Journals (Sweden)

    Jan Kostelecký

    2015-06-01

    Full Text Available The combined gravity field model EIGEN-6C4 (Förste et al., 2014 is the latest combined global gravity field model of GFZ Potsdam and GRGS Toulouse. EIGEN-6C4 has been generated including the satellite gravity gradiometry data of the entire GOCE mission (November 2009 till October 2013 and is of maximum spherical degree and order 2190. In this study EIGEN-6C4 has been compared with EGM2008 to its maximum degree and order via gravity disturbances and Tzz part of the Marussi tensor of the second derivatives of the disturbing potential. The emphasis is put on such areas where GOCE data (complete set of gradiometry measurements after reductions in EIGEN-6C4 obviously contributes to an improvement of the gravity field description. GNSS/levelling geoid heights are independent data source for the evaluation of gravity field models. Therefore, we use the GNSS/levelling data sets over the territories of Europe, Czech Republic and Slovakia for the evaluation of EIGEN-6C4 w.r.t. EGM2008.

  12. NTP Toxicology and Carcinogenesis Studies of Glycidol (CAS No. 556-52-5) In F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1990-03-01

    Glycidol is a viscous liquid that is used as a stabilizer in the manufacture of vinyl polymers, as an additive for oil and synthetic hydraulic fluids, and as a diluent in some epoxy resins. NTP Toxicology and Carcinogenesis studies were conducted by administering glycidol (94% pure, containing 1.2% 3-methoxy-1,2-propanediol, 0.4% 3-chloro-1,2-propanediol, 2.8% diglycidyl ether, and 1.1% 2,6-dimethanol-1,4-dioxane) in water by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary (CHO) cells, Drosophila melanogaster, and the bone marrow of male B6C3F1 mice. Sixteen-Day Studies: Glycidol doses for groups of five rats or five mice of each sex ranged from 37.5 to 600 mg/kg; vehicle controls received distilled water. All rats that received 600 mg/kg died between days 3 and 13. Edema and degeneration of the epididymal stroma, atrophy of the testis, and granulomatous inflammation of the epididymis occurred in males that received 300 mg/kg. All mice that received 600 mg/kg and two males and two females that received 300 mg/kg died by day 4 of the studies. Focal demyelination in the medulla and thalamus of the brain occurred in all female mice that received 300 mg/kg. Thirteen-Week Studies: Doses for groups of 10 rats ranged from 25 to 400 mg/kg, and doses for groups of 10 mice ranged from 19 to 300 mg/kg; vehicle controls received distilled water. All rats that received 400 mg/kg died by week 2; three males and one female that received 200 mg/kg died during weeks 11-12. Final mean body weights of male rats that received 50, 100, or 200 mg/kg were 96%-85% that of vehicle controls; final mean body weights of female rats receiving the same doses were 95%-89% that of vehicle controls. Sperm count and sperm motility were reduced in male rats that received 100 or 200 mg/kg. Necrosis of the cerebellum, demyelineation in the medulla of the brain

  13. Efficient polymer light-emit ting diodes with violet blue emission based on blends of PSiF6-PPP and PSiFC6C6

    Institute of Scientific and Technical Information of China (English)

    TIAN Renyu; MO Yueqi; PENG Junbiao

    2006-01-01

    Efficient polymer light-emitting diodes (PLEDs) with violet blue emission were fabricated using blends of copolymers of paraphenylene-cosilafluorene (PSiF6-PPP) and polymer of poly (9,9'alkyl-3,6-silafluorene) (PSiFC6C6). The performances of the devices are sensitive to the blend ratio.When the mass ratio of PSiF6-PPP to PSiFC6C6 is 1.96% at luminance of 105 cd.m-2, its electroluminescent (EL) spectrum peaks at 398 nm and full width at half maximum is 67 nm. The improvements of the device performances were due to the energy transfer from PSiFC6C6 to PSiF6-PPP and the balanced injection of electrons and holes.

  14. Low-frequency excitations in Rb{sub 3}C{sub 60} and Rb{sub 6}C{sub 60}

    Energy Technology Data Exchange (ETDEWEB)

    Schober, H. [Institut Max von Laue - Paul Langevin, 38 - Grenoble (France); Renker, B. [INFP, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany); Gompf, F. [INFP, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany)

    1996-04-01

    We present inelastic neutron scattering results for Rb{sub 3}C{sub 60} and Rb{sub 6}C{sub 60} covering the energy region from 0.5 to 14 meV. The different contributions to the spectra (translational, libronic, Rb-vibrations) are discussed on the basis of their Q and temperature dependence. In superconducting Rb{sub 3}C{sub 60} the scattering intensity observed in the range from 1.5 to 3.5 meV changes anomalously with temperature. No such behaviour is found in insulating Rb{sub 6}C{sub 60}. (orig.).

  15. A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene

    Science.gov (United States)

    Chang, Bo; Grau, Tanja; Dangel, Susann; Hurd, Ron; Jurklies, Bernhard; Sener, E. Cumhur; Andreasson, Sten; Dollfus, Helene; Baumann, Britta; Bolz, Sylvia; Artemyev, Nikolai; Kohl, Susanne; Heckenlively, John; Wissinger, Bernd

    2009-01-01

    Retinal cone photoreceptors mediate fine visual acuity, daylight vision, and color vision. Congenital hereditary conditions in which there is a lack of cone function in humans cause achromatopsia, an autosomal recessive trait, characterized by low vision, photophobia, and lack of color discrimination. Herein we report the identification of mutations in the PDE6C gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase as a cause of autosomal recessive achromatopsia. Moreover, we show that the spontaneous mouse mutant cpfl1 that features a lack of cone function and rapid degeneration of the cone photoreceptors represents a homologous mouse model for PDE6C associated achromatopsia. PMID:19887631

  16. Analysis of Large Seeds from Three Different Medicago truncatula Ecotypes Reveals a Potential Role of Hormonal Balance in Final Size Determination of Legume Grains

    Directory of Open Access Journals (Sweden)

    Kaustav Bandyopadhyay

    2016-09-01

    Full Text Available Legume seeds are important as protein and oil source for human diet. Understanding how their final seed size is determined is crucial to improve crop yield. In this study, we analyzed seed development of three accessions of the model legume, Medicago truncatula, displaying contrasted seed size. By comparing two large seed accessions to the reference accession A17, we described mechanisms associated with large seed size determination and potential factors modulating the final seed size. We observed that early events during embryogenesis had a major impact on final seed size and a delayed heart stage embryo development resulted to large seeds. We also observed that the difference in seed growth rate was mainly due to a difference in embryo cell number, implicating a role of cell division rate. Large seed accessions could be explained by an extended period of cell division due to a longer embryogenesis phase. According to our observations and recent reports, we observed that auxin (IAA and abscisic acid (ABA ratio could be a key determinant of cell division regulation at the end of embryogenesis. Overall, our study highlights that timing of events occurring during early seed development play decisive role for final seed size determination.

  17. Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-08-12

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

  18. Analysis of Large Seeds from Three Different Medicago truncatula Ecotypes Reveals a Potential Role of Hormonal Balance in Final Size Determination of Legume Grains

    Science.gov (United States)

    Bandyopadhyay, Kaustav; Uluçay, Orhan; Şakiroğlu, Muhammet; Udvardi, Michael K.; Verdier, Jerome

    2016-01-01

    Legume seeds are important as protein and oil source for human diet. Understanding how their final seed size is determined is crucial to improve crop yield. In this study, we analyzed seed development of three accessions of the model legume, Medicago truncatula, displaying contrasted seed size. By comparing two large seed accessions to the reference accession A17, we described mechanisms associated with large seed size determination and potential factors modulating the final seed size. We observed that early events during embryogenesis had a major impact on final seed size and a delayed heart stage embryo development resulted to large seeds. We also observed that the difference in seed growth rate was mainly due to a difference in embryo cell number, implicating a role of cell division rate. Large seed accessions could be explained by an extended period of cell division due to a longer embryogenesis phase. According to our observations and recent reports, we observed that auxin (IAA) and abscisic acid (ABA) ratio could be a key determinant of cell division regulation at the end of embryogenesis. Overall, our study highlights that timing of events occurring during early seed development play decisive role for final seed size determination. PMID:27618017

  19. CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes.

    Science.gov (United States)

    Kim, Jin Hyoung; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebileg; Hossain, Ferdaus Mohd Altaf; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis virus (JEV) is a re-emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2-CCL2 axis plays an important role in trafficking CD11b(+) Ly-6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2- and CCL2-ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2-ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2- and CCL2-ablated mice was unlikely to be mediated by innate natural killer and adaptive T-cell responses. Furthermore, CCL2 produced by haematopoietic stem cell-derived leucocytes played a dominant role in CNS accumulation of Ly-6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.

  20. NTP Toxicology and Carcinogenesis Studies of Diethanolamine (CAS No. 111-42-2) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Diethanolamine is widely used in the preparation of diethanolamides and diethanolamine salts of long-chain fatty acids that are formulated into soaps and surfactants used in liquid laundry and dishwashing detergents, cosmetics, shampoos, and hair conditioners. Diethanolamine is also used in textile processing, in industrial gas purification to remove acid gases, as an anticorrosion agent in metalworking fluids, and in preparations of agricultural chemicals. Aqueous diethanolamine solutions are used as solvents for numerous drugs that are administered intravenously. Diethanolamine was selected for evaluation because its large-scale production and pattern of use indicate the potential for widespread human exposure. Male and female F344/N rats and B6C3F1 mice received dermal applications of diethanolamine in 95% ethanol for 2 years. Genetic toxicology studies were performed in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and B6C3F1 mouse peripheral blood erythrocytes. RATS: Groups of 50 male rats were administered 0, 16, 32, or 64 mg diethanolamine/kg body weight in ethanol dermally for 2 years. Groups of 50 female rats were administered 0, 8, 16, or 32 mg/kg in ethanol dermally for 2 years. Survival, Body Weights, and Clinical Findings Survival of vehicle control and dosed male and female rats was similar. Mean body weights of 64 mg/kg males were less than those of the vehicle controls beginning week 8, and mean body weights of females were generally similar to those of the vehicle control group. The only clinical finding attributed to diethanolamine administration was irritation of the skin at the site of application. Pathology Findings: Minimal to mild nonneoplastic lesions occurred at the site of application in the epidermis of dosed male and female rats. The incidence of acanthosis in 64 mg/kg males, the incidences of hyperkeratosis in 32 and 64 mg/kg males and in all dosed female groups, and the incidences of exudate

  1. Proteomic profiling of Pseudomonas aeruginosa AES-1R, PAO1 and PA14 reveals potential virulence determinants associated with a transmissible cystic fibrosis-associated strain

    Directory of Open Access Journals (Sweden)

    Hare Nathan J

    2012-01-01

    Full Text Available Abstract Background Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF. While most CF patients are thought to acquire P. aeruginosa from the environment, person-person transmissible strains have been identified in CF clinics worldwide. The molecular basis for transmissibility and colonization of the CF lung remains poorly understood. Results A dual proteomics approach consisting of gel-based and gel-free comparisons were undertaken to analyse protein profiles in a transmissible, early (acute isolate of the Australian epidemic strain 1 (AES-1R, the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1. Over 1700 P. aeruginosa proteins were confidently identified. AES-1R protein profiles revealed elevated abundance of proteins associated with virulence and siderophore biosynthesis and acquisition, antibiotic resistance and lipopolysaccharide and fatty acid biosynthesis. The most abundant protein in AES-1R was confirmed as a previously hypothetical protein with sequence similarity to carbohydrate-binding proteins and database search revealed this gene is only found in the CF-associated strain PA2192. The link with CF infection may suggest that transmissible strains have acquired an ability to rapidly interact with host mucosal glycoproteins. Conclusions Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients.

  2. Genome-wide RNAi screen reveals the E3 SUMO-protein ligase gene SIZ1 as a novel determinant of furfural tolerance in Saccharomyces cerevisiae

    OpenAIRE

    Xiao, Han; Zhao, Huimin

    2014-01-01

    Background Furfural is a major growth inhibitor in lignocellulosic hydrolysates and improving furfural tolerance of microorganisms is critical for rapid and efficient fermentation of lignocellulosic biomass. In this study, we used the RNAi-Assisted Genome Evolution (RAGE) method to select for furfural resistant mutants of Saccharomyces cerevisiae, and identified a new determinant of furfural tolerance. Results By using a genome-wide RNAi (RNA-interference) screen in S. cerevisiae for genes in...

  3. Ambiguity Revealed

    OpenAIRE

    Subir Bose; Matthew Polisson; Ludovic Renou

    2012-01-01

    We derive necessary and suffcient conditions for data sets composed of state-contingent prices and consumption to be consistent with two prominent models of decision making under ambiguity: variational preferences and smooth ambiguity. The revealed preference conditions for the maxmin expected utility and subjective expected utility models are characterized as special cases.

  4. Ambiguity revealed

    OpenAIRE

    Bayer, Ralph-C; Bose, Subir; Polisson, Matthew; Renou, Ludovic

    2013-01-01

    We derive necessary and sufficient conditions for data sets composed of state-contingent prices and consumption to be consistent with two prominent models of decision making under uncertainty: variational preferences and smooth ambiguity. The revealed preference conditions for subjective expected utility, maxmin expected utility, and multiplier preferences are characterised as special cases. We implement our tests on data from a portfolio choice experiment.

  5. Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

    Directory of Open Access Journals (Sweden)

    Potti Anil

    2003-01-01

    Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

  6. EVALUATION OF THE IMMUNOMODULATORY EFFECTS OF THE DISINFECTION BYPRODUCT, SODIUM CHLORITE, IN FEMALE B6C3F1 MICE: A DRINKING WATER STUDY

    Science.gov (United States)

    Evaluation of the Immunomodulatory Effects of the Disinfection By-product, Sodium chlorite, in Female B6C3f1 mice: A Drinking Water Study. Niel A. Karrow, Tal, L. Guo, J. Ann McCay, Greg W. Johnson, Ronnetta D. Brown, Debrorah L. Musgrove, Dori R. Germolec, Robert W. Lueb...

  7. Quantitative Assessment of Peroxisome Proliferation in B6C3F1 Mouse Liver after Subchronic Exposure to Trichloroethylene by Gavage.

    Science.gov (United States)

    1997-07-01

    be genotoxic (reviewed in ECETOC , 1994). The others are considered non-genotoxic carcinogens. Mechanisms of non-genotoxic carcinogenesis have been...the B6C3F1 mouse. Toxicol. Lett. 49, 255-265. ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals) (1994). Trichloroethylene

  8. EFFECT OF TRICHLOROETHYLENE ON DNA METHYLATION AND EXPRESSION OF EARLY-INTERMEDIATE PROTOONCOGENES IN THE LIVER OF B6C3F1 MICE. (R825384)

    Science.gov (United States)

    Trichloroethylene (TCE) is a multimedia environmental pollution that is carcinogenic in mouse liver. The ability of TCE to modulate DNA methylation and the expression of immediate-early protooncogenes was evaluated. Female B6C3F1 mice were administered 1000 mg/kg TCE by gavage 5 ...

  9. Identification of a human ABCC10 orthologue in Catharanthus roseus reveals a U12-type intron determinant for the N-terminal domain feature

    Indian Academy of Sciences (India)

    Taissir El-Guizani; Clotilde Guibert; Saïda Triki; Benoit St-Pierre; Eric Ducos

    2014-04-01

    ABC (ATP-binding cassette) transporters are members of a large superfamily of proteins that utilize ATP hydrolysis to translocate a wide range of substrates across biological membranes. In general, members of C subfamily (ABCC) are structurally characterized by an additional (N-terminal) transmembrane domain (TMD0). Phylogenetic analysis of plant ABCCs separates their protein sequences into three distinct clusters: I and II are plant specific whereas cluster III contains both human and plant ABCCs. Screening of the Plant Medicinal Genomics Resource database allowed us to identify 16 ABCCs partial sequences in Catharanthus roseus; two of which belong to the unique CrABCC1 transcript that we identified in cluster III. Genomic organization of CrABCC1 TMD0 coding sequence displays an AT-AC U12-type intron that is conserved in higher plant orthologues. We showed that CrABCC1, like its human orthologue ABCC10, produces alternative transcripts that encode protein sequences with a truncated form of TMD0 without the first transmembrane span (TM1). Subcellular localization of CrABCC1 TMD0 variants using yellow fluorescent protein fusions reveals that the TM1 is required for a correct routing of the TMD0 to the tonoplast. Finally, the specific repartition of CrABCC1 orthologues in some species suggests that this gene was lost several times during evolution and that its physiological function may, rely on a common feature of multicellular eukaryotes.

  10. Intrinsic determinants of Aβ(12-24 pH-dependent self-assembly revealed by combined computational and experimental studies.

    Directory of Open Access Journals (Sweden)

    Weixin Xu

    Full Text Available The propensity of amyloid-β (Aβ peptide to self-assemble into highly ordered amyloid structures lies at the core of their accumulation in the brain during Alzheimer's disease. By using all-atom explicit solvent replica exchange molecular dynamics simulations, we elucidated at the atomic level the intrinsic determinants of the pH-dependent dimerization of the central hydrophobic segment Aβ(12-24 and related these with the propensity to form amyloid fibrils measured by experimental tools such as atomic force microscopy and fluorescence. The process of Aβ(12-24 dimerization was evaluated in terms of free energy landscape, side-chain two-dimensional contact probability maps, β-sheet registries, potential mean force as a function of inter-chain distances, secondary structure development and radial solvation distributions. We showed that dimerization is a key event in Aβ(12-24 amyloid formation; it is highly prompted in the order of pH 5.0>2.9>>8.4 and determines further amyloid growth. The dimerization is governed by a dynamic interplay of hydrophobic, electrostatic and solvation interactions permitting some variability of β-sheets at each pH. These results provide atomistic insight into the complex process of molecular recognition detrimental for amyloid growth and pave the way for better understanding of the molecular basis of amyloid diseases.

  11. Structure of Yeast OSBP-Related Protein Osh1 Reveals Key Determinants for Lipid Transport and Protein Targeting at the Nucleus-Vacuole Junction.

    Science.gov (United States)

    Manik, Mohammad Kawsar; Yang, Huiseon; Tong, Junsen; Im, Young Jun

    2017-03-10

    Yeast Osh1 belongs to the oxysterol-binding protein (OSBP) family of proteins and contains multiple targeting modules optimized for lipid transport at the nucleus-vacuole junction (NVJ). The key determinants for NVJ targeting and the role of Osh1 at NVJs have remained elusive because of unknown lipid specificities. In this study, we determined the structures of the ankyrin repeat domain (ANK), and OSBP-related domain (ORD) of Osh1, in complex with Nvj1 and ergosterol, respectively. The Osh1 ANK forms a unique bi-lobed structure that recognizes a cytosolic helical segment of Nvj1. We discovered that Osh1 ORD binds ergosterol and phosphatidylinositol 4-phosphate PI(4)P in a competitive manner, suggesting counter-transport function of the two lipids. Ergosterol is bound to the hydrophobic pocket in a head-down orientation, and the structure of the PI(4)P-binding site in Osh1 is well conserved. Our results suggest that Osh1 performs non-vesicular transport of ergosterol and PI(4)P at the NVJ.

  12. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  13. Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection.

    Directory of Open Access Journals (Sweden)

    Nathan C Peters

    2014-12-01

    Full Text Available In contrast to the ability of long-lived CD8(+ memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+ T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1 concomitant immunity, in which protection against reinfection coincides with a persisting primary infection. In these situations, pre-existing effector CD4 T cells generated by ongoing chronic infection, not memory cells, may be essential for protection against reinfection. We present a systematic study of the tissue homing properties, functionality, and life span of subsets of memory and effector CD4 T cells activated in the setting of chronic Leishmania major infection in resistant C57Bl/6 mice. We found that pre-existing, CD44(+CD62L(-T-bet(+Ly6C+ effector (T(EFF cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity. Upon adoptive transfer and challenge, non-dividing Ly6C(+ T(EFF cells preferentially homed to the skin, released IFN-γ, and conferred protection as compared to CD44(+CD62L(-Ly6C(- effector memory or CD44(+CD62L(+Ly6C(- central memory cells. During chronic infection, Ly6C(+ T(EFF cells were maintained at high frequencies via reactivation of T(CM and the T(EFF themselves. The lack of effective vaccines for many chronic diseases may be because protection against infectious challenge requires the maintenance of pre-existing T(EFF cells, and is therefore not amenable to conventional, memory inducing, vaccination strategies.

  14. CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

    Science.gov (United States)

    Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-12-02

    Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

  15. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity.

    Directory of Open Access Journals (Sweden)

    Daniel J Cole

    2011-07-01

    Full Text Available The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code onetep. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and

  16. Analysis of integrated multiple 'omics' datasets reveals the mechanisms of initiation and determination in the formation of tuberous roots in Rehmannia glutinosa.

    Science.gov (United States)

    Li, Mingjie; Yang, Yanhui; Li, Xinyu; Gu, Li; Wang, Fengji; Feng, Fajie; Tian, Yunhe; Wang, Fengqing; Wang, Xiaoran; Lin, Wenxiong; Chen, Xinjian; Zhang, Zhongyi

    2015-09-01

    All tuberous roots in Rehmannia glutinosa originate from the expansion of fibrous roots (FRs), but not all FRs can successfully transform into tuberous roots. This study identified differentially expressed genes and proteins associated with the expansion of FRs, by comparing the tuberous root at expansion stages (initiated tuberous root, ITRs) and FRs at the seedling stage (initiated FRs, IFRs). The role of miRNAs in the expansion of FRs was also explored using the sRNA transcriptome and degradome to identify miRNAs and their target genes that were differentially expressed between ITRs and FRs at the mature stage (unexpanded FRs, UFRs, which are unable to expand into ITRs). A total of 6032 genes and 450 proteins were differentially expressed between ITRs and IFRs. Integrated analyses of these data revealed several genes and proteins involved in light signalling, hormone response, and signal transduction that might participate in the induction of tuberous root formation. Several genes related to cell division and cell wall metabolism were involved in initiating the expansion of IFRs. Of 135 miRNAs differentially expressed between ITRs and UFRs, there were 27 miRNAs whose targets were specifically identified in the degradome. Analysis of target genes showed that several miRNAs specifically expressed in UFRs were involved in the degradation of key genes required for the formation of tuberous roots. As far as could be ascertained, this is the first time that the miRNAs that control the transition of FRs to tuberous roots in R. glutinosa have been identified. This comprehensive analysis of 'omics' data sheds new light on the mechanisms involved in the regulation of tuberous roots formation.

  17. Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

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    Rosario D. C. Hirata

    2011-09-01

    Full Text Available Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks. They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C and SLCO2B1 (−71T>C gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034. Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05. Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

  18. Determination of plasmid copy number reveals the total plasmid DNA amount is greater than the chromosomal DNA amount in Bacillus thuringiensis YBT-1520.

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    Chunying Zhong

    Full Text Available Bacillus thuringiensis is the most widely used bacterial bio-insecticide, and most insecticidal crystal protein-coding genes are located on plasmids. Most strains of B. thuringiensis harbor numerous diverse plasmids, although the plasmid copy numbers (PCNs of all native plasmids in this host and the corresponding total plasmid DNA amount remains unknown. In this study, we determined the PCNs of 11 plasmids (ranging from 2 kb to 416 kb in a sequenced B. thuringiensis subsp. kurstaki strain YBT-1520 using real-time qPCR. PCNs were found to range from 1.38 to 172, and were negatively correlated to plasmid size. The amount of total plasmid DNA (∼8.7 Mbp was 1.62-fold greater than the amount of chromosomal DNA (∼5.4 Mbp at the mid-exponential growth stage (OD(600 = 2.0 of the organism. Furthermore, we selected three plasmids with different sizes and replication mechanisms to determine the PCNs over the entire life cycle. We found that the PCNs dynamically shifted at different stages, reaching their maximum during the mid-exponential growth or stationary phases and remaining stable and close to their minimum after the prespore formation stage. The PCN of pBMB2062, which is the smallest plasmid (2062 bp and has the highest PCN of those tested, varied in strain YBT-1520, HD-1, and HD-136 (172, 115, and 94, respectively. These findings provide insight into both the total plasmid DNA amount of B. thuringiensis and the strong ability of the species to harbor plasmids.

  19. Multispectral airborne imagery in the field reveals genetic determinisms of morphological and transpiration traits of an apple tree hybrid population in response to water deficit.

    Science.gov (United States)

    Virlet, Nicolas; Costes, Evelyne; Martinez, Sébastien; Kelner, Jean-Jacques; Regnard, Jean-Luc

    2015-09-01

    Genetic studies of response to water deficit in adult trees are limited by low throughput of the usual phenotyping methods in the field. Here, we aimed at overcoming this bottleneck, applying a new methodology using airborne multispectral imagery and in planta measurements to compare a high number of individuals.An apple tree population, grafted on the same rootstock, was submitted to contrasting summer water regimes over two years. Aerial images acquired in visible, near- and thermal-infrared at three dates each year allowed calculation of vegetation and water stress indices. Tree vigour and fruit production were also assessed. Linear mixed models were built accounting for date and year effects on several variables and including the differential response of genotypes between control and drought conditions.Broad-sense heritability of most variables was high and 18 quantitative trait loci (QTLs) independent of the dates were detected on nine linkage groups of the consensus apple genetic map. For vegetation and stress indices, QTLs were related to the means, the intra-crown heterogeneity, and differences induced by water regimes. Most QTLs explained 15-20% of variance.Airborne multispectral imaging proved relevant to acquire simultaneous information on a whole tree population and to decipher genetic determinisms involved in response to water deficit.

  20. REVEALED ALTRUISM

    OpenAIRE

    Cox, James C; Friedman, Daniel; Sadiraj, Vjollca

    2009-01-01

    This pap er develops a theory of revealed preferences over oneís own and othersímonetary payo§s. We intro duce ìmore altruistic thanî(MAT), a partial ordering over preferences, and interpret it with known parametric mo dels. We also intro duce and illustrate ìmore generous thanî (MGT), a partial ordering over opp ortunity sets. Several recent discussions of altruism fo cus on two player extensive form games of complete information in which the Örst mover (FM) cho oses a more or less gen...

  1. Closed-Flow Column Experiments - A Numerical Study on Breakthrough Oscillations Reveals a Decreased Uncertainty in the Inverse Determination of Transport Parameters

    Science.gov (United States)

    Ritschel, Thomas; Totsche, Kai Uwe

    2016-04-01

    The identification of transport parameters by inverse modeling often suffers from large uncertainties due to equifinality or parameter correlation when models are fitted to observations of the solute breakthrough in column outflow experiments. This issue can be approached by increasing the information potential of the observation, e.g. by running multiple experiments at different boundary conditions. A promising complementary approach of designing soil column experiments in order to further increase the obtained information is the closed-flow mode that is characterized by the recirculation of the effluent solution into the solution supply vessel. Depending on the experimental conditions, the solute concentration in the mixing vessel and the effluent follows a damped sinusoidal oscillation. As a result, the closed-flow experiment provides additional observables in the breakthrough curve, which are the initial exponential decrease in concentration in mixing vessel concentration, the oscillation wavelength and the extent of damping, each indicative for corresponding transport parameters. Furthermore, the concentration in the porous medium and the mixing vessel converges to equilibrium due to the closed loop. The evaluation of these emergent features allows intrinsic control over boundary conditions and impacts the uncertainty of parameters in inverse modeling. We present a comprehensive numerical sensitivity analysis to illustrate the potential application of closed-flow experiments. We can show that the sensitivity with respect to the apparent dispersion can be controlled by the experimenter leading to a decrease in parameter uncertainty as compared to classical experiments by an order of magnitude for optimal settings. With these finding we are also able to show a reduction of equifinality found for situations, where rate-limited interactions impede a proper determination of the apparent dispersion and rate coefficients. This renders the closed-flow mode a useful

  2. Genetic manipulation of a transcription-regulating sequence of porcine reproductive and respiratory syndrome virus reveals key nucleotides determining its activity.

    Science.gov (United States)

    Zheng, Haihong; Zhang, Keyu; Zhu, Xing-Quan; Liu, Changlong; Lu, Jiaqi; Gao, Fei; Zhou, Yan; Zheng, Hao; Lin, Tao; Li, Liwei; Tong, Guangzhi; Wei, Zuzhang; Yuan, Shishan

    2014-08-01

    The factors that determine the transcription-regulating sequence (TRS) activity of porcine reproductive and respiratory syndrome virus (PRRSV) remain largely unclear. In this study, the effect of mutagenesis of conserved C nucleotides at positions 5 and 6 in the leader TRS (TRS-L) and/or canonical body TRS7 (TRS-B7) on the synthesis of subgenomic (sg) mRNA and virus infectivity was investigated in the context of a type 2 PRRSV infectious cDNA clone. The results showed that a double C mutation in the leader TRS completely abolished sg mRNAs synthesis and virus infectivity, but a single C mutation did not. A single C or double C mutation in TRS-B7.1 or/and TRS-B7.2 impaired or abolished the corresponding sg mRNA synthesis. Introduction of identical mutations in the leader and body TRSs partially restored sg mRNA7.1 and/or sg mRNA7.2 transcription, indicating that the base-pairing interaction between sense TRS-L and cTRS-B is a crucial factor influencing sg mRNA synthesis. Analysis of the mRNA leader-body junctions of mutants provided evidence for a mechanism of discontinuous minus-strand transcription. This study also showed that mutational inactivation of TRS-B7.1 or TRS-B7.2 did not affect the production of infectious progeny virus, and the sg mRNA formed from each of them could express N protein. However, TRS-B7.1 plays more important roles than TRS-B7.2 in maintaining the growth characteristic of type 2 PRRSV. These results provide more insight into the molecular mechanism of genome expression and subgenomic mRNA transcription of PRRSV.

  3. Investigation of specificity determinants in bacterial tRNA-guanine transglycosylase reveals queuine, the substrate of its eucaryotic counterpart, as inhibitor.

    Directory of Open Access Journals (Sweden)

    Inna Biela

    Full Text Available Bacterial tRNA-guanine transglycosylase (Tgt catalyses the exchange of the genetically encoded guanine at the wobble position of tRNAs(His,Tyr,Asp,Asn by the premodified base preQ1, which is further converted to queuine at the tRNA level. As eucaryotes are not able to synthesise queuine de novo but acquire it through their diet, eucaryotic Tgt directly inserts the hypermodified base into the wobble position of the tRNAs mentioned above. Bacterial Tgt is required for the efficient pathogenicity of Shigella sp, the causative agent of bacillary dysentery and, hence, it constitutes a putative target for the rational design of anti-Shigellosis compounds. Since mammalian Tgt is known to be indirectly essential to the conversion of phenylalanine to tyrosine, it is necessary to create substances which only inhibit bacterial but not eucaryotic Tgt. Therefore, it seems of utmost importance to study selectivity-determining features within both types of proteins. Homology models of Caenorhabditis elegans Tgt and human Tgt suggest that the replacement of Cys158 and Val233 in bacterial Tgt (Zymomonas mobilis Tgt numbering by valine and accordingly glycine in eucaryotic Tgt largely accounts for the different substrate specificities. In the present study we have created mutated variants of Z. mobilis Tgt in order to investigate the impact of a Cys158Val and a Val233Gly exchange on catalytic activity and substrate specificity. Using enzyme kinetics and X-ray crystallography, we gained evidence that the Cys158Val mutation reduces the affinity to preQ1 while leaving the affinity to guanine unaffected. The Val233Gly exchange leads to an enlarged substrate binding pocket, that is necessary to accommodate queuine in a conformation compatible with the intermediately covalently bound tRNA molecule. Contrary to our expectations, we found that a priori queuine is recognised by the binding pocket of bacterial Tgt without, however, being used as a substrate.

  4. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

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    Daniel T Grimes

    2016-06-01

    Full Text Available During mammalian development, left-right (L-R asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM. Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo.

  5. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

    Science.gov (United States)

    Grimes, Daniel T; Keynton, Jennifer L; Buenavista, Maria T; Jin, Xingjian; Patel, Saloni H; Kyosuke, Shinohara; Vibert, Jennifer; Williams, Debbie J; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M; Norris, Dominic P

    2016-06-01

    During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo.

  6. Ins(1,4,5)P3 interacts with PIP2 to regulate activation of TRPC6/C7 channels by diacylglycerol in native vascular myocytes.

    Science.gov (United States)

    Ju, Min; Shi, Jian; Saleh, Sohag N; Albert, Anthony P; Large, William A

    2010-05-01

    We investigated synergism between inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and diacylglycerol (DAG) on TRPC6-like channel activity in rabbit portal vein myocytes using single channel recording and immunoprecipitation techniques. Ins(1,4,5)P(3) at 10 microm increased 3-fold TRPC6-like activity induced by 10 microm 1-oleoyl-2-acetyl-sn-glycerol (OAG), a DAG analogue. Ins(1,4,5)P(3) had no effect on OAG-induced TRPC6 activity in mesenteric artery myocytes. Anti-TRPC6 and anti-TRPC7 antibodies blocked channel activity in portal vein but only anti-TRPC6 inhibited activity in mesenteric artery. TRPC6 and TRPC7 proteins strongly associated in portal vein but only weakly associated in mesenteric artery tissue lysates. Therefore in portal vein the conductance consists of TRPC6/C7 subunits, while OAG activates a homomeric TRPC6 channel in mesenteric artery myocytes. Wortmannin at 20 microm reduced phosphatidylinositol 4,5-bisphosphate (PIP(2)) association with TRPC6 and TRPC7, and produced a 40-fold increase in OAG-induced TRPC6/C7 activity. Anti-PIP(2) antibodies evoked TRPC6/C7 activity, which was blocked by U73122, a phospholipase C inhibitor. DiC8-PIP(2), a water-soluble PIP(2) analogue, inhibited OAG-induced TRPC6/C7 activity with an IC(50) of 0.74 microm. Ins(1,4,5)P(3) rescued OAG-induced TRPC6/C7 activity from inhibition by diC8-PIP(2) in portal vein myocytes, and this was not prevented by the Ins(1,4,5)P(3) receptor antagonist heparin. In contrast, Ins(1,4,5)P(3) did not overcome diC8-PIP(2)-induced inhibition of TRPC6 activity in mesenteric artery myocytes. 2,3,6-Tri-O-butyryl-Ins(1,4,5)P(3)/AM (6-Ins(1,4,5)P(3)), a cell-permeant analogue of Ins(1,4,5)P(3), at 10 microm increased TRPC6/C7 activity in portal vein and reduced association between TRPC7 and PIP(2), but not TRPC6 and PIP(2). In contrast, 10 microm OAG reduced association between TRPC6 and PIP(2), but not between TRPC7 and PIP(2). The present work provides the first evidence that Ins(1,4,5)P(3

  7. Determination of the melon chloroplast and mitochondrial genome sequences reveals that the largest reported mitochondrial genome in plants contains a significant amount of DNA having a nuclear origin

    Science.gov (United States)

    2011-01-01

    Background The melon belongs to the Cucurbitaceae family, whose economic importance among vegetable crops is second only to Solanaceae. The melon has a small genome size (454 Mb), which makes it suitable for molecular and genetic studies. Despite similar nuclear and chloroplast genome sizes, cucurbits show great variation when their mitochondrial genomes are compared. The melon possesses the largest plant mitochondrial genome, as much as eight times larger than that of other cucurbits. Results The nucleotide sequences of the melon chloroplast and mitochondrial genomes were determined. The chloroplast genome (156,017 bp) included 132 genes, with 98 single-copy genes dispersed between the small (SSC) and large (LSC) single-copy regions and 17 duplicated genes in the inverted repeat regions (IRa and IRb). A comparison of the cucumber and melon chloroplast genomes showed differences in only approximately 5% of nucleotides, mainly due to short indels and SNPs. Additionally, 2.74 Mb of mitochondrial sequence, accounting for 95% of the estimated mitochondrial genome size, were assembled into five scaffolds and four additional unscaffolded contigs. An 84% of the mitochondrial genome is contained in a single scaffold. The gene-coding region accounted for 1.7% (45,926 bp) of the total sequence, including 51 protein-coding genes, 4 conserved ORFs, 3 rRNA genes and 24 tRNA genes. Despite the differences observed in the mitochondrial genome sizes of cucurbit species, Citrullus lanatus (379 kb), Cucurbita pepo (983 kb) and Cucumis melo (2,740 kb) share 120 kb of sequence, including the predicted protein-coding regions. Nevertheless, melon contained a high number of repetitive sequences and a high content of DNA of nuclear origin, which represented 42% and 47% of the total sequence, respectively. Conclusions Whereas the size and gene organisation of chloroplast genomes are similar among the cucurbit species, mitochondrial genomes show a wide variety of sizes, with a non

  8. A quantitative, high-throughput reverse genetic screen reveals novel connections between Pre-mRNA splicing and 5' and 3' end transcript determinants.

    Directory of Open Access Journals (Sweden)

    Laura-Oana Albulescu

    Full Text Available Here we present the development and implementation of a genome-wide reverse genetic screen in the budding yeast, Saccharomyces cerevisiae, that couples high-throughput strain growth, robotic RNA isolation and cDNA synthesis, and quantitative PCR to allow for a robust determination of the level of nearly any cellular RNA in the background of ~5,500 different mutants. As an initial test of this approach, we sought to identify the full complement of factors that impact pre-mRNA splicing. Increasing lines of evidence suggest a relationship between pre-mRNA splicing and other cellular pathways including chromatin remodeling, transcription, and 3' end processing, yet in many cases the specific proteins responsible for functionally connecting these pathways remain unclear. Moreover, it is unclear whether all pathways that are coupled to splicing have been identified. As expected, our approach sensitively detects pre-mRNA accumulation in the vast majority of strains containing mutations in known splicing factors. Remarkably, however, several additional candidates were found to cause increases in pre-mRNA levels similar to that seen for canonical splicing mutants, none of which had previously been implicated in the splicing pathway. Instead, several of these factors have been previously implicated to play roles in chromatin remodeling, 3' end processing, and other novel categories. Further analysis of these factors using splicing-sensitive microarrays confirms that deletion of Bdf1, a factor that links transcription initiation and chromatin remodeling, leads to a global splicing defect, providing evidence for a novel connection between pre-mRNA splicing and this component of the SWR1 complex. By contrast, mutations in 3' end processing factors such as Cft2 and Yth1 also result in pre-mRNA splicing defects, although only for a subset of transcripts, suggesting that spliceosome assembly in S. cerevisiae may more closely resemble mammalian models of exon

  9. Aspirin revealed

    Science.gov (United States)

    Lacey, D.; Hu, X. K.; Loboda, A. V.; Mosey, N. J.; Lipson, R. H.

    2007-03-01

    Experiments are described where the experimental conditions have been optimized to detect aspirin by MALDI mass spectrometry. Although protonated aspirin was not observed by MALDI, sodium and potassium aspirin adducts could be found. Significantly better signals could be obtained by using Rb and Cs salts as cationization sources. Quantum calculations were carried out to determine the structure and energetics of the Li, K, Rb, and Cs alkali--aspirin adducts.

  10. A conceptual framework for using DOE 5700. 6C and the other DOE orders as an integrated management system; the Fermilab experience

    Energy Technology Data Exchange (ETDEWEB)

    Bodnarczuk, M.

    1992-06-01

    In this paper, I describe a conceptual framework that uses DOE Order 5700.6C and more than 140 other DOE Orders as an integrated management system -- but I describe it within the context of the broader sociological and cultural issues of doing research at DOE funded facilities. The conceptual framework has two components. The first involves an interpretation of the 10 criteria of DOE 5700.6C that is tailored for a research environment. The second component involves using the 10 criteria as functional categories that orchestrate and integrate the other DOE Orders into a total management system. The Fermilab approach aims at reducing (or eliminating) the redundancy and overlap within the DOE Orders system at the contractor level.

  11. A conceptual framework for using DOE 5700.6C and the other DOE orders as an integrated management system; the Fermilab experience

    Energy Technology Data Exchange (ETDEWEB)

    Bodnarczuk, M.

    1992-06-01

    In this paper, I describe a conceptual framework that uses DOE Order 5700.6C and more than 140 other DOE Orders as an integrated management system -- but I describe it within the context of the broader sociological and cultural issues of doing research at DOE funded facilities. The conceptual framework has two components. The first involves an interpretation of the 10 criteria of DOE 5700.6C that is tailored for a research environment. The second component involves using the 10 criteria as functional categories that orchestrate and integrate the other DOE Orders into a total management system. The Fermilab approach aims at reducing (or eliminating) the redundancy and overlap within the DOE Orders system at the contractor level.

  12. Data on IL-6 c.-174 G>C genotype and allele frequencies in patients with coronary heart disease in dependence of cardiovascular outcome

    Directory of Open Access Journals (Sweden)

    Stefan Reichert

    2016-09-01

    Full Text Available In this data article we present data on the distribution of alleles and genotypes of the interleukin (IL-6 c.-174 G>C polymorphism (rs 1800795 in patients with coronary heart disease (CHD in dependence of the incidence of new cardiovascular events (combined endpoint: myocardial infarction, stroke/TIA, cardiac death, death according to stroke within three years follow-up. Moreover, we investigated putative associations between individual expression of IL-6 genotypes and IL-6 serum level. This investigation is a subanalysis of the article entitled “The Interleukin 6 c.-174 CC genotype is a predictor for new cardiovascular events in patients with coronary heart disease within three years follow-up“ (ClinicalTrials.gov identifier: NCT01045070 (Reichert et al., 2016 [1].

  13. A self-limiting regulation of vasoconstrictor-activated TRPC3/C6/C7 channels coupled to PI(4,5)P₂-diacylglycerol signalling.

    Science.gov (United States)

    Imai, Yuko; Itsuki, Kyohei; Okamura, Yasushi; Inoue, Ryuji; Mori, Masayuki X

    2012-03-01

    Activation of transient receptor potential (TRP) canonical TRPC3/C6/C7 channels by diacylglycerol (DAG) upon stimulation of phospholipase C (PLC)-coupled receptors results in the breakdown of phosphoinositides (PIPs). The critical importance of PIPs to various ion-transporting molecules is well documented, but their function in relation to TRPC3/C6/C7 channels remains controversial. By using an ectopic voltage-sensing PIP phosphatase (DrVSP), we found that dephosphorylation of PIPs robustly inhibits currents induced by carbachol (CCh), 1-oleolyl-2-acetyl-sn-glycerol (OAG) or RHC80267 in TRPC3, TRPC6 and TRPC7 channels, though the strength of the DrVSP-mediated inhibition (VMI) varied among the channels with a rank order of C7>C6>C3. Pharmacological and molecular interventions suggest that depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) is most likely the critical event for VMI in all three channels.When the PLC catalytic signal was vigorously activated through overexpression of the muscarinic type-I receptor (M1R), the inactivation of macroscopic TRPC currents was greatly accelerated in the same rank order as the VMI, and VMI of these currents was attenuated or lost. VMI was also rarely detected in vasopressin-induced TRPC6-like currents inA7r5 vascular smooth muscle cells, indicating that the inactivation by PI(4,5)P₂ depletion underlies the physiological condition. Simultaneous fluorescence resonance energy transfer (FRET)-based measurement of PI(4,5)P₂ levels and TRPC6 currents confirmed that VMI magnitude reflects the degree of PI(4,5)P₂ depletion. These results demonstrate that TRPC3/C6/C7 channels are differentially regulated by depletion of PI(4,5)P₂, and that the bimodal signal produced by PLC activation controls these channels in a self-limiting manner.

  14. A self-limiting regulation of vasoconstrictor-activated TRPC3/C6/C7 channels coupled to PI(4,5)P2-diacylglycerol signalling

    Science.gov (United States)

    Imai, Yuko; Itsuki, Kyohei; Okamura, Yasushi; Inoue, Ryuji; Mori, Masayuki X

    2012-01-01

    Activation of transient receptor potential (TRP) canonical TRPC3/C6/C7 channels by diacylglycerol (DAG) upon stimulation of phospholipase C (PLC)-coupled receptors results in the breakdown of phosphoinositides (PIPs). The critical importance of PIPs to various ion-transporting molecules is well documented, but their function in relation to TRPC3/C6/C7 channels remains controversial. By using an ectopic voltage-sensing PIP phosphatase (DrVSP), we found that dephosphorylation of PIPs robustly inhibits currents induced by carbachol (CCh), 1-oleolyl-2-acetyl-sn-glycerol (OAG) or RHC80267 in TRPC3, TRPC6 and TRPC7 channels, though the strength of the DrVSP-mediated inhibition (VMI) varied among the channels with a rank order of C7 > C6 > C3. Pharmacological and molecular interventions suggest that depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is most likely the critical event for VMI in all three channels. When the PLC catalytic signal was vigorously activated through overexpression of the muscarinic type-I receptor (M1R), the inactivation of macroscopic TRPC currents was greatly accelerated in the same rank order as the VMI, and VMI of these currents was attenuated or lost. VMI was also rarely detected in vasopressin-induced TRPC6-like currents in A7r5 vascular smooth muscle cells, indicating that the inactivation by PI(4,5)P2 depletion underlies the physiological condition. Simultaneous fluorescence resonance energy transfer (FRET)-based measurement of PI(4,5)P2 levels and TRPC6 currents confirmed that VMI magnitude reflects the degree of PI(4,5)P2 depletion. These results demonstrate that TRPC3/C6/C7 channels are differentially regulated by depletion of PI(4,5)P2, and that the bimodal signal produced by PLC activation controls these channels in a self-limiting manner. PMID:22183723

  15. Ethylene oxide in blood of ethylene-exposed B6C3F1 mice, Fischer 344 rats, and humans.

    Science.gov (United States)

    Filser, Johannes Georg; Kessler, Winfried; Artati, Anna; Erbach, Eva; Faller, Thomas; Kreuzer, Paul Erich; Li, Qiang; Lichtmannegger, Josef; Numtip, Wanwiwa; Klein, Dominik; Pütz, Christian; Semder, Brigitte; Csanády, György András

    2013-12-01

    The gaseous olefin ethylene (ET) is metabolized in mammals to the carcinogenic epoxide ethylene oxide (EO). Although ET is the largest volume organic chemical worldwide, the EO burden in ET-exposed humans is still uncertain, and only limited data are available on the EO burden in ET-exposed rodents. Therefore, EO was quantified in blood of mice, rats, or 4 volunteers that were exposed once to constant atmospheric ET concentrations of between 1 and 10 000 ppm (rodents) or 5 and 50 ppm (humans). Both the compounds were determined by gas chromatography. At ET concentrations of between 1 and 10 000 ppm, areas under the concentration-time curves of EO in blood (µmol × h/l) ranged from 0.039 to 3.62 in mice and from 0.086 to 11.6 in rats. At ET concentrations ≤ 30 ppm, EO concentrations in blood were 8.7-fold higher in rats and 3.9-fold higher in mice than that in the volunteer with the highest EO burdens. Based on measured EO concentrations, levels of EO adducts to hemoglobin and lymphocyte DNA were calculated for diverse ET concentrations and compared with published adduct levels. For given ET exposure concentrations, there were good agreements between calculated and measured levels of adducts to hemoglobin in rats and humans and to DNA in rats and mice. Reported hemoglobin adduct levels in mice were higher than calculated ones. Furthermore, information is given on species-specific background adduct levels. In summary, the study provides most relevant data for an improved assessment of the human health risk from exposure to ET.

  16. Evidence of CCR2-independent transmigration of Ly6C(hi) monocytes into the brain after permanent cerebral ischemia in mice.

    Science.gov (United States)

    Chu, Hannah X; Kim, Hyun Ah; Lee, Seyoung; Broughton, Brad R S; Drummond, Grant R; Sobey, Christopher G

    2016-04-15

    Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6C(hi) monocytes into the brain after ischemia-reperfusion. Here we tested the effect of CCR2 inhibition during permanent cerebral ischemia. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (30 or 100mg/kg IP) 1h before middle cerebral artery occlusion and at 2 and 6h after the initiation of ischemia. After 24h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6C(hi) monocytes, but not the infiltration of those cells into the brain, was blocked by the CCR2 antagonist. INCB3344 had no effect on either neurological deficit or infarct volume. Our data confirm that cerebral ischemia triggers a CCR2-dependent increase in circulating Ly6C(hi) monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.

  17. 电场作用下1.6%C-UHCS/40Cr钢的超塑性焊接

    Institute of Scientific and Technical Information of China (English)

    张柯柯; 孙敬; 吴志伟; 马宁; 邱然锋; 张占领

    2011-01-01

    基于对40Cr钢淬火后与经热机械处理超高碳钢1.6% C-UHCS电场作用下超塑性焊接可行性的分析,在非真空、无保护气氛下,进行了电场作用下1.6% C-UHCS/40Cr的超塑性焊接工艺试验.结果表明,当施加试样接正极、环状电极接负极的电场时,可明显提高40Cr钢淬火后与经热机械处理超高碳钢1.6% C-UHCS的超塑性焊接效果.与不加电场相比,当两者在外加电场+3 kV/cm、预压应力56.6 MPa、焊接温度780℃、初始应变速率1.5×10-4/s的条件下,经20 min超塑性焊接,接头强度提高26.8%.

  18. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  19. NTP Toxicity Studies of Cyclohexanone Oxime Administered by Drinking Water to B6C3F1 Mice (CAS No. 100-64-1).

    Science.gov (United States)

    1996-04-01

    Cyclohexanone oxime is used primarily as a captive intermediate in the synthesis of caprolactam for the production of polycaprolactam (Nylon-6) fibers and plastics and also in a variety of industrial applications. Cyclohexanone oxime was selected for study because of the potential for human exposure and the interest in oximes as a chemical class. Toxicity studies of cyclohexanone oxime (approximately 99% pure) were carried out in male and female B6C3F1 mice; the compound was administered in drinking water for 2 weeks or 13 weeks. In addition, the genetic toxicity of cyclohexanone oxime was evaluated by determining mutagenicity in Salmonella typhimurium and induction of chromosomal aberrations in cultured Chinese hamster ovary cells in vitro, with and without S9 activation. The frequency of micronucleated normochromatic erythrocytes in the bone marrow and peripheral blood of mice from the 13-week study was also determined. In the 2-week study, groups of five male and five female mice were given drinking water containing 0, 106, 312, 625, 1,250, or 2,500 ppm cyclohexanone oxime. No deaths occurred, and there was no decrease in weight gain in any group. No gross lesions were observed; there were significant increases in relative spleen weights of males and females in the 2,500 ppm group and increases in the relative liver weight of male mice exposed to 312 ppm or greater. In the 13-week studies, groups of 10 male and 10 female mice were given drinking water containing 625, 1,250, 2,500, 5,000 or 10,000 ppm cyclohexanone oxime. Deaths occurred in the 10,000 ppm groups and weight gain was depressed in males and females given 10,000 ppm and in females given 5,000 ppm. There were significant increases in relative spleen weight at exposure levels of 5,000 and 10,000 ppm and significant increases in the relative liver weights of males and females that received 10,000 ppm. Microscopically, hematopoietic cell proliferation was observed in the spleen of males and females in

  20. Caldicellulosiruptor Core and Pangenomes Reveal Determinants for

    Energy Technology Data Exchange (ETDEWEB)

    Blumer-Schuette, Sara E. [North Carolina State University; Giannone, Richard J [ORNL; Zurawski, Jeffrey V [North Carolina State University; Ozdemir, Inci [North Carolina State University; Ma, Qin [University of Georgia, Athens, GA; Yin, Yanbin [University of Georgia, Athens, GA; Xu, Ying [University of Georgia, Athens, GA; Kataeva, Irena [University of Georgia, Athens, GA; Poole, Farris [University of Georgia, Athens, GA; Adams, Michael W. W. [University of Georgia, Athens, GA; Hamilton-Brehm, Scott [ORNL; Elkins, James G [ORNL; Larimer, Frank W [ORNL; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Cottingham, Robert W [ORNL; Hettich, Robert {Bob} L [ORNL; Kelly, Robert M [North Carolina State University

    2012-01-01

    Extremely thermophilic bacteria of the genus Caldicellulosiruptor utilize carbohydrate components of plant cell walls, including cellulose and hemicellulose, facilitated by a diverse set of glycoside hydrolases (GHs). From a biofuel perspective, this capability is crucial for deconstruction of plant biomass into fermentable sugars. While all species from the genus grow on xylan and acidpretreated switchgrass, growth on crystalline cellulose is variable. The basis for this variability was examined using microbiological, genomic, and proteomic analyses of eight globally diverse Caldicellulosiruptor species. The open Caldicellulosiruptor pangenome (4,009 open reading frames [ORFs]) encodes 106 GHs, representing 43 GH families, but only 26 GHs from 17 families are included in the core (noncellulosic) genome (1,543 ORFs). Differentiating the strongly cellulolytic Caldicellulosiruptor species from the others is a specific genomic locus that encodes multidomain cellulases from GH families 9 and 48, which are associated with cellulose-binding modules. This locus also encodes a novel adhesin associated with type IV pili, which was identified in the exoproteome bound to crystalline cellulose. Taking into account the core genomes, pangenomes, and individual genomes, the ancestral Caldicellulosiruptor was likely cellulolytic and evolved, in some cases, into species that lost the ability to degrade crystalline cellulose while maintaining the capacity to hydrolyze amorphous cellulose and hemicellulose.

  1. Cross-reactions in the HLA system revealed by red blood cells expressing HLA determinants, with particular reference to cross-reaction between HLA-A2 and B17.

    Science.gov (United States)

    Nordhagen, R

    1983-01-01

    Sera with cytotoxic and haemagglutinating activity towards HLA-A2/28 were also shown to react with red blood cells (RBC) expressing the HLA-B17 antigen determinant. Absorption procedures with white blood cells (WBC) indicated that this was due to an HLA-A2/B17 cross-reaction. Absorption experiments with some other sera which previously had shown cytotoxic and haemagglutinating activity towards different HLA specificities, revealed broad cross-reaction related to HLA-B locus antigens.

  2. Muramyl dipeptide induces NOD2-dependent Ly6C(high monocyte recruitment to the lungs and protects against influenza virus infection.

    Directory of Open Access Journals (Sweden)

    François Coulombe

    Full Text Available Bacterial peptidoglycan-derived muramyl dipeptide (MDP and derivatives have long-recognized antiviral properties but their mechanism of action remains unclear. In recent years, the pattern-recognition receptor NOD2 has been shown to mediate innate responses to MDP. Here, we show that MDP treatment of mice infected with Influenza A virus (IAV significantly reduces mortality, viral load and pulmonary inflammation in a NOD2-dependent manner. Importantly, the induction of type I interferon (IFN and CCL2 chemokine was markedly increased in the lungs following MDP treatment and correlated with a NOD2-dependent enhancement in circulating monocytes. Mechanistically, the protective effect of MDP could be explained by the NOD2-dependent transient increase in recruitment of Ly6C(high "inflammatory" monocytes and, to a lesser extent, neutrophils to the lungs. Indeed, impairment in both Ly6C(high monocyte recruitment and survival observed in infected Nod2-/- mice treated with MDP was recapitulated in mice deficient for the chemokine receptor CCR2 required for CCL2-mediated Ly6C(high monocyte migration from the bone marrow into the lungs. MDP-induced pulmonary monocyte recruitment occurred normally in IAV-infected and MDP-treated Ips-1-/- mice. However, IPS-1 was required for improved survival upon MDP treatment. Finally, mycobacterial N-glycolyl MDP was more potent than N-acetyl MDP expressed by most bacteria at reducing viral burden while both forms of MDP restored pulmonary function following IAV challenge. Overall, our work sheds light on the antiviral mechanism of a clinically relevant bacterial-derived compound and identifies the NOD2 pathway as a potential therapeutic target against IAV.

  3. The effect of study type on body weight and tumor incidence in B6C3F1 mice fed the NTP-2000 diet.

    Science.gov (United States)

    Marino, Dale J

    2012-07-01

    The B6C3F1 mouse is the standard mouse strain used in National Toxicology Program (NTP) carcinogenesis studies. Over time, increased liver tumorigenesis that was correlated with elevated body weights was noted in males and females. NTP therefore replaced the NIH-07 diet with the NTP-2000 diet and returned to group housing of females as lower body weights were noted in group housed mice. However, recent studies reported study-type differences in body weights at 3 months using the NTP-2000 diet with higher weights evident in drinking water and inhalation studies compared to feed studies. Therefore, body weight and tumor incidence data were collected for untreated control mice from all 2-year NTP feed (12), drinking water (8), water gavage (6) and inhalation (10) studies that used the NTP-2000 diet in order to assess the impact of study type on body weights and tumor incidences. Results show statistically significant elevated body weights and liver tumor incidences in males and females from drinking water, water gavage and inhalation studies compared to results from feed studies. Thus, the elevated body weights and liver tumorigenesis noted in mice using the NIH-07 diet were also evident using the NTP-2000 diet, which was introduced to address body weight elevations. Given the study-type dependent effects noted, these results emphasize the importance of carefully selecting historical control data for B6C3F1 mice. Moreover, because of the association between body weight and liver tumorigenesis, these results may have implications regarding dose-level selection for carcinogenicity studies involving B6C3F1 mice based on the maximum tolerated dose.

  4. Genetic Alterations in K-ras and p53 Cancer Genes in Lung Neoplasms From B6C3F1 Mice Exposed to Cumene

    OpenAIRE

    Hong, Hue-Hua L.; Ton, Thai-Vu T.; Kim, Yongbaek; Wakamatsu, Nobuko; Clayton, Natasha P.; Chan, Po-Chuen; Sills, Robert C.; Lahousse, Stephanie A.

    2008-01-01

    The incidences of alveolar/bronchiolar adenomas and carcinomas in cumene-treated B6C3F1 mice were significantly greater than those of the controls. We evaluated these lung neoplasms for point mutations in the K-ras and p53 genes that are often mutated in humans. K-ras and p53 mutations were detected by cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded neoplasms. K-ras mutations were detected in 87 % cumene-induced lung neoplasms, and the predominant mutations were exon 1 c...

  5. Nanosized Na{sub 4}Fe(CN){sub 6}/C composite as a low-cost and high-rate cathode material for sodium-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Jianfeng; Zhou, Min; Cao, Yuliang; Ai, Xinping; Yang, Hanxi [Hubei Key Laboratory of Electrochemical Power Sources, College of Chemistry and Molecular Science, Wuhan University (China)

    2012-04-15

    A Na{sub 4}Fe(CN){sub 6}/C nanocomposite prepared simply by ball-milling Na{sub 4}Fe(CN){sub 6} with carbon powder displays a full utilization of its one-electron redox capacity, excellent cyclability, and high rate capability as a Na-storage cathode, offering a promising possibility to develop environmentally benign and low-cost Na ion batteries for large-scale electric storage applications. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Traumatic posterior atlantooccipital dislocation with Jefferson fracture and fracture-dislocation of C6-C7: a case report with survival

    OpenAIRE

    Park, Jong-Beom; Ha, Kee-Yong; Chang, Han

    2001-01-01

    Atlantooccipital dislocation (AOD) is a rare and usually fatal injury. In the current study, the authors reported an extremely rare case of posterior AOD with Jefferson fracture and fracture-dislocation of C6-C7. The patient survived the injury and had only incomplete quadriplegia below the C7 segment with anterior cord syndrome. He was successfully managed with in situ occipitocervical fusion using the Cotrel-Dubousset rod system, corpectomy of C6, and anterior interbody fusion of C5–C7 with...

  7. Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1511, LB4829_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1511, LB4829_V)' providing data from direct measurement of low-pressure thermodynamic speed of sound at variable mole fraction and constant temperature, in the single-phase region(s).

  8. Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1212, LB4824_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1212, LB4824_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  9. Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1111, LB4819_V0029

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1111, LB4819_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  10. A modification potential method of calculating total cross sections of electrons scattering from complex molecules C2H6, C2F6, C6H6 and C6F6 at 100 eV-5000 eV

    Institute of Scientific and Technical Information of China (English)

    Shi De-Heng; Sun Jin-Feng; Zhu Zun-Lue; Liu Yu-Fang; Yang Xiang-Dong

    2006-01-01

    A complex optical model potential modified by incorporating the concept of bonded atom, which takes into consideration the overlapping effect of electron clouds between two atoms in a molecule, is first employed to calculate the total cross sections for electrons scattering from such complex molecules as C2H6, C2F6, C6H6 and C6F6 using the additivity rule model at Hartree-Fock level over the energy range from 100 eV to 5000 eV. The total cross sections are quantitatively compared with those obtained by experiments wherever available, and they are in good agreement with each other over a wide energy range. It is shown that the modified potential together with the additivity rule model is completely suitable for the calculation of total cross sections of electrons scattering from such complex molecules as C2H6, C2F6, C6H6 and C6F6 above 200 eV-300 eV.

  11. Structure, ferroelectric ordering, and semiempirical quantum calculations of lanthanide based metal-organic framework: [Nd(C4H5O6)(C4H4O6)][3H2O

    Science.gov (United States)

    Ahmad, Bhat Zahoor; Want, Basharat

    2016-04-01

    We investigate the structure and ferroelectric behavior of a lanthanide based metal-organic framework (MOF), [Nd(C4H5O6)(C4H4O6)][3H2O]. X-ray crystal structure analyses reveal that it crystallizes in the P41212 space group with Nd centres, coordinated by nine oxygen atoms, forming a distorted capped square antiprismatic geometry. The molecules, bridged by tartrate ligands, form a 2D chiral structure. The 2D sheets are further linked into a 3D porous framework via strong hydrogen-bonding scheme (O-H…O ≈ 2.113 Å). Dielectric studies reveal two anomalies at 295 K and 185 K. The former is a paraelectric-ferroelectric transition, and the later is attributed to the freezing down of the motion of the hydroxyl groups. The phase transition is of second order, and the spontaneous polarization in low temperature phase is attributed to the ordering of protons of hydroxyl groups. The dielectric nonlinearity parameters have been calculated using Landau- Devonshire phenomenological theory. In addition, the most recent semiempirical models, Sparkle/PM7, Sparkle/RM1, and Sparkle/AM1, are tested on the present system to assay the accuracy of semiempirical quantum approaches to predict the geometries of solid MOFs. Our results show that Sparkle/PM7 model is the most accurate to predict the unit cell structure and coordination polyhedron geometry. The semiempirical methods are also used to calculate different ground state molecular properties.

  12. Degradation of Swainsonine by the NADP-Dependent Alcohol Dehydrogenase A1R6C3 in Arthrobacter sp. HW08

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2016-05-01

    Full Text Available Swainsonine is an indolizidine alkaloid that has been found in locoweeds and some fungi. Our previous study demonstrated that Arthrobacter sp. HW08 or its crude enzyme extract could degrade swainsonie efficiently. However, the mechanism of swainsonine degradation in bacteria remains unclear. In this study, we used label-free quantitative proteomics method based on liquid chromatography-electrospray ionization-tandem mass spectrometry to dissect the mechanism of swainsonine biodegradation by Arthrobacter sp. HW08. The results showed that 129 differentially expressed proteins were relevant to swainsonine degradation. These differentially expressed proteins were mostly related to the biological process of metabolism and the molecular function of catalytic activity. Among the 129 differentially expressed proteins, putative sugar phosphate isomerase/epimerase A1R5X7, Acetyl-CoA acetyltransferase A0JZ95, and nicotinamide adenine dinucleotide phosphate (NADP-dependent alcohol dehydrogenase A1R6C3 were found to contribute to the swainsonine degradation. Notably, NADP-dependent alcohol dehyrodgenase A1R6C3 appeared to play a major role in degrading swainsonine, but not as much as Arthrobacter sp. HW08 did. Collectively, our findings here provide insights to understand the mechanism of swainsonine degradation in bacteria.

  13. Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

    Science.gov (United States)

    Guo, Tai L; Germolec, Dori R; Collins, Bradley J; Luebke, Robert W; Auttachoat, Wimolnut; Smith, Matthew J; White, Kimber L

    2011-01-01

    Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B(6)C(3)F(1) mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm.

  14. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    Energy Technology Data Exchange (ETDEWEB)

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  15. [Use of the recombinant baculovirus BacVP6C for the construction of an internal positive control of rotavirus C].

    Science.gov (United States)

    Abid-Ayadi, I; Guix, S; Pintó, R M; Bosch, A

    2011-06-01

    Unlike group A, a few studies have interested other groups of the rotavirus, especially in Tunisia. The role of rotavirus C (RVC) infection is underestimated because of its sporadic nature. The aim of our study was to develop rapid diagnostic procedures of RVC by using an internal positive control of reverse transcription PCR (RT-PCR). The internal positive control (386pb) was designed from the recombinant baculovirus BacVP6C containing the full length cDNA of the Cowden strain gene 5 (1353pb). A fragment of 596pb was amplified by PCR using the BacVP6C DNA ds as template. Then, a central part of 210pb was deleted and the remaining fragment (386pb) was cloned into pGEM-3Zf(+) plasmid between SP6 and T7 RNA polymerase promoters. The obtained recombinant plasmid "pIAM1" was then used for the generation of the internal positive control by in vitro transcription. The sensibility of the RT-PCR was about 3.66×10(5) molecules of RNA/μl. The use of a shorter positive control, as compared to the wild type, allows increased specificity of the RT-PCR reaction, and could be used for efficient diagnostic and surveillance of RVC-caused diseases. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  16. Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.

    Science.gov (United States)

    Cullen, John M; Ward, Jerrold M; Thompson, Chad M

    2016-02-01

    Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response.

  17. Salivaricin D, a novel intrinsically trypsin-resistant lantibiotic from Streptococcus salivarius 5M6c isolated from a healthy infant.

    Science.gov (United States)

    Birri, Dagim Jirata; Brede, Dag Anders; Nes, Ingolf F

    2012-01-01

    In this work, we purified and characterized a newly identified lantibiotic (salivaricin D) from Streptococcus salivarius 5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (salI) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogens Streptococcus pyogenes and Streptococcus pneumoniae. Thus, Streptococcus salivarius 5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium.

  18. Nido-Carborane building-block reagents. 3. Cyclic and open-chain oligomers incorporating -CB/sub 4/H/sub 6/C - units. Crown carboranes

    Energy Technology Data Exchange (ETDEWEB)

    Boyter, H.A. Jr.; Grimes, R.N.

    1988-09-07

    The open-chain dialkynes EtC/identical to/C(CH/sub 2/)/sub n/C/identical to/CEt (n = 4, 6), the trialkyne HC/identical to/C(CH/sub 2/)/sub 5/C/identical to/CH, and the cyclic dialkynes CH/sub 2/(CH/sub 2/)/sub 4/C/identical to/C(CH/sub 2/)/sub n/C/identical to/C (n = 4-6) were treated with B/sub 5/H/sub 9/ and (C/sub 2/H/sub 5/)/sub 3/ to give the corresponding nido-carborane oligomers, in which the original -C/identical to/C- units are converted to -CB/sub 4/H/sub 6/C- nido-carborane cages. In each case, all available -C/identical to/C- groups were transformed to carborane moieties. No partially converted products (having both carborane and -C/identical to/C- groups in the chain) were found; when the B/sub 5/H/sub 9//-C/identical to/C- ratio employed was < 1, only completely converted products and unreacted starting materials were recovered at the end of the reaction. The open-chain carborane oligomers are viscous air-sensitive liquids that under undergo bridge deprotonation on treatment with NaH in THF solution; with excess NaH, one proton per carborane unit is removed. The resulting ionic species undergo complexation with Fe/sup 2+/ and oxidative fusion, forming products incorporating C/sub 4/B/sub 8/ cages. The cyclic bis(carborane) CH/sub 2/(CH/sub 2/)/sub 4/CB/sub 4/H/sub 6/C(CH/sub 2/)/sub 5/CB/sub 4/H/sub 6/C is an air-stable oil that can be deprotonated but does not under metal-promoted oxidative fusion. All products were characterized by /sup 11/B and /sup 1/H NMR, infrared, visible-uv, and mass spectroscopy, and the /sup 13/C NMR spectra of linear bis(carboranes) are reported. 9 references, 7 figures, 4 tables.

  19. Fracture-dislocation at C6-C7 level with Quadriplegia after Traditional Massage in a Patient with Ankylosing Spondylitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Abilash KAK

    2017-07-01

    Full Text Available Ankylosing spinal disorders (ASD tend to result in fractures and/or dislocations after minor trauma because of the altered biomechanical properties. The relative risk of traumatic vertebral fractures in patients with ankylosing spondylitis has been estimated as three times higher than in the general population. These spine traumas, which are located at cervical level in 81% of patients with ankylosing spondylitis, are complicated by neurological lesions in 65% of patients, due to the high inherent instability of these fractures. Traditional massage is an ancient practice in many parts of Asia. It has many benefits that are currently recognized world-wide. However, it can be dangerous and even lethal if practised without adequate knowledge and skill. We report a case of C6-C7 fracture-dislocation with complete neurology and neurogenic shock in a middle aged man with undiagnosed ankylosing spondylitis.

  20. Benzene metabolite levels in blood and bone marrow of B6C3F{sub 1} mice after low-level exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bechtold, W.E.; Strunk, M.R.; Thornton-Manning, J.R. [and others

    1995-12-01

    Studies at the Inhalation Toxicology Research Institute (ITRI) have explored the species-specific uptake and metabolism of benzene. Results have shown that metabolism is dependent on both dose and route of administration. Of particular interest were shifts in the major metabolic pathways as a function of exposure concentration. In these studies, B6C3F{sub 1} mice were exposed to increasing levels of benzene by either gavage or inhalation. As benzene internal dose increased, the relative amounts of muconic acid and hydroquinone decreased. In contrast, the relative amount of catechol increased with increasing exposure. These results show that the relative levels of toxic metabolites are a function of exposure level. Based on these results and assuming a linear relationship between exposure concentration and levels of bone marrow metabolites, it would be difficult to detect an elevation of any phenolic metabolites above background after occupational exposures to the OSHA Permissible Exposure Limit of 1 ppm benzene.

  1. Cloning of a novel 6-chloronicotinic acid chlorohydrolase from the newly isolated 6-chloronicotinic acid mineralizing Bradyrhizobiaceae strain SG-6C.

    Directory of Open Access Journals (Sweden)

    Madhura Shettigar

    Full Text Available A 6-chloronicotinic acid mineralizing bacterium was isolated from enrichment cultures originating from imidacloprid-contaminated soil samples. This Bradyrhizobiaceae, designated strain SG-6C, hydrolytically dechlorinated 6-chloronicotinic acid to 6-hydroxynicotinic acid, which was then further metabolised via the nicotinic acid pathway. This metabolic pathway was confirmed by growth and resting cell assays using HPLC and LC-MS studies. A candidate for the gene encoding the initial dechlorination step, named cch2 (for 6-chloronicotinic acid chlorohydrolase, was identified using genome sequencing and its function was confirmed using resting cell assays on E. coli heterologously expressing this gene. The 464 amino acid enzyme was found to be a member of the metal dependent hydrolase superfamily with similarities to the TRZ/ATZ family of chlorohydrolases. We also provide evidence that cch2 was mobilized into this bacterium by an Integrative and Conjugative Element (ICE that feeds 6-hydroxynicotinic acid into the existing nicotinic acid mineralization pathway.

  2. Crystalline and Molecular Structure of Hexaaqua-1,3-diammoniumpropane Cobalt(II Nitrate, Co(H2O 6 [C3H12N2] (NO34

    Directory of Open Access Journals (Sweden)

    M. L. Mrad

    2010-01-01

    Full Text Available Chemical preparation and x-ray characterization of a new compound hexaaqua-1,3-diammoniumpropane cobalt(II nitrate, Co(H2O 6 [C3H12N2] (NO34 are reported. This mixed organo-mineral compound crystallizes in the orthorhombic system with Cmcm space group. The unit cell dimensions are: a = 10.795(7, b = 11.969(4, c = 14.685(5 Å, Z = 4 and V = 1897.5(12 Å3. The structure was solved using the direct method and refined to reliability R-factor of 0.036 using 2554 independent reflections. In this atomic arrangement the different species built a three-dimensional network.

  3. NTP Toxicology and Carcinogenesis Studies of Roxarsone (CAS No. 121-19-7) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-03-01

    Roxarsone is a veterinary drug used as a growth promoter and as an anticoccidial agent and for treatment of swine dysentery. Toxicology and carcinogenesis studies were conducted by administering roxarsone (greater than 99.4% pure) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, or 2 years. Fourteen-Day and Thirteen-Week Studies: In the 14-day studies, the diets fed to rats contained 0 or 100-1,600 ppm roxarsone, and those fed to mice contained 0 or 60-1,000 ppm. Deaths occurred in rats and mice that received the highest doses. Rats that received 800 or 1,600 ppm lost weight. Male mice that received 1,000 ppm and female mice that received 500 ppm lost weight. In the first 13-week studies, roxarsone was fed to rats and mice at dietary concentrations of 0 or 50-800 ppm. Decreases (more than 10%) in final mean body weights of dosed rats relative to those of controls were observed for males that received 200, 400, or 800 ppm and for females that received 400 or 800 ppm. Deaths occurred in groups that received 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats that received 800 ppm. Kidney lesions were observed in rats that received 800 ppm. These lesions were characterized by tubular necrosis and mineralization in the rats that died during the studies and by tubular dilatation and casts, interstitial inflammation, and tubular epithelial cell regeneration in the rats that lived to the end of the studies. Additional 13-week studies were conducted in rats at dietary concentrations of 0, 100, or 400 ppm to demonstrate the absorption of roxarsone from the gastrointestinal tract; to determine its distribution in liver, kidney, and blood; and to study its effects on various hematologic and clinical chemical values. No deaths occurred. Renal lesions of minimal severity observed in male rats that received 400 ppm were characterized by tubular epithelial cell degeneration and regeneration, tubular

  4. Evaluation of the immunomodulatory effects of the disinfection by-product, sodium chlorite, in female B6C3F1 mice: a drinking water study.

    Science.gov (United States)

    Karrow, N A; Guo, T L; McCay, J A; Johnson, G W; Brown, R D; Musgrove, D L; Germolec, D R; Luebke, R W; White, K L

    2001-08-01

    Sodium chlorite is an inorganic by-product of chlorine dioxide formed during the chlorination of drinking water. Relatively little is known about the adverse health effects of exposure to sodium chlorite in drinking water. In this study, we evaluated sodium chlorite's immunomodulatory properties using female B6C3F1 mice and a panel of immune assays that were designed to evaluate potential changes in innate and acquired cellular and humoral immune responses. Female B6C3F1 mice were exposed to sodium chlorite in their drinking water (0, 0.1, 1, 5, 15, and 30 mg/L) for 28 days, and then evaluated for immunomodulation. Overall, minimal toxicological and immunological changes were observed after exposure to sodium chlorite. Increases in the percentages of blood reticulocytes, and the relative spleen weights were both observed at different sodium chlorite treatment levels; however, these increases were not dose-dependent. An increasing trend in the number of spleen antibody-forming cells was observed over the range of sodium chlorite concentrations. This increase was not, however, significant at any individual treatment level, and was not reflected by changes in serum IgM levels. A significant increase (26%) in the total number of splenic CD8+ cells was observed in mice treated with 30 mg/L of sodium chlorite, but not at the other concentrations. Splenic mixed leukocyte response and peritoneal macrophage activity were unaffected by sodium chlorite. Lastly, exposure to sodium chlorite did not affect natural killer cell activity, although a decrease in augmented natural killer cell activity (42%) was observed at the lowest sodium chlorite treatment level. These results suggest that sodium chlorite, within the range 0.1-30 mg/L, produces minimal immunotoxicity in mice.

  5. Influence of Al on the fatigue crack growth behavior of Fe–22Mn–(3Al)–0.6C TWIP steels

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Penghui [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); National Engineering Research Center for Equipment and Technology of Cold Strip Rolling, Yanshan University, Qinhuangdao 066004 (China); Qian, Lihe, E-mail: dlhqian@yahoo.com [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); National Engineering Research Center for Equipment and Technology of Cold Strip Rolling, Yanshan University, Qinhuangdao 066004 (China); Meng, Jiangying [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Liu, Shuai; Zhang, Fucheng [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); National Engineering Research Center for Equipment and Technology of Cold Strip Rolling, Yanshan University, Qinhuangdao 066004 (China)

    2015-10-01

    The influence of Al on fatigue crack growth (FCG) behavior of the high-Mn austenitic twinning-induced plasticity (TWIP) steel was investigated by conducting FCG tests on Fe–22Mn–0Al–0.6C and Fe–22Mn–3Al–0.6C TWIP steels (hereafter, referred to as 0Al and 3Al TWIP steel, respectively). The FCG tests were performed at stress ratio of 0.1 under the control of stress intensity factor range using three-point bending specimens. Excepting that the traditional two-dimensional (2D) observation methods (optical, scanning and transmission electron microscopes) were used to observe the crack paths, fracture surfaces and microstructure features, a high-resolution synchrotron X-ray computed tomography was also applied to observe the three-dimensional (3-D) crack morphology. The results indicate that the FCG resistance of the 0Al TWIP steel is superior to that of 3Al TWIP steel in the near threshold regime. Observed from the 2D crack paths and 3D crack morphologies, it can be found that the crack surface roughness and crack deflection of the 0Al steel are greater than those of 3Al steel. It is suggested that the degree of roughness-induced crack closure decreases with the addition of Al. And the 0Al steel shows much larger plastic zone sizes ahead of the crack tip than the 3Al steel, suggesting that plasticity-induced crack closure may also play an important role in decreasing the FCG rate in the 0Al steel. By excluding the crack closure effects, the 0Al steel still exhibits a higher effective crack growth threshold value than the 3Al steel; this is considered to be due to the higher planarity of slip in the 0Al steel than in the 3Al steel, and the mechanical twins generated in the 0Al steel reduce the stress concentration at crack tip.

  6. Technological experiment research of superplastic welding of 1.6C%-UHCS/40Cr with preset interlayer%预置中间层的1.6C-UHCS/40Cr超塑性焊接工艺试验

    Institute of Scientific and Technical Information of China (English)

    衡中皓; 张柯柯; 邱然锋; 涂益民; 乔騻; 李臣阳

    2012-01-01

    The experiments without vacuum or protection atmosphere was conducted based on the optimized design of superplastic welding of 1.6C%-UHCS/40Cr with preset interlayer. The results showed that choosing rolled industrial pure iron as an interlayer could improve the 1.6C%-UHCS/40Cr interface's plastic deformation and their weldability effectively. When the initial pressure was 56.6 MPa, welding temperature was 750 XI, initial strain rate was 1.5x10- 4s-1, after 10 min welding, the joint tensile strength could reach 702 MPa, which was 35% larger than without interlayer and equal with the tensile strength of 40Cr base metal after thermodynamic cycle.%基于对预置中间层的1.6C-UHCS/40Cr超塑性焊接工艺方案的优化设计,在非真空及无保护气氛下,进行了超塑性焊接工艺试验.试验结果表明:选用轧制态工业纯铁中间层,能有效改善1.6C-UHCS/40Cr超塑焊界面区的塑性变形能力,提高焊接性.在预压应力56.6 MPa、焊接温度750℃、初始应变速率1.5×10-4/s的条件下,经10 min压接,接头抗拉强度为702 MPa,比不加中间层的接头强度提高35%,达相同热力循环下40Cr母材的抗拉强度.

  7. Organically templated uranium(IV) fluorooxalates with layer structures: (H4TREN)[U2F6(C2O4)3].4H2O (TREN = tris(2-aminoethyl)amine) and (H4APPIP)[U2F6(C2O4)3].4H2O (APPIP = 1,4-bis(3-amino-propyl)piperazine).

    Science.gov (United States)

    Wang, Chih-Min; Wu, Yi-Ying; Chen, Pei-Lin; Lii, Kwang-Hwa

    2007-03-14

    Two organically-templated layered uranium(IV) fluorooxalates, (H(4)TREN)[U(2)F(6)(C(2)O(4))(3)].4H(2)O (1) (TREN = tris(2-aminoethyl)amine) and (H(4)APPIP)[U(2)F(6)(C(2)O(4))(3)].4H(2)O (2) (APPIP = 1,4-bis(3-aminopropyl)piperazine), have been synthesized by hydrothermal methods and structurally characterized by single-crystal X-ray diffraction, thermogravimetric analysis, and magnetic susceptibility. Both structures consist of anionic [U(2)F(6)(C(2)O(4))(3)](4-) layers separated by organic ammonium cations and lattice water molecules. The UF(3)O(6) polyhedra are connected by oxalate ligands in different ways within the layers. They are the first examples of organically-templated uranium fluorooxalates. Crystal data for compound 1 follow: monoclinic, P2(1)/c (No. 14), a = 19.1563(5) A, b = 8.9531(2) A, c = 16.6221(4) A, beta = 114.633(1) degrees, and Z = 4. Crystal data for compound are the same as those for 1 except a = 10.3309(8) A, b = 15.564(1) A, c = 17.537(1) A, and beta = 95.430(4) degrees.

  8. Non-Linear Thermal Lens Signal of the (Δυ = 6) C-H Vibrational Overtone of Benzene in Liquid Solutions of Hexane

    Science.gov (United States)

    Nyaupane, Parashu R.; Manzanares, Carlos

    2016-06-01

    The thermal lens technique is applied to vibrational overtone spectroscopy of solutions of benzene. The pump and probe thermal lens technique has been found to be very sensitive for detecting samples of low concentration in transparent solvents. The C-H fifth vibrational (Δυ = 6) overtone spectrum of benzene is detected at room temperature for compositions per volume in the range (1 to 1× 10-4) using n-C_6H14 as the solvent. By detecting the absorption band in a 100 ppm solution, the peak absorption of the signal is approximately (2.2 ± 0.3)× 10-7 cm-1. The parameters that determine the magnitude of the thermal lens signal such as the pump laser power and the thermodynamic properties of the solvent and solute are discussed. A plot of normalized integrated intensity as a function of composition of benzene in solution reveals a non-linear behavior. The non-linearity cannot be explained assuming solvent enhancement at low concentrations. A two color absorption model that includes the simultaneous absorption of the pump and probe lasers could explain the enhanced magnitude and the non-linear behavior of the thermal lens signal for solutions of composition below 0.01.

  9. Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice.

    Science.gov (United States)

    Nyska, Abraham; Ghanayem, Burhan I

    2003-04-01

    Methacrylonitrile is an unsaturated aliphatic nitrile. It is widely used in the preparation of homopolymers and copolymers, elastomers, and plastics, and as a chemical intermediate in the preparation of acids, amides, amines, esters, and other nitriles. Methacrylonitrile was nominated for study by the National Cancer Institute (USA) because of the potential for human exposure, structural similarity to the known carcinogen acrylonitrile, and a lack of toxicity and carcinogenicity data. Doses selected for the 2-year study were based on the results of the 13-week gavage studies. Groups of 50 male and 50 female animals were exposed by gavage to 0, 3, 10, or 30 mg/kg in F344 rats, and 0, 1.5, 3 or 6 mg/kg in B6C3F1 mice, 5 days per week for 2 years. Urinary excretion of N-acetyl- S-(2-cyanopropyl)- l-cysteine (NACPC) and N-acetyl- S-(2-hydroxypropyl)- l-cysteine (NAHPC) were measured as markers of exposure at various time points after methacrylonitrile administration, and demonstrated that exposure of animals to methacrylonitrile occurred as intended. Urinary excretion of NACPC and NAHPC increased in rats and mice in a dose-dependent manner. In contrast to observations in rats, the ratios of NACPC/creatinine were generally higher in female than in male mice. Further, the ratios of NAHPC/creatinine in rats were significantly greater at all time points and all doses than the corresponding ratios of NACPC/creatinine in male and female mice. In both rats and mice, survival was not affected by treatment. In rats, mean body weights of the 30 mg/kg groups were less than those of the vehicle controls after weeks 21 and 37 for males and females, respectively. No treatment-related effect on body weight was seen in mice. There were no neoplasms (in either species) or non-neoplastic lesions (mice only) that were attributed to methacrylonitrile administration. In rats, the incidences of olfactory epithelial atrophy and metaplasia of the nose were significantly greater in 30 mg

  10. Photoelectrochemical solar energy conversion based on blend of poly(3-hexylthiophene (P3HT and 1-(3-methoxycarbonyl propyl-1-phenyl [6,6]C61 (PCBM

    Directory of Open Access Journals (Sweden)

    Teketel Yohannes

    2012-08-01

    Full Text Available A solid-state photoelectrochemical solar energy conversion device based on blend of poly(3-hexylthiophene (P3HT and 1-(3-methoxycarbonylpropyl-1-phenyl[6,6]C61 (PCBM, and an amorphous poly(ethylene oxide complexed with I3-/I- redox couple has been constructed and characterized. The photoelectrochemical performance parameters of the device were compared with pure P3HT and P3HT:C60 blend solid-state photoelectrochemical cell. The current density-voltage characteristics in the dark and under white light illumination and photocurrent spectra for front and backside illuminations have been studied. An open-circuit voltage of 140 mV and a short-circuit current density of 28.4 μA/cm2 at light intensity of 100 mW/cm2; IPCE% of 1.52% for front side illumination (ITO|PEDOT and IPCE% of 0.17% for backside illumination (ITO|P3HT:PCBM at a wavelength of 510 nm were obtained. The dependence of the short-circuit current density and an open-circuit voltage on the light intensity and time have also been studied.DOI: http://dx.doi.org/10.4314/bcse.v26i2.12

  11. Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from B6C3F1 mice exposed to cumene.

    Science.gov (United States)

    Hong, Hue-Hua L; Ton, Thai-Vu T; Kim, Yongbaek; Wakamatsu, Nobuko; Clayton, Natasha P; Chan, Po-Chuen; Sills, Robert C; Lahousse, Stephanie A

    2008-07-01

    The incidences of alveolar/bronchiolar adenomas and carcinomas in cumene-treated B6C3F1 mice were significantly greater than those of the control animals. We evaluated these lung neoplasms for point mutations in the K-ras and p53 genes that are often mutated in humans. K-ras and p53 mutations were detected by cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded neoplasms. K-ras mutations were detected in 87% of cumene-induced lung neoplasms, and the predominant mutations were exon 1 codon 12 G to T transversions and exon 2 codon 61 A to G transitions. P53 protein expression was detected by immunohistochemistry in 56% of cumene-induced neoplasms, and mutations were detected in 52% of neoplasms. The predominant mutations were exon 5, codon 155 G to A transitions, and codon 133 C to T transitions. No p53 mutations and one of seven (14%) K-ras mutations were detected in spontaneous neoplasms. Cumene-induced lung carcinomas showed loss of heterozygosity (LOH) on chromosome 4 near the p16 gene (13%) and on chromosome 6 near the K-ras gene (12%). No LOH was observed in spontaneous carcinomas or normal lung tissues examined. The pattern of mutations identified in the lung tumors suggests that DNA damage and genomic instability may be contributing factors to the mutation profile and development of lung cancer in mice exposed to cumene.

  12. Toxic responses in F344 rats and B6C3F1 mice given roxarsone in their diets for up to 13 weeks.

    Science.gov (United States)

    Abdo, K M; Elwell, M R; Montgomery, C A; Thompson, M B; Thompson, R B; Prejean, J D

    1989-01-01

    Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound-related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were greater than 6 times higher in rats than in mice and were about 2 time higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex.

  13. NTP Toxicology and Carcinogenesis Studies of Polyvinyl Alcohol (CAS No.9002-89-5) in Female B6C3F1 Mice (Intravaginal Studies).

    Science.gov (United States)

    1998-05-01

    Polyvinyl alcohol is produced primarily for use in textile sizing, adhesives, polymerization aids, and paper coatings. It is also used in surgical drapes, towels, and gauze sponges; protective gloves; cosmetic formulations; topical ophthalmic preparations; plastic sponge implants for reconstructive surgery; and intravaginal contraceptive foam and film. In addition, polyvinyl alcohol is used with magnesium sulfate to dilate the cervix of women prior to induction of labor. It is estimated that hundreds of thousands of women in the United States use an intravaginal product containing polyvinyl alcohol each year. The Food and Drug Administration nominated low-viscosity polyvinyl alcohol for a 2-year study because of concern about the lack of information about the long-term toxic and carcinogenic effects by the intravaginal route. Female B6C3F1 mice received polyvinyl alcohol (approximately 99% pure) in deionized water by intravaginal administration for 30 days or 2 years. 30-DAY STUDY IN MICE: Three groups of 50 female B6C3F1 mice were used in this intravaginal study. The vehicle control group received only 20 &mgr;L of a deionized water vehicle. The other two groups each received 20 &mgr;L of 25% polyvinyl alcohol in deionized water. Animals in one dose group were returned to their cages after dosing; animals in the other dose group were restrained in a vertical nose-down position in restraint bags for several minutes after dosing. Animals were dosed daily for 30 consecutive days. All mice survived to the end of the study. The final mean body weights and body weight gains of dosed mice were similar to those of the vehicle control group. Abnormalities noted in the vaginal area after dosing included vaginal plugs, secretions, and swelling. These vaginal changes were minimal to mild and occurred in vehicle controls as well as in dosed mice. Restraint of mice after dosing appeared to eliminate vaginal secretions but increased both the incidence of vaginal irritation and

  14. An efficient code for calculation of the 6C, 9C and 12C symbols for C3v, T, and O point groups

    Science.gov (United States)

    Nikitin, A. V.

    2012-03-01

    A new code designed to calculate the 6 C, 9 C, and 12 C symbols for C3v, T, and O point groups is presented. The program is based on an algorithm that uses the symmetry property between pair and impair representations. This algorithm allows one to speed up the C-symbols calculation and increase the efficiency of spectroscopic programs based on the irreducible tensorial formalism. Program summaryProgram title: 6912C Catalogue identifier: AEKZ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKZ_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 1214 No. of bytes in distributed program, including test data, etc.: 22 097 Distribution format: tar.gz Programming language: C++ Computer: Any computer with C, C++ compiler Operating system: Linux SUSE, Windows XP64 RAM: 400 Kb Classification: 4.2, 16.2, 16.3 Nature of problem: Spectroscopy of symmetric atmospheric molecules. Solution method: The program is based on an algorithm that uses the symmetry property between pair and impair representations. Running time: The test program provided takes a few seconds for C3v, a few minutes for T and a few days for O.

  15. Density functional results for isotropic and anisotropic multipole polarizabilities and C6, C7, and C8 Van der Waals dispersion coefficients for molecules

    Science.gov (United States)

    Osinga, V. P.; van Gisbergen, S. J. A.; Snijders, J. G.; Baerends, E. J.

    1997-03-01

    The generalized gradient-approximated (GGA) energy functionals used in density functional theory (DFT) provide accurate results for many different properties. However, one of their weaknesses lies in the fact that Van der Waals forces are not described. In spite of this, it is possible to obtain reliable long-range potential energy surfaces within DFT. In this paper, we use time-dependent density functional response theory to obtain the Van der Waals dispersion coefficients C6, C7, and C8 (both isotropic and anisotropic). They are calculated from the multipole polarizabilities at imaginary frequencies of the two interacting molecules. Alternatively, one might use one of the recently-proposed Van der Waals energy functionals for well-separated systems, which provide fairly good approximations to our isotropic results. Results with the local density approximation (LDA), Becke-Perdew (BP) GGA and the Van Leeuwen-Baerends (LB94) exchange-correlation potentials are presented for the multipole polarizabilities and the dispersion coefficients of several rare gases, diatomics and the water molecule. The LB94 potential clearly performs best, due to its correct Coulombic asymptotic behavior, yielding results which are close to those obtained with many-body perturbation theory (MBPT). The LDA and BP results are systematically too high for the isotropic properties. This becomes progressively worse for the higher dispersion coefficients. The results for the relative anisotropies are quite satisfactory for all three potentials, however.

  16. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  17. CH4、CO2及CH4+C2H6+C3H8在纯水、SDS水溶液和含石英砂体系中水合物相平衡条件的测定%Measurements of Hydrate Equilibrium Conditions for CH4, CO2, and CH4+ C2H6 + C3H8 in Various Systems by Step-heating Method

    Institute of Scientific and Technical Information of China (English)

    陈立涛; 孙长宇; 陈光进; 聂运强; 孙占松; 刘延涛

    2009-01-01

    Phase equilibrium conditions of gas hydrate in several systems were measured by the step-heating method using the cylindrical transparent sapphire cell device. The experimental data for pure CH4or CO2 + deion-ized water systems showed good agreement with those in the literatures. This kind of method was then applied to CH4/CO2 + sodium dodecyl sulfate (SDS) aqueous solution, CH4/CO2+SDS aqueous solution+silica sand, and (CH4+C2H6+C3H8) gas mixture+SDS aqueous solution systems, where SDS was added to increase the hydrate formation rate without evident influence on the equilibrium conditions. The feasibility and reliability of the step-heating method, especially for porous media systems and gas mixtures systems were determined. The experimental data for CO2+silica sand data shows that the equilibrium pressure will change significantly when the particle size of silica sand is less than 96 μm. The formation equilibrium pressure was also measured by the reformation of hydrate.

  18. Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water.

    Science.gov (United States)

    Frawley, Rachel P; Smith, Matthew J; White, Kimber L; Elmore, Susan A; Herbert, Ron; Moore, Rebecca; Staska, Lauren M; Behl, Mamta; Hooth, Michelle J; Kissling, Grace E; Germolec, Dori R

    2016-09-01

    Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0-2000 mg STD/L in their drinking water for 28 d, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3(+) T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely affect cell-mediated immunity.

  19. Differential genotoxicity of acrylamide in the micronucleus and Pig-a gene mutation assays in F344 rats and B6C3F1 mice.

    Science.gov (United States)

    Hobbs, Cheryl A; Davis, Jeffrey; Shepard, Kim; Chepelev, Nikolai; Friedman, Marvin; Marroni, Dennis; Recio, Leslie

    2016-11-01

    Acrylamide is used in many industrial processes and is present in a variety of fried and baked foods. In rodent carcinogenicity assays, acrylamide exposure leads to tumour formation at doses lower than those demonstrated to induce genotoxic damage. We evaluated the potential of acrylamide to induce structural DNA damage and gene mutations in rodents using highly sensitive flow cytometric analysis of micronucleus and Pig-a mutant frequencies, respectively. Male F344 rats and B6C3F1 mice were administered acrylamide in drinking water for 30 days at doses spanning and exceeding the range of acrylamide exposure tested in cancer bioassays-top dose of 12.0 and 24.0mg/kg/day in mice and in rats, respectively. A positive control, N-ethyl-N-nitrosourea, was administered at the beginning and end of the study to meet the expression time for the two DNA damage phenotypes. The results of the micronucleus and Pig-a assays were negative and equivocal, respectively, for male rats exposed to acrylamide at the concentrations tested. In contrast, acrylamide induced a dose-dependent increase in micronucleus formation but tested negative in the Pig-a assay in mice. Higher plasma concentrations of glycidamide in mice than rats are hypothesized to explain, at least in part, the differences in the response. Benchmark dose modelling indicates that structural DNA damage as opposed to point mutations is most relevant to the genotoxic mode of action of acrylamide-induced carcinogenicity. Moreover, the lack of genotoxicity detected at acrylamide-induced carcinogenicity in rodents. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Development of a Single Station 6C-Approach for Array Analysis and Microzonation: Using Vertical Rotation Rate to Estimate Love-Wave Disperion Curves and Direction Finding

    Science.gov (United States)

    Wassermann, J. M.; Wietek, A.; Hadziioannou, C.; Igel, H.

    2014-12-01

    Microzonation, i.e. the estimation of (shear) wave velocity profiles of the upper few 100m in dense 2D surface grids is one of the key methods to understand the variation in seismic hazard caused by ground shaking events. In this presentation we introduce a novel method for estimating the Love-wave phase velocity dispersion by using ambient noise recordings. We use the vertical component of rotational motions inherently present in ambient noise and the well established relation to simultaneous recordings of transverse acceleration. In this relation the frequency dependent phase velocity of a plane SH (or Love)-type wave acts as a proportionality factor between the anti-correlated amplitudes of both measures. In a first step we used synthetic data sets with increasing complexity to evaluate the proposed technique and the developed algorithm to extract the direction and amplitude of the incoming ambient noise wavefield measured at a single site. Since reliable weak rotational motion sensors are not yet readily available, we apply array derived rotation measurements in order to test our method. We next use the technique to analyze different real data sets of ambient noise measurements as well as seismic recordings at active volcanoes and compare these results with findings of the Spatial AutoCorrelation technique which was applied to the same data set. We demonstrate that the newly developed technique shows comparable results to more classical, strictly array based methods. Furthermore, we show that as soon as portable weak motion rotational motion sensors are available, a single 6C-station approach will be feasible, not only for microzonation but also for general array applications, with performance comparable to more classical techniques. An important advantage, especially in urban environments, is that with this approach, the number of seismic stations needed is drastically reduced.

  1. Microwave-assisted synthesis of arene Ru(Ⅱ) complex [(η6-C6H5) Ru(PIP) Cl]Cl·2H2O%微波辅助合成芳烃钌(Ⅱ)配合物[(η6-C6H5)Ru(PIP)Cl]Cl·2H2O

    Institute of Scientific and Technical Information of China (English)

    陈艾纯; 吴琼; 陈燕华; 梅文杰; 吴韦黎; 胡晓莹; 吴剑; 汪保国

    2013-01-01

    目的 探讨应用微波辅助合成技术制备芳烃钌(Ⅱ)化合物[(η6-C6H6)Ru(PIP) Cl] Cl·2H2O(3).方法 首先以RuCl3·nH2O、1,3-环己二烯和1,10-邻菲哕啉为原料微波辐射下制备得到芳烃钌前体[(η6-C6H6)RuCl2]2(1)和2-苯基-咪唑并[4,5f][1,10]菲哕啉(PIP,2),然后,在二氯甲烷溶液中,微波辐射1与2制备芳烃钌(Ⅱ)配合物3;采用ESI-MS、IR、1H-NMR、13C-NMR对目标配合物进行表征.结果 60℃条件下,化合物1与2在二氯甲烷溶液微波辐射30 min,制备得到了芳烃钌配合物3,反应产率为90.3%;目标产物经ESI-MS、IR、1H-NMR和13C-NMR表征,实验值与理论值基本一致.结论 与传统加热方法相比,微波辅助合成芳烃钌配合物明显缩短了反应时间,提高了反应产率.%Objective To research the preparation of arene Ru( Ⅱ ) complex [η6-C6H6)RU(PIP)Cl]Cl· 2H2O(3) by using microwave-assisted synthesis technology. Methods [ ( η6 -C6H6 ) RuCl2 ]2 (1) was synthesized from RuCl2 · nH2O and 1,3-cyclohexadiene by using microwave-assisted synthesis technology, and 2-phenyl-imidazole[4,5/] [1,10]phenanthroline (PIP,2) also synthesized from 1,10-phenanthroline-5 ,6-dione and benzaldehyde under microwave irradiation, and then 2 and 3 were mixed in CH2Cl2 solution to prepare [ (η6-C6H6)Ru( PIP) Cl] Cl · 2H2O (3) under the irradiation microwave. The target complex 3 was characterized by using ESI-MS, IR,1H-NMR and 13C-NMR spectra. Results Arene Ru( Ⅱ ) complex 3 was prepared from 1 and 2 in CH2Cl2 at 60℃ for 30 min under microwave irradiation with a yield of 90. 3%,and characterized by ESI-MS, IR,1H-NMR and 13C-NMR spectra. Conclusion A novel arene ruthenium ( Ⅱ ) complexes 3 have been synthesized under the irradiation of microwave, and with far more less time and higher yield compared with the conventional method.

  2. NTP toxicity studies of toxicity studies of 2,4-decadienal (CAS No. 25152-84-5) administered by gavage to F344/N Rats and B6C3F1 mice.

    Science.gov (United States)

    Chan, P C

    2011-01-01

    2,4-Decadienal is used as a synthetic flavoring and fragrance material and has been evaluated as a corrosion inhibitor for steel in oil field operations. 2,4-Decadienal was nominated by the National Cancer Institute for toxicity testing because the dienaldehydes occur naturally in a variety of foods and food components, are used as food additive/flavoring agents, and the potential for human exposure is high. In the toxicity studies, male and female F344/N rats and B6C3F1 mice received 2,4-decadienal (at least 93% pure) in corn oil by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. In the 2-week studies, groups of five male and five female rats and mice received 2,4-decadienal in corn oil by gavage at doses of 0, 45, 133, 400, 1,200, or 3,600 mg 2,4-decadienal/kg body weight 5 days per week for 16 days. All animals in the 3,600 mg/kg groups were found dead or sacrificed moribund by day 3 (rats) or day 9 (mice). One 133 mg/kg female rat was found dead on day 8, and one male and one female mouse in the 1,200 mg/kg groups were found dead on days 12 and 16, respectively. At 1,200 mg/kg, treatment-related ulceration of the forestomach was observed in male and female rats and mice. Focal necrosis of the forestomach occurred in a 1,200 mg/kg female mouse. Mean body weights of all 1,200 mg/kg groups were less than those of the vehicle controls, and 1,200 mg/kg female mice lost weight during the study. Diarrhea, lethargy, abnormal breathing (rats), and thinness (mice) occurred in the 1,200 and 3,600 mg/kg groups. Gross lesions seen at necropsy included ulcerations of the forestomach in 1,200 mg/kg rats and 1,200 and 3,600 mg/kg mice. Adhesions involving the stomach and other abdominal organs were also seen in 1,200 and 3,600 mg/kg mice. In the 3-month studies, groups of 10 male and 10 female rats and mice received 2,4-decadienal in corn oil by gavage

  3. Investigation of the DNA adducts formed in B6C3F1 mice treated with benzene: Implications for molecular dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Bodell, W.J.; Pathak, D.N.; Levay, G. [Univ. of California, San Francisco, CA (United States)] [and others

    1996-12-01

    We have investigated the formation of DNA adducts in the bone marrow and white blood cells of male B6C3F1 mice treated with benzene using P1-enhanced {sup 32}P-postlabeling. No adducts were detected in the bone marrow of controls or mice treated with various doses of benzene once a day. After twice-daily treatment for 1 to 7 days with benzene, 440 mg/kg, one major (no. 1) and UP to two minor DNA adducts were detected in both the bone marrow and white blood cells. The relative adduct levels in these cells ranged from 0.06 to 1.46 x 10{sup -7}. A significant correlation (r 0.95) between levels of adducts in bone marrow and white blood cells was observed. After a 7-day treatment with benzene, 440 mg/kg twice a day, the number of cells per femur decreased from 1.6 x 10{sup 7} to 0.85 X 10{sup 7}, indicating myelotoxicity. In contrast, administration of benzene once a day produced only a small decrease in bone marrow cellularity. The observed induction of toxicity in bone marrow was paralleled by formation of DNA adducts. In vitro treatment of bone marrow with hydroquinone (HQ) for 24 hr produced the same DNA adducts as found after treatment of mice with benzene, suggesting that HQ is the principal metabolite of benzene leading to DNA adduct formation in vivo. Using {sup 32}P-postlabeling the principal DNA adduct formed in vivo was compared with N{sup 2}-(4-hydroxyphenyl)-2-deoxyguanosine-3-phosphate. The results of this comparison demonstrates that the DNA adduct formed in vivo co-chromatographs with N{sup 2}-(4-hydroxyphenyl)-2-deoxyguanosine-3{prime}-phosphate. These studies indicate that metabolic activation of benzene leads to the formation of DNA adducts in bone marrow and white blood cells and suggest that measurement of DNA adducts in white blood cells may be an indicator of biological effect following benzene exposure. 34 refs., 4 figs., 2 tabs.

  4. Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship with CYP2B6 c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis

    Science.gov (United States)

    Chau, Tran Thi Hong; Fisher, Martin; Nelson, Mark; Winston, Alan; Else, Laura; Carr, Daniel F.; Taylor, Steven; Ustianowski, Andrew; Back, David; Pirmohamed, Munir; Solomon, Tom; Farrar, Jeremy; Törok, M. Estée; Khoo, Saye

    2016-01-01

    Efavirenz (EFZ) has been associated with neuropsychiatric side effects. Recently, the 8-hydroxy-EFZ (8OH-EFZ) metabolite has been shown to be a potent neurotoxin in vitro, inducing neuronal damage at concentrations of 3.3 ng/ml. EFZ induced similar neuronal damage at concentrations of 31.6 ng/ml. We investigated the effect of genotype and blood-brain barrier integrity on EFZ metabolite concentrations in cerebrospinal fluid (CSF). We measured CSF drug concentrations in subjects from two separate study populations: 47 subjects with tuberculous meningitis (TBM) coinfection in Vietnam receiving 800 mg EFZ with standard antituberculous treatment and 25 subjects from the PARTITION study in the United Kingdom without central nervous system infection receiving 600 mg EFZ. EFZ and metabolite concentrations in CSF and plasma were measured and compared with estimates of effectiveness and neurotoxicity from available published in vitro and in vivo data. The effect of the CYP2B6 c.516G→T genotype (GG genotype, fast EFV metabolizer status; GT genotype, intermediate EFV metabolizer status; TT genotype, slow EFV metabolizer status) was examined. The mean CSF concentrations of EFZ and 8OH-EFZ in the TBM group were 60.3 and 39.3 ng/ml, respectively, and those in the no-TBM group were 15.0 and 5.9 ng/ml, respectively. Plasma EFZ and 8OH-EFZ concentrations were similar between the two groups. CSF EFZ concentrations were above the in vitro toxic concentration in 76% of samples (GG genotype, 61%; GT genotype, 90%; TT genotype, 100%) in the TBM group and 13% of samples (GG genotype, 0%; GT genotype, 18%; TT genotype, 50%) in the no-TBM group. CSF 8OH-EFZ concentrations were above the in vitro toxic concentration in 98% of the TBM group and 87% of the no-TBM group; levels were independent of genotype but correlated with the CSF/plasma albumin ratio. Potentially neurotoxic concentrations of 8OH-EFZ are frequently observed in CSF independently of the CYP2B6 genotype, particularly in those

  5. NTP Carcinogenesis Bioassay of Propyl Gallate (CAS No. 121-79-9) in F344/N Rats and B6C3F1 Mice (Feed Study).

    Science.gov (United States)

    1982-12-01

    Propyl gallate is a white to nearly white odorless powder having a slightly bitter taste. Solutions of propyl gallate turn dark in the presence of iron or iron salts. Propyl gallate has been used since 1948 as an antioxidant to stabilize cosmetics, food packaging materials, and foods containing fats. As an additive, it may be found in edible fats, oils, mayonnaise, shortening, baked goods, candy, dried meat, fresh pork sausage, and dried milk, and it is used in hair grooming products, pressure-sensitive adhesives, lubricating oil additives, and transforming oils. A NTP Carcinogenesis bioassay of propyl gallate was conducted by feeding diets containing 6,000 or 12,000 ppm propyl gallate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 untreated rats and 50 untreated mice of each sex served as controls. Survival of rats and mice was not adversely affected by propyl gallate, but mean body weights of dosed rats and mice of each sex were lower than those of the controls. At 104 weeks, mean body weights of low-and high-dose rats were 4% and 8% lower than those of the controls for males and 11% and 19% lower than those of the controls for females. Similarly, mean body weights of low-and high-dose mice were 5% and 8% lower than those of the controls for males and 11% (both dose groups) lower than those of the controls for females. Thyroid follicular-cell adenomas or carcinomas (combined) occurred in male rats with a statistically significant (P<0.05) positive trend, but the incidences in the dosed groups were not statistically significant in direct comparisons with the control groups. Moreover, the incidence of high-dose male rats with follicular-cell tumors (3/50, 6%) was not statistically different from the historical control rate (14/584, 2.4%) for the laboratory that conducted this bioassay. Rare tumors (an astrocytoma or a glioma) were found in the brains of two low-dose female rats. The incidence of all brain tumors in the

  6. NTP Toxicology and Carcinogenesis Studies of Propylene (CAS No. 115-07-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1985-11-01

    Propylene is used as a starting material in the production of polypropylene plastics and various other chemicals, including acrylonitrile, isopropyl alcohol, propylene oxide, butyraldehyde, cumene, dodecane, nonene, and allyl chloride. The major derivatives are polypropylene (25%), acrylonitrile (15%), isopropyl alcohol (10%), and propylene oxide (10%). It is also a valuable feed-stock chemical for the production of gasoline. Other miscellaneous applications include use as a starting material for polymerization reactions to form vinyl chloride copolymers and low-molecular-weight homopolymers that are used as additives in lubricating oils and in the manufacture of hydroquinone. The chemical is also used as an aerosol propellant or component. The major end uses of propylene are in the production of fabricated plastics (50%) and fibers (15%). Toxicology and carcinogenesis studies of propylene (greater than 99% pure) were conducted by exposing groups of 50 F344/N rats and 49 or 50 B6C3F1 mice of each sex to propylene in air by inhalation at concentrations of 5,000 or 10,000 ppm, 6 hours per day, 5 days per week, for 103 weeks. Other groups of 50 rats and 50 mice of each sex in chambers received air only on the same schedule and served as chamber controls. The highest concentration of propylene that was considered safe for these studies was 10,000 ppm because of the risk of explosion that can occur at higher concentrations. The survival of exposed and control rats and mice was comparable. Throughout most of the studies, mean body weights of exposed male and female rats were slightly lower (0%-5%) than those of the controls, but the decrements were not concentration related. After week 59 of the study, mean body weights of 10,000-ppm male mice were usually slightly lower (5%) than those of the controls, whereas those in other exposed groups of male and female mice were generally comparable with those of the controls. No compound-related adverse clinical signs were

  7. Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

    Science.gov (United States)

    Yun, Tatyana; Park, Arnold; Hill, Terence E.; Pernet, Olivier; Beaty, Shannon M.; Juelich, Terry L.; Smith, Jennifer K.; Zhang, Lihong; Wang, Yao E.; Vigant, Frederic; Gao, Junling; Wu, Ping

    2014-01-01

    ABSTRACT Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. Despite their high sequence similarity, NiV and HeV exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. To investigate the molecular basis for these differences, we first established a highly efficient reverse genetics system that increased rescue titers by ≥3 log units, which offset the difficulty of generating multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We then replaced, singly and in combination, the matrix (M), fusion (F), and attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV) with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in primary human endothelial and neuronal cells, indicating efficient heterotypic complementation. The determinants of budding efficiency, fusogenicity, and replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M, accounting for the higher replicative titers of HeV-M-bearing chimeras at early times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not correlate with increased replicative fitness. Furthermore, to facilitate spatiotemporal studies on henipavirus pathogenesis, we generated a firefly luciferase-expressing NiV and monitored virus replication and spread in infected interferon alpha/beta receptor knockout mice via bioluminescence imaging. While intraperitoneal inoculation resulted in neuroinvasion following systemic spread and replication in the respiratory tract, intranasal inoculation resulted in confined spread to regions corresponding to olfactory bulbs and salivary glands before subsequent neuroinvasion. This optimized henipavirus reverse genetics system will facilitate future investigations into

  8. Pulsed Discharge Characteristics of SF6/H2 and SF6/C2 H6 Mixtures and Their Effects on Output Laser%SF6/H2和SF6/C2 H6气体激光介质脉冲放电特性及其对输出激光的影响

    Institute of Scientific and Technical Information of China (English)

    易爱平; 唐影; 黄珂; 朱峰; 黄超; 马连英; 于力; 刘晶儒

    2016-01-01

    在未采取预电离措施的情况下,研究了纯SF6气体及SF6/H2和SF6/C2 H6两种混合气体激光介质脉冲放电特性。实验结果表明,无预电离时 SF6及其混合气体介质可以实现自引发体放电,气体介质体放电维持电压主要由 SF6含量决定,C2 H 6具有抑制电弧的作用,可以有效延长体放电维持时间。分析认为,SF6气体高折合场强E/p导致的放电通道电流密度受限和高电负度χa 引起的放电通道中负离子分解产生二次电子,是介质实现自引发体放电的重要机理。%Stable volume discharge of gas mixture is the foundation for discharge pumped gas laser.In this paper,the pulsed discharge characteristics of SF6 ,SF6/H2 mixture,and SF6/C2 H6 mixture are studied without pre-ionization.The experimental results show that the pulsed self-initiation volume discharge in SF6 mixture can be realized without pre-ionization, and the voltage of volume discharge depends on SF6 partial pressure.C2 H6 can suppress the development of arc,and extend the time of volume discharge,and obviously improve the vol-ume discharge of SF6 gas.The discharge mechanisms of SF6 and its mixture are discussed.

  9. Age, introduction of solid feed and weaning are more important determinants of gut bacterial succession in piglets than breed and nursing mother as revealed by a reciprocal cross-fostering model

    NARCIS (Netherlands)

    Bian, Gaorui; Ma, Shouqing; Zhu, Zhigang; Su, Yong; Zoetendal, Erwin G.; Mackie, Roderick; Liu, Junhua; Mu, Chunlong; Huang, Ruihua; Smidt, Hauke; Zhu, Weiyun

    2016-01-01

    A reciprocal cross-fostering model with an obese typical Chinese piglet breed and a lean Western breed was used to identify genetic and maternal effects on the acquisition and development gut bacteria from birth until after weaning. Pyrosequencing of 16S rRNA genes results revealed an age- and di

  10. NTP Toxicology and Carcinogenesis Studies of Salicylazosulfapyridine (CAS No. 599-79-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1997-05-01

    Salicylazosulfapyridine is widely used for the treatment of ulcerative colitis and Crohn's disease. It has been beneficial in the treatment of psoriasis and rheumatoid arthritis, and it has been used in veterinary medicine for the treatment of granulomatous colitis. Salicylazosulfapyridine was nominated for toxicity and carcinogenicity testing by the National Cancer Institute on the basis of its widespread use in humans and because it is a representative chemical from a class of aryl sulfonamides. Salicylazosulfapyridine is a suspect carcinogen because reductive cleavage of the azo linkage yields a p-amino aryl sulfonamide (sulfapyridine), and a related p-amino aryl sulfonamide (sulfamethoxazole) has been shown to produce thyroid neoplasms in rats. Toxicology and carcinogenicity studies were conducted in F344/N rats and B6C3F1 mice. Rats and mice were administered salicylazosulfapyridine (96% to 98% pure) in corn oil by gavage for 16 days, 13 weeks, or 2 years. The gavage route of administration was selected for these studies because it approximates the typical route of human exposure to the chemical. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow and mouse peripheral blood cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends. All rats survived to the end of the study. With the exception of the 675 mg/kg male group, the final mean body weights of all dosed groups of males and females were significantly lower than those of controls. Mean body weight gains of all dosed groups were less than those of controls. Clinical findings included ruffled fur and distended abdomens in male and female rats receiving 2,700 mg/kg. Hypothyroidism, evidenced by decreased serum triiodothyronine and thyroxine concentrations

  11. Clonning the Promoter of AtHsp17. 6-C2 and Its Heat Inducible Kinetics%基因AtHsp17.6-C2启动子的克隆及其热诱导动力学研究

    Institute of Scientific and Technical Information of China (English)

    曾卫军; 王水平; 李小方; 徐萍; 王瑞刚

    2010-01-01

    介绍一个植物表达系统,由热激蛋白基因(AtHsp17.6-C2)的启动子来驱动GUS基因的表达.在22℃生长条件下,稳定遗传的转基因植株中几乎检测不到GUS的活性.但是当温度升至34~37℃时,GUS的活性迅速升高.37℃是该植物表达系统最适诱导温度.转基因植株经37℃热诱导2小时后再返回22℃培育2小时,GUS的活性增加80多倍.多次热诱导实验表明这个表达系统是能够被重复多次热诱导的.实验结果表明这个植物诱导表达系统能够适用于多种目的需要.

  12. X-ray crystallographic characterization of new soluble endohedral fullerenes utilizing the popular C82 bucky cage. Isolation and structural characterization of Sm@C3v(7)-C82, Sm@C(s)(6)-C82, and Sm@C2(5)-C82.

    Science.gov (United States)

    Yang, Hua; Jin, Hongxiao; Wang, Xinqing; Liu, Ziyang; Yu, Meilan; Zhao, Fukun; Mercado, Brandon Q; Olmstead, Marilyn M; Balch, Alan L

    2012-08-29

    Three isomers of Sm@C(82) that are soluble in organic solvents were obtained from the carbon soot produced by vaporization of hollow carbon rods doped with Sm(2)O(3)/graphite powder in an electric arc. These isomers were numbered as Sm@C(82)(I), Sm@C(82)(II), and Sm@C(82)(III) in order of their elution times from HPLC chromatography on a Buckyprep column with toluene as the eluent. The identities of isomers, Sm@C(82)(I) as Sm@C(s)(6)-C(82), Sm@C(82)(II) as Sm@C(3v)(7)-C(82), and Sm@C(82)(III) as Sm@C(2)(5)-C(82), were determined by single-crystal X-ray diffraction on cocrystals formed with Ni(octaethylporphyrin). For endohedral fullerenes like La@C(82), which have three electrons transferred to the cage to produce the M(3+)@(C(82))(3-) electronic distribution, generally only two soluble isomers (e.g., La@C(2v)(9)-C(82) (major) and La@C(s)(6)-C(82) (minor)) are observed. In contrast, with samarium, which generates the M(2+)@(C(82))(2-) electronic distribution, five soluble isomers of Sm@C(82) have been detected, three in this study, the other two in two related prior studies. The structures of the four Sm@C(82) isomers that are currently established are Sm@C(2)(5)-C(82), Sm@C(s)(6)-C(82), Sm@C(3v)(7)-C(82), and Sm@C(2v)(9)-C(82). All of these isomers obey the isolated pentagon rule (IPR) and are sequentially interconvertable through Stone-Wales transformations.

  13. Toxicology and carcinogenesis studies of 1-bromopropane (CAS No. 106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies).

    Science.gov (United States)

    2011-08-01

    In the early to mid 1990s, 1-bromopropane was used primarily as an intermediate in the production of pesticides, quaternary ammonium compounds, flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, closed processes. In the mid to late 1990s, it was introduced as a less toxic replacement for methylene chloride in emissive applications such as vapor and immersion degreasing operations and critical cleaning of electronics and metals. 1-Bromopropane was also introduced as a nonflammable, nontoxic, fast-drying, and inexpensive solvent for adhesive resins, and has been marketed as a replacement for ozone depleting refrigerants. 1-Bromopropane was nominated for study by the Occupational Safety and Health Administration based on the potential for widespread occupational and environmental exposure and a lack of toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1 mice were exposed to 1-bromopropane (99% or greater pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse peripheral blood. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 days. All rats survived to the end of the study except one 500 ppm male. Mean body weights of 2,000 ppm rats were significantly less than those of the chamber controls. The absolute kidney weight of 1,000 ppm males, relative kidney weights of all exposed groups of males, and absolute and relative kidney weights of all exposed groups of females were significantly increased. The absolute and relative liver weights of 1,000 ppm males, relative liver weights of 500 and 2,000 ppm males, and absolute and relative liver weights of 500 ppm or greater females were significantly increased. Nasal lesions included suppurative inflammation in

  14. Nqrs Data for C3H10INO6 [C3H7NO2·HIO3·(1/2)(H2O)] (Subst. No. 0642)

    Science.gov (United States)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C3H10INO6 [C3H7NO2·HIO3·(1/2)(H2O)] (Subst. No. 0642)

  15. Synthesis, crystal structure and thermal properties of Ca6(C12H14O4)4(CO3)(OH)2(H2O)x – a 3D inorganic hybrid material

    DEFF Research Database (Denmark)

    Nielsen, Renie Birkedal; Norby, Poul; Kongshaug, Kjell Ove

    2012-01-01

    of Ca6(C12H14O4)4(CO3)(OH)2(H2O)14 is tetragonal, space group I41/amd (141) with a = 29.12 Å, c = 15.85 Å, V = 13 440 Å3 and Z = 8. The compound is classified as a 3D inorganic hybrid material with a 3-dimensional inorganic framework consisting of Ca and O, connected to 1,3-adamantanedicarboxylate...

  16. A quadruple mutant of Arabidopsis reveals a β-carotene hydroxylation activity for LUT1/CYP97C1 and a regulatory role of xanthophylls on determination of the PSI/PSII ratio

    Directory of Open Access Journals (Sweden)

    Fiore Alessia

    2012-04-01

    Full Text Available Abstract Background Xanthophylls are oxygenated carotenoids playing an essential role as structural components of the photosynthetic apparatus. Xanthophylls contribute to the assembly and stability of light-harvesting complex, to light absorbance and to photoprotection. The first step in xanthophyll biosynthesis from α- and β-carotene is the hydroxylation of ε- and β-rings, performed by both non-heme iron oxygenases (CHY1, CHY2 and P450 cytochromes (LUT1/CYP97C1, LUT5/CYP97A3. The Arabidopsis triple chy1chy2lut5 mutant is almost completely depleted in β-xanthophylls. Results Here we report on the quadruple chy1chy2lut2lut5 mutant, additionally carrying the lut2 mutation (affecting lycopene ε-cyclase. This genotype lacks lutein and yet it shows a compensatory increase in β-xanthophylls with respect to chy1chy2lut5 mutant. Mutant plants show an even stronger photosensitivity than chy1chy2lut5, a complete lack of qE, the rapidly reversible component of non-photochemical quenching, and a peculiar organization of the pigment binding complexes into thylakoids. Biochemical analysis reveals that the chy1chy2lut2lut5 mutant is depleted in Lhcb subunits and is specifically affected in Photosystem I function, showing a deficiency in PSI-LHCI supercomplexes. Moreover, by analyzing a series of single, double, triple and quadruple Arabidopsis mutants in xanthophyll biosynthesis, we show a hitherto undescribed correlation between xanthophyll levels and the PSI-PSII ratio. The decrease in the xanthophyll/carotenoid ratio causes a proportional decrease in the LHCII and PSI core levels with respect to PSII. Conclusions The physiological and biochemical phenotype of the chy1chy2lut2lut5 mutant shows that (i LUT1/CYP97C1 protein reveals a major β-carotene hydroxylase activity in vivo when depleted in its preferred substrate α-carotene; (ii xanthophylls are needed for normal level of Photosystem I and LHCII accumulation.

  17. Age, introduction of solid feed and weaning are more important determinants of gut bacterial succession in piglets than breed and nursing mother as revealed by a reciprocal cross-fostering model.

    Science.gov (United States)

    Bian, Gaorui; Ma, Shouqing; Zhu, Zhigang; Su, Yong; Zoetendal, Erwin G; Mackie, Roderick; Liu, Junhua; Mu, Chunlong; Huang, Ruihua; Smidt, Hauke; Zhu, Weiyun

    2016-05-01

    A reciprocal cross-fostering model with an obese typical Chinese piglet breed and a lean Western breed was used to identify genetic and maternal effects on the acquisition and development gut bacteria from birth until after weaning. Pyrosequencing of 16S rRNA genes results revealed an age- and diet-dependent bacterial succession process in piglets. During the first 3 days after birth, the bacterial community was relatively simple and dominated by Firmicutes with 79% and 65% relative abundance for Meishan and Yorkshire piglets, respectively. During the suckling period until day 14, the piglet breed and the nursing mother lead to increasing differentiation of the fecal bacterial community, with specific bacteria taxa associated with breed, and others with the nursing sow most likely due to its milk composition. Although the effect of nursing mother and the breed were evident through the suckling period, the introduction of solid feed and subsequent weaning were the major events occurring that dominated succession of the gut microbiota in the early life of piglets. This piglet cross-fostering model is a useful tool for studying the effects of diet, host genetics and the environment on the development and acquisition of the gut microbiota and over longer studies the subsequent impact on growth, health and performance of pigs.

  18. Central-to-axial chirality transfer revealed by liquid crystals: a combined experimental and computational approach for the determination of absolute configuration of carboxylic acids with an α chirality centre.

    Science.gov (United States)

    Ferrarini, Alberta; Ferroni, Fiammetta; Pieraccini, Silvia; Rosini, Carlo; Superchi, Stefano; Spada, Gian Piero

    2011-10-01

    The conversion into 6,7-dihydro-5H-dibenz[c,e]azepine (DAZ) N-protected amides is a viable route for the determination of the absolute configuration of chiral 2-substituted carboxylic acids. The biphenyl moiety of DAZ, besides being a probe of chirality for the electronic circular dichroism (ECD) spectroscopy, makes these systems suitable for configuration assignment by exploiting the chirality amplification which occurs in nematic liquid crystals. To assess the reliability of the liquid crystal method in detecting the absolute stereochemistry of chiral amides bound to a biphenyl group, we measured the helical twisting power of a series of DAZ-N-protected amides and compared these data with the results obtained from ECD measurements. We will show that the liquid crystal method, corroborated by HTP predictions, is trustworthy with our biphenyl derivatives, even when ECD spectra are ambiguous for the presence of aryl moieties displaying strong UV absorptions in the same range of the biphenyl chromophore.

  19. Reactive organic air components (C{sub 6}-C{sub 12}) of anthropogenic and biogenic origin in deciduous and coniferous forests. Final report; Reaktive organische Luftkomponenten (C{sub 6}-C{sub 12}) anthropogenen und biogenen Ursprungs in Laub- und Nadelwaeldern. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Steinbrecher, R.; Fehsenfeld, U.; Hauff, K.; Jocher, M.; Kolb, C.; Reichmann, A.; Steinbrecher, J.; Tranos, S.; Wiedemann, M.

    1996-08-01

    -/Eichenwaeldern, Grasland und der mediterranen Garigue wurde das Emissions- und Depositionsverhalten von fluechtigen organischen Verbindungen (C{sub 6}-C{sub 12}; VOC) untersucht. Die Boden-, Stamm- und Zweigemissionen in einem Fichtenwald wurden mit Hilfe der Kuevettentechnik im Detail charakterisiert. Mit der Gradient- und REA-Technik wurden Bestandfluesse fuer VOC bestimmt. Waelder und die mediterrane Garigue stellen, im Gegensatz zu Grasland, bedeutende Quellen fuer VOC, ueberwiegend Monoterpene, dar. Waelder koennen zudem auch Senken fuer anthropogene VOC darstellen. In einem geschlossenen Fichtenbestand traegt der Boden nur unwesentlich zur Bestandemission an Monoterpenen bei. Der Beitrag des Stammraums kann zwischen 1 und 64% schwanken. In einem geschlossenen Fichtenbestand stellt die Sonnenkrone mit ca. 80% der Nadelflaeche den groessten Anteil der emissionsaktiven Flaeche. Fuer die Fichtenzweige der Sonnenkrone wurde ein Emissionsfaktor von 636 pmol {alpha}-Pinen m{sup -2} Gesamtnadelflaeche s{sup -1} (30 C Blattemperatur; PAR 1000 {mu}E) errechnet. Im Gegensatz zu bisheringen Annahmen, wird die {alpha}-Pinen-Emission von Fichtenzweigen, wie auch die Monoterpenemission von mediterranen Eichen, durch Licht und Temperatur kontrolliert. Die Ergebnisse dieser Arbeit flossen in neue biogene Emissionsinventuren auf europaeischer und globaler Ebene ein. (orig.)

  20. Liver tumors induced in B6C3F{sub 1} mice by benz[a]anthracene and two of its halogenated derivatives contain K-RAS oncogene mutations

    Energy Technology Data Exchange (ETDEWEB)

    Xia, O.; Yi, P.; Zhan, D. [and others

    1997-10-01

    Polycyclic aromatic hydrocarbons (PAHs) and halogenated PAHs are genotoxic environmental contaminants. We previously examined the tumorigenicity of benz[a]anthracene (BA), 7-Cl-BA, and 7-Br-BA in the neonatal mouse tumorigenicity bioassay. Male B6C3F{sub 1} mice were administered i.p. injections at a total dose of 400 nmol per mouse on 1, 8, and 15 days after birth. BA, 7-Cl-BA, and 7-Br-BA induced hepatocellular adenoma in 67, 92, and 96% of the mice, respectively, and induced hepatocellular carcinoma in 15, 100 and 83% of the mice, respectively. In the present study, mRNA was isolated from each of the liver tumors induced by the three compounds, reversed-transcribed to cDNA, and portions of the K- and H-ras oncogene coding sequences were amplified and analyzed for DNA sequence alterations. 92% (11/12) of BA-induced, 79% (19/24) of 7-Cl-BA-induced and 86% (19/22) of 7-Br-BA-induced liver tumors had activated ras protooncogenes. In contrast to the general finding of H-ras mutations in B6C3F{sub 1} mouse liver tumors, all the mutations were at the first base of K-ras codon 13, resulting in a pattern of GGC{yields}CGC. No other ras oncogene mutations were detected. Our results clearly demonstrate that these chemicals induce a unique type of ras (K-ras) oncogene activation in the liver tumors of B6C3F{sub 1} mice.

  1. Solvato-polymorph of [(η6-C6H6)RuCl (L)]PF6 (L = (2,6-dimethyl-phenyl-pyridin-2-yl methylene amine)

    Science.gov (United States)

    Gichumbi, Joel M.; Friedrich, Holger B.; Omondi, Bernard

    2016-06-01

    A half-sandwich complex salt of ruthenium containing the Schiff base ligand, 2, 6-dimethyl-N-(pyridin-2-ylmethylene)aniline has been synthesized and structurally characterized. The complex salt 1, [(η6-C6H6)RuCl(C5H4NCHdbnd N(2,6-(CH3)2C6H3)]PF6 was obtained from the reaction of the ruthenium arene precursor, [(η6- C6H6)Ru(μ-Cl)Cl]2 with the Schiff base in a 1:2 ratio followed by treatment with NH4PF6. Its acetone solvate 2, [(η6-C6H6)RuCl(C5H4NCHdbnd N (2, 6- (CH3)2C6H3)]PF6. (CH3)2CO was obtained by recrystallization of 1 from a solution of hexane and acetone. 1 and 2 crystallize in the monoclinic P21/c and P21/n space groups as blocks and as prisms respectively. The ruthenium centers in 1 and 2 are coordinated to the bidentate Schiff base, to a chloride atom, and to the arene ring to give a pseudo-octahedral geometry around them. The whole arrangement is referred to as the familiar three-legged piano stool in which the Schiff base and the Cl atom serve as the base while the arene ring serve as the apex of the stool. Polymorph 2 has an acetone molecule in the asymmetric unit. Of interest is the similar behavior of the solvate on heating which shows the crystals shuttering at about 531.6 and 523.4 K for 1 and 2 respectively.

  2. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids.

    Science.gov (United States)

    Maes, M; Smith, R; Christophe, A; Cosyns, P; Desnyder, R; Meltzer, H

    1996-04-26

    Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

  3. Point mutations of K-ras and H-ras genes in forestomach neoplasms from control B6C3F1 mice and following exposure to 1,3-butadiene, isoprene or chloroprene for up to 2-years.

    Science.gov (United States)

    Sills, R C; Hong, H L; Boorman, G A; Devereux, T R; Melnick, R L

    2001-06-01

    1,3 Butadiene (BD), isoprene (IP) and chloroprene (CP) are structural analogs. There were significantly increased incidences of forestomach neoplasms in B6C3F1 mice exposed to BD, IP or CP by inhalation for up to 2-years. The present study was designed to characterize genetic alterations in K- and H-ras proto-oncogenes in a total of 52 spontaneous and chemically induced forestomach neoplasms. ras mutations were identified by restriction fragment length polymorphism, single strand conformational polymorphism analysis, and cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded forestomach neoplasms. A higher frequency of K- and H-ras mutations was identified in BD-, IP- and CP-induced forestomach neoplasms (83, 70 and 57%, respectively, or combined 31/41, 76%) when compared to spontaneous forestomach neoplasms (4/11, 36%). Also a high frequency of H-ras codon 61 CAA-->CTA transversions (10/41, 24%) was detected in chemically induced forestomach neoplasms, but none were present in the spontaneous forestomach neoplasms examined. Furthermore, an increased frequency (treated 13/41, 32% versus untreated 1/11, 9%) of GGC-->CGC transversion at K-ras codon 13 was seen in BD-, and IP-induced forestomach neoplasms, similar to the predominant K-ras mutation pattern observed in BD-induced mouse lung neoplasms. These data suggest that the epoxide intermediates of the structurally related chemicals (BD, IP, and CP) may cause DNA damage in K-ras and H-ras proto-oncogenes of B6C3F1 mice following inhalation exposure and that mutational activation of these genes may be critical events in the pathogenesis of forestomach neoplasms induced in the B6C3F1 mouse.

  4. C_(12)C_6C_(12)Br_2/C_(12)E_(10)混合表面活性剂与DNA之间的相互作用%Interaction between Mixed C_(12)C_6C_(12)Br_2/C_(12)E_(10) Surfactant System and DNA

    Institute of Scientific and Technical Information of China (English)

    王瑜; 曹以诚; 韩玉淳

    2011-01-01

    本文以构建有效的非病毒基因载体为目的,研究了C12C6C12Br2/C12E10混合表面活性剂组成对其与DNA之间相互作用的影响,并对混合表面活性剂与DNA形成的聚集体结构和形貌进行了表征。结果表明,当固定混合表面活性剂的总浓度为1.0 mmol/L时,混合表面活性剂组成的改变会引起混合体系浊度、聚集体表面电荷和聚集体形貌发生变化。当C12E10的摩尔分数(X(C12E10))较低时,混合表面活性剂以带有正电荷并具有两条疏水链的C12C6C12Br2为主,其与DNA分子能发生很强的静电吸引作用和疏水相互作用,使DNA分子发生凝聚;随着X(C12E10)的提高,混合表面活性剂中C12C6C12Br2减少,导致混合表面活性剂与DNA之间的静电吸引作用和疏水相互作用减弱,并由于C12E10头基上EO链的空间位阻作用,使得DNA分子的"球状"凝聚体松散成为较大的"类网状"聚集体,最后呈"无规则自由卷曲"状态。%To develop an effective non-viral gene delivery system,the interaction between the mixed cationic/nonionic surfactant system(C12C6C12Br2/C12E10) and DNA was studied.The effect of the composition of mixed surfactants on the interaction of C12C6C12Br2/C12E10 with DNA was investigated,and the structure and morphology of complex formed by the mixed surfactants and DNA were characterized.The results showed that the properties of C12C6C12Br2/C12E10-DNA complexes including turbidity,surface charge,and morphologies depend on the molar fraction of C12E10(X(C12E10)).At lower X(C12E10),the cationic Gemini surfactant C12C6C12Br2 with bi-charged hydrophilic headgroups and twin hydrophobic chains is the dominant.C12C6C12Br2 can strongly interact with DNA by both electrostatic and hydrophobic interactions,thus the DNA molecules are condensed to "globule" structures.As increasing of the X(C12E10),the ratio of C12C6C12Br2 in the mixed surfactant composition is reduced so that

  5. Heat reveals faults

    Energy Technology Data Exchange (ETDEWEB)

    Weinreich, Bernhard [Solarschmiede GmbH, Muenchen (Germany). Engineering Dept.

    2010-07-01

    Gremlins cannot hide from the all-revealing view of a thermographic camera, whereby it makes no difference whether it is a roof-mounted system or a megawatt-sized farm. Just as diverse are the range of faults that, with the growing level of expertise, can now be detected and differentiated with even greater detail. (orig.)

  6. Toxicity and Carcinogenicity of Ozone in Combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and Dibutyl Phthalate in B6C3F1 Mice for 16 and 32 Weeks

    Institute of Scientific and Technical Information of China (English)

    MIN YOUNG KIM; M YUNG CHO

    2009-01-01

    Objective To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyddyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP). Methods Male and female B6C3F1 mice were exposed,through inhalation,intravenous administration and diet,to 0.5 ppm of ozone,1.0 mg/kg of NNK and 5000 ppm of DBP,individually and in combination for 16 and 32 weeks. Results No treatment-related death was seen,but significant differences in body and organ weights between control and treated mice were observed during the study.No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment.Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks. Conclusion Although ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions,they induce oviductal carcinomas in B6C3F1 mice.

  7. DOE 5700.6C, 10CFR830.120, DOE-ER-STD-6001-92, and Covey-based TQM: A historical perspective on current issues in research environments

    Energy Technology Data Exchange (ETDEWEB)

    Bodnarczuk, M

    1994-06-01

    Three years ago there were no standards or published guidelines for quality in research environments. Today, one standard has been published, and three guidelines documents are in final draft form and about to be published. In this paper, I describe the events that led to the writing of DOE 5700.6C, 10CFR830.120, and DOE-ER-STD-6001-92, focusing on the cultural barriers that arose (largely in the community of quality assurance professionals) during this process. I go on to describe why I believe that implementing DOE 5700.6C and 10CFR830.120 must be pushed even further toward an approach that embodies the Malcolm Baldrige National Quality Award and why even this is not far enough. The reason is because the most crucial aspect of successfully implementing a quality initiative is to base it on a cohesive, unified foundation of organizational and individual values and beliefs. Stephen Covey`s 7 Habits of Highly Effective People and Principle Centered Leadership provide such a foundations.

  8. DOE 5700.6C, 10CFR830.120, DOE-ER-STD-6001-92, and Covey-based TQM: A historical perspective on current issues in research environments

    Energy Technology Data Exchange (ETDEWEB)

    Bodnarczuk, M

    1994-06-01

    Three years ago there were no standards or published guidelines for quality in research environments. Today, one standard has been published, and three guidelines documents are in final draft form and about to be published. In this paper, I describe the events that led to the writing of DOE 5700.6C, 10CFR830.120, and DOE-ER-STD-6001-92, focusing on the cultural barriers that arose (largely in the community of quality assurance professionals) during this process. I go on to describe why I believe that implementing DOE 5700.6C and 10CFR830.120 must be pushed even further toward an approach that embodies the Malcolm Baldrige National Quality Award and why even this is not far enough. The reason is because the most crucial aspect of successfully implementing a quality initiative is to base it on a cohesive, unified foundation of organizational and individual values and beliefs. Stephen Covey`s 7 Habits of Highly Effective People and Principle Centered Leadership provide such a foundations.

  9. Comparison of Acoustic Radiation Force Impulse (ARFI) Elastography Measurements with the 4C1 Transducer to the 6C1HD Transducer: A Phantom and Patient Study.

    Science.gov (United States)

    Pfeifer, L; Goertz, R S; Neurath, M F; Strobel, D; Wildner, D

    2016-10-01

    Purpose: The aim of this study was to evaluate whether acoustic radiation force impulse (ARFI) elastography done with the 4C1 probe yields comparable results to the recently introduced 6C1HD probe. Materials and Methods: Measurements with the 4C1 and 6C1HD probes (Acuson S2000) were performed and compared in four different inclusions of an elasticity phantom model (QA049 CIRS) as well as in the liver of healthy individuals and patients with liver cirrhosis. Results: Measurements with the 6C1HD probe were slightly higher in all phantom inclusions (8, 14, 45, 80kPA) with a mean of 1.48 m/s (95 %-CI; 1.47 - 1.49), 2.18 m/s (95 %-CI; 2.17 - 2.19), 3.61 m/s (95 %-CI; 3.57 - 3.64) and 4.34 m/s (95 %-CI; 4.29 - 4.39) compared to the 4C1 transducer with 1.46 m/s (95 %-CI; 1.45 - 1.47), 2.15 m/s (95 %-CI; 2.14 - 2.16), 3.39 m/s (95 %-CI; 3.37 - 3.41) and 3.98 m/s (95 %-CI; 3.75 - 4.21), respectively (p = 0.04, p transducer compared to 2.81 m/s (95 %-CI; 2.64 - 2.99) with the 4C1 transducer (p = 0.03). Healthy individuals (n = 20) had a mean shear wave speed of 1.12 m/s (95 %-CI; 1.06 - 1.17) with the 6C1HD probe and 1.12 m/s (95 %-CI; 1.05 - 1.19) with the 4C1 probe (p = 0.96). Conclusion: ARFI values assessed with a 6C1HD transducer are slightly higher than measurements with a 4C1 transducer in an ARFI phantom and in patients with liver cirrhosis. As the difference is small, current cut-off values keep their usefulness but should be interpreted with caution if measurements are close to the cut-off. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Spatial interactions determine temporal feature integration as revealed by unmasking

    Directory of Open Access Journals (Sweden)

    Michael H. Herzog

    2006-01-01

    Full Text Available Feature integration is one of the most fundamental problems in neuroscience. In a recent contribution, we showed that a trailing grating can diminish the masking effects one vernier exerts on another, preceding vernier. Here, we show that this temporal unmasking depends on neural spatial interactions related to the trailing grating. Hence, our paradigm allows us to study the spatio-temporal interactions underlying feature integration.

  11. NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice.

    Science.gov (United States)

    Hebert, Charles

    1993-07-01

    Cupric sulfate is an inorganic salt which is widely used in industry, agriculture, and veterinary medicine. Its applications include use as an algicide in potable waters and as a feed additive and therapeutic agent in swine, sheep, and cattle. Because copper salts are found in human water supplies, toxicity studies of cupric sulfate pentahydrate were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed routes (2-week and 13-week studies). Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation, and histopathology. In the 2-week drinking water studies, groups of five rats and five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm for 15 days. One female rat, one male mouse, and three female mice in the 3000 ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before the end of the studies. The remaining mice and rats in the 3000 ppm groups gained little or lost weight. Water consumption in the three highest dose groups of both species was reduced by more than 65%. Clinical signs observed in these groups were typical of those seen in moribund animals and were attributed to dehydration. The only gross or microscopic change specifically related to cupric sulfate toxicity was an increase in the size and number of cytoplasmic protein droplets in the epithelium of the renal proximal convoluted tubule in male rats from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric sulfate. No chemical-related deaths occurred in any dose group. Compared to the controls, rats and mice in the two highest dose groups had reduced body weight gains which were attributed to decreased feed consumption. Hyperplasia with hyperkeratosis of the squamous epithelium on the limiting ridge of the forestomach was seen in rats and

  12. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  13. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because the textb......One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...... process for which process recordings are a valuable communication media in order to enhance the learning process. Student feedback indicates both high learning outcome and superior learning potential compared to traditional classroom teaching....

  14. Phase coexistence in NaZn{sub 13}-type LaFe{sub 11.4}Al{sub 1.6}C{sub 0.02} compound

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jing [State Key Laboratory of Magnetism, Institute of Physics and Centre for Condensed Matter Physics, Chinese Academy of Sciences, Beijing 100190 (China); Department of Applied Physics, Wuhan University of Science and Technology, Wuhan 430065 (China); Dong Qiaoyan [State Key Laboratory of Magnetism, Institute of Physics and Centre for Condensed Matter Physics, Chinese Academy of Sciences, Beijing 100190 (China); Zhang Hongwei [State Key Laboratory of Magnetism, Institute of Physics and Centre for Condensed Matter Physics, Chinese Academy of Sciences, Beijing 100190 (China)], E-mail: hwzhang@aphy.iphy.ac.cn; Zhang Ligang [Department of Applied Physics, Wuhan University of Science and Technology, Wuhan 430065 (China); Sun Jirong; Shen Baogen [State Key Laboratory of Magnetism, Institute of Physics and Centre for Condensed Matter Physics, Chinese Academy of Sciences, Beijing 100190 (China)

    2009-10-15

    In NaZn{sub 13}-type LaFe{sub 11.4}Al{sub 1.6}C{sub 0.02} compound, a signature of weak ferromagnetism is observed at {approx}100 K under a low field by ac magnetic-susceptibility and electrical-resistivity measurements, implying the coexistence of ferromagnetic (FM) and antiferromagnetic (AFM) phases. The hysteresis in isofield magnetization curves and large magnetic relaxation demonstrate the metastability of the magnetic state in the AFM-FM transition region. The variations of magnetization with temperature, time and field show distinct step-like behaviors, which is probably attributed to the discontinuous growth of ferromagnetic cluster in antiferromagnetic matrix.

  15. Sm(eta/sup 6/-C/sub 6/Me/sub 6/)(eta/sup 2/-AlCl/sub 4/)/sub 3/: the first structure of a rare earth complex with a neutral. pi. -ligand

    Energy Technology Data Exchange (ETDEWEB)

    Cotton, F.A.; Schwotzer, W.

    1986-07-23

    The authors and others have demonstrated before that one of these intercalators, UCl/sub 4/, can undergo arylation reactions to yield eta/sup 6/-arene complexes and they have structurally characterized such compounds of U(IV) and U(III). In light of the fact that U arene complexes are the only examples of neutral ..pi..-ligands bonded to f-elements, they were wondering whether uranium constitutes a special case and whether an f-orbital contribution was instrumental in the bonding. It was therefore tempting to challenge this synthetic approach with lanthanide metals for which there is no structurally characterized complex with neutral ..pi..-ligands on record. They have chosen a known intercalator of graphite and wish to report here on the first arene complex of a rare earth element, Sm(eta/sup 6/-C/sub 6/Me/sub 6/)(AlCl/sub 4/)/sub 3/-1.5 toluene.

  16. Comparison of the effects of hexavalent chromium in the alimentary canal of F344 rats and B6C3F1 mice following exposure in drinking water: implications for carcinogenic modes of action.

    Science.gov (United States)

    Thompson, Chad M; Proctor, Deborah M; Suh, Mina; Haws, Laurie C; Hébert, Charles D; Mann, Jill F; Shertzer, Howard G; Hixon, J Gregory; Harris, Mark A

    2012-01-01

    Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1-182 mg/l Cr(VI), administered as 0.3-520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well.

  17. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...

  18. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...

  19. NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide (CAS No. 1303-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    2000-09-01

    Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 &mgr;m) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium

  20. Ground-based solar absorption measurements of CH{sub 4}, CO, C{sub 2}H{sub 6}, C2H2 and HCN in the tropics

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Anna K.; Warneke, Thorsten; Velasco, Voltaire; Notholt, Justus [Institute of Environmental Physics (IUP), University of Bremen (Germany); Schrems, Otto [Alfred Wegener Institute for Polar and Marine Research (AWI), Bremerhaven (Germany)

    2007-07-01

    The composition of the tropical atmosphere and its change is of significant importance for global climate. Currently large uncertainties in the budgets of many trace gases in the tropics exist, mainly due to a lack of measurements in the tropics. We have performed solar absorption Fourier Transform InfraRed measurements at Paramaribo, Suriname (5.83 N, 55.17 W) during four consecutive dry seasons, starting in autumn 2004. Currently these are the only remote sensing measurements performed in the inner-tropics over a longer time period. In the case of methane these measurements represent the only tropical ground-based remote sensing data of sufficient precision to validate satellite retrievals of CH4. Here we present first results on methane (CH{sub 4}) and trace gases related to biomass burning. Methane retrievals are compared with model simulations, satellite retrievals from SCIAMACHY and in situ data. In addition we investigate the pollution from biomass burning using CO, C{sub 2}H{sub 6}, C{sub 2}H{sub 2} and HCN. Backwardtrajectories and global fire maps were used to identify the origin of the polluted air masses. Correlations between the different gases are analysed and compared to literature data.

  1. Crystal growth and characterization of gadolinium tartrate trihydrate: Gd(C{sub 4}H{sub 4}O{sub 6})(C{sub 4}H{sub 5}O{sub 6}).3H{sub 2}O

    Energy Technology Data Exchange (ETDEWEB)

    Want, Basharat [Department of Physics, University of Kashmir, Srinagar 190006, J and K (India); Ahmad, Farooq [Department of Physics, University of Kashmir, Srinagar 190006, J and K (India); Kotru, P.N. [Department of Physics and Electronics, University of Jammu, Jammu 180006 (India)]. E-mail: pn_kotru@yahoo.com

    2006-09-15

    The growth of gadolinium tartrate trihydrate crystals is achieved in silica and agar-agar gels. The crystals are grown by diffusion of gadolinium ions through silica and agar-agar gels impregnated with L-tartaric acid. The type of medium influences the morphology of grown crystals: silica gel yielding single crystals and spherulites whereas agar-agar gel leads to growth of only single crystals. The grown crystals are characterized using energy dispersive analysis of X-rays (EDAX), carbon and hydrogen analysis (CHN), X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric (TG), differential thermogravimetric (DTG) and differential thermal analysis. The chemical formula of the grown crystals is suggested to be Gd(C{sub 4}H{sub 4}O{sub 6})(C{sub 4}H{sub 5}O{sub 6}).3H{sub 2}O. The infrared spectrum indicates the presence of tartrate ligands and suggests that one of the tartrate ions is singly ionized. The thermal analysis shows that the material is thermally stable up to about 205 deg. C.

  2. Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

    Science.gov (United States)

    Rose, C S; King, A A; Summers, D; Palmer, R; Yang, S; Wilkie, A O; Reardon, W; Malcolm, S; Winter, R M

    1994-08-01

    Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

  3. Gene expression analysis of livers from female B6C3F1 mice exposed to carcinogenic and non-carcinogenic doses of furan, with or without bromodeoxyuridine (BrdU treatment

    Directory of Open Access Journals (Sweden)

    Anna Francina Webster

    2014-12-01

    Full Text Available Standard methodology for identifying chemical carcinogens is both time-consuming and resource intensive. Researchers are actively investigating how new technologies can be used to identify chemical carcinogens in a more rapid and cost-effective manner. Here we performed a toxicogenomic case study of the liver carcinogen furan. Full study and mode of action details were previously published in the Journal of Toxicology and Applied Pharmacology. Female B6C3F1 mice were sub-chronically treated with two non-carcinogenic (1 and 2 mg/kg bw and two carcinogenic (4 and 8 mg/kg bw doses of furan for 21 days. Half of the mice in each dose group were also treated with 0.02% bromodeoxyuridine (BrdU for five days prior to sacrifice [13]. Agilent gene expression microarrays were used to measure changes in liver gene and long non-coding RNA expression (published in Toxicological Sciences. Here we describe the experimental and quality control details for the microarray data. We also provide the R code used to analyze the raw data files, produce fold change and false discovery rate (FDR adjusted p values for each gene, and construct hierarchical clustering between datasets.

  4. Gene expression analysis of livers from female B6C3F1 mice exposed to carcinogenic and non-carcinogenic doses of furan, with or without bromodeoxyuridine (BrdU) treatment.

    Science.gov (United States)

    Webster, Anna Francina; Williams, Andrew; Recio, Leslie; Yauk, Carole L

    2014-12-01

    Standard methodology for identifying chemical carcinogens is both time-consuming and resource intensive. Researchers are actively investigating how new technologies can be used to identify chemical carcinogens in a more rapid and cost-effective manner. Here we performed a toxicogenomic case study of the liver carcinogen furan. Full study and mode of action details were previously published in the Journal of Toxicology and Applied Pharmacology. Female B6C3F1 mice were sub-chronically treated with two non-carcinogenic (1 and 2 mg/kg bw) and two carcinogenic (4 and 8 mg/kg bw) doses of furan for 21 days. Half of the mice in each dose group were also treated with 0.02% bromodeoxyuridine (BrdU) for five days prior to sacrifice [13]. Agilent gene expression microarrays were used to measure changes in liver gene and long non-coding RNA expression (published in Toxicological Sciences). Here we describe the experimental and quality control details for the microarray data. We also provide the R code used to analyze the raw data files, produce fold change and false discovery rate (FDR) adjusted p values for each gene, and construct hierarchical clustering between datasets.

  5. Ntp technical report on toxicity, reproductive, and developmental studies of 60-Hz magnetic fields, administered by whole body exposure to F344/N rats, Sprague-Dawley rats, and B6C3F1 mice. Toxicity report series

    Energy Technology Data Exchange (ETDEWEB)

    Boorman, G.A.

    1996-09-01

    Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz) and generally of low intensity. The prevailing view among physicists is that exposure to these low-frequency, low-intensity fields does not pose a health hazard. However, this view has been challenged by reports linking magnetic field exposure to the development of leukemia and other cancers. Because multiple epidemiologic studies suggested a potential for increased cancer rates with increasing exposure, and because of public concern, the effects of 60-Hz magnetic field exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body-exposure studies. Animals were evaluated for hematology and clinical chemistry (rats only) parameters, pineal gland hormone concentrations, and histopathology. Additional studies were performed in Sprague-Dawley rats to examine teratologic and reproductive effects of magnetic field exposure.

  6. Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (gorlin) syndrome and fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Farndon, P.A.; Hardy, C.; Kilpatrick, M.W. [Birmingham Maternity Hospital, Edgbaston (United Kingdom)] [and others

    1994-09-15

    Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S12/D9S151) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map. 19 refs., 2 figs., 1 tab.

  7. A New Rerouting Technique for the Extensor Pollicis Longus in Palliative Treatment for Wrist and Finger Extension Paralysis Resulting From Radial Nerve and C5C6C7 Root Injury.

    Science.gov (United States)

    Laravine, Jennifer; Cambon-Binder, Adeline; Belkheyar, Zoubir

    2016-03-01

    Wrist and finger extension paralysis is a consequence of an injury to the radial nerve or the C5C6C7 roots. Despite these 2 different levels of lesions, palliative treatment for this type of paralysis depends on the same tendon transfers. A large majority of the patients are able to compensate for a deficiency of the extension of the wrist and fingers. However, a deficiency in the opening of the first web space, which could be responsible for transfers to the abductor pollicis longus, the extensor pollicis brevis, and the extensor pollicis longus (EPL), frequently exists. The aim of this work was to evaluate the feasibility of a new EPL rerouting technique outside of Lister's tubercle. Another aim was to verify whether this technique allows a better opening of the thumb-index pinch in this type of paralysis. In the first part, we performed an anatomic study comparing the EPL rerouting technique and the frequently used technique for wrist and finger extension paralyses. In the second part, we present 2 clinical cases in which this new technique will be practiced. Preliminary results during this study favor the EPL rerouting technique. This is a simple and reproducible technique that allows for good opening of the first web space in the treatment of wrist and finger extension paralysis.

  8. Puerto Rico Revealed Preference data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

  9. Revealing the Beast Within

    Science.gov (United States)

    2003-07-01

    Deeply Embedded Massive Stellar Clusters Discovered in Milky Way Powerhouse Summary Peering into a giant molecular cloud in the Milky Way galaxy - known as W49 - astronomers from the European Southern Observatory (ESO) have discovered a whole new population of very massive newborn stars . This research is being presented today at the International Astronomical Union's 25th General Assembly held in Sydney, Australia, by ESO-scientist João Alves. With the help of infrared images obtained during a period of excellent observing conditions with the ESO 3.5-m New Technology Telescope (NTT) at the La Silla Observatory (Chile), the astronomers looked deep into this molecular cloud and discovered four massive stellar clusters, with hot and energetic stars as massive as 120 solar masses. The exceedingly strong radiation from the stars in the largest of these clusters is "powering" a 20 light-year diameter region of mostly ionized hydrogen gas (a "giant HII region"). W49 is one of the most energetic regions of star formation in the Milky Way. With the present discovery, the true sources of the enormous energy have now been revealed for the first time, finally bringing to an end some decades of astronomical speculations and hypotheses. PR Photo 21a/03 : Colour Composite of W49A (NTT+SOFI). PR Photo 21b/03 : Radio and Near-Infrared Composite of W49A Giant molecular clouds Stars form predominantly inside Giant Molecular Clouds which populate our Galaxy, the Milky Way. One of the most prominent of these is W49 , which has a mass of a million solar masses. It is located some 37,000 light-years away and is the most luminous star-forming region known in our home galaxy: its luminosity is several million times the luminosity of our Sun. A smaller region within this cloud is denoted W49A - this is one of the strongest radio-emitting areas known in the Galaxy . Massive stars are excessive in all ways. Compared to their smaller and ligther brethren, they form at an Olympic speed and

  10. NTP technical report on the toxicity studies of Castor Oil (CAS No. 8001-79-4) in F344/N Rats and B6C3F1 Mice (Dosed Feed Studies).

    Science.gov (United States)

    Irwin, R

    1992-03-01

    Castor oil is a natural oil derived from the seeds of the castor bean, Ricinus communis. It is comprised largely of triglycerides with a high ricinolin content. Toxicity studies with castor oil were performed by incorporating the material at concentrations as high as 10% in diets given to F344/N rats and B6C3F1 mice of both sexes for 13 weeks. Genetic toxicity studies also were performed and were negative for mutation induction in Salmonella typhimurium, for induction of sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells, and for induction of micronuclei in the peripheral blood erythrocytes of mice evaluated at the end of the 13-week studies. Exposure to castor oil at dietary concentrations as high as 10% in 13-week studies did not affect survival or body weight gains of rats or mice (10 per sex and dose). There were no biologically significant effects noted in hematologic analyses in rats. Mild increases in total bile acids and in serum alkaline phosphatase were noted at various times during the studies in rats receiving the higher dietary concentrations of castor oil. Liver weights were increased in male rats receiving the 10% dietary concentration and in male and female mice receiving diets containing 5% or 10% castor oil. However, there were no histopathologic lesions associated with these liver changes, nor were there any compound-related morphologic changes in any organ in rats or mice. No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of estrous cycles of rats or mice given diets containing castor oil. Thus, no significant adverse effects of castor oil administration were noted in these studies. Synonyms: Ricinus Oil, oil of Palma Christi, tangantangan oil, phorboyl, Neoloid.

  11. Hepatocarcinogenic potential of the glucocorticoid antagonist RU486 in B6C3F1 mice: effect on apoptosis, expression of oncogenes and the tumor suppressor gene p53

    Directory of Open Access Journals (Sweden)

    Badr Mostafa Z

    2003-01-01

    Full Text Available Abstract Background Glucocorticoids inhibit hepatocellular proliferation and modulate the expression of oncogenes and tumor suppressor genes via mechanisms involving the glucocorticoid receptor. Glucocorticoids also produce a receptor-mediated inhibitory effect on both basal and hormone-stimulated expression of a newly discovered family of molecules important for shutting off cytokine action. We therefore hypothesized that inhibiting glucocorticoid receptors may disturb hepatocellular growth and apoptosis. Consequently, we investigated the effect of RU486, a potent antagonist of the glucocorticoid receptor, on basal levels of hepatocellular proliferation and apoptosis in male B6C3F1 mice. Furthermore, we evaluated the effect of this compound on cellular genes involved in the regulation of these important processes. Results Data show that treatment of male B6F3C1 mice with RU486 (2 mg/kg/d, ip for 7 days dramatically inhibited liver cell proliferation by about 45% and programmed hepatocellular death by approximately 66%. RU 486 also significantly increased hepatic expression of the oncogenes mdm2 and JunB, while reducing that of the tumor suppressor gene p53. Conclusion Exposure to RU486 may ultimately enhance the susceptibility of the liver to cancer risk by diminishing its ability to purge itself of pre-cancerous cells via apoptosis. This effect may be mediated through increases in the hepatic expression of the oncogene mdm2, coupled with decreases in that of the tumor suppressor gene p53. The decrease in hepatocellular proliferation caused by RU 486 may be related to effects other than its anti-glucocorticoid activity.

  12. Lemon (Citrus limon, Burm.f.) essential oil enhances the trans-epidermal release of lipid-(A, E) and water-(B6, C) soluble vitamins from topical emulsions in reconstructed human epidermis.

    Science.gov (United States)

    Valgimigli, L; Gabbanini, S; Berlini, E; Lucchi, E; Beltramini, C; Bertarelli, Y L

    2012-08-01

    Topical bioavailability of lipid- and water-soluble vitamins is a critical issue for protecting or anti-ageing formulations. Using 17-day-old SkinEthic(®) reconstructed human epidermis, we investigated (at 34°C) the role of lemon EO in enhancing the penetration of α-tocopherol (E) and retinyl acetate (A), pyridoxine (B(6)) and ascorbic acid (C), released from O/W or W/O emulsions. D-limonene, α-pinene and p-cymene (65.9, 2.2 and 0.5%w/w of the oil) had skin permeability coefficients Ps (10(-3) cm h(-1)) of 0.56 ± 0.03 (or 0.73 ± 0.02), 0.72 ± 0.05 (or 0.98 ± 0.05) and 0.84 ± 0.04 (or 1.14 ± 0.04), respectively, when incorporated in a W/O (or O/W) emulsion. Vitamins B6, C and A had Ps values of (3.0 ± 0.4) × 10(-3), (7.9 ± 0.6) × 10(-3) and (0.37 ± 0.02) × 10(-5) cm h(-1), respectively, and their flux through the skin was enhanced by a factor of 4.1, 3.4 and 5.8, respectively, in the presence of lemon EO. The penetration of vitamin E was nine-fold enhanced. Lemon EO produced only reversible modification of TEWL, and it is a safe and effective penetration enhancer for topical administration of lipid- and water-soluble vitamins.

  13. Implementation guide for use with suspect/counterfeit items: Requirements of DOE O 440.1, worker protection management; 10 CFR 830.120; and DOE 5700.6C, quality assurance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    Department of Energy (DOE) Order (O) 440.1, Worker Protection Management For DOE Federal and Contractors Employees, [7] sets forth requirements for DOE and its contractors to implement suspect and counterfeit items (S/CI) controls as part of the quality assurance (QA) programs required by 10 Code of Federal Regulations (CFR) 830.120 [8] or DOE 5700.6C, Quality Assurance [9]. DOE G-830.120, Implementation Guide for Use with 10 CFR Part 830.120, Quality Assurance, [10] provides additional guidance on establishing and implementing effective QA processes to control S/CIs. DOE O 232.1, Occurrence Reporting and Processing of Operations, [11] specifies requirements for reporting S/CIs under the DOE Occurrence Reporting and Processing System (ORPS). DOE promulgated the requirements and guidance to control or eliminate the hazards posed by S/CIs, which can lead to unexpected equipment failures and undue risks to the DOE mission, the environment, and personnel. This Guide is a compendium of information contained in the referenced DOE directives and other documents concerning S/CI controls. It incorporates, updates, and supersedes earlier guidance issued in Plan for the Suspect/Counterfeit Products Issue in the Department of Energy, dated October 1993, [4] and in memoranda issued by Defense Programs (DP) [12-16] and other DOE program offices. This guidance was developed to strengthen the procurement process, identify and eliminate S/CIs, and improve the reporting of S/CIs. The information in this Guide, when implemented by DOE and its contractors, will satisfy the S/CI requirements contained in the referenced DOE directives.

  14. Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

    Science.gov (United States)

    2012-07-01

    Acrylamide, a water-soluble α,β-unsaturated amide, is a contaminant in baked and fried starchy foods, including french fries, potato chips, and bread, as a result of Maillard reactions involving asparagine and reducing sugars. Additional sources of acrylamide exposure include cigarettes, laboratory procedures involving polyacrylamide gels, and various occupations (e.g, monomer production and polymerization processes). Acrylamide is carcinogenic in experimental animals. To obtain data for developing quantitative risk assessments for dietary exposures to acrylamide, the Food and Drug Administration nominated acrylamide for an in-depth toxicological evaluation by the National Toxicology Program. As part of this evaluation, male and female B6C3F1/Nctr (C57BL/6N x C3H/HeN MTV-) mice and male and female F344/N Nctr rats were exposed to acrylamide (at least 99.4% pure) in drinking water for 2 years. 2-WEEK STUDY IN RATS: Groups of four male and four female F344/N rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. One male rat administered 7.03 mM acrylamide in the drinking water died on day 14. Male and female rats receiving 7.03 mM acrylamide weighed 56% and 64% of controls, respectively. Male and female rats fed 370 mg acrylamide per kg diet weighed 74% and 83% of controls, respectively. Female rats receiving 3.52 mM acrylamide in drinking water and male rats fed 185 mg acrylamide per kg diet weighed 85% and 89% of controls, respectively. Rats receiving 7.03 mM acrylamide in drinking water or 370 mg acrylamide per kg diet exhibited hind-leg paralysis on day 14. Mild to moderate dilatation of the urinary bladder was observed in all rats given 370 mg acrylamide per kg diet, and in three of four male rats and all four female rats given 7.03 mM acrylamide in drinking water, and in one of four male

  15. NTP Toxicology and Carcinogenesis Studies of d-Limonene (CAS No. 5989-27-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1990-01-01

    Toxicology and carcinogenesis studies of d-limonene, a naturally occurring monoterpene found in many volatile oils, especially in citrus oils, were conducted because of its widespread use as a flavor and fragrance additive for food and household cleaning products and its increasing use as an industrial solvent. The d-limonene used in these studies was more than 99% pure and was administered in corn oil by gavage. Short-term studies were conducted in F344/N rats and B6C3F1 mice to identify toxic effects and affected sites and to help establish doses for the 2-year studies. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse L5178Y cells, and Chinese hamster ovary (CHO) cells. The doses selected for the 16-day studies ranged from 413 to 6,600 mg/kg for both rats and mice; deaths and reduction in body weight gain occurred at the two highest doses. No compound-related clinical signs or histopathologic lesions were observed in any of the surviving dose groups. In the 13-week studies, doses of d-limonene ranged from 150 to 2,400 mg/kg for rats and from 125 to 2,000 mg/kg for mice. Deaths occurred in the high dose group of each species and sex. Greater than 10% reductions in body weight gain were observed in the two highest dose groups of male rats and male mice and the high dose female rats. Rough hair coats and decreased activity were observed at the two highest doses in both rats and mice. There were no chemical-related histopathologic lesions in female rats or in mice of either sex. A compound-related increased severity of nephropathy was observed in the kidney of male rats. This lesion was characterized by degeneration of epithelial cells in the convoluted tubules, granular casts in the outer stripe of the outer medulla, and epithelial regeneration. These lesions have been described as reasonably characteristic of the hyaline droplet nephropathy that is associated with an accumulation of liver-generated a2u-globulin in the cytoplasm of tubular

  16. NTP Toxicology and Carcinogenesis Studies of Lauric Acid Diethanolamine Condensate (CAS NO. 120-40-1) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Lauric acid diethanolamine condensate is widely used in cosmetics, shampoos, soaps, and related consumer products, to which there is extensive human exposure. Because of the lack of information about potential risks associated with long-term exposure, lauric acid diethanolamine condensate, coconut oil acid diethanolamine condensate, and oleic acid diethanolamine condensate were selected as representative of the class of diethanolamides for evaluation of prechronic toxicity and carcinogenic potential. Male and female F344/N rats and B6C3F1 mice were exposed to lauric acid diethanolamine condensate dermally for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until study termination. Final mean body weights and body weight gains of males receiving 200 or 400 mg/kg were significantly less than those of the vehicle control group. Irritation of the skin at the site of application was observed in males receiving 100 mg/kg or greater and in females receiving 200 or 400 mg/kg. Kidney weights of females administered 200 or 400 mg/kg were significantly greater than those of the vehicle control group. There were dose-dependent increases in the incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, chronic inflammation, parakeratosis, and ulcer. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were admin istered 0, 50, 100, 200, 400, or 800 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until the end of the study, and final mean body weights and

  17. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

  18. NTP Toxicology and Carcinogenesis Studies of Pentaerythritol Tetranitrate (CAS No. 78-11-5) with 80% D-Lactose Monohydrate (PETN, NF) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-08-01

    Pentaerythritol tetranitrate (PETN, NF) is a drug used to prevent angina pectoris. PETN without a lactose stabilizer is used as an explosive. NTP Toxicology and Carcinogenesis studies were conducted by administering PETN, NF, to groups of F344/N rats and B6C3F1 mice of each sex once by gavage or in feed for 14 days, 13 or 14 weeks, or 2 years. The PETN component was greater than 99% pure. Genetic toxicology studies were conducted with Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Fourteen-Day and Thirteen-Week Studies: All rats and mice lived to the end of the 14-day studies (dietary concentrations up to 50,000 ppm). Final mean body weights of dosed and control rats were comparable. The final mean body weight of female mice that received 50,000 ppm was 13% lower than that of controls. No clinical signs or toxic lesions were attributed to PETN, NF, administration. All rats and mice lived to the end of the 13-week (mice) and 14-week (rats) studies (dietary concentrations up to 50,000 ppm). Final mean body weights of dosed and control rats and mice were similar, although weight gains of female rats at 25,000 and 50,000 ppm were less than that of controls. The nitrite level in urine of rats and methemoglobin levels in whole blood of rats and mice were not affected by administration of PETN, NF. An adenoma of the Zymbal gland was seen in a female rat that received 50,000 ppm. A hepatocellular adenoma was seen in a female mouse that received 50,000 ppm. Based on these results and the NTP convention of limiting concentrations in 2-year feed studies to 5% of the diet, the 2-year studies were conducted by administering 0, 25,000 or 50,000 ppm PETN, NF, in feed for 104 weeks to groups of 50 male rats and for 103 weeks to groups of 49 or 50 mice of each sex. Groups of 50 female rats were given feed containing 0, 6,200, or 12,500 ppm PETN, NF, for 104 weeks. Body Weight and Survival in the Two-Year Studies: Mean body weights of high dose male rats were 2

  19. Fermion Determinants

    OpenAIRE

    Fry, M. P.

    2001-01-01

    The current status of bounds on and limits of fermion determinants in two, three and four dimensions in QED and QCD is reviewed. A new lower bound on the two-dimensional QED determinant is derived. An outline of the demonstration of the continuity of this determinant at zero mass when the background magnetic field flux is zero is also given.

  20. 缺失Df(3R)Espl3/TM6C基因片段影响黑腹果蝇的睡眠时间%Deletion of gene fragment Df(3R)Espl3/TM6C affects sleep duration in Drosophila melanogaster

    Institute of Scientific and Technical Information of China (English)

    张可兴; 李廷利

    2012-01-01

    [Aim] Sleep in Drosophila melanogaster shows biological rhythm, and it can be controlled by different genes. In order to find the proper gene that affects sleep duration, we screened the genotypes of D. melanogaster associated with sleep duration. [ Methods] The 7-day-old adults of the wild CS strain and the strains with gene deletion including 5601 , 8904, 7061, 7146, 27327, 669, 8103, 691, 9697, 24416, 26525, 5411, 3096, 5877 and 7682 of D. melanogaster were used for screening. Drosophila Activity Monitoring System (DAMS) was used to record the total sleep duration within 24 h. The data obtained were compared among different strains. [ Results ] Compared with the wild CS strain, strain 5601 with deletion of gene fragment Df (3R) Espl3/TM6C had significantly shorter total sleep duration (P<0.001). [Conclusion] The gene fragment Df(3R)EspJ3/TM6C is related to the sleep duration in D. melanogaster. This research provides data support for revealing the genes which are related to sleep in D. melanogaster and more clues to studying human sleep.%[目的]果蝇的睡眠活动具有生物节律性,可受到基因的调控.为了寻找影响果蝇睡眠时间的基因,本研究对与果蝇睡眠时间相关的基因型进行了筛选.[方法]选择黑腹果蝇Drosophila melanogaster基因缺失系5601,8904,7061,7146,27327,669,8103,691,9697,24416,26525,5411,3096,5877和7682的7日龄成虫和野生CS品系7日龄成虫为研究对象,利用果蝇活动监测器系统(Drosophila Activity Monitoring System,DAMS),记录果蝇的睡眠时间,累计计算24h内果蝇睡眠时间,将测得的各品系果蝇睡眠时间进行对比分析.[结果]与野生型CS品系7日龄成虫相比,缺失Df(3R)Espl3/TM6C基因片段的5601品系7日龄成虫睡眠时间明显缩短(P<0.001).[结论]缺失Df(3R)Espl3/TM6C基因片段与果蝇睡眠有关.本研究结果为揭示影响果蝇睡眠时间的基因提供数据支持,进而为研究人类睡眠提供线索.

  1. Determinants of marriage dissolution

    Science.gov (United States)

    Rahim, Mohd Amirul Rafiq Abu; Shafie, Siti Aishah Mohd; Hadi, Az'lina Abdul; Razali, Nornadiah Mohd; Azid @ Maarof, Nur Niswah Naslina

    2015-10-01

    Nowadays, the number of divorce cases among Muslim couples is very worrisome whereby the total cases reported in 2013 increased by half of the total cases reported in the previous year. The questions on the true key factors of dissolution of marriage continue to arise. Thus, the objective of this study is to reveal the factors that contribute to the dissolution of marriage. A total of 181 cases and ten potential determinants were included in this study. The potential determinants considered were age at marriage of husband and wife, educational level of husband and wife, employment status of husband and wife, income of husband and wife, the number of children and the presence at a counseling session. Logistic regression analysis was used to analyze the data. The findings revealed that four determinants, namely the income of husband and wife, number of children and the presence at a counselling session were significant in predicting the likelihood of divorce among Muslim couples.

  2. NTP Toxicology and Carcinogenesis Studies of Cobalt Sulfate Heptahydrate (CAS No. 10026-24-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-08-01

    Cobalt sulfate is used in the electroplating and electro chemical industries. It is also used as a coloring agent for ceramics and as a drying agent in inks, paints, varnishes, and linoleum. Cobalt sulfate may be added to animal feed as a mineral supplement and has been used as a top dressing on pasture lands. Cobalt sulfate was nominated by the National Cancer Institute for study based on a lack of information on the toxicity of soluble salts. Male and female F344/N rats and B6C3F1 mice were exposed to cobalt sulfate heptahydrate (approximately 99% pure) by inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium. The results of prechronic inhalation toxicity studies were reported previously (Bucher et al., 1990; NTP, 1991). 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of exposed male and female rats were similar to those of the chamber controls throughout the study. Pathology Findings The incidences and severities of proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were markedly greater in all exposed groups of male and female rats than in the chamber controls. The incidences of alveolar epithelial hyperplasia in all groups of exposed males and in females exposed to 3.0 mg/m3 were significantly greater than those in the chamber control groups, as were the incidences of squamous metaplasia in 1.0 mg/m3 females and atypical alveolar epithelial hyperplasia in 3.0 mg/m3 females. In 3.0 mg/m3 males, the combined incidence of alveolar/ bronchiolar neoplasms (adenoma and/or carcinoma) was significantly greater than in the chamber controls. In female rats exposed to 1.0 or 3.0 mg/m3, the incidences of

  3. NTP Toxicology and Carcinogenesis Studies of Oleic Acid Diethanolamine Condensate (CAS No. 93-83-4) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Oleic acid diethanolamine condensate is widely used as an emollient, thickener, and foam stabilizer present in cosmetic formulations of bath additives, shampoos, conditioners, lipsticks, and hair dyes. Male and female F344/N rats and B6C3F1 mice received dermal applications of diethanolamine in 95% ethanol for 13 weeks or 2 years. Genetic toxicology studies were performed in Salmonella typhimurium and L5178Y mouse lymphoma cells. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 13 weeks. All male and female rats survived until the end of the study. The final mean body weights and body weight gains of 200 and 400 mg/kg males and the mean body weight gain of 400 mg/kg females were significantly less than those of the vehicle controls. The only chemical-related clinical finding was irritation of the skin at the site of application in most males administered 100 mg/kg or greater and in all females administered 50 mg/kg or greater. Segmented neutrophil counts were increased relative to the vehicle controls in the 400 mg/kg male group on days 5 and 19, in the 200 mg/kg female group on day 19 and at week 13, and in the 400 mg/kg female group on days 5 and 19 and at week 13. Alkaline phosphatase concentrations were significantly increased in the 200 mg/kg male group on day 19, the 200 mg/kg female group at week 13, and in the 400 mg/kg groups of males and females at week 13. Kidney weights of 200 and 400 mg/kg females were significantly greater than those of the vehicle controls. Lesions of the skin at the site of application included epidermal hyperplasia, parakeratosis, chronic active dermal inflammation, suppurative epidermal inflammation, and sebaceous gland hypertrophy in dosed rats. The severities of these lesions generally increased with increasing dose. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were admin istered

  4. The Value studies of serum Procalcttonin, Interleukin-6, C-reactive, and White Blood Cell Combined Detecting in Diagnosis of Children with Sepsis%PCT、IL-6、CRP和WBC检测在小儿脓毒症的诊断价值

    Institute of Scientific and Technical Information of China (English)

    汤正珍; 陈寿珊; 李文莲; 黄波

    2015-01-01

    OBJECTIVE To explore the values of serum Procalcitonin(PCT),Interleukin-6(IL-6).C-reactive protein(CRP)levelsandWhitebloodcell(WBC)countfordiagnosisofchildrenwithsepsis.METHODS 89of children who entered into PICU treatment.were divided into two groups: Sepsis group and Non-sepsis group.According to the diagnostic criteria of ACCP/SCM Conference,The PCT,IL-6,CRP and WBC level of the two groups were determined and compared with each other.RESULTS Compared to Non-sepsis group,Serum Procalci-tonin,Interleukin-6,C-reactive protein levels of Sepsis group had significant difference (P>0.05),and it was not significant difference of white blood cell levels.The specificity Sensitivity, Accuracy, Positive predictive value and Negative predictive value of PCT were higher than other projects.CONCLUSION WBC count was not be the diag-nostic indicators of sepsis in children.Compared with WBC count,CRP and IL-6,PCT may reflect the most sensitive indicators of sepsis in children,PCT and IL-6 can be used as clinical assessment of sepsis in Children.%目的:探讨小儿脓毒症患儿血清降钙素原(PCT)、白介素-6(IL-6)、全血超敏 C-反应蛋白(CRP)、白细胞计数(WBC)在小儿脓毒症的诊断价值。方法选择ICU危重患者89例,根据国际儿科脓毒症会议制定的标准,脓毒症组47例,非脓毒症组42例。检测比较两组间 PCT、IL-6、CRP、WBC,将两组数据进行统计学分析。结果脓毒症组PCT、IL-6、CRP显著高于非脓毒症组(P<0.01),但组间 WBC计数差异无统计学意义( P>0.05);PCT对小儿脓毒症的敏感性、特异性、准确率、阳性预测值、阴性预测值均较高于其他各个检测指标。结论 WBC计数不能作为小儿脓毒症的诊断指标;与WBC、CRP、IL-6相比较,PCT是检测小儿脓毒症最灵敏的指标;PCT和IL-6可作为小儿脓毒症的疗效评估。

  5. NTP Toxicology and Carcinogenesis Studies of Talc (CAS No. 14807-96-6)(Non-Asbestiform) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1993-09-01

    Talc ore may contain several other minerals including calcite, dolomite, magnesite, tremolite, anthophyllite, antigorite, quartz, pyrophyllite, micas, or chlorites. Talc products are sold in a multitude of grades which have physical or functional characteristics especially suited for particular applications, so occupational and consumer exposures to talc are complex. Epidemiology studies have suggested an association between non-fibrous talc and lung cancer risk. Talc was nominated by the National Institute of Occupational Safety and Health (NIOSH) for study by the NTP because of widespread human exposure and because of the lack of adequate information on its chronic toxicity and potential carcinogenicity. Toxicology and carcinogenicity studies of talc (non-asbestiform, cosmetic grade), a finely powdered hydrous magnesium silicate, were conducted by exposing groups of F344/N rats to aerosols for 6 hours per day, 5 days per week for up to 113 weeks (males) or 122 weeks (females). Groups of B6C3F1 mice were exposed similarly for up to 104 weeks. LIFETIME STUDY IN RATS: Groups of 49 or 50 male and 50 female rats were exposed to aerosols of 0, 6, or 18 mg/m(3) talc until mortality in any exposure group reached 80% (113 weeks for males and 122 weeks for females). These exposures were selected based on 4-week inhalation studies of the terminal lung talc burden in F344/N rats; concentrations greater than 18 mg/m(3) were expected to overwhelm lung clearance mechanisms and impair lung function. These exposure concentrations provided a dose equivalent of 0, 2.8, or 8.4 mg/kg per day for male rats and 0, 3.2, or 9.6 mg/kg per day for female rats. In a special study, additional groups of 22 male and 22 female rats were similarly exposed and examined for interim pathology evaluations or pulmonary function tests after 6, 11, 18, and 24 months and lung biochemistry and cytology studies after 24 months. The talc aerosols had a median mass aerodynamic diameter of 2.7 mm in the 6 mg

  6. Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies).

    Science.gov (United States)

    2013-03-01

    Ginkgo biloba extract has been used primarily as a medicinal agent in the treatment or prevention of cardiovascular and cerebrovascular dysfunction. Ginkgo biloba extract was nominated for study by the National Cancer Institute because of its widespread use as an herbal supplement to promote mental function and the limited availability of toxicity and carcinogenicity data. Furthermore, one of the major ingredients in Ginkgo biloba extract, quercetin, is a known mutagen. The Ginkgo biloba extract used in the current studies was procured from a supplier known to provide material to United States companies and contained 31.2% flavonol glycosides, 15.4% terpene lactones (6.94% bilo-balide, 3.74% ginkgolide A, 1.62% ginkgolide B, 3.06% ginkgolide C), and 10.45 ppm ginkgolic acid. Male and female F344/N rats and B6C3F1/N mice were administered Ginkgo biloba extract in corn oil by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg Ginkgo biloba extract/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses, 5 days per week for 23 days. All rats survived to the end of the study. Mean body weights of all dosed groups were similar to those of the vehicle control groups. Liver weights of all dosed groups of males and females were significantly greater than those of the vehicle control groups. The incidences of hepatocyte hypertrophy in all dosed groups of males and in 500 and 1,000 mg/kg females were significantly greater than those in the vehicle control groups; there was a dose-related increase in severity of this lesion in males. Hepatocyte fatty change occurred in all dosed males. The incidences of thyroid gland follicular cell

  7. Sex determination

    OpenAIRE

    McCullagh, W. McK. H.

    2013-01-01

    How the sex of offspring is determined has puzzled philosophers and scientists for millennia. Modern science has identified both genetic and environmental factors, but the question is still not yet fully answered.

  8. 2. Determinants

    African Journals Online (AJOL)

    Sitwala

    ... P.O Box 50110, Lusaka. National Food and Nutrition Commission, Ministry of Health, Lusaka ... malnourished case of admissions among HIV infected children and were .... However, service factors emerged as important determinants during.

  9. Decision Making and Revealed Preference

    DEFF Research Database (Denmark)

    de la Rosa, Leonidas Enrique

    If our decision-making processes are to some extent shaped by evolutionary pressures and our environment is different from that to which we adapted, some of our choices will not be in our best interest. But revealed preference is the only tool that we have so far to conduct a normative analysis...

  10. Revealed preference with limited consideration

    NARCIS (Netherlands)

    Demuynck, T.; Seel, C.

    2014-01-01

    We derive revealed preference tests for models where individuals use consideration sets to simplify their consumption problem. Our basic test provides necessary and sufficient conditions for consistency of observed choices with the existence of consideration set restrictions. The same conditions can

  11. Revealed comparative advantage of Russian agricultural exports

    Directory of Open Access Journals (Sweden)

    Natalia Ishchukova

    2013-01-01

    Full Text Available This paper studies the issue of revealed comparative advantage in the case of the Russian foreign trade in agricultural products and foodstuffs. The objective of this study is to analyze specialization and the competitive performance of the Russian agricultural sector and to determine whether or not patterns of comparative advantage for Russia have undergone significant changes over the period 1998–2010.The analysis is performed using several measures of revealed comparative advantage: classical Balassa’s index, Vollrath’s index and Lafay index. Balassa’s index identified a group of products, which has relatively stable comparative advantage during the whole period. Among those products we can count cereals (wheat, barley, etc., their by-products (for example bran of wheat and products of their processing (cereals preparations, etc., as well as oilseeds, vegetable oils and chocolate.Vollrath’s index showed that the number of products that have revealed competitive advantage was steadily growing during the period. Lafay index, used in the analysis by regions, showed that Russia has comparative advantages in relation to CIS countries and Asian countries due to its geographical location and good trade relations.Primary products have the comparative advantage in relation to EU and Asian countries. In relation to the Commonwealth of Independent States and Americas on the contrary the processed products have comparative advantages, while the most of primary products have comparative disadvantage.In relation to the whole world, analysis has also revealed a shift of comparative advantage from by-products (e.g. bran of wheat, sunflower cake etc. in 1998–2001 to primary products in 2002–2010 (wheat, barley, whole cow milk, sunflower seed etc..

  12. Gender determination in populus

    Energy Technology Data Exchange (ETDEWEB)

    McLetchie, D.N. [Univ. of Kentucky, Lexington, KY (United States). Dept. of Biological Sciences; Tuskan, G.A. [Oak Ridge National Lab., TN (United States)

    1994-12-31

    Gender, the expression of maleness or femaleness, in dioecious plants has been associated with changes in morphology, physiology, ecological position, and commercial importance of several species, including members of the Salicaceae family. Various mechanisms have been proposed to explain the expression of gender in Salicaceae, including sex chromosomes, simple Mendelian genes, quantitative genes, environment, and genotype-by-environment interactions. Published reports would favor a genetic basis for gender. The objective of this study was to identify molecular markers associated with gender in a segregating family of hybrid poplars. Bulked segregant analysis and chi-squared analysis were used to test for the occurrence of sex chromosomes, individual loci, and chromosome ratios (i.e., ploidy levels) as the mechanisms for gender determination. Examination of 2488 PCR based RAPD markers from 1219 primers revealed nine polymorphic bands between male and female bulked samples. However, linkage analysis indicated that none of these markers were significantly associated with gender. Chisquared results for difference in male-to-female ratios between diploid and triploid genotypes also revealed no significant differences. These findings suggest gender is not controlled via sex chromosomes, simple Mendelian loci or ratios of autosome to gender-determining loci. It is possible that gender is determined genetically by regions of the genome not sampled by the tested markers or by a complex of loci operating in an additive threshold manner or in an epistatic manner. It is also possible that gender is determined environmentally at an early zygote stage, canalizing gender expression.

  13. Visibility of gingiva - An important determinant for an esthetic smile

    Directory of Open Access Journals (Sweden)

    Shipra Sepolia

    2014-01-01

    Full Text Available Background: Need for having better esthetics is the new emerging trend seen in patients′ demands and expectations. Various periodontal procedures including the mucogingival procedures have been designed to enhance the esthetics. The amount of gingival display of the patient is also an important parameter while considering the esthetics of the patient. Till date, very few studies have been done in which the amount of gingival visibility have been determined. So, the aim of this study was to evaluate the amount of visibility of gingiva during natural smile and forced smile in the patients visiting Himachal Dental College and Hospital. Materials and Methods: A total of 400 patients (242 females and 158 males, aged between 18 to 49 years, attending the outpatient department of Himachal Dental College, were included in this study. Patients were divided into two groups according to age and gender. Clinical photographs of the patients were taken and analyzed according to the following classification: (1 Very high smile line that is more than 2 mm of marginal gingiva visible or more than 2 mm apical to the cementoenamel junction visible for the reduced but healthy periodontium, (2 high smile line that is between 0 and 2 mm of marginal gingiva visible or between 0 and 2 mm apical to the cementoenamel junction visible for the reduced but healthy periodontium, (3 average smile line in which only gingival embrasures are visible, (4 low smile line in which gingival embrasures and cementoenamel junction not visible. Examination of the gingiva was done for both natural smile and forced smile. Results: During smile analysis, the following results were revealed for Natural smile and forced smile. Natural smile analysis revealed following: C1: 1%, C2: 6%, C3: 43.50% and C4 was 49.50%. Forced smile analysis revealed the following: C1: 1%, C2: 15.50%, C3: 59% and C4: 24.50%. Conclusions: Excessive gingival display is an esthetic concern both to the patient and

  14. [Endobronchial hamartoma revealed by hemoptysis].

    Science.gov (United States)

    Smati, Belhassen; Boudaya, Mohamed Sadok; Mestiri, Taher; Djilani, Habiba; Mezni, Faouzi; Kilani, Tarek

    2005-05-01

    Hamartoma is the most frequent benign tumor of the lung. Its endo bronchial location is rare. We report two cases of endo bronchial hamartoma occurring in 2 men aged 68 and 60 years respectively. The two cases were revealed by hemoptysis. Bronchial fibroscopy showed a bud respectively in the left stump and in the lower left bronchus. Treatment consisted in a pneumonectomy and a lower lobectomy. A histological examination confirmed the diagnosis of endo bronchial hamartoma. Diagnosis of endobronchial hamartoma before surgery is difficult. Pulmonary resections are often necessary because of parenchyma lelions caused bronchial obstruction.

  15. Transparency masters for mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1980-01-01

    Transparency Masters for Mathematics Revealed focuses on master diagrams that can be used for transparencies for an overhead projector or duplicator masters for worksheets. The book offers information on a compilation of master diagrams prepared by John R. Stafford, Jr., audiovisual supervisor at the University of Missouri at Kansas City. Some of the transparencies are designed to be shown horizontally. The initial three masters are number lines and grids that can be used in a mathematics course, while the others are adaptations of text figures which are slightly altered in some instances. The

  16. Density,Viscosity,Refractive Index,and Speed of Sound in Binary Mixtures of Pyridine and 1-Alkanols(C6,C7,C8,C10)at 303.15 K

    Institute of Scientific and Technical Information of China (English)

    ALI Anwar; TARIQ Mohd; NABI Firdosa; SHAHJAHAN

    2008-01-01

    The densities(ρ),viscosities(η),refractive indices(nD),and speeds of sound(u),of binary mixtures of pyridine with 1-hexanoi,1-heptanol,1-octanol and 1-decanol,including those of pure liquids,were measured over the entire composition range at 303.15 K and atmospheric pressure.From these experimental data,the values of excess molar volumes(VE),deviations in isentropic compressibilities(△ks),viscosities(△η),molar refractions(△Rm),apparent and partial molar volumes(Vφ,2 and V0φ,2 ),apparent and partial molar compressibilities(Kφ,2 and K0φ,2 ),of alkanols in pyridine and their corresponding deviations(△V and △K)were calculated.The variations of these parameters with composition of the mixtures suggest that the strength of interactions in these mixtures follow the order:1-hexanol 1-heptanol 1-octanol 1-decanol.All the excess and deviation functions were fitted to Redlich-Kister polynomial equation to determine the fitting coefficients and the standard deviations.

  17. The Deceptively Simple Thermolysis of Trivalent Permethyltitanocene Derivatives (η5-C5Me5)2TiR. Formation of a Tetramethylfulvene Titanium Compound (η6-C5Me4CH2)(η5-C5Me5)Ti and RH, Catalyzed by Permethyltitanocene Hydride, (η5-C5Me5)2TiH

    NARCIS (Netherlands)

    Luinstra, Gerrit A.; Teuben, Jan H.

    1992-01-01

    The complexes Cp*2TiR (Cp* = η5-C5Me5; R = Me, Et, n-Pr, C2H3, CH2CMe3, Ph) undergo thermolysis to yield the fulvene complex Cp*FvTi (Fv = η6-C5Me4CH2) and RH. Kinetic measurements and deuterium labeling studies show that the decomposition is catalyzed by Cp*2TiH, which is formed either by β-hydroge

  18. THE DECEPTIVELY SIMPLE THERMOLYSIS OF TRIVALENT PERMETHYLTITANOCENE DERIVATIVES (ETA-5-C5ME5)2TIR - FORMATION OF A TETRAMETHYLFULVENE TITANIUM COMPOUND (ETA-6-C5ME4CH2)(ETA-5-C5ME5)TI AND RH, CATALYZED BY PERMETHYLTITANOCENE HYDRIDE, (ETA-5-C5ME5)2TIH

    NARCIS (Netherlands)

    LUINSTRA, GA; TEUBEN, JH

    1992-01-01

    The complexes Cp*2TiR (Cp* = eta-5-C5Me5; R = Me, Et, n-Pr, C2H3, CH2CMe3, Ph) undergo thermolysis to yield the fulvene complex Cp*FvTi (Fv = eta-6-C5Me4CH2) and RH. Kinetic measurements and deuterium labeling studies show that the decomposition is catalyzed by Cp*2TiH, which is formed either by

  19. The Deceptively Simple Thermolysis of Trivalent Permethyltitanocene Derivatives (η5-C5Me5)2TiR. Formation of a Tetramethylfulvene Titanium Compound (η6-C5Me4CH2)(η5-C5Me5)Ti and RH, Catalyzed by Permethyltitanocene Hydride, (η5-C5Me5)2TiH

    NARCIS (Netherlands)

    Luinstra, Gerrit A.; Teuben, Jan H.

    1992-01-01

    The complexes Cp*2TiR (Cp* = η5-C5Me5; R = Me, Et, n-Pr, C2H3, CH2CMe3, Ph) undergo thermolysis to yield the fulvene complex Cp*FvTi (Fv = η6-C5Me4CH2) and RH. Kinetic measurements and deuterium labeling studies show that the decomposition is catalyzed by Cp*2TiH, which is formed either by

  20. Revealing ontological commitments by magic.

    Science.gov (United States)

    Griffiths, Thomas L

    2015-03-01

    Considering the appeal of different magical transformations exposes some systematic asymmetries. For example, it is more interesting to transform a vase into a rose than a rose into a vase. An experiment in which people judged how interesting they found different magic tricks showed that these asymmetries reflect the direction a transformation moves in an ontological hierarchy: transformations in the direction of animacy and intelligence are favored over the opposite. A second and third experiment demonstrated that judgments of the plausibility of machines that perform the same transformations do not show the same asymmetries, but judgments of the interestingness of such machines do. A formal argument relates this sense of interestingness to evidence for an alternative to our current physical theory, with magic tricks being a particularly pure source of such evidence. These results suggest that people's intuitions about magic tricks can reveal the ontological commitments that underlie human cognition. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Plan competitions reveal entrepreneurial talent

    Energy Technology Data Exchange (ETDEWEB)

    Madison, Alison L.

    2011-05-15

    Monthly economic diversity column for Tri-City Herald business section. Excerpt below: There’s something to be said for gaining valuable real-world experience in a structured, nurturing environment. Take for instance learning to scuba dive in the comfort of my resort pool rather than immediately hanging out with sharks while I figure out little things like oxygen tanks and avoiding underwater panic attacks. Likewise, graduate students are getting some excellent, supportive real-world training through university business plan competitions. These competitions are places where smart minds, new technologies, months of preparation and coaching, and some healthy pre-presentation jitters collide to reveal not only solid new business ideas, but also some promising entrepreneurial talent. In fact, professionals from around our region descend upon college campuses every spring to judge these events, which help to bridge the gap between academics and the real technology and business-driven economy.

  2. Transcriptome classification reveals molecular subtypes in psoriasis

    Directory of Open Access Journals (Sweden)

    Ainali Chrysanthi

    2012-09-01

    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  3. Esters with water esters 2-c to 6-c

    CERN Document Server

    Getzen, F W; Hefter, G T; Maczynski, Andrzej

    1992-01-01

    This volume is the first of two devoted to esters and water. It includes solubility data for binary systems containing an ester and water up to the end of 1988. The critical evaluations were all prepared by one author and an introductory section has been included to elaborate the philosophy and methodology followed in the evaluations.

  4. Integrated genomics of Mucorales reveals novel therapeutic targets

    Science.gov (United States)

    Mucormycosis is a life-threatening infection caused by Mucorales fungi. We sequenced 30 fungal genomes and performed transcriptomics with three representative Rhizopus and Mucor strains with human airway epithelial cells during fungal invasion to reveal key host and fungal determinants contributing ...

  5. Focus groups reveal consumer ambivalence.

    Science.gov (United States)

    1983-01-01

    According to qualitative research, Salvadoreans are ambivalent about the use of contraceptives. Since complete responsibility for management of the CSM project was accepted by the Association Demografica Salvadorena (ADS), the agency which operates the contraceptive social marketing project in El Salvador, in November 1980, the need for decisions in such areas as product price increases, introduction of new condom brands, promotion of the vaginal foaming tablet, and assessment of product sales performance had arisen. The ICSMP funded market research, completed during 1983, was intended to provide the data on which such decisions by ADS could be based. The qualitative research involved 8 focus groups, comprised of men and women, aged 18-45, contraceptive users and nonusers, from the middle and lower socioeconomic strata of the city of San Salvador and other suburban areas. In each group a moderator led discussion of family planning and probed respondents for specific attitudes, knowledge, and behavior regarding the use of contraceptives. To assess attitudes at a more emotional level, moderators asked respondents to "draw" their ideas on certain issues. A marked discrepancy was revealed between respondents' intellectual responses to the issues raised in group discussion, as opposed to their feelings expressed in the drawings. Intellectually, participants responded very positively to family planning practice, but when they were asked to draw their perceptions, ambivalent feelings emerged. Drawings of both the user and the nonuser convey primarily negative aspects for either choice. The user is tense and moody toward her children; the nonuser loses her attractiveness and "dies." Figures also show drawings of some of the attitudes of single and married male participants. 1 drawing shows an incomplete and a complete circle, symbolizing a sterilized man (incomplete) and a nonsterilized man (complete). Another picture depicts a chained man who has lost his freedom

  6. Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5- Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 6. Volume 1

    Science.gov (United States)

    1984-04-01

    viruses : GD-VII virus , K virus , Mouse Adenovirus, Sendai virus , Reovirus 3...Pneumonia virus of mice, Lymphocytic Choriomeningitis, Polyoma virus , Minute virus of mice, Mouse Hepatitis and Ectomelia. These tests for antibody...OC" " N " N " NN C. C% N " C" N " C’ C" N N N C" C’ C, C" C" 04 C"J C" N C" C" N N" C"d N C" 04 04 C" CS C" C’) NCV C" cc I-XLU -I 0 1c Mc -tm WrL

  7. Radioactivity reveals how crisps mix

    Energy Technology Data Exchange (ETDEWEB)

    Parker, David [School of Physics and Astronomy, University of Birmingham, Birmingham (United Kingdom)

    2000-01-01

    Many of the ''fluids'' processed in the food industry have strange flow properties that cannot easily be predicted. This is an important question in industry, since engineers need to know how such systems flow through pipes in production plants or how different components mix together. To counter this lack of knowledge, the fluids are generally processed for longer than necessary, which often proves expensive and may affect the quality of the final product. The University of Birmingham Positron Imaging Centre has developed a powerful technique to study the behaviour of crisps, yoghurt and ice cream - together with many other granular materials and viscous fluids - in a variety of industrial processes. In one case, the group labelled a single crisp using a positron-emitting radioisotope and added it to a rotating drum full of crisps. By tracking the movement of the labelled crisp, they could determine how uniformly the crisps were exposed to the flavouring that was added in the mixing process. In this article the author describes the research at the university's Positron Imaging Centre. (UK)

  8. Quantitative determination of four constituents of Tinospora sps. by a reversed-phase HPLC-UV-DAD method. Broad-based studies revealing variation in content of four secondary metabolites in the plant from different eco-geographical regions of India.

    Science.gov (United States)

    Ahmed, S M; Manhas, L R; Verma, V; Khajuria, R K

    2006-09-01

    This paper describes the separation and quantitation of important markers, such as 20beta-hydroxyecdysone, tinosporaside, cordioside, and columbin, present in three species of Tinospora viz, T. cordifolia, T. malabrica, and T. crispa. A reverse-phase (RP) high-performance liquid chromatography (HPLC)-UV-diode array detection (DAD) method employing gradient elution is thus developed. The marker compounds isolated from 70% ethanolic extract of T. cordfolia by repeated column chromatography are identified on the basis of (1)H NMR, (13)C NMR, and mass spectral data. The compounds are separated on a RP (RP-18, 5 microm, 250 x 4.6-mm i.d.) column using water-acetonitrile gradient and are detected by the HPLC-UV-DAD method. The calibration curves that result from marker compounds in the concentration range of 100-2000 ng on column exhibit a good correlation (r(2) > or = 0.99978). The method is successfully applied to separate and study the content of four marker compounds in 40 different accessions of three Tinospora species collected from different regions of India. The studies reveal that the maximum amount of the marker compounds is present in Tinospora cordifolia species, especially from accessions collected from higher altitudes of the Jammu province (North India).

  9. Revealing conceptual understanding of international business

    NARCIS (Netherlands)

    Ashley, S.; Schaap, H.; Bruijn, E. de

    2016-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual

  10. Revealing conceptual understanding of international business

    NARCIS (Netherlands)

    Ashley, S.M.; Schaap, H.; de Bruijn, E.

    2016-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual underst

  11. Revealing conceptual understanding of international business

    NARCIS (Netherlands)

    Sue Ashley; Dr. Harmen Schaap; Prof.Dr. Elly de Bruijn

    2017-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual

  12. Revealing conceptual understanding of international business

    NARCIS (Netherlands)

    Ashley, S.M.; Schaap, H.; de Bruijn, E.

    2016-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual

  13. Structure determination from XAFS using high-accuracy measurements of x-ray mass attenuation coefficients of silver, 11 keV-28 keV, and development of an all-energies approach to local dynamical analysis of bond length, revealing variation of effective thermal contributions across the XAFS spectrum

    Science.gov (United States)

    Tantau, L. J.; Chantler, C. T.; Bourke, J. D.; Islam, M. T.; Payne, A. T.; Rae, N. A.; Tran, C. Q.

    2015-07-01

    We use the x-ray extended range technique (XERT) to experimentally determine the mass attenuation coefficient of silver in the x-ray energy range 11 kev-28 kev including the silver K absorption edge. The results are accurate to better than 0.1%, permitting critical tests of atomic and solid state theory. This is one of the most accurate demonstrations of cross-platform accuracy in synchrotron studies thus far. We derive the mass absorption coefficients and the imaginary component of the form factor over this range. We apply conventional XAFS analytic techniques, extended to include error propagation and uncertainty, yielding bond lengths accurate to approximately 0.24% and thermal Debye-Waller parameters accurate to 30%. We then introduce the FDMX technique for accurate analysis of such data across the full XAFS spectrum, built on full-potential theory, yielding a bond length accuracy of order 0.1% and the demonstration that a single Debye parameter is inadequate and inconsistent across the XAFS range. Two effective Debye-Waller parameters are determined: a high-energy value based on the highly-correlated motion of bonded atoms ({σ\\text{DW}}=0.1413(21) Å), and an uncorrelated bulk value ({σ\\text{DW}}=0.1766(9) Å) in good agreement with that derived from (room-temperature) crystallography.

  14. Structure determination from XAFS using high-accuracy measurements of x-ray mass attenuation coefficients of silver, 11 keV-28 keV, and development of an all-energies approach to local dynamical analysis of bond length, revealing variation of effective thermal contributions across the XAFS spectrum.

    Science.gov (United States)

    Tantau, L J; Chantler, C T; Bourke, J D; Islam, M T; Payne, A T; Rae, N A; Tran, C Q

    2015-07-08

    We use the x-ray extended range technique (XERT) to experimentally determine the mass attenuation coefficient of silver in the x-ray energy range 11 kev-28 kev including the silver K absorption edge. The results are accurate to better than 0.1%, permitting critical tests of atomic and solid state theory. This is one of the most accurate demonstrations of cross-platform accuracy in synchrotron studies thus far. We derive the mass absorption coefficients and the imaginary component of the form factor over this range. We apply conventional XAFS analytic techniques, extended to include error propagation and uncertainty, yielding bond lengths accurate to approximately 0.24% and thermal Debye-Waller parameters accurate to 30%. We then introduce the FDMX technique for accurate analysis of such data across the full XAFS spectrum, built on full-potential theory, yielding a bond length accuracy of order 0.1% and the demonstration that a single Debye parameter is inadequate and inconsistent across the XAFS range. Two effective Debye-Waller parameters are determined: a high-energy value based on the highly-correlated motion of bonded atoms (σ(DW) = 0.1413(21) Å), and an uncorrelated bulk value (σ(DW) = 0.1766(9) Å) in good agreement with that derived from (room-temperature) crystallography.

  15. POSITIVE MOTIVATION DETERMINANTS IN PSYCHOLOGY

    Directory of Open Access Journals (Sweden)

    Svyatoslav Vasilyevich KOTOV

    2014-01-01

    Full Text Available The paper considered the study of determinants of moti-vation and operation achievement. The paper revealed (with description in details the following factors: want for competence and self-determination, orientation in purpose of live, values, self-efficacy, resilience, and in-trinsic motivation. The study rationalized psychology regularities in the above determinants and the part they played in shaping resilience, personal mental wellbeing and further reinforcement of achievement motivation where the levels at the value scale of an individual served for the basis, those described in details in this paper. All the above determinants of positive motivation enable the individual to get over inner personal tensions, to become an autotelic free person. This paper reviewed the deter-minants of positive motivation in both Russian and for-eign studies of psychologists.

  16. Studies of the mechanism of the olefin metathesis reaction and the process of active site formation on photoreduced molybdenum-silicate catalysts. 2. Productive and degenerative metathesis of C/sub 2/H/sub 4/-C/sub 2/D/sub 4/ and C/sub 3/H/sub 6/-C/sub 3/D/sub 6/ mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Elev, I.V.; Shelimov, B.N.; Kazanskii, V.B.

    1987-10-01

    The specific catalytic activity of photoreduced Mo/sup 4 +//SiO/sub 2/ samples has been compared for productive and degenerate metathesis reactions of C/sub 3/H/sub 6/-C/sub 3/D/sub 6/ and C/sub 2/H/sub 4/-C/sub 2/D/sub 4/ mixtures. It has been found, that, under comparable conditions, the rate of degenerate metathesis of ethylene is 4-5 times slower than the rate of productive metathesis of propylene, although the rate of degenerate metathesis of propylene is 5 x 10/sup 3/-10/sup 4/ times greater than its rate of productive metathesis. Based on these results, it is concluded that degenerate metathesis of propylene occurs via the involvement of secondary (ethylidene) carbenes.

  17. Revealing atropisomer axial chirality in drug discovery.

    Science.gov (United States)

    LaPlante, Steven R; Edwards, Paul J; Fader, Lee D; Jakalian, Araz; Hucke, Oliver

    2011-03-07

    An often overlooked source of chirality is atropisomerism, which results from slow rotation along a bond axis due to steric hindrance and/or electronic factors. If undetected or not managed properly, this time-dependent chirality has the potential to lead to serious consequences, because atropisomers can be present as distinct enantiomers or diastereoisomers with their attendant different properties. Herein we introduce a strategy to reveal and classify compounds that have atropisomeric chirality. Energy barriers to axial rotation were calculated using quantum mechanics, from which predicted high barriers could be experimentally validated. A calculated rotational energy barrier of 20 kcal mol(-1) was established as a suitable threshold to distinguish between atropisomers and non-atropisomers with a prediction accuracy of 86%. This methodology was applied to subsets of drug databases in the course of which atropisomeric drugs were identified. In addition, some drugs were exposed that were not yet known to have this chiral attribute. The most valuable utility of this tool will be to predict atropisomerism along the drug discovery pathway. When used in concert with our compound classification scheme, decisions can be made during early discovery stages such as "hit-to-lead" and "lead optimization," to foresee and validate the presence of atropisomers and to exercise options of removing, further stabilizing, or rendering the chiral axis of interest more freely rotatable via SAR design, thereby decreasing this potential liability within a compound series. The strategy can also improve drug development plans, such as determining whether a drug or series should be developed as a racemic mixture or as an isolated single compound. Moreover, the work described herein can be extended to other chemical fields that require the assessment of potential chiral axes.

  18. Revealing Conceptual Understanding of International Business

    Science.gov (United States)

    Ashley, Sue; Schaap, Harmen; de Bruijn, Elly

    2017-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students' conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual understanding in higher education. Essays and concept…

  19. Artificial gravity reveals that economy of action determines the stability of sensorimotor coordination.

    Directory of Open Access Journals (Sweden)

    Richard G Carson

    Full Text Available BACKGROUND: When we move along in time with a piece of music, we synchronise the downward phase of our gesture with the beat. While it is easy to demonstrate this tendency, there is considerable debate as to its neural origins. It may have a structural basis, whereby the gravitational field acts as an orientation reference that biases the formulation of motor commands. Alternatively, it may be functional, and related to the economy with which motion assisted by gravity can be generated by the motor system. METHODOLOGY/PRINCIPAL FINDINGS: We used a robotic system to generate a mathematical model of the gravitational forces acting upon the hand, and then to reverse the effect of gravity, and invert the weight of the limb. In these circumstances, patterns of coordination in which the upward phase of rhythmic hand movements coincided with the beat of a metronome were more stable than those in which downward movements were made on the beat. When a normal gravitational force was present, movements made down-on-the-beat were more stable than those made up-on-the-beat. CONCLUSIONS/SIGNIFICANCE: The ubiquitous tendency to make a downward movement on a musical beat arises not from the perception of gravity, but as a result of the economy of action that derives from its exploitation.

  20. Principles of Bacterial Cell-Size Determination Revealed by Cell-Wall Synthesis Perturbations

    Directory of Open Access Journals (Sweden)

    Carolina Tropini

    2014-11-01

    Full Text Available Although bacterial cell morphology is tightly controlled, the principles of size regulation remain elusive. In Escherichia coli, perturbation of cell-wall synthesis often results in similar morphologies, making it difficult to deconvolve the complex genotype-phenotype relationships underlying morphogenesis. Here we modulated cell width through heterologous expression of sequences encoding the essential enzyme PBP2 and through sublethal treatments with drugs that inhibit PBP2 and the MreB cytoskeleton. We quantified the biochemical and biophysical properties of the cell wall across a wide range of cell sizes. We find that, although cell-wall chemical composition is unaltered, MreB dynamics, cell twisting, and cellular mechanics exhibit systematic large-scale changes consistent with altered chirality and a more isotropic cell wall. This multiscale analysis enabled identification of distinct roles for MreB and PBP2, despite having similar morphological effects when depleted. Altogether, our results highlight the robustness of cell-wall synthesis and physical principles dictating cell-size control.

  1. Structure-function analysis of Staphylococcus aureus amidase reveals the determinants of peptidoglycan recognition and cleavage.

    Science.gov (United States)

    Büttner, Felix Michael; Zoll, Sebastian; Nega, Mulugeta; Götz, Friedrich; Stehle, Thilo

    2014-04-18

    The bifunctional major autolysin AtlA of Staphylococcus aureus cleaves the bacterium's peptidoglycan network (PGN) at two distinct sites during cell division. Deletion of the enzyme results in large cell clusters with disordered division patterns, indicating that AtlA could be a promising target for the development of new antibiotics. One of the two functions of AtlA is performed by the N-acetylmuramyl-l-alanine amidase AmiA, which cleaves the bond between the carbohydrate and the peptide moieties of PGN. To establish the structural requirements of PGN recognition and the enzymatic mechanism of cleavage, we solved the crystal structure of the catalytic domain of AmiA (AmiA-cat) in complex with a peptidoglycan-derived ligand at 1.55 Å resolution. The peptide stem is clearly visible in the structure, forming extensive contacts with protein residues by docking into an elongated groove. Less well defined electron density and the analysis of surface features indicate likely positions of the carbohydrate backbone and the pentaglycine bridge. Substrate specificity analysis supports the importance of the pentaglycine bridge for fitting into the binding cleft of AmiA-cat. PGN of S. aureus with l-lysine tethered with d-alanine via a pentaglycine bridge is completely hydrolyzed, whereas PGN of Bacillus subtilis with meso-diaminopimelic acid directly tethered with d-alanine is not hydrolyzed. An active site mutant, H370A, of AmiA-cat was completely inactive, providing further support for the proposed catalytic mechanism of AmiA. The structure reported here is not only the first of any bacterial amidase in which both the PGN component and the water molecule that carries out the nucleophilic attack on the carbonyl carbon of the scissile bond are present; it is also the first peptidoglycan amidase complex structure of an important human pathogen.

  2. Enantiomers of 3-methylspermidine selectively modulate deoxyhypusine synthesis and reveal important determinants for spermidine transport.

    Science.gov (United States)

    Hyvönen, Mervi T; Khomutov, Maxim; Petit, Marine; Weisell, Janne; Kochetkov, Sergey N; Alhonen, Leena; Vepsäläinen, Jouko; Khomutov, Alex R; Keinänen, Tuomo A

    2015-06-19

    Eukaryotic translation initiation factor 5A (eIF5A) is essential for cell proliferation, becoming functionally active only after post-translational conversion of a specific Lys to hypusine [N(ε)-(4-amino-2-hydroxybutyl)lysine]. Deoxyhypusine synthase (DHS) is the rate-limiting enzyme of this two-step process, and the polyamine spermidine is the only natural donor of the butylamine group for this reaction, which is very conserved-hypusine biosynthesis suffers last when the intracellular spermidine pool is depleted. DHS has a very strict substrate specificity, and only a few spermidine analogs are substrates of the enzyme and can support long-term growth of spermidine-depleted cells. Herein, we compared the biological properties of earlier unknown enantiomers of 3-methylspermidine (3-MeSpd) in deoxyhypusine synthesis, in supporting cell growth and in polyamine transport. Long-term treatment of DU145 cells with α-difluoromethylornithine (inhibitor of polyamine biosynthesis) and (R)-3-MeSpd did not cause depletion of hypusinated eIF5A, and the cells were still able to grow, whereas the combination of α-difluoromethylornithine with a racemate or (S)-3-MeSpd caused cessation of cell growth. Noticeably, DHS preferred the (R)- over the (S)-enantiomer as a substrate. (R)-3-MeSpd competed with [(14)C]-labeled spermidine for cellular uptake less efficiently than the (S)-3-MeSpd (Ki = 141 μM vs 19 μM, respectively). The cells treated with racemic 3-MeSpd accumulated intracellularly mainly (S)-3-MeSpd, but not DHS substrate (R)-3-MeSpd, explaining the inability of the racemate to support long-term growth. The distinct properties of 3-MeSpd enantiomers can be exploited in designing polyamine uptake inhibitors, facilitating drug delivery and modulating deoxyhypusine synthesis.

  3. The photochemical determinants of color vision: revealing how opsins tune their chromophore's absorption wavelength.

    Science.gov (United States)

    Wang, Wenjing; Geiger, James H; Borhan, Babak

    2014-01-01

    The evolution of a variety of important chromophore-dependent biological processes, including microbial light sensing and mammalian color vision, relies on protein modifications that alter the spectral characteristics of a bound chromophore. Three different color opsins share the same chromophore, but have three distinct absorptions that together cover the entire visible spectrum, giving rise to trichromatic vision. The influence of opsins on the absorbance of the chromophore has been studied through methods such as model compounds, opsin mutagenesis, and computational modeling. The recent development of rhodopsin mimic that uses small soluble proteins to recapitulate the binding and wavelength tuning of the native opsins provides a new platform for studying protein-regulated spectral tuning. The ability to achieve far-red shifted absorption in the rhodopsin mimic system was attributed to a combination of the lack of a counteranion proximal to the iminium, and a uniformly neutral electrostatic environment surrounding the chromophore.

  4. Comparative Genomics Reveals Chd1 as a Determinant of Nucleosome Spacing in Vivo.

    Science.gov (United States)

    Hughes, Amanda L; Rando, Oliver J

    2015-07-14

    Packaging of genomic DNA into nucleosomes is nearly universally conserved in eukaryotes, and many features of the nucleosome landscape are quite conserved. Nonetheless, quantitative aspects of nucleosome packaging differ between species because, for example, the average length of linker DNA between nucleosomes can differ significantly even between closely related species. We recently showed that the difference in nucleosome spacing between two Hemiascomycete species-Saccharomyces cerevisiae and Kluyveromyces lactis-is established by trans-acting factors rather than being encoded in cis in the DNA sequence. Here, we generated several S. cerevisiae strains in which endogenous copies of candidate nucleosome spacing factors are deleted and replaced with the orthologous factors from K. lactis. We find no change in nucleosome spacing in such strains in which H1 or Isw1 complexes are swapped. In contrast, the K. lactis gene encoding the ATP-dependent remodeler Chd1 was found to direct longer internucleosomal spacing in S. cerevisiae, establishing that this remodeler is partially responsible for the relatively long internucleosomal spacing observed in K. lactis. By analyzing several chimeric proteins, we find that sequence differences that contribute to the spacing activity of this remodeler are dispersed throughout the coding sequence, but that the strongest spacing effect is linked to the understudied N-terminal end of Chd1. Taken together, our data find a role for sequence evolution of a chromatin remodeler in establishing quantitative aspects of the chromatin landscape in a species-specific manner.

  5. SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture.

    Science.gov (United States)

    Hilbert, Manuel; Noga, Akira; Frey, Daniel; Hamel, Virginie; Guichard, Paul; Kraatz, Sebastian H W; Pfreundschuh, Moritz; Hosner, Sarah; Flückiger, Isabelle; Jaussi, Rolf; Wieser, Mara M; Thieltges, Katherine M; Deupi, Xavier; Müller, Daniel J; Kammerer, Richard A; Gönczy, Pierre; Hirono, Masafumi; Steinmetz, Michel O

    2016-04-01

    Centrioles are critical for the formation of centrosomes, cilia and flagella in eukaryotes. They are thought to assemble around a nine-fold symmetric cartwheel structure established by SAS-6 proteins. Here, we have engineered Chlamydomonas reinhardtii SAS-6-based oligomers with symmetries ranging from five- to ten-fold. Expression of a SAS-6 mutant that forms six-fold symmetric cartwheel structures in vitro resulted in cartwheels and centrioles with eight- or nine-fold symmetries in vivo. In combination with Bld10 mutants that weaken cartwheel-microtubule interactions, this SAS-6 mutant produced six- to eight-fold symmetric cartwheels. Concurrently, the microtubule wall maintained eight- and nine-fold symmetries. Expressing SAS-6 with analogous mutations in human cells resulted in nine-fold symmetric centrioles that exhibited impaired length and organization. Together, our data suggest that the self-assembly properties of SAS-6 instruct cartwheel symmetry, and lead us to propose a model in which the cartwheel and the microtubule wall assemble in an interdependent manner to establish the native architecture of centrioles.

  6. 78 FR 17744 - Culturally Significant Objects Imported for Exhibition Determinations: “Maya: Hidden Worlds...

    Science.gov (United States)

    2013-03-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Objects Imported for Exhibition Determinations: ``Maya: Hidden Worlds Revealed... determine that the objects to be included in the exhibition ``Maya: Hidden Worlds Revealed,'' imported...

  7. Saturn's Rings Reveal Unexpected Phenomena

    Institute of Scientific and Technical Information of China (English)

    李颖

    2004-01-01

    Safely in orbit around Saturn, NASA's Cassini spacecraft sent back its first close-up images of the massive planet's rings on July 1, revealing an unexpectedly varied terrain featuring surprisingly sharp edges, braids and delicate ridges.

  8. Channels with ordered water and bipyridine mol-ecules in the porous coordination polymer {[Cu(SiF6)(C10H8N2)2]·2C10N2H8·5H2O} n.

    Science.gov (United States)

    Aubert, Emmanuel; Doudouh, Abdelatif; Peluso, Paola; Mamane, Victor

    2016-11-01

    The coordination polymer {[Cu(SiF6)(C10H8N2)2]·2C10H8N2·5H2O} n , systematic name: poly[[bis-(μ2-4,4'-bi-pyridine)(μ2-hexa-fluorido-silicato)copper(II)] 4,4'-bi-pyridine disolvate penta-hydrate], contains pores which are filled with water and 4,4'-bi-pyridine mol-ecules. As a result of the presence of these ordered species, the framework changes its symmetry from P4/mmm to P21/c. The 4,4'-bi-pyridine guest mol-ecules form chains inside the 6.5 × 6.9 Å pores parallel to [100] in which the mol-ecules inter-act through π-π stacking. Ordered water mol-ecules form infinite hydrogen-bonded chains inside a second pore system (1.6 × 5.3 Å free aperture) perpendicular to the 4,4'-bi-pyridine channels.

  9. Kinematic viscosity and speed of sound in gaseous CO, CO{sub 2}, SiF{sub 4}, SF{sub 6}, C{sub 4}F{sub 8}, and NH{sub 3} from 220 K to 375 K and pressures up to 3.4 MPa

    Energy Technology Data Exchange (ETDEWEB)

    Estrada-Alexanders, Andres F. [Fluid Metrology Group, Process Measurement Division, NIST, Gaithersburg, MD 20899-8360 (United States)], E-mail: afea@xanum.uam.mx; Hurly, John J. [Fluid Metrology Group, Process Measurement Division, NIST, Gaithersburg, MD 20899-8360 (United States)

    2008-02-15

    An acoustic Greenspan viscometer was used to measure the kinematic viscosity and speed of sound in the gases: CO, CO{sub 2}, SiF{sub 4}, SF{sub 6}, C{sub 4}F{sub 8}, and NH{sub 3}. The measurements cover the temperature range 220 K to 375 K, and pressures up to 3.4 MPa or 80% of the saturation pressure. The viscometer was calibrated at 298.16 K using five reference gases, Ar, He, N{sub 2}, CH{sub 4}, and C{sub 3}H{sub 8}, for which the viscosity and the speed of sound are known. With this calibration, we estimated the relative standard uncertainty of the kinematic viscosity u{sub r}({eta}/{rho}) = 0.006 and the uncertainty of speed of sound u{sub r}(c) = 0.0001, except for very low pressures where the signal-to-noise ratio deteriorates and quality factor for the Helmholtz mode is {<=}20.

  10. Determination of Human Hemoglobin Derivatives.

    Science.gov (United States)

    Attia, Atef M M; Ibrahim, Fatma A A; Abd El-Latif, Noha A; Aziz, Samir W; Abdelmottaleb Moussa, Sherif A; Elalfy, Mohsen S

    2015-01-01

    The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4-1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The method is highly sensitive, accurate and reproducible.

  11. REVEAL: Software Documentation and Platform Migration

    Science.gov (United States)

    Wilson, Michael A.; Veibell, Victoir T.

    2011-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA's Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This presentation specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as an overview of the content of the final report for that internship.

  12. Omics strategies for revealing Yersinia pestis virulence

    Science.gov (United States)

    Yang, Ruifu; Du, Zongmin; Han, Yanping; Zhou, Lei; Song, Yajun; Zhou, Dongsheng; Cui, Yujun

    2012-01-01

    Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis. PMID:23248778

  13. Revealing and Characterizing Dark Excitons Through Coherent Multidimensional Spectroscopy

    CERN Document Server

    Tollerud, Jonathan O; Davis, Jeffrey A

    2016-01-01

    Dark excitons are of fundamental importance in a broad range of contexts, but are difficult to study using conventional optical spectroscopy due to their weak interaction with light. We show how coherent multidimensional spectroscopy can reveal and characterize dark states. Using this approach, we identify different types of dark excitons in InGaAs/GaAs quantum wells and determine details regarding lifetimes, homogeneous and inhomogeneous linewidths, broadening mechanisms and coupling strengths. The observations of coherent coupling between bright and dark excitons hint at a role for a multi-step process by which excitons in the barrier can relax into the quantum wells.

  14. Health inequality - determinants and policies

    DEFF Research Database (Denmark)

    Diderichsen, Finn; Andersen, Ingelise; Manual, Celie;

    2012-01-01

    The review ”Health inequality – determinants and policies” identifies key-areas to be addressed with the aim to reduce the social inequality in health. The general life expectancy has steadily been increasing, but the data reveals marked social inequalities in health as well as life expectancy....... The review seeks to identify the causes of this social inequality. The analysis finds 12 areas of great importance for the inequality in health. This is i.e. early child development, schooling and education, the health behavior of the population, and the role of the health system. Within each of the 12 areas...

  15. [Mastitis revealing Churg-Strauss syndrome].

    Science.gov (United States)

    Dannepond, C; Le Fourn, E; de Muret, A; Ouldamer, L; Carmier, D; Machet, L

    2014-01-01

    Churg-Strauss syndrome often involves the skin, and this may sometimes reveal the disease. A 25-year-old woman was referred to a gynaecologist for inflammation of the right breast with breast discharge. Cytological analysis of the liquid showed numerous inflammatory cells, particularly polymorphonuclear eosinophils and neutrophils. Ultrasound examination of the breast was consistent with galactophoritis. CRP was normal, and hypereosinophilia was seen. The patient was subsequently referred to a dermatology unit. Skin examination revealed inflammation of the entire breast, which was painful, warm and erythematous; the border was oedematous with blisters. Necrotic lesions were also present on the thumbs and knees. Skin biopsy of the breast showed a dermal infiltrate with abundant infiltrate of polymorphonuclear eosinophils, including patchy necrosis and intraepidermal vesicles. Histological examination of a biopsy sample from a thumb revealed eosinophilic granuloma and leukocytoclastic vasculitis. The patient was also presenting asthma, pulmonary infiltrates and mononeuropathy at L3, consistent with Churg-Strauss syndrome. Breast involvement in Churg-Strauss syndrome is very rare (only one other case has been reported). This is the first case in which the breast condition revealed the disease. Cutaneous involvement of the breast is, however, also compatible with Wells' cellulitis. The lesions quickly disappeared with 1mg/kg/d oral prednisolone. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Genomics of sex determination.

    Science.gov (United States)

    Zhang, Jisen; Boualem, Adnane; Bendahmane, Abdelhafid; Ming, Ray

    2014-04-01

    Sex determination is a major switch in the evolutionary history of angiosperm, resulting 11% monoecious and dioecious species. The genomic sequences of papaya sex chromosomes unveiled the molecular basis of recombination suppression in the sex determination region, and candidate genes for sex determination. Identification and analyses of sex determination genes in cucurbits and maize demonstrated conservation of sex determination mechanism in one lineage and divergence between the two systems. Epigenetic control and hormonal influence of sex determination were elucidated in both plants and animals. Intensive investigation of potential sex determination genes in model species will improve our understanding of sex determination gene network. Such network will in turn accelerate the identification of sex determination genes in dioecious species with sex chromosomes, which are burdensome due to no recombination in sex determining regions. The sex determination genes in dioecious species are crucial for understanding the origin of dioecy and sex chromosomes, particularly in their early stage of evolution.

  17. Df(3R)Esp13/TM6C片段RNA干扰不同基因对黑腹果蝇睡眠时间的影响%INTERFERENCE OF DIFFERENT GENES IN Df(3R)Esp13/TM6C RNA FRAGMENT AFFECT SLEEP DURATION OF DROSOPHILA MELANOGASTER

    Institute of Scientific and Technical Information of China (English)

    张迪; 张可兴; 黄莉莉; 李廷利

    2013-01-01

    Objective:To find the proper genes that affect sleep duration.Methods:Different genes of RNA interference in Df(3R)Espl3/TM6C fragment of the 7 -day old Drosophila melanogaster and CS strains of D.melanogaster were used in the research.Drosophila Activity Monitor System( DAMS) was used to record the Drosophila' s total sleep duration within 24 hours.The data was analyzed according to different kinds of strains.Results:Compared with the prosopon of wild CS strains, the total sleep duration of genes of RNA inference dys, exo84 and Nf1 were significantly different(P<0.001).Conclusion:The genes of Nf1, exo84 and gro are related to the sleep duration of D.melanogaster.%目的:寻找影响果蝇睡眠时间的基因.方法:选择Df(3R) Esp13/TM6C片段RNA干扰不同基因的7日龄黑腹果蝇与野生型CS品系7日龄黑腹果蝇为研究对象,利用果蝇活动监测器系统(Drosophila Activity Monitor System,DAMS),记录果蝇的睡眠时间,累计计算24 h内果蝇睡眠时间,将测得的各品系果蝇睡眠时间进行对比分析.结果:RNA干扰dys,exo84和Nfl基因的黑腹果蝇与野生型CS品系黑腹果蝇相比较具有极显著性差异(P<0.00l).结论:Nfl,exo84和gro基因与睡眠有关.

  18. NTP Toxicology and Carcinogenesis Studies of Xylenes (Mixed) (60% m-Xylene, 14% p-Xylene, 9% o-Xylene, and 17% Ethylbenzene) (CAS No. 1330-20-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1986-12-01

    The technical grade of xylenes (mixed) (hereafter termed xylenes) contains the three isomeric forms and ethylbenzene (percentage composition shown above). The annual production for 1985 was approximately 7.4 x 108 gallons. Xylenes is used as a solvent and a cleaning agent and as a degreaser and is a constituent of aviation and automobile fuels. Xylenes is also used in the production of benzoic acid, phthalate anhydride, and isophthalic and terephthalic acids as well as their dimethyl esters. Toxicology and carcinogenesis studies of xylenes were conducted in laboratory animals because a large number of workers are exposed and because the long- term effects of exposure to xylenes were not known. Exposure for the present studies was by gavage in corn oil. In single-administration studies, groups of five F344/N rats and B6C3F1 mice of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of xylenes caused deaths at 6,000 mg/kg in rats and mice of each sex and at 4,000 mg/kg in male rats. In rats, clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. Tremors, prone position, and slowed breathing were recorded for mice on day 3, but all mice appeared normal by the end of the 2- week observation period. In 14- day studies, groups of five rats of each sex were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg, and groups of five mice of each sex received 0, 250, 500, 1,000, 2,000, or 4,000 mg/kg. Chemical- related mortality occurred only at 2,000 mg/kg in rats and at 4,000 mg/kg in mice. Rats and mice exhibited shallow breathing and prostration within 48 hours following dosing at 2,000 mg/kg. These signs persisted until day 12 for rats, but no clinical signs were noted during the second week for mice. In 13- week studies, groups of 10 rats of each sex received 0, 62.5, 125, 250, 500, or 1,000 mg

  19. Recurrence Relations and Determinants

    CERN Document Server

    Janjic, Milan

    2011-01-01

    We examine relationships between two minors of order n of some matrices of n rows and n+r columns. This is done through a class of determinants, here called $n$-determinants, the investigation of which is our objective. We prove that 1-determinants are the upper Hessenberg determinants. In particular, we state several 1-determinants each of which equals a Fibonacci number. We also derive relationships among terms of sequences defined by the same recurrence equation independently of the initial conditions. A result generalizing the formula for the product of two determinants is obtained. Finally, we prove that the Schur functions may be expressed as $n$-determinants.

  20. Revealing the Anatomy of Vote Trading

    CERN Document Server

    Guerrero, Omar A

    2016-01-01

    Cooperation in the form of vote trading, also known as logrolling, is central for law-making processes, shaping the development of democratic societies. Empirical evidence of logrolling is scarce and limited to highly specific situations because existing methods are not easily applicable to broader contexts. We have developed a general and scalable methodology for revealing a network of vote traders, allowing us to measure logrolling on a large scale. Analysis on more than 9 million votes spanning 40 years in the U.S. Congress reveals a higher logrolling prevalence in the Senate and an overall decreasing trend over recent congresses, coincidental with high levels of political polarization. Our method is applicable in multiple contexts, shedding light on many aspects of logrolling and opening new doors in the study of hidden cooperation.

  1. Revealing interference by continuous variable discordant states.

    Science.gov (United States)

    Meda, A; Olivares, S; Degiovanni, I P; Brida, G; Genovese, M; Paris, M G A

    2013-08-15

    In general, a pair of uncorrelated Gaussian states mixed in a beam splitter (BS) produces a correlated state at the output. However, when the inputs are identical Gaussian states the output state is equal to the input, and no correlations appear, as the interference had not taken place. On the other hand, since physical phenomena do have observable effects, and the BS is there, a question arises on how to reveal the interference between the two beams. We prove theoretically and demonstrate experimentally that this is possible if at least one of the two beams is prepared in a discordant, i.e., Gaussian correlated, state with a third beam. We also apply the same technique to reveal the erasure of polarization information. Our experiment involves thermal states and the results show that Gaussian discordant states, even when they show a positive Glauber P-function, may be useful to achieve specific tasks.

  2. Reveal quantum correlation in complementary bases

    OpenAIRE

    Shengjun Wu; Zhihao Ma; Zhihua Chen; Sixia Yu

    2013-01-01

    An essential feature of genuine quantum correlation is the simultaneous existence of correlation in complementary bases. We reveal this feature of quantum correlation by defining measures based on invariance under a basis change. For a bipartite quantum state, the classical correlation is the maximal correlation present in a certain optimum basis, while the quantum correlation is characterized as a series of residual correlations in the mutually unbiased bases. Compared with other approaches ...

  3. Genes but not genomes reveal bacterial domestication of Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Delphine Passerini

    Full Text Available BACKGROUND: The population structure and diversity of Lactococcus lactis subsp. lactis, a major industrial bacterium involved in milk fermentation, was determined at both gene and genome level. Seventy-six lactococcal isolates of various origins were studied by different genotyping methods and thirty-six strains displaying unique macrorestriction fingerprints were analyzed by a new multilocus sequence typing (MLST scheme. This gene-based analysis was compared to genomic characteristics determined by pulsed-field gel electrophoresis (PFGE. METHODOLOGY/PRINCIPAL FINDINGS: The MLST analysis revealed that L. lactis subsp. lactis is essentially clonal with infrequent intra- and intergenic recombination; also, despite its taxonomical classification as a subspecies, it displays a genetic diversity as substantial as that within several other bacterial species. Genome-based analysis revealed a genome size variability of 20%, a value typical of bacteria inhabiting different ecological niches, and that suggests a large pan-genome for this subspecies. However, the genomic characteristics (macrorestriction pattern, genome or chromosome size, plasmid content did not correlate to the MLST-based phylogeny, with strains from the same sequence type (ST differing by up to 230 kb in genome size. CONCLUSION/SIGNIFICANCE: The gene-based phylogeny was not fully consistent with the traditional classification into dairy and non-dairy strains but supported a new classification based on ecological separation between "environmental" strains, the main contributors to the genetic diversity within the subspecies, and "domesticated" strains, subject to recent genetic bottlenecks. Comparison between gene- and genome-based analyses revealed little relationship between core and dispensable genome phylogenies, indicating that clonal diversification and phenotypic variability of the "domesticated" strains essentially arose through substantial genomic flux within the dispensable

  4. Mediastinal Mature Teratoma Revealed by Empyema

    Directory of Open Access Journals (Sweden)

    Mohammed Raoufi

    2016-01-01

    Full Text Available Teratomas are germ cell tumors, manifested with a great variety of clinical features; the most common extragonadal site is the anterior mediastinum. In this case, we report the patient with a large mature mediastinal teratoma with several components of ectodermal and endothermal epithelium. A 24-year-old female patient presented with history of persistent chest pain and progressively aggravating dyspnea for the previous 3 months. A chest X-ray showed a large opacity of the entire left hemithorax. Transcutaneous needle aspiration revealed a purulent fluid. The tube thoracostomy was introduced and the effusion was evacuated. Some weeks later, patient was seen in emergency for persistent cough and lateral chest pain. CT scan revealed a mass of the left hemithorax. The mass showed heterogeneous density, without compressing mediastinum great vessels and left hilar structures. Lipase value was elevated in needle aspiration. The patient underwent a total resection of the mediastinum mass via a left posterolateral thoracotomy. Microscopy revealed a mature teratoma with cystic structures. The patient subsequently made a full recovery. This case provide benign mediastinal teratoma with total atelectasis of left lung and elevated lipase value in needle transcutaneous aspiration; this event is explained by pancreatic component in the cystic tumor. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.

  5. Genetic diversity of Toxoplasma gondii isolates in Egyptian feral cats reveals new genotypes.

    Science.gov (United States)

    Al-Kappany, Y M; Rajendran, C; Abu-Elwafa, S A; Hilali, M; Su, C; Dubey, J P

    2010-12-01

    Cats are important in the epidemiology of Toxoplasma gondii because they are the only hosts that excrete environmentally resistant oocysts in feces. In the present study, 115 viable T. gondii isolates from tissues of cats from Egypt were genotyped using 10 PCR-restriction fragment length polymorphism markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) and DNA from tachyzoites. Seven genotypes were recognized including the clonal Type II, Type III (2 genotypes), and 4 atypical genotypes. Ninety percent (103 of 115) of isolates were clonal, i.e., Type II (n  =  61) and Type III (n  =  42) strains. Of the 61 Type II strains, all had the Type II alleles at all loci, except for 2 strains that had allele I at Apico. Eight isolates were divided into 4 atypical genotypes. One of these genotypes (with 4 isolates) was previously reported in dogs from Sri Lanka and in sand cats from the United Arab Emirates. Four isolates had mixed infections. These results revealed a strong clonal population structure with the dominance of clonal Type II and III lineages of T. gondii in feral cats from Egypt.

  6. Genetic characterization of Toxoplasma gondii from Brazilian wildlife revealed abundant new genotypes

    Directory of Open Access Journals (Sweden)

    S.N. Vitaliano

    2014-12-01

    Full Text Available This study aimed to isolate and genotype T. gondii from Brazilian wildlife. For this purpose, 226 samples were submitted to mice bioassay and screened by PCR based on 18S rRNA sequences. A total of 15 T. gondii isolates were obtained, including samples from four armadillos (three Dasypus novemcinctus, one Euphractus sexcinctus, three collared anteaters (Tamandua tetradactyla, three whited-lipped peccaries (Tayassu pecari, one spotted paca (Cuniculus paca, one oncilla (Leopardus tigrinus, one hoary fox (Pseudalopex vetulus, one lineated woodpecker (Dryocopus lineatus and one maned wolf (Chrysocyon brachyurus. DNA from the isolates, originated from mice bioassay, and from the tissues of the wild animal, designated as “primary samples”, were genotyped by PCR–restriction fragment length polymorphism (PCR/RFLP, using 12 genetic markers (SAG1, SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L258, PK1, CS3 and Apico. A total of 17 genotypes were identified, with 13 identified for the first time and four already reported in published literature. Results herein obtained corroborate previous studies in Brazil, confirming high diversity and revealing unique genotypes in this region. Given most of genotypes here identified are different from previous studies in domestic animals, future studies on T. gondii from wildlife is of interest to understand population genetics and structure of this parasite.

  7. Revealing digital documents. Concealed structures in data

    CERN Document Server

    Voß, Jakob

    2011-01-01

    This short paper gives an introduction to a research project to analyze how digital documents are structured and described. Using a phenomenological approach, this research will reveal common patterns that are used in data, independent from the particular technology in which the data is available. The ability to identify these patterns, on different levels of description, is important for several applications in digital libraries. A better understanding of data structuring will not only help to better capture singular characteristics of data by metadata, but will also recover intended structures of digital objects, beyond long term preservation.

  8. Revealing Cosmic Magnetism with Radio Polarimetry

    CERN Document Server

    Gaensler, Bryan M

    2007-01-01

    While gravitation sustains the on-going evolution of the cosmos, it is magnetism that breaks gravity's symmetry and that provides the pathway to the non-thermal Universe. By enabling processes such as anisotropic pressure support, particle acceleration, and jet collimation, magnetism has for billions of years regulated the feedback vital for returning matter to the interstellar and intergalactic medium. After reviewing recent results that demonstrate the unique view of magnetic fields provided by radio astronomy, I explain how the Square Kilometre Array will provide data that will reveal what cosmic magnets look like, how they formed, and what role they have played in the evolving Universe.

  9. Infections Revealing Complement Deficiency in Adults

    Science.gov (United States)

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  10. Superstitious perceptions reveal properties of internal representations.

    Science.gov (United States)

    Gosselin, Frédéric; Schyns, Philippe G

    2003-09-01

    Everyone has seen a human face in a cloud, a pebble, or blots on a wall. Evidence of superstitious perceptions has been documented since classical antiquity, but has received little scientific attention. In the study reported here, we used superstitious perceptions in a new principled method to reveal the properties of unobservable object representations in memory. We stimulated the visual system with unstructured white noise. Observers firmly believed that they perceived the letter S in Experiment 1 and a smile on a face in Experiment 2. Using reverse correlation and computational analyses, we rendered the memory representations underlying these superstitious perceptions.

  11. Apocalypto: revealing lost text with XMT

    Science.gov (United States)

    Mills, David; Davis, Graham R.; Lai, Yu-kun; Rosin, Paul

    2014-09-01

    "Can brute-force high-contrast tomography techniques and image processing techniques retrieve textual content from damaged heritage materials?" The Dental Institute at Queen Mary University of London (QMUL) is the leading centre for very high contrast X-Ray Microtomography imaging. The Apocalypto Project is our collaboration with the heritage community and experts in Computer Vision systems in the Computer Science Department at Cardiff University. This collaboration has developed techniques and a workflow that allows us to reveal textual content from moisture-damaged parchment rolls. This article will also present some initial results from burned and heat shrunken parchment rolls, an insect damaged Mamluk cap and a birch bark roll.

  12. Putative bioactive motif of tritrpticin revealed by an antibody with biological receptor-like properties.

    Directory of Open Access Journals (Sweden)

    Raghava Sharma

    Full Text Available Antimicrobial peptides represent one of the most promising future strategies for combating infections and microbial drug resistance. Tritrpticin is a 13mer tryptophan-rich cationic antimicrobial peptide with a broad spectrum of activity whose application in antimicrobial therapy has been hampered by ambiguity about its biological target and consequently the molecular interactions necessary for its antimicrobial activity. The present study provides clues about the mechanism of action of tritripticin by using a unique monoclonal antibody (mAb as a 'physiological' structural scaffold. A pool of mAbs were generated against tritrpticin and based on its high affinity and ability to bind tritrpticin analogs, mAb 6C6D7 was selected and characterized further. In a screening of phage displayed random peptides, this antibody was able to identify a novel antimicrobial peptide with low sequence homology to tritrpticin, suggesting that the mAb possessed the physico-chemical characteristics mimicking the natural receptor. Subsequently, thermodynamics and molecular modeling identified a core group of hydrophobic residues in tritrpticin arranged in a distorted's' shaped conformation as critical for antibody binding. Comparison of the mAb induced conformation with the micelle bound structure of tritrpticin reveals how a common motif may be able to interact with multiple classes of biomolecules thus extending the target range of this innate immune peptide. Based on the concurrence between thermodynamic and structural data our results reveal a template that can be used to design novel antimicrobial pharmacophores while simultaneously demonstrating at a more fundamental level the potential of mAbs to act as receptor surrogates.

  13. Revealing Event Saliency in Unconstrained Video Collection.

    Science.gov (United States)

    Zhang, Dingwen; Han, Junwei; Jiang, Lu; Ye, Senmao; Chang, Xiaojun

    2017-04-01

    Recent progresses in multimedia event detection have enabled us to find videos about a predefined event from a large-scale video collection. Research towards more intrinsic unsupervised video understanding is an interesting but understudied field. Specifically, given a collection of videos sharing a common event of interest, the goal is to discover the salient fragments, i.e., the curt video fragments that can concisely portray the underlying event of interest, from each video. To explore this novel direction, this paper proposes an unsupervised event saliency revealing framework. It first extracts features from multiple modalities to represent each shot in the given video collection. Then, these shots are clustered to build the cluster-level event saliency revealing framework, which explores useful information cues (i.e., the intra-cluster prior, inter-cluster discriminability, and inter-cluster smoothness) by a concise optimization model. Compared with the existing methods, our approach could highlight the intrinsic stimulus of the unseen event within a video in an unsupervised fashion. Thus, it could potentially benefit to a wide range of multimedia tasks like video browsing, understanding, and search. To quantitatively verify the proposed method, we systematically compare the method to a number of baseline methods on the TRECVID benchmarks. Experimental results have demonstrated its effectiveness and efficiency.

  14. Symptomatic hypopituitarism revealing primary suprasellar lymphoma

    Directory of Open Access Journals (Sweden)

    M'rabti Hind

    2010-11-01

    Full Text Available Abstract Background The most common cause of hypopituitarism is pituitary adenoma. However, in the case of suprasellar masses different etiologies are possible. We report an unusual case of primary suprasellar lymphoma presented with hypopituitarism. Case presentation A 26 year old woman presented with amenorrhea, galactorrhea and neurological disorders. Also, the laboratory work-up revealed partial hypopituitarism. The magnetic resonance imaging of the head showed a suprasellar mass. A presumptive diagnosis of granulomatous processes was made and the patient was given steroid therapy. Repeated brain MRI detected new lesions in the brain with regression of the suprasellar mass. Stereotactic biopsy of the paraventricular lesion revealed the diagnosis of B-cell lymphoma. Conclusion This case presentation reports a rare cause of hypopituitarism. Primary suprasellar lymphoma is extremely rare and represented a real diagnostic challenge. Besides, suprasellar masses are varied in aetiology and can present diagnostic problems for a radiologist. Also, because of the increased incidence of PCNSL, lymphoma must be kept in mind in the differential diagnosis of lesions in the suprasellar region.

  15. Fluorine for Hydrogen Exchange in the Hydrofluorobenzene Derivatives C6HxF(6-x), where x = 2, 3, 4 and 5 by Monomeric [1,2,4-(Me3C)3C5H2]2CeH; The Solid State Isomerization of [1,2,4-(Me3C)3C5H2]2Ce(2,3,4,5-C6HF4) to [1,2,4-(Me3C)3C5H2]2Ce(2,3,4,6-C6HF4)

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Richard; Werkema, Evan L.; Andersen, Richard A.

    2008-04-21

    The reaction between monomeric bis(1,2,4-tri-t-butylcyclopentadienyl)cerium hydride, Cp'2CeH, and several hydrofluorobenzene derivatives is described. The aryl derivatives that are the primary products, Cp'2Ce(C6H5-xFx) where x = 1,2,3,4, are thermally stable enough to be isolated in only two cases, since all of them decompose at different rates to Cp'2CeF and a fluorobenzyne; the latter is trapped by either solvent when C6D6 is used or by a Cp'H ring when C6D12 is the solvent. The trapped products are identified by GCMS analysis after hydrolysis. The aryl derivatives are generated cleanly by reaction of the metallacycle, Cp'((Me3C)2C5H2C(Me2)CH2)Ce, with a hydrofluorobenzene and the resulting arylcerium products, in each case, are identified by their 1H and 19F NMR spectra at 20oC. The stereochemical principle that evolves from these studies is that the thermodynamic isomer is the one in which the CeC bond is flanked by two ortho-CF bonds. This orientation is suggested to arise from the negative charge that is localized on the ipso-carbon atom due to Co(delta+)-Fo(delta-) polarization. The preferred regioisomer is determined by thermodynamic rather than kinetic effects; this is illustrated by the quantitative, irreversible solid-state conversion at 25oC over two months of Cp'2Ce(2,3,4,5-C6HF4) to Cp'2Ce(2,3,4,6-C6HF4), an isomerization that involves a CeC(ipso) for C(ortho)F site exchange.

  16. Fluorine for Hydrogen Exchange in the Hydrofluorobenzene Derivatives C6HxF(6-x), where x = 2, 3, 4 and 5 by Monomeric [1,2,4-(Me3C)3C5H2]2CeH; The Solid State Isomerization of [1,2,4-(Me3C)3C5H2]2Ce(2,3,4,5-C6HF4) to [1,2,4-(Me3C)3C5H2]2Ce(2,3,4,6-C6HF4)

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Richard; Werkema, Evan L.; Andersen, Richard A.

    2008-04-21

    The reaction between monomeric bis(1,2,4-tri-t-butylcyclopentadienyl)cerium hydride, Cp'2CeH, and several hydrofluorobenzene derivatives is described. The aryl derivatives that are the primary products, Cp'2Ce(C6H5-xFx) where x = 1,2,3,4, are thermally stable enough to be isolated in only two cases, since all of them decompose at different rates to Cp'2CeF and a fluorobenzyne; the latter is trapped by either solvent when C6D6 is used or by a Cp'H ring when C6D12 is the solvent. The trapped products are identified by GCMS analysis after hydrolysis. The aryl derivatives are generated cleanly by reaction of the metallacycle, Cp'((Me3C)2C5H2C(Me2)CH2)Ce, with a hydrofluorobenzene and the resulting arylcerium products, in each case, are identified by their 1H and 19F NMR spectra at 20oC. The stereochemical principle that evolves from these studies is that the thermodynamic isomer is the one in which the CeC bond is flanked by two ortho-CF bonds. This orientation is suggested to arise from the negative charge that is localized on the ipso-carbon atom due to Co(delta+)-Fo(delta-) polarization. The preferred regioisomer is determined by thermodynamic rather than kinetic effects; this is illustrated by the quantitative, irreversible solid-state conversion at 25oC over two months of Cp'2Ce(2,3,4,5-C6HF4) to Cp'2Ce(2,3,4,6-C6HF4), an isomerization that involves a CeC(ipso) for C(ortho)F site exchange.

  17. Revealed Quantum Information in Weak Interaction Processes

    CERN Document Server

    Hiesmayr, B C

    2014-01-01

    We analyze the achievable limits of the quantum information processing of the weak interaction revealed by hyperons with spin. We find that the weak decay process corresponds to an interferometric device with a fixed visibility and fixed phase difference for each hyperon. Nature chooses rather low visibilities expressing a preference to parity conserving or violating processes (except for the decay $\\Sigma^+\\longrightarrow p \\pi^0$). The decay process can be considered as an open quantum channel that carries the information of the hyperon spin to the angular distribution of the momentum of the daughter particles. We find a simple geometrical information theoretic interpretation of this process: two quantization axes are chosen spontaneously with probabilities $\\frac{1\\pm\\alpha}{2}$ where $\\alpha$ is proportional to the visibility times the real part of the phase shift. Differently stated the weak interaction process corresponds to spin measurements with an imperfect Stern-Gerlach apparatus. Equipped with this...

  18. Social patterns revealed through random matrix theory

    Science.gov (United States)

    Sarkar, Camellia; Jalan, Sarika

    2014-11-01

    Despite the tremendous advancements in the field of network theory, very few studies have taken weights in the interactions into consideration that emerge naturally in all real-world systems. Using random matrix analysis of a weighted social network, we demonstrate the profound impact of weights in interactions on emerging structural properties. The analysis reveals that randomness existing in particular time frame affects the decisions of individuals rendering them more freedom of choice in situations of financial security. While the structural organization of networks remains the same throughout all datasets, random matrix theory provides insight into the interaction pattern of individuals of the society in situations of crisis. It has also been contemplated that individual accountability in terms of weighted interactions remains as a key to success unless segregation of tasks comes into play.

  19. Revealing effective classifiers through network comparison

    CERN Document Server

    Gallos, Lazaros K

    2014-01-01

    The ability to compare complex systems can provide new insight into the fundamental nature of the processes captured in ways that are otherwise inaccessible to observation. Here, we introduce the $n$-tangle method to directly compare two networks for structural similarity, based on the distribution of edge density in network subgraphs. We demonstrate that this method can efficiently introduce comparative analysis into network science and opens the road for many new applications. For example, we show how the construction of a phylogenetic tree across animal taxa according to their social structure can reveal commonalities in the behavioral ecology of the populations, or how students create similar networks according to the University size. Our method can be expanded to study a multitude of additional properties, such as network classification, changes during time evolution, convergence of growth models, and detection of structural changes during damage.

  20. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Jeffrey [ORNL; Bilheux, Hassina Z [ORNL; Kang, Misun [ORNL; Voisin, Sophie [ORNL; Cheng, Chu-Lin [ORNL; Horita, Jusuke [ORNL; Perfect, Edmund [ORNL

    2013-01-01

    Many terrestrial ecosystem processes are constrained by water availability and transport within the soil. Knowledge of plant water fluxes is thus critical for assessing mechanistic processes linked to biogeochemical cycles, yet resolution of root structure and xylem water transport dynamics has been a particularly daunting task for the ecologist. Through neutron imaging, we demonstrate the ability to non-invasively monitor individual root functionality and water fluxes within Zea mays L. (maize) and Panicum virgatum L. (switchgrass) seedlings growing in a sandy medium. Root structure and growth were readily imaged by neutron radiography and neutron computed tomography. Seedlings were irrigated with water or deuterium oxide and imaged through time as a growth lamp was cycled on to alter leaf demand for water. Sub-millimeter scale resolution reveals timing and magnitudes of root water uptake, redistribution within the roots, and root-shoot hydraulic linkages, relationships not well characterized by other techniques.

  1. [Pneumothorax revealed by postoperative computed tomography].

    Science.gov (United States)

    Ikeda, Shizuka; Katori, Kiyoshi; Fujimoto, Minoru; Nitahara, Keiichi; Higa, Kazuo

    2005-11-01

    We report a case of pneumothorax revealed by postoperative computed tomography. A 39-year-old obese woman (height 153 cm, weight 70 kg) with fractures of the radius, ulna, clavicle, and femur in a traffic accident, was scheduled for osteosynthesis. Anesthesia was induced with thiopental and maintained with 50% nitrous oxide in oxygen and sevoflurane. The Spo2 decreased from 99% to 94% during the surgery. Bilateral chest sounds were symmetrical. The Spo2 increased to 100% after discontinuation of nitrous oxide. Pneumothorax was not evident on a postoperative chest X-ray, but computed tomography of the chest demonstrated right-sided pneumothorax. An ECG electrode had overlapped the fractured rib on the preoperative chest X-ray.

  2. Can Clustering in Genotype Space Reveal "Niches"?

    Science.gov (United States)

    D'Andrea, Rafael; Ostling, Annette

    2016-01-01

    Community ecology lacks the success enjoyed by population genetics to quantify the relative roles played by deterministic and stochastic processes. It has been proposed that clustered patterns of abundance in genotype space provide evidence of selection in microbial communities, since no such clustering would arise in the absence of selection. We critique this test for its unrealistic null hypothesis. We show mathematically and with simulations that point mutations alone lead to clustering in genotype space by causing correlations between abundances of similar genotypes. We also show potential deviations from the mutation-only pattern caused by immigration from a source pool. Clustered patterns in genotype space may still be revealing of selection if analyzed quantitatively but only if neutral and selective regimes can be distinguished once mutation and immigration are included in the null model.

  3. Reward reveals dissociable aspects of sustained attention.

    Science.gov (United States)

    Esterman, Michael; Reagan, Andrew; Liu, Guanyu; Turner, Caroline; DeGutis, Joseph

    2014-12-01

    Although reward is known to have a powerful influence on performance, its effects on the ability to continuously sustain performance over time are poorly understood. The current study examines multiple measures of sustained attention (accuracy and variability) and their decrements over time, while introducing reward in the form of a monetary incentive or the promise of early completion. Compared with unrewarded participants, rewarded participants demonstrated greater overall accuracy and lower reaction time variability. However, rewarded and unrewarded participants displayed nearly identical decrements in performance over time, suggesting that these aspects of sustained attention are far less malleable by enhanced effort. This study helps to resolve conflicting models of sustained attention as it reveals that some aspects of performance are due to motivational lapses whereas others are due to the depletion of cognitive resources that cannot be easily overcome.

  4. Double peaks reveal rare diplomonad sex.

    Science.gov (United States)

    Andersson, Jan O

    2012-02-01

    Diplomonads, single-celled eukaryotes, are unusual in having two nuclei. Each nucleus contains two copies of the genome and is transcriptionally active. It has long been assumed that diplomonads in general and Giardia intestinalis in particular are asexual. Genomic and population genetic data now challenge that assumption and extensive allelic sequence heterogeneity has been reported in some but not all examined diplomonad lineages. Here it is argued, in contrast to common assumptions, that allelic differences indicate recent sexual events, and isolates that have divided asexually for many generations have lost their allelic variation owing to within-cell recombination. Consequently, directed studies of the allelic sequence heterogeneity in diverse diplomonad lineages are likely to reveal details about the enigmatic diplomonad sexual life cycle.

  5. Chemotaxis: new role for Ras revealed

    Institute of Scientific and Technical Information of China (English)

    Jianshe Yan; Dale Hereld; Tian Jin

    2010-01-01

    @@ A recent study of chemotaxis revealed a new role for the proto-oncogene Ras in the social ameba Dictyostelium discoideum.Chemotaxis,the directional movement of cells toward chemokines and other chemoattractants,plays critical roles in diverse physiological processes,such as mobilization of immune cells to fight invading microorganisms,targeting of metastatic cancer cells to specific tissues,and guidance of sperm cells to ova during fertilization.This work,published in the July 26 issue of The Journal of Cell Biology,was conducted in Dr.Devreotes' lab at John Hopkins University and Dr.Parent's lab at National Cancer Institute.This research team demonstrated that RasC functions as an upstream regulator of TORC2 and thereby governs the effects of TORC2-PKB signaling on the cytoskeleton and cell migration.

  6. Licking microstructure reveals rapid attenuation of neophobia.

    Science.gov (United States)

    Monk, Kevin J; Rubin, Benjamin D; Keene, Jennifer C; Katz, Donald B

    2014-03-01

    Many animals hesitate when initially consuming a novel food and increase their consumption of that food between the first and second sessions of access-a process termed attenuation of neophobia (AN). AN has received attention as a model of learning and memory; it has been suggested that plasticity resulting from an association of the novel tastant with "safe outcome" results in a change in the neural response to the tastant during the second session, such that consumption increases. Most studies have reported that AN emerges only an hour or more after the end of the first exposure to the tastant, consistent with what is known of learning-related plasticity. But these studies have typically measured consumption, rather than real-time behavior, and thus the possibility exists that a more rapidly developing AN remains to be discovered. Here, we tested this possibility, examining both consumption and individual lick times in a novel variant of a brief-access task (BAT). When quantified in terms of consumption, data from the BAT accorded well with the results of a classic one-bottle task-both revealed neophobia/AN specific to higher concentrations (for instance, 28mM) of saccharin. An analysis of licking microstructure, however, additionally revealed a real-time correlate of neophobia-an explicit tendency, similarly specific for 28-mM saccharin, to cut short the initial bout of licks in a single trial (compared with water). This relative hesitancy (i.e., the shortness of the first lick bout to 28-mM saccharin compared with water) that constitutes neophobia not only disappeared between sessions but also gradually declined in magnitude across session 1. These data demonstrate that the BAT accurately measures AN, and that aspects of AN-and the processes underlying familiarization-begin within minutes of the very first taste.

  7. Stochastic homothetically revealed preference for tight stochastic demand functions

    OpenAIRE

    Jan Heufer

    2009-01-01

    This paper strengthens the framework of stochastic revealed preferences introduced by Bandyopadhyay et al. (1999, 2004) for stochastic homothetically revealed preferences for tight stochastic demand functions.

  8. Airborne observations reveal elevational gradient in tropical forest isoprene emissions

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Dasa; Guenther, Alex B.; Shilling, John E.; Yu, Haofei; Huang, Maoyi; Zhao, Chun; Yang, Qing; Martin, Scot T.; Artaxo, Paulo; Kim, Saewung; Seco, Roger; Stavrakou, T.; Longo, Karla; Tota, Julio; Augusto Ferreira de Souza, Rodrigo; Vega, Oscar; Liu, Ying; Shrivastava, ManishKumar B.; Alves, Eliane; Cavalcante Dos Santos, Fernando; Leng, Guoyong; Hu, Zhiyuan

    2017-05-23

    Isoprene dominates global non-methane volatile organic compound emissions, and impacts tropospheric chemistry by influencing oxidants and aerosols. Isoprene emission rates vary over several orders of magnitude for different plants, and characterizing this immense biological chemodiversity is a challenge for estimating isoprene emission from tropical forests. Here we present the isoprene emission estimates from aircraft eddy covariance measurements over the Amazonian forest. We report isoprene emission rates that are three times higher than satellite top-down estimates and 35% higher than model predictions. The results reveal strong correlations between observed isoprene emission rates and terrain elevations, which are confirmed by similar correlations between satellite-derived isoprene emissions and terrain elevations. We propose that the elevational gradient in the Amazonian forest isoprene emission capacity is determined by plant species distributions and can substantially explain isoprene emission variability in tropical forests, and use a model to demonstrate the resulting impacts on regional air quality.

  9. Metabolomics reveals metabolic biomarkers of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  10. Demand Model Combining Stated And Revealed Preference Data

    Directory of Open Access Journals (Sweden)

    Luciana Londero Brandli

    2007-10-01

    Full Text Available The revealed and stated preference methods have been contributing a lot for the development of the econometric literature in the attempt of determining the variables that influence the individual decision in a choice process. This article combines preference data, with the objective of obtaining the advantages of the complementarity of the forces and frankness of both types of data. The approach involves the estimate of a model only with RP data, only with SP data and combining RP and SP data. The application is in the housing market, where it is observed, through the literature, that most of the papers of the consumer's choice has restricted the only one approaches. The utility functions obtained show the relative importance of the attributes, the tendency of behavior through the signs and its significance statistical. The results analysis of the models indicates differences and similarities about the attribute’s behavior.

  11. Stochastic heart-rate model can reveal pathologic cardiac dynamics

    Science.gov (United States)

    Kuusela, Tom

    2004-03-01

    A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

  12. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

  13. Ancient DNA sequence revealed by error-correcting codes.

    Science.gov (United States)

    Brandão, Marcelo M; Spoladore, Larissa; Faria, Luzinete C B; Rocha, Andréa S L; Silva-Filho, Marcio C; Palazzo, Reginaldo

    2015-07-10

    A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code.

  14. SIS - Status Determination

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Status Determination dataset within the Species Information System (SIS) contains information related to overfishing, overfished, and approaching overfished...

  15. Standardization of hormone determinations.

    Science.gov (United States)

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization.

  16. determinants of mate selection choice among university students in ...

    African Journals Online (AJOL)

    Elizabeth

    This study sought to identify factors that determine mate selection choice among .... become unemployed, lack career motivation or show laziness (Betzig,. 1989). .... (2005) which revealed that emotional characteristics, personality traits.

  17. Internal Migration Determinants: Evidence from Northern Region of ...

    African Journals Online (AJOL)

    2016-05-01

    May 1, 2016 ... important determinants of migration decisions, while gender is not. ..... the result of the data analysis revealed that majority of both current and .... of females in migration is perhaps due to changes in gender roles at the study.

  18. Speeding Clouds May Reveal Invisible Black Holes

    Science.gov (United States)

    Kohler, Susanna

    2017-07-01

    Several small, speeding clouds have been discovered at the center of our galaxy. A new study suggests that these unusual objects may reveal the lurking presence of inactive black holes.Peculiar Cloudsa) Velocity-integrated intensity map showing the location of the two high-velocity compact clouds, HCN0.0090.044 and HCN0.0850.094, in the context of larger molecular clouds. b) and c) Latitude-velocity and longitude-velocity maps for HCN0.0090.044 and HCN0.0850.094, respectively. d) and e) spectra for the two compacts clouds, respectively. Click for a closer look. [Takekawa et al. 2017]Sgr A*, the supermassive black hole marking the center of our galaxy, is surrounded by a region roughly 650 light-years across known as the Central Molecular Zone. This area at the heart of our galaxy is filled with large amounts of warm, dense molecular gas that has a complex distribution and turbulent kinematics.Several peculiar gas clouds have been discovered within the Central Molecular Zone within the past two decades. These clouds, dubbed high-velocity compact clouds, are characterized by their compact sizes and extremely broad velocity widths.What created this mysterious population of energetic clouds? The recent discovery of two new high-velocity compact clouds, reported on in a paper led by Shunya Takekawa (Keio University, Japan), may help us to answer this question.Two More to the CountUsing the James Clerk Maxwell Telescope in Hawaii, Takekawa and collaborators detected the small clouds near the circumnuclear disk at the centermost part of our galaxy. These two clouds have velocity spreads of -80 to -20 km/s and -80 to 0 km/s and compact sizes of just over 1 light-year. The clouds similar appearances and physical properties suggest that they may both have been formed by the same process.Takekawa and collaborators explore and discard several possible origins for these clouds, such as outflows from massive protostars (no massive, luminous stars have been detected affiliated

  19. Determinants of State Aid

    NARCIS (Netherlands)

    Buiren, K.; Brouwer, E.

    2010-01-01

    From economic theory we derive a set of hypotheses on the determination of state aid. Econometric analysis on EU state aid panel data is carried out to test whether the determinants we expect on the basis of theory, correspond to the occurrence of state aid in practice in the EU. We find that politi

  20. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  1. Balance Trees Reveal Microbial Niche Differentiation.

    Science.gov (United States)

    Morton, James T; Sanders, Jon; Quinn, Robert A; McDonald, Daniel; Gonzalez, Antonio; Vázquez-Baeza, Yoshiki; Navas-Molina, Jose A; Song, Se Jin; Metcalf, Jessica L; Hyde, Embriette R; Lladser, Manuel; Dorrestein, Pieter C; Knight, Rob

    2017-01-01

    Advances in sequencing technologies have enabled novel insights into microbial niche differentiation, from analyzing environmental samples to understanding human diseases and informing dietary studies. However, identifying the microbial taxa that differentiate these samples can be challenging. These issues stem from the compositional nature of 16S rRNA gene data (or, more generally, taxon or functional gene data); the changes in the relative abundance of one taxon influence the apparent abundances of the others. Here we acknowledge that inferring properties of individual bacteria is a difficult problem and instead introduce the concept of balances to infer meaningful properties of subcommunities, rather than properties of individual species. We show that balances can yield insights about niche differentiation across multiple microbial environments, including soil environments and lung sputum. These techniques have the potential to reshape how we carry out future ecological analyses aimed at revealing differences in relative taxonomic abundances across different samples. IMPORTANCE By explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss. Author Video: An author video summary of this article is available.

  2. VISTA Reveals the Secret of the Unicorn

    Science.gov (United States)

    2010-10-01

    A new infrared image from ESO's VISTA survey telescope reveals an extraordinary landscape of glowing tendrils of gas, dark clouds and young stars within the constellation of Monoceros (the Unicorn). This star-forming region, known as Monoceros R2, is embedded within a huge dark cloud. The region is almost completely obscured by interstellar dust when viewed in visible light, but is spectacular in the infrared. An active stellar nursery lies hidden inside a massive dark cloud rich in molecules and dust in the constellation of Monoceros. Although it appears close in the sky to the more familiar Orion Nebula it is actually almost twice as far from Earth, at a distance of about 2700 light-years. In visible light a grouping of massive hot stars creates a beautiful collection of reflection nebulae where the bluish starlight is scattered from parts of the dark, foggy outer layers of the molecular cloud. However, most of the new-born massive stars remain hidden as the thick interstellar dust strongly absorbs their ultraviolet and visible light. In this gorgeous infrared image taken from ESO's Paranal Observatory in northern Chile, the Visible and Infrared Survey Telescope for Astronomy (VISTA [1], eso0949) penetrates the dark curtain of cosmic dust and reveals in astonishing detail the folds, loops and filaments sculpted from the dusty interstellar matter by intense particle winds and the radiation emitted by hot young stars. "When I first saw this image I just said 'Wow!' I was amazed to see all the dust streamers so clearly around the Monoceros R2 cluster, as well as the jets from highly embedded young stellar objects. There is such a great wealth of exciting detail revealed in these VISTA images," says Jim Emerson, of Queen Mary, University of London and leader of the VISTA consortium. With its huge field of view, large mirror and sensitive camera, VISTA is ideal for obtaining deep, high quality infrared images of large areas of the sky, such as the Monoceros R2 region

  3. Revealing the values behind convenience food consumption.

    Science.gov (United States)

    Botonaki, Anna; Mattas, Konstadinos

    2010-12-01

    The increasing importance of convenience in consumer food choices has attracted researchers' interest. In the effort to understand how convenience affects consumers' food preferences, values are believed to play an important role. The present study attempts to examine the way personal values suggested by Schwartz (1992) are associated with behaviour and attitudes regarding convenience food. A number of constructs describing food related attitudes and behaviours were developed and their relationship with personal values was analyzed following the methodology proposed by Brunsø, Scholderer, and Grunert (2004). Data were collected through a questionnaire survey from a random sample of consumers in Thessaloniki city, Greece. The results reveal that convenience food consumption and convenience orientation in the food domain are mainly connected with values that motivate people to seek new experiences, act independently and enhance their own personal interests, while are in conflict with values of conservation and self-transcendence. The opposite holds for other food related attitudes and behaviours like involvement with cooking and variety in diet. The findings seem to be of particular interest not only for marketers of food products, but also for food policy makers.

  4. Myasthenia Revealed Following Laparotomy - A Case Report

    Directory of Open Access Journals (Sweden)

    Abdelilah GHANNAM

    2015-06-01

    Full Text Available Myasthenia (muscle weakness is a rare neuromuscular disease of which respiratory failure is the main complication. The accidental discovery of such disease in the perioperative period is rare and potentially serious.We report a case of a woman who underwent emergency operation for appendiceal peritonitis, and failed repeatedly at weaning from postoperative mechanical ventilation. The usual etiologies such as postoperative respiratory complications, ventilator-associated pneumonia, acute respiratory distress syndrome complicating the septic shock or having no impact on it, and neuromyopathy’s resuscitation were considered, researched, examined or eliminated.Faced with the diagnostic impasse and the obvious weaning failure, another interview revealed signs of muscle fatigue which led to the diagnosis of myasthenia gravis decompensated perioperatively. Once the diagnosis was confirmed by means of a neostigmine test, the specific treatment began, particularly through plasma exchange sessions, and the process of weaning resumed. The result was complete weaning. A three-month follow-up showed a stable patient with no significant muscular disability.

  5. Balance Trees Reveal Microbial Niche Differentiation

    Science.gov (United States)

    Morton, James T.; Sanders, Jon; Quinn, Robert A.; McDonald, Daniel; Gonzalez, Antonio; Vázquez-Baeza, Yoshiki; Navas-Molina, Jose A.; Metcalf, Jessica L.; Hyde, Embriette R.; Lladser, Manuel; Dorrestein, Pieter C.

    2017-01-01

    ABSTRACT Advances in sequencing technologies have enabled novel insights into microbial niche differentiation, from analyzing environmental samples to understanding human diseases and informing dietary studies. However, identifying the microbial taxa that differentiate these samples can be challenging. These issues stem from the compositional nature of 16S rRNA gene data (or, more generally, taxon or functional gene data); the changes in the relative abundance of one taxon influence the apparent abundances of the others. Here we acknowledge that inferring properties of individual bacteria is a difficult problem and instead introduce the concept of balances to infer meaningful properties of subcommunities, rather than properties of individual species. We show that balances can yield insights about niche differentiation across multiple microbial environments, including soil environments and lung sputum. These techniques have the potential to reshape how we carry out future ecological analyses aimed at revealing differences in relative taxonomic abundances across different samples. IMPORTANCE By explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss. Author Video: An author video summary of this article is available. PMID:28144630

  6. Can body volume be determined by PET?

    Science.gov (United States)

    Hentschel, Michael; Paul, Dominik; Korsten-Reck, Ulrike; Mix, Michael; Müller, Frank; Merk, Stefan; Moser, Ernst; Brink, Ingo

    2005-05-01

    To avoid dependence on body weight, the standardised uptake value (SUV) in positron emission tomography (PET) can instead be normalised to the lean body mass (LBM), which can be determined from body volume and mass. This study was designed to answer the following questions: Firstly, can the total body volume in principle be determined using PET? Secondly, is the precision of this measurement comparable to that achieved using an established standard method. Ten patients were examined during oncological whole-body PET examinations. The whole-body volume of the patients was determined from the transmission scan in PET. Air displacement plethysmography with BOD POD was used for comparison as the standard method of volume determination. In all patients, the whole-body volumes could be determined using PET and the standard method. Bland and Altman [23] analysis for agreement between the volumes determined by the two methods (presentation of differences vs means) revealed a very small difference of -0.14 l. With a mean patient volume of 71.81+/-15.93 l, the relative systematic error is only <0.1%. On this basis, equality of the volume values determined by the two methods can be assumed. PET can be used as a supplementary method for experimental determination of whole-body volume and total body fat in tumour patients. The fat content can be used to calculate the LBM and to determine body weight-independent SUVs (SUV(LBM)).

  7. Can body volume be determined by PET?

    Energy Technology Data Exchange (ETDEWEB)

    Hentschel, Michael; Paul, Dominik; Mix, Michael; Moser, Ernst; Brink, Ingo [University Hospital Freiburg, Division of Nuclear Medicine, Section of Positron Emission Tomography, Freiburg (Germany); Korsten-Reck, Ulrike [University Hospital Freiburg, Division of Sports Medicine, Freiburg (Germany); Mueller, Frank [PET-Institute Rhein-Neckar, Ludwigshafen (Germany); Merk, Stefan [Kantonsspital Basel, Division of Nuclear Medicine, Basel (Switzerland)

    2005-04-01

    To avoid dependence on body weight, the standardised uptake value (SUV) in positron emission tomography (PET) can instead be normalised to the lean body mass (LBM), which can be determined from body volume and mass. This study was designed to answer the following questions: Firstly, can the total body volume in principle be determined using PET? Secondly, is the precision of this measurement comparable to that achieved using an established standard method. Ten patients were examined during oncological whole-body PET examinations. The whole-body volume of the patients was determined from the transmission scan in PET. Air displacement plethysmography with BOD POD was used for comparison as the standard method of volume determination. In all patients, the whole-body volumes could be determined using PET and the standard method. Bland and Altman [23] analysis for agreement between the volumes determined by the two methods (presentation of differences vs means) revealed a very small difference of -0.14 l. With a mean patient volume of 71.81{+-}15.93 l, the relative systematic error is only <0.1%. On this basis, equality of the volume values determined by the two methods can be assumed. PET can be used as a supplementary method for experimental determination of whole-body volume and total body fat in tumour patients. The fat content can be used to calculate the LBM and to determine body weight-independent SUVs (SUV{sub LBM}). (orig.)

  8. Determinants of Serum Glycerophospholipid Fatty Acids in Cystic Fibrosis

    Science.gov (United States)

    Drzymała-Czyż, Sławomira; Krzyżanowska, Patrycja; Koletzko, Berthold; Nowak, Jan; Miśkiewicz-Chotnicka, Anna; Moczko, Jerzy A.; Lisowska, Aleksandra; Walkowiak, Jarosław

    2017-01-01

    The etiology of altered blood fatty acid (FA) composition in cystic fibrosis (CF) is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids’ FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS). We assessed Fas’ profile (gas chromatography/mass spectrometry), CF transmembrane conductance regulator (CFTR) genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0) and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9) were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases’ activity is warranted. PMID:28106773

  9. Determinants of Serum Glycerophospholipid Fatty Acids in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Sławomira Drzymała-Czyż

    2017-01-01

    Full Text Available The etiology of altered blood fatty acid (FA composition in cystic fibrosis (CF is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids’ FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS. We assessed Fas’ profile (gas chromatography/mass spectrometry, CF transmembrane conductance regulator (CFTR genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0 and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9 were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases’ activity is warranted.

  10. Plant Sex Determination.

    Science.gov (United States)

    Pannell, John R

    2017-03-06

    Sex determination is as important for the fitness of plants as it is for animals, but its mechanisms appear to vary much more among plants than among animals, and the expression of gender in plants differs in important respects from that in most animals. In this Minireview, I provide an overview of the broad variety of ways in which plants determine sex. I suggest that several important peculiarities of plant sex determination can be understood by recognising that: plants show an alternation of generations between sporophytic and gametophytic phases (either of which may take control of sex determination); plants are modular in structure and lack a germ line (allowing for a quantitative expression of gender that is not common in animals); and separate sexes in plants have ultimately evolved from hermaphroditic ancestors. Most theorising about sex determination in plants has focused on dioecious species, but we have much to learn from monecious or hermaphroditic species, where sex is determined at the level of modules, tissues or cells. Because of the fundamental modularity of plant development and potentially important evolutionary links between monoecy and dioecy, it may be useful to relax the distinction often made between 'developmental sex determination' (which underpins the development of male versus female flowers in monoecious species) and 'genetic sex determination' (which underpins the separation of males and females in dioecious species, often mediated by a genetic polymorphism and sex chromosomes). I also argue for relaxing the distinction between sex determination involving a genetic polymorphism and that involving responses to environmental or hormonal cues, because non-genetic cues might easily be converted into genetic switches.

  11. Airborne geoid determination

    DEFF Research Database (Denmark)

    Forsberg, René; Olesen, Arne Vestergaard; Bastos, L.

    2000-01-01

    Airborne geoid mapping techniques may provide the opportunity to improve the geoid over vast areas of the Earth, such as polar areas, tropical jungles and mountainous areas, and provide an accurate "seam-less" geoid model across most coastal regions. Determination of the geoid by airborne methods......-suited for geoid determination, with high-frequency survey and downward continuation noise being offset by the low-pass gravity to geoid filtering operation. In the paper the basic principles of airborne geoid determination are outlined, and examples of results of recent airborne gravity and geoid surveys...

  12. Determinants of Actor Rationality

    DEFF Research Database (Denmark)

    Ellegaard, Chris

    Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer......-supplier relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

  13. Quantitative proteomics reveals cellular targets of celastrol.

    Directory of Open Access Journals (Sweden)

    Jakob Hansen

    Full Text Available Celastrol, a natural substance isolated from plant extracts used in traditional Chinese medicine, has been extensively investigated as a possible drug for treatment of cancer, autoimmune diseases, and protein misfolding disorders. Although studies focusing on celastrol's effects in specific cellular pathways have revealed a considerable number of targets in a diverse array of in vitro models there is an essential need for investigations that can provide a global view of its effects. To assess cellular effects of celastrol and to identify target proteins as biomarkers for monitoring treatment regimes, we performed large-scale quantitative proteomics in cultured human lymphoblastoid cells, a cell type that can be readily prepared from human blood samples. Celastrol substantially modified the proteome composition and 158 of the close to 1800 proteins with robust quantitation showed at least a 1.5 fold change in protein levels. Up-regulated proteins play key roles in cytoprotection with a prominent group involved in quality control and processing of proteins traversing the endoplasmic reticulum. Increased levels of proteins essential for the cellular protection against oxidative stress including heme oxygenase 1, several peroxiredoxins and thioredoxins as well as proteins involved in the control of iron homeostasis were also observed. Specific analysis of the mitochondrial proteome strongly indicated that the mitochondrial association of certain antioxidant defense and apoptosis-regulating proteins increased in cells exposed to celastrol. Analysis of selected mRNA transcripts showed that celastrol activated several different stress response pathways and dose response studies furthermore showed that continuous exposure to sub-micromolar concentrations of celastrol is associated with reduced cellular viability and proliferation. The extensive catalog of regulated proteins presented here identifies numerous cellular effects of celastrol and constitutes

  14. Quadrupole transitions revealed by Borrmann spectroscopy.

    Science.gov (United States)

    Pettifer, Robert F; Collins, Stephen P; Laundy, David

    2008-07-10

    The Borrmann effect-a dramatic increase in transparency to X-ray beams-is observed when X-rays satisfying Bragg's law diffract through a perfect crystal. The minimization of absorption seen in the Borrmann effect has been explained by noting that the electric field of the X-ray beam approaches zero amplitude at the crystal planes, thus avoiding the atoms. Here we show experimentally that under conditions of absorption suppression, the weaker electric quadrupole absorption transitions are effectively enhanced to such a degree that they can dominate the absorption spectrum. This effect can be exploited as an atomic spectroscopy technique; we show that quadrupole transitions give rise to additional structure at the L(1), L(2) and L(3) absorption edges of gadolinium in gadolinium gallium garnet, which mark the onset of excitations from 2s, 2p(1/2) and 2p(3/2) atomic core levels, respectively. Although the Borrmann effect served to underpin the development of the theory of X-ray diffraction, this is potentially the most important experimental application of the phenomenon since its first observation seven decades ago. Identifying quadrupole features in X-ray absorption spectroscopy is central to the interpretation of 'pre-edge' spectra, which are often taken to be indicators of local symmetry, valence and atomic environment. Quadrupolar absorption isolates states of different symmetries to that of the dominant dipole spectrum, and typically reveals orbitals that dominate the electronic ground-state properties of lanthanides and 3d transition metals, including magnetism. Results from our Borrmann spectroscopy technique feed into contemporary discussions regarding resonant X-ray diffraction and the nature of pre-edge lines identified by inelastic X-ray scattering. Furthermore, because the Borrmann effect has been observed in photonic materials, it seems likely that the quadrupole enhancement reported here will play an important role in modern optics.

  15. Health promotion: challenges revealed in successful practices

    Science.gov (United States)

    Silva, Kênia Lara; de Sena, Roseni Rosângela; Belga, Stephanie Marques Moura Franco; Silva, Paloma Morais; Rodrigues, Andreza Trevenzoli

    2014-01-01

    OBJECTIVE To examine successful practices of health promotion in health, education, culture, welfare and sport, leisure, identifying the elements of success and challenges in the field. METHODS A qualitative study with data obtained from in-depth analysis that included participant observation, interviews with managers, coordinators, professionals and participants from 29 practices reported as successful for promoting health in six municipalities of the metropolitan region of Belo Horizonte, MG, Southeastern Brazil, in 2011. The variables of the study were concept, dimension, dissemination and ease of access, identified in practices guided by content analysis. RESULTS The results indicate a conceptual and methodological uncertainty about health promotion as evidenced by conflicting objects and contradictory purposes. The practices differ in size, coverage and ease of access, determined by inter-sector coordination and political and financial investment. CONCLUSIONS We identified challenges to health promotion focusing on vulnerable populations, limits to financing and intersectoral partnerships. PMID:24789640

  16. Attitude measurements and determination

    Science.gov (United States)

    Foliard, J.

    Satellite attitude determination using an inertial reference system is explained. The utility of being able to determine attitude is outlined. Construction of an attitude matrix from the Euler and Cardan angles of the satellite-Earth system is illustrated. Static and dynamic analysis methods are shown. The sensors employed when using the Sun, Earth's magnetic field, the Earth, and the stars as reference direction are described.

  17. Brain Death Determination.

    Science.gov (United States)

    Spinello, Irene M

    2015-09-01

    In the United States, each year 1% to 2% of deaths are brain deaths. Considerable variation in the practice of determining brain death still remains, despite the publication of practice parameters in 1995 and an evidence-based guideline update in 2010. This review is intended to give bedside clinicians an overview of definition, the causes and pitfalls of misdiagnosing brain death, and a focus on the specifics of the brain death determination process.

  18. Determining postural stability

    Science.gov (United States)

    Lieberman, Erez (Inventor); Forth, Katharine E. (Inventor); Paloski, William H. (Inventor)

    2011-01-01

    A method for determining postural stability of a person can include acquiring a plurality of pressure data points over a period of time from at least one pressure sensor. The method can also include the step of identifying a postural state for each pressure data point to generate a plurality of postural states. The method can include the step of determining a postural state of the person at a point in time based on at least the plurality of postural states.

  19. Protein Nitrogen Determination

    Science.gov (United States)

    Nielsen, S. Suzanne

    The protein content of foods can be determined by numerous methods. The Kjeldahl method and the nitrogen combustion (Dumas) method for protein analysis are based on nitrogen determination. Both methods are official for the purposes of nutrition labeling of foods. While the Kjeldahl method has been used widely for over a hundred years, the recent availability of automated instrumentation for the Dumas method in many cases is replacing use of the Kjeldahl method.

  20. The Streptococcus milleri population of a cystic fibrosis clinic reveals patient specificity and intraspecies diversity.

    Science.gov (United States)

    Sibley, Christopher D; Sibley, Kristen A; Leong, Tara A; Grinwis, Margot E; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2010-07-01

    The genetic relatedness of Streptococcus milleri group isolates from the airways of cystic fibrosis patients was determined by using pulsed-field gel electrophoresis. This study reveals no evidence for patient-to-patient transmission in our patient population; however, within individual patients, complex inter- and intraspecies diversity and dynamics can be observed.

  1. Opening the Big Black Box: European study reveals visitors' impressions of science laboratories

    CERN Multimedia

    2004-01-01

    "On 29 - 30 March the findings of 'Inside the Big Black Box'- a Europe-wide science and society project - will be revealed during a two-day seminar hosted by CERN*. The principle aim of Inside the Big Black Box (IN3B) is to determine whether a working scientific laboratory can capture the curiosity of the general public through visits" (1 page)

  2. Frantic activity revealed in dusty stellar factories

    Science.gov (United States)

    2009-01-01

    Thanks to the Very Large Telescope's acute and powerful near-infrared eye, astronomers have uncovered a host of new young, massive and dusty stellar nurseries in nearby galaxy NGC 253. The centre of this galaxy appears to harbour a twin of our own Milky Way's supermassive black hole. ESO PR Photo 02a/09 The Spiral Galaxy NGC 253 Astronomers from the Instituto de Astrofísica de Canarias (Spain) used NACO, a sharp-eyed adaptive optics instrument on ESO's Very Large Telescope (VLT), to study the fine detail in NGC 253, one of the brightest and dustiest spiral galaxies in the sky. Adaptive Optics (AO) corrects for the blurring effect introduced by the Earth's atmosphere. This turbulence causes the stars to twinkle in a way that delights poets, but frustrates astronomers, since it smears out the images. With AO in action the telescope can produce images that are as sharp as is theoretically possible, as if the telescope were in space. NACO revealed features in the galaxy that were only 11 light-years across. "Our observations provide us with so much spatially resolved detail that we can, for the first time, compare them with the finest radio maps for this galaxy -- maps that have existed for more than a decade," says Juan Antonio Fernández-Ontiveros, the lead author of the paper reporting the results [1]. Astronomers identified 37 distinct bright regions, a threefold increase on previous results, packed into a tiny region at the core of the galaxy, comprising just one percent of the galaxy's total size. The astronomers combined their NACO images with data from another VLT instrument, VISIR, as well as with images from the NASA/ESA Hubble Space Telescope and radio observations made by the Very Large Array and the Very Large Baseline Interferometer. Combining these observations, taken in different wavelength regimes, provided a clue to the nature of these regions. "We now think that these are probably very active nurseries that contain many stars bursting from their

  3. Dramatic Outburst Reveals Nearest Black Hole

    Science.gov (United States)

    2000-01-01

    Sgr. The radio observations revealed the presence of a jet escaping from the system at mind-boggling speeds. Only three other galactic X-ray stellar systems have been found to eject material at such speeds. They have been dubbed "microquasars" because, on a smaller scale, they resemble quasars, which lie at the hearts of distant galaxies and also spew out high-velocity jets of particles. In galaxy-core quasars, the black holes are millions of times more massive than the Sun; in the more nearby microquasars the black holes are roughly three to twenty times more massive than the Sun. The extremely high velocity of the jets suggests that their origin lies close to the event horizon of a black hole. Microquasar activity is thought to arise when the black hole in the binary system draws material away from its companion star. The material surrounding the black hole forms a rapidly spinning disk called an accretion disk. This disk is heated by friction to millions of degrees, causing it to emit X-rays. As spiralling gas moves into the gravity well of the black hole, it moves faster and faster. Magnetic fields in the disk are believed to expel the charged subatomic particles at speeds close to that of light. As the charged particles interact with the magnetic fields, they emit radio waves. If some of the material escapes by being magnetically expelled into space, the matter may continue moving at the tremendous speed it had attained near the black hole. After their ejection, the jets of particles expand and cool, fading from astronomers' view. V4641 Sgr excites astronomers because it is close and because it acted so differently from other microquasars. In other microquasars, outbursts have dimmed more slowly over weeks or months rather than hours. "There's something fundamentally different about this one; it's more extreme than any other example," Hjellming said. "And because this system happens to be so close to us, `it is very likely that there are more objects like V4641

  4. Microradiometers Reveal Ocean Health, Climate Change

    Science.gov (United States)

    2013-01-01

    When NASA researcher Stanford Hooker is in the field, he pays close attention to color. For Hooker, being in the field means being at sea. On one such research trip to the frigid waters of the Arctic, with a Coast Guard icebreaker looming nearby and the snow-crusted ice shelf a few feet away, Hooker leaned over the edge of his small boat and lowered a tethered device into the bright turquoise water, a new product devised by a NASA partner and enabled by a promising technology for oceanographers and atmospheric scientists alike. Color is a function of light. Pure water is clear, but the variation in color observed during a visit to the beach or a flight along a coastline depends on the water s depth and the constituents in it, how far down the light penetrates and how it is absorbed and scattered by dissolved and suspended material. Hooker cares about ocean color because of what it can reveal about the health of the ocean, and in turn, the health of our planet. "The main thing we are interested in is the productivity of the water," Hooker says. The seawater contains phytoplankton, microscopic plants, which are the food base for the ocean s ecosystems. Changes in the water s properties, whether due to natural seasonal effects or human influence, can lead to problems for delicate ecosystems such as coral reefs. Ocean color can inform researchers about the quantities and distribution of phytoplankton and other materials, providing clues as to how the world ocean is changing. NASA s Coastal Zone Color Scanner, launched in 1978, was the first ocean color instrument flown on a spacecraft. Since then, the Agency s ocean color research capabilities have become increasingly sophisticated with the launch of the SeaWiFS instrument in 1997 and the twin MODIS instruments carried into orbit on NASA s Terra (1999) and Aqua (2002) satellites. The technology provides sweeping, global information on ocean color on a scale unattainable by any other means. One issue that arises from

  5. Molecular mechanisms of sex determination in reptiles.

    Science.gov (United States)

    Rhen, T; Schroeder, A

    2010-01-01

    Charles Darwin first provided a lucid explanation of how gender differences evolve nearly 140 years ago. Yet, a disconnect remains between his theory of sexual selection and the mechanisms that underlie the development of males and females. In particular, comparisons between representatives of different phyla (i.e., flies and mice) reveal distinct genetic mechanisms for sexual differentiation. Such differences are hard to comprehend unless we study organisms that bridge the phylogenetic gap. Analysis of variation within monophyletic groups (i.e., amniotes) is just as important if we hope to elucidate the evolution of mechanisms underlying sexual differentiation. Here we review the molecular, cellular, morphological, and physiological changes associated with sex determination in reptiles. Most research on the molecular biology of sex determination in reptiles describes expression patterns for orthologs of mammalian sex-determining genes. Many of these genes have evolutionarily conserved expression profiles (i.e., DMRT1 and SOX9 are expressed at a higher level in developing testes vs. developing ovaries in all species), which suggests functional conservation. However, expression profiling alone does not test gene function and will not identify novel sex-determining genes or gene interactions. For that reason, we provide a prospectus on various techniques that promise to reveal new sex-determining genes and regulatory interactions among these genes. We offer specific examples of novel candidate genes and a new signaling pathway in support of these techniques.

  6. Natural history of chronic hepatitis B: what exactly has REVEAL revealed?

    Science.gov (United States)

    Iloeje, Uchenna H; Yang, Hwai-I; Chen, Chien-Jen

    2012-10-01

    Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL-HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver-related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver-related mortality compared with HBsAg -seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non-invasive clinical parameters to predict long-term HCC risk. These will hopefully contribute to evidence-based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL-HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL-HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward. © 2012 John Wiley & Sons A/S.

  7. Revealing remodeler function: Varied and unique

    Science.gov (United States)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  8. Dimming titan revealed by the Cassini observations.

    Science.gov (United States)

    Li, Liming

    2015-02-04

    Here we report the temporal variation of Titan's emitted energy with the Cassini/CIRS observations. In the northern hemisphere, the hemispheric-average emitted power decreased from 2007 to 2009 and increased from 2009 to 2012-13, which make the net change insignificant (0.1 ± 0.2%) during the period 2007-2013. The decrease from 2007 to 2009 is mainly due to the cooling around the stratospause, and the increase from 2009 to 2012-13 is probably related to temporal variation of atmospheric temperature around the tropopuase in the northern hemisphere. In the southern hemisphere, the emitted power continuously decreased by 5.0 ± 0.6% from 2.40 ± 0.01 W/m(2) in 2007 to 2.28 ± 0.01 in 2012-13, which is mainly related to Titan's seasonal variation. The asymmetry in the temporal variation between the two hemispheres results in the global-average emitted power decreasing by 2.5 ± 0.6% from 2.41 ± 0.01 W/m(2) in 2007 to 2.35 ± 0.01 W/m(2) in 2012-13. The solar constant at Titan decreased by ~13.0% in the same period 2007-2013, which is much stronger than the temporal variation of emitted power. The measurements of Titan's absorbed solar power are needed to determine the temporal variation of the global energy budget.

  9. Inherited alleles revealing an incestuous paternity.

    Science.gov (United States)

    Jankova-Ajanovska, R; Jakovski, Z; Janeska, B; Simjanovska, L; Duma, A

    2010-01-01

    Some rape cases result in the pregnancy of the victim and if the case is not reported to the police after the act with a subsequent gynaecological examination of the girl and the taking of a vaginal swab, there is no way of connecting the rape case with the perpetrator, except by parentage determination using DNA (deoxyribonucleic acid) analysis after abortion or induced delivery. In order to solve the rape case of a minor girl of 14 years which resulted with pregnancy, where a 60-year-old man was accused of the rape, DNA was extracted from blood samples from the girl and the putative assailant and from the foetus after its induced delivery. The autosomal short tandem repeats (STR) typing for 15 different loci showed differences in 6 STR loci between the putative assailant as a father and the foetus, thus excluding the tested paternity. A large number of identical loci between the mother's and the child's genotype led us to consider the possibility of incestuous paternity. Analysis of DNA samples from the girl's father and brother clarified the case as brother-sister incest.

  10. Can multilocus heterozygosity reveal inbreeding depression?

    Science.gov (United States)

    Syukri, F; Nakajima, T; Nakajima, M

    2016-07-01

    Inbred lines of fish have been widely exploited as model organisms to determine the effect of inbreeding, which is often closely related to fitness such as endurance and productivity compared to morphological traits. Until now, much is unknown about the effects of inbreeding to fish. In the present study, inbred lines of guppies were used to examine the inbreeding effect on morphological traits corresponding to genotype variation. Two strains, called AY and NA1, were selected from the closed culture system. Both strains showed different levels of inbreeding coefficients when compared to microsatellite markers. The AY strain was less inbred as compared to NA1 strain. However, correlation between the standard lengths with multilocus heterozygosity (MLH) at the individual level was observed in the AY, but not in the NA1 strain. This indicated that highly inbred animals have higher similarity in morphological traits as compared to less inbred ones. The inbreeding process showed the importance of heterozygosity, even in laboratory-reared animals. This experiment illustrated the effects of inbreeding towards morphological and genetic changes. ?

  11. Cyp1a reporter zebrafish reveals target tissues for dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kun-Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Park, Hye-Jeong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Jin Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Suhyun [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Williams, Darren R. [New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Kim, Myeong-Kyu [Department of Neurology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jung, Young Do [Department of Biochemistry, Chonnam National University Medical School, Gwangju (Korea, Republic of); Teraoka, Hiroki [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Park, Hae-Chul [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Choy, Hyon E., E-mail: hyonchoy@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Shin, Boo Ahn, E-mail: bashin@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Choi, Seok-Yong, E-mail: zebrafish@chonnam.ac.kr [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of)

    2013-06-15

    Highlights: •2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic anthropogenic substance ever identified. •Transgenic cyp1a reporter zebrafish reveals target tissues for TCDD. •The retinal bipolar cells, otic vesicle, lateral line, pancreas, cloaca and pectoral fin bud are novel targets in zebrafish for TCDD. •Our findings will further understanding of human health risks by TCDD. -- Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

  12. Antibody protection reveals extended epitopes on the human TSH receptor.

    Directory of Open Access Journals (Sweden)

    Rauf Latif

    Full Text Available Stimulating, and some blocking, antibodies to the TSH receptor (TSHR have conformation-dependent epitopes reported to involve primarily the leucine rich repeat region of the ectodomain (LRD. However, successful crystallization of TSHR residues 22-260 has omitted important extracellular non-LRD residues including the hinge region which connects the TSHR ectodomain to the transmembrane domain and which is involved in ligand induced signal transduction. The aim of the present study, therefore, was to determine if TSHR antibodies (TSHR-Abs have non-LRD binding sites outside the LRD. To obtain this information we employed the method of epitope protection in which we first protected TSHR residues 1-412 with intact TSHR antibodies and then enzymatically digested the unprotected residues. Those peptides remaining were subsequently delineated by mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR-Ab crystal contact residues were protected by this technique which may reflect the higher binding energies of certain residues detected in this approach. Comparing the protected epitopes of two stimulating TSHR-Abs we found both similarities and differences but both antibodies also contacted the hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously been shown to be important for TSH binding and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of binding regions but the residues that it contacted on the LRD were again distinct. These data demonstrated that conformationally dependent TSHR-Abs had epitopes not confined to the LRDs but also incorporated epitopes not revealed in the available crystal structure. Furthermore, the data also indicated that in addition to overlapping contact regions within the LRD, there are unique epitope patterns for each of the antibodies which may contribute to their functional heterogeneity.

  13. A systems biology approach reveals common metastatic pathways in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Flores Ricardo J

    2012-05-01

    Full Text Available Abstract Background Osteosarcoma (OS is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the Sa

  14. Stoichiometry of the Human Glycine Receptor Revealed by Direct Subunit counting

    Science.gov (United States)

    Durisic, Nela; Godin, Antoine G.; Wever, Claudia M.; Heyes, Colin D.; Lakadamyali, Melike; Dent, Joseph A.

    2012-01-01

    The subunit stoichiometry of heteromeric glycine-gated channels (GlyRs) determines fundamental properties of these key inhibitory neurotransmitter receptors; however the ratio of α1 to β-subunits per receptor remains controversial. We used single molecule imaging and stepwise photobleaching in Xenopus oocytes to directly determine the subunit stoichiometry of a glycine receptor to be 3α1:2β. This approach allowed us to determine the receptor stoichiometry in mixed populations consisting of both heteromeric and homomeric channels, additionally revealing the quantitative proportions for the two populations. PMID:22973015

  15. Labor Market Structure and Salary Determination among Professional Basketball Players.

    Science.gov (United States)

    Wallace, Michael

    1988-01-01

    The author investigates the labor market structure and determinants of salaries for professional basketball players. An expanded version of the resource perspective is used. A three-tiered model of labor market segmentation is revealed for professional basketball players, but other variables also are important in salary determination. (Author/CH)

  16. Spacecraft Attitude Determination

    DEFF Research Database (Denmark)

    Bak, Thomas

    This thesis describes the development of an attitude determination system for spacecraft based only on magnetic field measurements. The need for such system is motivated by the increased demands for inexpensive, lightweight solutions for small spacecraft. These spacecraft demands full attitude...... determination based on simple, reliable sensors. Meeting these objectives with a single vector magnetometer is difficult and requires temporal fusion of data in order to avoid local observability problems. In order to guaranteed globally nonsingular solutions, quaternions are generally the preferred attitude...... is a detailed study of the influence of approximations in the modeling of the system. The quantitative effects of errors in the process and noise statistics are discussed in detail. The third contribution is the introduction of these methods to the attitude determination on-board the Ørsted satellite...

  17. Inertinite fusibility determination

    Energy Technology Data Exchange (ETDEWEB)

    Philip Bennett; Daniel Rigg [ALS-ACIRL (Australia)

    2008-08-15

    The project was to develop a simple tool todetermine the fusibility of inertinite in Australian coals. The first step in determining the fusible inertinite component is to convert the petrographic analysis to a mass basis. Using mineralogical data determined by QEMSCAN on selected float sink samples of the each coal arelationship between the ash with minerals wasdetermined.. The calculated densities of vitrinite and inertinite for eight coals tested showed similar relationships with rank (carbon %daf) to those given by van Krevelen. It is recommended the relationships derived by curve fit to the data of van Krevelen be used to determine the density of the maceral groups. Step two in determining the fusible inertinite is to estimate the loss of volatile components during carbonisation. Degassing experiments were conducted in small cast iron 'mini pots' to determine the yield of coke and to prepare coke samples for coke microtexture analysis. The mini pot coke tests shows that more of the inertinite can be fused when in close proximity to vitrinite. This project wasextended to include the examination of the data from ACARP project C12057 in which twelve coals were coked in a pilot scale oven and coke microtexture analysis was conducted on the cokes. There is good agreement between the calculated coke yields and the actual pilot scale coke yield using the coke yield determinations approaches given above. The predicted coke yield based on the pilot scale correlation and the measured volatile matter is very good. All pilot oven cokes show that more than 50% of the semifusinite is fusible with some having more than 90% of the semifusinite fusible. Several different methods for the prediction of fused carbon in coke were evaluated using the pilot scale data. The minerals in the coal seem to have a slight influence on fused carbon when dispersed evenly through the coal. This influence is not seen in the pilot scale tests.

  18. Sex determination in amphibians.

    Science.gov (United States)

    Nakamura, Masahisa

    2009-05-01

    The heterogametic sex is male in all mammals, whereas it is female in almost all birds. By contrast, there are two heterogametic types (XX/XY and ZZ/ZW) for genetic sex determination in amphibians. Though the original heterogametic sex was female in amphibians, the two heterogametic types were probably interchangeable, suggesting that sex chromosomes evolved several times in this lineage. Indeed, the frog Rana rugosa has the XX/XY and ZZ/ZW sex-determining systems within a single species, depending on the local population in Japan. The XY and ZW geographic forms with differentiated sex chromosomes probably have a common origin as undifferentiated sex chromosomes resulted from the hybridization between the primary populations of West Japan and Kanto forms. It is clear that the sex chromosomes are still undergoing evolution in this species group. Regardless of the presence of a sex-determining gene in amphibians, the gonadal sex of some species can be changed by sex steroids. Namely, sex steroids can induce the sex reversal, with estrogens inducing the male-to-female sex reversal, whereas androgens have the opposite effect. In R. rugosa, gonadal activity of CYP19 (P450 aromatase) is correlated with the feminization of gonads. Of particular interest is that high levels of CYP19 expression are observed in indifferent gonads at time before sex determination. Increases in the expression of CYP19 in female gonads and CYP17 (P450 17alpha-hydroxylase/C17-20 lyase) in male gonads suggest that the former plays an important role in phenotypic female determination, whereas the latter is needed for male determination. Thus, steroids could be the key factor for sex determination in R. rugosa. In addition to the role of sex steroids in gonadal sex determination in this species, Foxl2 and Sox3 are capable of promoting CYP19 expression. Since both the genes are autosomal, another factor up-regulating CYP19 expression must be recruited. The factor, which may be located on the X or W

  19. Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin

    Science.gov (United States)

    Fogl, Claudia; Mohammed, Fiyaz; Al-Jassar, Caezar; Jeeves, Mark; Knowles, Timothy J.; Rodriguez-Zamora, Penelope; White, Scott A.; Odintsova, Elena; Overduin, Michael; Chidgey, Martyn

    2016-03-01

    Plakin proteins form critical connections between cell junctions and the cytoskeleton; their disruption within epithelial and cardiac muscle cells cause skin-blistering diseases and cardiomyopathies. Envoplakin has a single plakin repeat domain (PRD) which recognizes intermediate filaments through an unresolved mechanism. Herein we report the crystal structure of envoplakin's complete PRD fold, revealing binding determinants within its electropositive binding groove. Four of its five internal repeats recognize negatively charged patches within vimentin via five basic determinants that are identified by nuclear magnetic resonance spectroscopy. Mutations of the Lys1901 or Arg1914 binding determinants delocalize heterodimeric envoplakin from intracellular vimentin and keratin filaments in cultured cells. Recognition of vimentin is abolished when its residues Asp112 or Asp119 are mutated. The latter slot intermediate filament rods into basic PRD domain grooves through electrosteric complementarity in a widely applicable mechanism. Together this reveals how plakin family members form dynamic linkages with cytoskeletal frameworks.

  20. Isotope analysis reveals foraging area dichotomy for atlantic leatherback turtles.

    Directory of Open Access Journals (Sweden)

    Stéphane Caut

    Full Text Available BACKGROUND: The leatherback turtle (Dermochelys coriacea has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI. Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. METHODOLOGY/PRINCIPAL FINDINGS: Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal and foraging latitude (North Atlantic vs. West African coasts, respectively. Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. CONCLUSIONS/SIGNIFICANCE: Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by

  1. Ion Mass Determination

    DEFF Research Database (Denmark)

    2010-01-01

    An apparatus (100) is described for determining the mass of ions, the apparatus configured to hold a plasma (101 ) having a plasma potential. The apparatus (100) comprises an electrode (102) having a surface extending in a surface plane and an insulator (104) interfacing with the electrode (102...

  2. SPECTROPHOTOMETRIC DETERMINATION OF PIZOTEFIN ...

    African Journals Online (AJOL)

    B. S. Chandravanshi

    common additives by applying the standard addition technique. The developed methods have been validated statistically for ... Several analytical methods have been reported for the determination of PZT in pure drug, ... (Kontron Instruments, Munchen, Germany) with a scanning speed of 200 nm/min and a band width of 2.0 ...

  3. Ultrasonic Determination Of Recrystallization

    Science.gov (United States)

    Generazio, Edward R.

    1988-01-01

    State of recrystallization identified. Measurement of ultrasonic attenuation shows promise as means of detecting recrystallization in metal. Technique applicable to real-time acoustic monitoring of thermomechanical treatments. Starting with work-hardened material, one ultrasonically determines effect of annealing, using correlation between ultrasonic attenuation and temperature.

  4. Determinants of Disciplinary Discontent.

    Science.gov (United States)

    Hargens, Lowell L.; Kelly-Wilson, Lisa

    1994-01-01

    Data from the 1984 Carnegie survey of faculty at U.S. universities show substantial disciplinary variation in pessimism that one's field is stagnant. Field-level variations in both anomie and consensus exert strong effects on average levels of scholarly pessimism within fields and are stronger determinants of scholarly pessimism than individual…

  5. Determining TOC in Waters

    Science.gov (United States)

    Kehoe, Thomas J.

    1977-01-01

    The instrumental method for detecting total organic carbon (TOC) in water samples is detailed. The method's limitations are discussed and certain precautions that must be taken are emphasized. The subject of TOC versus COD and BOD is investigated and TOC is determined to be a valid indication of biological demand. (BT)

  6. Colorimetric Determination of Hydroxylurea

    Institute of Scientific and Technical Information of China (English)

    ZHANGYu; ZHUZhao-wu

    2003-01-01

    Hydroxyurea is able to form colored complex with amminoprusside (TPF) which has strong absorption at 500 nm suitable for the colorimetric determination of hydroxyurea. Present paper studies the effects of temperature, quantity of buffer solution, quantity of TPF used and so on, on the complex absorption.

  7. Determination of Fat Content

    Science.gov (United States)

    Carpenter, Charles

    The term "lipid" refers to a group of compounds that are sparingly soluble in water, but show variable solubility in a number of organic solvents (e.g., ethyl ether, petroleum ether, acetone, ethanol, methanol, benzene). The lipid content of a food determined by extraction with one solvent may be quite different from the lipid content as determined with another solvent of different polarity. Fat content is determined often by solvent extraction methods (e.g., Soxhlet, Goldfish, Mojonnier), but it also can be determined by nonsolvent wet extraction methods (e.g., Babcock, Gerber), and by instrumental methods that rely on the physical and chemical properties of lipids (e.g., infrared, density, X-ray absorption). The method of choice depends on a variety of factors, including the nature of the sample (e.g., dry versus moist), the purpose of the analysis (e.g., official nutrition labeling or rapid quality control), and instrumentation available (e.g., Babcock uses simple glassware and equipment; infrared requires an expensive instrument).

  8. Determinants of Disciplinary Discontent.

    Science.gov (United States)

    Hargens, Lowell L.; Kelly-Wilson, Lisa

    1994-01-01

    Data from the 1984 Carnegie survey of faculty at U.S. universities show substantial disciplinary variation in pessimism that one's field is stagnant. Field-level variations in both anomie and consensus exert strong effects on average levels of scholarly pessimism within fields and are stronger determinants of scholarly pessimism than individual…

  9. Determinants for gallstone formation

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Monsted; Sorensen, Lars Tue; Jørgensen, Torben

    2016-01-01

    associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. Conclusions: Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk...

  10. 21 CFR 1.21 - Failure to reveal material facts.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Failure to reveal material facts. 1.21 Section 1... GENERAL ENFORCEMENT REGULATIONS General Labeling Requirements § 1.21 Failure to reveal material facts. (a) Labeling of a food, drug, device, or cosmetic shall be deemed to be misleading if it fails to reveal...

  11. Optical tweezers reveal how proteins alter replication

    Science.gov (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  12. Structural determinants of glomerular permeability.

    Science.gov (United States)

    Deen, W M; Lazzara, M J; Myers, B D

    2001-10-01

    Recent progress in relating the functional properties of the glomerular capillary wall to its unique structure is reviewed. The fenestrated endothelium, glomerular basement membrane (GBM), and epithelial filtration slits form a series arrangement in which the flow diverges as it enters the GBM from the fenestrae and converges again at the filtration slits. A hydrodynamic model that combines morphometric findings with water flow data in isolated GBM has predicted overall hydraulic permeabilities that are consistent with measurements in vivo. The resistance of the GBM to water flow, which accounts for roughly half that of the capillary wall, is strongly dependent on the extent to which the GBM surfaces are blocked by cells. The spatial frequency of filtration slits is predicted to be a very important determinant of the overall hydraulic permeability, in keeping with observations in several glomerular diseases in humans. Whereas the hydraulic resistances of the cell layers and GBM are additive, the overall sieving coefficient for a macromolecule (its concentration in Bowman's space divided by that in plasma) is the product of the sieving coefficients for the individual layers. Models for macromolecule filtration reveal that the individual sieving coefficients are influenced by one another and by the filtrate velocity, requiring great care in extrapolating in vitro observations to the living animal. The size selectivity of the glomerular capillary has been shown to be determined largely by the cellular layers, rather than the GBM. Controversial findings concerning glomerular charge selectivity are reviewed, and it is concluded that there is good evidence for a role of charge in restricting the transmural movement of albumin. Also discussed is an effect of albumin that has received little attention, namely, its tendency to increase the sieving coefficients of test macromolecules via steric interactions. Among the unresolved issues are the specific contributions of the

  13. SAGE2Splice: unmapped SAGE tags reveal novel splice junctions.

    Directory of Open Access Journals (Sweden)

    Byron Yu-Lin Kuo

    2006-04-01

    Full Text Available Serial analysis of gene expression (SAGE not only is a method for profiling the global expression of genes, but also offers the opportunity for the discovery of novel transcripts. SAGE tags are mapped to known transcripts to determine the gene of origin. Tags that map neither to a known transcript nor to the genome were hypothesized to span a splice junction, for which the exon combination or exon(s are unknown. To test this hypothesis, we have developed an algorithm, SAGE2Splice, to efficiently map SAGE tags to potential splice junctions in a genome. The algorithm consists of three search levels. A scoring scheme was designed based on position weight matrices to assess the quality of candidates. Using optimized parameters for SAGE2Splice analysis and two sets of SAGE data, candidate junctions were discovered for 5%-6% of unmapped tags. Candidates were classified into three categories, reflecting the previous annotations of the putative splice junctions. Analysis of predicted tags extracted from EST sequences demonstrated that candidate junctions having the splice junction located closer to the center of the tags are more reliable. Nine of these 12 candidates were validated by RT-PCR and sequencing, and among these, four revealed previously uncharacterized exons. Thus, SAGE2Splice provides a new functionality for the identification of novel transcripts and exons. SAGE2Splice is available online at http://www.cisreg.ca.

  14. Revealing catastrophic failure of leaf networks under stress.

    Science.gov (United States)

    Brodribb, Timothy J; Bienaimé, Diane; Marmottant, Philippe

    2016-04-26

    The intricate patterns of veins that adorn the leaves of land plants are among the most important networks in biology. Water flows in these leaf irrigation networks under tension and is vulnerable to embolism-forming cavitations, which cut off water supply, ultimately causing leaf death. Understanding the ways in which plants structure their vein supply network to protect against embolism-induced failure has enormous ecological and evolutionary implications, but until now there has been no way of observing dynamic failure in natural leaf networks. Here we use a new optical method that allows the initiation and spread of embolism bubbles in the leaf network to be visualized. Examining embolism-induced failure of architecturally diverse leaf networks, we found that conservative rules described the progression of hydraulic failure within veins. The most fundamental rule was that within an individual venation network, susceptibility to embolism always increased proportionally with the size of veins, and initial nucleation always occurred in the largest vein. Beyond this general framework, considerable diversity in the pattern of network failure was found between species, related to differences in vein network topology. The highest-risk network was found in a fern species, where single events caused massive disruption to leaf water supply, whereas safer networks in angiosperm leaves contained veins with composite properties, allowing a staged failure of water supply. These results reveal how the size structure of leaf venation is a critical determinant of the spread of embolism damage to leaves during drought.

  15. Diagnostic phylogenetics reveals a new Porcine circovirus 2 cluster.

    Science.gov (United States)

    Davies, Brendan; Wang, Xiong; Dvorak, Cheryl M T; Marthaler, Douglas; Murtaugh, Michael P

    2016-06-02

    Porcine circovirus 2 (PCV2) was prevalent in swine in the United States before PCV2-associated disease (PCVAD) appeared in 2006. Limited nucleotide sequencing of open reading frame 2 (ORF2) encoding capsid, the only structural protein, revealed the presence of two genotypes, PCV2a and PCV2b. Later, PCV2c and mutant PCV2b, or PCV2d, were also described. However, extensive PCV2 ORF2 sequence databases in veterinary diagnostic laboratories have not been analyzed systematically to determine the genetic diversity of field isolates. Here, we interrogated >1100 PCV2 ORF2 nucleotide sequences to assess population diversity and genetic variation. We detected a novel PCV2 genotype that is substantially different, primarily in ORF2, from all known PCV2. Notably, ORF2 contains a unique carboxyl terminal amino acid insertion resulting in a 238 amino acid ORF2. All other PCV2 ORF2 proteins are 233 or 234 aa in length. Phylogenetic analysis indicates that it is more ancient than other PCV2 genotypes. The findings demonstrate the value of analyzing routine diagnostic laboratory sequence databases in population genetic analyses of animal pathogens.

  16. Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Bruce A.; Tanifuji, Goro; Burki, Fabien; Gruber, Ansgar; Irimia, Manuuel; Maruyama, Shinichiro; Arias, Maria C.; Ball, Steven G.; Gile, Gillian H.; Hirakawa, Yoshihisa; Hopkins, Julia F.; Kuo, Alan; Rensing, Stefan A.; Schmutz, Jeremy; Symeonidi, Aikaterini; Elias, Marek; Eveleigh, Robert J. M.; Herman, Emily K.; Klute, Mary J.; Nakayama, Takuro; Obornik, Miroslav; Reyes-Prieto, Adrian; Armbrust, E. Virginia; Aves, Stephen J.; Beiko, Robert G.; Coutinho, Pedro; Dacks, Joel B.; Durnford, Dion G.; Fast, Naomi M.; Green, Beverley R.; Grisdale, Cameron J.; Hempel, Franziska; Henrissat, Bernard; Hoppner, Marc P.; Ishida, Ken-Ichiro; Kim, Eunsoo; Koreny, Ludek; Kroth, Peter G.; Liu, Yuan; Malik, Shehre-Banoo; Maier, Uwe G.; McRose, Darcy; Mock, Thomas; Neilson, Jonathan A. D.; Onodera, Naoko T.; Poole, Anthony M.; Pritham, Ellen J.; Richards, Thomas A.; Rocap, Gabrielle; Roy, Scott W.; Sarai, Chihiro; Schaack, Sarah; Shirato, Shu; Slamovits, Claudio H.; Spencer, Davie F.; Suzuki, Shigekatsu; Worden, Alexandra Z.; Zauner, Stefan; Barry, Kerrie; Bell, Callum; Bharti, Arvind K.; Crow, John A.; Grimwood, Jane; Kramer, Robin; Lindquist, Erika; Lucas, Susan; Salamov, Asaf; McFadden, Geoffrey I.; Lane, Christopher E.; Keeling, Patrick J.; Gray, Michael W.; Grigoriev, Igor V.; Archibald, John M.

    2012-08-10

    Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have 21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host- and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.

  17. An extensive vertebral hydatidosis revealed by a lumbosciatica.

    Science.gov (United States)

    Rkain, H; Bahiri, R; Benbouazza, K; Hajjaj-Hassouni, N

    2007-08-01

    The vertebral hydatidosis is uncommon. It causes problems in diagnosis and in management. A case of an extensive vertebral hydatidosis with few symptoms is reported. A 21-year-old man has consulted for recurrent lumbosciatica that has been evolving for 1 year. Clinical exam was normal. Plain radiographic films disclosed a lytic lesion throughout the bodies of L4 and L5 and calcifications thrown on the liver area. The computed tomography (CT) and the magnetic resonance (MR) images revealed multicystic bony lesions involving the lumbar spine with extension into the spinal canal. Abdominal ultrasound showed also cyst lesions in the right kidney and in the liver. The diagnosis of vertebral and abdominal (liver and kidney) hydatidosis was retained. Four sets of 4-week albendazole cures were given with a 2-week interval in between. Our case of extended vertebral hydatidosis with few symptoms confirms the clinical latency and diagnosis difficulties usually encountered in this disease. This often leads to a late diagnosis of the stage of spinal cord compression. Radiological diagnosis and determination of extension of the hydatid cyst are usually provided by CT and MRI. Vertebral hydatidosis should be evoked in lumbosciatica especially in endemic regions.

  18. Geometric morphometric analysis reveals sexual dimorphism in the distal femur.

    Science.gov (United States)

    Cavaignac, Etienne; Savall, Frederic; Faruch, Marie; Reina, Nicolas; Chiron, Philippe; Telmon, Norbert

    2016-02-01

    An individual's sex can be determined by the shape of their distal femur. The goal of this study was to show that differences in distal femur shape related to sexual dimorphism could be identified, visualized, and quantified using 3D geometric morphometric analysis. Geometric morphometric analysis was carried out on CT scans of the distal femur of 256 subjects living in the south of France. Ten landmarks were defined on 3D reconstructions of the distal femur. Both traditional metric and geometric morphometric analyses were carried out on these bone reconstructions; these analyses identified trends in bone shape in sex-based subgroups. Sex-related differences in shape were statistically significant. The subject's sex was correctly assigned in 77.3% of cases using geometric morphometric analysis. This study has shown that geometric morphometric analysis of the distal femur is feasible and has revealed sexual dimorphism differences in this bone segment. This reliable, accurate method could be used for virtual autopsy and be used to perform diachronic and interethnic comparisons. Moreover, this study provides updated morphometric data for a modern population in the south of France. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Revealing accretion onto black holes through X-ray reflection

    Science.gov (United States)

    Plant, D.; Fender, R.; Ponti, G.; Munoz-Darias, T.; Coriat, M.

    2014-07-01

    Understanding the dynamics behind black hole state transitions and the changes they reflect in outbursts has become long-standing problem. The X-ray reflection spectrum describes the interaction between the hard X-ray source (the power-law continuum) and the cool accretion disc it illuminates, and thus permits an indirect view of how the two evolve. We present a systematic analysis of the reflection spectrum throughout three outbursts (500+ RXTE observations) of the black hole binary GX 339-4, representing the largest study applying a self-consistent treatment of reflection to date. Particular attention is payed to the coincident evolution of the power-law and reflection, which can be used to determine the accretion geometry. The hard state is found to be distinctly reflection weak, however the ratio of reflection to power-law gradually increases as the source luminosity rises. In contrast the reflection is found dominate the power-law throughout most of the soft state, with increasing supremacy as the source decays. Using results from archival and AO-12 observations of GX 339-4 with XMM-Newton we reveal the dynamics driving this evolution and the nature of accretion onto black holes in outburst.

  20. Supersaturation-limited amyloid fibrillation of insulin revealed by ultrasonication.

    Science.gov (United States)

    Muta, Hiroya; Lee, Young-Ho; Kardos, József; Lin, Yuxi; Yagi, Hisashi; Goto, Yuji

    2014-06-27

    Amyloid fibrils form in supersaturated solutions via a nucleation and growth mechanism. We proposed that ultrasonication may be an effective agitation to trigger nucleation that would otherwise not occur under the persistent metastability of supersaturation. However, the roles of supersaturation and effects of ultrasonication have not been elucidated in detail except for limited cases. Insulin is an amyloidogenic protein that is useful for investigating the mechanisms underlying amyloid fibrillation with biological relevance. We studied the alcohol-induced amyloid fibrillation of insulin using various concentrations of 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol at pH 2.0 and 4.8. Ultrasonic irradiation effectively triggered fibrillation under conditions in which insulin retained persistent supersaturation. Structural analyses by circular dichroism, Fourier transform infrared spectroscopy, transmission electron microscopy, and atomic force microscopy revealed that the dominant structures of fibrils varied between parallel and antiparallel β-sheets depending on the solvent conditions. pH and alcohol concentration-dependent phase diagrams showed a marked difference before and after the ultrasonic treatment, which indicated that the persistent metastability of supersaturation determined the conformations of insulin. These results indicate the importance of an alternative view of amyloid fibrils as supersaturation-limited crystal-like aggregates formed above the solubility limit. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Supersaturation-limited Amyloid Fibrillation of Insulin Revealed by Ultrasonication*

    Science.gov (United States)

    Muta, Hiroya; Lee, Young-Ho; Kardos, József; Lin, Yuxi; Yagi, Hisashi; Goto, Yuji

    2014-01-01

    Amyloid fibrils form in supersaturated solutions via a nucleation and growth mechanism. We proposed that ultrasonication may be an effective agitation to trigger nucleation that would otherwise not occur under the persistent metastability of supersaturation. However, the roles of supersaturation and effects of ultrasonication have not been elucidated in detail except for limited cases. Insulin is an amyloidogenic protein that is useful for investigating the mechanisms underlying amyloid fibrillation with biological relevance. We studied the alcohol-induced amyloid fibrillation of insulin using various concentrations of 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol at pH 2.0 and 4.8. Ultrasonic irradiation effectively triggered fibrillation under conditions in which insulin retained persistent supersaturation. Structural analyses by circular dichroism, Fourier transform infrared spectroscopy, transmission electron microscopy, and atomic force microscopy revealed that the dominant structures of fibrils varied between parallel and antiparallel β-sheets depending on the solvent conditions. pH and alcohol concentration-dependent phase diagrams showed a marked difference before and after the ultrasonic treatment, which indicated that the persistent metastability of supersaturation determined the conformations of insulin. These results indicate the importance of an alternative view of amyloid fibrils as supersaturation-limited crystal-like aggregates formed above the solubility limit. PMID:24847058

  2. Kinase/phosphatase overexpression reveals pathways regulating hippocampal neuron morphology.

    Science.gov (United States)

    Buchser, William J; Slepak, Tatiana I; Gutierrez-Arenas, Omar; Bixby, John L; Lemmon, Vance P

    2010-07-01

    Development and regeneration of the nervous system requires the precise formation of axons and dendrites. Kinases and phosphatases are pervasive regulators of cellular function and have been implicated in controlling axodendritic development and regeneration. We undertook a gain-of-function analysis to determine the functions of kinases and phosphatases in the regulation of neuron morphology. Over 300 kinases and 124 esterases and phosphatases were studied by high-content analysis of rat hippocampal neurons. Proteins previously implicated in neurite growth, such as ERK1, GSK3, EphA8, FGFR, PI3K, PKC, p38, and PP1a, were confirmed to have effects in our functional assays. We also identified novel positive and negative neurite growth regulators. These include neuronal-developmentally regulated kinases such as the activin receptor, interferon regulatory factor 6 (IRF6) and neural leucine-rich repeat 1 (LRRN1). The protein kinase N2 (PKN2) and choline kinase alpha (CHKA) kinases, and the phosphatases PPEF2 and SMPD1, have little or no established functions in neuronal function, but were sufficient to promote neurite growth. In addition, pathway analysis revealed that members of signaling pathways involved in cancer progression and axis formation enhanced neurite outgrowth, whereas cytokine-related pathways significantly inhibited neurite formation.

  3. Molecular analysis of sourdough reveals Lactobacillus mindensis sp. nov.

    Science.gov (United States)

    Ehrmann, Matthias A; Müller, Martin R A; Vogel, Rudi F

    2003-01-01

    Genotypic fingerprinting to analyse the bacterial flora of an industrial sourdough revealed a coherent group of strains which could not be associated with a valid species. Comparative 16S rDNA sequence analysis showed that these strains formed a homogeneous cluster distinct from their closest relatives, Lactobacillus farciminis, Lactobacillus alimentarius and Lactobacillus kimchii. To characterize them further, physiological (sugar fermentation, formation of DL-lactate, hydrolysis of arginine, growth temperature, CO2 production) and chemotaxonomic properties have been determined. The DNA G +C content was 37.5 0.2 mol%. The peptidoglycan was of the lysine-D-iso-asparagine (L-Lys-D-Asp) type. The strains were homofermentative, Gram-positive, catalase-negative, non-spore-forming, non-motile rods. They were found as a major stable component of a rye flour sourdough fermentation. Physiological, biochemical as well as genotypic data suggested them to be a new species of the genus Lactobacillus. This was confirmed by DNA-DNA hybridization of genomic DNA, and the name Lactobacillus mindensis is proposed. The type strain of this species is DSM 14500T (=LMG 21508T).

  4. A n