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Sample records for 4a fig 4b

  1. Real-time PCR quantification of human complement C4A and C4B genes

    PubMed Central

    Szilagyi, Agnes; Blasko, Bernadett; Szilassy, Denes; Fust, George; Sasvari-Szekely, Maria; Ronai, Zsolt

    2006-01-01

    Background The fourth component of human complement (C4), an essential factor of the innate immunity, is represented as two isoforms (C4A and C4B) in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are functionally different. Based on phenotypic determination, unbalanced production of C4A and C4B is associated with several diseases, such as systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases, moreover with higher morbidity and mortality of myocardial infarction and increased susceptibility for bacterial infections. Despite of this major clinical relevance, only low throughput, time and labor intensive methods have been used so far for the quantification of C4A and C4B genes. Results A novel quantitative real-time PCR (qPCR) technique was developed for rapid and accurate quantification of the C4A and C4B genes applying a duplex, TaqMan based methodology. The reliable, single-step analysis provides the determination of the copy number of the C4A and C4B genes applying a wide range of DNA template concentration (0.3–300 ng genomic DNA). The developed qPCR was applied to determine C4A and C4B gene dosages in a healthy Hungarian population (N = 118). The obtained data were compared to the results of an earlier study of the same population. Moreover a set of 33 samples were analyzed by two independent methods. No significant difference was observed between the gene dosages determined by the employed techniques demonstrating the reliability of the novel qPCR methodology. A Microsoft Excel worksheet and a DOS executable are also provided for simple and automated evaluation of the measured data. Conclusion This report describes a novel real-time PCR method for single-step quantification of C4A and C4B genes. The developed technique could facilitate studies investigating disease association of different C4 isotypes. PMID:16403222

  2. Yeast eukaryotic initiation factor 4B (eIF4B) enhances complex assembly between eIF4A and eIF4G in vivo.

    PubMed

    Park, Eun-Hee; Walker, Sarah E; Zhou, Fujun; Lee, Joseph M; Rajagopal, Vaishnavi; Lorsch, Jon R; Hinnebusch, Alan G

    2013-01-25

    Translation initiation factor eIF4F (eukaryotic initiation factor 4F), composed of eIF4E, eIF4G, and eIF4A, binds to the m(7)G cap structure of mRNA and stimulates recruitment of the 43S preinitiation complex and subsequent scanning to the initiation codon. The HEAT domain of eIF4G stabilizes the active conformation of eIF4A required for its RNA helicase activity. Mammalian eIF4B also stimulates eIF4A activity, but this function appears to be lacking in yeast, making it unclear how yeast eIF4B (yeIF4B/Tif3) stimulates translation. We identified Ts(-) mutations in the HEAT domains of yeast eIF4G1 and eIF4G2 that are suppressed by overexpressing either yeIF4B or eIF4A, whereas others are suppressed only by eIF4A overexpression. Importantly, suppression of HEAT domain substitutions by yeIF4B overexpression was correlated with the restoration of native eIF4A·eIF4G complexes in vivo, and the rescue of specific mutant eIF4A·eIF4G complexes by yeIF4B was reconstituted in vitro. Association of eIF4A with WT eIF4G in vivo also was enhanced by yeIF4B overexpression and was impaired in cells lacking yeIF4B. Furthermore, we detected native complexes containing eIF4G and yeIF4B but lacking eIF4A. These and other findings lead us to propose that yeIF4B acts in vivo to promote eIF4F assembly by enhancing a conformation of the HEAT domain of yeast eIF4G conducive for stable binding to eIF4A.

  3. Long noncoding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression.

    PubMed

    Aguilo, Francesca; Zhou, Ming-Ming; Walsh, Martin J

    2011-08-15

    Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15(INK4b), p14(ARF), and p16(INK4a), and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development. PMID:21828241

  4. Long Noncoding RNA, Polycomb, and the Ghosts Haunting INK4b-ARF-INK4a Expression

    PubMed Central

    Aguilo, Francesca; Zhou, Ming-Ming; Walsh, Martin J.

    2012-01-01

    Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15INK4b, p14ARF, and p16INK4a, and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development. PMID:21828241

  5. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus.

    PubMed

    Kia, Sima Kheradmand; Gorski, Marcin M; Giannakopoulos, Stavros; Verrijzer, C Peter

    2008-05-01

    Stable silencing of the INK4b-ARF-INK4a tumor suppressor locus occurs in a variety of human cancers, including malignant rhabdoid tumors (MRTs). MRTs are extremely aggressive cancers caused by the loss of the hSNF5 subunit of the SWI/SNF chromatin-remodeling complex. We found previously that, in MRT cells, hSNF5 is required for p16(INK4a) induction, mitotic checkpoint activation, and cellular senescence. Here, we investigated how the balance between Polycomb group (PcG) silencing and SWI/SNF activation affects epigenetic control of the INK4b-ARF-INK4a locus in MRT cells. hSNF5 reexpression in MRT cells caused SWI/SNF recruitment and activation of p15(INK4b) and p16(INK4a), but not of p14(ARF). Gene activation by hSNF5 is strictly dependent on the SWI/SNF motor subunit BRG1. SWI/SNF mediates eviction of the PRC1 and PRC2 PcG silencers and extensive chromatin reprogramming. Concomitant with PcG complex removal, the mixed lineage leukemia 1 (MLL1) protein is recruited and active histone marks supplant repressive ones. Strikingly, loss of PcG complexes is accompanied by DNA methyltransferase DNMT3B dissociation and reduced DNA methylation. Thus, various chromatin states can be modulated by SWI/SNF action. Collectively, these findings emphasize the close interconnectivity and dynamics of diverse chromatin modifications in cancer and gene control. PMID:18332116

  6. Human wound infections caused by Neisseria animaloris and Neisseria zoodegmatis, former CDC Group EF-4a and EF-4b

    PubMed Central

    Heydecke, Anna; Andersson, Birgitta; Holmdahl, Torsten; Melhus, Åsa

    2013-01-01

    Background Neisseria animaloris and Neisseria zoodegmatis, former CDC Group EF-4a and -4b, are considered to be rare zoonotic pathogens, usually associated with dog or cat bites. The aim of the study was to phenotypicaly characterize 13 EF-4 isolates from wound infections, determine their antibiotic susceptibility and to follow the clinical outcome of the patients. Methods 13 of the EF-4 isolates were cultured on agar plates. Conventional biochemical tests and the Biolog system were used for phenotypical identification. An arbitrary primed polymerase chain reaction (AP-PCR) was carried out to determine the genetic profiles. Minimum inhibitory concentration (MIC) values were determined for different antibiotics were determined. According to this, clinical data for the patients were recorded. Results 11 isolates were identified as N. animaloris and 2 as N. zoodegmatis due to the production of arginine dihydrolase. A majority of the patients had a history of dog bite. In 6 cases only grewth of N. animaloris or zoodegmatis was registered. When a patient received antibiotic treatment the most common drug of choice was penicillin V. Only 3 patients received treatment for which the isolated EF-4 bacterium was fully susceptible. Conclusion Human infections involving N. animaloris and N. zoodegmatis usually present themselves as local wound infection, but severe complications can occur. Despite their pathogenic potentia, l N. animaloris and N. zoodegmatis are often misidentified, dismissed as skin contaminants or not recognized at all. Due to the fact that N. animaloris and N. zoodegmatis are significant pathogens in animal bites, physicians should keep these bacteria in mind when choosing antibiotic therapy. PMID:23919115

  7. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

    PubMed Central

    Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C.; Wong, Kwong-Kwok; Bao, Wei

    2015-01-01

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

  8. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.

    PubMed

    Qiu, Mei-Ting; Fan, Qiong; Zhu, Zhu; Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C; Wong, Kwong-Kwok; Bao, Wei

    2015-10-13

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

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

    PubMed

    Kshirsagar; Job

    1997-10-01

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

  10. Gene Expression Status and Methylation Pattern in Promoter of P15INK4b and P16INK4a in Cord Blood CD34+ Stem Cells

    PubMed Central

    Azad, Mehdi; Kaviani, Saeid; Noruzinia, Mehrdad; Mortazavi, Yousef; Mobarra, Naser; Alizadeh, Shaban; Shahjahani, Mohammad; Skandari, Fatemeh; Ahmadi, Mohammad Hosein; Atashi, Amir; Abroun, Saeid; Zonoubi, Zahra

    2013-01-01

    Objective(s) : Stem cell differentiation into different cell lineages depends upon several factors, cell cycle control elements and intracellular signaling elements, including P15INK4b and P16INK4a genes. Epigenetics may be regarded as a control mechanism which is affected by these factors with respect to their promoter structure. Materials and Methods : The CD34 + cord blood stem cells were purified, isolated and then expanded. The undifferentiated day genome was isolated from part of the cultured cells, and the seventh day differentiated genome was isolated from the other part after differentiation to erythroid lineage. The procedure was followed by a separate Real-Time PCR for the two genes using the obtained cDNA. The processed DNA of the former stages was used for MSP (Methylation Specific PCR) reaction. Finally, pre- and post differentiation results were compared.  Results : After performing MSP for each gene, it became clear that P15INK4b gene has undergone methylation and expression in predifferentiation stage. In addition, its status has not been changed after differentiation. P15INK4b gene expression was reduced after the differentiation. The other gene, P16INK4a, showed no predifferentiation methylation. Itwas completely expressed methylated and underwent reduced expression after differentiation. Conclusion : Specific predifferentiation expression of P15INK4b and P16INK4a genes along with reduction in their expression after erythroid differentiation indicated animportant role for these two genes in biology of CD34+ cells in primary stages and before differentiation. In addition, both genes are capable of epigenetic modifications due to the structure of their promoters. PMID:23997911

  11. Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers.

    PubMed

    Zhang, H; Li, X; Ge, L; Yang, J; Sun, J; Niu, Q

    2015-02-01

    To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py's level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py's level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs' p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers.

  12. Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A

    SciTech Connect

    Carroll, M.C.; Fathallah, D.M.; Bergamaschini, L.; Alicot, E.M. ); Isenman, D.E. )

    1990-09-01

    The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1. C4A binds to a greater extent when C1 is on IgG immune aggregates. The differences in covalent binding properties correlate only with amino acid changes between residues 1101 and 1106 (pro-C4 numbering)-namely, Pro-1101, Cys-1102, Leu-1105, and Asp-1106 in C4A and Leu-1101, Ser-1102, Ile-1105, and His-1106 in C4B, which are located in the C4d region of the {alpha} chain. To more precisely identify the residues that are important for the functional differences, C4A-C4B hybrid proteins were constructed by using recombinant DNA techniques. Comparison of these by hemolytic assay and binding to IgG aggregates showed that the single substitution of aspartic acid for histidine at position 1106 largely accounted for the change in functional activity and nature of the chemical bond formed. Surprisingly, substitution of a neutral residue, alanine, for histidine at position 1106 resulted in an increase in binding to immune aggregates without subsequent reduction in the hemolytic activity. This result strongly suggests that position 1106 is not catalytic as previously proposed but interacts sterically/electrostatically with potential acceptor sites and serves to select binding sites on potential acceptor molecules.

  13. Characterization and expression analyses of five interferon regulatory factor transcripts (Irf4a, Irf4b, Irf7, Irf8, Irf10) in Atlantic cod (Gadus morhua).

    PubMed

    Inkpen, Sabrina M; Hori, Tiago S; Gamperl, A Kurt; Nash, Gordon W; Rise, Matthew L

    2015-05-01

    The interferon regulatory factor (IRF) family of genes encodes a group of transcription factors that have important roles not only in regulating the expression of Type I interferons (IFNs) and other genes in the IFN pathway, but also in growth, development and the regulation of oncogenesis. In this study, several IRF family members (Irf4a, Irf4b, Irf7, Irf8, Irf10) in Atlantic cod (Gadus morhua) were characterized at the cDNA and putative amino acid levels, allowing for phylogenetic analysis of these proteins in teleost fish, as well as the development of gene-specific primers used in RT-PCR and quantitative PCR (QPCR) analyses. Two Atlantic cod Irf10 splice variants were identified and their presence confirmed by sequencing of the Irf10 genomic region. RT-PCR showed that Irf7, Irf8 and both Irf10 transcripts were expressed in all 15 cod tissues tested, while Irf4a and Irf4b were absent in some tissues. QPCR analysis of spleen expression expanded upon this, and upon previous work. All IRF transcripts in the study were responsive to stimulation by the viral mimic poly(I:C), and all except Irf4a were responsive to exposure to formalin-killed Aeromonas salmonicida (ASAL). These IRF genes, thus, are likely important in the cod immune response to both viral and bacterial infections. Increased temperature (10 °C to 16 °C) was also observed to modulate the antibacterial responses of all IRF transcripts, and the antiviral responses of Irf4b and Irf10-v2. This research supports earlier studies which reported that elevated temperature modulates the expression of many immune genes in Atlantic cod. PMID:25731920

  14. NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, fibroblast and neuronal cells and maintain ER morphology

    PubMed Central

    Rämö, Olli; Kumar, Darshan; Gucciardo, Erika; Joensuu, Merja; Saarekas, Maiju; Vihinen, Helena; Belevich, Ilya; Smolander, Olli-Pekka; Qian, Kui; Auvinen, Petri; Jokitalo, Eija

    2016-01-01

    Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets. PMID:27786289

  15. eIF4B, eIF4G and RNA regulate eIF4A activity in translation initiation by modulating the eIF4A conformational cycle.

    PubMed

    Harms, Ulf; Andreou, Alexandra Zoi; Gubaev, Airat; Klostermeier, Dagmar

    2014-07-01

    Eukaryotic translation initiation factor eIF4A is a DEAD-box helicase that resolves secondary structure elements in the 5'-UTR of mRNAs during ribosome scanning. Its RNA-stimulated ATPase and ATP-dependent helicase activities are enhanced by other translation initiation factors, but the underlying mechanisms are unclear. DEAD-box proteins alternate between open and closed conformations during RNA unwinding. The transition to the closed conformation is linked to duplex destabilization. eIF4A is a special DEAD-box protein that can adopt three different conformations, an open state in the absence of ligands, a half-open state stabilized by the translation initiation factor eIF4G and a closed state in the presence of eIF4G and eIF4B. We show here that eIF4A alone does not measurably sample the closed conformation. The translation initiation factors eIF4B and eIF4G accelerate the eIF4A conformational cycle. eIF4G increases the rate of closing more than the opening rate, and eIF4B selectively increases the closing rate. Strikingly, the rate constants and the effect of eIF4B are different for different RNAs, and are related to the presence of single-stranded regions. Modulating the kinetics of the eIF4A conformational cycle is thus central for the multi-layered regulation of its activity, and for its role as a regulatory hub in translation initiation. PMID:24848014

  16. AtCCR4a and AtCCR4b are Involved in Determining the Poly(A) Length of Granule-bound starch synthase 1 Transcript and Modulating Sucrose and Starch Metabolism in Arabidopsis thaliana.

    PubMed

    Suzuki, Yuya; Arae, Toshihiro; Green, Pamela J; Yamaguchi, Junji; Chiba, Yukako

    2015-05-01

    Removing the poly(A) tail is the first and rate-limiting step of mRNA degradation and apparently an effective step not only for modulating mRNA stability but also for translation of many eukaryotic transcripts. Carbon catabolite repressor 4 (CCR4) has been identified as a major cytoplasmic deadenylase in Saccharomyces cerevisiae. The Arabidopsis thaliana homologs of the yeast CCR4, AtCCR4a and AtCCR4b, were identified by sequence-based analysis; however, their role and physiological significance in plants remain to be elucidated. In this study, we revealed that AtCCR4a and AtCCR4b are localized to cytoplasmic mRNA processing bodies, which are specific granules consisting of many enzymes involved in mRNA turnover. Double mutants of AtCCR4a and AtCCR4b exhibited tolerance to sucrose application but not to glucose. The levels of sucrose in the seedlings of the atccr4a/4b double mutants were reduced, whereas no difference was observed in glucose levels. Further, amylose levels were slightly but significantly increased in the atccr4a/4b double mutants. Consistent with this observation, we found that the transcript encoding granule-bound starch synthase 1 (GBSS1), which is responsible for amylose synthesis, is accumulated to a higher level in the atccr4a/4b double mutant plants than in the control plants. Moreover, we revealed that GBSS1 has a longer poly(A) tail in the double mutant than in the control plant, suggesting that AtCCR4a and AtCCR4b can influence the poly(A) length of transcripts related to starch metabolism. Our results collectively suggested that AtCCR4a and AtCCR4b are involved in sucrose and starch metabolism in A. thaliana.

  17. APEX-CHAMP+ high-J CO observations of low-mass young stellar objects. III. NGC 1333 IRAS 4A/4B envelope, outflow, and ultraviolet heating

    NASA Astrophysics Data System (ADS)

    Yıldız, Umut A.; Kristensen, Lars E.; van Dishoeck, Ewine F.; Belloche, Arnaud; van Kempen, Tim A.; Hogerheijde, Michiel R.; Güsten, Rolf; van der Marel, Nienke

    2012-06-01

    Context. The NGC 1333 IRAS 4A and IRAS 4B sources are among the most well-studied Stage 0 low-mass protostars, which drive prominent bipolar outflows. Spectrally resolved molecular emission lines provide crucial information about the physical and chemical structure of the circumstellar material as well as the dynamics of the different components. Most studies have so far concentrated on the colder parts (T ≤ 30 K) of these regions. Aims: The aim is to characterize the warmer parts of the protostellar envelope using the new generation of submillimeter instruments. This will allow us to quantify the feedback of the protostars on their surroundings in terms of shocks, ultraviolet (UV) heating, photodissociation, and outflow dispersal. Methods: The dual frequency 2 × 7 pixel 650/850 GHz array receiver CHAMP+ mounted on APEX was used to obtain a fully sampled, large-scale ~4' × 4' map at 9″ resolution of the IRAS 4A/4B region in the 12CO J = 6-5 line. Smaller maps were observed in the 13CO 6-5 and [C i] J = 2-1 lines. In addition, a fully sampled 12CO J = 3-2 map made with HARP-B on the JCMT is presented and deep isotopolog observations are obtained at selected outflow positions to constrain the optical depth. Complementary Herschel-HIFI and ground-based lines of CO and its isotopologs, from J = 1-0 up to 10-9 (Eu/k ≈ 300 K), are collected at the source positions and used to construct velocity-resolved CO ladders and rotational diagrams. Radiative-transfer models of the dust and lines are used to determine the temperatures and masses of the outflowing and photon-heated gas and infer the CO abundance structure. Results: Broad CO emission-line profiles trace entrained shocked gas along the outflow walls, which have an average temperature of ~100 K. At other positions surrounding the outflow and the protostar, the 6-5 line profiles are narrow indicating UV excitation. The narrow 13CO 6-5 data directly reveal the UV heated gas distribution for the first time. The

  18. An allele-specific PCR system for rapid detection and discrimination of the CYP2C19∗4A, ∗4B, and ∗17 alleles: implications for clopidogrel response testing.

    PubMed

    Scott, Stuart A; Tan, Qian; Baber, Usman; Yang, Yao; Martis, Suparna; Bander, Jeffrey; Kornreich, Ruth; Hulot, Jean-Sébastien; Desnick, Robert J

    2013-11-01

    CYP2C19 is involved in the metabolism of clinically relevant drugs, including the antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19 genotyping. The CYP2C19∗4B allele is defined by both gain-of-function [c.-806C>T (∗17)] and loss-of-function [c.1A>G (∗4)] variants on the same haplotype; however, current genotyping and sequencing assays are unable to determine the phase of these variants. Thus, the aim of this study was to develop an assay that could rapidly detect and discriminate the related ∗4A, ∗4B, and ∗17 alleles. An allele-specific PCR assay, composed of four unique primer mixes that specifically interrogate the defining ∗17 and ∗4 variants, was developed by using samples (n = 20) with known genotypes, including the ∗4A, ∗4B, and/or ∗17 alleles. The assay was validated by testing 135 blinded samples, and the results were correlated with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly, among the six ∗4 carriers in the validation cohort, after allele-specific PCR testing both samples with a ∗1/∗4 genotype were reclassified to ∗1/∗4A, all three samples with a ∗4/∗17 genotype were reclassified to ∗1/∗4B, and a sample with a ∗4/∗17/∗17 genotype was reclassified to ∗4B/∗17. In conclusion, this rapid and robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer phenotype classification by determining the phase of the defining ∗17 and ∗4 variants, which may have utility when testing CYP2C19 for clopidogrel response.

  19. Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.

    PubMed

    Song, Pingping; Zou, Shasha; Chen, Tingting; Chen, Jianhua; Wang, Yanan; Yang, Juanjuan; Song, Zhijian; Jiang, Huayu; Shi, Huijuan; Huang, Yiran; Li, Zheng; Shi, Yongyong; Hu, Hongliang

    2015-02-01

    Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P < 0.001). Furthermore, the results of the meta-analysis support the conclusion that the T-786C and 4a4b loci were associated with male infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future.

  20. Carcinogen-specific mutational and epigenetic alterations in INK4A, INK4B and p53 tumour-suppressor genes drive induced senescence bypass in normal diploid mammalian cells.

    PubMed

    Yasaei, H; Gilham, E; Pickles, J C; Roberts, T P; O'Donovan, M; Newbold, R F

    2013-01-10

    Immortalization (senescence bypass) is a critical rate-limiting step in the malignant transformation of mammalian somatic cells. Human cells must breach at least two distinct senescence barriers to permit unfettered clonal evolution during cancer development: (1) stress- or oncogene-induced premature senescence (SIPS/OIS), mediated via the p16-Rb and/or ARF-p53-p21 tumour-suppressive pathways, and (2) replicative senescence triggered by telomere shortening. In contrast, because their telomerase is constitutively active, cells from small rodents possess only the SIPS/OIS barrier, and are therefore useful for studying SIPS/OIS bypass in isolation. Dermal fibroblasts from the Syrian hamster (SHD cells) are exceptionally resistant to spontaneous SIPS bypass, but it can be readily induced following exposure to a wide range of chemical and physical carcinogens. Here we show that a spectrum of carcinogen-specific mutational and epigenetic alterations involving the INK4A (p16), p53 and INK4B (p15) genes are associated with induced SIPS bypass. With ionizing radiation, immortalization is invariably accompanied by efficient biallelic deletion of the complete INK4/CDKN2 locus. In comparison, SHD cells immortalized by the powerful polycyclic hydrocarbon carcinogen benzo(a)pyrene display transversion point mutations in the DNA-binding domain of p53 coupled with INK4 alterations such as loss of expression of p15. Epimutational silencing of p16 is the primary event associated with immortalization by nickel, a human non-genotoxic carcinogen. As SIPS/OIS bypass is a prerequisite for the immortalization of normal diploid human epithelial cells, our results with the SHD model will provide a basis for delineating combinations of key molecular changes underpinning this important event in human carcinogenesis. PMID:22410783

  1. Why do fig wasps actively pollinate monoecious figs?

    PubMed

    Jousselin, Emmanuelle; Hossaert-McKey, Martine; Herre, Edward Allen; Kjellberg, Finn

    2003-02-01

    Active pollination, although rare, has been documented in a few pollination mutualisms. Such behaviour can only evolve if it benefits the pollinator in some way. The wasps that pollinate Ficus inflorescences can be active or passive pollinators. They lay their eggs in fig flowers, so that a proportion of flowers will host a wasp larva instead of a seed. We show in an actively pollinated monoecious fig that lack of pollination does not induce fig abortion or affect wasp offspring size but results in smaller numbers of offspring. Hence, conversely to other active pollination systems, seed formation is not obligatory to sustain developing pollinator larvae; however there is a direct fitness cost to active pollinators not to pollinate. We then compared the locations of eggs and fertilised flowers of three actively pollinated Ficus species and one passively pollinated species. We found that more flowers containing wasp eggs were fertilised in the actively pollinated species relative to those of the passively pollinated one. These results along with comparison with similar studies on dioecious figs, support the hypothesis that active pollination has evolved in fig wasps to ensure that more flowers containing wasp eggs are fertilised as this may increase the chances of successful gall development. The stigmatic platform characterising actively pollinated figs is probably an adaptation to increase pollen dispersion within the fig.

  2. Boeing F4B-4

    NASA Technical Reports Server (NTRS)

    1932-01-01

    The Boeing F4B-4 was seen to differ from earlier F4Bs in having a vertical fin with slightly more area. The Boeing model 235 was not fitted with a NACA cowling, but rather the less efficient 'Townend' ring around the Pratt & Whitney Wasp radials cylinders. This aircraft was much used by both the Navy and the Army Air Corps in the late 1920's and early 1930's. The Army variation was known as the P-12E. The engine cowling was a British development known as the 'Townend' ring. It differed from the NACA cowling and was less effective in reducing the drag.

  3. Selective Phosphodiesterase 4B Inhibitors: A Review

    PubMed Central

    Azam, Mohammed Afzal; Tripuraneni, Naga Srinivas

    2014-01-01

    Abstract Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B. PMID:25853062

  4. How to be an ant on figs

    NASA Astrophysics Data System (ADS)

    Bain, Anthony; Harrison, Rhett D.; Schatz, Bertrand

    2014-05-01

    Mutualistic interactions are open to exploitation by one or other of the partners and a diversity of other organisms, and hence are best understood as being embedded in a complex network of biotic interactions. Figs participate in an obligate mutualism in that figs are dependent on agaonid fig wasps for pollination and the wasps are dependent on fig ovules for brood sites. Ants are common insect predators and abundant in tropical forests. Ants have been recorded on approximately 11% of fig species, including all six subgenera, and often affect the fig-fig pollinator interaction through their predation of either pollinating and parasitic wasps. On monoecious figs, ants are often associated with hemipterans, whereas in dioecious figs ants predominantly prey on fig wasps. A few fig species are true myrmecophytes, with domatia or food rewards for ants, and in at least one species this is linked to predation of parasitic fig wasps. Ants also play a role in dispersal of fig seeds and may be particularly important for hemi-epiphytic species, which require high quality establishment microsites in the canopy. The intersection between the fig-fig pollinator and ant-plant systems promises to provide fertile ground for understanding mutualistic interactions within the context of complex interaction networks.

  5. Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

    PubMed Central

    Tzeng, E; Billiar, T R; Robbins, P D; Loftus, M; Stuehr, D J

    1995-01-01

    Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8524846

  6. RDR-4B doppler weather radar with forward looking wind shear detection capability

    NASA Technical Reports Server (NTRS)

    Grasley, Steven S.

    1992-01-01

    The topics are presented in viewgraph form and include the following: Bendix/King atmospheric transport and dispersion (ATAD) position; RDR-4A technical baseline; RTA-4A characteristics; RDR-4 antenna characteristics; modification of RDR-4A to RDR-4B; RDR-4A functional block diagram; RDR-4B characteristics; development/test plan; CV-580 testing capability; CV-580 test results; Continental A300 test configuration; Continental Data Recording Program operational considerations; Continental A300 test results; and display considerations.

  7. Ecology of a fig ant-plant

    NASA Astrophysics Data System (ADS)

    Harrison, Rhett D.

    2014-05-01

    Mutualistic interactions are embedded in networks of interactions that affect the benefits accruing to the mutualistic partners. Figs and their pollinating wasps are engaged in an obligate mutualism in which the fig is dependent on the fig pollinator for pollination services and the pollinator is dependent on fig ovules for brood sites. This mutualism is exploited by non-pollinating fig wasps that utilise the same ovules, but do not provide a pollination service. Most non-pollinating wasps oviposit from outside the inflorescence (syconium), where they are vulnerable to ant predation. Ficus schwarzii is exposed to high densities of non-pollinating wasps, but Philidris sp. ants patrolling the syconia prevent them from ovipositing. Philidris rarely catch wasps, but the fig encourages the patrolling by providing a reward through extra-floral nectaries on the surface of syconia. Moreover, the reward is apparently only produced during the phase when parasitoids are ovipositing. An ant-exclusion experiment demonstrated that, in the absence of ants, syconia were heavily attacked and many aborted as a consequence. Philidris was normally rare on the figs during the receptive phase or at the time of day when wasp offspring are emerging, so predation on pollinators was limited. However, Myrmicaria sp. ants, which only occurred on three trees, preyed substantially on pollinating as well as non-pollinating wasps. F. schwarzii occurs in small clusters of trees and has an exceptionally rapid crop turnover. These factors appear to promote high densities of non-pollinating wasps and, as a consequence, may have led to both a high incidence of ants on trees and increased selective pressure on fig traits that increase the payoffs of the fig-ant interaction for the fig. The fig receives no direct benefit from the reward it provides, but protects pollinating wasps that will disperse its pollen.

  8. Ants use odour cues to exploit fig-fig wasp interactions

    NASA Astrophysics Data System (ADS)

    Schatz, Bertrand; Hossaert-McKey, Martine

    2010-01-01

    Fig wasps may constitute a relatively abundant food source for ants associated with the fig-fig wasp nursery pollination mutualism. We found previously that a Mediterranean ant species detects fig wasps by chemical signals. In this paper we want to test the generality of this finding by studying two tropical ants, Oecophylla smaragdina and Crematogaster sp., preying on fig wasps on the dioecious Ficus fistulosa in Brunei (Borneo). Behavioural tests in a Y-tube olfactometer showed that these two ants were attracted both to odours emitted by receptive figs and to those emitted by fig wasps (male and female of the pollinator, and a non-pollinating fig wasp) used here as a kairomone. Naïve workers were not attracted to fig wasps, suggesting that olfactory learning may play a role in prey detection. We also found that O. smaragdina was much more likely to be present on figs of male trees (where fig wasps are more abundant), and that the abundance of this ant species varied strongly with developmental phase of figs on individual trees. Moreover, its aggressiveness was also strongly influenced by the nature of the object presented in our behavioural tests, the site of the test and the developmental phase of the fig tested. Investigation on the chemical and behavioural ecology of the different interacting species provides important insights into the intricate relationships supported by the fig-fig wasp mutualism.

  9. Larger fig wasps are more careful about which figs to enter--with good reason.

    PubMed

    Liu, Cong; Yang, Da-Rong; Compton, Stephen G; Peng, Yan-Qiong

    2013-01-01

    Floral longevity reflects a balance between gains in pollinator visitation and the costs of flower maintenance. Because rewards to pollinators change over time, older flowers may be less attractive, reducing the value of extended longevity. Un-pollinated figs, the inflorescences of Ficus species, can remain receptive for long periods, but figs that are older when entered by their host-specific fig wasp pollinators produce fewer seeds and fig wasp offspring. Our field experiments with Ficushispida, a dioecious fig tree, examined how the length of time that receptive figs have remained un-pollinated influences the behaviour and reproductive success of its short-lived fig wasp pollinator, Ceratosolensolmsi marchali. The results were consistent in three different seasons, and on male and female trees, although receptivity was greatly extended during colder months. Pollinators took longer to find the ostioles of older figs, and longer to penetrate them. They also became increasingly unwilling to enter figs as they aged, and increasing numbers of the wasps became trapped in the ostiolar bracts. Larger individuals were particularly unwilling to enter older figs, resulting in older figs being pollinated by smaller wasps. On female trees, where figs produce only seeds, seed production declined rapidly with fig age. On male trees, the numbers and size of fig wasp offspring declined, and a higher proportion were male. Older male figs are harder to enter, especially for larger individuals, and offer poorer quality oviposition opportunities. This study opens an interesting new perspective on the coevolution of figs and their pollinators, especially factors influencing pollinator body size and emphasises the subtleties of interactions between mutualists.

  10. Only pollinator fig wasps have males that collaborate to release their females from figs of an Asian fig tree.

    PubMed

    Suleman, Nazia; Raja, Shazia; Compton, Stephen G

    2012-06-23

    Male insects rarely collaborate with each other, but pollinator fig wasps (Hymenoptera: Agaonidae) are said to be an exception. Immature fig wasps feed on galled ovules located inside figs, the inflorescences of Ficus species (Moraceae). After mating, adult pollinator males chew communal exit-holes that allow mated females (which are often also their siblings) to escape. Figs also support non-pollinating fig wasps (NPFWs), some of which produce exit-holes independently. We determined whether collaboration between pollinator males (Kradibia tentacularis from Ficus montana) was necessary for the release of their females, and used the relationship between male numbers and likelihood of success to measure the extent of cooperation during exit-hole production. These attributes were then compared with those of an NPFW (Sycoscapter sp.) from the same host plant. Pollinators were more abundant than NPFW, but their more female-biased sex ratio meant male pollinator densities were only slightly higher. Individual males of both species could produce an exit-hole. Single males of the NPFW were just as successful as single male pollinators, but only male pollinators cooperated effectively, becoming more successful as their numbers increased. The lack of cooperation among NPFW may be linked to their earlier period of intense inter-male aggression.

  11. Structural basis for the design of selective phosphodiesterase 4B inhibitors.

    PubMed

    Fox, David; Burgin, Alex B; Gurney, Mark E

    2014-03-01

    Phosphodiesterase-4B (PDE4B) regulates the pro-inflammatory Toll Receptor -Tumor Necrosis Factor α (TNFα) pathway in monocytes, macrophages and microglial cells. As such, it is an important, although under-exploited molecular target for anti-inflammatory drugs. This is due in part to the difficulty of developing selective PDE4B inhibitors as the amino acid sequence of the PDE4 active site is identical in all PDE4 subtypes (PDE4A-D). We show that highly selective PDE4B inhibitors can be designed by exploiting sequence differences outside the active site. Specifically, PDE4B selectivity can be achieved by capture of a C-terminal regulatory helix, now termed CR3 (Control Region 3), across the active site in a conformation that closes access by cAMP. PDE4B selectivity is driven by a single amino acid polymorphism in CR3 (Leu674 in PDE4B1 versus Gln594 in PDE4D). The reciprocal mutations in PDE4B and PDE4D cause a 70-80 fold shift in selectivity. Our structural studies show that CR3 is flexible and can adopt multiple orientations and multiple registries in the closed conformation. The new co-crystal structure with bound ligand provides a guide map for the design of PDE4B selective anti-inflammatory drugs. PMID:24361374

  12. Ancient fig wasps indicate at least 34 Myr of stasis in their mutualism with fig trees.

    PubMed

    Compton, Stephen G; Ball, Alexander D; Collinson, Margaret E; Hayes, Peta; Rasnitsyn, Alexandr P; Ross, Andrew J

    2010-12-23

    Fig wasps and fig trees are mutually dependent, with each of the 800 or so species of fig trees (Ficus, Moraceae) typically pollinated by a single species of fig wasp (Hymenoptera: Agaonidae). Molecular evidence suggests that the relationship existed over 65 Ma, during the Cretaceous. Here, we record the discovery of the oldest known fossil fig wasps, from England, dated at 34 Ma. They possess pollen pockets that contain fossil Ficus pollen. The length of their ovipositors indicates that their host trees had a dioecious breeding system. Confocal microscopy and scanning electron microscopy reveal that the fossil female fig wasps, and more recent species from Miocene Dominican amber, display the same suite of anatomical characters associated with fig entry and pollen-carrying as modern species. The pollen is also typical of modern Ficus. No innovations in the relationship are discernible for the last tens of millions of years.

  13. Ancient fig wasps indicate at least 34 Myr of stasis in their mutualism with fig trees

    PubMed Central

    Compton, Stephen G.; Ball, Alexander D.; Collinson, Margaret E.; Hayes, Peta; Rasnitsyn, Alexandr P.; Ross, Andrew J.

    2010-01-01

    Fig wasps and fig trees are mutually dependent, with each of the 800 or so species of fig trees (Ficus, Moraceae) typically pollinated by a single species of fig wasp (Hymenoptera: Agaonidae). Molecular evidence suggests that the relationship existed over 65 Ma, during the Cretaceous. Here, we record the discovery of the oldest known fossil fig wasps, from England, dated at 34 Ma. They possess pollen pockets that contain fossil Ficus pollen. The length of their ovipositors indicates that their host trees had a dioecious breeding system. Confocal microscopy and scanning electron microscopy reveal that the fossil female fig wasps, and more recent species from Miocene Dominican amber, display the same suite of anatomical characters associated with fig entry and pollen-carrying as modern species. The pollen is also typical of modern Ficus. No innovations in the relationship are discernible for the last tens of millions of years. PMID:20554563

  14. The occurrence of fig wasps in the fruits of female gynodioecious fig trees

    NASA Astrophysics Data System (ADS)

    Wu, Tao; Dunn, Derek W.; Hu, Hao-Yuan; Niu, Li-Ming; Xiao, Jin-Hua; Pan, Xian-Li; Feng, Gui; Fu, Yue-Guan; Huang, Da-Wei

    2013-01-01

    Fig trees are pollinated by wasp mutualists, whose larvae consume some of the plant's ovaries. Many fig species (350+) are gynodioecious, whereby pollinators generally develop in the figs of 'male' trees and seeds generally in the 'females.' Pollinators usually cannot reproduce in 'female' figs at all because their ovipositors cannot penetrate the long flower styles to gall the ovaries. Many non-pollinating fig wasp (NPFW) species also only reproduce in figs. These wasps can be either phytophagous gallers or parasites of other wasps. The lack of pollinators in female figs may thus constrain or benefit different NPFWs through host absence or relaxed competition. To determine the rates of wasp occurrence and abundance we surveyed 11 dioecious fig species on Hainan Island, China, and performed subsequent experiments with Ficus tinctoria subsp. gibbosa to identify the trophic relationships between NPFWs that enable development in female syconia. We found NPFWs naturally occurring in the females of Ficus auriculata, Ficus hainanensis and F. tinctoria subsp. gibbosa. Because pollinators occurred only in male syconia, when NPFWs also occurred in female syconia, overall there were more wasps in male than in female figs. Species occurrence concurred with experimental data, which showed that at least one phytophagous galler NPFW is essential to enable multiple wasp species to coexist within a female fig. Individuals of galler NPFW species present in both male and female figs of the same fig species were more abundant in females than in males, consistent with relaxed competition due to the absence of pollinator. However, these wasps replaced pollinators on a fewer than one-to-one basis, inferring that other unknown mechanisms prevent the widespread exploitation by wasps of female figs. Because some NPFW species may use the holes chewed by pollinator males to escape from their natal fig, we suggest that dispersal factors could be involved.

  15. Asymmetric or diffusive co-evolution generates meta-populations in fig-fig wasp mutualisms.

    PubMed

    Wang, RuiWu; Yang, Yan; Wiggins, Natasha L

    2014-06-01

    Co-evolutionary theory assumes co-adapted characteristics are a positive response to counter those of another species, whereby co-evolved species reach an evolutionarily stable interaction through bilateral adaptation. However, evidence from the fig-fig wasp mutualistic system implies very different co-evolutionary selection mechanisms, due to the inherent conflict among interacted partners. Fig plants appear to have discriminatively enforced fig wasps to evolve "adaptation characteristics" that provide greater benefit to the fig, and fig wasps appear to have diversified their evolutionary strategies in response to discriminative enforcement by figs and competition among different fig wasp species. In what appears to be an asymmetric interaction, the prosperity of cooperative pollinating wasps should inevitably lead to population increases of parasitic individuals, thus resulting in localized extinctions of pollinating wasps. In response, the sanctioning of parasitic wasps by the fig should lead to a reduction in the parasitic wasp population. The meta-populations created by such asymmetric interactions may result in each population of coevolved species chaotically oscillated, temporally or evolutionarily.

  16. Asymmetric interaction and indeterminate fitness correlation between cooperative partners in the fig-fig wasp mutualism.

    PubMed

    Wang, Rui-Wu; Sun, Bao-Fa; Zheng, Qi; Shi, Lei; Zhu, Lixing

    2011-10-01

    Empirical observations have shown that cooperative partners can compete for common resources, but what factors determine whether partners cooperate or compete remain unclear. Using the reciprocal fig-fig wasp mutualism, we show that nonlinear amplification of interference competition between fig wasps-which limits the fig wasps' ability to use a common resource (i.e. female flowers)-keeps the common resource unsaturated, making cooperation locally stable. When interference competition was manually prevented, the fitness correlation between figs and fig wasps went from positive to negative. This indicates that genetic relatedness or reciprocal exchange between cooperative players, which could create spatial heterogeneity or self-restraint, was not sufficient to maintain stable cooperation. Moreover, our analysis of field-collected data shows that the fitness correlation between cooperative partners varies stochastically, and that the mainly positive fitness correlation observed during the warm season shifts to a negative correlation during the cold season owing to an increase in the initial oviposition efficiency of each fig wasp. This implies that the discriminative sanction of less-cooperative wasps (i.e. by decreasing the egg deposition efficiency per fig wasp) but reward to cooperative wasps by fig, a control of the initial value, will facilitate a stable mutualism. Our finding that asymmetric interaction leading to an indeterminate fitness interaction between symbiont (i.e. cooperative actors) and host (i.e. recipient) has the potential to explain why conflict has been empirically observed in both well-documented intraspecific and interspecific cooperation systems.

  17. Climate warming and the potential extinction of fig wasps, the obligate pollinators of figs.

    PubMed

    Jevanandam, Nanthinee; Goh, Alexander G R; Corlett, Richard T

    2013-06-23

    Figs (Ficus) have a reciprocally obligate mutualism with tiny, short-lived (1-2 days) fig wasps (Agaonidae). The small size and short life of these pollinators is expected to make them more vulnerable to climate change than their larger and longer-lived hosts. We experimentally tested the thermal tolerances of four species of adult female fig wasp from equatorial Singapore. The results suggest that an increase of 3°C or more above the current temperatures experienced across much of the equatorial tropics would markedly decrease the active adult lifespan of all four species. Fig plants are the centre of an intricate web of specialist and generalist animals. Unless fig wasps can acclimate or adapt to warmer temperatures in time, these responses may disrupt the mutualism, potentially affecting multiple trophic levels.

  18. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  19. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  20. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  1. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  2. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false De minimis exceptions. 173.4b Section 173.4b Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS General § 173.4b De minimis exceptions. (a) Packing Group II and III materials...

  3. Diffusive coevolution and mutualism maintenance mechanisms in a fig-fig wasp system.

    PubMed

    Wang, Rui-Wu; Sun, Bao-Fa; Zheng, Qi

    2010-05-01

    In reciprocal mutualism systems, the exploitation events by exploiters might disrupt the reciprocal mutualism, wherein one exploiter species might even exclude other coexisting exploiter species over an evolutionary time frame. What remains unclear is how such a community is maintained. Niche partitioning, or spatial heterogeneity among the mutualists and exploiters, is generally believed to enable stability within a mutualistic system. However, our examination of a reciprocal mutualism between a fig species (Ficus racemosa) and its pollinator wasp (Ceratosolen fusciceps) shows that spatial niche partitioning does not sufficiently prevent exploiters from overexploiting the common resource (i.e., the female flowers), because of the considerable niche overlap between the mutualists and exploiters. In response to an exploiter, our experiment shows that the fig can (1) abort syconia-containing flowers that have been galled by the exploiter, Apocryptophagus testacea, which oviposits before the pollinators do; and (2) retain syconia-containing flowers galled by Apocryptophagus mayri, which oviposit later than pollinators. However, as a result of (2), there is decreased development of adult non-pollinators or pollinator species in syconia that have not been sufficiently pollinated, but not aborted. Such discriminative abortion of figs or reduction in offspring development of exploiters while rewarding cooperative individuals with higher offspring development by the fig will increase the fitness of cooperative pollinating wasps, but decrease the fitness of exploiters. The fig-fig wasp interactions are diffusively coevolved, a case in which fig wasps diversify their genotype, phenotype, or behavior as a result of competition between wasps, while figs diverge their strategies to facilitate the evolution of cooperative fig waps or lessen the detrimental behavior by associated fig wasps. In habitats or syconia that suffer overexploitation, discriminative abortion of figs or

  4. An Extreme Case of Plant–Insect Codiversification: Figs and Fig-Pollinating Wasps

    PubMed Central

    Cruaud, Astrid; Rønsted, Nina; Chantarasuwan, Bhanumas; Chou, Lien Siang; Clement, Wendy L.; Couloux, Arnaud; Cousins, Benjamin; Genson, Gwenaëlle; Harrison, Rhett D.; Hanson, Paul E.; Hossaert-Mckey, Martine; Jabbour-Zahab, Roula; Jousselin, Emmanuelle; Kerdelhué, Carole; Kjellberg, Finn; Lopez-Vaamonde, Carlos; Peebles, John; Peng, Yan-Qiong; Pereira, Rodrigo Augusto Santinelo; Schramm, Tselil; Ubaidillah, Rosichon; van Noort, Simon; Weiblen, George D.; Yang, Da-Rong; Yodpinyanee, Anak; Libeskind-Hadas, Ran; Cook, James M.; Rasplus, Jean-Yves; Savolainen, Vincent

    2012-01-01

    It is thought that speciation in phytophagous insects is often due to colonization of novel host plants, because radiations of plant and insect lineages are typically asynchronous. Recent phylogenetic comparisons have supported this model of diversification for both insect herbivores and specialized pollinators. An exceptional case where contemporaneous plant–insect diversification might be expected is the obligate mutualism between fig trees (Ficus species, Moraceae) and their pollinating wasps (Agaonidae, Hymenoptera). The ubiquity and ecological significance of this mutualism in tropical and subtropical ecosystems has long intrigued biologists, but the systematic challenge posed by >750 interacting species pairs has hindered progress toward understanding its evolutionary history. In particular, taxon sampling and analytical tools have been insufficient for large-scale cophylogenetic analyses. Here, we sampled nearly 200 interacting pairs of fig and wasp species from across the globe. Two supermatrices were assembled: on an average, wasps had sequences from 77% of 6 genes (5.6 kb), figs had sequences from 60% of 5 genes (5.5 kb), and overall 850 new DNA sequences were generated for this study. We also developed a new analytical tool, Jane 2, for event-based phylogenetic reconciliation analysis of very large data sets. Separate Bayesian phylogenetic analyses for figs and fig wasps under relaxed molecular clock assumptions indicate Cretaceous diversification of crown groups and contemporaneous divergence for nearly half of all fig and pollinator lineages. Event-based cophylogenetic analyses further support the codiversification hypothesis. Biogeographic analyses indicate that the present-day distribution of fig and pollinator lineages is consistent with a Eurasian origin and subsequent dispersal, rather than with Gondwanan vicariance. Overall, our findings indicate that the fig-pollinator mutualism represents an extreme case among plant–insect interactions of

  5. An extreme case of plant-insect codiversification: figs and fig-pollinating wasps.

    PubMed

    Cruaud, Astrid; Rønsted, Nina; Chantarasuwan, Bhanumas; Chou, Lien Siang; Clement, Wendy L; Couloux, Arnaud; Cousins, Benjamin; Genson, Gwenaëlle; Harrison, Rhett D; Hanson, Paul E; Hossaert-McKey, Martine; Jabbour-Zahab, Roula; Jousselin, Emmanuelle; Kerdelhué, Carole; Kjellberg, Finn; Lopez-Vaamonde, Carlos; Peebles, John; Peng, Yan-Qiong; Pereira, Rodrigo Augusto Santinelo; Schramm, Tselil; Ubaidillah, Rosichon; van Noort, Simon; Weiblen, George D; Yang, Da-Rong; Yodpinyanee, Anak; Libeskind-Hadas, Ran; Cook, James M; Rasplus, Jean-Yves; Savolainen, Vincent

    2012-12-01

    It is thought that speciation in phytophagous insects is often due to colonization of novel host plants, because radiations of plant and insect lineages are typically asynchronous. Recent phylogenetic comparisons have supported this model of diversification for both insect herbivores and specialized pollinators. An exceptional case where contemporaneous plant-insect diversification might be expected is the obligate mutualism between fig trees (Ficus species, Moraceae) and their pollinating wasps (Agaonidae, Hymenoptera). The ubiquity and ecological significance of this mutualism in tropical and subtropical ecosystems has long intrigued biologists, but the systematic challenge posed by >750 interacting species pairs has hindered progress toward understanding its evolutionary history. In particular, taxon sampling and analytical tools have been insufficient for large-scale cophylogenetic analyses. Here, we sampled nearly 200 interacting pairs of fig and wasp species from across the globe. Two supermatrices were assembled: on an average, wasps had sequences from 77% of 6 genes (5.6 kb), figs had sequences from 60% of 5 genes (5.5 kb), and overall 850 new DNA sequences were generated for this study. We also developed a new analytical tool, Jane 2, for event-based phylogenetic reconciliation analysis of very large data sets. Separate Bayesian phylogenetic analyses for figs and fig wasps under relaxed molecular clock assumptions indicate Cretaceous diversification of crown groups and contemporaneous divergence for nearly half of all fig and pollinator lineages. Event-based cophylogenetic analyses further support the codiversification hypothesis. Biogeographic analyses indicate that the present-day distribution of fig and pollinator lineages is consistent with a Eurasian origin and subsequent dispersal, rather than with Gondwanan vicariance. Overall, our findings indicate that the fig-pollinator mutualism represents an extreme case among plant-insect interactions of

  6. Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform.

    PubMed Central

    Shepherd, Malcolm; McSorley, Theresa; Olsen, Aileen E; Johnston, Lee Ann; Thomson, Neil C; Baillie, George S; Houslay, Miles D; Bolger, Graeme B

    2003-01-01

    We have isolated cDNAs encoding PDE4B4, a new cAMP-specific phosphodiesterase (PDE4) isoform with novel properties. The amino acid sequence of PDE4B4 demonstrates that it is encoded by the PDE4B gene, but that it differs from the previously isolated PDE4B1, PDE4B2 and PDE4B3 isoforms by the presence of a novel N-terminal region of 17 amino acids. PDE4B4 contains both of the upstream conserved region 1 (UCR1) and UCR2 regulatory units that are characteristic of 'long' PDE4 isoforms. RNase protection demonstrated that PDE4B4 mRNA is expressed preferentially in liver, skeletal muscle and various regions of the brain, which differs from the pattern of tissue distribution of the other known PDE4B long forms, PDE4B1 and PDE4B3. Expression of PDE4B4 cDNA in COS7 cells produced a protein of 85 kDa under denaturing conditions. Subcellular fractionation of recombinant, COS7-cell expressed PDE4B4 showed that the protein was localized within the cytosol, which was confirmed by confocal microscopic analysis of living COS7 cells transfected with a green fluorescent protein-PDE4B4 chimaera. PDE4B4 exhibited a K(m) for cAMP of 5.4 microM and a V(max), relative to that of the long PDE4B1 isoform, of 2.1. PDE4B4 was inhibited by the prototypical PDE4 inhibitor rolipram [4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidinone] with an IC(50) of 83 nM. Treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which was associated with the phosphorylation of PDE4B4 on Ser-56 within UCR1. The unique tissue distribution and intracellular targeting of PDE4B4 suggests that this isoform may have a distinct functional role in regulating cAMP levels in specific cell types. PMID:12441002

  7. Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.

    PubMed

    Yin, Yan; Liu, Liren; Yang, Chenyi; Lin, Congxing; Veith, George Michael; Wang, Caihong; Sutovsky, Peter; Zhou, Pengbo; Ma, Liang

    2016-03-25

    CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell-specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis. PMID:26846852

  8. Prevalence and genetic diversity of fig mosaic virus isolates infecting fig tree in Iran.

    PubMed

    Danesh-Amuz, S; Rakhshandehroo, F; Rezaee, S

    2014-01-01

    Commercial and outdoor fig orchards in four Iranian provinces were surveyed for the incidence of fig mosaic virus (FMV), fig leaf mottle associated virus 2 (FLMaV-2) and fig mild mottle associated virus (FMMaV) from March 2011 to October 2012. A total of 350 asymptomatic and symptomatic fig samples were collected and tested by dot-immunobinding assay (DIBA) for the fig mosaic disease (FMD) using a polyclonal antiserum. According to DIBA results, FMD was present in 73% of the collected symptomatic samples from all visited regions. Samples with positive reactions in DIBA were then analyzed by RT-PCR using with specific primers. PCR results showed that about 14.8% of the FMD-positive samples from three inspected provinces are infected with at least one virus. FMV was the most widely spread virus (14%) followed by FLMaV-2 (1.5%), whereas FMMaV was not found. Phylogenetic analysis of the glycoprotein nucleotide and amino acid sequences of known FMV isolates showed two independent groups with high bootstrap values, with all Iranian isolates distinctly clustered in group I, subgroup IA beside those reported in Turkey. Nucleotide diversity was high within but low between different selected geographic regions and except for Europe, nucleotide distance within geographic regions was low. Statistical analyses indicated a correlation between the genetic structure of the FMV isolates and the geographical origin of isolation. Our analyses suggested that the FMV population is in a state of increase following a bottleneck or founder event in Iran. PMID:25283859

  9. Prevalence and genetic diversity of fig mosaic virus isolates infecting fig tree in Iran.

    PubMed

    Danesh-Amuz, S; Rakhshandehroo, F; Rezaee, S

    2014-01-01

    Commercial and outdoor fig orchards in four Iranian provinces were surveyed for the incidence of fig mosaic virus (FMV), fig leaf mottle associated virus 2 (FLMaV-2) and fig mild mottle associated virus (FMMaV) from March 2011 to October 2012. A total of 350 asymptomatic and symptomatic fig samples were collected and tested by dot-immunobinding assay (DIBA) for the fig mosaic disease (FMD) using a polyclonal antiserum. According to DIBA results, FMD was present in 73% of the collected symptomatic samples from all visited regions. Samples with positive reactions in DIBA were then analyzed by RT-PCR using with specific primers. PCR results showed that about 14.8% of the FMD-positive samples from three inspected provinces are infected with at least one virus. FMV was the most widely spread virus (14%) followed by FLMaV-2 (1.5%), whereas FMMaV was not found. Phylogenetic analysis of the glycoprotein nucleotide and amino acid sequences of known FMV isolates showed two independent groups with high bootstrap values, with all Iranian isolates distinctly clustered in group I, subgroup IA beside those reported in Turkey. Nucleotide diversity was high within but low between different selected geographic regions and except for Europe, nucleotide distance within geographic regions was low. Statistical analyses indicated a correlation between the genetic structure of the FMV isolates and the geographical origin of isolation. Our analyses suggested that the FMV population is in a state of increase following a bottleneck or founder event in Iran.

  10. A trophic cascade induced by predatory ants in a fig-fig wasp mutualism.

    PubMed

    Wang, Bo; Geng, Xiang-Zong; Ma, Li-Bin; Cook, James M; Wang, Rui-Wu

    2014-09-01

    A trophic cascade occurs when predators directly decrease the densities, or change the behaviour, of herbivores and thus indirectly increase plant productivity. The predator-herbivore-plant context is well known, but some predators attack species beneficial to plants (e.g. pollinators) and/or enemies of herbivores (e.g. parasites), and their role in the dynamics of mutualisms remains largely unexplored. We surveyed the predatory ant species and studied predation by the dominant ant species, the weaver ant Oecophylla smaragdina, associated with the fig tree Ficus racemosa in southwest China. We then tested the effects of weaver ants on the oviposition behaviour of pollinating and non-pollinating fig wasps in an ant-exclusion experiment. The effects of weaver ants on fig wasp community structure and fig seed production were then compared between trees with and without O. smaragdina. Oecophylla smaragdina captured more non-pollinating wasps (Platyneura mayri) than pollinators as the insects arrived to lay eggs. When ants were excluded, more non-pollinators laid eggs into figs and fewer pollinators entered figs. Furthermore, trees with O. smaragdina produced more pollinator offspring and fewer non-pollinator offspring, shifting the community structure significantly. In addition, F. racemosa produced significantly more seeds on trees inhabited by weaver ants. Oecophylla smaragdina predation reverses the dominance of the two commonest wasp species at the egg-laying stage and favours the pollinators. This behavioural pattern is mirrored by wasp offspring production, with pollinators' offspring dominating figs produced by trees inhabited by weaver ants, and offspring of the non-pollinator P. mayri most abundant in figs on trees inhabited by other ants. Overall, our results suggest that predation by weaver ants limits the success of the non-pollinating P. mayri and therefore indirectly benefits the mutualism by increasing the reproductive success of both the

  11. Discriminative host sanction together with relatedness promote the cooperation in fig/fig wasp mutualism.

    PubMed

    Wang, Rui-Wu; Sun, Bao-Fa; Yang, Yan

    2015-07-01

    Sanctioning or punishing is regarded as one of the most important dynamics in the evolution of cooperation. However, it has not been empirically examined yet whether or not such enforcement selection by sanctioning or punishing and classical theories like kin or reciprocity selection are separate mechanisms contributing to the evolution of cooperation. In addition, it remains largely unclear what factors determine the intensity or effectiveness of sanction. Here, we show that in the obligate, interspecific cooperation between figs and fig wasps, the hosted figs can discriminatively sanction cheating individuals by decreasing the offspring development ratio. Concurrently, the figs can reward the cooperative pollinators with a higher offspring development ratio. This sanction intensity and effectiveness largely depend on how closely the host and symbiont are related either in terms of reciprocity exchange or genetic similarity as measured by the reciprocal of the foundress number. Our results imply that in asymmetric systems, symbionts might be forced to evolve to be cooperative or even altruistic through discriminative sanction against the noncooperative symbiont and reward to the cooperative symbiont by the host (i.e. through a game of 'carrot and stick').

  12. Host sanctions and pollinator cheating in the fig tree-fig wasp mutualism.

    PubMed

    Jandér, K Charlotte; Herre, Edward Allen

    2010-05-22

    Theory predicts that mutualisms should be vulnerable to invasion by cheaters, yet mutualistic interactions are both ancient and diverse. What prevents one partner from reaping the benefits of the interaction without paying the costs? Using field experiments and observations, we examined factors affecting mutualism stability in six fig tree-fig wasp species pairs. We experimentally compared the fitness of wasps that did or did not perform their most basic mutualistic service, pollination. We found host sanctions that reduced the fitness of non-pollinating wasps in all derived, actively pollinated fig species (where wasps expend time and energy pollinating), but not in the basal, passively pollinated fig species (where wasps do not). We further screened natural populations of pollinators for wasp individuals that did not carry pollen ('cheaters'). Pollen-free wasps occurred only in actively pollinating wasp species, and their prevalence was negatively correlated with the sanction strength of their host species. Combined with previous studies, our findings suggest that (i) mutualisms can show coevolutionary dynamics analogous to those of 'arms races' in overtly antagonistic interactions; (ii) sanctions are critical for long-term mutualism stability when providing benefits to a host is costly, and (iii) there are general principles that help maintain cooperation both within and among species.

  13. Spatial heterogeneity and host repression in fig-fig wasp mutualism.

    PubMed

    Wang, RuiWu; Wen, XiaoLan; Chen, Chun; Shi, Lei; Compton, Stephen G

    2015-05-01

    It is generally believed that physical heterogeneity in common resource or evolutionary restraint can sufficiently prevent direct conflict between host and symbionts in mutualism systems. Our data on fig/fig wasp reciprocal mutualism (Ficus racemosa), however, show that structural barriers of female flowers or genetic constraints of pollinators previously hypothesized exist, but cannot sufficiently maintain the mutualism stability. The results show that a positive relationship between seed and wasp production could be maintained in warm season, which might be because of density dependence restraint among foundresses and their low oviposition and pollination efficiency, keeping common resource (female flowers) utilization unsaturated. Whilst, a negative correlation between wasp offspring and viable seed production was also observed in cold season, which might be that the increased oviposition and pollination efficiency maximized the common resource utilization. The fitness trade-off between fig and pollinator wasps is greatly affected by environmental or ecological variations. The local stability might result from temporal low exploitation efficiency of pollinators together with interference competition among pollinators. We suggest that host repression through the active regulation of bract closure, which can create interference competition among the foundresses and prevent extra more foundresses sequential entry in fruit cavities, would help the figs avoiding the cost of over-exploitation. This essentially takes the same role as sanctioning of cheating or competitive behaviors.

  14. 7 CFR 457.110 - Fig crop insurance provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Fig crop insurance provisions. 457.110 Section 457.110..., DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.110 Fig crop insurance provisions. The Fig... Department of Agriculture Federal Crop Insurance Corporation Fig Crop Provisions If a conflict exists...

  15. 7 CFR 457.110 - Fig crop insurance provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Fig crop insurance provisions. 457.110 Section 457.110..., DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.110 Fig crop insurance provisions. The Fig... Department of Agriculture Federal Crop Insurance Corporation Fig Crop Provisions If a conflict exists...

  16. 7 CFR 457.110 - Fig crop insurance provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Fig crop insurance provisions. 457.110 Section 457.110..., DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.110 Fig crop insurance provisions. The Fig... Department of Agriculture Federal Crop Insurance Corporation Fig Crop Provisions If a conflict exists...

  17. Biomechanics of substrate boring by fig wasps.

    PubMed

    Kundanati, Lakshminath; Gundiah, Namrata

    2014-06-01

    Female insects of diverse orders bore into substrates to deposit their eggs. Such insects must overcome several biomechanical challenges to successfully oviposit, which include the selection of suitable substrates through which the ovipositor can penetrate without itself fracturing. In many cases, the insect may also need to steer and manipulate the ovipositor within the substrate to deliver eggs at desired locations before rapidly retracting her ovipositor to avoid predation. In the case of female parasitoid ichneumonid wasps, this process is repeated multiple times during her lifetime, thus testing the ability of the ovipositioning apparatus to endure fracture and fatigue. What specific adaptations does the ovipositioning apparatus of a female ichneumonoid wasp possess to withstand these challenges? We addressed this question using a model system composed of parasitoid and pollinator fig wasps. First, we show that parasitoid ovipositor tips have teeth-like structures, preferentially enriched with zinc, unlike the smooth morphology of pollinator ovipositors. We describe sensillae present on the parasitoid ovipositor tip that are likely to aid in the detection of chemical species and mechanical deformations and sample microenvironments within the substrate. Second, using atomic force microscopy, we show that parasitoid tip regions have a higher modulus compared with regions proximal to the abdomen in parasitoid and pollinator ovipositors. Finally, we use videography to film wasps during substrate boring and analyse buckling of the ovipositor to estimate the forces required for substrate boring. Together, these results allow us to describe the biomechanical principles underlying substrate boring in parasitoid ichneumonid wasps. Such studies may be useful for the biomimetic design of surgical tools and in the use of novel mechanisms to bore through hard substrates.

  18. PROCEEDINGS: 1993 SO2 CONTROL SYMPOSIUM - VOLUME 2. SESSIONS 4A, 4B, AND 5A

    EPA Science Inventory

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

  19. High resolution crystal structure of human Dim2/TXNL4B

    Technology Transfer Automated Retrieval System (TEKTRAN)

    TXNL4A (thioredoxin like 4A) is an essential protein conserved from yeast to human and is a component of the pre-mRNA splicing machinery. TXNL4B was identified as a TXNL4 family protein that also interacts with prp6, an integral component of the U4/U6•U5 tri-snRNP complex, and was shown to function...

  20. Ecology of parasite Sycophilomorpha sp. on Ficus altissima and its effect on the fig-fig wasp mutualism.

    PubMed

    Peng, Y Q; Zhao, J B; Harrison, R D; Yang, D R

    2010-11-01

    Figs and their pollinating wasps are a classic example of an obligate mutualism. In addition, figs are parasitized by a suite of non-mutualistic wasps whose basic ecology is largely undescribed. Sycophilomorpha (subfamily Epichrysomallinae) fig wasps are ovule gallers and the genus contains only 1 described species. An undescribed Sycophilomorpha species parasitized Ficus altissima at Xishuangbana, Southwestern China. The wasp was observed ovipositing on the tiny immature figs that were still concealed beneath the involucral bracts. A Sycophilomorpha wasp oviposited on more than 1 fig and spent long time-periods to lay large clutches on a single fig. The wasps naturally occurred on all 7 sampled trees, but the occurrence of wasps was significantly different among trees, crops and months. These wasps were able to prevent unpollinated figs from being aborted, and their offspring were able to develop in the figs that otherwise had no pollinator wasps or seeds. The Sycophilomorpha wasp had a detrimental effect on the fig-fig wasp mutualism. Figs in which Sycophilomorpha wasps were present, produced significantly fewer seeds, pollinators and cheaters. However, the abundance of Sycophilomorpha in a fig was only significantly negatively correlated with pollinator production and not seed or cheater production. Our study illustrates a previously unknown fig wasp niche and expands our understanding of factors that can affect the fig-fig wasp interaction.

  1. Molecular phylogenies of figs and fig-pollinating wasps in the Ryukyu and Bonin (Ogasawara) islands, Japan.

    PubMed

    Azuma, Hiroshi; Harrison, Rhett D; Nakamura, Keiko; Su, Zhi-Hui

    2010-01-01

    The interaction between figs (Ficus, Moraceae) and fig-pollinating wasps (Chalcidoidea, Agaonidae) is one of the most specific mutualisms, and thus is a model system for studying coevolution and cospeciation. In this study we focused on figs and their associated fig-wasps found in the Ryukyu and Bonin (Ogasawara) Islands, Japan, because it has been suggested that breakdown in the specificity may occur in islands or at edge of a species' distribution. We collected 136 samples of 15 native fig species and 95 samples of 13 associated fig-wasps from all major islands in the Ryukyu Islands, including two fig species and one fig-wasp species endemic to the Bonin Islands. We performed molecular phylogenetic analyses using plastid DNA and nuclear ITS sequences for the figs and nuclear 28S rRNA and mitochondrial COI genes for the fig-wasps to investigate the interspecific phylogenies and intraspecific variation within the mutualism. Our phylogenetic analyses using multiple samples per species show the single clade of each fig (except the Bonin endemic species) and fig-pollinating wasp species. Fig species belonging to the same subgenera formed well-supported clades in both plastid and ITS trees, except for the subgenus Urostigma. Likewise, fig wasps emerging from host fig species belonging to the same subgenera formed mostly well supported clades in both 28S and COI trees. Host specificity between the figs and fig-wasps functions strictly in these islands. There was very little sequence variation within species, and that no major geographic structure was found. The two Bonin endemic species (F. boninsimae and F. nishimurae) or their common ancestor and the associated fig-wasps (Blastophaga sp.) are apparently derived from F. erecta and its associated fig-wasps (B. nipponica), respectively, and probably migrated from the Ryukyu Islands.

  2. Female figs as traps: Their impact on the dynamics of an experimental fig tree-pollinator-parasitoid community

    NASA Astrophysics Data System (ADS)

    Suleman, Nazia; Sait, Steve; Compton, Stephen G.

    2015-01-01

    Interactions between fig trees (Ficus) and their pollinating fig wasps (Agaonidae) result in both a highly species-specific nursery mutualism and mutual exploitation. Around half of the 800 or so fig tree species are functionally dioecious. Figs on male plants produce pollen and fig wasp offspring, whereas figs on female plants produce only seeds. Figs on female plants are traps for pollinators. The fig wasps enter the female figs to oviposit, but lose their wings on entry and are then prevented from oviposition by the long styles that characterise the flowers in female figs. Continuation of the mutualism depends on the pollinators' failure to distinguish between male and female figs before entry. Female plants may also have a negative impact on the parasitoid fig wasps that feed on pollinators, if they are also attracted to female figs. We used glasshouse populations of figs (with and without female plants), pollinators and parasitoids to infer the impact of female figs on fig wasp dynamics. Cyclic population fluctuations were present in both species. Female plants appeared to dampen the amplitudes of pollinator population cycles, and parasitoid populations may become less tightly coupled with host populations, but the presence of female figs did not reduce parasitism rates, nor parasitoid and pollinator densities, and only parasitoid sex ratios were affected. Our glasshouse experimental design was likely to favour the impact of female figs on the wasp populations, which suggests that female plants in the field are unlikely to have a major negative impact on their pollinators, despite being a major mortality factor.

  3. [Oviposition timing and community structure of Ficus curtipes fig wasps].

    PubMed

    Zhang, Feng-Ping; Yang, Da-Rong

    2009-08-01

    Through the behavioral observation of Ficus curtipes fig wasps and the counting of various kinds of flowerets in F. curtipes figs, the oviposition timing and community structure of 12 F. curtipes fig wasp species were studied. Besides the agaonid wasp Eupristina sp., the two non-agaonid wasps Diaziella yangi and Lipothymus sp. could enter into F. curtipes figs and oviposit. The other nine non-agaonid fig wasps ( Walkerella sp., Micranisa sp., Sycophilomorpha sp., Philotrypesis sp., Sycosapter sp., Sycobia sp., Ficomila sp., Ormyrus sp. and Sycophila sp.) oviposited outside the figs. In the fig wasp community, Eupristina sp. was the dominant species, accounting for 62.11% of the total, D. yangi and Lipothymus sp. accounted for 27.19% and 4.71%, respectively, while the other nine non-agaonid fig wasp species only occupied 5.99%. The non-agaonid fig wasps produced their progeny through the reproduction strategies of oviposition timing and diet allocation of female flowerets, so as to sustain the fig-wasp mutualism. The individuals of non-agaonid fig wasp progeny had significant negative correlation with those of agaonid fig wasp progeny, but no correlation with F. curtipes seed production.

  4. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Canned preserved figs. 145.134 Section 145.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Canned preserved figs. (a) Canned preserved figs is the food prepared from one of the optional...

  5. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Canned preserved figs. 145.134 Section 145.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Canned preserved figs. (a) Canned preserved figs is the food prepared from one of the optional...

  6. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Canned preserved figs. 145.134 Section 145.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Canned preserved figs. (a) Canned preserved figs is the food prepared from one of the optional...

  7. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Canned preserved figs. 145.134 Section 145.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Canned preserved figs. (a) Canned preserved figs is the food prepared from one of the optional...

  8. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Canned preserved figs. 145.134 Section 145.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Canned preserved figs. (a) Canned preserved figs is the food prepared from one of the optional...

  9. Floral ratios in the figs of Ficus montana span the range from actively to passively pollinated fig trees

    NASA Astrophysics Data System (ADS)

    Suleman, Nazia; Quinnell, Rupert J.; Compton, Stephen G.

    2014-05-01

    Fig trees (Ficus spp., Moraceae) and their associated obligate pollinator fig wasps (Agaonidae) are partners in what is often a pair-wise species-specific association. Their interaction centres on the unique enclosed inflorescence of Ficus species - the fig. Among dioecious fig tree species, only pollinated ovules in figs on female trees develop into seeds. On male trees, galled ovules support development of the fig wasp offspring that will transport their pollen, but no seeds develop. Some fig wasp species actively collect and disperse pollen, whereas others are typical insect pollinators in that pollen is transferred passively. Active pollination is associated with improved larval survivorship in pollinated figs. Because active pollination is much more efficient, their host figs need to contain far fewer male flowers and across numerous Ficus species anther-ovule ratios are a good predictor of pollination mode. We examined variation in inflorescence size and floral ratios among male figs of the Asian Ficus montana and its consequences for the amounts of pollen that would be available for each pollinator to collect. Inflorescence size (total flower number) was highly variable, and female pollinator offspring production was higher in figs with more female flowers. Pollinator offspring numbers and anther-ovule ratios were also highly variable, and encompassed the range typical of both actively and passively pollinated fig tree species. In combination, this variation resulted in large differences in the extent to which pollinators were competing for access to pollen, with potential fitness consequences for both partners in the mutualism.

  10. Aflatoxins, patulin and ergosterol contents of dried figs in Turkey.

    PubMed

    Karaca, H; Nas, S

    2006-05-01

    Dried figs of three different categories, palatable, fluorescent, and cull, were investigated for their contents of aflatoxins (B(1), B(2), G(1) and G(2)), patulin, and ergosterol. Samples were obtained from four fig processing plants located in a major fig producing area in the Aegean Region in Turkey. Affinity column clean-up methods were employed for aflatoxins. All aflatoxins, patulin, and ergosterol were determined using high performance liquid chromatography. Palatable figs contaminated with trace amounts of aflatoxins, patulin, and ergosterol, so they posed no risk for the consumer when national and/or international regulatory limits were considered. Fluorescent figs were contaminated with high (117.9-471.9 ppb) aflatoxin levels and cull figs with high patulin (39.3-151.6 ppb) and ergosterol (4.5-18 ppm) levels. The total aflatoxins content was significantly correlated with the patulin content (r(2) = 0.813, p < 0.002) and the ergosterol content (r(2) = 0.920, p < 0.002) only in fluorescent figs. However there was no significant correlation between patulin and ergosterol contents of fluorescent figs. Furthermore, there were no significant correlations between the contents of any two of the three substances in cull figs. This is the first report on the presence of patulin and its co-occurrence with aflatoxin in dried figs.

  11. Aflatoxins, patulin and ergosterol contents of dried figs in Turkey.

    PubMed

    Karaca, H; Nas, S

    2006-05-01

    Dried figs of three different categories, palatable, fluorescent, and cull, were investigated for their contents of aflatoxins (B(1), B(2), G(1) and G(2)), patulin, and ergosterol. Samples were obtained from four fig processing plants located in a major fig producing area in the Aegean Region in Turkey. Affinity column clean-up methods were employed for aflatoxins. All aflatoxins, patulin, and ergosterol were determined using high performance liquid chromatography. Palatable figs contaminated with trace amounts of aflatoxins, patulin, and ergosterol, so they posed no risk for the consumer when national and/or international regulatory limits were considered. Fluorescent figs were contaminated with high (117.9-471.9 ppb) aflatoxin levels and cull figs with high patulin (39.3-151.6 ppb) and ergosterol (4.5-18 ppm) levels. The total aflatoxins content was significantly correlated with the patulin content (r(2) = 0.813, p < 0.002) and the ergosterol content (r(2) = 0.920, p < 0.002) only in fluorescent figs. However there was no significant correlation between patulin and ergosterol contents of fluorescent figs. Furthermore, there were no significant correlations between the contents of any two of the three substances in cull figs. This is the first report on the presence of patulin and its co-occurrence with aflatoxin in dried figs. PMID:16644598

  12. Seasonality of Leaf and Fig Production in Ficus squamosa, a Fig Tree with Seeds Dispersed by Water

    PubMed Central

    Pothasin, Pornwiwan; Compton, Stephen G.; Wangpakapattanawong, Prasit

    2016-01-01

    The phenology of plants reflects selection generated by seasonal climatic factors and interactions with other plants and animals, within constraints imposed by their phylogenetic history. Fig trees (Ficus) need to produce figs year-round to support their short-lived fig wasp pollinators, but this requirement is partially de-coupled in dioecious species, where female trees only develop seeds, not pollinator offspring. This allows female trees to concentrate seed production at more favorable times of the year. Ficus squamosa is a riparian species whose dispersal is mainly by water, rather than animals. Seeds can float and travel in long distances. We recorded the leaf and reproductive phenology of 174 individuals for three years in Chiang Mai, Northern Thailand. New leaves were produced throughout the year. Fig production occurred year-round, but with large seasonal variations that correlated with temperature and rainfall. Female and male trees initiated maximal fig crops at different times, with production in female trees confined mainly to the rainy season and male figs concentrating fig production in the preceding months, but also often bearing figs continually. Ficus squamosa concentrates seed production by female plants at times when water levels are high, favouring dispersal by water, and asynchronous flowering within male trees allow fig wasps to cycle there, providing them with potential benefits by maintaining pollinators for times when female figs become available to pollinate. PMID:27010540

  13. Seasonality of Leaf and Fig Production in Ficus squamosa, a Fig Tree with Seeds Dispersed by Water.

    PubMed

    Pothasin, Pornwiwan; Compton, Stephen G; Wangpakapattanawong, Prasit

    2016-01-01

    The phenology of plants reflects selection generated by seasonal climatic factors and interactions with other plants and animals, within constraints imposed by their phylogenetic history. Fig trees (Ficus) need to produce figs year-round to support their short-lived fig wasp pollinators, but this requirement is partially de-coupled in dioecious species, where female trees only develop seeds, not pollinator offspring. This allows female trees to concentrate seed production at more favorable times of the year. Ficus squamosa is a riparian species whose dispersal is mainly by water, rather than animals. Seeds can float and travel in long distances. We recorded the leaf and reproductive phenology of 174 individuals for three years in Chiang Mai, Northern Thailand. New leaves were produced throughout the year. Fig production occurred year-round, but with large seasonal variations that correlated with temperature and rainfall. Female and male trees initiated maximal fig crops at different times, with production in female trees confined mainly to the rainy season and male figs concentrating fig production in the preceding months, but also often bearing figs continually. Ficus squamosa concentrates seed production by female plants at times when water levels are high, favouring dispersal by water, and asynchronous flowering within male trees allow fig wasps to cycle there, providing them with potential benefits by maintaining pollinators for times when female figs become available to pollinate. PMID:27010540

  14. Seasonality of Leaf and Fig Production in Ficus squamosa, a Fig Tree with Seeds Dispersed by Water.

    PubMed

    Pothasin, Pornwiwan; Compton, Stephen G; Wangpakapattanawong, Prasit

    2016-01-01

    The phenology of plants reflects selection generated by seasonal climatic factors and interactions with other plants and animals, within constraints imposed by their phylogenetic history. Fig trees (Ficus) need to produce figs year-round to support their short-lived fig wasp pollinators, but this requirement is partially de-coupled in dioecious species, where female trees only develop seeds, not pollinator offspring. This allows female trees to concentrate seed production at more favorable times of the year. Ficus squamosa is a riparian species whose dispersal is mainly by water, rather than animals. Seeds can float and travel in long distances. We recorded the leaf and reproductive phenology of 174 individuals for three years in Chiang Mai, Northern Thailand. New leaves were produced throughout the year. Fig production occurred year-round, but with large seasonal variations that correlated with temperature and rainfall. Female and male trees initiated maximal fig crops at different times, with production in female trees confined mainly to the rainy season and male figs concentrating fig production in the preceding months, but also often bearing figs continually. Ficus squamosa concentrates seed production by female plants at times when water levels are high, favouring dispersal by water, and asynchronous flowering within male trees allow fig wasps to cycle there, providing them with potential benefits by maintaining pollinators for times when female figs become available to pollinate.

  15. Molecular dating and biogeography of fig-pollinating wasps.

    PubMed

    Lopez-Vaamonde, Carlos; Wikström, Niklas; Kjer, Karl M; Weiblen, George D; Rasplus, Jean Yves; Machado, Carlos A; Cook, James M

    2009-09-01

    Figs and fig-pollinating wasps are obligate mutualists that have coevolved for over 60 million years. But when and where did pollinating fig wasps (Agaonidae) originate? Some studies suggest that agaonids arose in the Late Cretaceous and the current distribution of fig-wasp faunas can be explained by the break-up of the Gondwanan landmass. However, recent molecular-dating studies suggest divergence time estimates that are inconsistent with the Gondwanan vicariance hypothesis and imply that long distance oceanic dispersal could have been an important process for explaining the current distribution of both figs and fig wasps. Here, we use a combination of phylogenetic and biogeographical data to infer the age, the major period of diversification, and the geographic origin of pollinating fig wasps. Age estimates ranged widely depending on the molecular-dating method used and even when using the same method but with slightly different constraints, making it difficult to assess with certainty a Gondwanan origin of agaonids. The reconstruction of ancestral areas suggests that the most recent common ancestor of all extant fig-pollinating wasps was most likely Asian, although a southern Gondwana origin cannot be rejected. Our analysis also suggests that dispersal has played a more important role in the development of the fig-wasp biota than previously assumed.

  16. MCNP4B{sup {trademark}} verification and validation

    SciTech Connect

    Hendricks, J.S.; Court, J.D.

    1996-08-01

    Several new features and bug fixes have been incorporated into the new release of MCNP. As required by the MCNP Software Quality Assurance Plan, these changes to the code and the test set are documented here for user reference. This document summarizes the new MCNP4B features and corrections, separated into major and minor groupings. Also included are a code cleanup section and a section delineating problems identified in LA-12839 which have not been corrected. Finally, we document the MCNP4B test set modifications and explain how test set coverage has been improved.

  17. Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

    SciTech Connect

    Mitchell, Charlotte J.; Ballantine, Stuart P.; Coe, Diane M.; Cook, Caroline M.; Delves, Christopher J.; Dowle, Mike D.; Edlin, Chris D.; Hamblin, J. Nicole; Holman, Stuart; Johnson, Martin R.; Jones, Paul S.; Keeling, Sue E.; Kranz, Michael; Lindvall, Mika; Lucas, Fiona S.; Neu, Margarete; Solanke, Yemisi E.; Somers, Don O.; Trivedi, Naimisha A.; Wiseman, Joanne O.

    2012-05-03

    Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-{alpha} production from isolated human peripheral blood mononuclear cells.

  18. The hypervariable region of K-Ras4B is responsible for its specific interactions with calmodulin.

    PubMed

    Abraham, Sherwin J; Nolet, Ryan P; Calvert, Richard J; Anderson, Lucy M; Gaponenko, Vadim

    2009-08-18

    K-Ras4B belongs to the family of p21 Ras GTPases, which play an important role in cell proliferation, survival, and motility. The p21 Ras proteins, such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very similar signaling pathways. Only the C-terminal hypervariable regions differ significantly. A growing body of literature demonstrates that each Ras isoform possesses unique functions in normal physiological processes as well as in pathogenesis. One of the central questions in the field of Ras biology is how these very similar proteins achieve such remarkable specificity in protein-protein interactions that regulate signal transduction pathways. Here we explore specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal titration calorimetry, we demonstrate that the hypervariable region of K-Ras4B contributes in a major way to the interaction with calmodulin, while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca(2+)-loaded calmodulin with micromolar affinity, while the GTP-gamma-S-loaded catalytic domain of K-Ras4B may interact with the N-terminal domain of calmodulin.

  19. Exchange of hosts: can agaonid fig wasps reproduce successfully in the figs of non-host Ficus?

    NASA Astrophysics Data System (ADS)

    Yang, Pei; Li, Zongbo; Peng, Yanqiong; Yang, Darong

    2012-03-01

    In the obligate mutualism between figs ( Ficus) and their specific pollinators (Chalcidoidea, Agaonidae), each species of fig wasp typically reproduces in figs of a single host species. Host specificity is maintained largely because pollinators are attracted to tree-specific volatiles released from their host figs, but whether the wasps can reproduce if they enter figs of non-host species is unclear. We investigated the reproductive success of Ceratosolen emarginatus (associated with Ficus auriculata) and Ceratosolen sp. (associated with F. hainanensis) in atypical hosts by experimentally introducing foundresses into host and non-host figs. F. auriculata figs entered by Ceratosolen sp. were more likely to abort than if entered by C. emarginatus, but abortion of F. hainanensis figs was not affected by pollinator species. Single C. emarginatus foundresses produced more but smaller offspring in F. hainanensis than in their normal host. Conversely Ceratosolen sp. produced fewer but larger offspring in F. auriculata than in their normal host, probably as a result of having longer to develop. Mean style length differences, relative to the lengths of the wasps' ovipositors, may have dictated the number of offspring produced, with oviposition made easier by the shorter styles in F. hainanensis figs. Our results imply that, in addition to morphological constraints and tree-specific volatiles, reduced reproductive success in atypical hosts can be another factor maintaining host specificity, but for other species only behavioural changes are required for host switching to occur.

  20. Rain-fed fig yield as affected by rainfall distribution

    NASA Astrophysics Data System (ADS)

    Bagheri, Ensieh; Sepaskhah, Ali Reza

    2014-08-01

    Variable annual rainfall and its uneven distribution are the major uncontrolled inputs in rain-fed fig production and possibly the main cause of yield fluctuation in Istahban region of Fars Province, I.R. of Iran. This introduces a considerable risk in rain-fed fig production. The objective of this study was to find relationships between seasonal rainfall distribution and rain-fed fig production in Istahban region to determine the critical rainfall periods for rain-fed fig production and supplementary irrigation water application. Further, economic analysis for rain-fed fig production was considered in this region to control the risk of production. It is concluded that the monthly, seasonal and annual rainfall indices are able to show the effects of rainfall and its distribution on the rain-fed fig yield. Fig yield with frequent occurrence of 80 % is 374 kg ha-1. The internal rates of return for interest rate of 4, 8 and 12 % are 21, 58 and 146 %, respectively, that are economically feasible. It is concluded that the rainfall in spring especially in April and in December has negatively affected fig yield due to its interference with the life cycle of Blastophaga bees for pollination. Further, it is concluded that when the rainfall is limited, supplementary irrigation can be scheduled in March.

  1. An integrated badnavirus is prevalent in fig germplasm.

    PubMed

    Laney, Alma G; Hassan, Mohamed; Tzanetakis, Ioannis E

    2012-12-01

    Fig mosaic occurs worldwide and is the most common and important viral disease of fig. In the quest to identify the causal agent of the disease, several new viruses have been identified, including a new DNA virus, the subject of this communication. Phylogenetic analysis placed the virus, provisionally named Fig badnavirus-1 (FBV-1), in the genus Badnavirus, family Caulimoviridae. The experimental host range of FBV-1 was evaluated and the virus was mechanically transmitted to several herbaceous hosts. FBV-1 was detected in the National Clonal Germplasm Repository fig collection and additional samples from Arkansas, California, Florida, Michigan, Ohio, Oregon, and South Carolina, suggesting its wide distribution in the United States. Further tests revealed the presence of FBV-1 in seedlings and meristem tissue culture plants. Forty-four isolates were used in a study evaluating the population structure of the virus in the United States. Evidence that FBV-1 is integrated in the fig genome is presented and discussed.

  2. How chimpanzees integrate sensory information to select figs.

    PubMed

    Dominy, Nathaniel J; Yeakel, Justin D; Bhat, Uttam; Ramsden, Lawrence; Wrangham, Richard W; Lucas, Peter W

    2016-06-01

    Figs are keystone resources that sustain chimpanzees when preferred fruits are scarce. Many figs retain a green(ish) colour throughout development, a pattern that causes chimpanzees to evaluate edibility on the basis of achromatic accessory cues. Such behaviour is conspicuous because it entails a succession of discrete sensory assessments, including the deliberate palpation of individual figs, a task that requires advanced visuomotor control. These actions are strongly suggestive of domain-specific information processing and decision-making, and they call attention to a potential selective force on the origin of advanced manual prehension and digital dexterity during primate evolution. To explore this concept, we report on the foraging behaviours of chimpanzees and the spectral, chemical and mechanical properties of figs, with cutting tests revealing ease of fracture in the mouth. By integrating the ability of different sensory cues to predict fructose content in a Bayesian updating framework, we quantified the amount of information gained when a chimpanzee successively observes, palpates and bites the green figs of Ficus sansibarica. We found that the cue eliciting ingestion was not colour or size, but fig mechanics (including toughness estimates from wedge tests), which relays higher-quality information on fructose concentrations than colour vision. This result explains why chimpanzees evaluate green figs by palpation and dental incision, actions that could explain the adaptive origins of advanced manual prehension. PMID:27274803

  3. How chimpanzees integrate sensory information to select figs

    PubMed Central

    Yeakel, Justin D.; Bhat, Uttam; Ramsden, Lawrence; Wrangham, Richard W.; Lucas, Peter W.

    2016-01-01

    Figs are keystone resources that sustain chimpanzees when preferred fruits are scarce. Many figs retain a green(ish) colour throughout development, a pattern that causes chimpanzees to evaluate edibility on the basis of achromatic accessory cues. Such behaviour is conspicuous because it entails a succession of discrete sensory assessments, including the deliberate palpation of individual figs, a task that requires advanced visuomotor control. These actions are strongly suggestive of domain-specific information processing and decision-making, and they call attention to a potential selective force on the origin of advanced manual prehension and digital dexterity during primate evolution. To explore this concept, we report on the foraging behaviours of chimpanzees and the spectral, chemical and mechanical properties of figs, with cutting tests revealing ease of fracture in the mouth. By integrating the ability of different sensory cues to predict fructose content in a Bayesian updating framework, we quantified the amount of information gained when a chimpanzee successively observes, palpates and bites the green figs of Ficus sansibarica. We found that the cue eliciting ingestion was not colour or size, but fig mechanics (including toughness estimates from wedge tests), which relays higher-quality information on fructose concentrations than colour vision. This result explains why chimpanzees evaluate green figs by palpation and dental incision, actions that could explain the adaptive origins of advanced manual prehension. PMID:27274803

  4. The hypervariable region of K-Ras4B is responsible for its specific interactions with Calmodulin

    PubMed Central

    Abraham, Sherwin J.; Nolet, Ryan P.; Calvert, Richard J.; Anderson, Lucy M.; Gaponenko, Vadim

    2009-01-01

    K-Ras4B belongs to the family of p21 Ras GTPases, which play an important role in cell proliferation, survival and motility. The p21 Ras proteins such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very similar signaling pathways. Only the C-terminal hypervariable regions differ significantly. A growing body of literature demonstrates that each Ras isoform possesses unique functions in normal physiological processes as well as in pathogenesis. One of the central questions in the field of Ras biology is how these very similar proteins achieve such remarkable specificity in protein-protein interactions that regulate signal transduction pathways. Here we explore specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal titration calorimetry we demonstrate that the hypervariable region of K-Ras contributes in a major way to the interaction with calmodulin while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca2+-loaded calmodulin with micromolar affinity, while the GTP-γ-S loaded catalytic domain of K-Ras4B may interact with the N-terminal domain of calmodulin. PMID:19583261

  5. Regulation of transcription factors on sexual dimorphism of fig wasps.

    PubMed

    Sun, Bao-Fa; Li, Yong-Xing; Jia, Ling-Yi; Niu, Li-Hua; Murphy, Robert W; Zhang, Peng; He, Shunmin; Huang, Da-Wei

    2015-06-02

    Fig wasps exhibit extreme intraspecific morphological divergence in the wings, compound eyes, antennae, body color, and size. Corresponding to this, behaviors and lifestyles between two sexes are also different: females can emerge from fig and fly to other fig tree to oviposit and pollinate, while males live inside fig for all their lifetime. Genetic regulation may drive these extreme intraspecific morphological and behavioral divergence. Transcription factors (TFs) involved in morphological development and physiological activity may exhibit sex-specific expressions. Herein, we detect 865 TFs by using genomic and transcriptomic data of the fig wasp Ceratosolen solmsi. Analyses of transcriptomic data indicated that up-regulated TFs in females show significant enrichment in development of the wing, eye and antenna in all stages, from larva to adult. Meanwhile, TFs related to the development of a variety of organs display sex-specific patterns of expression in the adults and these may contribute significantly to their sexual dimorphism. In addition, up-regulated TFs in adult males exhibit enrichment in genitalia development and circadian rhythm, which correspond with mating and protandry. This finding is consistent with their sex-specific behaviors. In conclusion, our results strongly indicate that TFs play important roles in the sexual dimorphism of fig wasps.

  6. Urbanized landscapes favored by fig-eating birds increase invasive but not native juvenile strangler fig abundance.

    PubMed

    Caughlin, Trevor; Wheeler, Jessica H; Jankowski, Jill; Lichstein, Jeremy W

    2012-07-01

    Propagule pressure can determine the success or failure of invasive plant range expansion. Range expansion takes place at large spatial scales, often encompassing many types of land cover, yet the effect of landscape context on propagule pressure remains largely unknown. Many studies have reported a positive correlation between invasive plant abundance and human land use; increased propagule pressure in these landscapes may be responsible for this correlation. We tested the hypothesis that increased rates of seed dispersal by fig-eating birds, which are more common in urban habitats, result in an increase in invasive strangler fig abundance in landscapes dominated by human land use. We quantified abundance of an invasive species (Ficus microcarpa) and a native species (F. aurea) of strangler fig in plots spanning the entire range of human land use in South Florida, USA, from urban parking lots to native forest. We then compared models that predicted juvenile fig abundance based on distance to adult fig seed sources and fig-eating bird habitat quality with models that lacked one or both of these terms. The best model for juvenile invasive fig abundance included both distance to adult and fig-eating bird habitat terms, suggesting that landscape effects on invasive fig abundance are mediated by seed-dispersing birds. In contrast, the best model for juvenile native fig abundance included only presence/absence of adults, suggesting that distance from individual adult trees may have less effect on seed limitation for a native species compared to an invasive species undergoing range expansion. However, models for both species included significant effects of adult seed sources, implying that juvenile abundance is limited by seed arrival. This result was corroborated by a seed addition experiment that indicated that both native and invasive strangler figs were strongly seed limited. Understanding how landscape context affects the mechanisms of plant invasion may lead to

  7. KDM4B as a Target for Prostate Cancer: Structural Analysis and Selective Inhibition by a Novel Inhibitor

    PubMed Central

    2015-01-01

    The KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A–KDM4D), which selectively remove the methyl group(s) from tri/dimethylated lysine 9/36 of H3, modulate transcriptional activation and genome stability. The overexpression of KDM4A/KDM4B in prostate cancer and their association with androgen receptor suggest that KDM4A/KDM4B are potential progression factors for prostate cancer. Here, we report the crystal structure of the KDM4B·pyridine 2,4-dicarboxylic acid·H3K9me3 ternary complex, revealing the core active-site region and a selective K9/K36 site. A selective KDM4A/KDM4B inhibitor, 4, that occupies three subsites in the binding pocket is identified by virtual screening. Pharmacological and genetic inhibition of KDM4A/KDM4B significantly blocks the viability of cultured prostate cancer cells, which is accompanied by increased H3K9me3 staining and transcriptional silencing of growth-related genes. Significantly, a substantial portion of differentially expressed genes are AR-responsive, consistent with the roles of KDM4s as critical AR activators. Our results point to KDM4 as a useful therapeutic target and identify a new inhibitor scaffold. PMID:24971742

  8. How to be a fig wasp down under: The diversity and structure of an Australian fig wasp community

    NASA Astrophysics Data System (ADS)

    Segar, Simon T.; Dunn, Derek W.; Darwell, Clive T.; Cook, James M.

    2014-05-01

    Endophytic insects and their parasitoids provide valuable models for community ecology. The wasp communities in inflorescences of fig trees have great potential for comparative studies, but we must first describe individual communities. Here, we add to the few detailed studies of such communities by describing the one associated with Ficus rubiginosa in Australia. First, we describe community composition, using two different sampling procedures. Overall, we identified 14 species of non-pollinating fig wasp (NPFW) that fall into two size classes. Small wasps, including pollinators, gallers and their parasitoids, were more abundant than large wasps (both galler and parasitoid species). We show that in figs where wasps emerge naturally, the presence of large wasps may partly explain the low emergence of small wasps. During fig development, large gallers oviposit first, before and around the time of pollination, while parasitoids lay eggs after pollination. We further show that parasitoids in the subfamily Sycoryctinae, which comprise the majority of all individual NPFWs, segregate temporally by laying eggs at different stages of fig development. We discuss our results in terms of species co-existence and community structure and compare our findings to those from fig wasp communities on other continents.

  9. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants

    PubMed Central

    An, Yuyan; Qi, Lin; Wang, Liangju

    2016-01-01

    5-aminolevulinic acid (ALA), a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn.) plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC), and reduced leaf superoxide anion (O2⋅¯) production rate and malonaldehyde (MDA) content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD) and peroxidase (POD), root vigor, and activities of root alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH), indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance. PMID:26789407

  10. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants.

    PubMed

    An, Yuyan; Qi, Lin; Wang, Liangju

    2016-01-01

    5-aminolevulinic acid (ALA), a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn.) plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC), and reduced leaf superoxide anion ([Formula: see text]) production rate and malonaldehyde (MDA) content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD) and peroxidase (POD), root vigor, and activities of root alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH), indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance. PMID:26789407

  11. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants.

    PubMed

    An, Yuyan; Qi, Lin; Wang, Liangju

    2016-01-01

    5-aminolevulinic acid (ALA), a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn.) plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC), and reduced leaf superoxide anion ([Formula: see text]) production rate and malonaldehyde (MDA) content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD) and peroxidase (POD), root vigor, and activities of root alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH), indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance.

  12. PDE4B as a microglia target to reduce neuroinflammation.

    PubMed

    Pearse, Damien D; Hughes, Zoë A

    2016-10-01

    The importance of microglia in immune homeostasis within the brain is undisputed. Their role in a diversity of neurological and psychiatric diseases as well as CNS injury is the subject of much investigation. Cyclic adenosine monophosphate (AMP) is a critical regulator of microglia homeostasis; as the predominant negative modulator of cyclic AMP signaling within microglia, phosphodiesterase 4 (PDE4) represents a promising target for modulating immune function. PDE4 expression is regulated by inflammation, and in turn, PDE4 inhibition can alter microglia reactivity. As the prototypic PDE4 inhibitor, rolipram, was tested clinically in the 1980s, drug discovery and clinical development of PDE4 inhibitors have been severely hampered by tolerability issues involving nausea and emesis. The two PDE4 inhibitors approved for peripheral inflammatory disorders (roflumilast and apremilast) lack brain penetration and are dose-limited by side effects making them unsuitable for modulating microglial function. Subtype selective inhibitors targeting PDE4B are of high interest given the critical role PDE4B plays in immune function versus the association of PDE4D with nausea and emesis. The challenges and requirements for successful development of a novel brain-penetrant PDE4B inhibitor are discussed in the context of early clinical development strategies. Furthermore, the challenges of monitoring the state of microglia in vivo are highlighted, including a description of the currently available tools and their limitations. Continued drug discovery efforts to identify safe and well-tolerated, brain-penetrant PDE4 inhibitors are a reflection of the confidence in the rationale for modulation of this target to produce meaningful therapeutic benefit in a wide range of neurological conditions and injury. GLIA 2016;64:1698-1709. PMID:27038323

  13. Allergy to weeping fig--a new occupational disease.

    PubMed

    Axelsson, G; Skedinger, M; Zetterström, O

    1985-08-01

    During the last decade green plants have become more common in interior decoration. There are companies specializing in the leasing of green plants to public buildings and offices. Weeping fig is one of the most popular green plants. Dust and dry components of the plant are usually removed by vigorous shaking. In this way the allergen becomes airborne. During a few months we have seen several plant keepers who have developed airway allergy to weeping fig. Two of them have been thoroughly investigated. Both are atopics. Extracts were made from leaves and branches and both patients had positive skin prick tests and RAST. The risk of sensitization in plant keepers who work with weeping fig is probably considerable.

  14. Identification of phenylpropanoids in fig (Ficus carica L.) leaves.

    PubMed

    Takahashi, Toru; Okiura, Aya; Saito, Keita; Kohno, Masahiro

    2014-10-15

    In this study, the phenylpropanoid composition and antioxidant activity of identified components in fig (Ficus carica L.) leaves were examined. Known polyphenols rutin, isoschaftoside, isoquercetin, and chlorogenic acid were identified. Furthermore, caffeoylmalic acid (CMA) was the most abundant polyphenol and was identified for the first time. CMA exhibited antioxidant activity similar to that of vitamin C or catechin. Psoralen and bergapten were identified as known furanocoumarins, with psoralen being the most abundant. Moreover, psoralic acid glucoside (PAG) was identified for the first time. As a precursor of psoralen, PAG content was equivalent to the psoralen content in moles. Notably, the content of these compounds varied between the five fig varieties, and the furanocoumarin and PAG contents varied more than that of the polyphenols. Further investigations concerning the influence of CMA and PAG on human health are necessary to elucidate functionalities of fig leaves.

  15. Antioxidant activity of a Mediterranean food product: "fig syrup".

    PubMed

    Puoci, Francesco; Iemma, Francesca; Spizzirri, Umile G; Restuccia, Donatella; Pezzi, Vincenzo; Sirianni, Rosa; Manganaro, Lillo; Curcio, Manuela; Parisi, Ortensia I; Cirillo, Giuseppe; Picci, Nevio

    2011-03-01

    In this work, the efficacy of fig syrup, a Mediterranean fig derivative, as a nutraceutical supplement, was demonstrated. Fig syrup is a fruit concentrate used as a common ingredient in the preparation of typical foods, and particularly in cakes. In vitro assays were performed to determine the amount of nutraceutical ingredients, such as phenolic compounds (3.92 mg equivalent of gallic acid per g) and flavonoids (0.35 mg equivalent of catechin per g), while HPLC analyses provided specific information about the composition of antioxidants in the syrup. Furthermore, total antioxidant activity, scavenging properties against DPPH and peroxyl radicals, and the anticholinesterase activity, clearly showed the efficacy of the syrup in preventing damage induced by free radicals and, thus, the applicability of this food derivative as a nutraceutical supplement.

  16. Genetic mosaics in strangler fig trees: implications for tropical conservation.

    PubMed

    Thomson, J D; Herre, E A; Hamrick, J L; Stone, J L

    1991-11-22

    Single trees of six species of strangler figs (Ficus spp., Moraceae) in Panama were found to be made up of multiple genotypes, presumably formed by the fusion of different individuals. The phenomenon is frequent enough that strangler fig populations will contain considerably more genetic variation than would be expected from the number of trees. How this cryptic variation affects populations depends on the flowering phonology of composite trees. If the genetically different portions of trees flower asynchronously, populations of pollinating wasps may be more resistant to low host population sizes than previously thought. If different portions flower synchronously, attempts to infer mating-system parameters from the parentage of fruit crops will be misleading. The fruiting of figs, which are considered a keystone species in tropical forests, is important for maintaining biodiversity but is also particularly susceptible to failure at small population sizes. It is therefore important to know both the number of trees and the number of genotypes in a population.

  17. Pulmonary cytochrome P450 enzymes belonging to the CYP4B subfamily from an Australian marsupial, the tammar wallaby (Macropus eugenii).

    PubMed

    Milic, Natalie L; Ngo, Suong N T; Marchant, Ceilidh L; Height, Tamara A; McKinnon, Ross A

    2011-01-01

    Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a diverse array of xenobiotics and endogenous substrates. We have previously reported the cloning and characterisation of the koala CYP4A15, the first reported member of the CYP4 family from marsupials, and have demonstrated important species differences in CYP4A activity and tissue expression. In the present study, the cloning of CYP4B1 in the wallaby (Macropus eugenii) and their expression across marsupials is described. Rabbit anti-mouse CYP4B1 antibody detected immunoreactive proteins in lung and liver microsomes from all test marsupials, with relative weak signal detected from the koala, suggesting a species-specific expression. Microsomal 2-aminofluorene bio-activation (a CYP4B1 marker) in wallaby lung was comparable to that of rabbit, with significant higher activities detected in wallaby liver and kidneys compared to rabbit. A 1548bp wallaby lung CYP4B complete cDNA, designated CYP4B1, which encodes a protein of 510 amino acids and shares 72% nucleotide and 69% amino acid sequence identity to human CYP4B1, was cloned by polymerase chain reaction approaches. The results demonstrate the presence of wallaby CYP4B1 that shares several common features with other published CYP4Bs; however the wallaby CYP4B1 cDNA contains four extra amino acid residues at the NH₂-terminal, a fundamentally conserved transmembrane anchor of all eukaryote CYPs.

  18. Interference competition and high temperatures reduce the virulence of fig wasps and stabilize a fig-wasp mutualism.

    PubMed

    Wang, Rui-Wu; Ridley, Jo; Sun, Bao-Fa; Zheng, Qi; Dunn, Derek W; Cook, James; Shi, Lei; Zhang, Ya-Ping; Yu, Douglas W

    2009-11-12

    Fig trees are pollinated by fig wasps, which also oviposit in female flowers. The wasp larvae gall and eat developing seeds. Although fig trees benefit from allowing wasps to oviposit, because the wasp offspring disperse pollen, figs must prevent wasps from ovipositing in all flowers, or seed production would cease, and the mutualism would go extinct. In Ficus racemosa, we find that syconia ('figs') that have few foundresses (ovipositing wasps) are underexploited in the summer (few seeds, few galls, many empty ovules) and are overexploited in the winter (few seeds, many galls, few empty ovules). Conversely, syconia with many foundresses produce intermediate numbers of galls and seeds, regardless of season. We use experiments to explain these patterns, and thus, to explain how this mutualism is maintained. In the hot summer, wasps suffer short lifespans and therefore fail to oviposit in many flowers. In contrast, cooler temperatures in the winter permit longer wasp lifespans, which in turn allows most flowers to be exploited by the wasps. However, even in winter, only in syconia that happen to have few foundresses are most flowers turned into galls. In syconia with higher numbers of foundresses, interference competition reduces foundress lifespans, which reduces the proportion of flowers that are galled. We further show that syconia encourage the entry of multiple foundresses by delaying ostiole closure. Taken together, these factors allow fig trees to reduce galling in the wasp-benign winter and boost galling (and pollination) in the wasp-stressing summer. Interference competition has been shown to reduce virulence in pathogenic bacteria. Our results show that interference also maintains cooperation in a classic, cooperative symbiosis, thus linking theories of virulence and mutualism. More generally, our results reveal how frequency-dependent population regulation can occur in the fig-wasp mutualism, and how a host species can 'set the rules of the game' to ensure

  19. Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype

    PubMed Central

    Plog, Stephanie; Klymiuk, Nikolai; Binder, Stefanie; Van Hook, Matthew J.; Thoreson, Wallace B.; Gruber, Achim D.; Mundhenk, Lars

    2015-01-01

    The human CLCA4 (chloride channel regulator, calcium-activated) modulates the intestinal phenotype of cystic fibrosis (CF) patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological properties. The CLCA4b gene is a pig-specific duplication product of the CLCA4 ancestor and its protein is exclusively expressed in small and large intestinal crypt epithelial cells, a niche specifically occupied by no other porcine CLCA family member. Surprisingly, a unique deleterious mutation of the CLCA4b gene is spread among modern and ancient breeds in the pig population, but this mutation did not result in an apparent phenotype in homozygously affected animals. Electrophysiologically, neither the products of the wild type nor of the mutated CLCA4b genes were able to evoke a calcium-activated anion conductance, a consensus feature of other CLCA proteins. The apparently pig-specific duplication of the CLCA4 gene with unique expression of the CLCA4b protein variant in intestinal crypt epithelial cells where the porcine CFTR is also present raises the question of whether it may modulate the porcine CF phenotype. Moreover, the naturally occurring null variant of CLCA4b will be valuable for the understanding of CLCA protein function and their relevance in modulating the CF phenotype. PMID:26474299

  20. Aflatoxins in hazelnuts and dried figs: Occurrence and exposure assessment.

    PubMed

    Kabak, Bulent

    2016-11-15

    A total of 300 samples of hazelnuts and dried fig were analysed for the incidence of any aflatoxins (AFs). High-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) method was used to quantify the amounts of AFs. The limit of quantification varied from 0.21 to 0.30μgkg(-1). No AFs were detected in shells of the hazelnuts, while six raw hazelnut kernel samples (12%) and five roasted hazelnut kernel samples (8.3%) contained AFs ranging from 0.09 to 11.3μgkg(-1) and from 0.17 to 11.2μgkg(-1), respectively. Sixteen dried fig samples (12.3%) contained AFs ranging from 0.1 to 28.2μgkg(-1) and a mean value of 3.8μgkg(-1). Three hazelnuts and six dried fig samples exceeded the European maximum limits (MLs) of 5 and 2μgkg(-1) for aflatoxin B1 (AFB1), respectively. The contribution of hazelnuts to AFs exposure is higher than that of dried figs.

  1. Kinin-Induced Parthenocarpy in the Fig, Ficus carica L.

    PubMed

    Crane, J C; van Overbeek, J

    1965-03-19

    Parthenocarpic Calimyrna fig fruits induced with a kinin were identical morphologically to those previously produced parthenocarpically with auxin or gibberellin. Thus, the three types of endogenous hormones thought to originate in the seeds and to stimulate directly fruit growth can be supplied by plant parts other than seeds. PMID:17776628

  2. Genetic characterization of fig tree mutants with molecular markers.

    PubMed

    Rodrigues, M G F; Martins, A B G; Desidério, J A; Bertoni, B W; Alves, M C

    2012-08-06

    The fig (Ficus carica L.) is a fruit tree of great world importance and, therefore, the genetic improvement becomes an important field of research for better crops, being necessary to gather information on this species, mainly regarding its genetic variability so that appropriate propagation projects and management are made. The improvement programs of fig trees using conventional procedures in order to obtain new cultivars are rare in many countries, such as Brazil, especially due to the little genetic variability and to the difficulties in obtaining plants from gamete fusion once the wasp Blastophaga psenes, responsible for the natural pollinating, is not found in Brazil. In this way, the mutagenic genetic improvement becomes a solution of it. For this reason, in an experiment conducted earlier, fig plants formed by cuttings treated with gamma ray were selected based on their agronomic characteristics of interest. We determined the genetic variability in these fig tree selections, using RAPD and AFLP molecular markers, comparing them to each other and to the Roxo-de-Valinhos, used as the standard. For the reactions of DNA amplification, 140 RAPD primers and 12 primer combinations for AFLP analysis were used. The selections did not differ genetically between themselves and between them and the Roxo-de-Valinhos cultivar. Techniques that can detect polymorphism between treatments, such as DNA sequencing, must be tested. The phenotypic variation of plants may be due to epigenetic variation, necessitating the use of techniques with methylation-sensitive restriction enzymes.

  3. Aflatoxins in hazelnuts and dried figs: Occurrence and exposure assessment.

    PubMed

    Kabak, Bulent

    2016-11-15

    A total of 300 samples of hazelnuts and dried fig were analysed for the incidence of any aflatoxins (AFs). High-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) method was used to quantify the amounts of AFs. The limit of quantification varied from 0.21 to 0.30μgkg(-1). No AFs were detected in shells of the hazelnuts, while six raw hazelnut kernel samples (12%) and five roasted hazelnut kernel samples (8.3%) contained AFs ranging from 0.09 to 11.3μgkg(-1) and from 0.17 to 11.2μgkg(-1), respectively. Sixteen dried fig samples (12.3%) contained AFs ranging from 0.1 to 28.2μgkg(-1) and a mean value of 3.8μgkg(-1). Three hazelnuts and six dried fig samples exceeded the European maximum limits (MLs) of 5 and 2μgkg(-1) for aflatoxin B1 (AFB1), respectively. The contribution of hazelnuts to AFs exposure is higher than that of dried figs. PMID:27283601

  4. Genetic structure and differentiation in cultivated fig (Ficus carica L.).

    PubMed

    Aradhya, Mallikarjuna K; Stover, Ed; Velasco, Dianne; Koehmstedt, Anne

    2010-06-01

    One hundred ninety-four germplasm accessions of fig representing the four fig types, Common, Smyrna, San Pedro, and Caprifig were analyzed for genetic diversity, structure, and differentiation using genetic polymorphism at 15 microsatellite loci. The collection showed considerable polymorphism with observed number of alleles per locus ranging from four for five different loci, MFC4, LMFC14, LMFC22, LMFC31 and LMFC35 to nine for LMFC30 with an average of 4.9 alleles per locus. Seven of the 15 loci included in the genetic structure analyses exhibited significant deviation from panmixia, of which two showed excess and five showed deficiency of heterozygote. The cluster analysis (CA) revealed ten groups with 32 instances of synonymy among cultivars and groups differed significantly for frequency and composition of alleles for different loci. The principal components analysis (PCA) confirmed the results of CA with some groups more differentiated than the others. Further, the model based Bayesian approach clustering suggested a subtle population structure with mixed ancestry for most figs. The gene diversity analysis indicated that much of the total variation is found within groups (H (G) /H (T) = 0.853; 85.3%) and the among groups within total component (G (GT) = 0.147) accounted for the remaining 14.7%, of which approximately 64% accounted for among groups within clusters (G (GC) = 0.094) and approximately 36% among clusters (G (CT) = 0.053). The analysis of molecular variance (AMOVA) showed approximately similar results with nearly 87% of variation within groups and approximately 10% among groups within clusters, and approximately 3% among clusters. Overall, the gene pool of cultivated fig analyzed possesses substantial genetic polymorphism but exhibits narrow differentiation. It is evident that fig accessions from Turkmenistan are somewhat genetically different from the rest of the Mediterranean and the Caucasus figs. The long history of domestication and cultivation

  5. Generation and characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of Ipomeanol.

    PubMed

    Parkinson, Oliver T; Liggitt, H Denny; Rettie, Allan E; Kelly, Edward J

    2013-08-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 (-/-) mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 (-/-) mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 (+/+) animals. Administration of IPO (20mg/kg) to Cyp4b1 (+/+) mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 (-/-) mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 (-/-) mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity. PMID:23748241

  6. Generation and Characterization of a Cyp4b1 Null Mouse and the Role of CYP4B1 in the Activation and Toxicity of Ipomeanol

    PubMed Central

    Kelly, Edward J.

    2013-01-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 −/− mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 −/− mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 +/+ animals. Administration of IPO (20mg/kg) to Cyp4b1 +/+ mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 −/− mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 −/− mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity. PMID:23748241

  7. Initial assessment of natural diversity in Mexican fig landraces.

    PubMed

    García-Ruiz, M T; Mendoza-Castillo, V M; Valadez-Moctezuma, E; Muratalla-Lúa, A

    2013-09-23

    The common fig (Ficus carica L.) was introduced into Mexico by Spanish Franciscan missionaries in the 16th century. It is widely assumed that Mexican figs are the Spanish cultivar Black Mission. We collected and propagated 12 fig plants from six landraces from different states in Central Mexico that represent different climate. All of them were grown in a greenhouse at Universidad Autónoma Chapingo, in the State of Mexico. During the experimental period, the greenhouse had an average temperature and relative humidity of 29.2° ± 5.4°C (SEM) and 78.1 ± 6.7% (SEM), respectively. Morphological characterization was done following a selected set of quantitative and qualitative descriptors established by the IPGRI. DNA analysis was based on a combination of ISSR and RFLP markers. We observed great diversity mainly in fruit weight (28.1-96.2 g), fruit shape (ovoid, pyriform), and neck length (0.97-3.80 cm), which could not be explained by environmental conditions such as temperature and relative humidity. The Nei and Li/Dice similarity coefficient between landraces was determined by cluster analysis using the UPGMA method. Based on the morphological characterization and DNA fingerprinting data presented in this study, our results showed that after hundreds of years, black figs have adapted to local environmental condition in Central Mexico, yielding at least six clearly distinct landraces that represent valuable and previously undescribed genetic diversity. We also suggested names for those landraces according to their location and established a basis for further agronomic and molecular characterization of fig landraces.

  8. Secondary Eclipse Photometry of WASP-4b with Warm Spitzer

    NASA Astrophysics Data System (ADS)

    Beerer, Ingrid M.; Knutson, Heather A.; Burrows, Adam; Fortney, Jonathan J.; Agol, Eric; Charbonneau, David; Cowan, Nicolas B.; Deming, Drake; Desert, Jean-Michel; Langton, Jonathan; Laughlin, Gregory; Lewis, Nikole K.; Showman, Adam P.

    2011-01-01

    We present photometry of the giant extrasolar planet WASP-4b at 3.6 and 4.5 μm taken with the Infrared Array Camera on board the Spitzer Space Telescope as part of Spitzer's extended warm mission. We find secondary eclipse depths of 0.319% ± 0.031% and 0.343% ± 0.027% for the 3.6 and 4.5 μm bands, respectively, and show model emission spectra and pressure-temperature profiles for the planetary atmosphere. These eclipse depths are well fit by model emission spectra with water and other molecules in absorption, similar to those used for TrES-3 and HD 189733b. Depending on our choice of model, these results indicate that this planet has either a weak dayside temperature inversion or no inversion at all. The absence of a strong thermal inversion on this highly irradiated planet is contrary to the idea that highly irradiated planets are expected to have inversions, perhaps due the presence of an unknown absorber in the upper atmosphere. This result might be explained by the modestly enhanced activity level of WASP-4b's G7V host star, which could increase the amount of UV flux received by the planet, therefore reducing the abundance of the unknown stratospheric absorber in the planetary atmosphere as suggested in Knutson et al. We also find no evidence for an offset in the timing of the secondary eclipse and place a 2σ upper limit on |ecos ω| of 0.0024, which constrains the range of tidal heating models that could explain this planet's inflated radius.

  9. RAMONA-4B development for SBWR safety studies

    SciTech Connect

    Rohatgi, U.S.; Aronson, A.L.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.

    1993-12-31

    The Simplified Boiling Water Reactor (SBWR) is a revolutionary design of a boiling-water reactor. The reactor is based on passive safety systems such as natural circulation, gravity flow, pressurized gas, and condensation. SBWR has no active systems, and the flow in the vessel is by natural circulation. There is a large chimney section above the core to provide a buoyancy head for natural circulation. The reactor can be shut down by either of four systems; namely, scram, Fine Motion Control Rod Drive (FMCRD), Alternate Rod Insertion (ARI), and Standby Liquid Control System (SLCS). The safety injection is by gravity drain from the Gravity Driven Cooling System (GDCS) and Suppression Pool (SP). The heat sink is through two types of heat exchangers submerged in the tank of water. These heat exchangers are the Isolation Condenser (IC) and the Passive Containment Cooling System (PCCS). The RAMONA-4B code has been developed to simulate the normal operation, reactivity transients, and to address the instability issues for SBWR. The code has a three-dimensional neutron kinetics coupled to multiple parallel-channel thermal-hydraulics. The two-phase thermal hydraulics is based on a nonhomogeneous nonequilibrium drift-flux formulation. It employs an explicit integration to solve all state equations (except for neutron kinetics) in order to predict the instability without numerical damping. The objective of this project is to develop a Sun SPARC and IBM RISC 6000 based RAMONA-4B code for applications to SBWR safety analyses, in particular for stability and ATWS studies.

  10. Aggregation Properties of the Chromonic Liquid Crystal Benzopurpurin 4B

    NASA Astrophysics Data System (ADS)

    McKitterick, Christopher; Collings, Peter

    2009-03-01

    Benzopurpurin 4B (BPP) is a textile dye very similar to the common indicator Congo Red. As is true for all chromonics, the absorption spectrum is concentration dependent at low concentrations. If this dependence is used to estimate a free energy change for aggregation, it is higher than has been determined for other systems. Unlike other recently investigated chromonic liquid crystals, BPP forms a liquid crystal phase at extremely low concentrations, about 0.5 wt%. Also unlike these other chromonic liquid crystals, the aggregation kinetics are exceedingly slow. X-ray diffraction and light scattering measurements indicate that the aggregates of BPP are much larger than for chromonic systems that form liquid crystals at higher concentrations. BPP aggregates can be imaged using confocal microscopy, revealing a length distribution centered at 3 μm for a solution forced through a 0.2 μm filter. Over days the aggregates lengthen to well over 10 μm. The diameter of the aggregate images is slightly greater than the diffraction limit of the microscope, placing an upper limit on the diameter of 0.14 μm. These dimensions are consistent with the light scattering results.

  11. Generation and characterization of mouse monoclonal antibodies against NS4B protein of dengue virus.

    PubMed

    Xie, Xuping; Zou, Jing; Wang, Qing-Yin; Noble, Christian G; Lescar, Julien; Shi, Pei-Yong

    2014-02-01

    Dengue virus (DENV) non-structural protein 4B (NS4B) has been demonstrated to be an attractive antiviral target. Due to its nature as an integral membrane protein, NS4B remains poorly characterized. In this study, we generated and characterized two monoclonal antibodies (mAb) that selectively bind to DENV NS4B protein. One mAb, 10-3-7, is specific for DENV-2 NS4B, and its epitope was mapped to residues 5-15 of NS4B. The other mAb, 44-4-7, cross-reacts with all the four serotypes of DENV NS4B, and its epitope was mapped to residues 141-147 of NS4B. Using the mAbs, we probed the intracellular orientation of the epitopes of NS4B by an epitope accessibility assay. The results showed that the N-terminus of NS4B is located in the ER lumen, whereas amino acids 130-148 of NS4B are located in the cytosol. The study demonstrates that the two anti-NS4B mAbs will be useful for future structural and functional analyses of DENV NS4B. PMID:24503088

  12. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  13. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  14. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  15. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  16. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  17. The effect of fig wall thickness in Ficus erecta var. beecheyana on parasitism

    NASA Astrophysics Data System (ADS)

    Tzeng, Hsy-Yu; Ou, Chern-Hsiung; Lu, Fu-Yuan; Bain, Anthony; Chou, Lien-Siang; Kjellberg, Finn

    2014-05-01

    Fig wasp communities constitute a model system to analyse determinants of community complexity and to investigate how biological interaction networks are maintained. It has been suggested for monoecious figs, that fig pollinating wasps avoid ovipositing in flowers located close to the fig wall because of strong parasitic pressure by wasps ovipositing through the fig wall. This behaviour could help explain why mainly seeds are produced in flowers located close to the fig wall, thus stabilizing the fig-pollinating wasp mutualism. In this contribution we explore, for dioecious figs, whether ovipositor length of parasitic species may really be limiting. In dioecious figs, functionally male figs produce pollinating wasps and pollen while female figs produce only seeds, facilitating selection of traits favouring pollinator reproduction in male figs. We show in Ficus erecta that fig walls are thicker in male figs than in female figs. Male figs presenting thick walls, thicker than the length of the parasites' ovipositors, went unparasitized while male figs presenting thinner walls were systematically parasitized. Hence, in F. erecta, ovipositor length of the parasites is limiting access to some figs. However, we also show that in another dioecious species, Ficus formosana, presenting thin walled male figs, no fig is protected against oviposition by its two parasites. Hence in dioecious as well as in monoecious figs, in some Ficus species, ovipositors of the parasites are limiting access to ovules, while in other Ficus species all ovules are exposed to parasitism.

  18. Intersexual sibling interactions and male benevolence in a fig wasp.

    PubMed

    Zammit; Schwarz

    2000-11-01

    We studied interactions between males and females of the Australian pollinating fig wasp, Pleistodontes imperialis (Chalcidoidea, Agaonidae), in Ficus platypoda (Moraceae). As for many other fig wasps, all mating occurs within the confines of a syconium before females depart. We show that initially there is scramble competition between males for access to virgin females. During this time males excavated a small hole into a female's gall to mate through. These holes were just large enough for insemination, but not large enough for females to exit their galls. Males ignored mated females, and as virgin females became scarce males switched strategies and began to enlarge insemination holes until they were large enough for females to escape, showing that males enhance female fitness by means other than just mating. Syconia with experimentally reduced numbers of males had fewer liberated females, suggesting that female fitness is strongly affected by the number of males present. Females may be unable to escape their galls unassisted because of morphological adaptations to syconium founding. We argue that sex allocation should be affected not only by competition among males but also by intersexual interactions between siblings. This could potentially offset the strong female bias predicted by local mate competition. Copyright 2000 The Association for the Study of Animal Behaviour.

  19. Transcriptional and translational mapping and nucleotide sequence analysis of a vaccinia virus gene encoding the precursor of the major core polypeptide 4b.

    PubMed

    Rosel, J; Moss, B

    1985-12-01

    We prepared antiserum that reacted with a major core polypeptide of approximately 62,000 daltons (62K polypeptide), designated 4b, and its 74K precursor, designated P4b. A cell-free translation product of vaccinia virus late mRNA that comigrated with P4b was specifically immunoprecipitated. The late mRNA encoding P4b hybridized to restriction fragments derived from the left end of the HindIII A fragment and to a lesser extent from the right side of the HindIII D fragment. A polypeptide that comigrated with P4a, the precursor of another major core polypeptide, was synthesized by mRNA that hybridized to DNA segments upstream of the P4b gene. Complete nucleotide sequence analysis of the P4b gene revealed an open reading frame, entirely within the HindIII A fragment, that was sufficient to encode a 644-amino-acid polypeptide of 73K. The 5' end of the P4b mRNA was located at or just above the translational initiation site.

  20. Papain Induced Occupational Asthma with Kiwi and Fig Allergy.

    PubMed

    Jiang, Nannan; Yin, Jia; Wen, Liping

    2016-03-01

    Papain is a proteolytic enzyme which is widely used in food industry, pharmaceuticals, and cosmetics. Occupational and non-occupational papain allergies have previously been documented; however, there are limited publications about papain allergy with its relative fruit allergy. Here, we present a case of occupational, IgE-mediated papain allergy with kiwi fruit and fig fruit allergy. A 53-year-old man suffered from rhinitis for several years, with the onset of his symptoms coinciding with the time he started to work at a sausage processing plant where papain is often used as a meat tenderizer. He began to experience symptoms of chest tightness, shortness of breath and wheezing shortly after starting work 5 years ago. Furthermore, he experienced several episodes of oral itching, and tongue and oropharyngeal angioedema after injestion of kiwi fruit and fig fruit. The patient had a lifelong history of allergic conjunctivitis, allergic rhinitis, and childhood asthma. Specific IgE was positive to kiwi fruit, papain and chymopapain (2.95 kUA/L, >100 kUA/L, and 95.0 kUA/L, respectively). Similar bands at 10-15 kDa in blotting with papain and kiwi fruit extracts were found. This patient showed a potential association between papain allergy and sensitization to kiwi fruit. We also reviewed 13 patients with papain allergy published in the literature, with 85% (11/13) of the patients sensitized through the respiratory tract, and 40% (4/11) having atopy. Further studies should focus on the determination of cross-reactive allergens between papain and its fruit relatives, and the prevalence of food allergy in patients with papain allergy should be investigated in a relatively large cohort. PMID:26739411

  1. Papain Induced Occupational Asthma with Kiwi and Fig Allergy

    PubMed Central

    Jiang, Nannan; Yin, Jia

    2016-01-01

    Papain is a proteolytic enzyme which is widely used in food industry, pharmaceuticals, and cosmetics. Occupational and non-occupational papain allergies have previously been documented; however, there are limited publications about papain allergy with its relative fruit allergy. Here, we present a case of occupational, IgE-mediated papain allergy with kiwi fruit and fig fruit allergy. A 53-year-old man suffered from rhinitis for several years, with the onset of his symptoms coinciding with the time he started to work at a sausage processing plant where papain is often used as a meat tenderizer. He began to experience symptoms of chest tightness, shortness of breath and wheezing shortly after starting work 5 years ago. Furthermore, he experienced several episodes of oral itching, and tongue and oropharyngeal angioedema after injestion of kiwi fruit and fig fruit. The patient had a lifelong history of allergic conjunctivitis, allergic rhinitis, and childhood asthma. Specific IgE was positive to kiwi fruit, papain and chymopapain (2.95 kUA/L, >100 kUA/L, and 95.0 kUA/L, respectively). Similar bands at 10-15 kDa in blotting with papain and kiwi fruit extracts were found. This patient showed a potential association between papain allergy and sensitization to kiwi fruit. We also reviewed 13 patients with papain allergy published in the literature, with 85% (11/13) of the patients sensitized through the respiratory tract, and 40% (4/11) having atopy. Further studies should focus on the determination of cross-reactive allergens between papain and its fruit relatives, and the prevalence of food allergy in patients with papain allergy should be investigated in a relatively large cohort. PMID:26739411

  2. Papain Induced Occupational Asthma with Kiwi and Fig Allergy.

    PubMed

    Jiang, Nannan; Yin, Jia; Wen, Liping

    2016-03-01

    Papain is a proteolytic enzyme which is widely used in food industry, pharmaceuticals, and cosmetics. Occupational and non-occupational papain allergies have previously been documented; however, there are limited publications about papain allergy with its relative fruit allergy. Here, we present a case of occupational, IgE-mediated papain allergy with kiwi fruit and fig fruit allergy. A 53-year-old man suffered from rhinitis for several years, with the onset of his symptoms coinciding with the time he started to work at a sausage processing plant where papain is often used as a meat tenderizer. He began to experience symptoms of chest tightness, shortness of breath and wheezing shortly after starting work 5 years ago. Furthermore, he experienced several episodes of oral itching, and tongue and oropharyngeal angioedema after injestion of kiwi fruit and fig fruit. The patient had a lifelong history of allergic conjunctivitis, allergic rhinitis, and childhood asthma. Specific IgE was positive to kiwi fruit, papain and chymopapain (2.95 kUA/L, >100 kUA/L, and 95.0 kUA/L, respectively). Similar bands at 10-15 kDa in blotting with papain and kiwi fruit extracts were found. This patient showed a potential association between papain allergy and sensitization to kiwi fruit. We also reviewed 13 patients with papain allergy published in the literature, with 85% (11/13) of the patients sensitized through the respiratory tract, and 40% (4/11) having atopy. Further studies should focus on the determination of cross-reactive allergens between papain and its fruit relatives, and the prevalence of food allergy in patients with papain allergy should be investigated in a relatively large cohort.

  3. Magnitude and range of the RKKy interaction in SmRh4B4

    NASA Astrophysics Data System (ADS)

    Terris, B. D.; Gray, K. E.; Dunlap, B. D.

    1985-04-01

    The superconductive and magnetic transition temperatures taken together are shown to provide a unique probe which separately determines both the magnitude and range of the RKKY interaction in the RERh4B4 magnetic-superconductors (RE = Er, Sm). Experimentally, an unexpected peak is found in the antiferromagnetic ordering temperature of SmRh4B4 vs. electron mean free path, while for ErRh4B4 the ferromagnetic ordering temperature decreases monotonically. These qualitative features, as well as the quanitative differences between SmRh4B4 and ErRh4B4, are in excellent agreement with calculations using a mean free path dependent RKKY interaction.

  4. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    PubMed

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  5. Phosphodiesterase 4B is essential for TH2-cell function and development of airway hyperresponsiveness in allergic asthma

    PubMed Central

    Catherine Jin, S.-L.; Goya, Sho; Nakae, Susumu; Wang, Dan; Bruss, Matthew; Hou, Chiaoyin; Umetsu, Dale; Conti, Marco

    2010-01-01

    Background Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. Objectives We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and TH2-driven inflammatory responses. Methods Wild-type and PDE4B−/− mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and TH2 cytokine production were determined in cultured bronchial lymph node cells. Results Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased TH2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, TH2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the TH1 cytokine IFN-γ was not affected in PDE4B−/− mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. Conclusion By relieving a cAMP-negative constraint, PDE4B plays an essential role in TH2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment. PMID:21047676

  6. BPO4@B2O3 and (BPO4@B2O3):Eu3+: The novel single-emitting-component phosphors for near UV-white LEDs

    NASA Astrophysics Data System (ADS)

    Cao, Xiyu; Liu, Wei; Jiang, Yu; Cao, Lixin; Su, Ge; Gao, Rongjie

    2016-08-01

    Nowadays much effort has been devoted to exploring novel luminescent materials with low-cost, high stability and excellent luminescent properties. In this paper, a new kind of luminescent material BPO4@B2O3 was prepared by using a facile method. The as-obtained samples contain numerous BPO4 nanoparticles enclosed by amorphous and crystalline B2O3 homogeneously, which exhibits a broad emission band ranging from 380 to 700 nm under near-UV irradiation. More importantly, it is worth noting that the BPO4@B2O3 phosphor exhibits the excellent thermal quenching property, which endows it with a promising prospect as phosphors for high power white LEDs. To further promote its application as white light phosphors, Eu3+ ions were doped into the BPO4@B2O3 samples and prepared the (BPO4@B2O3):Eu3+ phosphors with chromaticity coordinates (0.3022, 0.3122). The corresponding packaging of LEDs indicates that both BPO4@B2O3 and (BPO4@B2O3):Eu3+ can be considered as the promising phosphors for WLEDs.

  7. Ficus spp. (fig): ethnobotany and potential as anticancer and anti-inflammatory agents.

    PubMed

    Lansky, Ephraim Philip; Paavilainen, Helena M; Pawlus, Alison D; Newman, Robert A

    2008-09-26

    This review explores medieval, ancient and modern sources for ethnopharmacological uses of Ficus (fig) species, specifically for employment against malignant disease and inflammation. The close connection between inflammatory/infectious and cancerous diseases is apparent both from the medieval/ancient merging of these concepts and the modern pharmacological recognition of the initiating and promoting importance of inflammation for cancer growth. Also considered are chemical groups and compounds underlying the anticancer and anti-inflammatory actions, the relationship of fig wasps and fig botany, extraction and storage of fig latex, and traditional methods of preparing fig medicaments including fig lye, fig wine and medicinal poultices.

  8. Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors.

    PubMed

    Qiu, Zongxing; Kuhn, Bernd; Aebi, Johannes; Lin, Xianfeng; Ding, Haiyuan; Zhou, Zheng; Xu, Zhiheng; Xu, Danqing; Han, Li; Liu, Cheng; Qiu, Hongxia; Zhang, Yuxia; Haap, Wolfgang; Riemer, Claus; Stahl, Martin; Qin, Ning; Shen, Hong C; Tang, Guozhi

    2016-08-11

    ATG4B or autophagin-1 is a cysteine protease that cleaves ATG8 family proteins. ATG4B plays essential roles in the autophagosome formation and the autophagy pathway. Herein we disclose the design and structural modifications of a series of fluoromethylketone (FMK)-based peptidomimetics as highly potent ATG4B inhibitors. Their structure-activity relationship (SAR) and protease selectivity are also discussed. PMID:27563406

  9. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.

    PubMed

    Cabrera, Sandra; Fernández, Alvaro F; Mariño, Guillermo; Aguirre, Alina; Suárez, María F; Español, Yaiza; Vega, José A; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M Soledad; Freije, José M P; Kroemer, Guido; López-Otín, Carlos

    2013-08-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b (-/-) mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b (-/-) mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency.

  10. DNA damage-induced activation of CUL4B targets HUWE1 for proteasomal degradation.

    PubMed

    Yi, Juan; Lu, Guang; Li, Li; Wang, Xiaozhen; Cao, Li; Lin, Ming; Zhang, Sha; Shao, Genze

    2015-05-19

    The E3 ubiquitin ligase HUWE1/Mule/ARF-BP1 plays an important role in integrating/coordinating diverse cellular processes such as DNA damage repair and apoptosis. A previous study has shown that HUWE1 is required for the early step of DNA damage-induced apoptosis, by targeting MCL-1 for proteasomal degradation. However, HUWE1 is subsequently inactivated, promoting cell survival and the subsequent DNA damage repair process. The mechanism underlying its regulation during this process remains largely undefined. Here, we show that the Cullin4B-RING E3 ligase (CRL4B) is required for proteasomal degradation of HUWE1 in response to DNA damage. CUL4B is activated in a NEDD8-dependent manner, and ubiquitinates HUWE1 in vitro and in vivo. The depletion of CUL4B stabilizes HUWE1, which in turn accelerates the degradation of MCL-1, leading to increased induction of apoptosis. Accordingly, cells deficient in CUL4B showed increased sensitivity to DNA damage reagents. More importantly, upon CUL4B depletion, these phenotypes can be rescued through simultaneous depletion of HUWE1, consistent with the role of CUL4B in regulating HUWE1. Collectively, these results identify CRL4B as an essential E3 ligase in targeting the proteasomal degradation of HUWE1 in response to DNA damage, and provide a potential strategy for cancer therapy by targeting HUWE1 and the CUL4B E3 ligase.

  11. Expression and evolutionary divergence of the non-conventional olfactory receptor in four species of fig wasp associated with one species of fig

    PubMed Central

    Lu, Bin; Wang, Nina; Xiao, Jinhua; Xu, Yongyu; Murphy, Robert W; Huang, Dawei

    2009-01-01

    Background The interactions of fig wasps and their host figs provide a model for investigating co-evolution. Fig wasps have specialized morphological characters and lifestyles thought to be adaptations to living in the fig's syconium. Although these aspects of natural history are well documented, the genetic mechanism(s) underlying these changes remain(s) unknown. Fig wasp olfaction is the key to host-specificity. The Or83b gene class, an unusual member of olfactory receptor family, plays a critical role in enabling the function of conventional olfactory receptors. Four Or83b orthologous genes from one pollinator (PFW) (Ceratosolen solmsi) and three non-pollinator fig wasps (NPFWs) (Apocrypta bakeri, Philotrypesis pilosa and Philotrypesis sp.) associated with one species of fig (Ficus hispida) can be used to better understand the molecular mechanism underlying the fig wasp's adaptation to its host. We made a comparison of spatial tissue-specific expression patterns and substitution rates of one orthologous gene in these fig wasps and sought evidence for selection pressures. Results A newly identified Or83b orthologous gene was named Or2. Expressions of Or2 were restricted to the heads of all wingless male fig wasps, which usually live in the dark cavity of a fig throughout their life cycle. However, expressions were widely detected in the antennae, legs and abdomens of all female fig wasps that fly from one fig to another for oviposition, and secondarily pollination. Weak expression was also observed in the thorax of PFWs. Compared with NPFWs, the Or2 gene in C. solmsi had an elevated rate of substitutions and lower codon usage. Analyses using Tajima's D, Fu and Li's D* and F* tests indicated a non-neutral pattern of nucleotide variation in all fig wasps. Unlike in NPFWs, this non-neutral pattern was also observed for synonymous sites of Or2 within PFWs. Conclusion The sex- and species-specific expression patterns of Or2 genes detected beyond the known primary

  12. Phenological Adaptations in Ficus tikoua Exhibit Convergence with Unrelated Extra-Tropical Fig Trees

    PubMed Central

    Zhao, Ting-Ting; Compton, Stephen G.; Yang, Yong-Jiang; Wang, Rong; Chen, Yan

    2014-01-01

    Flowering phenology is central to the ecology and evolution of most flowering plants. In highly-specific nursery pollination systems, such as that involving fig trees (Ficus species) and fig wasps (Agaonidae), any mismatch in timing has serious consequences because the plants must balance seed production with maintenance of their pollinator populations. Most fig trees are found in tropical or subtropical habitats, but the dioecious Chinese Ficus tikoua has a more northerly distribution. We monitored how its fruiting phenology has adapted in response to a highly seasonal environment. Male trees (where fig wasps reproduce) had one to three crops annually, whereas many seed-producing female trees produced only one fig crop. The timing of release of Ceratosolen fig wasps from male figs in late May and June was synchronized with the presence of receptive figs on female trees, at a time when there were few receptive figs on male trees, thereby ensuring seed set while allowing remnant pollinator populations to persist. F. tikoua phenology has converged with those of other (unrelated) northern Ficus species, but there are differences. Unlike F. carica in Europe, all F. tikoua male figs contain male flowers, and unlike F. pumila in China, but like F. carica, it is the second annual generation of adult wasps that pollinate female figs. The phenologies of all three temperate fig trees generate annual bottlenecks in the size of pollinator populations and for female F. tikoua also a shortage of fig wasps that results in many figs failing to be pollinated. PMID:25474008

  13. Phenological adaptations in Ficus tikoua exhibit convergence with unrelated extra-tropical fig trees.

    PubMed

    Zhao, Ting-Ting; Compton, Stephen G; Yang, Yong-Jiang; Wang, Rong; Chen, Yan

    2014-01-01

    Flowering phenology is central to the ecology and evolution of most flowering plants. In highly-specific nursery pollination systems, such as that involving fig trees (Ficus species) and fig wasps (Agaonidae), any mismatch in timing has serious consequences because the plants must balance seed production with maintenance of their pollinator populations. Most fig trees are found in tropical or subtropical habitats, but the dioecious Chinese Ficus tikoua has a more northerly distribution. We monitored how its fruiting phenology has adapted in response to a highly seasonal environment. Male trees (where fig wasps reproduce) had one to three crops annually, whereas many seed-producing female trees produced only one fig crop. The timing of release of Ceratosolen fig wasps from male figs in late May and June was synchronized with the presence of receptive figs on female trees, at a time when there were few receptive figs on male trees, thereby ensuring seed set while allowing remnant pollinator populations to persist. F. tikoua phenology has converged with those of other (unrelated) northern Ficus species, but there are differences. Unlike F. carica in Europe, all F. tikoua male figs contain male flowers, and unlike F. pumila in China, but like F. carica, it is the second annual generation of adult wasps that pollinate female figs. The phenologies of all three temperate fig trees generate annual bottlenecks in the size of pollinator populations and for female F. tikoua also a shortage of fig wasps that results in many figs failing to be pollinated.

  14. TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis

    PubMed Central

    Grive, Kathryn J.; Gustafson, Eric A.; Seymour, Kimberly A.; Baddoo, Melody; Schorl, Christoph; Golnoski, Kayla; Rajkovic, Aleksandar; Brodsky, Alexander S.; Freiman, Richard N.

    2016-01-01

    TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women. PMID:27341508

  15. TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis.

    PubMed

    Grive, Kathryn J; Gustafson, Eric A; Seymour, Kimberly A; Baddoo, Melody; Schorl, Christoph; Golnoski, Kayla; Rajkovic, Aleksandar; Brodsky, Alexander S; Freiman, Richard N

    2016-06-01

    TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women.

  16. Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression.

    PubMed

    Uribe, Rosa A; Buzzi, Ailín L; Bronner, Marianne E; Strobl-Mazzulla, Pablo H

    2015-11-23

    In vertebrates, the inner ear arises from the otic placode, a thickened swathe of ectoderm that invaginates to form the otic vesicle. We report that histone demethylase KDM4B is dynamically expressed during early stages of chick inner ear formation. A loss of KDM4B results in defective invagination and striking morphological changes in the otic epithelium, characterized by abnormal localization of adhesion and cytoskeletal molecules and reduced expression of several inner ear markers, including Dlx3. In vivo chromatin immunoprecipitation reveals direct and dynamic occupancy of KDM4B and its target, H3K9me3, at regulatory regions of the Dlx3 locus. Accordingly, coelectroporations of DLX3 or KDM4B encoding constructs, but not a catalytically dead mutant of KDM4B, rescue the ear invagination phenotype caused by KDM4B knockdown. Moreover, a loss of DLX3 phenocopies a loss of KDM4B. Collectively, our findings suggest that KDM4B play a critical role during inner ear invagination via modulating histone methylation of the direct target Dlx3. PMID:26598618

  17. Standard Neutron, Photon, and Electron Data Libraries for MCNP4B.

    1997-04-01

    Version 00 US DOE 10CFR810 Jurisdiction. DLC-189/MCNPXS is for use with Version 4B and later of the MCNP transport code. This data library provides a comprehensive set of cross sections for a wide range of radiation transport applications using the Monte Carlo code package CCC-660/MCNP4B.

  18. 75 FR 18509 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... 21, 2008 (73 FR 9575), FDA made available a guidance on the Q4B process entitled ``Q4B Evaluation and.... In the Federal Register of August 14, 2009 (74 FR 41143), FDA published a notice announcing the... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference...

  19. LAPTM4B-35 protein is a weak tumor-associated antigen candidate

    PubMed Central

    SHI, GUILAN; ZHOU, CHUNXIA; WANG, DONGMEI; MA, WENBO; ZHANG, SHUREN

    2014-01-01

    Lysosome-associated protein transmembrane 4β (LAPTM4B) is a gene that has been indicated to be involved in cancer. It is located at chromosome 8q22 and is composed of seven exons and six introns. LAPTM4B encodes two protein isoforms: LAPTM4B-35 and LAPTM4B-24. LAPTM4B-35 is markedly upregulated and LAPTM4B-24 is downregulated in several types of cancer. LAPTM4B-35 is 91 amino acids (N91) longer than LAPTM4B-24 at the N-terminus. In the present study, western blotting, enzyme-linked immunosorbent spot analysis and the B16F10-N91 tumor bearing-mice experiments were used to evaluate whether the overexpression of N91 indicates its potential as a candidate tumor-associated antigen. The results revealed that N91 was expressed in a wide range of normal mouse tissues and human peripheral blood mononuclear cells, with varying expression levels. The weak immunogenicity of N91 protein suggested it was a weak candidate antigen; however, the N91 protein was associated with cell proliferation. PMID:24396432

  20. Mutations in the classical swine fever virus NS4B protein affects virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Inte...

  1. Monoclonal antibodies against NS4B protein of japanese encephalitis virus.

    PubMed

    Ruan, Xindi; Huang, Shaomei; Shao, Lin; Ye, Jing; Chen, Zheng; Chen, Huanchun; Cao, Shengbo

    2013-12-01

    Japanese encephalitis (JE) is one of the most prevalent global viral encephalitis viruses. The functions of JEV (virus) NS4B protein are still under investigation. In our study, NS4B was expressed in Escherichia coli and purified by dialysis. Two clones of monoclonal antibodies (MAbs 1B1 and 1C3) against NS4B protein were generated and their characterizations were investigated. IFA, Western blot, and ELISA results showed that the MAbs were specific against JEV NS4B protein. The epitope of the MAbs was further identified using pairs of synthesized overlapping peptides. These MAbs may provide valuable tools for further exploration of the functions of NS4B and the pathogenesis of Japanese encephalitis virus. PMID:24328740

  2. Interferon regulatory factor 4b (IRF4b) in Japanese flounder, Paralichthys olivaceus: Sequencing, ubiquitous tissue distribution and inducible expression by poly(I:C) and DNA virus.

    PubMed

    Liu, Dahai; Chen, Jinjing; Zhang, Haiyan; Hu, Mengzhu; Lou, Huimin; Liu, Qiuming; Zhang, Shicui; Hu, Guobin

    2016-09-01

    Interferon regulatory factor 4 (IRF4) in mammals is known to be critical in regulation of development and functions of lymphomyeloid cell lineages. Recent studies have demonstrated its involvement in immune responses to bacterial and viral challenges in teleosts. In this study, an IRF4 gene was cloned from Japanese flounder (Paralichthys olivaceus) and its expression in response to polyinosinic:polycytidylic acid [poly(I:C)] and lymphocystis disease virus (LCDV) stimulations was studied in vivo. The cloned gene spans over 5.9 kb, comprises eight exons and seven introns and encodes a putative protein of 456 amino acids. The deduced amino acid sequence possesses a conserved DNA-binding domain (DBD), an IRF-association domain (IAD) and a nuclear localization signal (NLS). Phylogenetic analysis clustered it into the teleost IRF4b clade and, thus, it was named Paralichthys olivaceus (Po)IRF4b. The constitutive expression of PoIRF4b transcripts was detectable in all examined organs, with highest levels found in lymphomyeloid-rich tissues. They were induced by both poly(I:C) and LCDV with a similar inducibility in immune or non-immune organs. Two waves of induced expression of PoIRF4b were observed with the two stimuli during a 7-day time course in the immune organs, with the early-phase induction being stronger. The maximum increases of PoIRF4b transcript levels ranged from 1.3 to 4.0-fold and appeared at day 1-5 post-injection depending on different organs and stimuli. In both stimulation cases, the strongest induction was detected in spleen and the weakest in muscle. These results indicate that PoIRF4b may participate in regulation of immune responses of flounders to both RNA and DNA virus infections. PMID:27084058

  3. Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis

    PubMed Central

    Zeng, Yang; Pan, I-Wen

    2015-01-01

    Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a “coactivator” of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development. PMID:26258622

  4. Smaller tumor size is associated with poor survival in T4b colon cancer

    PubMed Central

    Huang, Ben; Feng, Yang; Mo, Shao-Bo; Cai, San-Jun; Huang, Li-Yong

    2016-01-01

    AIM: To hypothesize that in patients with colon cancer showing heavy intestinal wall invasion without distant metastasis (T4bN0-2M0), small tumor size would correlate with more aggressive tumor behaviors and therefore poorer cancer-specific survival (CSS). METHODS: We analyzed T4bN0-2M0 colon cancer patients in the Surveillance, Epidemiology and End Results (SEER) database. A preliminary analysis of T4bN0-2M0 colon cancer patients at the Fudan University Shanghai Cancer Center is also presented. RESULTS: A total of 1734 T4bN0-2M0 colon cancer patients from the SEER database were included. Kaplan-Meier analysis revealed decreasing CSS with decreasing tumor size (P < 0.001). Subgroup analysis showed a significant association between poorer CSS with smaller tumor size in T4bN0 patients (P = 0.024), and a trend of association in T4bN1 (P = 0.182) and T4bN2 patients (P = 0.191). Multivariate analysis identified tumor size as an independent prognostic factor for CSS in T4bN0-2M0 patients (P = 0.024). Preliminary analysis of Fudan University Shanghai Cancer Center samples suggested the 5-year CSS was 50.0%, 72.9% and 77.1% in patients with tumors ≤ 4.0 cm, 4.0-7.0 cm and ≥ 7.0 cm. CONCLUSION: Smaller tumor size is associated with poorer CSS in the T4bN0-2M0 subset of colon cancer, particularly in the T4bN0M0 subgroup. PMID:27547015

  5. Sensory profiles for dried fig (Ficus carica L.) cultivars commercially grown and processed in California.

    PubMed

    Haug, Megan T; King, Ellena S; Heymann, Hildegarde; Crisosto, Carlos H

    2013-08-01

    A trained sensory panel evaluated the 6 fig cultivars currently sold in the California dried fig market. The main flavor and aroma attributes determined by the sensory panel were "caramel," "honey," "raisin," and "fig," with additional aroma attributes: "common date," "dried plum," and "molasses." Sensory differences were observed between dried fig cultivars. All figs were processed by 2 commercial handlers. Processing included potassium sorbate as a preservative and SO2 application as an antibrowning agent for white cultivars. As a consequence of SO2 use during processing, high sulfite residues affected the sensory profiles of the white dried fig cultivars. Significant differences between dried fig cultivars and sources demonstrate perceived differences between processing and storage methods. The panel-determined sensory lexicon can help with California fig marketing. PMID:23957419

  6. Olfactive detection of fig wasps as prey by the ant Crematogaster scutellaris (Formicidae; Myrmicinae).

    PubMed

    Schatz, Bertrand; Anstett, Marie-Charlotte; Out, Welmoed; Hossaert-McKey, Martine

    2003-10-01

    In the species-specific and obligate mutualism between the fig (Ficus carica) and its pollinator (the fig wasps Blastophaga psenes), a third participant, the ant Crematogaster scutellaris, is a predator of the wasps. Here, we ask how ant workers can rapidly localise such prey, whose availability is limited in time and space. Using a Y-tube olfactometer, we tested ant response to odours emitted by different types of figs (receptive female, ripe female or male figs) and by fig wasps (pollinators or non-pollinators). We demonstrate that ants were significantly attracted only to odours emitted by pollinators, either alone or associated with odours of male figs (releasing wasps). Detection of prey odour by ants is an important trait that can explain their observed high rate of predation on pollinators, and could have important implications on the stability of the fig/fig wasp mutualism. PMID:14564404

  7. Sensory profiles for dried fig (Ficus carica L.) cultivars commercially grown and processed in California.

    PubMed

    Haug, Megan T; King, Ellena S; Heymann, Hildegarde; Crisosto, Carlos H

    2013-08-01

    A trained sensory panel evaluated the 6 fig cultivars currently sold in the California dried fig market. The main flavor and aroma attributes determined by the sensory panel were "caramel," "honey," "raisin," and "fig," with additional aroma attributes: "common date," "dried plum," and "molasses." Sensory differences were observed between dried fig cultivars. All figs were processed by 2 commercial handlers. Processing included potassium sorbate as a preservative and SO2 application as an antibrowning agent for white cultivars. As a consequence of SO2 use during processing, high sulfite residues affected the sensory profiles of the white dried fig cultivars. Significant differences between dried fig cultivars and sources demonstrate perceived differences between processing and storage methods. The panel-determined sensory lexicon can help with California fig marketing.

  8. CUL4B promotes replication licensing by up-regulating the CDK2-CDC6 cascade.

    PubMed

    Zou, Yongxin; Mi, Jun; Wang, Wenxing; Lu, Juanjuan; Zhao, Wei; Liu, Zhaojian; Hu, Huili; Yang, Yang; Gao, Xiaoxing; Jiang, Baichun; Shao, Changshun; Gong, Yaoqin

    2013-03-18

    Cullin-RING ubiquitin ligases (CRLs) participate in the regulation of diverse cellular processes including cell cycle progression. Mutations in the X-linked CUL4B, a member of the cullin family, cause mental retardation and other developmental abnormalities in humans. Cells that are deficient in CUL4B are severely selected against in vivo in heterozygotes. Here we report a role of CUL4B in the regulation of replication licensing. Strikingly, CDC6, the licensing factor in replication, was positively regulated by CUL4B and contributed to the loading of MCM2 to chromatin. The positive regulation of CDC6 by CUL4B depends on CDK2, which phosphorylates CDC6, protecting it from APC(CDH1)-mediated degradation. Thus, aside being required for cell cycle reentry from quiescence, CDK2 also contributes to pre-replication complex assembly in G1 phase of cycling cells. Interestingly, the up-regulation of CDK2 by CUL4B is achieved via the repression of miR-372 and miR-373, which target CDK2. Our findings thus establish a CUL4B-CDK2-CDC6 cascade in the regulation of DNA replication licensing.

  9. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis

    PubMed Central

    Cabrera, Sandra; Fernández, Álvaro F.; Mariño, Guillermo; Aguirre, Alina; Suárez, María F.; Español, Yaiza; Vega, José A.; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M. Soledad; Freije, José M.P.; Kroemer, Guido; López-Otín, Carlos

    2013-01-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b−/− mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b−/− mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency. PMID:23782979

  10. Structure based virtual screening to identify selective phosphodiesterase 4B inhibitors.

    PubMed

    Gangwal, Rahul P; Damre, Mangesh V; Das, Nihar R; Dhoke, Gaurao V; Bhadauriya, Anuseema; Varikoti, Rohith A; Sharma, Shyam S; Sangamwar, Abhay T

    2015-04-01

    Phosphodiesterase 4 (PDE4), is a hydrolytic enzyme, is proposed as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B selective inhibitors are desirable to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. To achieve this goal, ligand based pharmacophore modeling and molecular docking approach is employed. Pharmacophore hypotheses for PDE4B and PDE4D are generated using HypoGen algorithm. The best PDE4B pharmacophore hypothesis (Hypo1_PDE4B) consist of one hydrogen-bond acceptor and two ring aromatic features, whereas PDE4D pharmacophore hypothesis (Hypo1_PDE4D) consist of one hydrogen-bond acceptor, one hydrophobic aliphatic, and two ring aromatic features. The validated pharmacophore hypotheses are used in virtual screening to identify selective PDE4B inhibitors. The hits were screened for their estimated activity, FitValue, and quantitative estimation of drug likeness. After molecular docking analysis, ten hits were purchased for in vitro analysis. Out of these, six hits have shown potent and selective inhibitory activity against PDE4B with IC50 values ranging from 2 to 378nM.

  11. Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells.

    PubMed

    Huygens, Caroline; Liénart, Stéphanie; Dedobbeleer, Olivier; Stockis, Julie; Gauthy, Emilie; Coulie, Pierre G; Lucas, Sophie

    2015-08-14

    Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression.

  12. Modeling of two-phase flow instabilities during startup transients utilizing RAMONA-4B methodology

    SciTech Connect

    Paniagua, J.; Rohatgi, U.S.; Prasad, V.

    1996-10-01

    RAMONA-4B code is currently under development for simulating thermal hydraulic instabilities that can occur in Boiling Water Reactors (BWRs) and the Simplified Boiling Water Reactor (SBWR). As one of the missions of RAMONA-4B is to simulate SBWR startup transients, where geysering or condensation-induced instability may be encountered, the code needs to be assessed for this application. This paper outlines the results of the assessments of the current version of RAMONA-4B and the modifications necessary for simulating the geysering or condensation-induced instability. The test selected for assessment are the geysering tests performed by Prof Aritomi (1993).

  13. Tracking the elusive history of diversification in plant-herbivorous insect-parasitoid food webs: insights from figs and fig wasps.

    PubMed

    Kjellberg, Finn; Proffit, Magali

    2016-02-01

    The food webs consisting of plants, herbivorous insects and their insect parasitoids are a major component of terrestrial biodiversity. They play a central role in the functioning of all terrestrial ecosystems, and the number of species involved is mind-blowing (Nyman et al. 2015). Nevertheless, our understanding of the evolutionary and ecological determinants of their diversity is still in its infancy. In this issue of Molecular Ecology, Sutton et al. (2016) open a window into the comparative analysis of spatial genetic structuring in a set of comparable multitrophic models, involving highly species-specific interactions: figs and fig wasps. This is the first study to compare genetic structure using population genetics tools in a fig-pollinating wasp (Pleistodontes imperialis sp1) and its main parasitoid (Sycoscapter sp.A). The fig-pollinating wasp has a discontinuous spatial distribution that correlates with genetic differentiation, while the parasitoid bridges the discontinuity by parasitizing other pollinator species on the same host fig tree and presents basically no spatial genetic structure. The full implications of these results for our general understanding of plant-herbivorous insect-insect parasitoids diversification become apparent when envisioned within the framework of recent advances in fig and fig wasp biology.

  14. Tracking the elusive history of diversification in plant-herbivorous insect-parasitoid food webs: insights from figs and fig wasps.

    PubMed

    Kjellberg, Finn; Proffit, Magali

    2016-02-01

    The food webs consisting of plants, herbivorous insects and their insect parasitoids are a major component of terrestrial biodiversity. They play a central role in the functioning of all terrestrial ecosystems, and the number of species involved is mind-blowing (Nyman et al. 2015). Nevertheless, our understanding of the evolutionary and ecological determinants of their diversity is still in its infancy. In this issue of Molecular Ecology, Sutton et al. (2016) open a window into the comparative analysis of spatial genetic structuring in a set of comparable multitrophic models, involving highly species-specific interactions: figs and fig wasps. This is the first study to compare genetic structure using population genetics tools in a fig-pollinating wasp (Pleistodontes imperialis sp1) and its main parasitoid (Sycoscapter sp.A). The fig-pollinating wasp has a discontinuous spatial distribution that correlates with genetic differentiation, while the parasitoid bridges the discontinuity by parasitizing other pollinator species on the same host fig tree and presents basically no spatial genetic structure. The full implications of these results for our general understanding of plant-herbivorous insect-insect parasitoids diversification become apparent when envisioned within the framework of recent advances in fig and fig wasp biology. PMID:26876231

  15. Development of molecular tools for characterization and genetic diversity analysis in Tunisian fig (Ficus carica) cultivars.

    PubMed

    Chatti, Khaled; Baraket, Ghada; Ben Abdelkrim, Ahmed; Saddoud, Olfa; Mars, Messaoud; Trifi, Mokhtar; Salhi Hannachi, Amel

    2010-10-01

    Fig, Ficus carica L., is a useful genetic resource for commercial cultivation. In this study, RAPD (60), ISSR (48), RAMPO (63), and SSR (34) markers were compared to detect polymorphism and to establish genetic relationships among Tunisian fig tree cultivars. The statistical procedures conducted on the combined data show considerable genetic diversity, and the tested markers discriminated all fig genotypes studied. The identification key established on the basis of SSR permitted the unambiguous discrimination of cultivars and confirmed the reliability of SSR for fingerprinting fig genotypes. The study findings are discussed in relation to the establishment of a national reference collection that will aid in the conservation of Tunisian fig resources. PMID:20628809

  16. Development of molecular tools for characterization and genetic diversity analysis in Tunisian fig (Ficus carica) cultivars.

    PubMed

    Chatti, Khaled; Baraket, Ghada; Ben Abdelkrim, Ahmed; Saddoud, Olfa; Mars, Messaoud; Trifi, Mokhtar; Salhi Hannachi, Amel

    2010-10-01

    Fig, Ficus carica L., is a useful genetic resource for commercial cultivation. In this study, RAPD (60), ISSR (48), RAMPO (63), and SSR (34) markers were compared to detect polymorphism and to establish genetic relationships among Tunisian fig tree cultivars. The statistical procedures conducted on the combined data show considerable genetic diversity, and the tested markers discriminated all fig genotypes studied. The identification key established on the basis of SSR permitted the unambiguous discrimination of cultivars and confirmed the reliability of SSR for fingerprinting fig genotypes. The study findings are discussed in relation to the establishment of a national reference collection that will aid in the conservation of Tunisian fig resources.

  17. Multiple Horizontal Transfers of Bacteriophage WO and Host Wolbachia in Fig Wasps in a Closed Community.

    PubMed

    Wang, Ningxin; Jia, Sisi; Xu, Heng; Liu, Yong; Huang, Dawei

    2016-01-01

    Wolbachia-bacteriophage WO is a good model system for studying interactions between bacteria and viruses. Previous surveys of insect hosts have been conducted via sampling from open or semi-open communities; however, no studies have reported the infection patterns of phage WO of insects living in a closed community. Figs and fig wasps form a peculiar closed community in which the Ficus tree provides a compact syconium habitat for a variety of fig wasp. Therefore, in this study, we performed a thorough survey of Wolbachia and bacteriophage WO infection patterns in a total of 1406 individuals from 23 fig wasps species living on three different fig tree species. The infection rates of Wolbachia and phage WO were 82.6% (19/23) and 39.1% (9/23), respectively. Additionally, phage WO from fig wasps showed strong insect host specificity based on orf7 sequences from fig wasps and 21 other insect species. Probably due to the physical barrier of fig syconium, most phage WO from fig wasps form a specific clade. Phylogenetic analysis showed the absence of congruence between WO and host Wolbachia, WO and insect host, as well as Wolbachia and fig wasps, suggesting that both Wolbachia and phage WO exchanged frequently and independently within the closed syconium. Thus, the infection pattern of bacteriophage WO from fig wasps appeared quite different from that in other insects living outside, although the effect and the transfer routes of phage WO are unclear, which need to be investigated in the future.

  18. Multiple Horizontal Transfers of Bacteriophage WO and Host Wolbachia in Fig Wasps in a Closed Community

    PubMed Central

    Wang, Ningxin; Jia, Sisi; Xu, Heng; Liu, Yong; Huang, Dawei

    2016-01-01

    Wolbachia-bacteriophage WO is a good model system for studying interactions between bacteria and viruses. Previous surveys of insect hosts have been conducted via sampling from open or semi-open communities; however, no studies have reported the infection patterns of phage WO of insects living in a closed community. Figs and fig wasps form a peculiar closed community in which the Ficus tree provides a compact syconium habitat for a variety of fig wasp. Therefore, in this study, we performed a thorough survey of Wolbachia and bacteriophage WO infection patterns in a total of 1406 individuals from 23 fig wasps species living on three different fig tree species. The infection rates of Wolbachia and phage WO were 82.6% (19/23) and 39.1% (9/23), respectively. Additionally, phage WO from fig wasps showed strong insect host specificity based on orf7 sequences from fig wasps and 21 other insect species. Probably due to the physical barrier of fig syconium, most phage WO from fig wasps form a specific clade. Phylogenetic analysis showed the absence of congruence between WO and host Wolbachia, WO and insect host, as well as Wolbachia and fig wasps, suggesting that both Wolbachia and phage WO exchanged frequently and independently within the closed syconium. Thus, the infection pattern of bacteriophage WO from fig wasps appeared quite different from that in other insects living outside, although the effect and the transfer routes of phage WO are unclear, which need to be investigated in the future. PMID:26913026

  19. TAF4b is required for mouse spermatogonial stem cell development

    PubMed Central

    Lovasco, Lindsay A.; Gustafson, Eric A.; Seymour, Kimberly A.; de Rooij, Dirk G.; Freiman, Richard N.

    2014-01-01

    Long-term mammalian spermatogenesis requires proper development of spermatogonial stem cells (SSCs) that replenish the testis with germ cell progenitors during adult life. TAF4b is a gonadal-enriched component of the general transcription factor complex, TFIID, which is required for the maintenance of spermatogenesis in the mouse. Successful germ cell transplantation assays into adult TAF4b-deficient host testes suggested that TAF4b performs an essential germ cell autonomous function in SSC establishment and/or maintenance. To elucidate the SSC function of TAF4b, we characterized the initial gonocyte pool and rounds of spermatogenic differentiation in the context of the Taf4b-deficient mouse testis. Here we demonstrate a significant reduction in the late embryonic gonocyte pool and a deficient expansion of this pool soon after birth. Resulting from this reduction of germ cell progenitors is a developmental delay in meiosis initiation, as compared to age-matched controls. While GFRα1+ spermatogonia are appropriately present as Asingle and Apaired in wild type testes, TAF4b-deficient testes display an increased proportion of long and clustered chains of GFRα1+ cells. In the absence of TAF4b, seminiferous tubules in the adult testis either lack germ cells altogether or are found to have missing generations of spermatogenic progenitor cells. Together these data indicate that TAF4b-deficient spermatogenic progenitor cells display a tendency for differentiation at the expense of self-renewal and a renewing pool of SSCs fail to establish during the critical window of SSC development. PMID:25727968

  20. VizieR Online Data Catalog: XO-4b 3yr observations with DEMONEX (Villanueva+, 2016)

    NASA Astrophysics Data System (ADS)

    Villanueva, S. Jr; Eastman, J. D.; Gaudi, B. S.

    2016-06-01

    New observations of XO-4b were made using DEdicated MONitor of EXotransits (DEMONEX). DEMONEX monitored bright stars hosting known transiting planets over a 3yr period from 2008 to 2011 in order to provide a homogeneous data set of precise relative photometry for over 40 transiting systems. There are 20 nights of data from 2008 November to 2010 May taken during primary transits of XO-4b. All observations were made in the Sloan z band. (1 data file).

  1. Order Parameter measurements of Chromonic Liquid Crystal Benzopurpurin 4B using polarized Raman scattering

    NASA Astrophysics Data System (ADS)

    Nayani, Karthik; Park, Jung Ok; Srinivasarao, Mohan

    2012-02-01

    Benzopurpurin 4B (BPP4B), a commonly used textile dye, is known to form chromonic liquid crystal phases in aqueous solutions at fairly low concentrations (<0.5 wt%) in comparison with other chromonic liquid crystals. Also the aggregation properties and the structure of the aggregates in aqueous solutions of BPP4B are not well understood. Recently McKitterick et al. reported a study on the aggregation and phase behavior of BPP4B in water.ootnotetextC. B. McKitterick, N. L. Erb-Satullo, N. D. LaRacuente, A. J. Dickson, P. J. Collings. J. Phys. Chem. B. 2010. 114, 1888. Further understanding of the behavior of BPP4B in aqueous solutions can be gained by studying how the order parameter of its liquid crystalline phase varies with some relevant parameters. Planar monodomains of BPP4B were obtained using a flat rectangular capillary. Thermal evolution of the order parameter of these aligned monodomains was carried out using polarized Raman scattering measurements. Further, the concentration dependence and the effect of salt on the order parameter were studied. The variation of the order parameter with the above parameters was correlated to the structure of the aggregates using the UV-Vis absorption data.

  2. Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

    PubMed Central

    Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

  3. Relative investment in egg load and poison sac in fig wasps: Implications for physiological mechanisms underlying seed and wasp production in figs

    NASA Astrophysics Data System (ADS)

    Martinson, Ellen O.; Jandér, K. Charlotte; Peng, Yan-Qiong; Chen, Huan-Huan; Machado, Carlos A.; Arnold, A. Elizabeth; Herre, Edward Allen

    2014-05-01

    Fig pollinating wasps and most non-pollinator wasps apply secretions from their poison sacs into oviposited flowers that appear necessary to the formation of the galls that their developing offspring consume. Thus, both eggs and poison sac secretions appear to be essential for wasp reproduction, but the relative investment in each is unknown. We measured relative investment in poison sac and egg production in pollinating and non-pollinating wasps associated with seven species of monoecious Panamanian figs representing both active and passive pollination syndromes. We then collected similar data for four fig hosts in China, where some wasp species in the genus Eupristina have lost the ability to pollinate ("cheaters"). All wasps examined possessed large poison sacs, and we found a strong positive correlation between poison sac size and absolute egg production. In the Panamanian species, the relative poison sac to egg investment was highest in the externally ovipositing non-pollinator wasps, followed by active pollinators, then by passive pollinators. Further, pollinator wasps of fig species with demonstrated host sanctions against "cheating" wasps showed higher investment in the poison sac than wasps of species without sanctions. In the Chinese samples, relative investment in the poison sac was indistinguishable between pollinators and "cheaters" associated with the same fig species. We suggest that higher relative investment in poison sac across fig wasp species reflects higher relative difficulty in initiating formation of galls and subsequently obtaining resources from the fig. We discuss the implications for the stability of the fig-wasp mutualism, and for the ability of non-pollinators to exploit this mutualism.

  4. Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B

    PubMed Central

    Woodfield, Sarah E.; Guo, Rong Jun; Liu, Yin; Major, Angela M.; Hollingsworth, Emporia Faith; Indiviglio, Sandra; Whittle, Sarah B.; Mo, Qianxing; Bean, Andrew J.; Ittmann, Michael; Lopez-Terrada, Dolores; Zage, Peter E.

    2016-01-01

    Background UBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology. Methods We evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines. Results Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK. Conclusions We have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation. PMID:27014418

  5. Same but different: Larval development and gall-inducing process of a non-pollinating fig wasp compared to that of pollinating fig-wasps

    NASA Astrophysics Data System (ADS)

    Jansen-González, Sergio; Teixeira, Simone de Padua; Kjellberg, Finn; Pereira, Rodrigo A. Santinelo

    2014-05-01

    The receptacles of fig trees (Ficus spp.) can harbor a highly diversified and complex community of chalcid wasps. Functional groups of fig wasps (e.g. gallers, cleptoparasites and parasitoids) oviposit into the fig at different developmental stages, reflecting different feeding regimes for these insect larvae. There are few direct data available on larval feeding regimes and access to resources. We studied the gall induction and larval feeding strategy of an Idarnes (group flavicollis) species, a non-pollinating fig wasp (NPFW) associated to Ficus citrifolia P. Miller in Brazil. This Idarnes species shares with the pollinator characteristics such as time of oviposition, ovipositor insertion through flower and location of the egg inside plant ovaries. Nevertheless, we show that the gall induction differs considerably from that of the pollinating species. This Idarnes species relies on the induction of nucellus cell proliferation for gall formation and as the main larval resource. This strategy enables it to develop in both pollinated and unpollinated figs. The large differences between this NPFW and other fig wasps in how ovules are galled suggest that there are different ways to be a galler. A functional analysis of NPFW community structure may require descriptions of the histological processes associated with larval development.

  6. Pollinator sharing and gene flow among closely related sympatric dioecious fig taxa.

    PubMed

    Wang, Gang; Cannon, Charles H; Chen, Jin

    2016-04-13

    Hybridization and insect pollination are widely believed to increase rates of plant diversification. The extreme diversity of figs (Ficus) and their obligate pollinators, fig wasps (Agaonidae), provides an opportunity to examine the possible role of pollinator-mediated hybridization in plant diversification. Increasing evidence suggests that pollinator sharing and hybridization occurs among fig taxa, despite relatively strict coevolution with the pollinating wasp. Using five sympatric dioecious fig taxa and their pollinators, we examine the degree of pollinator sharing and inter-taxa gene flow. We experimentally test pollinator preference for floral volatiles, the main host recognition signal, from different figs. All five fig taxa shared pollinators with other taxa, and gene flow occurred between fig taxa within and between sections. Floral volatiles of each taxon attracted more than one pollinator species. Floral volatiles were more similar between closely related figs, which experienced higher levels of pollinator sharing and inter-taxa gene flow. This study demonstrates that pollinator sharing and inter-taxa gene flow occurs among closely related sympatric dioecious fig taxa and that pollinators choose the floral volatiles of multiple fig taxa. The implications of pollinator sharing and inter-taxa gene flow on diversification, occurring even in this highly specialized obligate pollination system, require further study. PMID:27075252

  7. Pollinator sharing and gene flow among closely related sympatric dioecious fig taxa.

    PubMed

    Wang, Gang; Cannon, Charles H; Chen, Jin

    2016-04-13

    Hybridization and insect pollination are widely believed to increase rates of plant diversification. The extreme diversity of figs (Ficus) and their obligate pollinators, fig wasps (Agaonidae), provides an opportunity to examine the possible role of pollinator-mediated hybridization in plant diversification. Increasing evidence suggests that pollinator sharing and hybridization occurs among fig taxa, despite relatively strict coevolution with the pollinating wasp. Using five sympatric dioecious fig taxa and their pollinators, we examine the degree of pollinator sharing and inter-taxa gene flow. We experimentally test pollinator preference for floral volatiles, the main host recognition signal, from different figs. All five fig taxa shared pollinators with other taxa, and gene flow occurred between fig taxa within and between sections. Floral volatiles of each taxon attracted more than one pollinator species. Floral volatiles were more similar between closely related figs, which experienced higher levels of pollinator sharing and inter-taxa gene flow. This study demonstrates that pollinator sharing and inter-taxa gene flow occurs among closely related sympatric dioecious fig taxa and that pollinators choose the floral volatiles of multiple fig taxa. The implications of pollinator sharing and inter-taxa gene flow on diversification, occurring even in this highly specialized obligate pollination system, require further study.

  8. Insights into K-Ras 4B regulation by post-translational lysine acetylation.

    PubMed

    Knyphausen, Philipp; Lang, Franziska; Baldus, Linda; Extra, Antje; Lammers, Michael

    2016-10-01

    Ras is a molecular switch cycling between an active, GTP-bound and an inactive, GDP-bound state. Mutations in Ras, mostly affecting the off-switch, are found in many human tumours. Recently, it has been shown that K-Ras 4B is targeted by lysine acetylation at K104. Based on results obtained for an acetylation mimetic Ras mutant (K104Q), it was hypothesised that K104-acetylation might interfere with its oncogenicity by impairing SOS-catalysed guanine-nucleotide exchange. We prepared site-specifically K104-acetylated K-Ras 4B and the corresponding oncogenic mutant protein G12V using the genetic-code expansion concept. We found that SOS-catalysed nucleotide exchange, also of allosterically activated SOS, was neither affected by acetylation of K104 in wildtype K-Ras 4B nor in the G12V mutant, suggesting that glutamine is a poor mimetic for acetylation at this site. In vitro, the lysine-acetyltransferases CBP and p300 were able to acetylate both, wildtype and G12V K-Ras 4B. In addition to K104 we identified further acetylation sites in K-Ras 4B, including K147, within the important G5/SAK-motif. However, the intrinsic and the SOS-catalysed nucleotide exchange was not affected by K147-acetylation of K-Ras 4B. Finally, we show that Sirt2 and HDAC6 do neither deacetylate K-Ras 4B if acetylated at K104 nor if acetylated at K147 in vitro.

  9. Structural and functional comparison of the non-structural protein 4B in flaviviridae.

    PubMed

    Welsch, Christoph; Albrecht, Mario; Maydt, Jochen; Herrmann, Eva; Welker, Martin Walter; Sarrazin, Christoph; Scheidig, Axel; Lengauer, Thomas; Zeuzem, Stefan

    2007-09-01

    Flaviviridae are evolutionarily related viruses, comprising the hepatitis C virus (HCV), with the non-structural protein 4B (NS4B) as one of the least characterized proteins. NS4B is located in the endoplasmic reticulum membrane and is assumed to be a multifunctional protein. However, detailed structure information is missing. The hydrophobic nature of NS4B is a major difficulty for many experimental techniques. We applied bioinformatics methods to analyse structural and functional properties of NS4B in different viruses. We distinguish a central non-globular membrane portion with four to five transmembrane regions from an N- and C-terminal part with non-transmembrane helical elements. We demonstrate high similarity in sequence and structure for the C-terminal part within the flaviviridae family. A palmitoylation site contained in the C-terminal part of HCV is equally conserved in GB virus B. Furthermore, we identify and characterize an N-terminal basic leucine zipper (bZIP) motif in HCV, which is suggestive of a functionally important interaction site. In addition, we model the interaction of the bZIP region with the recently identified interaction partner CREB-RP/ATF6beta, a human activating transcription factor involved in ER-stress. In conclusion, the versatile structure, together with functional sites and motifs, possibly enables NS4B to adopt a role as protein hub in the membranous web interaction network of virus and host proteins. Important structural and functional properties of NS4B are predicted with implications for ER-stress response, altered gene expression and replication efficacy.

  10. Caprine herpesvirus 1 (CpHV-1) vaginal infection of goats: clinical efficacy of fig latex.

    PubMed

    Camero, Michele; Marinaro, Mariarosaria; Losurdo, Michele; Larocca, Vittorio; Bodnar, Livia; Patruno, Giovanni; Buonavoglia, Canio; Tempesta, Maria

    2016-01-01

    The latex of Ficus carica Linn. (Moraceae) has been shown to interfere with the replication of caprine herpesvirus (CpHV)-1 in vitro. The present study was undertaken to determine the efficacy of vaginal administration of fig latex in goats experimentally infected with CpHV-1. The fig latex reduced the clinical signs of the herpetic disease although it slightly influenced the titres of CpHV-1 shed. Thus, the fig latex maintained a partial efficacy in vivo.

  11. Utilisation of chemical signals by inquiline wasps in entering their host figs.

    PubMed

    Gu, Ding; Yang, Da-Rong

    2013-10-01

    The fig tree, Ficus curtipes, hosts an obligate pollinating wasp, an undescribed Eupristina sp., but can also be pollinated by two inquiline (living in the burrow, nest, gall, or other habitation of another animal) wasps, Diaziella yangi and an undescribed Lipothymus sp. The two inquilines are unable to independently induce galls and depend on the galls induced by the obligate pollinator for reproduction and, therefore, normally enter receptive F. curtipes figs colonised by the obligate pollinators. However, sometimes the inquilines also enter figs that are not colonised by the pollinators, despite consequent reproductive failure. It is still unknown which signal(s) the inquilines use in entering the colonised and non-colonised figs. We conducted behavioural experiments to investigate several possible signals utilised by the inquilines in entering their host receptive figs. Our investigation showed that both inquiline species enter the receptive F. curtipes figs in response to the body odours of the obligate wasps and one of the main compounds emitted by the figs, 6-methyl-5-hepten-2-one. The compound was not found in the pollinator body odours, suggesting that the two inquiline wasps can utilise two signals to enter their host figs, which is significant for the evolution of the fig-fig wasp system. These inquilines could evolve to become mutualists of the figs if they evolve the ability to independently gall fig flowers; there is, however, another possibility that a monoecious Ficus species hosting such inquilines may evolve into a dioecious one if these inquilines cannot evolve the above-mentioned ability. Additionally, this finding provides evidence for the evolution of chemical communication between plants and insects.

  12. High-Pressure Synthesis and Crystal Structure of Ce4B14O27

    PubMed Central

    Hinteregger, Ernst; Perfler, Lukas; Huppertz, Hubert

    2013-01-01

    Ce4B14O27 was synthesized under conditions of 2.6 GPa and 750 °C in a Walker-type multianvil apparatus. The crystal structure was determined on the basis of single-crystal X-ray diffraction data, collected at room temperature, revealing that Ce4B14O27 is isotypic to La4B14O27. Ce4B14O27 crystallizes monoclinically with four formula units in the space group C2/c (No. 15) and the lattice parameters a = 1117.8(2), b = 640.9(2), c = 2531.7(5) pm, and β = 100.2(1)°. The three-dimensional boron-oxygen framework consists of [BO4]5– tetrahedra and trigonal-planar [BO3]3– groups. The structure contains two crystallographically different cerium ions. Furthermore, Raman spectroscopy was performed on single crystals of Ce4B14O27. PMID:25995523

  13. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

    PubMed

    Cabrera, Sandra; Maciel, Mariana; Herrera, Iliana; Nava, Teresa; Vergara, Fabián; Gaxiola, Miguel; López-Otín, Carlos; Selman, Moisés; Pardo, Annie

    2015-04-01

    Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

  14. TAF4b Promotes Mouse Primordial Follicle Assembly and Oocyte Survival

    PubMed Central

    Grive, Kathryn J.; Seymour, Kimberly A.; Mehta, Rajvi; Freiman, Richard N.

    2014-01-01

    Primary ovarian insufficiency (POI) affects 1% of women under the age of 40 and is associated with premature ovarian follicle depletion. TAF4b deficiency in adult female mouse models results in hallmarks of POI including stereotyped gonadotropin alterations indicative of early menopause, poor oocyte quality, and infertility. However, the precise developmental mechanisms underlying these adult deficits remain unknown. Here we show that TAF4b is required for the initial establishment of the primordial follicle reserve at birth. Ovaries derived from TAF4b-deficient mice at birth exhibit delayed germ cell cyst breakdown and a significant increase in Activated Caspase 3 staining compared to control ovaries. Culturing neonatal TAF4b-deficient ovaries with the pan-caspase inhibitor ZVAD-FMK suppresses the excessive loss of these oocytes around the time of birth. These data reveal a novel TAF4b function in orchestrating the correct timing of germ cell cyst breakdown and establishment of the primordial follicle reserve during a critical window of development. PMID:24836512

  15. A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms.

    PubMed

    Perez-Lorenzo, Rolando; Gill, Kamraan Z; Shen, Che-Hung; Zhao, Feng X; Zheng, Bin; Schulze, Hans-Joachim; Silvers, David N; Brunner, Georg; Horst, Basil A

    2014-05-01

    The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

  16. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors.

    PubMed

    Akin, Debra; Wang, S Keisin; Habibzadegah-Tari, Pouran; Law, Brian; Ostrov, David; Li, Min; Yin, Xiao-Ming; Kim, Jae-Sung; Horenstein, Nicole; Dunn, William A

    2014-01-01

    Autophagy has been implicated in the progression and chemoresistance of various cancers. In this study, we have shown that osteosarcoma Saos-2 cells lacking ATG4B, a cysteine proteinase that activates LC3B, are defective in autophagy and fail to form tumors in mouse models. By combining in silico docking with in vitro and cell-based assays, we identified small compounds that suppressed starvation-induced protein degradation, LC3B lipidation, and formation of autophagic vacuoles. NSC185058 effectively inhibited ATG4B activity in vitro and in cells while having no effect on MTOR and PtdIns3K activities. In addition, this ATG4B antagonist had a negative impact on the development of Saos-2 osteosarcoma tumors in vivo. We concluded that tumor suppression was due to a reduction in ATG4B activity, since we found autophagy suppressed within treated tumors and the compound had no effects on oncogenic protein kinases. Our findings demonstrate that ATG4B is a suitable anti-autophagy target and a promising therapeutic target to treat osteosarcoma. PMID:25483883

  17. Longevity, early emergence and body size in a pollinating fig wasp--implications for stability in a fig-pollinator mutualism.

    PubMed

    Dunn, Derek W; Yu, Douglas W; Ridley, Jo; Cook, James M

    2008-09-01

    1. Fig trees (Ficus) are pollinated only by agaonid wasps, whose larvae also gall fig ovules. Each ovule develops into either a seed (when pollinated) or a wasp (when an egg is also laid inside) but not both. 2. Ovipositing wasps (foundresses) favour ovules near the centre of the enclosed inflorescence (syconium or 'fig'), leaving ovules near the outer wall to develop into seeds. This spatial stratification of wasps and seeds ensures reproduction in both partners, and thereby enables mutualism persistence. However, the mechanism(s) responsible remain(s) unknown. 3. Theory shows that foundresses will search for increasingly rare inner ovules and ignore outer ovules, as long as ovipositing in outer ovules is sufficiently slow and/or if inner ovules confer greater fitness to wasps. The fig-pollinator mutualism can therefore be stabilized by strong time constraints on foundresses and by offspring fitness gradients over variation in ovule position. 4. Female fig wasps cannot leave their galls without male assistance. We found that females in outer ovules were unlikely to be released. Inner ovules thus have added value to foundresses, because their female offspring are more likely to mate and disperse. 5. For those offspring that did emerge, gall position (inner/outer) and body size did not influence the order in which female pollinators exited syconia, nor did early emerging wasps enjoy increased life spans. 6. We also found that the life spans of female wasps nearly doubled when given access to moisture. We suggest that conflict resolution in the fig-pollinator mutualism may thus be influenced by tropical seasonality, because wasps may be less able to over-exploit ovules in dry periods due to time constraints.

  18. Lack of Cul4b, an E3 Ubiquitin Ligase Component, Leads to Embryonic Lethality and Abnormal Placental Development

    PubMed Central

    Yuan, Jupeng; Qian, Yanyan; Sun, Wenjie; Zou, Yongxin; Guo, Chenhong; Chen, Bingxi; Shao, Changshun; Gong, Yaoqin

    2012-01-01

    Cullin-RING ligases (CRLs) complexes participate in the regulation of diverse cellular processes, including cell cycle progression, transcription, signal transduction and development. Serving as the scaffold protein, cullins are crucial for the assembly of ligase complexes, which recognize and target various substrates for proteosomal degradation. Mutations in human CUL4B, one of the eight members in cullin family, are one of the major causes of X-linked mental retardation. We here report the generation and characterization of Cul4b knockout mice, in which exons 3 to 5 were deleted. In contrast to the survival to adulthood of human hemizygous males with CUL4B null mutation, Cul4b null mouse embryos show severe developmental arrest and usually die before embryonic day 9.5 (E9.5). Accumulation of cyclin E, a CRL (CUL4B) substrate, was observed in Cul4b null embryos. Cul4b heterozygotes were recovered at a reduced ratio and exhibited a severe developmental delay. The placentas in Cul4b heterozygotes were disorganized and were impaired in vascularization, which may contribute to the developmental delay. As in human CUL4B heterozygotes, Cul4b null cells were selected against in Cul4b heterozygotes, leading to various degrees of skewed X-inactivation in different tissues. Together, our results showed that CUL4B is indispensable for embryonic development in the mouse. PMID:22606329

  19. Protection against Asiatic Taenia solium induced by a recombinant 45W-4B protein.

    PubMed

    Luo, Xuenong; Zheng, Yadong; Hou, Junling; Zhang, Shaohua; Cai, Xuepeng

    2009-02-01

    Taenia solium is a great threat not only to human health but also to the pig-raising industry. Oncospheral stage-specific 45W proteins are good candidates for the development of anticysticercosis vaccines. In this study, a recombinant 45W-4B protein was highly produced and used for vaccination. Two animal trials resulted in a significant reduction in parasite burden induced by the definite protein against Asiatic T. solium, up to 97.0% and 98.4%, respectively. These provide informative results for the development of effective 45W-4B vaccines against cysticercosis caused by both Chinese and Mexican T. solium isolates and even by other isolates.

  20. Evolution and Expression Plasticity of Opsin Genes in a Fig Pollinator, Ceratosolen solmsi

    PubMed Central

    Bian, Sheng-Nan; Niu, Li-Ming; Murphy, Robert W.; Huang, Da-Wei

    2013-01-01

    Figs and fig pollinators have co-evolved species-specific systems of mutualism. So far, it was unknown how visual opsin genes of pollinators have evolved in the light conditions inside their host figs. We cloned intact full-length mRNA sequences of four opsin genes from a species of fig pollinator, Ceratosolen solmsi, and tested for selective pressure and expressional plasticity of these genes. Molecular evolutionary analysis indicated that the four opsin genes evolved under different selective constraints. Subsets of codons in the two long wavelength sensitive opsin (LW1, LW2) genes were positively selected in ancestral fig pollinators. The ultraviolet sensitive opsin (UV) gene was under strong purifying selection, whereas a relaxation of selective constrains occurred on several amino acids in the blue opsin. RT-qPCR analysis suggested that female and male fig pollinators had different expression patterns possibly due to their distinct lifestyles and different responses to light within the syconia. Co-evolutionary history with figs might have influenced the evolution and expression plasticity of opsin genes in fig pollinators. PMID:23342036

  1. Describing the appearance and flavor profiles of fresh fig (Ficus carica L.) cultivars.

    PubMed

    King, Ellena S; Hopfer, Helene; Haug, Megan T; Orsi, Jennifer D; Heymann, Hildegarde; Crisosto, Gayle M; Crisosto, Carlos H

    2012-12-01

    Twelve fig cultivars, including cultivars destined for the fresh and dried markets, were harvested from 6 locations and evaluated by a trained panel using descriptive sensory analysis. Instrumental measurements were taken at harvest and also during sensory analysis. Each fresh fig cultivar had a characteristic appearance and flavor sensory profile regardless of the source. The primary flavor attributes used to describe the fig cultivars were "fruity,"melon,"stone fruit,"berry,"citrus,"honey,"green," and "cucumber." Maturity levels significantly affected the chemical composition and sensory profiles of the fig cultivars. Less mature figs had a higher compression force, a thicker outer skin, and higher ratings for "green" and "latex" flavors, firmness, graininess, bitterness, tingling, and seed adhesiveness. Meanwhile, more mature figs had higher soluble solids concentration, and were perceptibly higher in "fruit" flavors, juiciness, stickiness, sliminess, and sweetness. The specific sensory terminology used for fig appearance and flavor profiles will assist with communication between marketers and consumers, which can increase fresh fig consumption. PMID:23170947

  2. Wine and vinegar-based attractants for the African fig fly (Diptera: Drosophilidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The African fig fly (AFF), Zaprionus indianus Gupta (Diptera: Drosophilidae), is an invasive fruit pest that has spread rapidly through much of the eastern United States after first being detected in Florida in 2005. This drosophilid is a primary pest of figs in Brazil, so there were initial concern...

  3. Study on Optimal Extracting Conditions and Anti-Cancer Effects of Fig Flavones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As dietary components, flavones have health-promoting properties due to their high antioxidant capacity both in vivo and in vitro systems. Figs have been consumed as both herb medicine and popular fruit in daily life due to its polyphones, flavones and anthocyanins. However, fig residue from juice...

  4. Chaos of Wolbachia Sequences Inside the Compact Fig Syconia of Ficus benjamina (Ficus: Moraceae)

    PubMed Central

    Niu, Li-Ming; Ma, Guang-Chang; Cook, James M.; Bian, Sheng-Nan; Fu, Yue-Guan; Huang, Da-Wei

    2012-01-01

    Figs and fig wasps form a peculiar closed community in which the Ficus tree provides a compact syconium (inflorescence) habitat for the lives of a complex assemblage of Chalcidoid insects. These diverse fig wasp species have intimate ecological relationships within the closed world of the fig syconia. Previous surveys of Wolbachia, maternally inherited endosymbiotic bacteria that infect vast numbers of arthropod hosts, showed that fig wasps have some of the highest known incidences of Wolbachia amongst all insects. We ask whether the evolutionary patterns of Wolbachia sequences in this closed syconium community are different from those in the outside world. In the present study, we sampled all 17 fig wasp species living on Ficus benjamina, covering 4 families, 6 subfamilies, and 8 genera of wasps. We made a thorough survey of Wolbachia infection patterns and studied evolutionary patterns in wsp (Wolbachia Surface Protein) sequences. We find evidence for high infection incidences, frequent recombination between Wolbachia strains, and considerable horizontal transfer, suggesting rapid evolution of Wolbachia sequences within the syconium community. Though the fig wasps have relatively limited contact with outside world, Wolbachia may be introduced to the syconium community via horizontal transmission by fig wasps species that have winged males and visit the syconia earlier. PMID:23145008

  5. Host-plant species conservatism and ecology of a parasitoid fig wasp genus (Chalcidoidea; Sycoryctinae; Arachonia).

    PubMed

    McLeish, Michael J; Beukman, Gary; van Noort, Simon; Wossler, Theresa C

    2012-01-01

    Parasitoid diversity in terrestrial ecosystems is enormous. However, ecological processes underpinning their evolutionary diversification in association with other trophic groups are still unclear. Specialisation and interdependencies among chalcid wasps that reproduce on Ficus presents an opportunity to investigate the ecology of a multi-trophic system that includes parasitoids. Here we estimate the host-plant species specificity of a parasitoid fig wasp genus that attacks the galls of non-pollinating pteromalid and pollinating agaonid fig wasps. We discuss the interactions between parasitoids and the Ficus species present in a forest patch of Uganda in context with populations in Southern Africa. Haplotype networks are inferred to examine intraspecific mitochondrial DNA divergences and phylogenetic approaches used to infer putative species relationships. Taxonomic appraisal and putative species delimitation by molecular and morphological techniques are compared. Results demonstrate that a parasitoid fig wasp population is able to reproduce on at least four Ficus species present in a patch. This suggests that parasitoid fig wasps have relatively broad host-Ficus species ranges compared to fig wasps that oviposit internally. Parasitoid fig wasps did not recruit on all available host plants present in the forest census area and suggests an important ecological consequence in mitigating fitness trade-offs between pollinator and Ficus reproduction. The extent to which parasitoid fig wasps exert influence on the pollination mutualism must consider the fitness consequences imposed by the ability to interact with phenotypes of multiple Ficus and fig wasps species, but not equally across space and time.

  6. Chaos of Wolbachia sequences inside the compact fig syconia of Ficus benjamina (Ficus: moraceae).

    PubMed

    Yang, Chun-Yan; Xiao, Jin-Hua; Niu, Li-Ming; Ma, Guang-Chang; Cook, James M; Bian, Sheng-Nan; Fu, Yue-Guan; Huang, Da-Wei

    2012-01-01

    Figs and fig wasps form a peculiar closed community in which the Ficus tree provides a compact syconium (inflorescence) habitat for the lives of a complex assemblage of Chalcidoid insects. These diverse fig wasp species have intimate ecological relationships within the closed world of the fig syconia. Previous surveys of Wolbachia, maternally inherited endosymbiotic bacteria that infect vast numbers of arthropod hosts, showed that fig wasps have some of the highest known incidences of Wolbachia amongst all insects. We ask whether the evolutionary patterns of Wolbachia sequences in this closed syconium community are different from those in the outside world. In the present study, we sampled all 17 fig wasp species living on Ficus benjamina, covering 4 families, 6 subfamilies, and 8 genera of wasps. We made a thorough survey of Wolbachia infection patterns and studied evolutionary patterns in wsp (Wolbachia Surface Protein) sequences. We find evidence for high infection incidences, frequent recombination between Wolbachia strains, and considerable horizontal transfer, suggesting rapid evolution of Wolbachia sequences within the syconium community. Though the fig wasps have relatively limited contact with outside world, Wolbachia may be introduced to the syconium community via horizontal transmission by fig wasps species that have winged males and visit the syconia earlier.

  7. Describing the appearance and flavor profiles of fresh fig (Ficus carica L.) cultivars.

    PubMed

    King, Ellena S; Hopfer, Helene; Haug, Megan T; Orsi, Jennifer D; Heymann, Hildegarde; Crisosto, Gayle M; Crisosto, Carlos H

    2012-12-01

    Twelve fig cultivars, including cultivars destined for the fresh and dried markets, were harvested from 6 locations and evaluated by a trained panel using descriptive sensory analysis. Instrumental measurements were taken at harvest and also during sensory analysis. Each fresh fig cultivar had a characteristic appearance and flavor sensory profile regardless of the source. The primary flavor attributes used to describe the fig cultivars were "fruity,"melon,"stone fruit,"berry,"citrus,"honey,"green," and "cucumber." Maturity levels significantly affected the chemical composition and sensory profiles of the fig cultivars. Less mature figs had a higher compression force, a thicker outer skin, and higher ratings for "green" and "latex" flavors, firmness, graininess, bitterness, tingling, and seed adhesiveness. Meanwhile, more mature figs had higher soluble solids concentration, and were perceptibly higher in "fruit" flavors, juiciness, stickiness, sliminess, and sweetness. The specific sensory terminology used for fig appearance and flavor profiles will assist with communication between marketers and consumers, which can increase fresh fig consumption.

  8. Pollinator-mediated reproductive isolation among dioecious fig species (Ficus, Moraceae).

    PubMed

    Moe, Annika M; Weiblen, George D

    2012-12-01

    The extent of isolation among closely related sympatric plant species engaged in obligate pollination mutualisms depends on the fitness consequences of interspecies floral visitation. In figs (Ficus), interspecific gene flow may occur when pollinating wasps (Agaonidae) visit species other than their natal fig species. We studied reproductive isolation in a clade of six sympatric dioecious fig species in New Guinea. Microsatellite genotyping and Bayesian clustering analysis of the fig community indicated strong reproductive barriers among sympatric species. A total of 1-2% of fig populations consisted of hybrid individuals. A new experimental method of manipulating fig wasps investigated the reproductive consequences of conspecific and heterospecific pollinator visitation for both mutualists. Fig wasps introduced to Ficus hispidioides pollinated and oviposited in receptive figs. Seed development and seedling growth were largely comparable between conspecific and heterospecific crosses. Heterospecific pollinator fitness, however, was significantly less than that of conspecific pollinators. Heterospecific pollinators induced gall formation but offspring did not develop to maturity in the new host. Selection on pollinators maintaining host specificity appears to be an important mechanism of contemporary reproductive isolation among these taxa that could potentially influence their diversification.

  9. Evolution and expression plasticity of opsin genes in a fig pollinator, Ceratosolen solmsi.

    PubMed

    Wang, Bo; Xiao, Jin-Hua; Bian, Sheng-Nan; Niu, Li-Ming; Murphy, Robert W; Huang, Da-Wei

    2013-01-01

    Figs and fig pollinators have co-evolved species-specific systems of mutualism. So far, it was unknown how visual opsin genes of pollinators have evolved in the light conditions inside their host figs. We cloned intact full-length mRNA sequences of four opsin genes from a species of fig pollinator, Ceratosolen solmsi, and tested for selective pressure and expressional plasticity of these genes. Molecular evolutionary analysis indicated that the four opsin genes evolved under different selective constraints. Subsets of codons in the two long wavelength sensitive opsin (LW1, LW2) genes were positively selected in ancestral fig pollinators. The ultraviolet sensitive opsin (UV) gene was under strong purifying selection, whereas a relaxation of selective constrains occurred on several amino acids in the blue opsin. RT-qPCR analysis suggested that female and male fig pollinators had different expression patterns possibly due to their distinct lifestyles and different responses to light within the syconia. Co-evolutionary history with figs might have influenced the evolution and expression plasticity of opsin genes in fig pollinators.

  10. Host-Plant Species Conservatism and Ecology of a Parasitoid Fig Wasp Genus (Chalcidoidea; Sycoryctinae; Arachonia)

    PubMed Central

    McLeish, Michael J.; Beukman, Gary; van Noort, Simon; Wossler, Theresa C.

    2012-01-01

    Parasitoid diversity in terrestrial ecosystems is enormous. However, ecological processes underpinning their evolutionary diversification in association with other trophic groups are still unclear. Specialisation and interdependencies among chalcid wasps that reproduce on Ficus presents an opportunity to investigate the ecology of a multi-trophic system that includes parasitoids. Here we estimate the host-plant species specificity of a parasitoid fig wasp genus that attacks the galls of non-pollinating pteromalid and pollinating agaonid fig wasps. We discuss the interactions between parasitoids and the Ficus species present in a forest patch of Uganda in context with populations in Southern Africa. Haplotype networks are inferred to examine intraspecific mitochondrial DNA divergences and phylogenetic approaches used to infer putative species relationships. Taxonomic appraisal and putative species delimitation by molecular and morphological techniques are compared. Results demonstrate that a parasitoid fig wasp population is able to reproduce on at least four Ficus species present in a patch. This suggests that parasitoid fig wasps have relatively broad host-Ficus species ranges compared to fig wasps that oviposit internally. Parasitoid fig wasps did not recruit on all available host plants present in the forest census area and suggests an important ecological consequence in mitigating fitness trade-offs between pollinator and Ficus reproduction. The extent to which parasitoid fig wasps exert influence on the pollination mutualism must consider the fitness consequences imposed by the ability to interact with phenotypes of multiple Ficus and fig wasps species, but not equally across space and time. PMID:22970309

  11. Secondary Structure and Membrane Topology of the Full-Length Dengue Virus NS4B in Micelles.

    PubMed

    Li, Yan; Wong, Ying Lei; Lee, Michelle Yueqi; Li, Qingxin; Wang, Qing-Yin; Lescar, Julien; Shi, Pei-Yong; Kang, CongBao

    2016-09-19

    Dengue virus nonstructural protein 4B (NS4B) is a membrane protein consisting of 248 residues with a crucial role in virus replication and interference with the host innate immunity. The dengue virus serotype 3 NS4B was reconstituted into lyso-myristoyl phosphatidylglycerol (LMPG) micelles. Backbone resonance assignment of NS4B was obtained using conventional solution NMR experiments. Further studies suggested that NS4B contained eleven helices and six of them form five potential transmembrane regions. This study provides atomic level information for an important drug target to control flavivirus infections. PMID:27554985

  12. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NEW SULFONAMIDE ISOXAZOLO[5,4-b]PYRIDINE DERIVATIVES.

    PubMed

    Poręba, Krystyna; Pawlik, Krzysztof; Rembacz, Krzysztof P; Kurowska, Ewa; Matuszyk, Janusz; Długosz, Anna

    2015-01-01

    A series of novel sulfonamide isoxazolo[5,4-b]pyridines were synthesized. The substrates for their synthesis were 3-aminoisoxazolo[5,4-b]pyridine and selected aryl sulfonic chlorides, chlorosulfonic acid and selected amines. Reactions were carried out using the classical and microwave methods. Selected compounds were tested towards antibacterial and antiproliferative activity. The structure of the obtained new derivatives was determined by elemental analysis and acquired IR and 1H NMR spectra. Among the tested compounds: N- isoxazolo[5,4-b]pyridine-3-yl-benzenesulfonamide (2) and N-isoxazolo[5,4-b]pyridine-3-yl-4-methylbenzene-sulfonamide (5) showed antimicrobial activity towards Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922) at doses: 125, 250 and 500 µg. Both compounds showed a 50% inhibition of proliferation of breast carcinoma cell line MCF7 at concentrations of 152.56 µg/mL and 160 161.08 µg/mL, respectively. PMID:26647630

  13. DISC1, PDE4B, and NDE1 at the centrosome and synapse

    SciTech Connect

    Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz; Chubb, Jennifer E.; Carlyle, Becky C.; Christie, Sheila; Claessens, Antoine; Porteous, David J.; Millar, J. Kirsty

    2008-12-26

    Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.

  14. Random UV mutagenesis approach for enhanced biodegradation of sulfonated azo dye, Green HE4B.

    PubMed

    Joshi, Swati M; Inamdar, Shrirang A; Jadhav, Jyoti P; Govindwar, Sanjay P

    2013-03-01

    The objective of the study was to execute mutant bacteria for efficient biodegradation of sulfonated azo dye, Green HE4B (GHE4B). UV irradiation was used to introduce random mutations in Pseudomonas sp. LBC1. Genetic alterations induced by UV irradiation in selected mutant bacteria were confirmed by random amplification of polymorphic DNA technique. The mutant bacteria named as Pseudomonas sp. 1 F reduced the time required for complete degradation of recalcitrant dye GHE4B by 25 % when compared with the wild one. The biodegradation was monitored by UV-Vis spectrophotometric analysis. Activities of enzymes like laccase, lignin peroxidase, veratryl alcohol oxidase, and NADH dichlorophenol indophenol reductase were found to be boosted in mutant bacteria as a consequence of UV-induced mutation. Matrix-assisted laser desorption/ionization-time of flight analysis of differentially expressed proteins of mutant bacteria suggested active role of antioxidant enzymes in the degradation of the dye. The degradation product was analyzed by Fourier transform infrared spectroscopy, high-performance thin-layer chromatography, and gas chromatography-mass spectrometry. Results revealed few variations in the degradation end products of wild-type and mutant bacteria. Phytotoxicity study underlined the safer biodegradation of GHE4B by mutant Pseudomonas sp. 1 F.

  15. IcmQ in the Type 4b secretion system contains a novel NAD+ binding domain

    PubMed Central

    Farelli, Jeremiah D.; Gumbart, James C.; Akey, Ildiko V.; Hempstead, Andrew; Amyot, Whitney; Head, James F.; McKnight, C. James; Isberg, Ralph R.; Akey, Christopher W.

    2013-01-01

    A Type4b secretion system (T4bSS) is required for Legionella growth in alveolar macrophages. IcmQ associates with IcmR, binds to membranes and has a critical role in the T4bSS. We have now solved a crystal structure of IcmR-IcmQ to further our understanding of this complex. This structure revealed an amphipathic four-helix bundle, formed by IcmR and the N-terminal domain of IcmQ, which is linked to a novel C-terminal domain of IcmQ (Qc) by a linker helix. The Qc domain has structural homology with ADP ribosyltransferase domains in certain bacterial toxins and binds NAD+ with a Kd in the physiological range. Structural homology and molecular dynamics were used to identify an extended NAD+ binding site on Qc and the resulting model was tested by mutagenesis and binding assays. Based on the data, we suggest that IcmR-IcmQ binds to membranes where it may interact with or perhaps modify a protein in the T4bSS when NAD+ is bound. PMID:23850453

  16. 16 CFR 1508.5 - Component spacing test method for § 1508.4(b).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Component spacing test method for § 1508.4(b). 1508.5 Section 1508.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS § 1508.5 Component spacing test method...

  17. 16 CFR 1508.5 - Component spacing test method for § 1508.4(b).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Component spacing test method for § 1508.4(b). 1508.5 Section 1508.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS § 1508.5 Component spacing test method...

  18. Atg4b-Dependent Autophagic Flux Alleviates Huntington’s Disease Progression

    PubMed Central

    Proenca, Catia C.; Stoehr, Natacha; Bernhard, Mario; Seger, Shanon; Genoud, Christel; Roscic, Ana; Paganetti, Paolo; Liu, Shanming; Murphy, Leon O.; Kuhn, Rainer; Bouwmeester, Tewis; Galimberti, Ivan

    2013-01-01

    The accumulation of aggregated mutant huntingtin (mHtt) inclusion bodies is involved in Huntigton’s disease (HD) progression. Medium sized-spiny neurons (MSNs) in the corpus striatum are highly vulnerable to mHtt aggregate accumulation and degeneration, but the mechanisms and pathways involved remain elusive. Here we have developed a new model to study MSNs degeneration in the context of HD. We produced organotypic cortico-striatal slice cultures (CStS) from HD transgenic mice mimicking specific features of HD progression. We then show that induction of autophagy using catalytic inhibitors of mTOR prevents MSNs degeneration in HD CStS. Furthermore, disrupting autophagic flux by overexpressing Atg4b in neurons and slice cultures, accelerated mHtt aggregation and neuronal death, suggesting that Atg4b-dependent autophagic flux influences HD progression. Under these circumstances induction of autophagy using catalytic inhibitors of mTOR was inefficient and did not affect mHtt aggregate accumulation and toxicity, indicating that mTOR inhibition alleviates HD progression by inducing Atg4b-dependent autophagic flux. These results establish modulators of Atg4b-dependent autophagic flux as new potential targets in the treatment of HD. PMID:23861892

  19. Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy

    PubMed Central

    Lim, Kue Peng; Chun, Nicole Ai Leng; Gan, Chai Phei; Teo, Soo-Hwang; Rahman, Zainal Ariff Abdul; Abraham, Mannil Thomas; Zain, Rosnah Binti; Ponniah, Sathibalan; Cheong, Sok Ching

    2014-01-01

    The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic. Further, T cells stimulated with peptide-pulsed dendritic cells showed enhanced T-cell cytotoxic activity against MAGED4B-overexpressing OSCC cell lines. In summary, we have identified MAGED4B peptides that induce anti-tumor immune responses advocating that they could be further developed as vaccine candidates for the treatment of OSCC. PMID:25483651

  20. 20. FOUR 4B17Gs BEING CONVERTED TO F9Cs. Photographic copy of ...

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

    20. FOUR 4B-17Gs BEING CONVERTED TO F-9Cs. Photographic copy of historic photograph. Jan.-June 1947 OAMA (original print located at Ogden Air Logistics Center, Hill Air Force Base, Utah). Photographer unknown. - Hill Field, Airplane Repair Hangars No. 1-No. 4, 5875 Southgate Avenue, Layton, Davis County, UT

  1. Identification of an NTPase motif in classical swine fever virus NS4B protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive sense single-stranded RNA virus in the genus Pestivirus of the Flaviviridae family. Here, we have identified, within CSFV non-structural (NS) protein NS4B, conserved sequence el...

  2. siRNA-mediated silencing of phosphodiesterase 4B expression affects the production of cytokines in endotoxin-stimulated primary cultured microglia

    PubMed Central

    Cheng, Hao; Wu, Zhifang; He, Xiaoyun; Liu, Qingzhen; Jia, Hongbin; Di, Yan; Ji, Qing

    2016-01-01

    Phosphodiesterase 4 (PDE4) has four subtypes: PDE4A, PDE4B, PDE4C and PDE4D. The expression of PDE4 subtypes in microglial cells and the specific contribution of each subtype to inflammation remain unclear. In this study, the expression of PDE4 subtypes in primary microglial cells was assayed. Primary microglial cells were then transfected with specific small interfering RNA (siRNA) against each PDE4 subtype. PDE4 subtype A-D knockdown was confirmed by quantitative polymerase chain reaction. Secreted cytokines in the supernatant and intracellular cyclic adenosine monophosphate (cAMP) levels of transfected cells were measured. The effect of PDE4B siRNA on the activation of extracellular regulated protein kinase (ERK) induced by lipopolysaccharide (LPS) in microglia was further tested by western blotting. Results showed that the primary microglial cells expressed all four types of PDE4s at the protein level. Transfection with the four siRNAs inhibited PDE4 subtype A-D mRNA expression, respectively. In primary microglial cells, treatment with PDE4B siRNA significantly inhibited the expression of tumor necrosis factor-α and interleukin (IL)-1β, and enhanced the expression of cAMP, while siRNAs to other subtypes had no significant effects. However, none of the four siRNAs had any significant effect on the expression of IL-10. Furthermore, in the PDE4B group, the level of phosphorylated ERK was reduced. Among the four PDE4 subtypes, PDE4B plays an important role in regulating inflammatory responses in microglia, potentially through initially regulating the intracellular cAMP concentration. PMID:27698721

  3. siRNA-mediated silencing of phosphodiesterase 4B expression affects the production of cytokines in endotoxin-stimulated primary cultured microglia

    PubMed Central

    Cheng, Hao; Wu, Zhifang; He, Xiaoyun; Liu, Qingzhen; Jia, Hongbin; Di, Yan; Ji, Qing

    2016-01-01

    Phosphodiesterase 4 (PDE4) has four subtypes: PDE4A, PDE4B, PDE4C and PDE4D. The expression of PDE4 subtypes in microglial cells and the specific contribution of each subtype to inflammation remain unclear. In this study, the expression of PDE4 subtypes in primary microglial cells was assayed. Primary microglial cells were then transfected with specific small interfering RNA (siRNA) against each PDE4 subtype. PDE4 subtype A-D knockdown was confirmed by quantitative polymerase chain reaction. Secreted cytokines in the supernatant and intracellular cyclic adenosine monophosphate (cAMP) levels of transfected cells were measured. The effect of PDE4B siRNA on the activation of extracellular regulated protein kinase (ERK) induced by lipopolysaccharide (LPS) in microglia was further tested by western blotting. Results showed that the primary microglial cells expressed all four types of PDE4s at the protein level. Transfection with the four siRNAs inhibited PDE4 subtype A-D mRNA expression, respectively. In primary microglial cells, treatment with PDE4B siRNA significantly inhibited the expression of tumor necrosis factor-α and interleukin (IL)-1β, and enhanced the expression of cAMP, while siRNAs to other subtypes had no significant effects. However, none of the four siRNAs had any significant effect on the expression of IL-10. Furthermore, in the PDE4B group, the level of phosphorylated ERK was reduced. Among the four PDE4 subtypes, PDE4B plays an important role in regulating inflammatory responses in microglia, potentially through initially regulating the intracellular cAMP concentration.

  4. A new role for reticulon-4B/NOGO-B in the intestinal epithelial barrier function and inflammatory bowel disease.

    PubMed

    Rodríguez-Feo, Juan Antonio; Puerto, Marta; Fernández-Mena, Carolina; Verdejo, Cristina; Lara, José Manuel; Díaz-Sánchez, María; Álvarez, Emilio; Vaquero, Javier; Marín-Jiménez, Ignacio; Bañares, Rafael; Menchén, Luis

    2015-06-15

    Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10(-/-) compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10(-/-) mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts.

  5. African parasitoid fig wasp diversification is a function of Ficus species ranges.

    PubMed

    McLeish, Michael J; van Noort, Simon; Tolley, Krystal A

    2010-10-01

    Host specificity is a fundamental property implicit in obligate insect-plant associations. Rigid life history constraints exhibited by parasitoid fig wasps are believed to select for specialization directed at fig trees and this is supported by evidence of phenotypic adaptation to figs and partial co-speciation with the fig wasps they attack. Conversely, the ability to colonize such novel communities occurs under relaxed specificity, a behavior typified by more generalist groups such as parasitoids. The specificity directed towards Ficus species by Sycoryctinae parasitoid fig wasps is important in order to understand how this form of specialization influences their diversification and interactions with other fig wasp guilds. We use genetic distance analyses and reconstruct ancestral patterns of Ficus trait association with two genera of Sycoryctinae parasitoid fig wasps to identify evolutionary conservatism in Ficus species utilization. Ancestral state reconstructions of (i) affiliate Ficus subsection and (ii) syconia diameters of natal Ficus species indicate contrasting Ficus species ranges between Arachonia and Sycoryctes parasitoid genera. This work demonstrates that parasitoid speciation is not tightly constrained to Ficus speciation and rather a function of Ficus range limitations. Ficus evolution, ecology, and functional compatibility between parasitoid and Ficus traits appear to constrain parasitoid Ficus utilization. These results suggest that contrasting ecological settings and potential number of hosts available impose different ramifications for the evolution of parasitoid host specificity and so to the species interactions within the communities to which they belong.

  6. [Sex ratio adjustment of a non-pollinating fig wasp species on Ficus semicordata in Xishuangbanna].

    PubMed

    Song, Bo; Peng, Yan-Qiong; Guan, Jun-Ming; Yang, Pei; Yang, Da-Rong

    2008-03-01

    Through controlling the number of ovipositing foundresses inside a fig, and combining with the observation of ovipositing behavior and mating behavior, this paper studied the sex ratio of Apocryptophagus sp., a species of non-pollinating fig wasps hosted on Ficus semicordata in Xishuangbanna. The results showed that female Apocryptophagus sp. started to visit the fig on the 3rd day after pollinator Ceratosolen gravelyi oviposited. Apocryptaphagus sp. oviposited on the outside of the fig, and the ovipositing lasted for 2 days. Male Apocryptophagus sp. emerged at the same time with pollinators. The males opened a small hole on the wall of gall where the females developed, and mated with the females. Mated females emerged from their development fig, and left for a new receptive fig. The sex ratio of Apocryptaphagus sp. was in agreement with local mate competition theory, i. e., it was female-biased. Meanwhile, the total number of offspring increased with increasing foundress number. In contrast, the average number of offspring per foundress decreased. At individual level, when a female laid eggs inside a fig, the sex ratio of offspring correlated negatively with the number of offspring.

  7. Obligate mutualism within a host drives the extreme specialization of a fig wasp genome

    PubMed Central

    2013-01-01

    Background Fig pollinating wasps form obligate symbioses with their fig hosts. This mutualism arose approximately 75 million years ago. Unlike many other intimate symbioses, which involve vertical transmission of symbionts to host offspring, female fig wasps fly great distances to transfer horizontally between hosts. In contrast, male wasps are wingless and cannot disperse. Symbionts that keep intimate contact with their hosts often show genome reduction, but it is not clear if the wide dispersal of female fig wasps will counteract this general tendency. We sequenced the genome of the fig wasp Ceratosolen solmsi to address this question. Results The genome size of the fig wasp C. solmsi is typical of insects, but has undergone dramatic reductions of gene families involved in environmental sensing and detoxification. The streamlined chemosensory ability reflects the overwhelming importance of females finding trees of their only host species, Ficus hispida, during their fleeting adult lives. Despite long-distance dispersal, little need exists for detoxification or environmental protection because fig wasps spend nearly all of their lives inside a largely benign host. Analyses of transcriptomes in females and males at four key life stages reveal that the extreme anatomical sexual dimorphism of fig wasps may result from a strong bias in sex-differential gene expression. Conclusions Our comparison of the C. solmsi genome with other insects provides new insights into the evolution of obligate mutualism. The draft genome of the fig wasp, and transcriptomic comparisons between both sexes at four different life stages, provide insights into the molecular basis for the extreme anatomical sexual dimorphism of this species. PMID:24359812

  8. Chemical mediation and niche partitioning in non-pollinating fig-wasp communities.

    PubMed

    Proffit, Magali; Schatz, Bertrand; Borges, Renée M; Hossaert-McKey, Martine

    2007-03-01

    1. The parasitic chalcidoid wasps associated with the species-specific and obligatory pollination mutualisms between Ficus spp. and their agaonid wasp pollinators provide a good model to study the functional organization of communities. 2. However, communities of non-pollinating fig wasps (NPFWs) remain little characterized, and their functioning and evolutionary dynamics are still poorly understood. 3. We studied the communities of NPFWs associated with the monoecious F. racemosa and the dioecious F. hispida. Associated with these two fig species are a total of seven wasp species belonging to three genera. These species present contrasts in life history traits and in timing of oviposition. The species studied are thus broadly representative of the communities of NPFWs associated specifically with fig-pollinator mutualisms. 4. In our study systems, there is temporal segregation of oviposition time among members of NPFW communities. 5. We tested the role of volatile chemicals in the attraction of NPFWs associated with these two fig species, and tried to determine if chemical mediation can explain the organization of the communities. 6. We conducted odour choice tests using a Y-tube olfactometer. All the NPFWs studied were shown to use volatile chemicals produced by the fig to locate their host. Furthermore, the signals used by each species depended on the phenological stage of the fig they exploit. 7. Results demonstrated that the pattern of oviposition results from the utilization of volatile signals produced by figs that vary in their composition at different stages of fig development. Thus, chemical mediation allows resource partitioning in the NPFW communities associated with fig-pollinator mutualisms, and suggests hypotheses to explain coexistence in other parasite communities.

  9. Competitive exclusion among fig wasps achieved via entrainment of host plant flowering phenology.

    PubMed

    Liu, Min; Zhao, Rui; Chen, Yan; Zhang, Jian; Compton, Stephen G; Chen, Xiao-Yong

    2014-01-01

    Molecular techniques are revealing increasing numbers of morphologically similar but co-existing cryptic species, challenging the niche theory. To understand the co-existence mechanism, we studied phenologies of morphologically similar species of fig wasps that pollinate the creeping fig (F. pumila) in eastern China. We compared phenologies of fig wasp emergence and host flowering at sites where one or both pollinators were present. At the site where both pollinators were present, we used sticky traps to capture the emerged fig wasps and identified species identity using mitochondrial DNA COI gene. We also genotyped F. pumila individuals of the three sites using polymorphic microsatellites to detect whether the host populations were differentiated. Male F. pumila produced two major crops annually, with figs receptive in spring and summer. A small partial third crop of receptive figs occurred in the autumn, but few of the second crop figs matured at that time. Hence, few pollinators were available to enter third crop figs and they mostly aborted, resulting in two generations of pollinating wasps each year, plus a partial third generation. Receptive figs were produced on male plants in spring and summer, timed to coincide with the release of short-lived adult pollinators from the same individual plants. Most plants were pollinated by a single species. Plants pollinated by Wiebesia sp. 1 released wasps earlier than those pollinated by Wiebesia sp. 3, with little overlap. Plants occupied by different pollinators were not spatially separated, nor genetically distinct. Our findings show that these differences created mismatches with the flight periods of the other Wiebesia species, largely 'reserving' individual plants for the resident pollinator species. This pre-emptive competitive displacement may prevent long term co-existence of the two pollinators.

  10. Water availability determines the richness and density of fig trees within Brazilian semideciduous forest landscapes

    NASA Astrophysics Data System (ADS)

    Coelho, Luís Francisco Mello; Ribeiro, Milton Cezar; Pereira, Rodrigo Augusto Santinelo

    2014-05-01

    The success of fig trees in tropical ecosystems is evidenced by the great diversity (+750 species) and wide geographic distribution of the genus. We assessed the contribution of environmental variables on the species richness and density of fig trees in fragments of seasonal semideciduous forest (SSF) in Brazil. We assessed 20 forest fragments in three regions in Sao Paulo State, Brazil. Fig tree richness and density was estimated in rectangular plots, comprising 31.4 ha sampled. Both richness and fig tree density were linearly modeled as function of variables representing (1) fragment metrics, (2) forest structure, and (3) landscape metrics expressing water drainage in the fragments. Model selection was performed by comparing the AIC values (Akaike Information Criterion) and the relative weight of each model (wAIC). Both species richness and fig tree density were better explained by the water availability in the fragment (meter of streams/ha): wAICrichness = 0.45, wAICdensity = 0.96. The remaining variables related to anthropic perturbation and forest structure were of little weight in the models. The rainfall seasonality in SSF seems to select for both establishment strategies and morphological adaptations in the hemiepiphytic fig tree species. In the studied SSF, hemiepiphytes established at lower heights in their host trees than reported for fig trees in evergreen rainforests. Some hemiepiphytic fig species evolved superficial roots extending up to 100 m from their trunks, resulting in hectare-scale root zones that allow them to efficiently forage water and soil nutrients. The community of fig trees was robust to variation in forest structure and conservation level of SSF fragments, making this group of plants an important element for the functioning of seasonal tropical forests.

  11. RAMONA-4B a computer code with three-dimensional neutron kinetics for BWR and SBWR system transient - models and correlations

    SciTech Connect

    Rohatgi, U.S.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.; Neymotin, L.Y.

    1998-03-01

    This document describes the major modifications and improvements made to the modeling of the RAMONA-3B/MOD0 code since 1981, when the code description and assessment report was completed. The new version of the code is RAMONA-4B. RAMONA-4B is a systems transient code for application to different versions of Boiling Water Reactors (BWR) such as the current BWR, the Advanced Boiling Water Reactor (ABWR), and the Simplified Boiling Water Reactor (SBWR). This code uses a three-dimensional neutron kinetics model coupled with a multichannel, non-equilibrium, drift-flux, two-phase flow formulation of the thermal hydraulics of the reactor vessel. The code is designed to analyze a wide spectrum of BWR core and system transients and instability issues. Chapter 1 is an overview of the code`s capabilities and limitations; Chapter 2 discusses the neutron kinetics modeling and the implementation of reactivity edits. Chapter 3 is an overview of the heat conduction calculations. Chapter 4 presents modifications to the thermal-hydraulics model of the vessel, recirculation loop, steam separators, boron transport, and SBWR specific components. Chapter 5 describes modeling of the plant control and safety systems. Chapter 6 presents and modeling of Balance of Plant (BOP). Chapter 7 describes the mechanistic containment model in the code. The content of this report is complementary to the RAMONA-3B code description and assessment document. 53 refs., 81 figs., 13 tabs.

  12. RAMONA-4B a computer code with three-dimensional neutron kinetics for BWR and SBWR system transient - user`s manual

    SciTech Connect

    Rohatgi, U.S.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.; Neymotin, L.Y.

    1998-03-01

    This document is the User`s Manual for the Boiling Water Reactor (BWR), and Simplified Boiling Water Reactor (SBWR) systems transient code RAMONA-4B. The code uses a three-dimensional neutron-kinetics model coupled with a multichannel, nonequilibrium, drift-flux, phase-flow model of the thermal hydraulics of the reactor vessel. The code is designed to analyze a wide spectrum of BWR core and system transients. Chapter 1 gives an overview of the code`s capabilities and limitations; Chapter 2 describes the code`s structure, lists major subroutines, and discusses the computer requirements. Chapter 3 is on code, auxillary codes, and instructions for running RAMONA-4B on Sun SPARC and IBM Workstations. Chapter 4 contains component descriptions and detailed card-by-card input instructions. Chapter 5 provides samples of the tabulated output for the steady-state and transient calculations and discusses the plotting procedures for the steady-state and transient calculations. Three appendices contain important user and programmer information: lists of plot variables (Appendix A) listings of input deck for sample problem (Appendix B), and a description of the plotting program PAD (Appendix C). 24 refs., 18 figs., 11 tabs.

  13. The non-pollinating fig wasps associated with Ficus guianensis: Community structure and impact of the large species on the fig/pollinator mutualism

    NASA Astrophysics Data System (ADS)

    Conchou, Lucie; Ciminera, Marina; Hossaert-McKey, Martine; Kjellberg, Finn

    2014-05-01

    Understanding the ecology of non-pollinating fig-wasp communities depends on a good knowledge of larval feeding habits of the species involved, which can be gall inducers, kleptoparasites, parasitoids or seed eaters. However, larval feeding habits are poorly known and most community ecology studies on NPFW are based on hypothetical feeding habits or data analyzed independently of feeding habit. Here we take advantage of the particular situation in Ficus guianensis whose community is dominated by large NPFW, i.e. species that are obviously larger than pollinators, to establish the community structure and feeding habits of the most frequent wasps. We provide the first non-ambiguous negative correlation between the number of NPFW and the production of pollinators and seeds. Each developing large NPFW represents a disproportionate cost to the mutualism as it is responsible for the loss of about ten seeds plus pollinators, i.e. about 10% of the production of a fig.

  14. Knockdown of CUL4B Suppresses the Proliferation and Invasion in Non-Small Cell Lung Cancer Cells.

    PubMed

    Wang, Xuguang; Chen, Zhe

    2016-01-01

    Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, was found to be overexpressed in many types of tumors. However, the expression pattern and role of CUL4B in non-small cell lung cancer (NSCLC) remain largely unknown. Therefore, in the present study, we investigated the role of CUL4B in NSCLC, and the underlying mechanism was also explored. Our results showed that CUL4B was highly expressed in NSCLC cell lines. Silencing CUL4B obviously inhibited proliferation and migration/invasion of NSCLC cells, and it also suppressed the epithelial-mesenchymal transition (EMT) progress in NSCLC cells. Furthermore, knockdown of CUL4B significantly inhibited the expression of β-catenin, cyclin D1, and c-Myc in NSCLC cells. Taken together, these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway in NSCLC cells. Therefore, CUL4B may represent a novel therapeutic target for the treatment of NSCLC. PMID:27656838

  15. Aflatoxin and Ochratoxin - a contamination of dried figs (Ficus carina L) from the 1988 crop.

    PubMed

    Ozay, G; Alperden, I

    1991-09-01

    The study examines the occurrence of aflatoxin and ochratoxin A in the !988 dried figs crop. Mycotoxin content, moisture, and aw (water activity) were analyzed in a total of 103 fig samples collected from various orchards and different stages of fig processing. Aflatoxins (B1, B2, G1, and G2) were present in 29% of the samples examined at 0.5-63.0, 0.5-37.7, 0.5-78.3, and 0.5-12.5μ/kg, respectively. Ochratoxin A was detected in only 3% of the samples at 5.2-8.3 μ/kg. The moisture (and aw) values of the fruits were found suitable for mycotoxin formation in firm ripened and shrivelled figs. PMID:23605655

  16. Mass modeling of fig (Ficus carica L.) fruit with some physical characteristics.

    PubMed

    Shahbazi, Feizollah; Rahmati, Satar

    2013-03-01

    Horticultural crops with the similar weight and uniform shape are in high demand in terms of marketing value, which are used as food. For proper design of grading systems, important relationships among the mass and other properties of fruits such as length, width, thickness, volumes, and projected areas must be known. The aim of this research was to measure and present some physical properties of fig fruits. In addition, Linear, Quadratic, S-curve, and Power models are used for mass predication of fig fruits based on measured physical properties. The results showed that all measured physical properties were statistically significant at the 1% probability level. For mass predication of fig fruits, the best and the worst models were obtained based on criteria projected area and thickness of the fruits with determination coefficients (R (2)) of 0.984 and 0.664, respectively. At last, from economical standpoint, mass modeling of fig fruits based on first projected area is recommended.

  17. The complete nucleotide sequence and genome organization of Fig cryptic virus, a novel bipartite dsRNA virus infecting fig, widely distributed in the Mediterranean basin.

    PubMed

    Elbeaino, Toufic; Kubaa, Raied Abou; Digiaro, Michele; Minafra, Angelantonio; Martelli, Giovanni P

    2011-06-01

    Two double-stranded RNA (dsRNA) segments of a virus with a bipartite genome identified in fig (Ficus carica L.) and denoted Fig cryptic virus (FCV) were cloned and sequenced. Viral dsRNAs are 1696 bp (RNA-1) and 1415 bp (RNA-2) in size. RNA-1 contains a single ORF (1419 nt) potentially encoding a 54 kDa protein and comprising the conserved amino acid motifs of the RNA-dependent RNA polymerase (RdRp) domain of species of the genus Alphacryptovirus. Its full-length amino acid sequence has the highest identity with Raphanus sativus cryptic virus 2 (RsCV-2) (36%), Beet cryptic virus 3 (BCV-3) (36%) and Fragaria chiloensis cryptic virus (FCCV) (34%). RNA-2 has also a single ORF (1014 nt) coding for a polypeptide with a predicted molecular mass of 38 kDa, identified as the viral coat protein (CP). In a phylogenetic tree constructed with the amino acid sequences of the RdRp domain, FCV clusters in a clade comprising BCV-3 and a number of tentative species of the genus Alphacryptovirus. FCV is not mechanically transmissible. It was detected in fig orchards of six Mediterranean countries (Albania, Algeria, Italy, Lebanon, Syria and Tunisia) where it does not seem to induce a visible disease.

  18. Phylogenetic relationships of fig wasps pollinating functionally dioecious Ficus based on mitochondrial DNA sequences and morphology.

    PubMed

    Weiblen, G D

    2001-04-01

    The obligate mutualism between pollinating fig wasps in the family Agaonidae (Hymenoptera: Chalcidoidea) and Ficus species (Moraceae) is often regarded as an example of co-evolution but little is known about the history of the interaction, and understanding the origin of functionally dioecious fig pollination has been especially difficult. The phylogenetic relationships of fig wasps pollinating functionally dioecious Ficus were inferred from mitochondrial cytochrome oxidase gene sequences (mtDNA) and morphology. Separate and combined analyses indicated that the pollinators of functionally dioecious figs are not monophyletic. However, pollinator relationships were generally congruent with host phylogeny and support a revised classification of Ficus. Ancestral changes in pollinator ovipositor length also correlated with changes in fig breeding systems. In particular, the relative elongation of the ovipositor was associated with the repeated loss of functionally dioecious pollination. The concerted evolution of interacting morphologies may bias estimates of phylogeny based on female head characters, but homoplasy is not so strong in other morphological traits. The lesser phylogenetic utility of morphology than of mtDNA is not due to rampant convergence in morphology but rather to the greater number of potentially informative characters in DNA sequence data; patterns of nucleotide substitution also limit the utility of mtDNA findings. Nonetheless, inferring the ancestral associations of fig pollinators from the best-supported phylogeny provided strong evidence of host conservatism in this highly specialized mutualism.

  19. [Spatial distribution of fig wasps in syconia of two monoecious Ficus sp].

    PubMed

    Wang, Zhen-Ji; Li, Guo-Chang; Peng, Yan-Qiong; Yang, Da-Rong

    2012-04-01

    In addition to pollinator fig wasps, there are several non-pollinating fig wasps associated with monoecious Ficus sp. In order to understand how pollinator fig wasps and non-pollinating fig wasps are distributed across the same syconium, the spatial distribution of fig wasps associated with Ficus altissima and F. benjamina were compared using the pedicle lengths of galls containing each species. The results indicate that in Ficus altissima, the average pedicel length of galls containing Eupristina sp. is longer than that containing E. altissima. Average pedicel length of galls containing Sycobia sp., Micranisa ralianga and Sycoscapter sp. two did not show significant difference. The range of pedicel lengths of galls containing Sycobia sp., M. ralianga or Sycoscapter sp. two is narrower than that of galls containing E. altissima, indicating these non-pollinating fig wasps and pollinator have partially separated spatial niches. In F. benjamina, E. koningsbergeri was distributed in galls from the outer layer to inner layer, while most Walkerella sp. were found in outer layer galls, indicating E. koningsbergeri and Walkerella sp. have partially separated spatial niches.

  20. Screening for the FIG-ROS1 fusion in biliary tract carcinomas by nested PCR.

    PubMed

    Peraldo Neia, Caterina; Cavalloni, Giuliana; Balsamo, Antonella; Venesio, Tiziana; Napoli, Francesca; Sassi, Francesco; Martin, Vittoria; Frattini, Milo; Aglietta, Massimo; Leone, Francesco

    2014-12-01

    ROS1 rearrangements have been detected in a variety of tumors and are considered as suitable targets of anticancer therapies. We developed a new, quick, specific, and sensitive PCR test to screen for the FIG-ROS1 fusion and applied it to a series of Italian patients with bile duct carcinoma (BTC). Formalin-fixed, paraffin-embedded tissues, derived from 65 Italian BTC patients, and six cell lines were analyzed by nested PCR to investigate the prevalence of a previously reported FIG-ROS1 fusion. The specificity and sensitivity of nested PCR were investigated in FIG-ROS1 positive U118MG cells in reconstitution experiments with peripheral blood mononuclear cells. We found that six out of 65 (9%) BTC patients were positive for the FIG-ROS1 fusion, comprising two out of 14 (14%) gallbladder carcinoma (GBC) patients and four out of 25 (16%) extrahepatic cholangiocarcinoma (ECC) patients. None of the 26 intrahepatic cholangiocarcinoma cases harbored the FIG-ROS1 fusion. All the cell lines were negative for this variant. In conclusion, 14-16% of GBC and ECC were positive for FIG-ROS1. This may have clinical implications, since these patients will potentially benefit from the treatment with specific ROS1 inhibitors.

  1. Study on mating ecology and sex ratio of three internally ovipositing fig wasps of Ficus curtipes.

    PubMed

    Zhang, F P; Yang, D R

    2010-04-01

    Studies on mating ecology and sex allocation in fig-parasitizing wasps ovipositing from outside the fig have given valuable insights into known factors that are responsible for the theory of sex ratio. Similarly, internally ovipositing fig-parasitizing wasps and fig-pollinating wasps provide interesting models for comparative analysis. In addition to the fig-pollinating wasp Eupristina sp., we found that Ficus curtipes hosts two species of internally ovipositing fig-parasitizing wasps: D. yangi and Lipothymus sp. Eupristina sp. males showed less aggression. Eupristina sp. has wingless males that mate only within the natal patch, providing excellent examples of full local-mate competition. D. yangi males showed high levels of aggression and lethal combat. D. yangi has winged males but mate mostly within the natal patch. Only a few matings occur after male dispersal. Its sex ratio was lower than the prediction of partial local mate competition theory. Wingless male Lipothymus sp., which mate partly after dispersal, did not present fatal fight. Therefore, the mating behaviour of D. yangi and Lipothymus sp. did not follow predicted patterns, based on wing morph. The mating pattern of D. yangi and Lipothymus sp. should follow the partial local mate competition theory. Furthermore, there was not a significant correlation between the proportion of males and the proportion of fruit parasitized in both winged D. yangi males and wingless Lipothymus sp. males.

  2. Detection of gamma irradiated fig seeds by analysing electron spin resonance.

    PubMed

    Engin, Birol; Aydaş, Canan; Polat, Mustafa

    2011-06-15

    Seeds of fig produced in Turkey were studied by electron spin resonance (ESR) technique for detection purposes. Unirradiated fig seeds (control) exhibited a weak ESR singlet at g=2.0052±0.0003 (native signal). Irradiation induced at least one additional intense singlet overlapping to the control signal and caused a significant increase in signal intensity without any changes in spectral patterns. Variation of ESR signal intensity of irradiated samples at room temperature with time in a long-term showed that free radicals responsible from the ESR spectrum of fig seeds were not stable but detectable after 80days. Annealing studies at five different temperatures were used to determine the kinetic behaviour and activation energy of the radiation-induced radicals in fig seeds. A study on microwave saturation characteristics and thermal behaviour of the ESR singlet (g=2.0052) in irradiated and unirradiated fig seed samples was also carried out by using ESR technique. These preliminary results indicate that microwave saturation characteristics of the ESR signal at room and low temperatures may be useful method to distinguish irradiated fig seeds from unirradiated ones.

  3. Odorant-binding protein (OBP) genes affect host specificity in a fig-pollinator mutualistic system.

    PubMed

    Wang, N; Wang, N X; Niu, L M; Bian, S N; Xiao, J H; Huang, D W

    2014-10-01

    The interaction between figs and their pollinating wasps is regarded as a model system for studying specialized co-evolved mutualism. Chemoreception of fig wasps plays an important role in this interaction, and odorant-binding proteins (OBP) function in the first step of odorant detection. The OBP repertoire of the fig wasp Ceratosolen solmsi is reported to be one of the smallest among insects; however, it is unknown how these OBPs are related to the complicated mating process occurring within the fig cavity and the extreme host specificity of the species. In the present study, we combined a structural analysis of the conserved cysteine pattern and motif order, a phylogenetic analysis, and previous studies on ligand-binding assays to deduce the function of OBPs. We also quantified the expression of OBP genes in different life stages of female and male fig wasps by using real-time quantitative PCR, which can help to predict the function of these genes. The results indicated that CsolOBP1 and CsolOBP2 (or CsolOBP5) in males may bind to pheromones and play important roles in mate choice, whereas CsolOBP4 and CsolOBP5 may primarily function in host localization by females through binding of volatile compounds emitted by receptive figs.

  4. Protection against Asiatic Taenia solium Induced by a Recombinant 45W-4B Protein▿

    PubMed Central

    Luo, Xuenong; Zheng, Yadong; Hou, Junling; Zhang, Shaohua; Cai, Xuepeng

    2009-01-01

    Taenia solium is a great threat not only to human health but also to the pig-raising industry. Oncospheral stage-specific 45W proteins are good candidates for the development of anticysticercosis vaccines. In this study, a recombinant 45W-4B protein was highly produced and used for vaccination. Two animal trials resulted in a significant reduction in parasite burden induced by the definite protein against Asiatic T. solium, up to 97.0% and 98.4%, respectively. These provide informative results for the development of effective 45W-4B vaccines against cysticercosis caused by both Chinese and Mexican T. solium isolates and even by other isolates. PMID:19091992

  5. Optical and Near-UV Observations of the Transiting Extrasolar Planet TrES-4b

    NASA Astrophysics Data System (ADS)

    Smith, Carter-Thaxton; Turner, J.; Carleton, T.; Crawford, B.; Guvenen, B.; Hardegree-Ullman, K.; Small, L.; Towner, A. P.; Walker-LaFollette, A.; Henz, T.

    2013-01-01

    Using the Steward Observatory 61” Kuiper Telescope, The University of Arizona Astronomy Club conducted photometric observations of the transiting extrasolar planet TrES-4b as part of the Exoplanet Observation Project. Observations were made in the Bessell U, Harris B, and Harris R filters. Initial observations were made in 2009, with follow up observations in 2011. Basic data reduction and photometry was done using IRAF and determination of transit parameters was done using Transit Analysis Package (TAP) and JKTEBOP transit modeling code. We present an updated planetary mass, radius, density, surface gravity, Safronov number, equilibrium temperature, orbital distance, and orbital inclination for TrES-4b. In addition, we also searched for asymmetries between the near-UV and optical light curves. This project, started in spring 2009, has introduced many undergraduate students to research and given them valuable experience with data reduction and observation techniques.

  6. Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)

    PubMed Central

    REILLY, B D; MOLD, C

    1997-01-01

    Complement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CR1 binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd ≍ 1.4 10−7M) than C4Bb2 (Kd ≍ 4–8 10−7M), indicating a preferential binding of CR1 for C4A. PMID:9367418

  7. Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

    PubMed Central

    Thornbrough, Joshua M.; Jha, Babal K.; Yount, Boyd; Goldstein, Stephen A.; Li, Yize; Elliott, Ruth; Sims, Amy C.; Baric, Ralph S.; Silverman, Robert H.

    2016-01-01

    ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention. PMID:27025250

  8. HATS-4b: A dense hot Jupiter transiting a super metal-rich G star

    SciTech Connect

    Jordán, Andrés; Brahm, Rafael; Rabus, M.; Suc, V.; Espinoza, N.; Bakos, G. Á.; Penev, K.; Hartman, J. D.; Csubry, Z.; Bhatti, W.; De Val Borro, M.; Bayliss, D.; Zhou, G.; Mancini, L.; Mohler-Fischer, M.; Ciceri, S.; Csák, B.; Henning, T.; Sato, B.; Buchhave, L.; and others

    2014-08-01

    We report the discovery by the HATSouth survey of HATS-4b, an extrasolar planet transiting a V = 13.46 mag G star. HATS-4b has a period of P ≈ 2.5167 days, mass of M{sub p} ≈ 1.32 M {sub Jup}, radius of R{sub p} ≈ 1.02 R {sub Jup}, and density of ρ {sub p} = 1.55 ± 0.16 g cm{sup –3} ≈1.24 ρ{sub Jup}. The host star has a mass of 1.00 M {sub ☉}, a radius of 0.92 R {sub ☉}, and a very high metallicity [Fe/H]=0.43 ± 0.08. HATS-4b is among the densest known planets with masses between 1 and 2 M {sub J} and is thus likely to have a significant content of heavy elements of the order of 75 M {sub ⊕}. In this paper we present the data reduction, radial velocity measurements, and stellar classification techniques adopted by the HATSouth survey for the CORALIE spectrograph. We also detail a technique for simultaneously estimating vsin i and macroturbulence using high resolution spectra.

  9. DISTRIBUTION OF CH{sub 3}OH IN NGC 1333 IRAS4B

    SciTech Connect

    Sakai, Nami; Yamamoto, Satoshi; Ceccarelli, Cecilia; Bottinelli, Sandrine; Sakai, Takeshi

    2012-07-20

    Distribution of the CH{sub 3}OH (J{sub K} = 2{sub K}-1{sub K}, 96.7 GHz) emission has been investigated toward NGC 1333 IRAS4B, a low-mass Class 0 protostar which harbors a hot corino, with Nobeyama Millimeter Array. The CH{sub 3}OH emission is found to be prominent in the shocked region caused by an impact of the molecular outflow from the protostars. The direction of the outflow which is responsible for the shock seems to be opposite to that of a compact outflow known previously in the CO (J = 2-1), HCN (J = 1-0), H{sub 2}CO (3{sub 12}-2{sub 11}), and CH{sub 3}OH (J{sub K} = 7{sub K}-6{sub K}) emissions, whereas it is the same as that of the faint second outflow found in the H{sub 2}CO emission. This double outflow structure can be interpreted most naturally by the existence of more than two protostars in IRAS4B. On the other hand, a centrally condensed component associated apparently with IRAS4B cannot be recognized in our CH{sub 3}OH observation. Our observation suggests that, in this source, the CH{sub 3}OH (J{sub K} 2{sub K}-1{sub K}) emission preferentially traces the shocked regions rather than the hot corino around the protostar.

  10. Mg{sub 8}Rh{sub 4}B - A new type of boron stabilized Ti{sub 2}Ni structure

    SciTech Connect

    Alekseeva, A.M. . E-mail: alekseev@cpfs.mpg.de; Abakumov, A.M.; Leithe-Jasper, A.; Schnelle, W.; Prots, Yu.; Chizhov, P.S.; Van Tendeloo, G.; Antipov, E.V.; Grin, Yu.

    2006-09-15

    The new magnesium rhodium boron compound Mg{sub 8}Rh{sub 4}B has been synthesized by reaction of the metal powders with crystalline or amorphous boron or the RhB precursor. The crystal structure of Mg{sub 8}Rh{sub 4}B was solved using single-crystal X-ray diffraction data (space group Fd3-bar m, a=12.1711(4)A, Z=8, 174 reflections, R{sub F}=0.016). The crystal structure can be described as a filled Ti{sub 2}Ni type where the interstitial sites 8b (12,12,12), located at the center of two nested Mg{sub 4}Rh{sub 4} tetrahedra, are occupied by boron atoms. Taking into account the absence of the Ti{sub 2}Ni-type phase in the binary Mg-Rh system, the boron atoms can be considered as stabilizing this structural motif. From the bonding analysis with the electron localization function the crystal structure is described as covalently bonded [Rh{sub 4}B]{sup 3-} anions, embedded in a cationic magnesium matrix.

  11. Metatranscriptome Analysis of Fig Flowers Provides Insights into Potential Mechanisms for Mutualism Stability and Gall Induction

    PubMed Central

    Martinson, Ellen O.; Hackett, Jeremiah D.; Machado, Carlos A.; Arnold, A. Elizabeth

    2015-01-01

    A striking property of the mutualism between figs and their pollinating wasps is that wasps consistently oviposit in the inner flowers of the fig syconium, which develop into galls that house developing larvae. Wasps typically do not use the outer ring of flowers, which develop into seeds. To better understand differences between gall and seed flowers, we used a metatranscriptomic approach to analyze eukaryotic gene expression within fig flowers at the time of oviposition choice and early gall development. Consistent with the unbeatable seed hypothesis, we found significant differences in gene expression between gall- and seed flowers in receptive syconia prior to oviposition. In particular, transcripts assigned to flavonoids and carbohydrate metabolism were significantly up-regulated in gall flowers relative to seed flowers. In response to oviposition, gall flowers significantly up-regulated the expression of chalcone synthase, which previously has been connected to gall formation in other plants. We propose several genes encoding proteins with signal peptides or associations with venom of other Hymenoptera as candidate genes for gall initiation or growth. This study simultaneously evaluates the gene expression profile of both mutualistic partners in a plant-insect mutualism and provides insight into a possible stability mechanism in the ancient fig-fig wasp association. PMID:26090817

  12. On the origin of the fig: phylogenetic relationships of Moraceae from ndhF sequences.

    PubMed

    Datwyler, Shannon L; Weiblen, George D

    2004-05-01

    The majority of species in the mulberry family (Moraceae) are figs (Ficus), marked by a specialized inflorescence (syconium) and an obligate mutualism with pollinating fig wasps. Because of the unique morphology of the syconium, it has been difficult to investigate the evolutionary position of the fig. We sequenced the chloroplast gene ndhF to examine relationships in Moraceae and to elucidate shifts in reproductive traits. The reclassification of tribes is warranted, and the limits of Artocarpeae, Moreae, and Castilleae are revised to reflect evolutionary relationships. The results point to ancestral dioecy in Moraceae and multiple origins of monoecy, androdioecy, and gynodioecy. Ancestral wind pollination gave way to insect pollination at least twice. Strong support for the sister-group relationship of a revised Castilleae with Ficus suggests that entomophily and involucral bracts encircling the flowers preceded the evolution of the syconium. Bracts surround flowers in Castilleae only during early development, but in Ficus the involucre and the receptacle enclose the fruit as well. Molecular dating suggests that fig pollination is at least 80-90 million years old. The diversity of Ficus relative to its sister group is a likely consequence of ancient specialization and cospeciation with pollinating fig wasps.

  13. Relationship between pollination and cell wall properties in common fig fruit.

    PubMed

    Trad, Mehdi; Ginies, Christian; Gaaliche, Badii; Renard, Catherine M G C; Mars, Messaoud

    2014-02-01

    Most botanical types in fig Ficus carica require pollination to fulfil their development and ensure quality onset of the fruit. Cell wall behaviour and composition was followed in fig fruit in response to pollination during maturity. Figs, when ripe, soften drastically and lose of their firmness and cell wall cohesion. Pollination increased peel thickness, flesh thickness, fresh weight and dry matter content of the fruit. Alcohol insoluble solids (AIS), more concentrated in the flesh tissue, were not influenced by the lack of pollination. Concentrations in uronic acids were higher in the AIS of the peel than that of the flesh and differences were significant between pollinated and non-pollinated fruits. Pectin polymers in figs were high methylated (DM>50). The methylation degree (DM) increased more with pollination affecting textural properties of the fig receptacle. The major neutral sugars from the AIS were glucose (Glc) from cellulose followed by arabinose (Ara). No significant changes in neutral sugars content could be allocated to pollination. Pollination is essential in fruit enlargement and softening. Minor changes were determined in the cell wall composition of the fruit at maturity. Fertile seeds resulting from pollination may possibly take place in hormonal activity stimulating many related enzymes of the wall matrix depolymerisation in particular polygalacturonase (PG) and pectin methylesterase (PME).

  14. Metatranscriptome Analysis of Fig Flowers Provides Insights into Potential Mechanisms for Mutualism Stability and Gall Induction.

    PubMed

    Martinson, Ellen O; Hackett, Jeremiah D; Machado, Carlos A; Arnold, A Elizabeth

    2015-01-01

    A striking property of the mutualism between figs and their pollinating wasps is that wasps consistently oviposit in the inner flowers of the fig syconium, which develop into galls that house developing larvae. Wasps typically do not use the outer ring of flowers, which develop into seeds. To better understand differences between gall and seed flowers, we used a metatranscriptomic approach to analyze eukaryotic gene expression within fig flowers at the time of oviposition choice and early gall development. Consistent with the unbeatable seed hypothesis, we found significant differences in gene expression between gall- and seed flowers in receptive syconia prior to oviposition. In particular, transcripts assigned to flavonoids and carbohydrate metabolism were significantly up-regulated in gall flowers relative to seed flowers. In response to oviposition, gall flowers significantly up-regulated the expression of chalcone synthase, which previously has been connected to gall formation in other plants. We propose several genes encoding proteins with signal peptides or associations with venom of other Hymenoptera as candidate genes for gall initiation or growth. This study simultaneously evaluates the gene expression profile of both mutualistic partners in a plant-insect mutualism and provides insight into a possible stability mechanism in the ancient fig-fig wasp association.

  15. Studies on preparation of mixed fruit toffee from Fig and Guava fruits.

    PubMed

    Kohinkar, S N; Chavan, U D; Pawar, V D; Amarowicz, R

    2014-09-01

    Studies were carried out to develop a technology for preparation of mixed fruit toffee from fig and guava fruit pulp and to evaluate the changes in quality of prepared toffees during storage under ambient as well as refrigerated conditions for 180 days. Among the various combinations of fig and guava fruit pulp, toffee prepared from75:25 w/w (fig: guava) ratios was found better than other combinations in respect to yield, organoleptic properties and nutritional quality. The cost of toffee prepared from higher level of fig pulp i.e. 75:25 (fig:guava) ratio was higher (Rs. 71.84/kg). The storage studies of toffees packed in 200 gauge polyethylene bags indicated that the TSS, reducing and total sugars increased with the advancement of storage period, while moisture and acidity content decreased. The rate of reactions was relatively higher at ambient temperature than refrigerated temperature. Though the sensory quality of toffees also decreased at faster rate during 180 days storage period at ambient condition than the refrigerated condition yet the toffees were found to be acceptable even after 180 days at both the conditions.

  16. Evaluation of genetic diversity in fig accessions by using microsatellite markers.

    PubMed

    do Val, A D B; Souza, C S; Ferreira, E A; Salgado, S M L; Pasqual, M; Cançado, G M A

    2013-04-25

    Fig (Ficus carica L.) is a fruit of great importance worldwide. Its propagation is carried out with stem cuttings, a procedure that favors the occurrence of synonymy among specimens. Thus, molecular markers have become an important tool for studies of DNA fingerprinting, germplasm characterization, and genetic diversity evaluation in this plant species. The aim of this study was the analysis of genetic diversity among accessions of fig and the detection of synonyms among samples using molecular markers. Five microsatellite markers previously reported as polymorphic to fig were used to characterize 11 fig cultivars maintained in the germplasm bank located in Lavras, Minas Gerais. A total of 21 polymorphic DNA fragments were amplified, with an average of 4.2 alleles per locus. The average allelic diversity and polymorphic information content were 0.6300 and 0.5644, respectively, whereas the total value for the probability of identity was 1.45 x 10(-4). The study allowed the identification of 10 genotypes and 2 synonymous individuals. The principal coordinate analysis showed no defined clusters despite the formation of groups according to geographical origin. However, neighbor-joining analysis identified the same case of synonymy detected using principal coordinate analysis. The data also indicated that the fig cultivars analyzed constitute a population of individuals with high genetic diversity and a broad range of genetic variation.

  17. Relationship between pollination and cell wall properties in common fig fruit.

    PubMed

    Trad, Mehdi; Ginies, Christian; Gaaliche, Badii; Renard, Catherine M G C; Mars, Messaoud

    2014-02-01

    Most botanical types in fig Ficus carica require pollination to fulfil their development and ensure quality onset of the fruit. Cell wall behaviour and composition was followed in fig fruit in response to pollination during maturity. Figs, when ripe, soften drastically and lose of their firmness and cell wall cohesion. Pollination increased peel thickness, flesh thickness, fresh weight and dry matter content of the fruit. Alcohol insoluble solids (AIS), more concentrated in the flesh tissue, were not influenced by the lack of pollination. Concentrations in uronic acids were higher in the AIS of the peel than that of the flesh and differences were significant between pollinated and non-pollinated fruits. Pectin polymers in figs were high methylated (DM>50). The methylation degree (DM) increased more with pollination affecting textural properties of the fig receptacle. The major neutral sugars from the AIS were glucose (Glc) from cellulose followed by arabinose (Ara). No significant changes in neutral sugars content could be allocated to pollination. Pollination is essential in fruit enlargement and softening. Minor changes were determined in the cell wall composition of the fruit at maturity. Fertile seeds resulting from pollination may possibly take place in hormonal activity stimulating many related enzymes of the wall matrix depolymerisation in particular polygalacturonase (PG) and pectin methylesterase (PME). PMID:24393459

  18. Citric and gluconic acid production from fig by Aspergillus niger using solid-state fermentation.

    PubMed

    Roukas, T

    2000-12-01

    The production of citric and gluconic acids from fig by Aspergillus niger ATCC 10577 in solid-state fermentation was investigated. The maximal citric and gluconic acids concentration (64 and 490 g/kg dry figs, respectively), citric acid yield (8%), and gluconic acid yield (63%) were obtained at a moisture level of 75%, initial pH 7.0, temperature 30 degrees C, and fermentation time in 15 days. However, the highest biomass dry weight (40 g/kg wet substrate) and sugar utilization (90%) were obtained in cultures grown at 35 degrees C. The addition of 6% (w/w) methanol into substrate increased the concentration of citric and gluconic acid from 64 and 490 to 96 and 685 g/kg dry fig, respectively.

  19. Finding hidden females in a crowd: Mate recognition in fig wasps

    NASA Astrophysics Data System (ADS)

    Krishnan, Anusha; Joshi, Kanchan Anand; Abraham, Ambily; Ayyub, Shreya; Lahiry, Mohini; Mukherjee, Ritwika; Javadekar, Saniya Milind; Narayan, Vignesh; Borges, Renee M.

    2014-05-01

    Multi-species mating aggregations are crowded environments within which mate recognition must occur. Mating aggregations of fig wasps can consist of thousands of individuals of many species that attain sexual maturity simultaneously and mate in the same microenvironment, i.e, in syntopy, within the close confines of an enclosed globular inflorescence called a syconium - a system that has many signalling constraints such as darkness and crowding. All wasps develop within individual galled flowers. Since mating mostly occurs when females are still confined within their galls, male wasps have the additional burden of detecting conspecific females that are "hidden" behind barriers consisting of gall walls. In Ficus racemosa, we investigated signals used by pollinating fig wasp males to differentiate conspecific females from females of other syntopic fig wasp species. Male Ceratosolen fusciceps could detect conspecific females using cues from galls containing females, empty galls, as well as cues from gall volatiles and gall surface hydrocarbons.

  20. Overexpression of Crocus carotenoid cleavage dioxygenase, CsCCD4b, in Arabidopsis imparts tolerance to dehydration, salt and oxidative stresses by modulating ROS machinery.

    PubMed

    Baba, Shoib Ahmad; Jain, Deepti; Abbas, Nazia; Ashraf, Nasheeman

    2015-09-15

    Apocarotenoids modulate vital physiological and developmental processes in plants. These molecules are formed by the cleavage of carotenoids, a reaction catalyzed by a family of enzymes called carotenoid cleavage dioxygenases (CCDs). Apocarotenoids like β-ionone and β-cyclocitral have been reported to act as stress signal molecules during high light stress in many plant species. In Crocus sativus, these two apocarotenoids are formed by enzymatic cleavage of β-carotene at 9, 10 and 7, 8 bonds by CsCCD4 enzymes. In the present study three isoforms of CsCCD4 were subjected to molecular modeling and docking analysis to determine their substrate specificity and all the three isoforms displayed high substrate specificity for β-carotene. Further, expression of these three CsCCD4 isoforms investigated in response to various stresses revealed that CsCCD4a and CsCCD4b exhibit enhanced expression in response to dehydration, salt and methylviologen, providing a clue towards their role in mediating plant defense response. This was confirmed by overexpressing CsCCD4b in Arabidopsis. The transgenic plants developed longer roots and possessed higher number of lateral roots. Further, overexpression of CsCCD4b imparted enhanced tolerance to salt, dehydration and oxidative stresses as was evidenced by higher survival rate, increased relative root length and biomass in transgenic plants as compared to wild type. Transgenic plants also displayed higher activity and expression of reactive oxygen species (ROS) metabolizing enzymes. This indicates that β-ionone and β-cyclocitral which are enzymatic products of CsCCD4b may act as stress signals and mediate reprogramming of stress responsive genes which ultimately leads to plant defense.

  1. The Cry4B toxin of Bacillus thuringiensis subsp. israelensis kills Permethrin-resistant Anopheles gambiae, the principal vector of malaria.

    PubMed

    Ibrahim, Mohamed A; Griko, Natalya B; Bulla, Lee A

    2013-04-01

    Resurgence of malaria has been attributed, in part, to the development of resistance by Anopheles gambiae, a principal vector of the disease, to various insecticidal compounds such as Permethrin. Permethrin, a neurotoxicant, is widely used to impregnate mosquito nets. An alternative strategy to control mosquitoes is the use of Bacillus thuringiensis subsp. israelensis (Bti) because there is no observable resistance in the field to the bacterium. Bti kills mosquitoes by targeting cadherin molecules residing in the midgut epithelium of larvae of the insect. Cry proteins (Cry4A, Cry4B, Cry10A and Cry11A) produced by the bacterium during the sporulation phase of its life cycle bind to the cadherin molecules, which serve as receptors for the proteins. These Cry proteins have variable specificity to a variety of mosquitoes, including Culex and Aedes as well as Anopheles. Importantly, selective mosquitocidal action is occasioned by binding of the respective Cry toxins to cadherins distinctive to individual mosquito species. Differential fractionation of the four Cry proteins from a novel Bti isolate (M1) and cloning and expression of their genes in Escherichia coli revealed that Cry4B is the only Cry protein that exerts insecticidal action against An. gambiae. Indeed, it does so against a Permethrin-resistant strain of the mosquito. The other three Cry proteins are ineffective. Multiple sequence alignments of the four Cry proteins revealed a divergent sequence motif in the Cry4B toxin, which most likely determines binding of the toxin to its cognate receptor, BT-R3, in An. gambiae and to its specific toxicity. A model showing Cry4B toxin binding to BT-R3 is presented. PMID:23760000

  2. Overexpression of Crocus carotenoid cleavage dioxygenase, CsCCD4b, in Arabidopsis imparts tolerance to dehydration, salt and oxidative stresses by modulating ROS machinery.

    PubMed

    Baba, Shoib Ahmad; Jain, Deepti; Abbas, Nazia; Ashraf, Nasheeman

    2015-09-15

    Apocarotenoids modulate vital physiological and developmental processes in plants. These molecules are formed by the cleavage of carotenoids, a reaction catalyzed by a family of enzymes called carotenoid cleavage dioxygenases (CCDs). Apocarotenoids like β-ionone and β-cyclocitral have been reported to act as stress signal molecules during high light stress in many plant species. In Crocus sativus, these two apocarotenoids are formed by enzymatic cleavage of β-carotene at 9, 10 and 7, 8 bonds by CsCCD4 enzymes. In the present study three isoforms of CsCCD4 were subjected to molecular modeling and docking analysis to determine their substrate specificity and all the three isoforms displayed high substrate specificity for β-carotene. Further, expression of these three CsCCD4 isoforms investigated in response to various stresses revealed that CsCCD4a and CsCCD4b exhibit enhanced expression in response to dehydration, salt and methylviologen, providing a clue towards their role in mediating plant defense response. This was confirmed by overexpressing CsCCD4b in Arabidopsis. The transgenic plants developed longer roots and possessed higher number of lateral roots. Further, overexpression of CsCCD4b imparted enhanced tolerance to salt, dehydration and oxidative stresses as was evidenced by higher survival rate, increased relative root length and biomass in transgenic plants as compared to wild type. Transgenic plants also displayed higher activity and expression of reactive oxygen species (ROS) metabolizing enzymes. This indicates that β-ionone and β-cyclocitral which are enzymatic products of CsCCD4b may act as stress signals and mediate reprogramming of stress responsive genes which ultimately leads to plant defense. PMID:26595090

  3. Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma.

    PubMed

    Das, Arabinda; Cheng, Ron Ron; Hilbert, Megan L T; Dixon-Moh, Yaenette N; Decandio, Michele; Vandergrift, William Alex; Banik, Naren L; Lindhorst, Scott M; Cachia, David; Varma, Abhay K; Patel, Sunil J; Giglio, Pierre

    2015-01-01

    Glioblastoma (GB) is the most common malignant brain tumor. Drug resistance frequently develops in these tumors during chemotherapy. Therefore, predicting drug response in these patients remains a major challenge in the clinic. Thus, to improve the clinical outcome, more effective and tolerable combination treatment strategies are needed. Robust experimental evidence has shown that the main reason for failure of treatments is signal redundancy due to coactivation of several functionally linked receptor tyrosine kinases (RTKs), including anaplastic lymphoma kinase (ALK), c-Met (hepatocyte growth factor receptor), and oncogenic c-ros oncogene1 (ROS1: RTK class orphan) fusion kinase FIG (fused in GB)-ROS1. As such, these could be attractive targets for GB therapy. The study subjects consisted of 19 patients who underwent neurosurgical resection of GB tissues. Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells. Our results also showed that ex vivo FIG-ROS1+ slices (obtained from GB patients) when cultured were able to preserve tissue architecture, cell viability, and global gene-expression profiles for up to 14 days. Both in vitro and ex vivo studies indicated that combination blockade of FIG, p-ROS1, p-ALK, and p-Met augmented apoptosis, which mechanistically involves activation of Bim and inhibition of survivin, p-Akt, and Mcl-1 expression. However, it is important to note that we did not see any significant synergistic effect of crizotinib and temozolomide on FIG-ROS1-negative GB cells. Thus, these ex vivo culture results will have a significant impact on patient selection for clinical trials and in predicting response to crizotinib and temozolomide therapy. Further studies in different animal models of FIG-ROS1-positive GB cells are warranted to determine useful therapies for the

  4. Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma

    PubMed Central

    Das, Arabinda; Cheng, Ron Ron; Hilbert, Megan L.T.; Dixon-Moh, Yaenette N.; Decandio, Michele; Vandergrift, William Alex; Banik, Naren L.; Lindhorst, Scott M.; Cachia, David; Varma, Abhay K.; Patel, Sunil J.; Giglio, Pierre

    2015-01-01

    Glioblastoma (GB) is the most common malignant brain tumor. Drug resistance frequently develops in these tumors during chemotherapy. Therefore, predicting drug response in these patients remains a major challenge in the clinic. Thus, to improve the clinical outcome, more effective and tolerable combination treatment strategies are needed. Robust experimental evidence has shown that the main reason for failure of treatments is signal redundancy due to coactivation of several functionally linked receptor tyrosine kinases (RTKs), including anaplastic lymphoma kinase (ALK), c-Met (hepatocyte growth factor receptor), and oncogenic c-ros oncogene1 (ROS1: RTK class orphan) fusion kinase FIG (fused in GB)-ROS1. As such, these could be attractive targets for GB therapy. The study subjects consisted of 19 patients who underwent neurosurgical resection of GB tissues. Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells. Our results also showed that ex vivo FIG-ROS1+ slices (obtained from GB patients) when cultured were able to preserve tissue architecture, cell viability, and global gene-expression profiles for up to 14 days. Both in vitro and ex vivo studies indicated that combination blockade of FIG, p-ROS1, p-ALK, and p-Met augmented apoptosis, which mechanistically involves activation of Bim and inhibition of survivin, p-Akt, and Mcl-1 expression. However, it is important to note that we did not see any significant synergistic effect of crizotinib and temozolomide on FIG-ROS1-negative GB cells. Thus, these ex vivo culture results will have a significant impact on patient selection for clinical trials and in predicting response to crizotinib and temozolomide therapy. Further studies in different animal models of FIG-ROS1-positive GB cells are warranted to determine useful therapies for the

  5. Research Paper: The Future or the Hoffman Paper. Curriculum for English 4A and 4B: College Prep English and English 12A and 12B: Life Communications.

    ERIC Educational Resources Information Center

    Davis, Joyce; And Others

    Written for a 12th grade English program at Wayne Central High School, this curriculum project is designed to take into account the affective dynamics/processes as well as the cognitive processes integral to writing research reports. There are two alternatives for this paper which is required of all 12th graders: The Future, a library based…

  6. New AP4B1 mutation in an African-American child associated with intellectual disability

    PubMed Central

    Lamichhane, Dronacharya

    2013-01-01

    Prevalence of intellectual disability (ID) varies from 1–3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously. PMID:27625858

  7. New AP4B1 mutation in an African-American child associated with intellectual disability.

    PubMed

    Lamichhane, Dronacharya

    2013-12-01

    Prevalence of intellectual disability (ID) varies from 1-3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously. PMID:27625858

  8. 75 FR 41871 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... Register of February 21, 2008 (73 FR 9575). Once finalized, the annex will provide guidance to assist... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a draft guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for...

  9. The predominant species of nonstructural protein 4B in hepatitis C virus-replicating cells is not palmitoylated.

    PubMed

    Paul, David; Bartenschlager, Ralf; McCormick, Christopher

    2015-07-01

    Hepatitis C virus (HCV) represents a significant global health burden. Viral replication is thought to occur in close association with remodelled host cell membranes, with non-structural protein 4B (NS4B) being a key player in this process. NS4B is a poorly characterized integral membrane protein, which has been reported to be palmitoylated at its carboxy-terminal end. In order to extend this observation and to establish a functional role for NS4B palmitoylation, we sought to determine the status of this post-translational modification when the protein was expressed as part of a functional viral replicase. We performed direct metabolic labelling and polyethylene glycol-maleimide palmitoylation reporter assays on NS4B expressed in cells containing subgenomic replicons and infectious viral RNA. In a vaccinia virus-based expression system NS4B palmitoylation was detected in a genotype-dependent manner. However, in spite of the high sensitivity of the methods used, no NS4B palmitoylation was found in physiologically more relevant systems. Thus, NS4B palmitoylation is most likely dispensable for HCV RNA replication. PMID:25740959

  10. Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles.

    PubMed

    Sumesh, Remani Vasudevan; Muthu, Muthumani; Almansour, Abdulrahman I; Suresh Kumar, Raju; Arumugam, Natarajan; Athimoolam, S; Jeya Yasmi Prabha, E Arockia; Kumar, Raju Ranjith

    2016-05-01

    The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

  11. The predominant species of nonstructural protein 4B in hepatitis C virus-replicating cells is not palmitoylated

    PubMed Central

    Paul, David

    2015-01-01

    Hepatitis C virus (HCV) represents a significant global health burden. Viral replication is thought to occur in close association with remodelled host cell membranes, with non-structural protein 4B (NS4B) being a key player in this process. NS4B is a poorly characterized integral membrane protein, which has been reported to be palmitoylated at its carboxy-terminal end. In order to extend this observation and to establish a functional role for NS4B palmitoylation, we sought to determine the status of this post-translational modification when the protein was expressed as part of a functional viral replicase. We performed direct metabolic labelling and polyethylene glycol-maleimide palmitoylation reporter assays on NS4B expressed in cells containing subgenomic replicons and infectious viral RNA. In a vaccinia virus-based expression system NS4B palmitoylation was detected in a genotype-dependent manner. However, in spite of the high sensitivity of the methods used, no NS4B palmitoylation was found in physiologically more relevant systems. Thus, NS4B palmitoylation is most likely dispensable for HCV RNA replication. PMID:25740959

  12. Itinerant ferromagnetism and superconductivity in bct ErRh/sub 4/B/sub 4/

    SciTech Connect

    Chaussy, J.; Genicon, J.L.; Lejay, P.; Odin, J.; Shao, L.Q.; Sulpice, A.; Tournier, R.; Chevalier, B.; Etourneau, J.

    1985-04-15

    The body centered tetragonal ErRh/sub 4/B/sub 4/ compound undergoes an itinerant ferromagnetic transition at T/sub m/ = 21 K characterized by a susceptibility equal to the inverse of the demagnetizing coefficient. The itinerant ferromagnetism does not prevent the simultaneous presence of the superconductivity from 7.7 K down to 0 K. The diamagnetic ac susceptibility can be calculated from the ferromagnetic one. The coexistence of itinerant ferromagnetism and superconductivity among d electrons would be one of the most convincing arguments in favor of ''odd-parity'' superconductivity.

  13. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge.

  14. Crystal structure features in a new compound C4B25Mg1.42

    NASA Astrophysics Data System (ADS)

    Konovalikhin, S. V.; Ponomarev, V. I.

    2015-09-01

    The composition of C4B25Mg1.42 crystal obtained by self-propagating high-temperature synthesis was determined using X-ray diffraction. This is the first crystalline structure where all boron atoms in the В12 icosahedron occupy crystallographically independent positions; this circumstance allowed us to analyze the effect of substituents on bond lengths in the icosahedron. The crystal structure features, including the channels filled with disordered Mg atoms and the spread of В—В endo- and exo-bond lengths in the icosahedra, are described. A crystallochemical analysis of pair bonds has been performed for the first time.

  15. Input files with ORNL—mathematical phantoms of the human body for MCNP-4B

    NASA Astrophysics Data System (ADS)

    Krstić, D.; Nikezić, D.

    2007-01-01

    Protection against ionizing radiation requires information on the absorbed doses in organs of the human body. Implantation of many dosimeters in the human body is undesirable (or impossible), so the doses in organs are not measurable and some kind of dose calculation has to be applied. Calculation of doses in organs requests: (a) an exact description of the geometry of organs, (b) the chemical constitution of tissues, and (c) appropriate computer programs. The first two items, (a) and (b), make a so-called "phantom". In another words, the "phantom of a human body" is a mathematical representation of the human body including all other relevant information. All organs are represented with geometrical bodies (like cylinders, ellipsoids, tori, cones etc.), which are described with suitable mathematical equations. A corresponding chemical constitution for various types of organ tissues is also defined. MCNP-4B ( Monte Carlo N- Particle) is often used as transport code. Users of this software prepare an "input file" providing all necessary information for program execution. This information includes: (a) source definition—type of ionizing radiation, energy spectrum, and geometry of the source; (b) target definition—material constitution, geometry, location in respect to the source etc.; (c) characterization of absorbing media between the source and target; (d) output tally, etc. This paper presents input files with "human phantoms" for the MCNP-4B code. The input files with "phantoms" were prepared based on publications issued by the Oak Ridge National Laboratory (ORNL). Seven input files relating to different age groups (newborn, 1, 5, 10, 15 years, as well as, male and female adults) are presented here. A test example and comparison with other data found in literature are also given. Program summaryTitle of program: INPUT FILES, AMALE, AFEMALE, AGE15, AGE10, AGE5, AGE01, NEWB Catalogue identifier:ADYF_v1_0 Program summary URL

  16. Complete Genome Sequence of the Larvicidal Bacterium Lysinibacillus sphaericus Strain OT4b.25

    PubMed Central

    Rey, Andrés; Silva-Quintero, Laura

    2016-01-01

    Lysinibacillus sphaericus OT4b.25 is a native Colombian strain isolated from coleopteran larvae in an oak forest near Bogotá D.C.; this strain has shown high levels of pathogenic activity against Culex quinquefasciatus larvae in laboratory assays compared to that of other members of the same species. Using Pacific Biosciences sequencing technology, we propose a chromosomal contig of 4,665,775 bp that, according to comparative analysis, is highly similar to that of reference strain L. sphaericus C3-41. PMID:27151786

  17. Host pollination mode and mutualist pollinator presence: net effect of internally ovipositing parasite in the fig-wasp mutualism.

    PubMed

    Zhang, Fengping; Peng, Yanqiong; Compton, Stephen G; Zhao, Yi; Yang, Darong

    2009-04-01

    The Ficus-their specific pollinating fig wasps (Chalcidoidea, Agaonidae) interaction presents a striking example of mutualism. Figs also shelter numerous non-pollinating fig wasps (NPFW) that exploit the fig-pollinator mutualism. Only a few NPFW species can enter figs to oviposit, they do not belong to the pollinating lineage Agaonidae. The internally ovipositing non-agaonid fig wasps can efficiently pollinate the Ficus species that were passively pollinated. However, there is no study to focus on the net effect of these internally ovipositing non-agaonid wasps in actively pollinated Ficus species. By collecting the data of fig wasp community and conducting controlled experiments, our results showed that internally ovipositing Diaziella bizarrea cannot effectively pollinate Ficus glaberrima, an actively pollinated monoecious fig tree. Furthermore, D. bizarrea failed to reproduce if they were introduced into figs without Eupristina sp., the regular pollinator, as all the figs aborted. Furthermore, although D. bizarrea had no effect on seed production in shared figs, it significantly reduced the number of Eupristina sp. progeny emerging from them. Thus, our experimental evidence shows that reproduction in Diaziella depends on the presence of agaonid pollinators, and whether internally ovipositing parasites can act as pollinators depends on the host fig's pollination mode (active or passive). Overall, this study and others suggest a relatively limited mutualistic role for internally ovipositing fig wasps from non-pollinator (non-Agaonidae) lineages.

  18. Identification of Amino Acid Determinants in CYP4B1 for Optimal Catalytic Processing of 4-Ipomeanol

    PubMed Central

    Wiek, Constanze; Schmidt, Eva M; Roellecke, Katharina; Freund, Marcel; Nakano, Mariko; Kelly, Edward J; Kaisers, Wolfgang; Yarov-Yarovoy, Vladimir; Kramm, Christof M; Rettie, Allan E; Hanenberg, Helmut

    2014-01-01

    Mammalian CYP4B1 enzymes are cytochrome P450 monooxygenases that are responsible for the bioactivation of several exogenous pro-toxins including 4-ipomeanol (4-IPO). In contrast to the orthologous rabbit enzyme, we show here that native human CYP4B1 with a serine at position 427 is unable to bio-activate 4-IPO and does not cause cytotoxicity in HepG2 cells and primary human T-cells that overexpress these enzymes. We also demonstrate that a proline residue in the meander region at position 427 in human CYB4B1 and 422 in rabbit CYP4B1 is important for protein stability and rescues the 4-IPO bioactivation of the human enzyme, but is not essential for the catalytic activity of the rabbit CYP4B1 protein. Systematic substitution of native and p.S427P human CYP4B1 with peptide regions from the highly active rabbit enzyme reveals that 18 amino acids in the wild-type rabbit CYP4B1 protein are key for conferring high 4-IPO metabolizing activity. Introduction of 12 of the 18 amino acids that are also present at corresponding positions in other human CYP4 family members into the p.S427P human CYP4B1 protein results in a mutant human enzyme (P+12) that is as stable and as active as the rabbit wild-type CYP4B1 protein. These 12 mutations cluster in the predicted B–C loop through F-helix regions and reveal new amino acid regions important to P450 enzyme stability. Finally, by minimally re-engineering the human CYP4B1 enzyme for efficient activation of 4-IPO, we have developed a novel human suicide gene system that is a candidate for adoptive cellular therapies in humans. PMID:25247810

  19. Generalized transduction of serotype 1/2 and serotype 4b strains of Listeria monocytogenes.

    PubMed

    Hodgson, D A

    2000-01-01

    This is the first report of generalized transduction in the gram-positive, food-borne pathogen Listeria monocytogenes. Bacteriophages were isolated from the environment and from lysogens, or were obtained from other laboratories. Of the 59 bacteriophages tested, 34 proved to be capable of transduction. We exploited the ability of L. monocytogenes to grow at room temperature and isolated bacteriophages that were incapable of growth at 37 degrees C. Transductions at this temperature therefore eliminated transductant killing and lysogeny, as did inclusion of citrate and the use of a low multiplicity of infection. Transducing bacteriophages were found for each of the well-characterized L. monocytogenes strains: EGD, 10403, Mack (serotype1/2a), L028 (serotype 1/2c), Scott A (serotype 4b) and strains from the Jalisco and Halifax, Nova Scotia outbreaks (serotype 4b). P35 (phiLMUP35) is a particularly useful generalized transducing bacteriophage with a wide host range (75% of all serotype 1/2 strains tested). Its disadvantages are that it is small and transduction is relatively infrequent. U153(phiCU-SI153/95) is larger than P35 and transduction frequency increased 100-fold, but it has a very narrow host range. We demonstrated interstrain transduction and used transduction to test linkage between transposon insertions and mutant phenotypes in a variety of strains.

  20. Spatial Distribution of Crown Gall in a Commercial Nursery of Weeping Fig

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agrobacterium larrymoorei causes tumors on the trunk and branches of weeping fig (Ficus benjamina L.). The extent to which this pathogen is spread through the mother tree planting and transmitted to daughter branches during the process of propagation was studied in a commercial nursery in 2007 and 2...

  1. New plant-parasitic nematode from the mostly mycophagous genus Bursaphelenchus discovered inside figs in Japan.

    PubMed

    Kanzaki, Natsumi; Tanaka, Ryusei; Giblin-Davis, Robin M; Davies, Kerrie A

    2014-01-01

    A new nematode species, Bursaphelenchus sycophilus n. sp. is described. The species was found in syconia of a fig species, Ficus variegata during a field survey of fig-associated nematodes in Japan. Because it has a well-developed stylet and pharyngeal glands, the species is considered an obligate plant parasite, and is easily distinguished from all other fungal-feeding species in the genus based upon these characters. Although B. sycophilus n. sp. shares an important typological character, male spicule possessing a strongly recurved condylus, with the "B. eremus group" and the "B. leoni group" of the genus, it was inferred to be monophyletic with the "B. fungivorus group". The uniquely shaped stylet and well-developed pharyngeal glands is reminiscent of the fig-floret parasitic but paraphyletic assemblage of "Schistonchus". Thus, these morphological characters appear to be an extreme example of convergent evolution in the nematode family, Aphelenchoididae, inside figs. Other characters shared by the new species and its close relatives, i.e., lack of ventral P1 male genital papilla, female vulval flap, and papilla-shaped P4 genital papillae in males, corroborate the molecular phylogenetic inference. The unique biological character of obligate plant parasitism and highly derived appearance of the ingestive organs of Bursaphelenchus sycophilus n. sp. expands our knowledge of the potential morphological, physiological and developmental plasticity of the genus Bursaphelenchus.

  2. Trapping African fig fly (Diptera: Drosophilidae) with combinations of vinegar and wine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The African fig fly, Zaprionus indianus Gupta (Diptera: Drosophilidae), is an invasive fruit pest that has spread rapidly through much of the eastern United States. Tests were conducted in southern Florida that recorded the response of Z. indianus to baits that included Merlot wine, rice vinegar, et...

  3. Oviposition strategies, host coercion and the stable exploitation of figs by wasps.

    PubMed Central

    Yu, Douglas W.; Ridley, Jo; Jousselin, Emmanuelle; Herre, Edward Allen; Compton, Stephen G.; Cook, James M.; Moore, Jamie C.; Weiblen, George D.

    2004-01-01

    A classic example of a mutualism is the one between fig plants (Ficus) and their specialized and obligate pollinating wasps. The wasps deposit eggs in fig ovules, which the larvae then consume. Because the wasps derive their fitness only from consumed seeds, this mutualism can persist only if the wasps are prevented from laying eggs in all ovules. The search for mechanisms that can limit oviposition and stabilize the wasp-seed conflict has spanned more than three decades. We use a simple foraging model, parameterized with data from two Ficus species, to show how fig morphology reduces oviposition rates and helps to resolve the wasp-seed conflict. We also propose additional mechanisms, based on known aspects of fig biology, which can prevent even large numbers of wasps from ovipositing in all ovules. It has been suggested that in mutualistic symbioses, the partner that controls the physical resources, in this case Ficus, ultimately controls the rate at which hosts are converted to visitors, regardless of relative evolutionary rates. Our approach provides a mechanistic implementation of this idea, with potential applications to other mutualisms and to theories of virulence. PMID:15306369

  4. Non-quantitative adjustment of offspring sex ratios in pollinating fig wasps

    PubMed Central

    Wang, Rui-Wu; Sun, Bao-Fa; He, Jun-Zhou; Dunn, Derek W.

    2015-01-01

    Fig wasp is one of the most well known model systems in examining whether or not the parents could adjust their offspring sex ratio to maximize their gene frequency transmission in next generations. Our manipulative experiments showed that, in all of the five pollinator wasps of figs (Agaonidae) that have different averages of foundress numbers per syconium, almost the same proportions of male offspring are produced in the experiment that foundresses deposit one hour then are killed with ether (66.1%–70.1%) and over the lifespan of each foundress (14.0%–21.0%). The foundresses tend to deposit their male eggs prior to female eggs. The observed increase in the proportion of male offspring as a function of foundress number results from density-dependent interference competition among the foundresses. These results showed that the selection of gene frequency transmission through the behavioral adjustment in the evolution of sex ratio does not exist in these five fig wasps. The results here implied that genetic adjustment mechanisms of the sex ratio of fig wasps can only be triggered to be on or off and that the foundresses can not quantitatively adjust their sex ratio according to increased environmental selection pressure. PMID:26293349

  5. Riparian Ficus Tree Communities: The Distribution and Abundance of Riparian Fig Trees in Northern Thailand

    PubMed Central

    Pothasin, Pornwiwan; Compton, Stephen G.; Wangpakapattanawong, Prasit

    2014-01-01

    Fig trees (Ficus) are often ecologically significant keystone species because they sustain populations of the many seed-dispersing animals that feed on their fruits. They are prominent components of riparian zones where they may also contribute to bank stability as well as supporting associated animals. The diversity and distributions of riparian fig trees in deciduous and evergreen forests in Chiang Mai Province, Northern Thailand were investigated in 2010–2012. To record the diversity and abundance of riparian fig trees, we (1) calculated stem density, species richness, and diversity indices in 20×50 m randomly selected quadrats along four streams and (2) measured the distances of individual trees from four streams to determine if species exhibit distinct distribution patterns within riparian zones. A total of 1169 individuals (from c. 4 ha) were recorded in the quadrats, representing 33 Ficus species (13 monoecious and 20 dioecious) from six sub-genera and about 70% of all the species recorded from northern Thailand. All 33 species had at least some stems in close proximity to the streams, but they varied in their typical proximity, with F. squamosa Roxb. and F. ischnopoda Miq the most strictly stream-side species. The riparian forests in Northern Thailand support a rich diversity and high density of Ficus species and our results emphasise the importance of fig tree within the broader priorities of riparian area conservation. Plans to maintain or restore properly functioning riparian forests need to take into account their significance. PMID:25310189

  6. New Plant-Parasitic Nematode from the Mostly Mycophagous Genus Bursaphelenchus Discovered inside Figs in Japan

    PubMed Central

    Kanzaki, Natsumi; Tanaka, Ryusei; Giblin-Davis, Robin M.; Davies, Kerrie A.

    2014-01-01

    A new nematode species, Bursaphelenchus sycophilus n. sp. is described. The species was found in syconia of a fig species, Ficus variegata during a field survey of fig-associated nematodes in Japan. Because it has a well-developed stylet and pharyngeal glands, the species is considered an obligate plant parasite, and is easily distinguished from all other fungal-feeding species in the genus based upon these characters. Although B. sycophilus n. sp. shares an important typological character, male spicule possessing a strongly recurved condylus, with the “B. eremus group” and the “B. leoni group” of the genus, it was inferred to be monophyletic with the “B. fungivorus group”. The uniquely shaped stylet and well-developed pharyngeal glands is reminiscent of the fig-floret parasitic but paraphyletic assemblage of “Schistonchus”. Thus, these morphological characters appear to be an extreme example of convergent evolution in the nematode family, Aphelenchoididae, inside figs. Other characters shared by the new species and its close relatives, i.e., lack of ventral P1 male genital papilla, female vulval flap, and papilla-shaped P4 genital papillae in males, corroborate the molecular phylogenetic inference. The unique biological character of obligate plant parasitism and highly derived appearance of the ingestive organs of Bursaphelenchus sycophilus n. sp. expands our knowledge of the potential morphological, physiological and developmental plasticity of the genus Bursaphelenchus. PMID:24940595

  7. Riparian Ficus tree communities: the distribution and abundance of riparian fig trees in northern Thailand.

    PubMed

    Pothasin, Pornwiwan; Compton, Stephen G; Wangpakapattanawong, Prasit

    2014-01-01

    Fig trees (Ficus) are often ecologically significant keystone species because they sustain populations of the many seed-dispersing animals that feed on their fruits. They are prominent components of riparian zones where they may also contribute to bank stability as well as supporting associated animals. The diversity and distributions of riparian fig trees in deciduous and evergreen forests in Chiang Mai Province, Northern Thailand were investigated in 2010-2012. To record the diversity and abundance of riparian fig trees, we (1) calculated stem density, species richness, and diversity indices in 20×50 m randomly selected quadrats along four streams and (2) measured the distances of individual trees from four streams to determine if species exhibit distinct distribution patterns within riparian zones. A total of 1169 individuals (from c. 4 ha) were recorded in the quadrats, representing 33 Ficus species (13 monoecious and 20 dioecious) from six sub-genera and about 70% of all the species recorded from northern Thailand. All 33 species had at least some stems in close proximity to the streams, but they varied in their typical proximity, with F. squamosa Roxb. and F. ischnopoda Miq the most strictly stream-side species. The riparian forests in Northern Thailand support a rich diversity and high density of Ficus species and our results emphasise the importance of fig tree within the broader priorities of riparian area conservation. Plans to maintain or restore properly functioning riparian forests need to take into account their significance.

  8. Non-quantitative adjustment of offspring sex ratios in pollinating fig wasps.

    PubMed

    Wang, Rui-Wu; Sun, Bao-Fa; He, Jun-Zhou; Dunn, Derek W

    2015-08-21

    Fig wasp is one of the most well known model systems in examining whether or not the parents could adjust their offspring sex ratio to maximize their gene frequency transmission in next generations. Our manipulative experiments showed that, in all of the five pollinator wasps of figs (Agaonidae) that have different averages of foundress numbers per syconium, almost the same proportions of male offspring are produced in the experiment that foundresses deposit one hour then are killed with ether (66.1%-70.1%) and over the lifespan of each foundress (14.0%-21.0%). The foundresses tend to deposit their male eggs prior to female eggs. The observed increase in the proportion of male offspring as a function of foundress number results from density-dependent interference competition among the foundresses. These results showed that the selection of gene frequency transmission through the behavioral adjustment in the evolution of sex ratio does not exist in these five fig wasps. The results here implied that genetic adjustment mechanisms of the sex ratio of fig wasps can only be triggered to be on or off and that the foundresses can not quantitatively adjust their sex ratio according to increased environmental selection pressure.

  9. Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B

    PubMed Central

    Kong, Lingbao; Fujimoto, Akira; Nakamura, Mariko; Aoyagi, Haruyo; Matsuda, Mami; Watashi, Koichi; Suzuki, Ryosuke; Arita, Minetaro; Yamagoe, Satoshi; Dohmae, Naoshi; Suzuki, Takehiro; Sakamaki, Yuriko; Ichinose, Shizuko; Suzuki, Tetsuro; Wakita, Takaji

    2016-01-01

    ABSTRACT It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCE The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication

  10. The LARK/RBM4a protein is highly expressed in cerebellum as compared to cerebrum.

    PubMed

    Pfuhl, Thorsten; Mamiani, Alfredo; Dürr, Matthias; Welter, Susanne; Stieber, Johanna; Ankara, Jasmin; Liss, Michael; Dobner, Thomas; Schmitt, Andrea; Falkai, Peter; Kremmer, Elisabeth; Jung, Volker; Barth, Stephanie; Grässer, Friedrich A

    2008-10-17

    The RNA binding motif protein 4 genes RBM4a and RBM4b are located on human chromosome 11q13.2 and encode highly similar proteins of 363 and 359 amino acids, respectively. They contain two RNA recognition motifs (RRMs) and a retroviral-type Zn-finger. RBM4a binds RNA, is involved in alternative splicing and is also a part of the microRNA-processing RISC complex. In particular, RBM4a is involved in exon 10 inclusion of the tau protein. The function of RBM4b is unknown. With new monoclonal antibodies we show that RBM4a is detectable in virtually all tissues and cell lines tested while RBM4b was only found in kidney and liver. Both RBM4a and RBM4b are nuclear phosphoproteins with half-lives of 2.5h and 4.5h, respectively. To our knowledge, this is the first description of RBM4b protein in human tissue. In human brain, expression of RBM4a was strongly up-regulated in cerebellum as compared to forebrain.

  11. Hepatitis C virus core, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection

    PubMed Central

    Sillanpää, Maarit; Melén, Krister; Porkka, Päivi; Fagerlund, Riku; Nevalainen, Kaisu; Lappalainen, Maija; Julkunen, Ilkka

    2009-01-01

    Background The viral genome of hepatitis C virus constitutes a 9.6-kb single-stranded positive-sense RNA which encodes altogether 11 viral proteins. In order to study the humoral immune responses against different HCV proteins in patients suffering from chronic HCV infection, we produced three structural (core, E1 and E2) and six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) in Sf9 insect cells by using the baculovirus expression system. Results The recombinant HCV core, E1, E2, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins were purified and used in Western blot analysis to determine antibody responses against individual HCV protein in 68 HCV RNA and antibody positive human sera that were obtained from patients suffering from genotype 1, 2, 3 or 4 infection. These sera were also analysed with INNO-LIA Score test for HCV antibodies against core, NS3, NS4AB and NS5A, and the results were similar to the ones obtained by Western blot method. Based on our Western blot analyses we found that the major immunogenic HCV antigens were the core, NS4B, NS3 and NS5A proteins which were recognized in 97%, 86%, 68% and 53% of patient sera, respectively. There were no major genotype specific differences in antibody responses to individual HCV proteins. A common feature within the studied sera was that all except two sera recognized the core protein in high titers, whereas none of the sera recognized NS2 protein and only three sera (from genotype 3) recognised NS5B. Conclusion The data shows significant variation in the specificity in humoral immunity in chronic HCV patients. PMID:19549310

  12. Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular arrhythmias in mice.

    PubMed

    Leroy, Jérôme; Richter, Wito; Mika, Delphine; Castro, Liliana R V; Abi-Gerges, Aniella; Xie, Moses; Scheitrum, Colleen; Lefebvre, Florence; Schittl, Julia; Mateo, Philippe; Westenbroek, Ruth; Catterall, William A; Charpentier, Flavien; Conti, Marco; Fischmeister, Rodolphe; Vandecasteele, Grégoire

    2011-07-01

    β-Adrenergic receptors (β-ARs) enhance cardiac contractility by increasing cAMP levels and activating PKA. PKA increases Ca²⁺-induced Ca²⁺ release via phosphorylation of L-type Ca²⁺ channels (LTCCs) and ryanodine receptor 2. Multiple cyclic nucleotide phosphodiesterases (PDEs) regulate local cAMP concentration in cardiomyocytes, with PDE4 being predominant for the control of β-AR-dependent cAMP signals. Three genes encoding PDE4 are expressed in mouse heart: Pde4a, Pde4b, and Pde4d. Here we show that both PDE4B and PDE4D are tethered to the LTCC in the mouse heart but that β-AR stimulation of the L-type Ca²⁺ current (ICa,L) is increased only in Pde4b-/- mice. A fraction of PDE4B colocalized with the LTCC along T-tubules in the mouse heart. Under β-AR stimulation, Ca²⁺ transients, cell contraction, and spontaneous Ca²⁺ release events were increased in Pde4b-/- and Pde4d-/- myocytes compared with those in WT myocytes. In vivo, after intraperitoneal injection of isoprenaline, catheter-mediated burst pacing triggered ventricular tachycardia in Pde4b-/- mice but not in WT mice. These results identify PDE4B in the CaV1.2 complex as a critical regulator of ICa,L during β-AR stimulation and suggest that distinct PDE4 subtypes are important for normal regulation of Ca²⁺-induced Ca²⁺ release in cardiomyocytes.

  13. Host pollination mode and mutualist pollinator presence: net effect of internally ovipositing parasite in the fig-wasp mutualism

    NASA Astrophysics Data System (ADS)

    Zhang, Fengping; Peng, Yanqiong; Compton, Stephen G.; Zhao, Yi; Yang, Darong

    2009-04-01

    The Ficus-their specific pollinating fig wasps (Chalcidoidea, Agaonidae) interaction presents a striking example of mutualism. Figs also shelter numerous non-pollinating fig wasps (NPFW) that exploit the fig-pollinator mutualism. Only a few NPFW species can enter figs to oviposit, they do not belong to the pollinating lineage Agaonidae. The internally ovipositing non-agaonid fig wasps can efficiently pollinate the Ficus species that were passively pollinated. However, there is no study to focus on the net effect of these internally ovipositing non-agaonid wasps in actively pollinated Ficus species. By collecting the data of fig wasp community and conducting controlled experiments, our results showed that internally ovipositing Diaziella bizarrea cannot effectively pollinate Ficus glaberrima, an actively pollinated monoecious fig tree. Furthermore, D. bizarrea failed to reproduce if they were introduced into figs without Eupristina sp., the regular pollinator, as all the figs aborted. Furthermore, although D. bizarrea had no effect on seed production in shared figs, it significantly reduced the number of Eupristina sp. progeny emerging from them. Thus, our experimental evidence shows that reproduction in Diaziella depends on the presence of agaonid pollinators, and whether internally ovipositing parasites can act as pollinators depends on the host fig’s pollination mode (active or passive). Overall, this study and others suggest a relatively limited mutualistic role for internally ovipositing fig wasps from non-pollinator (non-Agaonidae) lineages.

  14. 75 FR 6344 - Notice of Availability of Pest Risk Analyses for Importation of Fresh Figs, Pomegranates, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... of Fresh Figs, Pomegranates, and Baby Kiwi from Chile into the United States AGENCY: Animal and Plant... prepared two pest risk analyses, one with respect to fresh figs and pomegranates grown in Chile and one... the importation into the continental United States of fresh figs, pomegranates, and baby kiwi...

  15. Host sex-specific parasites in a functionally dioecious fig: a preference way of adaptation to their hosts.

    PubMed

    Wang, Qi; Jiang, Zi-Feng; Wang, Ning-Xin; Niu, Li-Ming; Li, Zi; Huang, Da-Wei

    2013-09-01

    Host-parasites interaction is a common phenomenon in nature. Diffusive coevolution might maintain stable cooperation in a fig-fig wasps system, in which the exploiter might diversify their genotype, phenotype, or behavior as a result of competition with pollinator, whereas the figs change flower syconia, fruits thickness, and syconia structure. In functionally dioecious Ficus auriculata, male figs and female figs contain two types of florets on separate plant, and share high similarities in outside morphology. Apocryptophagus (Sycophaginae, Chalcidoidea, Hymenoptera) is one of few groups of nonpollinating fig wasps that can reproduce within both male and female figs. On the basis of the morphology and DNA barcoding, evidence from partial sequences of mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 2, we found that there are two nonsibling Apocryptophagus species living on male and female F. auriculata figs, respectively. We estimated that these two species diverged about 19.2 million years ago. Our study suggests that the host shift from Ficus variegate or Ficus prostrata fig species to male figs is a preference way for Apocryptophagus wasps to adapt to the separation of sexual function in diecious figs. Furthermore, to escape the disadvantage or sanction impact of the host, the exploiter Apocryptophagus wasps can preferably adapt to exploiting each sex of the figs, by changing their oviposition, niche shift, and habitat.

  16. SLC4A Transporters

    PubMed Central

    Choi, Inyeong

    2016-01-01

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

  17. Characterization of an Additional Splice Acceptor Site Introduced into CYP4B1 in Hominoidae during Evolution

    PubMed Central

    Parkinson, Oliver T.; Roellecke, Katharina; Freund, Marcel; Gombert, Michael; Lottmann, Nadine; Steward, Charles A.; Kramm, Christof M.; Yarov-Yarovoy, Vladimir; Rettie, Allan E.; Hanenberg, Helmut

    2015-01-01

    CYP4B1 belongs to the cytochrome P450 family 4, one of the oldest P450 families whose members have been highly conserved throughout evolution. The CYP4 monooxygenases typically oxidize fatty acids to both inactive and active lipid mediators, although the endogenous ligand(s) is largely unknown. During evolution, at the transition of great apes to humanoids, the CYP4B1 protein acquired a serine instead of a proline at the canonical position 427 in the meander region. Although this alteration impairs P450 function related to the processing of naturally occurring lung toxins, a study in transgenic mice suggested that an additional serine insertion at position 207 in human CYP4B1 can rescue the enzyme stability and activity. Here, we report that the genomic insertion of a CAG triplet at the intron 5–exon 6 boundary in human CYP4B1 introduced an additional splice acceptor site in frame. During evolution, this change occurred presumably at the stage of Hominoidae and leads to two major isoforms of the CYP4B1 enzymes of humans and great apes, either with or without a serine 207 insertion (insSer207). We further demonstrated that the CYP4B1 enzyme with insSer207 is the dominant isoform (76%) in humans. Importantly, this amino acid insertion did not affect the 4-ipomeanol metabolizing activities or stabilities of the native rabbit or human CYP4B1 enzymes, when introduced as transgenes in human primary cells and cell lines. In our 3D modeling, this functional neutrality of insSer207 is compatible with its predicted location on the exterior surface of CYP4B1 in a flexible side chain. Therefore, the Ser207 insertion does not rescue the P450 functional activity of human CYP4B1 that has been lost during evolution. PMID:26355749

  18. Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair.

    PubMed

    Yu, Jun; Fernández-Hernando, Carlos; Suarez, Yajaira; Schleicher, Michael; Hao, Zhengrong; Wright, Paulette L; DiLorenzo, Annarita; Kyriakides, Themis R; Sessa, William C

    2009-10-13

    Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have reduced spreading and chemotaxis due to impaired Rac activation. Bone marrow reconstitution experiments show that Nogo in myeloid cells is necessary to promote macrophage homing and functional recovery after limb ischemia. Thus, endogenous Nogo coordinates macrophage-mediated inflammation with arteriogenesis, wound healing, and blood flow control. PMID:19805174

  19. A new experiment station on beamline 4B7A at Beijing Synchrotron Radiation Facility

    NASA Astrophysics Data System (ADS)

    Zheng, L.; Zhao, Y. D.; Tang, K.; Ma, C. Y.; Hong, C. H.; Han, Y.; Cui, M. Q.; Guo, Z. Y.

    2014-11-01

    A new experiment station was installed on beamline 4B7A at Beijing Synchrotron Radiation Facility (BSRF), making it possible to record X-ray absorption fine structure (XAFS) spectrum in three modes over an energy range from 1750 eV to 6000 eV. A 13-element Si(Li) array detector and a single-element SDD detector were used to acquire data in partial fluorescence yield (PFY) mode. Two low-pressure noble gas ion chambers were adopted for measuring XAFS in transmission mode. In total electron yield (TEY) mode the current of sample is recorded. Solid, wet and liquid samples were suitable for this experimental station. Some representative results obtained from this station were shown and discussed.

  20. BOREAS Level-4b AVHRR-LAC Ten-Day Composite Images: At-sensor Radiance

    NASA Technical Reports Server (NTRS)

    Cihlar, Josef; Chen, Jing; Nickerson, Jaime; Newcomer, Jeffrey A.; Huang, Feng-Ting; Hall, Forrest G. (Editor)

    2000-01-01

    The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Manitoba Remote Sensing Center (MRSC) and BOREAS Information System (BORIS) personnel acquired, processed, and archived data from the Advanced Very High Resolution Radiometer (AVHRR) instruments on the National Oceanic and Atmospheric Administration (NOAA-11) and -14 satellites. The AVHRR data were acquired by CCRS and were provided to BORIS for use by BOREAS researchers. These AVHRR level-4b data are gridded, 10-day composites of at-sensor radiance values produced from sets of single-day images. Temporally, the 10- day compositing periods begin 11-Apr-1994 and end 10-Sep-1994. Spatially, the data cover the entire BOREAS region. The data are stored in binary image format files.

  1. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge. PMID:26179097

  2. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

    PubMed Central

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. Methods: PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Results: Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). Results of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). Conclusion: It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII. PMID:26034723

  3. Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B

    PubMed Central

    Rao, Minxi; Smith, Brian C.

    2015-01-01

    ABSTRACT Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. PMID:25944856

  4. Fig leaf tanning lotion and sun-related burns: case reports.

    PubMed

    Bollero, D; Stella, M; Rivolin, A; Cassano, P; Risso, D; Vanzetti, M

    2001-11-01

    A sun tan is considered a symbol of well-being in our society, but incorrect methods of sun exposure can create serious problems. We present two cases of severe sun-related burns caused by fig leaf decoction used as home-made tanning lotion. Twenty four-thirty six hours after application and sun exposure, patients developed a phytophotodermatitis characterised by erythema, and blister formation involving all the photoexposed areas (45-70% BSA). Their general conditions became rapidly critical and they were admitted to our Burn Centre. The patients were discharged after 11 and 26 days, respectively. Haemolytic anaemia and retinal haemorrhages presented as systemic complications due to the furocoumarins present in the fig leaf decoction.

  5. Large-scale diversification without genetic isolation in nematode symbionts of figs.

    PubMed

    Susoy, Vladislav; Herrmann, Matthias; Kanzaki, Natsumi; Kruger, Meike; Nguyen, Chau N; Rödelsperger, Christian; Röseler, Waltraud; Weiler, Christian; Giblin-Davis, Robin M; Ragsdale, Erik J; Sommer, Ralf J

    2016-01-01

    Diversification is commonly understood to be the divergence of phenotypes accompanying that of lineages. In contrast, alternative phenotypes arising from a single genotype are almost exclusively limited to dimorphism in nature. We report a remarkable case of macroevolutionary-scale diversification without genetic divergence. Upon colonizing the island-like microecosystem of individual figs, symbiotic nematodes of the genus Pristionchus accumulated a polyphenism with up to five discrete adult morphotypes per species. By integrating laboratory and field experiments with extensive genotyping of individuals, including the analysis of 49 genomes from a single species, we show that rapid filling of potential ecological niches is possible without diversifying selection on genotypes. This uncoupling of morphological diversification and speciation in fig-associated nematodes has resulted from a remarkable expansion of discontinuous developmental plasticity.

  6. Large-scale diversification without genetic isolation in nematode symbionts of figs

    PubMed Central

    Susoy, Vladislav; Herrmann, Matthias; Kanzaki, Natsumi; Kruger, Meike; Nguyen, Chau N.; Rödelsperger, Christian; Röseler, Waltraud; Weiler, Christian; Giblin-Davis, Robin M.; Ragsdale, Erik J.; Sommer, Ralf J.

    2016-01-01

    Diversification is commonly understood to be the divergence of phenotypes accompanying that of lineages. In contrast, alternative phenotypes arising from a single genotype are almost exclusively limited to dimorphism in nature. We report a remarkable case of macroevolutionary-scale diversification without genetic divergence. Upon colonizing the island-like microecosystem of individual figs, symbiotic nematodes of the genus Pristionchus accumulated a polyphenism with up to five discrete adult morphotypes per species. By integrating laboratory and field experiments with extensive genotyping of individuals, including the analysis of 49 genomes from a single species, we show that rapid filling of potential ecological niches is possible without diversifying selection on genotypes. This uncoupling of morphological diversification and speciation in fig-associated nematodes has resulted from a remarkable expansion of discontinuous developmental plasticity. PMID:26824073

  7. Trade-offs and coexistence: a lottery model applied to fig wasp communities.

    PubMed

    Duthie, A Bradley; Abbott, Karen C; Nason, John D

    2014-06-01

    Ecological communities in which organisms complete their life cycles on discrete ephemeral patches are common and often support an unusually large number of species. Explaining this diversity is challenging for communities of ecologically similar species undergoing preemptive competition, where classic coexistence mechanisms may not readily apply. We use nonpollinating fig wasps as a model community characterized by high diversity and preemptive competition to show how subadditive population growth and a trade-off between competitor fecundity and dispersal ability can lead to coexistence. Because nonpollinator species are often closely related, have similar life histories, and compete for the same discrete resources, understanding their coexistence is challenging given competitive exclusion is expected. Empirical observations suggest that nonpollinating fig wasp species may face a trade-off between egg loads and dispersal abilities. We model a lottery in which a species' competitive ability is determined by a trade-off between fecundity and dispersal ability. Variation in interpatch distance between figs generates temporal variability in the relative benefit of fecundity versus dispersal. We show that the temporal storage effect leads to coexistence for a range of biologically realistic parameter values. We further use individual-based modeling to show that when species' traits evolve, coexistence is less likely but trait divergence can result. We discuss the implications of this coexistence mechanism for ephemeral patch systems wherein competition is strongly preemptive.

  8. Characterization of fig achenes' oil of Ficus carica grown in Tunisia.

    PubMed

    Soltana, Hala; Tekaya, Meriem; Amri, Zahra; El-Gharbi, Sinda; Nakbi, Amel; Harzallah, Arij; Mechri, Beligh; Hammami, Mohamed

    2016-04-01

    This work investigated the composition of the oil extract from achenes of "Kholi" variety of Ficus carica, grown in Tunisia. Fatty acid and sterol compositions were analyzed by gas chromatography (GC) coupled to flame ionization detector (FID). Furthermore, the antioxidant capacity in fig achenes' oil was assessed by employing two different in vitro assays such as DPPH, ABTS(+) radical scavenging capacities. Our results indicated that the fig achenes' oil is a rich source of bioactive molecules. The soxhlet n-hexane extraction of these achenes produced a total oil yield of 16.24%. The predominant fatty acid was linolenic acid. Concerning phytosterols, the total amount reached 1061.45 mg/100 g with a predominance of Δ(5,23)-stigmastadienol (73.78%). Regarding antioxidant activities, the half maximal inhibitory concentration (IC50) was 215.86 μg/ml and Trolox equivalent antioxidant capacity (TEAC) was 95.25 mM. These data indicate that fig achenes oil of F. carica could be potentially useful in food and pharmaceutical applications. PMID:26593597

  9. Influence of harvesting and drying techniques on microflora and mycotoxin contamination of figs.

    PubMed

    Ozay, G; Aran, N; Pala, M

    1995-01-01

    Mould growth and mycotoxin (aflatoxins and ochratoxin A) formation were examined in the 1993 dried figs crop. The relationships between mould/mycotoxin contamination and orchard conditions, different harvesting techniques, harvesting time and intactness of fruits were investigated. The fruits were examined during drying and effects of different pretreatments, sun drying and solar drying on the mould and mycotoxin contamination in figs were also studied. Aflatoxins (B1, B2, G1 and G2) were not present in the firm or shrivelled ripe figs. Among the samples examined during drying, only one of the 32 samples was found to be aflatoxin positive. Ochratoxin A was not detected in any of the samples analysed. The moisture content, aw and pH values of full ripe and shrivelled fruits were suitable for mould growth and mycotoxin formation while these parameters in pretreated and dried fruits were found to be too low to allow such outcome. It was observed that harvesting the fruit by hand-treating with different solutions and application of solar drying were effective in reducing contamination level. PMID:7783781

  10. Pollinating fig wasp Ceratosolen solmsi adjusts the offspring sex ratio to other foundresses.

    PubMed

    Hu, Hao-Yuan; Chen, Zhong-Zheng; Jiang, Zi-Feng; Huang, Da-Wei; Niu, Li-Ming; Fu, Yue-Guan

    2013-04-01

    Local mate competition theory predicts that offspring sex ratio in pollinating fig wasps is female-biased when there is only one foundress, and increased foundress density results in increased offspring sex ratio. Information of other foundresses and clutch size have been suggested to be the main proximate explanations for sex ratio adjustment under local mate competition. Our focus was to show the mechanism of sex ratio adjustment in a pollinating fig wasp, Ceratosolen solmsi Mayr, an obligate pollinator of the functionally dioecious fig, Ficus hispida Linn., with controlled experiments in the field. First, we obtained offspring from one pollinator and offspring at different oviposition sequences, and found that offspring sex ratio decreased with clutch size, and pollinators produced most of their male offspring at the start of bouts, followed by mostly females. Second, we found that offspring sex ratio increased with foundress density, and pollinators did adjust their offspring sex ratio to other females in the oviposition patches. We suggest that when oviposition sites are not limited, pollinators will mainly adjust their offspring sex ratio to other foundresses independent of clutch size changes, whereas adjusting clutch size may be used to adjust sex ratio when oviposition sites are limited.

  11. Characterization of fig achenes' oil of Ficus carica grown in Tunisia.

    PubMed

    Soltana, Hala; Tekaya, Meriem; Amri, Zahra; El-Gharbi, Sinda; Nakbi, Amel; Harzallah, Arij; Mechri, Beligh; Hammami, Mohamed

    2016-04-01

    This work investigated the composition of the oil extract from achenes of "Kholi" variety of Ficus carica, grown in Tunisia. Fatty acid and sterol compositions were analyzed by gas chromatography (GC) coupled to flame ionization detector (FID). Furthermore, the antioxidant capacity in fig achenes' oil was assessed by employing two different in vitro assays such as DPPH, ABTS(+) radical scavenging capacities. Our results indicated that the fig achenes' oil is a rich source of bioactive molecules. The soxhlet n-hexane extraction of these achenes produced a total oil yield of 16.24%. The predominant fatty acid was linolenic acid. Concerning phytosterols, the total amount reached 1061.45 mg/100 g with a predominance of Δ(5,23)-stigmastadienol (73.78%). Regarding antioxidant activities, the half maximal inhibitory concentration (IC50) was 215.86 μg/ml and Trolox equivalent antioxidant capacity (TEAC) was 95.25 mM. These data indicate that fig achenes oil of F. carica could be potentially useful in food and pharmaceutical applications.

  12. Magnetic anisotropy and crystalline electric field effects in RRh{sub 4}B{sub 4} single crystals.

    SciTech Connect

    Zhou, H.; Lambert, S. E.; Maple, M. B.; Dunlap, B. D.; Materials Science Division; Univ. of California at San Diego

    2009-08-01

    Research on polycrystalline RRh{sub 4}B{sub 4} samples has shown that crystalline electric field (CEF) effects play an important role in these compounds. The successful synthesis of single crystal samples of RRh{sub 4}B{sub 4} with R = Y, Sm, Gd, Tb, Dy, Ho, Er, Tm, and Lu has provided an opportunity to further investigate CEF effects in these materials. Magnetization and magnetic susceptibility measurements on the RRh{sub 4}B{sub 4} single crystals revealed strong magnetic anisotropy, and the experimental results could be described well by CEF calculations based on the parameters derived from an analysis of experimental data for ErRh{sub 4}B{sub 4} single crystals. The easy directions of magnetization of these compounds are consistent with the signs of the Stevens factor {alpha}J of the CEF Hamiltonian. A strong influence of magnetic anisotropy on superconductivity was also observed.

  13. Sesuvium portulacastrum (L.) L.: a potential halophyte for the degradation of toxic textile dye, Green HE4B.

    PubMed

    Patil, Asmita V; Lokhande, Vinayak H; Suprasanna, Penna; Bapat, Vishwas A; Jadhav, Jyoti P

    2012-05-01

    Sesuvium portulacastrum is a common halophyte growing well in adverse surroundings and is exploited mainly for the environmental protection including phytoremediation, desalination and stabilization of contaminated soil. In the present investigation, attempts have been made on the decolorization of a toxic textile dye Green HE4B (GHE4B) using in vitro grown Sesuvium plantlets. The plantlets exhibited significant (70%) decolorization of GHE4B (50 mg l(-1)) that sustain 200 mM sodium chloride (NaCl) within 5 days of incubation. The enzymatic analysis performed on the root and shoot tissues of the in vitro plantlets subjected to GHE4B decolorization in the presence of 200 mM NaCl showed a noteworthy induction of tyrosinase, lignin peroxidase and NADH-DCIP reductase activities, indicating the involvement of these enzymes in the metabolism of the dye GHE4B. The UV-visible spectrophotometer, HPLC and Fourier Transform Infrared Spectroscopy (FTIR) analyses of the samples before and after decolorization of the dye confirmed the efficient phytotransformation of GHE4B in the presence of 200 mM NaCl. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the products revealed the formation of three metabolites such as p -amino benzene, p -amino toluene and 1, 2, 7-amino naphthalene after phytotransformation of GHE4B. Based on the FTIR and GC-MS results, the possible pathway for the biodegradation of GHE4B in the presence of 200 mM NaCl has been proposed. The phytotoxicity experiments confirmed the non-toxicity of the degraded products. The present study demonstrates for the first time the potential of Sesuvium for the efficient degradation of textile dyes and its efficacy on saline soils contaminated with toxic compounds.

  14. Effect of Heating Rate on Soft Magnetic Properties in Nanocrystalline Fe80.5Cu1.5Si4B14 and Fe82Cu1Nb1Si4B12 Alloys

    NASA Astrophysics Data System (ADS)

    Ohta, Motoki; Yoshizawa, Yoshihito

    2009-02-01

    The effect of the heating rate in the annealing process of rapidly quenched Fe80.5Cu1.5Si4B14 and Fe82Cu1Nb1Si4B12 amorphous alloys on their soft magnetic properties is investigated. The iron loss in magnetic flux density region of B > 1.55 T in Fe80.5Cu1.5Si4B14 alloy decreases by high-heating-rate annealing (HA). The coercivity Hc and the saturation magnetic flux density Bs in HA specimen of Fe82Cu1Nb1Si4B12 alloy were about 3 A/m and 1.78 T. By applying HA to high-Fe-concentration amorphous alloys such as Fe82Cu1Nb1Si4B12, Fe82Cu1Nb1Si2B12P2, and Fe80.8Cu1.2Si5B11P2, the nanocrystalline alloys with a high Bs of more than 1.75 T and a low Hc of about 3 A/m are obtained.

  15. When should fig fruit produce volatiles? Pattern in a ripening process

    NASA Astrophysics Data System (ADS)

    Borges, Renee M.; Ranganathan, Yuvaraj; Krishnan, Anusha; Ghara, Mahua; Pramanik, Gautam

    2011-11-01

    Ripe fruit need to signal their presence to attract dispersal agents. Plants may employ visual and/or olfactory sensory channels to signal the presence of ripe fruit. Visual signals of ripe fruit have been extensively investigated. However, the volatile signatures of ripe fruit that use olfactorily-oriented dispersers have been scarcely investigated. Moreover, as in flowers, where floral scents are produced at times when pollinators are active (diurnal versus nocturnal), whether plants can modulate the olfactory signal to produce fruit odours when dispersers are active in the diel cycle is completely unknown. We investigated day-night differences in fruit odours in two species of figs, Ficus racemosa and Ficus benghalensis. The volatile bouquet of fruit of F. racemosa that are largely dispersed by bats and other mammals was dominated by fatty acid derivatives such as esters. In this species in which the ripe fig phase is very short, and where the figs drop off soon after ripening, there were no differences between day and night in fruit volatile signature. The volatile bouquet of fruit of F. benghalensis that has a long ripening period, however, and that remain attached to the tree for extended periods when ripe, showed an increase in fatty acid derivatives such as esters and of benzenoids such as benzaldehyde at night when they are dispersed by bats, and an elevation of sesquiterpenes during the day when they are dispersed by birds. For the first time we provide data that suggest that the volatile signal produced by fruit can show diel differences based on the activity period of the dispersal agent.

  16. Rapid analysis of fungal cultures and dried figs for secondary metabolites by LC/TOF-MS.

    PubMed

    Senyuva, Hamide Z; Gilbert, John; Oztürkoğlu, Sebnem

    2008-06-01

    A liquid chromatography-time-of-flight mass spectrometry (LC/TOF-MS) method has been developed for profiling fungal metabolites. The performance of the procedure in terms of mass accuracy, selectivity (specificity) and repeatability was established by spiking aflatoxins, ochratoxins, trichothecenes and other metabolites into blank growth media. After extracting, and carrying out LC/TOF-MS analysis, the standards were correctly identified by searching a specially constructed database of 465 secondary metabolites. To demonstrate the viability of this approach 11 toxigenic and four non-toxigenic fungi from reference collections were grown on various media, for 7-14 days. The method was also applied to two toxigenic fungi, A. flavus (200-138) and A. parasiticus (2999-465) grown on gamma radiation sterilised dried figs, for 7-14 days. The fungal hyphae plus a portion of growth media or portions of dried figs were solvent extracted and analysed by LC/TOF-MS using a rapid resolution microbore LC column. Data processing based on cluster analysis, showed that electrospray ionization (ESI)-TOF-MS could be used to unequivocally identify metabolites in crude extracts. Using the elemental metabolite database, it was demonstrated that from culture collection isolates, anticipated metabolites. The speed and simplicity of the method has meant that levels of these metabolites could be monitored daily in sterilised figs. Over a 14-day period, levels of aflatoxins and kojic acid maximised at 5-6 days, whilst levels of 5-methoxysterigmatocystin remained relatively constant. In addition to the known metabolites expected to be produced by these fungi, roquefortine A, fumagillin, fumigaclavine B, malformins (peptides), aspergillic acid, nigragillin, terrein, terrestric acid and penicillic acid were also identified. PMID:18486645

  17. Adsorption and thermal decomposition of 2-octylthieno[3,4-b]thiophene on Au(111).

    PubMed

    Park, Joon B; Zong, Kyukwan; Jeon, Il Chul; Hahn, Jae Ryang; Stacchiola, Dario; Starr, David; Müller, Kathrin; Noh, Jaegeun

    2012-10-15

    The adsorption and thermal stability of 2-octylthieno[3,4-b]thiophene (OTTP) on the Au(111) surfaces have been studied using scanning tunneling microscopy (STM), temperature programmed desorption (TPD), and X-ray photoelectron spectroscopy (XPS). UHV-STM studies revealed that the vapor-deposited OTTP on Au(111) generated disordered adlayers with monolayer thickness even at saturation coverage. XPS and TPD studies indicated that OTTP molecules on Au(111) are stable up to 450 K and further heating of the sample resulted in thermal decomposition to produce H(2) and H(2)S via C-S bond scission in the thieno-thiophene rings. Dehydrogenation continues to occur above 600 K and the molecules were ultimately transformed to carbon clusters at 900 K. Highly resolved air-STM images showed that OTTP adlayers on Au(111) prepared from solution are composed of a well-ordered and low-coverage phase where the molecules lie flat on the surface, which can be assigned as a (9×2√33)R5° structure. Finally, based on analysis of STM, TPD, and XPS results, we propose a thermal decomposition mechanism of OTTP on Au(111) as a function of annealing temperature. PMID:22818203

  18. High-temperature mass spectrometry - Vaporization of group 4-B metal carbides. [using Knudsen effusion

    NASA Technical Reports Server (NTRS)

    Stearns, C. A.; Kohl, F. J.

    1974-01-01

    The high temperature vaporization of the metal-carbon systems TiC, ZrC, HfC, and ThC was studied by the Knudsen effusion - mass spectrometric method. For each system the metal dicarbide and tetracarbide molecular species were identified in the gas phase. Relative ion currents of the carbides and metals were measured as a function of temperature. Second- and third-law methods were used to determine enthalpies. Maximum values were established for the dissociation energies of the metal monocarbide molecules TiC, ZrC, HfC, and ThC. Thermodynamic functions used in the calculations are discussed in terms of assumed molecular structures and electronic contributions to the partition functions. The trends shown by the dissociation energies of the carbides of Group 4B are compared with those of neighboring groups and discussed in relation to the corresponding oxides and chemical bonding. The high temperature molecular beam inlet system and double focusing mass spectrometer are described.

  19. Study of Historical 4B/X17 Mega Flare on 28 October 2003 (P58)

    NASA Astrophysics Data System (ADS)

    Uddin, W.; Chandra, R.; Ali, S. S.

    2006-11-01

    wuddin_99@yahoo.com We analysed multi-wavelength data of 28 October 2003 4B/X17.2 class extremely energetic parallel ribbon solar flare, which occurred in NOAA 10486. The flare was well observed in H-alpha at ARIES, Nainital and various space (SOHO, TRACE, RHESSI, WIND etc.) and ground based Observatories. The H-alpha observations show the stretching/detwisting and eruption of helically twisted S shaped (sigmoid) filament in the South-West direction of the active region with bright shock front followed by rapid increase in intensity and area of the gigantic flare. The flare is associated with a bright/fast full halo earth directed CME, strong type II, III and IV radio bursts, an intense proton event and GLE. It seems that the filament eruption triggered the halo CME because the helical structure is clearly visible in the SOHO/LASCO C2, C3 images. This indicates helicity transfer from chromosphere to corona and interplanetary medium. The magnetic field of the flaring region was most complex with high magnetic shear. From the above analysis we feel that the energy buildup/release process of this unique flare support helically twisted magnetic flux rope model.

  20. CD4(+)B220(+)TCRγδ(+) T cells produce IL-17 in lupus-prone MRL/lpr mice.

    PubMed

    Qiu, Feng; Li, Tingting; Zhang, Kui; Wan, Jun; Qi, Xiaokun

    2016-09-01

    Systemic lupus erythematosus is an autoimmune disease with comprehensive immune cell disorders. Recent studies suggested that pro-inflammatory cytokine IL-17 plays important role in lupus, leaving the cellular sources and their pathogenic and physiologic characters largely unknown. In the current study, by using lupus-prone MRL/lpr mice, we demonstrated that Th17 response prevails in lupus disease regarding significantly accumulated serum IL-17, increased IL-17-producing splenocytes, and elevated phospho-STAT3 in CD4(+) T cells. Intracellular staining revealed that unusual CD4(+)B220(+) T cells are major IL-17-producing cells, whereas conventional CD4(+)B220(-) T cells are major IFN-γ-producing cells. Subsequent studies showed that CD4(+)B220(+) cells contains both αβ and γδ T cells in the spleen and thymus of MRL/lpr mice. Further study showed that around 60% of γδ T cells in MRL/lpr mice co-express both B220 and CD4 on their surface, and are the major RORγt(+) cells in MRL/lpr mice. Finally, CD4(+)B220(+) T cells alone do not proliferate, but could enhance the proliferation and IFN-γ-production of conventional CD4(+)B220(-) T cells. Our findings suggest the pathogenic role of unusual CD4(+)B220(+) T cells in lupus disease in MRL/lpr mice according to their IL-17-producing ability and stimulatory function for conventional CD4(+)B220(-) T cells. PMID:27235595

  1. Identification of an AAA ATPase VPS4B-Dependent Pathway That Modulates Epidermal Growth Factor Receptor Abundance and Signaling during Hypoxia

    PubMed Central

    Lin, H. Helen; Li, Xu; Chen, Jo-Lin; Sun, Xiuzhu; Cooper, Fariba Norouziyan; Chen, Yun-Ru; Zhang, Wenyu; Chung, Yiyin; Li, Angela; Cheng, Chun-Ting; Yang, Lixin; Deng, XuTao; Liu, Xiyong; Yen, Yun; Johnson, Deborah L.; Shih, Hsiu-Ming; Yang, Austin

    2012-01-01

    VPS4B, an AAA ATPase (ATPase associated with various cellular activities), participates in vesicular trafficking and autophagosome maturation in mammalian cells. In solid tumors, hypoxia is a common feature and an indicator of poor treatment outcome. Our studies demonstrate that exogenous or endogenous (assessed with anchorage-independent three-dimensional multicellular spheroid culture) hypoxia induces VPS4B downregulation by the ubiquitin-proteasome system. Inhibition of VPS4B function by short hairpin VPS4B (sh-VPS4B) or expression of dominant negative VPS4B(E235Q) promotes anchorage-independent breast cancer cell growth and resistance to gefitinib, U0126, and genotoxicity. Biochemically, hyperactivation of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase essential for cell proliferation and survival, accompanied by increased EGFR accumulation and altered intracellular compartmentalization, is observed in cells with compromised VPS4B. Furthermore, enhanced FOS/JUN induction and AP-1 promoter activation are noted in EGF-treated cells with VPS4B knockdown. However, VPS4B depletion does not affect EGFRvIII stability or its associated signaling. An inverse correlation between VPS4B expression and EGFR abundance is observed in breast tumors, and high-grade or recurrent breast carcinomas exhibit lower VPS4B expression. Together, our findings highlight a potentially critical role of VPS4B downregulation or chronic-hypoxia-induced VPS4B degradation in promoting tumor progression, unveiling a nongenomic mechanism for EGFR overproduction in human breast cancer. PMID:22252323

  2. FigA, a putative homolog of low-affinity calcium system member Fig1 in Saccharomyces cerevisiae, is involved in growth and asexual and sexual development in Aspergillus nidulans.

    PubMed

    Zhang, Shizhu; Zheng, Hailin; Long, Nanbiao; Carbó, Natalia; Chen, Peiying; Aguilar, Pablo S; Lu, Ling

    2014-02-01

    Calcium-mediated signaling pathways are widely employed in eukaryotes and are implicated in the regulation of diverse biological processes. In Saccharomyces cerevisiae, at least two different calcium uptake systems have been identified: the high-affinity calcium influx system (HACS) and the low-affinity calcium influx system (LACS). Compared to the HACS, the LACS in fungi is not well known. In this study, FigA, a homolog of the LACS member Fig1 from S. cerevisiae, was functionally characterized in the filamentous fungus Aspergillus nidulans. Loss of figA resulted in retardant hyphal growth and a sharp reduction of conidial production. Most importantly, FigA is essential for the homothallic mating (self-fertilization) process; further, FigA is required for heterothallic mating (outcrossing) in the absence of HACS midA. Interestingly, in a figA deletion mutant, adding extracellular Ca(2+) rescued the hyphal growth defects but could not restore asexual and sexual reproduction. Furthermore, quantitative PCR results revealed that figA deletion sharply decreased the expression of brlA and nsdD, which are known as key regulators during asexual and sexual development, respectively. In addition, green fluorescent protein (GFP) tagging at the C terminus of FigA (FigA::GFP) showed that FigA localized to the center of the septum in mature hyphal cells, to the location between vesicles and metulae, and between the junctions of metulae and phialides in conidiophores. Thus, our findings suggest that FigA, apart from being a member of a calcium uptake system in A. nidulans, may play multiple unexplored roles during hyphal growth and asexual and sexual development.

  3. FigA, a Putative Homolog of Low-Affinity Calcium System Member Fig1 in Saccharomyces cerevisiae, Is Involved in Growth and Asexual and Sexual Development in Aspergillus nidulans

    PubMed Central

    Zhang, Shizhu; Zheng, Hailin; Long, Nanbiao; Carbó, Natalia; Chen, Peiying; Aguilar, Pablo S.

    2014-01-01

    Calcium-mediated signaling pathways are widely employed in eukaryotes and are implicated in the regulation of diverse biological processes. In Saccharomyces cerevisiae, at least two different calcium uptake systems have been identified: the high-affinity calcium influx system (HACS) and the low-affinity calcium influx system (LACS). Compared to the HACS, the LACS in fungi is not well known. In this study, FigA, a homolog of the LACS member Fig1 from S. cerevisiae, was functionally characterized in the filamentous fungus Aspergillus nidulans. Loss of figA resulted in retardant hyphal growth and a sharp reduction of conidial production. Most importantly, FigA is essential for the homothallic mating (self-fertilization) process; further, FigA is required for heterothallic mating (outcrossing) in the absence of HACS midA. Interestingly, in a figA deletion mutant, adding extracellular Ca2+ rescued the hyphal growth defects but could not restore asexual and sexual reproduction. Furthermore, quantitative PCR results revealed that figA deletion sharply decreased the expression of brlA and nsdD, which are known as key regulators during asexual and sexual development, respectively. In addition, green fluorescent protein (GFP) tagging at the C terminus of FigA (FigA::GFP) showed that FigA localized to the center of the septum in mature hyphal cells, to the location between vesicles and metulae, and between the junctions of metulae and phialides in conidiophores. Thus, our findings suggest that FigA, apart from being a member of a calcium uptake system in A. nidulans, may play multiple unexplored roles during hyphal growth and asexual and sexual development. PMID:24376003

  4. Crystal structure of 7-isopropyl-1,4a,N-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodeca-hydro-phenanthrene-1-carb-ox-amide.

    PubMed

    Liu, Li; Yan, Xin-Yan; Rao, Xiao-Ping

    2015-10-01

    In the title compound, C26H37NO, a new derivative of di-hydro-abietic acid, the two cyclo-hexene rings adopt half chair conformations, whereas the cyclo-hexane ring has a chair conformation. Each of the methyl groups is in an axial position with respect to the tricyclic hydro-phenanthrene residue. In the crystal packing, methyl-ene-C-H⋯π(phen-yl) inter-actions lead to supra-molecular helical chains along [010]; the amide-H atom does not form a significant inter-molecular inter-action owing to steric pressure.

  5. Crystal structure of 7-isopropyl-1,4a,N-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodeca-hydro-phenanthrene-1-carb-ox-amide.

    PubMed

    Liu, Li; Yan, Xin-Yan; Rao, Xiao-Ping

    2015-10-01

    In the title compound, C26H37NO, a new derivative of di-hydro-abietic acid, the two cyclo-hexene rings adopt half chair conformations, whereas the cyclo-hexane ring has a chair conformation. Each of the methyl groups is in an axial position with respect to the tricyclic hydro-phenanthrene residue. In the crystal packing, methyl-ene-C-H⋯π(phen-yl) inter-actions lead to supra-molecular helical chains along [010]; the amide-H atom does not form a significant inter-molecular inter-action owing to steric pressure. PMID:26594487

  6. Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets

    PubMed Central

    Yang, Yang; Ye, Fei; Zhu, Na; Wang, Wenling; Deng, Yao; Zhao, Zhengdong; Tan, Wenjie

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε, and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production

  7. The mechanism of sex ratio adjustment in a pollinating fig wasp.

    PubMed

    Raja, Shazia; Suleman, Nazia; Compton, Stephen G; Moore, Jamie C

    2008-07-22

    Sex ratio strategies in species subject to local mate competition (LMC), and in particular their fit to quantitative theoretical predictions, provide insight into constraints upon adaptation. Pollinating fig wasps are widely used in such studies because their ecology resembles theory assumptions, but the cues used by foundresses to assess potential LMC have not previously been determined. We show that Liporrhopalum tentacularis females (foundresses) use their clutch size as a cue. First, we make use of species ecology (foundresses lay multiple clutches, with second clutches smaller than first) to show that increases in sex ratio in multi-foundress figs occur only when foundresses are oviposition site limited, i.e. that there is no direct response to foundress density. Second, we introduce a novel technique to quantify foundress oviposition sequences and show, consistent with the theoretical predictions concerning clutch size-only strategies, that they produce mainly male offspring at the start of bouts, followed by mostly females interspersed by a few males. We then discuss the implications of our findings for our understanding of the limits of the ability of natural selection to produce 'perfect' organisms, and for our understanding of when different cue use patterns evolve. PMID:18430647

  8. Labile male morphology and intraspecific male polymorphism in the Philotrypesis fig wasps.

    PubMed

    Jousselin, Emmanuelle; van Noort, Simon; Greeff, Jaco M

    2004-12-01

    We investigate the evolution of male morphology in the fig wasps belonging to the genus Philotrypesis (Chalcidoidea, Sycorectinae). We first reconstruct the phylogenetic relationships of Philotrypesis associated with African figs using nuclear and mitochondrial DNA. We then determine male morphotypes in the species included in our phylogeny and show that intraspecific polymorphism is common. Most species present two types of males and some species have up to three types. These morphotypes are believed to represent alternative mating tactics: some males show morphological adaptations to fighting, others are winged dispersers and others are small sneakers. Mapping out these variations onto our phylogeny reveals that the combination of morphs changes randomly along the branches of the tree. Both parsimony and likelihood approaches indicate that there has been at least one transition from dimorphism to trimorphism, several gains and losses of the small morph and two independent acquisitions of the winged morph. Using maximum likelihood analyses of character evolution, we estimate transition rates for each morph and show that the evolution of each type of morph are not correlated and that forward and backward transition rates are not significantly different. Our results altogether suggest that male morphology is evolutionary labile, it responds quickly to selection imposed by the mating environment. This study, also suggests that seemingly complex phenotypes, such as winged males, can evolve several times and can even be recreated after having been lost.

  9. The mechanism of sex ratio adjustment in a pollinating fig wasp.

    PubMed

    Raja, Shazia; Suleman, Nazia; Compton, Stephen G; Moore, Jamie C

    2008-07-22

    Sex ratio strategies in species subject to local mate competition (LMC), and in particular their fit to quantitative theoretical predictions, provide insight into constraints upon adaptation. Pollinating fig wasps are widely used in such studies because their ecology resembles theory assumptions, but the cues used by foundresses to assess potential LMC have not previously been determined. We show that Liporrhopalum tentacularis females (foundresses) use their clutch size as a cue. First, we make use of species ecology (foundresses lay multiple clutches, with second clutches smaller than first) to show that increases in sex ratio in multi-foundress figs occur only when foundresses are oviposition site limited, i.e. that there is no direct response to foundress density. Second, we introduce a novel technique to quantify foundress oviposition sequences and show, consistent with the theoretical predictions concerning clutch size-only strategies, that they produce mainly male offspring at the start of bouts, followed by mostly females interspersed by a few males. We then discuss the implications of our findings for our understanding of the limits of the ability of natural selection to produce 'perfect' organisms, and for our understanding of when different cue use patterns evolve.

  10. Purification and autolysis of the ficin isoforms from fig (Ficus carica cv. Sabz) latex

    PubMed Central

    Zare, Hamid; Moosavi-Movahedi, Ali Akbar; Salami, Maryam; Mirzaei, Morteza; Saboury, Ali Akbar; Sheibani, Nader

    2013-01-01

    Ficin (EC 3.4.22.3), a cysteine endoproteolytic protease in fig trees’ latex, has multiple isoforms. Until now, no data on autolysis of individual ficins (ficin isoforms) are available. Following purification, ficins’ autolysis was determined by HPLC chromatogram changes and ultrafiltrations at different temperatures and storage times. These results showed that the number of HPLC peaks in latex proteins purification of Ficus carica cv. Sabz varied from previous fig varieties or cultivars. Proteolytic activity of ficins was inhibited by specific cysteine protease inhibitors, confirming the participation of the cysteine residue in the active site. The zeta potential of the first two eluted peaks (I and II) was negative, while that of other peaks were positive. All ficins were susceptible to autolysis when stored at high temperatures. In contrast, only the last two ficins (B, C) were prone to autolysis at cold temperature after long storage period. The rate of degradation of the ficins was significantly increased with the increased storage time. The ficin (A) related to peak (III) had the highest and the lowest surface hydrophobic patches and ratio of autolytic to proteolytic activity, respectively. PMID:23312458

  11. Yeasts isolated from figs (Ficus carica L.) as biocontrol agents of postharvest fruit diseases.

    PubMed

    Ruiz-Moyano, S; Martín, A; Villalobos, M C; Calle, A; Serradilla, M J; Córdoba, M G; Hernández, A

    2016-08-01

    Fresh fruit is highly perishable during postharvest life, mainly due to fungal growth. Thus, fungal control is an important goal for the fruit industry. In this work, a selection of antagonistic yeasts isolated from fig and breba crops were screened in vitro. The isolated yeasts were challenged with three moulds isolated from decayed figs and breba crops, identified as Penicillium expansum M639 and Cladosporium cladosporioides M310 and M624, and pathogenic moulds Botrytis cinerea CECT20518 and Monilia laxa CA1 from culture collections. Two yeast isolates, Hanseniaspora opuntiae L479 and Metschnikowia pulcherrima L672, were selected for their ability to inhibit the growth of aforementioned moulds. These yeasts reduced the radial growth of moulds on PDA by between 45.23% and 66.09%. Antagonistic activity was associated with the interaction of live yeast cells with moulds. M. pulcherrima L672 apparently parasitised C. cladosporioides isolates. In addition, challenges were assayed using wounded apples and nectarines, with significant reductions in percent infection and lesion size for all moulds tested. To our knowledge, this is the first report identifying H. opuntiae as an antagonist against different pathogenic moulds. PMID:27052701

  12. Complete sequence of Fig fleck-associated virus, a novel member of the family Tymoviridae.

    PubMed

    Elbeaino, Toufic; Digiaro, Michele; Martelli, Giovanni P

    2011-11-01

    The complete nucleotide sequence and the genome organization were determined of a novel virus, tentatively named Fig fleck-associated virus (FFkaV). The viral genome is a positive-sense, single-stranded RNA 7046 nucleotides in size excluding the 3'-terminal poly(A) tract, and comprising two open reading frames. ORF1 encodes a polypeptide of 2161 amino acids (p240), which contains the signatures of replication-associated proteins and the coat protein cistron (p24) at its 3' end. ORF2 codes for a 461 amino acid protein (p50) identified as a putative movement proteins (MP). In phylogenetic trees constructed with sequences of the putative polymerase and CP proteins FFkaV consistently groups with members of the genus Maculavirus, family Tymoviridae. However, the genome organization diverges from that of the two completely sequenced maculaviruses, Grapevine fleck virus (GFkV) and Bombix mori Macula-like virus (BmMLV), as it exhibits a structure resembling that of Maize rayado fino virus (MRFV), the type species of the genus Marafivirus and of Olive latent virus 3 (OLV-3), an unclassified virus in the family Tymoviridae. FFkaV was found in field-grown figs from six Mediterranean countries with an incidence ranging from 15% to 25%.

  13. Yeasts isolated from figs (Ficus carica L.) as biocontrol agents of postharvest fruit diseases.

    PubMed

    Ruiz-Moyano, S; Martín, A; Villalobos, M C; Calle, A; Serradilla, M J; Córdoba, M G; Hernández, A

    2016-08-01

    Fresh fruit is highly perishable during postharvest life, mainly due to fungal growth. Thus, fungal control is an important goal for the fruit industry. In this work, a selection of antagonistic yeasts isolated from fig and breba crops were screened in vitro. The isolated yeasts were challenged with three moulds isolated from decayed figs and breba crops, identified as Penicillium expansum M639 and Cladosporium cladosporioides M310 and M624, and pathogenic moulds Botrytis cinerea CECT20518 and Monilia laxa CA1 from culture collections. Two yeast isolates, Hanseniaspora opuntiae L479 and Metschnikowia pulcherrima L672, were selected for their ability to inhibit the growth of aforementioned moulds. These yeasts reduced the radial growth of moulds on PDA by between 45.23% and 66.09%. Antagonistic activity was associated with the interaction of live yeast cells with moulds. M. pulcherrima L672 apparently parasitised C. cladosporioides isolates. In addition, challenges were assayed using wounded apples and nectarines, with significant reductions in percent infection and lesion size for all moulds tested. To our knowledge, this is the first report identifying H. opuntiae as an antagonist against different pathogenic moulds.

  14. A multilocus phylogeny of the world Sycoecinae fig wasps (Chalcidoidea: Pteromalidae).

    PubMed

    Cruaud, Astrid; Underhill, Jenny G; Huguin, Maïlis; Genson, Gwenaëlle; Jabbour-Zahab, Roula; Tolley, Krystal A; Rasplus, Jean-Yves; van Noort, Simon

    2013-01-01

    The Sycoecinae is one of five chalcid subfamilies of fig wasps that are mostly dependent on Ficus inflorescences for reproduction. Here, we analysed two mitochondrial (COI, Cytb) and four nuclear genes (ITS2, EF-1α, RpL27a, mago nashi) from a worldwide sample of 56 sycoecine species. Various alignment and partitioning strategies were used to test the stability of major clades. All topologies estimated using maximum likelihood and Bayesian methods were similar and well resolved but did not support the existing classification. A high degree of morphological convergence was highlighted and several species appeared best described as species complexes. We therefore proposed a new classification for the subfamily. Our analyses revealed several cases of probable speciation on the same host trees (up to 8 closely related species on one single tree of F. sumatrana), which raises the question of how resource partitioning occurs to avoid competitive exclusion. Comparisons of our results with fig phylogenies showed that, despite sycoecines being internally ovipositing wasps host-switches are common incidents in their evolutionary history. Finally, by studying the evolutionary properties of the markers we used and profiling their phylogenetic informativeness, we predicted their utility for resolving phylogenetic relationships of Chalcidoidea at various taxonomic levels.

  15. Newly isolated Penicillium oxalicum A592-4B secretes enzymes that degrade milled rice straw with high efficiency.

    PubMed

    Aoyama, Akihisa; Kurane, Ryuichiro; Matsuura, Akira; Nagai, Kazuo

    2015-01-01

    An enzyme producing micro-organism, which can directly saccharify rice straw that has only been crushed without undergoing the current acid or alkaline pretreatment, was found. From the homology with the ITS, 28S rDNA sequence, the strain named A592-4B was identified as Penicillium oxalicum. Activities of the A592-4B enzymes and commercial enzyme preparations were compared by Novozymes Cellic CTec2 and Genencore GC220. In the present experimental condition, activity of A592-4B enzymes was 2.6 times higher than that of CTec2 for degrading milled rice straw. Furthermore, even when a quarter amount of A592-4B enzyme was applied to the rice straw, the conversion rate was still higher than that by CTec2. By utilizing A592-4B enzymes, improved lignocellulose degradation yields can be achieved without pre-treatment of the substrates; thus, contributing to cost reduction as well as reducing environmental burden.

  16. AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B

    PubMed Central

    Johanns, M.; Lai, Y.-C.; Hsu, M.-F.; Jacobs, R.; Vertommen, D.; Van Sande, J.; Dumont, J. E.; Woods, A.; Carling, D.; Hue, L.; Viollet, B.; Foretz, M; Rider, M H

    2016-01-01

    Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation. PMID:26952277

  17. UBE4B Protein Couples Ubiquitination and Sorting Machineries to Enable Epidermal Growth Factor Receptor (EGFR) Degradation*

    PubMed Central

    Sirisaengtaksin, Natalie; Gireud, Monica; Yan, Qing; Kubota, Yoshihisa; Meza, Denisse; Waymire, Jack C.; Zage, Peter E.; Bean, Andrew J.

    2014-01-01

    The signaling of plasma membrane proteins is tuned by internalization and sorting in the endocytic pathway prior to recycling or degradation in lysosomes. Ubiquitin modification allows recognition and association of cargo with endosomally associated protein complexes, enabling sorting of proteins to be degraded from those to be recycled. The mechanism that provides coordination between the cellular machineries that mediate ubiquitination and endosomal sorting is unknown. We report that the ubiquitin ligase UBE4B is recruited to endosomes in response to epidermal growth factor receptor (EGFR) activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0. We identify the EGFR as a substrate for UBE4B, establish UBE4B as a regulator of EGFR degradation, and describe a mechanism by which UBE4B regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. We propose a model in which the coordinated action of UBE4B, ESCRT-0, and the deubiquitinating enzyme USP8 enable the endosomal sorting and lysosomal degradation of the EGFR. PMID:24344129

  18. Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

    PubMed Central

    Sandhu, C; Garbe, J; Bhattacharya, N; Daksis, J; Pan, C H; Yaswen, P; Koh, J; Slingerland, J M; Stampfer, M R

    1997-01-01

    The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited. PMID:9111314

  19. Investigation of the process chain leading to the development of convection during COP IOP 4b

    NASA Astrophysics Data System (ADS)

    Bauer, H.-S.; Schwitalla, T.; Aoshima, F.; Behrendt, A.; Wulfmeyer, V.

    2012-04-01

    The COPS IOP 4b took place from June 20th to June 21st 2007. It was characterized by widespread convection in the COPS domain. The development was steered by a strong low pressure system southwest of the British Isles. On its eastern side warm and moist subtropical air was directed to central Europe. First convection was triggered over the Vosges Mountains around noon on the 20th of June long before the front approached the COPS region. After a calm early afternoon, severe convection was triggered in wide regions of the COPS region in the evening and moved eastwards to Bavaria during the night to the 21st of June. In contrast to other IOPs, the situation was not captured correctly by most of the involved prediction models, no matter whether they were operated with or without sophisticated data assimilation. Aim of this presentation is to unravel the mechanisms responsible for the triggering of convection and to understand the processes preparing the atmosphere for the development of severe convection during the afternoon and night. For this purpose, many different data sets will be investigated ranging from the high resolution Vienna Enhanced Resolution Analysis (VERA), high resolution radar and satellite images and composites to soundings and data as well as retrieved products from the instruments at the COPS supersites. First impression is that the complicated low-level wind field is the major driver for the preparation of the atmosphere and therefore for the development of convection during the day. The inaccuracies in representing the low level wind field are also expected to be the major reason for the failure of the models to correctly predict the situation.

  20. The Dedicated Monitor of Exotransits (DEMONEX): Seven Transits of XO-4b

    NASA Astrophysics Data System (ADS)

    Villanueva, S., Jr.; Eastman, J. D.; Gaudi, B. S.

    2016-04-01

    The DEdicated MONitor of EXotransits (DEMONEX) was a 20-inch robotic and automated telescope to monitor bright stars hosting transiting exoplanets to discover new planets and improve constraints on the properties of known transiting planetary systems. We present results for the misaligned hot Jupiter XO-4b containing seven new transits from the DEMONEX telescope, including three full and four partial transits. We combine these data with archival light curves and archival radial velocity measurements to derive the host star mass {M}*={1.293}-0.029+0.030 {M}⊙ and radius {R}*={1.554}-0.030+0.042 {R}⊙ , the planet mass {M}P={1.615}-0.099+0.10 {M}{{J}} and radius {R}P={1.317}-0.029+0.040\\\\{R}{{J}}, and a refined ephemeris of P=4.1250687+/- 0.0000024 days and {T}0=2,4547,58.18978+/- 0.00024 {{BJD}}{TDB}. We include archival Rossiter-McLaughlin measurements of XO-4 to infer the stellar spin-planetary orbit alignment of λ =-{40.0}-7.5+8.8 degrees. We test the effects of including various detrend parameters, theoretical and empirical mass-radius relations, and Rossiter-McLaughlin models. We infer that detrending against CCD position and time or airmass can improve data quality but can have significant effects on the inferred values of many parameters—most significantly {R}P/{R}* and the observed central transit times TC. In the case of {R}P/{R}* we find that the systematic uncertainty due to detrending can be three times that of the quoted statistical uncertainties. The choice of mass-radius relation has little effect on our inferred values of the system parameters. The choice of Rossiter-McLaughlin models can have significant effects on the inferred values of v{sin}{I}* and the stellar spin-planet orbit angle λ.

  1. Genome sequence and description of the heavy metal tolerant bacterium Lysinibacillus sphaericus strain OT4b.31

    PubMed Central

    Peña-Montenegro, Tito David; Dussán, Jenny

    2013-01-01

    Lysinibacillus sphaericus strain OT4b.31 is a native Colombian strain having no larvicidal activity against Culex quinquefasciatus and is widely applied in the bioremediation of heavy-metal polluted environments. Strain OT4b.31 was placed between DNA homology groups III and IV. By gap-filling and alignment steps, we propose a 4,096,672 bp chromosomal scaffold. The whole genome (consisting of 4,856,302 bp long, 94 contigs and 4,846 predicted protein-coding sequences) revealed differences in comparison to the L. sphaericus C3-41 genome, such as syntenial relationships, prophages and putative mosquitocidal toxins. Sphaericolysin B354, the coleopteran toxin Sip1A and heavy metal resistance clusters from nik, ars, czc, cop, chr, czr and cad operons were identified. Lysinibacillus sphaericus OT4b.31 has applications not only in bioremediation efforts, but also in the biological control of agricultural pests. PMID:24501644

  2. Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation. Methods Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups. Results We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05). Conclusions Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB. PMID:24484408

  3. Bioactivation of 4-ipomeanol by CYP4B1: adduct characterization and evidence for an enedial intermediate.

    PubMed

    Baer, Brian R; Rettie, Allan E; Henne, Kirk R

    2005-05-01

    4-Ipomeanol (IPO) is a pneumotoxin that is bioactivated to a reactive intermediate that binds to DNA and other cellular macromolecules. Despite over 30 years of research in this area, detailed structural information on the nature of the IPO reactive intermediate is still lacking. In the present study, we reacted IPO with rabbit CYP4B1 in the presence of exogenous nucleophiles and analyzed the products by liquid chromatography/electrospray ionization-mass spectrometry. Coincubation of IPO and rabbit CYP4B1 with glutathione gave rise to multiple products due likely to the presence of both sulfur and nitrogen nucleophiles in the same trapping molecule. Reaction mixtures containing equimolar N-acetyl cysteine (NAC) and N-acetyl lysine (NAL) provided a major NADPH- and CYP4B1-dependent product. A combination of high-resolution mass spectrometry and two-dimensional NMR analysis following large-scale isolation of the biologically derived material provided evidence for an N-substituted cysteinyl pyrrole derivative of IPO, analogous to that characterized previously in model chemical studies conducted with cis-2-butene-1,4-dial. Purified native rabbit lung CYP4B1 and purified recombinant rabbit CYP4B1 produced the trapped NAC/NAL-IPO pyrrole adduct at rates of 600-700 nmol/nmol P450/30 min. A panel of 14 commercially available recombinant human CYPs was also studied, and substantial rates of IPO bioactivation (>100 nmol/nmol/30 min) were observed with CYP1A2, CYP2C19, CYP2D6, and CYP3A4. These studies provide evidence for the formation of an enedial reactive intermediate during CYP-mediated IPO bioactivation, identify multiple human liver P450s capable of IPO bioactivation, and demonstrate that the same reactive intermediate is formed by both rabbit CYP4B1 and human P450s. PMID:15892579

  4. Regulation of ATG4B Stability by RNF5 Limits Basal Levels of Autophagy and Influences Susceptibility to Bacterial Infection

    PubMed Central

    Kuang, Ersheng; Varsano, Tal; Shu, Vincent Chih-Wen; Qi, Jianfei; Niesman, Ingrid R.; Yang, Huei-Jiun; López-Otín, Carlos; Yang, Wei Yuan; Reed, John C.; Broday, Limor; Nizet, Victor; Ronai, Ze'ev A.

    2012-01-01

    Autophagy is the mechanism by which cytoplasmic components and organelles are degraded by the lysosomal machinery in response to diverse stimuli including nutrient deprivation, intracellular pathogens, and multiple forms of cellular stress. Here, we show that the membrane-associated E3 ligase RNF5 regulates basal levels of autophagy by controlling the stability of a select pool of the cysteine protease ATG4B. RNF5 controls the membranal fraction of ATG4B and limits LC3 (ATG8) processing, which is required for phagophore and autophagosome formation. The association of ATG4B with—and regulation of its ubiquitination and stability by—RNF5 is seen primarily under normal growth conditions. Processing of LC3 forms, appearance of LC3-positive puncta, and p62 expression are higher in RNF5−/− MEF. RNF5 mutant, which retains its E3 ligase activity but does not associate with ATG4B, no longer affects LC3 puncta. Further, increased puncta seen in RNF5−/− using WT but not LC3 mutant, which bypasses ATG4B processing, substantiates the role of RNF5 in early phases of LC3 processing and autophagy. Similarly, RNF-5 inactivation in Caenorhabditis elegans increases the level of LGG-1/LC3::GFP puncta. RNF5−/− mice are more resistant to group A Streptococcus infection, associated with increased autophagosomes and more efficient bacterial clearance by RNF5−/− macrophages. Collectively, the RNF5-mediated control of membranalATG4B reveals a novel layer in the regulation of LC3 processing and autophagy. PMID:23093945

  5. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    SciTech Connect

    Min, Joong Won; Kim, Kwang Il; Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu; Kim, Jae-Sung

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  6. Chronic dietary supplementation of 4% figs on the modification of oxidative stress in Alzheimer's disease transgenic mouse model.

    PubMed

    Subash, Selvaraju; Essa, Musthafa Mohamed; Al-Asmi, Abdullah; Al-Adawi, Samir; Vaishnav, Ragini

    2014-01-01

    We assessed the changes in the plasma Aβ, oxidative stress/antioxidants, and membrane bound enzymes in the cerebral cortex and hippocampus of Alzheimer's disease (AD) transgenic mice (Tg2576) after dietary supplementation of Omani figs fruits for 15 months along with spatial memory and learning test. AD Tg mice on control diet without figs showed significant impairment in spatial learning ability compared to the wild-type mice on same diet and figs fed Tg mice as well. Significant increase in oxidative stress and reduced antioxidant status were observed in AD Tg mice. 4% figs treated AD Tg mice significantly attenuated oxidative damage, as evident by decreased lipid peroxidation and protein carbonyls and restoration of antioxidant status. Altered activities of membrane bound enzymes (Na(+) K(+) ATPase and acetylcholinesterase (AChE)) in AD Tg mice brain regions and was restored by figs treatment. Further, figs supplementation might be able to decrease the plasma levels of Aβ (1-40, 1-42) significantly in Tg mice suggesting a putative delay in the formation of plaques, which might be due to the presence of high natural antioxidants in figs. But this study warrants further extensive investigation to find a novel lead for a therapeutic target for AD from figs. PMID:25050360

  7. How to be a dioecious fig: Chemical mimicry between sexes matters only when both sexes flower synchronously.

    PubMed

    Hossaert-McKey, M; Proffit, M; Soler, C C L; Chen, C; Bessière, J-M; Schatz, B; Borges, R M

    2016-02-18

    In nursery pollination mutualisms, which are usually obligate interactions, olfactory attraction of pollinators by floral volatile organic compounds (VOCs) is the main step in guaranteeing partner encounter. However, mechanisms ensuring the evolutionary stability of dioecious fig-pollinator mutualisms, in which female fig trees engage in pollination by deceit resulting in zero reproductive success of pollinators that visit them, are poorly understood. In dioecious figs, individuals of each sex should be selected to produce odours that their pollinating wasps cannot distinguish, especially since pollinators have usually only one choice of a nursery during their lifetime. To test the hypothesis of intersexual chemical mimicry, VOCs emitted by pollen-receptive figs of seven dioecious species were compared using headspace collection and gas chromatography-mass spectrometry analysis. First, fig-flower scents varied significantly among species, allowing host-species recognition. Second, in species in which male and female figs are synchronous, intersexual VOC variation was not significant. However, in species where figs of both sexes flower asynchronously, intersexual variation of VOCs was detectable. Finally, with one exception, there was no sexual dimorphism in scent quantity. We show that there are two ways to use scent to be a dioecious fig based on differences in flowering synchrony between the sexes.

  8. Chronic Dietary Supplementation of 4% Figs on the Modification of Oxidative Stress in Alzheimer's Disease Transgenic Mouse Model

    PubMed Central

    Essa, Musthafa Mohamed; Al-Asmi, Abdullah; Vaishnav, Ragini

    2014-01-01

    We assessed the changes in the plasma Aβ, oxidative stress/antioxidants, and membrane bound enzymes in the cerebral cortex and hippocampus of Alzheimer's disease (AD) transgenic mice (Tg2576) after dietary supplementation of Omani figs fruits for 15 months along with spatial memory and learning test. AD Tg mice on control diet without figs showed significant impairment in spatial learning ability compared to the wild-type mice on same diet and figs fed Tg mice as well. Significant increase in oxidative stress and reduced antioxidant status were observed in AD Tg mice. 4% figs treated AD Tg mice significantly attenuated oxidative damage, as evident by decreased lipid peroxidation and protein carbonyls and restoration of antioxidant status. Altered activities of membrane bound enzymes (Na+ K+ ATPase and acetylcholinesterase (AChE)) in AD Tg mice brain regions and was restored by figs treatment. Further, figs supplementation might be able to decrease the plasma levels of Aβ (1–40, 1–42) significantly in Tg mice suggesting a putative delay in the formation of plaques, which might be due to the presence of high natural antioxidants in figs. But this study warrants further extensive investigation to find a novel lead for a therapeutic target for AD from figs. PMID:25050360

  9. How to be a dioecious fig: Chemical mimicry between sexes matters only when both sexes flower synchronously.

    PubMed

    Hossaert-McKey, M; Proffit, M; Soler, C C L; Chen, C; Bessière, J-M; Schatz, B; Borges, R M

    2016-01-01

    In nursery pollination mutualisms, which are usually obligate interactions, olfactory attraction of pollinators by floral volatile organic compounds (VOCs) is the main step in guaranteeing partner encounter. However, mechanisms ensuring the evolutionary stability of dioecious fig-pollinator mutualisms, in which female fig trees engage in pollination by deceit resulting in zero reproductive success of pollinators that visit them, are poorly understood. In dioecious figs, individuals of each sex should be selected to produce odours that their pollinating wasps cannot distinguish, especially since pollinators have usually only one choice of a nursery during their lifetime. To test the hypothesis of intersexual chemical mimicry, VOCs emitted by pollen-receptive figs of seven dioecious species were compared using headspace collection and gas chromatography-mass spectrometry analysis. First, fig-flower scents varied significantly among species, allowing host-species recognition. Second, in species in which male and female figs are synchronous, intersexual VOC variation was not significant. However, in species where figs of both sexes flower asynchronously, intersexual variation of VOCs was detectable. Finally, with one exception, there was no sexual dimorphism in scent quantity. We show that there are two ways to use scent to be a dioecious fig based on differences in flowering synchrony between the sexes. PMID:26888579

  10. Living on the edge: Fig tree phenology at the northern range limit of monoecious Ficus in China

    NASA Astrophysics Data System (ADS)

    Zhang, Lu-Shui; Compton, Stephen G.; Xiao, Hui; Lu, Qian; Chen, Yan

    2014-05-01

    Fig trees (Ficus) are a species-rich group of mainly tropical and subtropical plants that are of ecological importance because of the large numbers of vertebrates that utilise their figs for food. Factors limiting their distributions to warmer regions are still poorly understood, but are likely to include factors linked to their specialised pollination biology, because each Ficus species is dependent on one or a small number of host-specific fig wasps (Agaonidae) for pollination. Adult fig wasps are short-lived, but some species are capable of dispersing extremely long distances to pollinate their hosts. Close to its northern range limit we investigated the phenology of Ficus virens, the monoecious fig tree that reaches furthest north in China. Relatively few trees produced any figs, and very few retained figs throughout the winter. Despite this, new crops produced in spring were pollinated, with seasonally migrant pollinators from plants growing further south the most likely pollen vectors. An inability to initiate new crops at low temperatures may limit the distribution of monoecious fig trees to warmer areas.

  11. The Bisphenol A analogue Bisphenol S binds to K-Ras4B--implications for 'BPA-free' plastics.

    PubMed

    Schöpel, Miriam; Herrmann, Christian; Scherkenbeck, Jürgen; Stoll, Raphael

    2016-02-01

    K-Ras4B is a small GTPase that belongs to the Ras superfamily of guanine nucleotide-binding proteins. GTPases function as molecular switches in cells and are key players in intracellular signalling. Ras has been identified as an oncogene and is mutated in more than 20% of human cancers. Here, we report that Bisphenol S binds into a binding pocket of K-Ras4B previously identified for various low molecular weight compounds. Our results advocate for more comprehensive safety studies on the toxicity of Bisphenol S, as it is frequently used for Bisphenol A-free food containers. PMID:26867649

  12. Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

    NASA Technical Reports Server (NTRS)

    Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

    1995-01-01

    A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

  13. 3,4,6-Trimethyl-1-phenyl-1H-pyrazolo­[3,4-b]pyridine

    PubMed Central

    Hamri, Salha; Hafid, Abderrafia; Zouihri, Hafid; Lazar, Saïd; Khouili, Mostafa

    2010-01-01

    In the title compound, C15H15N3, the 1H-pyrazolo­[3,4-b]pyridine system and the phenyl ring are each individually planar, with r.m.s. deviations of 0.017 (2) and 0.011 (2) Å, respectively; the dihedral angle between the two aromatic systems is 9.33 (10)°. The crystal packing is stabilized by offset π–π stacking between parallel pyrazolo­[3,4-b]pyridine ring systems [face-to-face distance = 3.449 (6) Å]. PMID:21588287

  14. The Bisphenol A analogue Bisphenol S binds to K-Ras4B--implications for 'BPA-free' plastics.

    PubMed

    Schöpel, Miriam; Herrmann, Christian; Scherkenbeck, Jürgen; Stoll, Raphael

    2016-02-01

    K-Ras4B is a small GTPase that belongs to the Ras superfamily of guanine nucleotide-binding proteins. GTPases function as molecular switches in cells and are key players in intracellular signalling. Ras has been identified as an oncogene and is mutated in more than 20% of human cancers. Here, we report that Bisphenol S binds into a binding pocket of K-Ras4B previously identified for various low molecular weight compounds. Our results advocate for more comprehensive safety studies on the toxicity of Bisphenol S, as it is frequently used for Bisphenol A-free food containers.

  15. Sm-Nd dating of Fig Tree clay minerals of the Barberton greenstone belt, South Africa

    NASA Technical Reports Server (NTRS)

    Toulkeridis, T.; Goldstein, S. L.; Clauer, N.; Kroner, A.; Lowe, D. R.

    1994-01-01

    Sm-Nd isotopic data from carbonate-derived clay minerals of the 3.22-3.25 Ga Fig Tree Group, Barberton greenstone belt, South Africa, form a linear array corresponding to an age of 3102 +/- 64 Ma, making these minerals the oldest dated clays on Earth. The obtained age is 120-160 m.y. younger than the depositional age determined by zircon geochronology. Nd model ages for the clays range from approximately 3.39 to 3.44 Ga and almost cover the age variation of the Barberton greenstone belt rocks, consistent with independent evidence that the clay minerals are derived from material of the belt. The combined isotopic and mineralogical data provide evidence for a cryptic thermal overprint in the sediments of the belt. However, the highest temperature reached by the samples since the time of clay-mineral formation was <300 degrees C, lower than virtually any known early Archean supracrustal sequence.

  16. Autolysis control and structural changes of purified ficin from Iranian fig latex with synthetic inhibitors.

    PubMed

    Zare, H; Moosavi-Movahedi, A A; Salami, M; Sheibani, N; Khajeh, K; Habibi-Rezaei, M

    2016-03-01

    The fig's ficin is a cysteine endoproteolytic enzyme, which plays fundamental roles in many plant physiological processes, and has many applications in different industries such as pharmaceutical and food. In this work, we report the inhibition and activation of autolysis and structural changes associated with reaction of ficin with iodoacetamide and tetrathionate using high-performance liquid chromatography (HPLC), ultra filtration membrane, and dynamic light scattering (DLS) methods. The ficin structural changes were also determined using UV-absorption, circular dichroism (CD), fluorescence spectroscopy, and differential scanning calorimetry (DSC) techniques. These techniques demonstrated that iodoacetamide completely inhibited ficin autolysis, which was irreversible. However, tetrathionate partially and reversibility inhibited its autolysis. The ficin structural changes with two synthetic inhibitors were associated with secondary structural changes related to decreased alpha-helix and increased beta sheet and random coil conformations, contributing to its aggregation.

  17. The effect of high speed shearing on disaggregation and degradation of pectin from creeping fig seeds.

    PubMed

    Chen, Jun; Wu, Shuang-Shuang; Liang, Rui-Hong; Liu, Wei; Liu, Cheng-Mei; Shuai, Xi-Xiang; Wang, Zhao-Jun

    2014-12-15

    The effect of high speed shearing (HSS) on disaggregation and degradation of pectin from creeping fig seeds was investigated. It was found that disaggregation and degradation occurred during the whole shearing process. When pectin solution was sheared at 24,000 rpm for less than 8h, degradation happened but disaggregation was dominant during this period. After 8h, degradation became obvious, however, a small amount of aggregates remained even after 24h treatment, indicating that HSS may not eliminate aggregates efficiently. The presence of aggregates is one of the most probable causes for the inaccurate determination of molecular weight of pectin. A new method was proposed for calculating more accurately the molecular weight based on the change of the reducing sugar content and the variation of molecular weight. Determination of unsaturated uronide and FT-IR spectra analysis indicated that neither β-elimination nor demethoxylation occurred during the HSS, and no new functional group was formed during the HSS process.

  18. An image-processing software package: UU and Fig for optical metrology applications

    NASA Astrophysics Data System (ADS)

    Chen, Lujie

    2013-06-01

    Modern optical metrology applications are largely supported by computational methods, such as phase shifting [1], Fourier Transform [2], digital image correlation [3], camera calibration [4], etc, in which image processing is a critical and indispensable component. While it is not too difficult to obtain a wide variety of image-processing programs from the internet; few are catered for the relatively special area of optical metrology. This paper introduces an image-processing software package: UU (data processing) and Fig (data rendering) that incorporates many useful functions to process optical metrological data. The cross-platform programs UU and Fig are developed based on wxWidgets. At the time of writing, it has been tested on Windows, Linux and Mac OS. The userinterface is designed to offer precise control of the underline processing procedures in a scientific manner. The data input/output mechanism is designed to accommodate diverse file formats and to facilitate the interaction with other independent programs. In terms of robustness, although the software was initially developed for personal use, it is comparably stable and accurate to most of the commercial software of similar nature. In addition to functions for optical metrology, the software package has a rich collection of useful tools in the following areas: real-time image streaming from USB and GigE cameras, computational geometry, computer vision, fitting of data, 3D image processing, vector image processing, precision device control (rotary stage, PZT stage, etc), point cloud to surface reconstruction, volume rendering, batch processing, etc. The software package is currently used in a number of universities for teaching and research.

  19. Probing the water and CO snow lines in the young protostar NGC 1333-IRAS4B

    NASA Astrophysics Data System (ADS)

    Anderl, Sibylle; Maret, Sébastien; André, Philippe; Maury, Anaëlle; Belloche, Arnaud; Cabrit, Sylvie; Codella, Claudio; Lefloch, Bertrand

    2015-08-01

    Today, we believe that the onset of life requires free energy, water, and complex, probably carbon-based chemistry. In the interstellar medium, complex organic molecules seem to mostly form in reactions happening on the icy surface of dust grains, such that they are released into the gas phase when the dust is heated. The resulting “snow lines”, marking regions where ices start to sublimate, play an important role for planet growth and bulk composition in protoplanetary disks. However, they can already be observed in the envelopes of the much younger, low-mass Class 0 protostars that are still in their early phase of heavy accretion. The information on the sublimation regions of different kinds of ices can be used to understand the chemistry of the envelope, its temperature and density structure, and may even hint at the history of the accretion process. Accordingly, it is a crucial piece of information in order to get the full picture of how organic chemistry evolves already at the earliest stages of the formation of sun-like stars. As part of the CALYPSO Large Program (http://irfu.cea.fr/Projets/Calypso/), we have obtained observations of C18O, N2H+ and CH3OH towards the Class 0 protostar NGC 1333-IRAS4B with the IRAM Plateau de Bure interferometer at sub-arcsecond resolution. Of these we use the methanol observations as a proxy for the water snow line, assuming methanol is trapped in water ice. The observed anti-correlation of C18O and N2H+, with N2H+ forming a ring around the centrally peaked C18O emission, reveals for the first time the CO snow line in this protostellar envelope, with a radius of ~300 AU. The methanol emission is much more compact than that of C18O, and traces the water snow line with a radius of ~40 AU. We have modeled the emission using a chemical model coupled with a radiative transfer module. We find that the CO snow line appears further inwards than expected from the binding energy of pure CO ices. This may hint at CO being frozen out

  20. 28 CFR Appendix to Part 51 - Jurisdictions Covered Under Section 4(b) of the Voting Rights Act, as Amended

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) of the Voting Rights Act, as Amended Appendix to Part 51 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED Pt. 51, App. Appendix to Part 51—Jurisdictions Covered Under Section 4(b) of the Voting Rights...

  1. Establishment of a cell line panel for the detection of antibodies against human platelet antigen 4b.

    PubMed

    Hayashi, Tomoya; Amakishi, Etsuko; Inoue, Masayasu; Hirayama, Fumiya

    2011-02-01

    Antibodies against human platelet antigens (HPAs) play important roles in thrombocytopenia. In Japan, HPA-4b antibody is frequently responsible for HPA-related neonatal alloimmune thrombocytopenia. A highly sensitive assay using platelets has been developed for the detection of antibodies against HPAs. However, it is difficult to obtain the platelets expressing specific HPAs required for the assay. Therefore, an alternative method not requiring platelets would be helpful to detect antibodies against HPAs. Glycoprotein IIIa (GPIIIa) cDNA encoding HPA-4b was individually co-transduced with that of wild-type GPIIb in K562 cells, which is a non-adherent cell line, using a retroviral vector. The expression of transgene products in cultured cells were observed for over 6 months. Next, to evaluating the sensitivity and specificity of this cell line panel, we performed monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay with a serum previously identified by another method. All HPA-4b antibodies in serum samples were positive, and all serum samples, including normal serum and serum containing HLA antibodies were negative. No difference was observed in the specificity and sensitivity between our method and conventional MAIPA using platelets. The present results indicate that this established cell line panel permits highly sensitive detection of specific antibodies against HPA-4b. PMID:21286877

  2. Role of the inositol polyphosphate-4-phosphatase type II Inpp4b in the generation of ovarian teratomas

    PubMed Central

    Balakrishnan, Ashwini; Chaillet, J. Richard

    2012-01-01

    Teratomas are a unique class of tumors composed of ecto- meso- and endodermal tissues, all foreign to the site of origin. In humans, the most common teratoma is the ovarian teratoma. Not much is known about the molecular and genetic etiologies of these tumors. Female carriers of the Tgkd transgene are highly susceptible to developing teratomas. Ovaries of Tgkd/+ hemizygous female mice exhibit defects in luteinization, with numerous corpora lutea, some of which contain central trapped, fully-grown oocytes. Genetically, Tgkd teratomas originate from mature oocytes that have completed meiosis I, suggesting that Tgkd teratomas originate from these trapped oocytes. The insertion of Tgkd 3′ of the Inpp4b gene is associated with decreased expression of Inpp4b and changes in intracellular PI3 Kinase/AKT signaling in follicular granulosa cells. Because Inpp4b is not expressed in fully-grown wild-type or Tgkd oocytes, these findings suggest that hyperactivation of the PI3K/AKT pathway caused by the decrease in INPP4B in granulosa cells promotes an ovarian environment defective in folliculogenesis and conducive to teratoma formation. PMID:23078915

  3. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease.

    PubMed

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-05-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status.

  4. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease

    PubMed Central

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-01-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status. PMID:27162595

  5. 75 FR 71145 - San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... Register on September 9, 2009 (74 FR 46453). This revised proposal would include measures for the... Bureau of Reclamation San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and Structural Improvements Project, Merced County, CA AGENCY: Bureau of...

  6. 75 FR 40843 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ..., which was made available in the Federal Register of February 21, 2008 (73 FR 9575). DATES: Although you... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Pharmacopoeial Texts for Use in the ICH Regions; Annex 13: Bulk Density and Tapped Density of Powders...

  7. 75 FR 43172 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... Administration (FDA) is correcting a notice that appeared in the Federal Register of July 14, 2010 (75 FR 40843...-0002, 301-796-9148. SUPPLEMENTARY INFORMATION: In FR Doc. 2010-17055, appearing on page 40843 in the... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference...

  8. VizieR Online Data Catalog: TrES-4b RV and Ic curves (Sozzetti+, 2015)

    NASA Astrophysics Data System (ADS)

    Sozzetti, A.; Bonomo, A. S.; Biazzo, K.; Mancini, L.; Damasso, M.; Desidera, S.; Gratton, R.; Lanza, A. F.; Poretti, E.; Rainer, M.; Malavolta, L.; Affer, L.; Barbieri, M.; Bedin, L. R.; Boccato, C.; Bonavita, M.; Borsa, F.; Ciceri, S.; Claudi, R. U.; Gandolfi, D.; Giacobbe, P.; Henning, T.; Knapic, C.; Latham, D. W.; Lodato, G.; Maggio, A.; Maldonado, J.; Marzari, F.; Martinez Fiorenzano, A. F.; Micela, G.; Molinari, E.; Mordasini, C.; Nascimbeni, V.; Pagano, I.; Pedani, M.; Pepe, F.; Piotto, G.; Santos, N.; Scandariato, G.; Shkolnik, E.; Southworth, J.

    2015-06-01

    The TrES-4 system was observed with HARPS-N on 17 individual epochs between March 2013 and July 2014. We carried out Ic-band precision photometric observations of two complete transit events of TrES-4 b with the CAHA 1.23-m on UT 2013 July 6 and UT 2014 June 30. (2 data files).

  9. Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Listeria monocytogenes serotype 4b from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resi...

  10. How to be a dioecious fig: Chemical mimicry between sexes matters only when both sexes flower synchronously

    PubMed Central

    Hossaert-McKey, M.; Proffit, M.; Soler, C. C. L.; Chen, C.; Bessière, J.-M.; Schatz, B.; Borges, R. M.

    2016-01-01

    In nursery pollination mutualisms, which are usually obligate interactions, olfactory attraction of pollinators by floral volatile organic compounds (VOCs) is the main step in guaranteeing partner encounter. However, mechanisms ensuring the evolutionary stability of dioecious fig–pollinator mutualisms, in which female fig trees engage in pollination by deceit resulting in zero reproductive success of pollinators that visit them, are poorly understood. In dioecious figs, individuals of each sex should be selected to produce odours that their pollinating wasps cannot distinguish, especially since pollinators have usually only one choice of a nursery during their lifetime. To test the hypothesis of intersexual chemical mimicry, VOCs emitted by pollen-receptive figs of seven dioecious species were compared using headspace collection and gas chromatography-mass spectrometry analysis. First, fig-flower scents varied significantly among species, allowing host-species recognition. Second, in species in which male and female figs are synchronous, intersexual VOC variation was not significant. However, in species where figs of both sexes flower asynchronously, intersexual variation of VOCs was detectable. Finally, with one exception, there was no sexual dimorphism in scent quantity. We show that there are two ways to use scent to be a dioecious fig based on differences in flowering synchrony between the sexes. PMID:26888579

  11. The influence of fig proteases on the inhibition of angiotensin I-converting and GABA formation in meat.

    PubMed

    Li, Jinyue; Izumimoto, Masatoshi; Yonehara, Makiko; Hirotsu, Seiya; Kuriki, Takayoshi; Naito, Ichiro; Yamada, Hidenori

    2009-12-01

    The purposes of this research were to use fig protease for texture tenderizing, and to inhibit angiotensin I-converting enzyme (ACE) action and gamma-aminobutyric acid (GABA) formation of meat. Liberated peptides by the enzymatic action of fig protease in processing meat and free amino acids were determined and ACE inhibitory activity was assayed. Meat treated with fig protease became tender as indicated by shear force value (SFV) which was half of those of non-fig treated meat during storage even at 5 degrees C. Liberated peptides, free amino acids and GABA increased while extremely low levels of Glu were detected after storage. The optimal temperature of fig protease against meat was 80 degrees C. However, the activity of fig protease decreased after pre-heating more than 40 degrees C. High ACE inhibitory activity of a mixture of fig and meat was found around 80 degrees C, and the value corresponded to the amount of liberated peptide. A lot of liberated peptides were found at 60-80 degrees C and pasterization of meat product becomes convenient to produce peptides. Production of ACE inhibitory peptides and GABA can be expected as the healthy functional meat product such as antihypertensive activity and improve brain function.

  12. Insect responses to host plant provision beyond natural boundaries: latitudinal and altitudinal variation in a Chinese fig wasp community.

    PubMed

    Wang, Rong; Compton, Stephen G; Quinnell, Rupert J; Peng, Yan-Qiong; Barwell, Louise; Chen, Yan

    2015-09-01

    Many plants are grown outside their natural ranges. Plantings adjacent to native ranges provide an opportunity to monitor community assembly among associated insects and their parasitoids in novel environments, to determine whether gradients in species richness emerge and to examine their consequences for host plant reproductive success. We recorded the fig wasps (Chalcidoidea) associated with a single plant resource (ovules of Ficus microcarpa) along a 1200 km transect in southwest China that extended for 1000 km beyond the tree's natural northern range margin. The fig wasps included the tree's agaonid pollinator and other species that feed on the ovules or are their parasitoids. Phytophagous fig wasps (12 species) were more numerous than parasitoids (nine species). The proportion of figs occupied by fig wasps declined with increasing latitude, as did the proportion of utilized ovules in occupied figs. Species richness, diversity, and abundance of fig wasps also significantly changed along both latitudinal and altitudinal gradients. Parasitoids declined more steeply with latitude than phytophages. Seed production declined beyond the natural northern range margin, and at high elevation, because pollinator fig wasps became rare or absent. This suggests that pollinator climatic tolerances helped limit the tree's natural distribution, although competition with another species may have excluded pollinators at the highest altitude site. Isolation by distance may prevent colonization of northern sites by some fig wasps and act in combination with direct and host-mediated climatic effects to generate gradients in community composition, with parasitoids inherently more sensitive because of declines in the abundance of potential hosts. PMID:26380693

  13. Insect responses to host plant provision beyond natural boundaries: latitudinal and altitudinal variation in a Chinese fig wasp community

    PubMed Central

    Wang, Rong; Compton, Stephen G; Quinnell, Rupert J; Peng, Yan-Qiong; Barwell, Louise; Chen, Yan

    2015-01-01

    Many plants are grown outside their natural ranges. Plantings adjacent to native ranges provide an opportunity to monitor community assembly among associated insects and their parasitoids in novel environments, to determine whether gradients in species richness emerge and to examine their consequences for host plant reproductive success. We recorded the fig wasps (Chalcidoidea) associated with a single plant resource (ovules of Ficus microcarpa) along a 1200 km transect in southwest China that extended for 1000 km beyond the tree's natural northern range margin. The fig wasps included the tree's agaonid pollinator and other species that feed on the ovules or are their parasitoids. Phytophagous fig wasps (12 species) were more numerous than parasitoids (nine species). The proportion of figs occupied by fig wasps declined with increasing latitude, as did the proportion of utilized ovules in occupied figs. Species richness, diversity, and abundance of fig wasps also significantly changed along both latitudinal and altitudinal gradients. Parasitoids declined more steeply with latitude than phytophages. Seed production declined beyond the natural northern range margin, and at high elevation, because pollinator fig wasps became rare or absent. This suggests that pollinator climatic tolerances helped limit the tree's natural distribution, although competition with another species may have excluded pollinators at the highest altitude site. Isolation by distance may prevent colonization of northern sites by some fig wasps and act in combination with direct and host-mediated climatic effects to generate gradients in community composition, with parasitoids inherently more sensitive because of declines in the abundance of potential hosts. PMID:26380693

  14. Insect responses to host plant provision beyond natural boundaries: latitudinal and altitudinal variation in a Chinese fig wasp community.

    PubMed

    Wang, Rong; Compton, Stephen G; Quinnell, Rupert J; Peng, Yan-Qiong; Barwell, Louise; Chen, Yan

    2015-09-01

    Many plants are grown outside their natural ranges. Plantings adjacent to native ranges provide an opportunity to monitor community assembly among associated insects and their parasitoids in novel environments, to determine whether gradients in species richness emerge and to examine their consequences for host plant reproductive success. We recorded the fig wasps (Chalcidoidea) associated with a single plant resource (ovules of Ficus microcarpa) along a 1200 km transect in southwest China that extended for 1000 km beyond the tree's natural northern range margin. The fig wasps included the tree's agaonid pollinator and other species that feed on the ovules or are their parasitoids. Phytophagous fig wasps (12 species) were more numerous than parasitoids (nine species). The proportion of figs occupied by fig wasps declined with increasing latitude, as did the proportion of utilized ovules in occupied figs. Species richness, diversity, and abundance of fig wasps also significantly changed along both latitudinal and altitudinal gradients. Parasitoids declined more steeply with latitude than phytophages. Seed production declined beyond the natural northern range margin, and at high elevation, because pollinator fig wasps became rare or absent. This suggests that pollinator climatic tolerances helped limit the tree's natural distribution, although competition with another species may have excluded pollinators at the highest altitude site. Isolation by distance may prevent colonization of northern sites by some fig wasps and act in combination with direct and host-mediated climatic effects to generate gradients in community composition, with parasitoids inherently more sensitive because of declines in the abundance of potential hosts.

  15. Role of RNA Interference (RNAi) in Dengue Virus Replication and Identification of NS4B as an RNAi Suppressor

    PubMed Central

    Kakumani, Pavan Kumar; Ponia, Sanket Singh; S, Rajgokul K.; Sood, Vikas; Chinnappan, Mahendran; Banerjea, Akhil C.; Medigeshi, Guruprasad R.; Malhotra, Pawan

    2013-01-01

    RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by in vitro dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication. PMID:23741001

  16. Treatments with gras compounds to keep fig fruit (Ficus carica L.) quality during cold storage.

    PubMed

    Venditti, T; Molinu, M G; Dore, A; D'Hallewin, G; Fiori, P; Tedde, M; Agabbio, M

    2005-01-01

    The trade of fresh fig fruit is restricted by its high perishability and numerous attempts have been done to extend the postharvest life. The main difficulties can be found in the fast ripening and the easiness of pathogen spread. Although the ripening can be slowed by low storage temperatures (close to 0 degrees C) the control of pathogens remains still unsolved since no pesticide treatments are allowed. Generally Recognized As Save Compounds (G.R.A.S.) are possible candidates to fulfil this void. Sodium carbonate (SC) solutions (0.5, 1, 2 and 3%) and acetic acid (AAC) vapours (25, 50 and 100 ppm) have been used as postharvest treatments to control Botrytis cinerea on black (Craxiou de Porcu) and white (Rampelina) fig varieties. Fruit was subsequently stored at 2 or 8 degrees C and 90% relative humidity for two weeks. At the end of the experiment decay, weight loss, pH, acidity, total soluble solids and visual assessment were performed. SC treatment at 1% reduced significantly the decay while, lower and higher concentrations did not. Between the two studied varieties the lowest decay percentage (9.8%) was found for the Craxiou de Porcu. Using AAC a good efficacy was achieved only with 100 ppm, this treatment decrease to 2.4% the incidence of decay irrespective to storage temperature. Lower concentrations were lesser effective and the efficacy was strictly dependent on the storage temperature, being higher at 2 degrees C. No treatment damages were observed following SC or AAC applications. Regarding fruit weight loss all treatments did not affect this parameter that was 10.1% and 16.9% at 2 and 8 degrees C, respectively. Chemical analyses performed at the end of the storage period did not evidenced differences among the treatments and slight ones if compared to initial values. Visual score of the fruit at the end of storage evidenced a better keeping quality for Craxiou de Porcu especially when stored at 2 degrees C. Both G.R.A.S. compounds are promising, but in

  17. The distribution of Wolbachia in fig wasps: correlations with host phylogeny, ecology and population structure.

    PubMed Central

    Shoemaker, D DeWayne; Machado, Carlos A; Molbo, Drude; Werren, John H; Windsor, Donald M; Herre, Edward Allen

    2002-01-01

    We surveyed for the presence and identity of Wolbachia in 44 species of chalcid wasps associated with 18 species of Panamanian figs. We used existing detailed knowledge of the population structures of the host wasps, as well as the ecological and evolutionary relationships among them, to explore the relevance of each of these factors to Wolbachia prevalence and mode of transmission. Fifty-nine per cent of these wasp species have Wolbachia infections, the highest proportion reported for any group of insects. Further, neither the presence nor the frequency of Wolbachia within hosts was correlated with the population structure of pollinator hosts. Phylogenetic analyses of wsp sequence data from 70 individuals representing 22 wasp species show that neither the close phylogenetic relationship nor close ecological association among host species is consistently linked to close phylogenetic affinities of the Wolbachia associated with them. Moreover, no genetic variation was detected within any Wolbachia strain from a given host species. Thus, the spread of Wolbachia within host species exceeds the rate of horizontal transmission among species and both exceed the rate of mutation of the wsp gene in Wolbachia. The presence and, in some cases, high frequency of Wolbachia infections within highly inbred species indicate that the Wolbachia either directly increase host fitness or are frequently horizontally transferred within these wasp species. However, the paucity of cospeciation of Wolbachia and their wasp hosts indicates that Wolbachia do not persist within a given host lineage for long time-periods relative to speciation times. PMID:12427319

  18. Antioxidant and hepatoprotective properties of dried fig against oxidative stress and hepatotoxicity in rats.

    PubMed

    Turan, Abdullah; Celik, Ismail

    2016-10-01

    The aim of this study was to investigate the hepatoprotective effect and antioxidant role of dried fig (DF) (Ficus carica L.) against ethanol-induced oxidative stress. Experiment was designed as normal Control, 20% ethanol, 10% DF and 10% DF+20% ethanol groups. The hepatoprotective and antioxidant role of the dried DF supplementation feed against ethanol induced oxidatif stress were evaluated by liver histopathological changes, measuring liver damage serum enzymes (LDSE), antioxidant defense system (ADS) and malondialdehyde (MDA) content in various tissues of rats following the exposure of experimental for 50days. The biochemical analysis showed a considerable increase the LDSE in the ethanol group as compared to that of control group whereas, decreased in 10% DF+20% ethanol group as compared to that of ethanol group. In addition, the DF supplementation diet restored the ethanol-induced MDA and ADS towards to control. The hepatoprotection of DF is further substantiated by the almost normal histologic findings of liver in 10% DF+20% ethanol group against degenerative changes in ethanol group. The results indicated that the DF could be as important as diet-derived antioxidants and antihepatotoxicity in preventing oxidative damage in the tissues by inhibiting the production of ethanol-induced free radicals and hepatotoxicity in rats. PMID:27268385

  19. Biosorption of Ni(II) by Fig Male: Optimization and Modeling Using a Full Factorial Design.

    PubMed

    Madjene, F; Chergui, A; Trari, M

    2016-06-01

    The fig male (FM) is successfully used as biosorbent for Ni(2+) removal. The maximum removal efficiency (96.6%) is obtained at pH ~ 5 for a concentration of 1.70 mmol L(-1) and catalyst dose of 5 g L(-1) in less than 10 minutes. The Ni(2+) uptake follows a pseudo-second-order kinetic, the rate constants increase with increasing temperature, and an activation energy of 55.48 kJ mol(-1) is found. The thermodynamic parameters indicate a spontaneous endothermic bisorption. The isotherm data are fitted by the Langmuir and Dubinin-Radushkevich models. The former indicates a maximum Ni(2+) uptake of 0.459 mmol g(-1), which is higher than that of most biosorbents investigated to date. The FTIR spectra reveal the biosorption mechanism between Ni(2+) and FM functional groups. An empirical modeling is performed by using a 2(3) full factorial design, and a regression equation for Ni(2+) biosorption is determined. The biosorbent mass and pH are the most significant parameters affecting the Ni(2+) biosorption. PMID:27225783

  20. Pectinesterase inhibitor from jelly-fig (Ficus awkeotsang Makino) achenes reduces methanol content in carambola wine.

    PubMed

    Wu, James Swi-Bea; Wu, Ming-Chang; Jiang, Chii-Ming; Hwang, Ya-Ping; Shen, Szu-Chuan; Chang, Hung-Min

    2005-11-30

    Crude pectinesterase (PE) inhibitor (PEI) extracted from jelly-fig achenes (JFA) (Ficus awakeosang Makino) was added to carambola (Averrhoa carambola L.) puree to determine the change in methanol production during fermentation. Addition of pectin or microbial pectic enzyme to puree increased dose-dependently the methanol content in fermented products. Decreasing ratio (from 1:0 to 1:19, v:v) of pectic enzyme to diluted crude PEI solution in the puree-enzyme mixture decreased the PE activity remarkably. Except for transmittance (%T), addition of crude PEI to puree did not affect apparently the physical and chemical properties of wine; however, it reduced methanol content in the control from 256 to 58 ppm. The degree of esterification (DE) of pectin in starting puree was approximately 70%. It decreased to approximately 27% in the control group and reduced slightly to approximately 67% in fermented puree with crude PEI added after 14 days of fermentation. This reveals that crude PEI solution was potent in inhibiting intrinsic carambola PE activity and appeared to be a potential alternative for methanol reduction in wines.

  1. Antioxidant and hepatoprotective properties of dried fig against oxidative stress and hepatotoxicity in rats.

    PubMed

    Turan, Abdullah; Celik, Ismail

    2016-10-01

    The aim of this study was to investigate the hepatoprotective effect and antioxidant role of dried fig (DF) (Ficus carica L.) against ethanol-induced oxidative stress. Experiment was designed as normal Control, 20% ethanol, 10% DF and 10% DF+20% ethanol groups. The hepatoprotective and antioxidant role of the dried DF supplementation feed against ethanol induced oxidatif stress were evaluated by liver histopathological changes, measuring liver damage serum enzymes (LDSE), antioxidant defense system (ADS) and malondialdehyde (MDA) content in various tissues of rats following the exposure of experimental for 50days. The biochemical analysis showed a considerable increase the LDSE in the ethanol group as compared to that of control group whereas, decreased in 10% DF+20% ethanol group as compared to that of ethanol group. In addition, the DF supplementation diet restored the ethanol-induced MDA and ADS towards to control. The hepatoprotection of DF is further substantiated by the almost normal histologic findings of liver in 10% DF+20% ethanol group against degenerative changes in ethanol group. The results indicated that the DF could be as important as diet-derived antioxidants and antihepatotoxicity in preventing oxidative damage in the tissues by inhibiting the production of ethanol-induced free radicals and hepatotoxicity in rats.

  2. Actinoalloteichus nanshanensis sp. nov., isolated from the rhizosphere of a fig tree (Ficus religiosa).

    PubMed

    Xiang, Wensheng; Liu, Chongxi; Wang, Xiangjing; Du, Jing; Xi, Lijun; Huang, Ying

    2011-05-01

    A Gram-positive, aerobic actinomycete, designated strain NEAU 119(T), was isolated from the rhizosphere of a fig tree and was characterized using a polyphasic approach. The isolate formed branching, non-fragmenting vegetative hyphae and produced black pigment on yeast extract/malt extract (ISP medium 2). The G+C content of the DNA was 76.6 mol%. The organism had chemotaxonomic characteristics typical of the genus Actinoalloteichus and was closely related to the type strains of Actinoalloteichus cyanogriseus, Actinoalloteichus spitiensis and Actinoalloteichus hymeniacidonis, currently the only three recognized species of the genus Actinoalloteichus, sharing 16S rRNA gene similarities of 96.4, 96.6 and 98.1 %, respectively. However, the results of DNA-DNA hybridization studies demonstrated that the novel strain showed only 46.8 % relatedness with the type strain of A. hymeniacidonis. In addition, a set of phenotypic characteristics also readily distinguished strain NEAU 119(T) from the type strains of recognized species of the genus Actinoalloteichus. According to the above data, it is proposed that strain NEAU 119(T) represents a novel species, Actinoalloteichus nanshanensis sp. nov. The type strain of Actinoalloteichus nanshanensis is NEAU 119(T) ( = CGMCC 4.5714(T) = NBRC 106685(T)). PMID:20562245

  3. Fig1, an interleukin 4-induced mouse B cell gene isolated by cDNA representational difference analysis

    PubMed Central

    Chu, Charles C.; Paul, William E.

    1997-01-01

    Interleukin 4 (IL-4) is a cytokine that regulates growth and differentiation of lymphoid and nonlymphoid cells. To study the molecular basis of IL-4 function, we used a cDNA subtraction approach based on the representational difference analysis method. This subtractive amplification technique allowed us to use small amounts of RNA from lipopolysaccharide ± IL-4-stimulated normal B cells to obtain IL-4-induced genes from these cells. We report here on one such gene, Fig1 (interleukin-four induced gene 1), the first characterized immediate–early IL-4 inducible gene from B cells. Fig1 expression is strikingly limited to the lymphoid compartment. B cells, but not T cells or mast cells, express Fig1 in response to IL-4 within 2 hr in a cycloheximide resistant manner. IL-2, IL-5, and Il-6 do not induce Fig1 in culture. Fig1 maps between Klk1 and Ldh3 on mouse chromosome 7, near two loci involved with murine lupus, Sle3 and Lbw5. The Fig1 cDNA sequence encodes a predicted 70-kDa flavoprotein with best homology to the monoamine oxidases, particularly in domains responsible for FAD binding. PMID:9122225

  4. The FIGS (focused identification of germplasm strategy) approach identifies traits related to drought adaptation in Vicia faba genetic resources.

    PubMed

    Khazaei, Hamid; Street, Kenneth; Bari, Abdallah; Mackay, Michael; Stoddard, Frederick L

    2013-01-01

    Efficient methods to explore plant agro-biodiversity for climate change adaptive traits are urgently required. The focused identification of germplasm strategy (FIGS) is one such approach. FIGS works on the premise that germplasm is likely to reflect the selection pressures of the environment in which it developed. Environmental parameters describing plant germplasm collection sites are used as selection criteria to improve the probability of uncovering useful variation. This study was designed to test the effectiveness of FIGS to search a large faba bean (Vicia faba L.) collection for traits related to drought adaptation. Two sets of faba bean accessions were created, one from moisture-limited environments, and the other from wetter sites. The two sets were grown under well watered conditions and leaf morpho-physiological traits related to plant water use were measured. Machine-learning algorithms split the accessions into two groups based on the evaluation data and the groups created by this process were compared to the original climate-based FIGS sets. The sets defined by trait data were in almost perfect agreement to the FIGS sets, demonstrating that ecotypic differentiation driven by moisture availability has occurred within the faba bean genepool. Leaflet and canopy temperature as well as relative water content contributed more than other traits to the discrimination between sets, indicating that their utility as drought-tolerance selection criteria for faba bean germplasm. This study supports the assertion that FIGS could be an effective tool to enhance the discovery of new genes for abiotic stress adaptation.

  5. Stomatal Ultrastructure, Molecular Phylogeny, and Description of Parasitodiplogaster laevigata n. sp. (Nematoda: Diplogastridae), a Parasite of Fig Wasps

    PubMed Central

    Giblin-Davis, Robin M.; Ye, Weimin; Kanzaki, Natsumi; Williams, Donna; Morris, Krystalynne; Thomas, W. Kelley

    2006-01-01

    Parasitodiplogaster comprises a potentially large radiation of nematode species that appear to be parasitically bound to their Agaonid fig wasp hosts, which are mutualistically associated in the syconia (figs) of the diverse plant genus Ficus. Parasitodiplogaster laevigata n. sp. is described and illustrated as an associate of the fig wasp, Pegoscapus sp. from Ficus laevigata from southern Florida. It is the first species of Parasitodiplogaster reported from North America and is closest to P. trigonema from F. trigonata from Panama. Parasitodiplogaster laevigata n. sp. can be differentiated from all described species of Parasitodiplogaster based on stomatal morphology (presence of a large dorsal and a right subventral tooth) in the adults of both sexes, molecular comparisons of two expansion segments (D2,D3) of the large subunit (LSU) rRNAgene, and fig-fig wasp host affinities. The ultrastructure of P. laevigata n. sp. was elucidated using TEM and SEM for comparisons with other species of Parasitodiplogaster. The stoma of P. laevigata n. sp. possesses a nonsegmented cheilostomal ring that connects to the longitudinal body musculature per- and interradially, a claw-like dorsal tooth, a right subventral tooth, and telostegostomatal apodemes arising from the dorsal side of each subventral sector. The unification of the pro-, meso-, and metastegostom with the gymnostom in P. laevigata n. sp. and further simplification in other described species may be due to derived adaptations associated with the internal parasitism of fig wasps. PMID:19259439

  6. Distribution of nuclear mitochondrial pseudogenes in three pollinator fig wasps associated with Ficus pumila

    NASA Astrophysics Data System (ADS)

    Chen, Yan; Liu, Min; Compton, Stephen G.; Chen, Xiao-Yong

    2014-05-01

    Nuclear mitochondrial pseudogenes (NUMTs) are nuclear sequences transferred from mitochondrial genomes. Although widespread, their distribution patterns among populations or closely related species are rarely documented. We amplified and sequenced the mitochondrial cytochrome b (Cytb) gene to check for NUMTs in three fig wasp species that pollinate Ficus pumila (Wiebesia sp. 1, 2 and 3) in Southeastern China using direct and cloned sequencing. Unambiguous sequences (332) of 487 bp in length belonging to 33 haplotypes were found by direct sequencing. Their distribution was highly concordant with those of cytochrome c oxidase subunit I (COI). Obvious signs of co-amplification of NUMTs were indicated by their uneven distribution. NUMTs were observed in all individuals of 12 populations of Wiebesia sp. 3, and 13 individuals of three northern populations of Wiebesia sp. 1. Sequencing clones of potential co-amplification products confirmed that they were NUMTs. These NUMTs either clustered as NUMT clades basal to mtDNA Cytb clades (basal NUMTs), or together with Cytb haplotypes. Basal NUMTs had either stop codons or frame-shifting mutations resulting from deletion of a 106 bp fragment. In addition, no third codon or synonymous substitutions were detected within each NUMT clade. The phylogenetic tree indicated that basal NUMTs had been inserted into nuclei before divergence of the three species. No significant pairwise differences were detected in their ratios of third codon substitutions, suggesting that these NUMTs originated from one transfer event, with duplication in the nuclear genome resulting in the coexistence of the 381 bp copy. No significant substitution differences were detected between Cytb haplotypes and NUMTs that clustered with Cytb haplotypes. However, these NUMTs coexisted with Cytb haplotypes in multiple populations, suggesting that these NUMT haplotypes were recently inserted into the nuclear genome. Both basal and recently inserted NUMTs were rare

  7. Report on inspection of compliance with DOE Order 2030.4B at the Savannah River Site

    SciTech Connect

    1997-03-01

    The purpose of this inspection was to evaluate contractor compliance at the Savannah River Site (SRS) with Department of Energy (DOE) Order 2030.4B, {open_quotes}Reporting Fraud, Waste, And Abuse To The Office Of Inspector General.{close_quotes} The specific objective was to determine if the SRS management and operating (M&O) contractors were complying with the requirements in Paragraph 6.c. of DOE Order 2030.4B. These requirements are: (1) annual notification to employees of their duty to report allegations of fraud, waste, abuse, corruption, or mismanagement; (2) display and publish the DOE Office of Inspector General (OIG) Hotline telephone number in common areas of buildings; (3) display and publish the DOE OIG Hotline number in telephone books and newsletters; and (4) notify the OIG cases referred to other law enforcement entities.

  8. Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein.

    PubMed

    Tai, Vincent W-F; Garrido, Dulce; Price, Daniel J; Maynard, Andrew; Pouliot, Jeffrey J; Xiong, Zhiping; Seal, John W; Creech, Katrina L; Kryn, Luz H; Baughman, Todd M; Peat, Andrew J

    2014-05-15

    Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5nM and 1.2nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC50's of 10.9nM and 6.1nM against 1a and 1b replicons, respectively. Both compounds 6p and 27c bound directly to non-structural NS4B protein in vitro (IC50's=10.2 and 30.4nM, respectively) and exhibited reduced potency in replicons containing resistance mutations encoding changes in the NS4B protein.

  9. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents.

    PubMed

    Nagender, P; Naresh Kumar, R; Malla Reddy, G; Krishna Swaroop, D; Poornachandra, Y; Ganesh Kumar, C; Narsaiah, B

    2016-09-15

    A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule. PMID:27528432

  10. Isolation and Characterization of Noncytopathic Pestivirus Mutants Reveals a Role for Nonstructural Protein NS4B in Viral Cytopathogenicity

    PubMed Central

    Qu, Lin; McMullan, Laura K.; Rice, Charles M.

    2001-01-01

    Isolates of bovine viral diarrhea virus (BVDV), the prototype pestivirus, are divided into cytopathic (cp) and noncytopathic (ncp) biotypes according to their effect on cultured cells. The cp viruses also differ from ncp viruses by the production of viral nonstructural protein NS3. However, the mechanism by which cp viruses induce cytopathic effect in cell culture remains unknown. Here we used a genetic approach to isolate ncp variants that arose from a cp virus at low frequency. A bicistronic BVDV (cp strain NADL) was created that expressed puromycin acetyltransferase as a dominant selectable marker. This bicistronic virus exhibited slightly slower growth kinetics and smaller plaques than NADL but remained cp. A number of independent ncp variants were isolated by puromycin selection. Remarkably, these ncp variants produced NS3 and viral RNA at levels comparable to those of the cp parent. Sequence analyses uncovered no change in NS3, but for all ncp variants a Y2441C substitution at residue 15 of NS4B was found. Introduction of the Y2441C substitution into the NADL or bicistronic cp viruses reconstituted the ncp phenotype. Y2441 is highly conserved among pestiviruses and is located in a region of NS4B predicted to be on the cytosolic side of the endoplasmic reticulum membrane. Other engineered substitutions for Y2441 also affected viral cytopathogenicity and viability, with Y2441V being cp, Y2441A being ncp, and Y2441D rendering the virus unable to replicate. The ncp substitutions for Y2441 resulted in slightly increased levels of NS2-3 relative to NS3. We also showed that NS3, NS4B, and NS5A could be chemically cross-linked in NADL-infected cells, indicating that they are associated as components of a multiprotein complex. Although the mechanism remains to be elucidated, these results demonstrate that mutations in NS4B can attenuate BVDV cytopathogenicity despite NS3 production. PMID:11602707

  11. Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells.

    PubMed

    Saxena, Ashwini; Bachelor, Martha; Park, Yong H; Carreno, Flavia R; Nedungadi, T Prashant; Cunningham, J Thomas

    2014-10-15

    Transient receptor potential vanilloid family type 4 (TRPV4) channels are expressed in central neuroendocrine neurons and have been shown to be polymodal in other systems. We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 μM) and by a Src kinase inhibitor PP2 (10 μM). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 ± 2.8% n = 5 and ANG II 80.5 ± 2.4% n = 5). This ANG II-induced increase in calcium influx was also blocked by 1 μM losartan and 10 μM PP2 (losartan 26.4 ± 3.8% n = 5 and PP2 19.7 ± 3.9% n = 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway. PMID:25080500

  12. A Flight Investigation of the Spinning of the F4B-2 Biplane with Various Loads and Tail Surfaces

    NASA Technical Reports Server (NTRS)

    Scudder, N F; Seidman, Oscar

    1936-01-01

    A flight investigation of the spinning of the F4B-2 single-seat fighter airplane was made for the purpose of finding modifications that would eliminate dangerous spin tendencies exhibited by this type of airplane in service. The effects on steady spins and on recoveries of changing the loading, enlarging the fin areas, changing the elevator plan form, and raising the horizontal surfaces, were determined.

  13. The complement regulator C4b-binding protein analyzed by molecular modeling, bioinformatics and computer-aided experimental design.

    PubMed

    Villoutreix, B O; Blom, A M; Webb, J; Dahlbäck, B

    1999-05-01

    Molecular modeling and bioinformatics have gained recognition as scientific disciplines of importance in the field of biomedical research. Molecular modeling not only allows to predict the three-dimensional structure of a protein but also helps to define its function. Careful incorporation of the experimental findings in the structural/theoretical data provides means to understand molecular mechanisms for highly complex biological systems. C4b-binding protein (C4BP) is composed of one beta-chain and seven alpha-chains essentially built from three- and eight-complement control protein (CCP) modules, respectively, followed by a non-repeat carboxy-terminal region involved in polymerization of the chains. C4BP is involved in the regulation of the complement system and interacts with many molecules such as C4b, Arp, protein S and heparin. Here, we report experimental and computer data obtained for C4BP. Protein modeling together with site directed mutagenesis indicate that R39, R64 and R66 from the C4BP alpha-chain form a key binding site for heparin, suggesting that this region could be of major importance for interaction with C4b. We also propose that the first CCP of the C4BP beta-chain displays a key hydrophobic surface of major importance for the interaction with the coagulation cofactor protein S. PMID:10408373

  14. Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication.

    PubMed

    van Cleef, Koen W R; Overheul, Gijs J; Thomassen, Michael C; Kaptein, Suzanne J F; Davidson, Andrew D; Jacobs, Michael; Neyts, Johan; van Kuppeveld, Frank J M; van Rij, Ronald P

    2013-08-01

    Dengue virus (DENV) is an important human arthropod-borne virus with a major impact on public health. Nevertheless, a licensed vaccine or specific treatment is still lacking. We therefore screened the NIH Clinical Collection (NCC), a library of drug-like small molecules, for inhibitors of DENV replication using a cell line that contains a stably replicating DENV serotype 2 (DENV2) subgenomic replicon. The most potent DENV inhibitor in the NCC was δ opioid receptor antagonist SDM25N. This compound showed antiviral activity against wild-type DENV2 in both Hela and BHK-21 cells, but not in the C6/36 cell line derived from the mosquito Aedes albopictus. The structurally related compound naltrindole also inhibited DENV replication, albeit less potently. Using a transient subgenomic replicon, we demonstrate that SDM25N restricts genomic RNA replication rather than translation of the viral genome. We identified a single amino acid substitution (F164L) in the NS4B protein that confers resistance to SDM25N. Remarkably, an NS4B amino acid substitution (P104L), which was previously shown to confer resistance to the DENV inhibitor NITD-618, also provided resistance to SDM25N. In conclusion, we have identified a new DENV inhibitor, SDM25N, which restricts genomic RNA replication by - directly or indirectly - targeting the viral NS4B protein. PMID:23735301

  15. Dithiazolo[5,4-b:4',5'-d]phosphole: a highly luminescent electron-accepting building block.

    PubMed

    He, Xiaoming; Woo, Alva Y Y; Borau-Garcia, Javier; Baumgartner, Thomas

    2013-06-01

    A family of highly emissive dithiazolo[5,4-b:4',5'-d]phospholes has been designed and synthesized. The structures of two trivalent P species, as well as their corresponding P oxides, have been confirmed by X-ray crystallography. The parent dithiazolo[5,4-b:4',5'-d]phosphole oxide exhibits strong blue photoluminescence at λem = 442 nm, with an excellent quantum yield efficiency of ϕPL = 0.81. The photophysical properties of these compounds can be easily tuned by extension of the conjugation and modification of the phosphorus center. Compared with the established dithieno[3,2-b:2',3'-d]phosphole system, the incorporation of electronegative nitrogen atoms leads to significantly lowered frontier orbital energy levels, as validated by both electrochemistry and theoretical calculations, thus suggesting that the dithiazolo[5,4-b:4',5'-d]phospholes are valuable, air-stable, n-type conjugated materials. These new building blocks have been further applied to the construction of an extended oligomer with fluorene. Extension of the dithiazolophosphole core with triazole units through click reactions also provides a suitable N,N-chelating moiety for metal binding and a representative molecular species was successfully used as a selective colorimetric and fluorescent sensor for Cu(II) ions.

  16. The GAPS programme with HARPS-N at TNG. VI. The curious case of TrES-4b

    NASA Astrophysics Data System (ADS)

    Sozzetti, A.; Bonomo, A. S.; Biazzo, K.; Mancini, L.; Damasso, M.; Desidera, S.; Gratton, R.; Lanza, A. F.; Poretti, E.; Rainer, M.; Malavolta, L.; Affer, L.; Barbieri, M.; Bedin, L. R.; Boccato, C.; Bonavita, M.; Borsa, F.; Ciceri, S.; Claudi, R. U.; Gandolfi, D.; Giacobbe, P.; Henning, T.; Knapic, C.; Latham, D. W.; Lodato, G.; Maggio, A.; Maldonado, J.; Marzari, F.; Martinez Fiorenzano, A. F.; Micela, G.; Molinari, E.; Mordasini, C.; Nascimbeni, V.; Pagano, I.; Pedani, M.; Pepe, F.; Piotto, G.; Santos, N.; Scandariato, G.; Shkolnik, E.; Southworth, J.

    2015-03-01

    We update the TrES-4 system parameters using high-precision HARPS-N radial-velocity measurements and new photometric light curves. A combined spectroscopic and photometric analysis allows us to determine a spectroscopic orbit with a semi-amplitude K = 51 ± 3 m s-1. The derived mass of TrES-4b is found to be Mp = 0.49 ± 0.04 MJup, significantly lower than previously reported. Combined with the large radius () inferred from our analysis, TrES-4b becomes the transiting hot Jupiter with the second-lowest density known. We discuss several scenarios to explain the puzzling discrepancy in the mass of TrES-4b in the context of the exotic class of highly inflated transiting giant planets. Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated on the island of La Palma by the Fundacion Galileo Galilei of the INAF at the Spanish Observatorio del Roque de los Muchachos of the IAC in the frame of the program Global Architecture of Planetary Systems (GAPS), and with the Zeiss 1.23-m telescope at the German-Spanish Astronomical Center at Calar Alto, Spain. Tables 1 and 3 are available in electronic form at http://www.aanda.org

  17. Regulation of Protein Quality Control by UBE4B and LSD1 through p53-Mediated Transcription

    PubMed Central

    Periz, Goran; Lu, Jiayin; Zhang, Tao; Kankel, Mark W.; Jablonski, Angela M.; Kalb, Robert; McCampbell, Alexander; Wang, Jiou

    2015-01-01

    Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B) and lysine-specific demethylase 1 (LSD1), respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy. PMID:25837623

  18. Spatial Scales of Genetic Structure in Free-Standing and Strangler Figs (Ficus, Moraceae) Inhabiting Neotropical Forests.

    PubMed

    Heer, Katrin; Kalko, Elisabeth K V; Albrecht, Larissa; García-Villacorta, Roosevelt; Staeps, Felix C; Herre, Edward Allen; Dick, Christopher W

    2015-01-01

    Wind-borne pollinating wasps (Agaonidae) can transport fig (Ficus sp., Moraceae) pollen over enormous distances (> 100 km). Because of their extensive breeding areas, Neotropical figs are expected to exhibit weak patterns of genetic structure at local and regional scales. We evaluated genetic structure at the regional to continental scale (Panama, Costa Rica, and Peru) for the free-standing fig species Ficus insipida. Genetic differentiation was detected only at distances > 300 km (Jost´s Dest = 0.68 ± 0.07 & FST = 0.30 ± 0.03 between Mesoamerican and Amazonian sites) and evidence for phylogeographic structure (RST>permuted RST) was only significant in comparisons between Central and South America. Further, we assessed local scale spatial genetic structure (SGS, d ≤ 8 km) in Panama and developed an agent-based model parameterized with data from F. insipida to estimate minimum pollination distances, which determine the contribution of pollen dispersal on SGS. The local scale data for F. insipida was compared to SGS data collected for an additional free-standing fig, F. yoponensis (subgenus Pharmacosycea), and two species of strangler figs, F. citrifolia and F. obtusifolia (subgenus Urostigma) sampled in Panama. All four species displayed significant SGS (mean Sp = 0.014 ± 0.012). Model simulations indicated that most pollination events likely occur at distances > > 1 km, largely ruling out spatially limited pollen dispersal as the determinant of SGS in F. insipida and, by extension, the other fig species. Our results are consistent with the view that Ficus develops fine-scale SGS primarily as a result of localized seed dispersal and/or clumped seedling establishment despite extensive long-distance pollen dispersal. We discuss several ecological and life history factors that could have species- or subgenus-specific impacts on the genetic structure of Neotropical figs. PMID:26226482

  19. Spatial Scales of Genetic Structure in Free-Standing and Strangler Figs (Ficus, Moraceae) Inhabiting Neotropical Forests

    PubMed Central

    Heer, Katrin; Albrecht, Larissa; García-Villacorta, Roosevelt; Staeps, Felix C.; Herre, Edward Allen; Dick, Christopher W.

    2015-01-01

    Wind-borne pollinating wasps (Agaonidae) can transport fig (Ficus sp., Moraceae) pollen over enormous distances (> 100 km). Because of their extensive breeding areas, Neotropical figs are expected to exhibit weak patterns of genetic structure at local and regional scales. We evaluated genetic structure at the regional to continental scale (Panama, Costa Rica, and Peru) for the free-standing fig species Ficus insipida. Genetic differentiation was detected only at distances > 300 km (Jost´s Dest = 0.68 ± 0.07 & FST = 0.30 ± 0.03 between Mesoamerican and Amazonian sites) and evidence for phylogeographic structure (RST>>permuted RST) was only significant in comparisons between Central and South America. Further, we assessed local scale spatial genetic structure (SGS, d ≤ 8 km) in Panama and developed an agent-based model parameterized with data from F. insipida to estimate minimum pollination distances, which determine the contribution of pollen dispersal on SGS. The local scale data for F. insipida was compared to SGS data collected for an additional free-standing fig, F. yoponensis (subgenus Pharmacosycea), and two species of strangler figs, F. citrifolia and F. obtusifolia (subgenus Urostigma) sampled in Panama. All four species displayed significant SGS (mean Sp = 0.014 ± 0.012). Model simulations indicated that most pollination events likely occur at distances > > 1 km, largely ruling out spatially limited pollen dispersal as the determinant of SGS in F. insipida and, by extension, the other fig species. Our results are consistent with the view that Ficus develops fine-scale SGS primarily as a result of localized seed dispersal and/or clumped seedling establishment despite extensive long-distance pollen dispersal. We discuss several ecological and life history factors that could have species- or subgenus-specific impacts on the genetic structure of Neotropical figs. PMID:26226482

  20. Spatial Scales of Genetic Structure in Free-Standing and Strangler Figs (Ficus, Moraceae) Inhabiting Neotropical Forests.

    PubMed

    Heer, Katrin; Kalko, Elisabeth K V; Albrecht, Larissa; García-Villacorta, Roosevelt; Staeps, Felix C; Herre, Edward Allen; Dick, Christopher W

    2015-01-01

    Wind-borne pollinating wasps (Agaonidae) can transport fig (Ficus sp., Moraceae) pollen over enormous distances (> 100 km). Because of their extensive breeding areas, Neotropical figs are expected to exhibit weak patterns of genetic structure at local and regional scales. We evaluated genetic structure at the regional to continental scale (Panama, Costa Rica, and Peru) for the free-standing fig species Ficus insipida. Genetic differentiation was detected only at distances > 300 km (Jost´s Dest = 0.68 ± 0.07 & FST = 0.30 ± 0.03 between Mesoamerican and Amazonian sites) and evidence for phylogeographic structure (RST>permuted RST) was only significant in comparisons between Central and South America. Further, we assessed local scale spatial genetic structure (SGS, d ≤ 8 km) in Panama and developed an agent-based model parameterized with data from F. insipida to estimate minimum pollination distances, which determine the contribution of pollen dispersal on SGS. The local scale data for F. insipida was compared to SGS data collected for an additional free-standing fig, F. yoponensis (subgenus Pharmacosycea), and two species of strangler figs, F. citrifolia and F. obtusifolia (subgenus Urostigma) sampled in Panama. All four species displayed significant SGS (mean Sp = 0.014 ± 0.012). Model simulations indicated that most pollination events likely occur at distances > > 1 km, largely ruling out spatially limited pollen dispersal as the determinant of SGS in F. insipida and, by extension, the other fig species. Our results are consistent with the view that Ficus develops fine-scale SGS primarily as a result of localized seed dispersal and/or clumped seedling establishment despite extensive long-distance pollen dispersal. We discuss several ecological and life history factors that could have species- or subgenus-specific impacts on the genetic structure of Neotropical figs.

  1. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease

    SciTech Connect

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-08-16

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.

  2. LAPTM4B is associated with poor prognosis in NSCLC and promotes the NRF2-mediated stress response pathway in lung cancer cells

    PubMed Central

    Maki, Yuho; Fujimoto, Junya; Lang, Wenhua; Xu, Li; Behrens, Carmen; Wistuba, Ignacio I.; Kadara, Humam

    2015-01-01

    We recently demonstrated that lysosomal protein transmembrane 4 beta (LAPTM4B) is elevated in non-small cell lung cancers (NSCLCs) and in the surrounding premalignant airway field of cancerization. In the present study, we sought to begin to understand the relevance of LAPTM4B expression and signaling to NSCLC pathogenesis. In situ hybridization analysis of LAPTM4B transcript in tissue microarrays comprised of 368 NSCLCs demonstrated that LAPTM4B expression was significantly increased in smoker compared to non-smoker lung adenocarcinoma tumors (P < 0.001) and was significantly associated with poor overall survival (P < 0.05) in adenocarcinoma patients. Knockdown of LAPTM4B expression inhibited cell growth, induced cellular apoptosis and decreased cellular autophagy in serum starved lung cancer cells. Expression profiling coupled with pathways analysis revealed decreased activation of the nuclear factor erythroid 2-like 2 (NRF2) stress response pathway following LAPTM4B knockdown. Further analysis demonstrated that LAPTM4B augmented the expression and nuclear translocation of the NRF2 transcription factor following serum deprivation as well as increased the expression of NRF2 target genes such as heme oxygenase 1/HMOX1). Our study points to the relevance of LAPTM4B expression to NSCLC pathogenesis as well as to the probable role of LAPTM4B/NRF2 signaling in promoting lung cancer cell survival. PMID:26343532

  3. Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies

    PubMed Central

    Feng, Yanguo; Cheng, Dejun; Zhang, Chaofeng; Li, Yuchun; Zhang, Zhiying; Wang, Juan; Shi, Yuzhong

    2016-01-01

    Background The PDE4B single nucleotide polymorphisms (SNPs) have been reported to be associated with schizophrenia risk. However, current findings are ambiguous or even conflicting. To better facilitate the understanding the genetic role played by PDE4B in susceptibility to schizophrenia, we collected currently available data and conducted this meta-analysis. Methods A comprehensive electronic literature searching of PubMed, Embase, Web of Science and Cochrane Library was performed. The association between PDE4B SNPs and schizophrenia was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under allelic, dominant and recessive genetic models. The random effects model was utilized when high between-study heterogeneity (I2 > 50%) existed, otherwise the fixed effects model was used. Results Five studies comprising 2376 schizophrenia patients and 3093 controls were finally included for meta-analysis. The rs1040716 was statistically significantly associated with schizophrenia risk in Asian and Caucasian populations under dominant model (OR = 0.87, 95% CI: 0.76–0.99, P = 0.04). The rs2180335 was significantly related with schizophrenia risk in Asian populations under allelic (OR = 0.82, 95% CI: 0.72–0.93, P = 0.003) and dominant (OR = 0.75, 95% CI: 0.64–0.88, P < 0.001) models. A significant association was also observed between rs4320761 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.75–1.00, P = 0.048). In addition, a strong association tendency was found between rs6588190 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.76–1.00, P = 0.055). Conclusion This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia. However, due to limited sample size, more large-scale, multi-racial association studies are needed to further clarify the genetic association between various PDE4B variants and schizophrenia. PMID:26756575

  4. Identification and characterization of two novel genomic RNA segments of fig mosaic virus, RNA5 and RNA6.

    PubMed

    Ishikawa, Kazuya; Maejima, Kensaku; Komatsu, Ken; Kitazawa, Yugo; Hashimoto, Masayoshi; Takata, Daisuke; Yamaji, Yasuyuki; Namba, Shigetou

    2012-07-01

    Fig mosaic virus (FMV), a negative-strand RNA virus, is recognized as a causal agent of fig mosaic disease. We performed RT-PCR for 14 FMV isolates collected from symptomatic fig plants in Japan and Serbia using primers corresponding to the conserved 13 nt stretches found at the termini of FMV genomic segments. The resulting simultaneous amplification of all FMV genomic segments yielded four previously identified segments of FMV and two novel segments. These novel FMV genomic RNA segments were found in each of the 14 FMV isolates analysed. In Northern blot studies, both the sense and antisense strands of these novel RNA molecules accumulated in FMV-infected fig leaves but not in uninfected fig leaves, confirming that they replicate as FMV genomic segments. Sequence analysis showed that the novel RNA segments are similar, in their structural organization and molecular evolutionary patterns, to those of known FMV genomic RNA segments. Our findings thus indicate that these newly discovered RNA segments are previously unidentified FMV genomic segments, which we have designated RNA5 and RNA6.

  5. Allelic Variation and Differential Expression of the mSIN3A Histone Deacetylase Complex Gene Arid4b Promote Mammary Tumor Growth and Metastasis

    PubMed Central

    Winter, Scott F.; Lukes, Luanne; Walker, Renard C.; Welch, Danny R.; Hunter, Kent W.

    2012-01-01

    Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT–rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA–mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer. PMID:22693453

  6. Delimitation and description of the immature stages of a pollinating fig wasp, Ceratosolen solmsi marchali Mayr (Hymenoptera: Agaonidae).

    PubMed

    Jia, Ling-Yi; Xiao, Jin-Hua; Niu, Li-Ming; Ma, Guang-Chang; Fu, Yue-Guan; Dunn, Derek W; Huang, Da-Wei

    2014-04-01

    The mutualism between fig trees and their wasp pollinators is a model system for many ecological and evolutionary studies. However, the immature stages of pollinating fig wasps have rarely been studied. We monitored developing fig wasps of known ages and performed a series of dissections at 24 h intervals to identify key developmental traits of Ceratosolen solmsi marchali Mayr (Hymenoptera: Agaonidae), a pollinator of Ficus hispida L. (Moraceae). We identified where in the Ficus ovary eggs were deposited and time to hatch. We were also able to identify the timing and key underlying characters of five larval instars, three sub-pupal stages, and a single prepupal stage. We provide detailed morphological descriptions for the key stages and report some behavioral observations of the wasps in the several developmental stages we recorded. Scanning electron microscope images were taken.

  7. Douglas OA-4A Dolphin

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Douglas OA-4A Dolphin: This twin-engine Douglas OA-4A Dolphin was unusual in comparison with other OA-4s in that it employed a nose wheel instead of a tail wheel during its NACA testing at Langley. Here is is seen in the NACA hangar in September 1938.

  8. Regulatory mechanisms of ethylene biosynthesis in response to various stimuli during maturation and ripening in fig fruit (Ficus carica L.).

    PubMed

    Owino, W O; Manabe, Y; Mathooko, F M; Kubo, Y; Inaba, A

    2006-01-01

    In order to obtain a greater uniformity of maturation, the growth of the fig fruit (Ficus carica L.) can be stimulated by the application of either olive oil, ethrel/ethephon or auxin. The three treatments induce ethylene production in figs. In this study, we investigated the regulatory mechanisms responsible for oil, auxin and ethylene induced ethylene production in figs. The ethylene production in response to olive oil, auxin, and propylene treatments and during ripening were all induced by 1-methylcyclopropene (1-MCP) and inhibited by propylene indicating a negative feedback regulation mechanism. Three 1-aminocyclopropane-1-carboxylic acid (ACC) synthase genes (Fc-ACS1, Fc-ACS2 and Fc-ACS3) and one ACC oxidase gene (Fc-ACO1) were isolated and their expression patterns in response to either oil, propylene or auxin treatment in figs determined. The expression patterns of Fc-ACS1 and Fc-ACO1 were clearly inhibited by 1-MCP and induced by propylene in oil treated and ripe fruits indicating positive regulation by ethylene, whereas Fc-ACS2 gene expression was induced by 1-MCP and inhibited by propylene indicating negative regulation by ethylene. The Fc-ACS3 mRNA showed high level accumulation in the auxin treated fruit. The inhibition of Fc-ACS3 gene by 1-MCP in oil treated and in ripe fruits suggests that auxin and ethylene modulate the expression of this gene by multi-responsive signal transduction pathway mechanisms. We further report that the olive oil-induced ethylene in figs involves the ACC-dependent pathway and that multiple ethylene regulatory pathways are involved during maturation and ripening in figs and each specific pathway depends on the inducer/stimulus. PMID:16889975

  9. Serial Radiohippurate Renal Scintiphotography

    PubMed Central

    Rosenthall, Leonard; Greyson, N. David; Martin, Robert H.

    1970-01-01

    The results of serial radiohippurate scintiphotography in 222 patients are analyzed. The findings in various renal diseases are discussed and compared with those obtained from the excretory urogram, BUN, serum creatinine and creatinine clearance. ImagesFIG. 1FIG. 2FIG. 3FIG. 4aFIG. 4bFIG. 5aFIG. 5b PMID:5536740

  10. Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility

    PubMed Central

    Lin, Chien-Yu; Chen, Chun-Yu; Yu, Chih-Hsiang; Yu, I-Shing; Lin, Shu-Rung; Wu, June-Tai; Lin, Ying-Hung; Kuo, Pao-Lin; Wu, Jui-Ching; Lin, Shu-Wha

    2016-01-01

    In this study, we demonstrate that an E3-ubiquitin ligase associated with human X-linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4bΔ/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities. In post-meiotic spermatids, CUL4B was dynamically expressed and mitosis of spermatogonia and meiosis of spermatocytes both appeared unaffected. However, the spermatids exhibited significantly higher levels of apoptosis during spermiogenesis, particularly during the acrosome phase through the cap phase. Comparative proteomic analyses identified a large-scale shift between wild-type and Cul4b mutant testes during early post-meiotic sperm development. Ultrastructural pathology studies further detected aberrant acrosomes in spermatids and nuclear morphology. The protein levels of both canonical and non-canonical histones were also affected in an early spermatid stage in the absence of Cul4b. Thus, X-linked CUL4B appears to play a critical role in acrosomal formation, nuclear condensation, and in regulating histone dynamics during haploid male germ cell differentiation in relation to male fertility in mice. Thus, it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis. PMID:26832838

  11. 15 CFR 744.9 - Restrictions on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... reexports of cameras controlled by ECCN 6A003.b.4.b. 744.9 Section 744.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General...

  12. 15 CFR 744.9 - Restrictions on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... reexports of cameras controlled by ECCN 6A003.b.4.b. 744.9 Section 744.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General...

  13. 15 CFR 744.9 - Restrictions on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... reexports of cameras controlled by ECCN 6A003.b.4.b. 744.9 Section 744.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General...

  14. Evolution of the local superconducting density of states in ErRh4B4 close to the ferromagnetic transition.

    PubMed

    Crespo, V; Rodrigo, J G; Suderow, H; Vieira, S; Hinks, D G; Schuller, I K

    2009-06-12

    We present local tunneling spectroscopy experiments in the superconducting and ferromagnetic phases of the reentrant superconductor ErRh4B4. The tunneling conductance curves jump from showing normal to superconducting features within a few mK close to the ferromagnetic transition temperature, with a clear hysteretic behavior. Within the ferromagnetic phase, we do not detect any superconducting correlations. Within the superconducting phase we find a peculiar V-shaped density of states at low energies, which is produced by the magnetically modulated phase that coexists with superconductivity just before ferromagnetism sets in. PMID:19658962

  15. Thermo-optical properties of 1H[3,4-b] quinoline films used in electroluminescent devices

    NASA Astrophysics Data System (ADS)

    Jaglarz, Janusz; Kępińska, Mirosława; Sanetra, Jerzy

    2014-06-01

    Electroluminescence cells with H[3,4-b] quinoline layers are promising devices for a blue light emitting EL diode. This work measured the optical reflectance as a function of temperature in copolymers PAQ layers deposited on Si crystalline substrate. Using the extended Cauchy dispersion model of the film refractive index we determined the thermo-optical coefficients for quinoline layers in the temperature range of 76-333 K from combined ellipsometric and spectrofotometric studies. The obtained values of thermo-optical coefficients of thin PAQ film, were negative and ranged in 5-10 × 10-4 [1/K].

  16. Dithieno[3,4-b:3',4'-d]thiophene-annelated antiaromatic planar cyclooctatetraene with olefinic protons.

    PubMed

    Aita, Kazunari; Ohmae, Takeshi; Takase, Masayoshi; Nomura, Kotohiro; Kimura, Hideaki; Nishinaga, Tohru

    2013-07-19

    The design and synthesis of a new planar cyclooctatetraene (COT) with protons directly connected to the COT ring was attained by monoannelation with dithieno[3,4-b:3',4'-d]thiophene. The planar structure of the COT core was unambiguously confirmed by X-ray crystallography. The magnetic antiaromaticity of the COT core was found to be higher than that of the previously synthesized planar COTs with olefinic protons, according to the results of (1)H NMR and absorption spectra as well as NICS calculations.

  17. 6-(Azaindol-2-yl)pyridine-3-sulfonamides as potent and selective inhibitors targeting hepatitis C virus NS4B.

    PubMed

    Chen, Guangming; Ren, Hongyu; Zhang, Nanjing; Lennox, William; Turpoff, Anthony; Paget, Steven; Li, Chunshi; Almstead, Neil; Njoroge, F George; Gu, Zhengxian; Graci, Jason; Jung, Stephen P; Colacino, Joseph; Lahser, Fred; Zhao, Xin; Weetall, Marla; Nomeir, Amin; Karp, Gary M

    2015-02-15

    A structure-activity relationship investigation of various 6-(azaindol-2-yl)pyridine-3-sulfonamides using the HCV replicon cell culture assay led to the identification of a potent series of 7-azaindoles that target the hepatitis C virus NS4B. Compound 2ac, identified via further optimization of the series, has excellent potency against the HCV 1b replicon with an EC50 of 2nM and a selectivity index of >5000 with respect to cellular GAPDH RNA. Compound 2ac also has excellent oral plasma exposure levels in rats, dogs and monkeys and has a favorable liver to plasma distribution profile in rats. PMID:25613678

  18. Farnesylated and methylated KRAS4b: high yield production of protein suitable for biophysical studies of prenylated protein-lipid interactions.

    PubMed

    Gillette, William K; Esposito, Dominic; Abreu Blanco, Maria; Alexander, Patrick; Bindu, Lakshman; Bittner, Cammi; Chertov, Oleg; Frank, Peter H; Grose, Carissa; Jones, Jane E; Meng, Zhaojing; Perkins, Shelley; Van, Que; Ghirlando, Rodolfo; Fivash, Matthew; Nissley, Dwight V; McCormick, Frank; Holderfield, Matthew; Stephen, Andrew G

    2015-11-02

    Prenylated proteins play key roles in several human diseases including cancer, atherosclerosis and Alzheimer's disease. KRAS4b, which is frequently mutated in pancreatic, colon and lung cancers, is processed by farnesylation, proteolytic cleavage and carboxymethylation at the C-terminus. Plasma membrane localization of KRAS4b requires this processing as does KRAS4b-dependent RAF kinase activation. Previous attempts to produce modified KRAS have relied on protein engineering approaches or in vitro farnesylation of bacterially expressed KRAS protein. The proteins produced by these methods do not accurately replicate the mature KRAS protein found in mammalian cells and the protein yield is typically low. We describe a protocol that yields 5-10 mg/L highly purified, farnesylated, and methylated KRAS4b from insect cells. Farnesylated and methylated KRAS4b is fully active in hydrolyzing GTP, binds RAF-RBD on lipid Nanodiscs and interacts with the known farnesyl-binding protein PDEδ.

  19. Intracellular membrane association of the N-terminal domain of classical swine fever virus NS4B determines viral genome replication and virulence.

    PubMed

    Tamura, Tomokazu; Ruggli, Nicolas; Nagashima, Naofumi; Okamatsu, Masatoshi; Igarashi, Manabu; Mine, Junki; Hofmann, Martin A; Liniger, Matthias; Summerfield, Artur; Kida, Hiroshi; Sakoda, Yoshihiro

    2015-09-01

    Classical swine fever virus (CSFV) causes a highly contagious disease in pigs that can range from a severe haemorrhagic fever to a nearly unapparent disease, depending on the virulence of the virus strain. Little is known about the viral molecular determinants of CSFV virulence. The nonstructural protein NS4B is essential for viral replication. However, the roles of CSFV NS4B in viral genome replication and pathogenesis have not yet been elucidated. NS4B of the GPE-  vaccine strain and of the highly virulent Eystrup strain differ by a total of seven amino acid residues, two of which are located in the predicted trans-membrane domains of NS4B and were described previously to relate to virulence, and five residues clustering in the N-terminal part. In the present study, we examined the potential role of these five amino acids in modulating genome replication and determining pathogenicity in pigs. A chimeric low virulent GPE- -derived virus carrying the complete Eystrup NS4B showed enhanced pathogenicity in pigs. The in vitro replication efficiency of the NS4B chimeric GPE-  replicon was significantly higher than that of the replicon carrying only the two Eystrup-specific amino acids in NS4B. In silico and in vitro data suggest that the N-terminal part of NS4B forms an amphipathic α-helix structure. The N-terminal NS4B with these five amino acid residues is associated with the intracellular membranes. Taken together, this is the first gain-of-function study showing that the N-terminal domain of NS4B can determine CSFV genome replication in cell culture and viral pathogenicity in pigs. PMID:26018962

  20. Evidence for the circadian gene period as a proximate mechanism of protandry in a pollinating fig wasp.

    PubMed

    Gu, Hai-Feng; Xiao, Jin-Hua; Dunn, Derek W; Niu, Li-Ming; Wang, Bo; Jia, Ling-Yi; Huang, Da-Wei

    2014-03-01

    Protandry in insects is the tendency for adult males to emerge before females and usually results from intra-sexual selection. However, the genetic basis of this common phenomenon is poorly understood. Pollinating fig wasp (Agaonidae) larvae develop in galled flowers within the enclosed inflorescences ('figs') of fig trees. Upon emergence, males locate and mate with the still galled females. After mating, males release females from their galls to enable dispersal. Females cannot exit galls or disperse from a fig without male assistance. We sampled male and female Ceratosolen solmsi (the pollinator of Ficus hispida) every 3 h over a 24 h emergence period, and then measured the expression of five circadian genes: period (per), clock (clk), cycle (cyc), pigment-dispersing factor (pdf) and clockwork orange (cwo). We found significant male-biased sexual dimorphism in the expression of all five genes. per showed the greatest divergence between the sexes and was the only gene rhythmically expressed. Expression of per correlated closely with emergence rates at specific time intervals in both male and female wasps. We suggest that this rhythmical expression of per may be a proximate mechanism of protandry in this species.

  1. Identification of Substituted Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands

    PubMed Central

    2013-01-01

    A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NFκB activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold at the carboxamide, N-3, and N-5 positions revealed differential TLR4 dependent production of NFκB and type I interferon associated cytokines, IL-6 and interferon γ-induced protein 10 (IP-10) respectively. Specifically, a subset of compounds bearing phenyl and substituted phenyl carboxamides induced lower IL-6 release while maintaining higher IP-10 production, skewing toward the type I interferon pathway. Substitution at N-5 with short alkyl substituents reduced the cytotoxicity of the leading hit compound. Computational studies supported that active compounds appeared to bind primarily to MD-2 in the TLR4/MD-2 complex. These small molecules, which stimulate innate immune cells with minimal toxicity, could potentially be used as adjuvants or immune modulators. PMID:23656327

  2. Influenza A Virus-Induced Degradation of Eukaryotic Translation Initiation Factor 4B Contributes to Viral Replication by Suppressing IFITM3 Protein Expression

    PubMed Central

    Wang, Song; Chi, Xiaojuan; Wei, Haitao; Chen, Yuhai; Chen, Zhilong; Huang, Shile

    2014-01-01

    ABSTRACT Although alteration in host cellular translation machinery occurs in virus-infected cells, the role of such alteration and the precise pathogenic processes are not well understood. Influenza A virus (IAV) infection shuts off host cell gene expression at transcriptional and translational levels. Here, we found that the protein level of eukaryotic translation initiation factor 4B (eIF4B), an integral component of the translation initiation apparatus, was dramatically reduced in A549 cells as well as in the lung, spleen, and thymus of mice infected with IAV. The decrease in eIF4B level was attributed to lysosomal degradation of eIF4B, which was induced by viral NS1 protein. Silencing eIF4B expression in A549 cells significantly promoted IAV replication, and conversely, overexpression of eIF4B markedly inhibited the viral replication. Importantly, we observed that eIF4B knockdown transgenic mice were more susceptible to IAV infection, exhibiting faster weight loss, shorter survival time, and more-severe organ damage. Furthermore, we demonstrated that eIF4B regulated the expression of interferon-induced transmembrane protein 3 (IFITM3), a critical protein involved in immune defense against a variety of RNA viruses, including influenza virus. Taken together, our findings reveal that eIF4B plays an important role in host defense against IAV infection at least by regulating the expression of IFITM3, which restricts viral entry and thereby blocks early stages of viral production. These data also indicate that influenza virus has evolved a strategy to overcome host innate immunity by downregulating eIF4B protein. IMPORTANCE Influenza A virus (IAV) infection stimulates the host innate immune system, in part, by inducing interferons (IFNs). Secreted IFNs activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, leading to elevated transcription of a large group of IFN-stimulated genes that have antiviral function. To circumvent

  3. Is the old world fig, Ficus carica L. (Moraceae), an alternate host for the Asian citrus psyllid, Diaphorina citri (Kuwayama) (Homoptera: Psyllidae)?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The only non-rutaceous plant on which D. citri has been found breeding in Texas is the edible fig, Ficus carica (Moraceae). In the summer of 2010, we discovered D. citri nymphs on a dooryard fig tree. Fig has its own species of psyllid, Homatoma ficus, but both adults and nymphs of that species ar...

  4. Evidence of quinonoid structures in the vibrational spectra of thiophene based conducting polymers: Poly(thiophene), poly(thieno[3,4-b]benzene), and poly(thieno[3,4-b]pyrazine)

    NASA Astrophysics Data System (ADS)

    Cuff, Lilee; Kertesz, Miklos

    1997-04-01

    By combining vibrational spectra and ab initio calculations, we obtained a consistent description of the IR and nonresonant Raman spectra, including intensities, of four thiophene based polymers—undoped and heavily doped poly(thiophene) (PTh), undoped poly(thieno[3,4-b]benzene) (PITN), and poly(thieno[3,4-b]pyrazine) (PThP) for the first time. Predicted spectra for poly(thiophene) agree with experiment very well. Based on the calculated force constants and Badger's rule, we also estimated the average inter-ring bond lengths of undoped and doped PTh to be 1.47 and 1.42 Å, respectively. The latter leads to an estimated 33% quinonoid character on average for heavily doped PTh. The average inter-ring bond lengths of undoped PITN and PThP, that are consistent with their vibrational spectra, are estimated to be 1.41, and 1.42 Å, respectively. These values showed that undoped PITN and PThP have quinonoid character close to that of heavily doped PTh. Further, we also estimated that, upon doping the average bond lengths of PTh changed by -0.01, 0.11, and -0.05 Å for intra-ring Cβ-Cβ, Cα-Cβ, and inter-ring bonds, respectively. These bond length changes are significantly different from those of Hartree-Fock-type calculations, reflecting significant correlation contributions and are also in conflict with earlier empirical fits of the vibrational spectrum of the highly doped phase of PTh. However, our results are more in line with the generally accepted picture of an aromatic to quinonoid "transition" of the doping process. Furthermore, the counterintuitive downward frequency shifts in the vibrational spectra of PTh upon doping can be explained by the structural change from an essentially aromatic to a partially quinonoid form.

  5. PDE4B mediates local feedback regulation of β₁-adrenergic cAMP signaling in a sarcolemmal compartment of cardiac myocytes.

    PubMed

    Mika, Delphine; Richter, Wito; Westenbroek, Ruth E; Catterall, William A; Conti, Marco

    2014-03-01

    Multiple cAMP phosphodiesterase (PDE) isoforms play divergent roles in cardiac homeostasis but the molecular basis for their non-redundant function remains poorly understood. Here, we report a novel role for the PDE4B isoform in β-adrenergic (βAR) signaling in the heart. Genetic ablation of PDE4B disrupted βAR-induced cAMP transients, as measured by FRET sensors, at the sarcolemma but not in the bulk cytosol of cardiomyocytes. This effect was further restricted to a subsarcolemmal compartment because PDE4B regulates β1AR-, but not β2AR- or PGE2-induced responses. The spatially restricted function of PDE4B was confirmed by its selective effects on PKA-mediated phosphorylation patterns. PDE4B limited the PKA-mediated phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca(2+) channels and ryanodine receptors, but not phosphorylation of distal cytosolic proteins. β1AR- but not β2AR-ligation induced PKA-dependent activation of PDE4B and interruption of this negative feedback with PKA inhibitors increased sarcolemmal cAMP. Thus, PDE4B mediates a crucial PKA-dependent feedback that controls β1AR-dependent cAMP signals in a restricted subsarcolemmal domain. Disruption of this feedback augments local cAMP/PKA signals, leading to an increased intracellular Ca(2+) level and contraction rate.

  6. Rab4b controls an early endosome sorting event by interacting with the γ-subunit of the clathrin adaptor complex 1.

    PubMed

    Perrin, Laura; Laura, Perrin; Lacas-Gervais, Sandra; Sandra, Lacas-Gervais; Gilleron, Jérôme; Jérôme, Gilleron; Ceppo, Franck; Franck, Ceppo; Prodon, François; François, Prodon; Benmerah, Alexandre; Alexandre, Benmerah; Tanti, Jean-François; Jean-François, Tanti; Cormont, Mireille; Mireille, Cormont

    2013-11-01

    The endocytic pathway is essential for cell homeostasis and numerous small Rab GTPases are involved in its control. The endocytic trafficking step controlled by Rab4b has not been elucidated, although recent data suggested it could be important for glucose homeostasis, synaptic homeostasis or adaptive immunity. Here, we show that Rab4b is required for early endosome sorting of transferrin receptors (TfRs) to the recycling endosomes, and we identified the AP1γ subunit of the clathrin adaptor AP-1 as a Rab4b effector and key component of the machinery of early endosome sorting. We show that internalised transferrin (Tf) does not reach Vamp3/Rab11 recycling endosomes in the absence of Rab4b, whereas it is rapidly recycled back to the plasma membrane. By contrast, overexpression of Rab4b leads to the accumulation of internalised Tf within AP-1- and clathrin-coated vesicles. These vesicles are poor in early and recycling endocytic markers except for TfR and require AP1γ for their formation. Furthermore, the targeted overexpression of the Rab4b-binding domain of AP1γ to early endosome upon its fusion with FYVE domains inhibited the interaction between Rab4b and endogenous AP1γ, and perturbed Tf traffic. We thus proposed that the interaction between early endocytic Rab4b and AP1γ could allow the budding of clathrin-coated vesicles for subsequent traffic to recycling endosomes. The data also uncover a novel type of endosomes, characterised by low abundance of either early or recycling endocytic markers, which could potentially be generated in cell types that naturally express high level of Rab4b.

  7. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein.

    PubMed

    Buffalo, Cosmo Z; Bahn-Suh, Adrian J; Hirakis, Sophia P; Biswas, Tapan; Amaro, Rommie E; Nizet, Victor; Ghosh, Partho

    2016-01-01

    No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently ∼90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant 'reading head' in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M-C4BP interaction, and also inform a path towards vaccine design. PMID:27595425

  8. Magnetic properties and glass formability of Fe61Co10Zr5W4B20 bulk metallic glassy alloy

    NASA Astrophysics Data System (ADS)

    Pawlik, P.; Davies, H. A.; Gibbs, M. R. J.

    2003-10-01

    Amorphous melt spun ribbon samples of Fe61Co10Zr5W4B20 alloy of various thicknesses up to ˜350 μm and suction cast 1 mm diameter rod and 2, 3, and 4 mm outside diameter tube samples of the same alloy were produced. The experimental results for the rod samples indicate a relatively high saturation polarization μ0Ms=0.8 T and a Curie temperature TC=615 K, as well as a very low coercive field Hc=1.4±0.5 A/m with high anisotropy that lowers the permeability of the samples. Thermal analysis by differential scanning calorimetry carried out on ribbon and rod samples revealed a large supercooled liquid region ΔTx of ˜60 K for this alloy.

  9. Spectral properties of 1H-pyrazolo[3,4-b]quinoline substituted with N,N-diethylamine moiety

    NASA Astrophysics Data System (ADS)

    Kolbus, Anna; Grabka, Danuta; Danel, Andrzej; Szary, Karol

    2016-07-01

    Photophysical properties of 6-N,N-diethyl-3-methyl-1-phenyl-1H-pyrazol[3,4-b]quinoline (DEPQ), a potential material for electroluminescent applications, were investigated. The absorption and fluorescence spectra and fluorescence lifetimes were recorded in a great number of solvents with different polarity. The red shifts in absorption and fluorescence maxima with the solvent's polarity were observed. Different trends in values of quantum yield for non-polar and polar solvents suggest two different deactivation ways of the excited state, depending on solvent polarity. DEPQ in non-polar solvents emits from locally excited states while deactivation DEPQ in polar solvents indicates charge transfer (CT) fluorescence. Several electro-optical parameters were also calculated.

  10. Anillin-dependent organization of septin filaments promotes intercellular bridge elongation and Chmp4B targeting to the abscission site.

    PubMed

    Renshaw, Matthew J; Liu, Jinghe; Lavoie, Brigitte D; Wilde, Andrew

    2014-01-01

    The final step of cytokinesis is abscission when the intercellular bridge (ICB) linking the two new daughter cells is broken. Correct construction of the ICB is crucial for the assembly of factors involved in abscission, a failure in which results in aneuploidy. Using live imaging and subdiffraction microscopy, we identify new anillin-septin cytoskeleton-dependent stages in ICB formation and maturation. We show that after the formation of an initial ICB, septin filaments drive ICB elongation during which tubules containing anillin-septin rings are extruded from the ICB. Septins then generate sites of further constriction within the mature ICB from which they are subsequently removed. The action of the anillin-septin complex during ICB maturation also primes the ICB for the future assembly of the ESCRT III component Chmp4B at the abscission site. These studies suggest that the sequential action of distinct contractile machineries coordinates the formation of the abscission site and the successful completion of cytokinesis.

  11. Discovery of Spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as Potent NOP and Opioid Receptor Agonists.

    PubMed

    Schunk, Stefan; Linz, Klaus; Frormann, Sven; Hinze, Claudia; Oberbörsch, Stefan; Sundermann, Bernd; Zemolka, Saskia; Englberger, Werner; Germann, Tieno; Christoph, Thomas; Kögel, Babette-Y; Schröder, Wolfgang; Harlfinger, Stephanie; Saunders, Derek; Kless, Achim; Schick, Hans; Sonnenschein, Helmut

    2014-08-14

    We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors. PMID:25147602

  12. Photocatalytic degradation of Chicago Sky Blue 6B and Benzopurpurin 4B using titanium dioxide thin film.

    PubMed

    Mohammed, Abdul K; McKenzie, Katrina T

    2005-01-01

    Aqueous solutions of azo dyes undergo degradation to form harmless intermediates and colorless products following irradiation by visible light in the presence of titanium dioxide thin films. The dyes that were studied in this work are: Chicago Sky Blue 6B and Benzopurpurin 4B. Results obtained indicated that complete mineralization of the dyes took place under the experimental conditions. There was an increase in conductivity after the complete mineralization experiments possibly indicating the formation of ions such as NO3- and SO4(2-). Chemical oxygen demand (COD) measurements show a decrease in organic matter for both dyes following complete degradation. The effect of how changing experimental conditions such as pH, temperature and starting concentrations of dyes affected the rate of dye degradation was measured. There was an increase in the rate of disappearance of the dye color at lower pH. High concentrations of dye solutions required long degradation time.

  13. Burns or phytophotodermatitis, abuse or neglect: confusing aspects of skin lesions caused by the superstitious use of fig leaves.

    PubMed

    Abali, Ayse Ebru Sakallioglu; Aka, Mehmet; Aydogan, Cem; Haberal, Mehmet

    2012-01-01

    As a superstition, homemade decoctions are believed to be beneficial for several diseases. This kind of medical therapy, however, can lead to serious adverse effects. In this report, we present three cases from a single family. Each of the family members developed phytophotodermatitis after the application of a fig leaf decoction. The most severe effect was in the case of a 13-year-old boy who had been bathed with the fig leaf decoction; the two other cases were the parents who prepared and applied the medicine to their child's skin to heal the boy's congenital mental-motor retardation. Silver sulfadiazine was used for wound care. The mother was discharged 6 days after admission, the father, after 8 days, and the boy, after 14 days. Burnlike wounds in all three cases healed completely.

  14. Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target.

    PubMed

    Saborowski, Anna; Saborowski, Michael; Davare, Monika A; Druker, Brian J; Klimstra, David S; Lowe, Scott W

    2013-11-26

    Cholangiocarcinoma is the second most common primary liver cancer and responds poorly to existing therapies. Intrahepatic cholangiocarcinoma (ICC) likely originates from the biliary tree and develops within the hepatic parenchyma. We have generated a flexible orthotopic allograft mouse model of ICC that incorporates common genetic alterations identified in human ICC and histologically resembles the human disease. We examined the utility of this model to validate driver alterations in ICC and tested their suitability as therapeutic targets. Specifically, we showed that the fused-in-glioblastoma-c-ros-oncogene1 (FIG-ROS1(S); FIG-ROS) fusion gene dramatically accelerates ICC development and that its inactivation in established tumors has a potent antitumor effect. Our studies establish a versatile model of ICC that will be a useful preclinical tool and validate ROS1 fusions as potent oncoproteins and therapeutic targets in ICC and potentially other tumor types.

  15. Poly(thieno[3,4-b]thiophene)-poly(styrene sulfonate): a low band gap, water dispersible conjugated polymer.

    PubMed

    Lee, Byoungchul; Seshadri, Venkataramanan; Sotzing, Gregory A

    2005-11-01

    Herein we report the oxidative chemical polymerization of thieno[3,4-b]thiophene (T34bT) using several different oxidants including ferric sulfate, ammonium persulfate, and hydrogen peroxide in the presence of poly(styrenesulfonic acid) in water and properties of the resulting poly(thieno[3,4-b]thiophene)-poly(styrenesulfonic acid) (PT34bT-PSS) dispersion. The PT34bT-PSS is rendered a colloidal dispersion in water with a particle size diameter ranging between 180 and 220 nm depending on the oxidant used for polymerization. PT34bT-PSS films have band gaps of ca. 1 eV (1260 nm) as determined by the onset of the pi to pi transition from the vis-NIR spectrum with absorption maxima ranging from 1.4 eV (912 nm) to 1.7 eV (724 nm). The neutral and oxidized forms of PT34bT-PSS prepared from ferric sulfate dispersed in water were blue and lime green, respectively, whereas the neutral and oxidized forms of PT34bT-PSS prepared from ammonium persulfate and hydrogen peroxide were blue and blue-green, respectively. Spectral properties of the PT34bT-PSS dispersion can be tuned by the combination of oxidants. PT34bT-PSS films showed ca. 100% cation dominant ion transport behavior as determined by electrochemical gravimetry with each charge-discharge cycle and the doping level of the polymer was calculated to be 26%. Electrical conductivities for these polymers were found to be dependent on chemical oxidants used and varied from 10(-2) to 10(-4) S/cm. PMID:16262354

  16. Donor Splice-Site Mutation in CUL4B is Likely Cause of X-Linked Intellectual Disability

    PubMed Central

    Londin, Eric R.; Adijanto, Jeffrey; Philp, Nancy; Novelli, Antonio; Vitale, Emilia; Perria, Chiara; Serra, Gigliola; Alesi, Viola; Surrey, Saul; Fortina, Paolo

    2015-01-01

    X-linked intellectual disability is the most common form of cognitive disability in males. Syndromic intellectual disability encompasses cognitive deficits with other medical and behavioral manifestations. Recently, a large family with a novel form of syndromic X-linked intellectual disability was characterized. Eight of 24 members of the family are male and had cognitive dysfunction, short stature, aphasia, skeletal abnormalities, and minor anomalies. To identify the causative gene(s), we performed exome sequencing in three affected boys, both parents, and an unaffected sister. We identified a haplotype consisting of eight variants located in cis within the linkage region that segregated with affected members in the family. Of these variants, two were novel. The first was at the splice-donor site of intron 7 (c.974+1G>T) in the cullin-RING ubiquitin ligase (E3) gene, CUL4B. This variant is predicted to result in failure to splice and remove intron 7 from the primary transcript. The second variant mapped to the 3′-UTR region of the KAISO gene (c.1127T>G). Sanger sequencing validated the variants in these relatives as well as in three affected males and five carriers. The KAISO gene variant was predicted to create a binding site for the microRNAs miR-4999 and miR-4774; however, luciferase expression assays failed to validate increased targeting of these miRNAs to the variant 3′-UTR. This SNP may affect 3′-UTR structure leading to decreased mRNA stability. Our results suggest that the intellectual disability phenotype in this family is caused by aberrant splicing and removal of intron 7 from CUL4B gene primary transcript. PMID:24898194

  17. Two newly introduced tropical bark and ambrosia beetles (Coleoptera: Curculionidae, Scolytinae) damaging figs (Ficus carica) in southern Italy.

    PubMed

    Faccoli, Massimo; Campo, Giuseppe; Perrotta, Giancarlo; Rassati, Davide

    2016-01-01

    In summer 2014, the bark beetle Hypocryphalus scabricollis (Eichhoff) and the ambrosia beetle Xyleborus bispinatus Eichhoff, species new to Italy and Europe, respectively, were found for the first time in south-eastern Sicily (Italy). Large infestations of the two species were recorded in many plantations of common fig (Ficus carica L.) both in 2014 and 2015. Data concerning insect characteristics, taxonomy, and distribution are briefly reported. PMID:27470760

  18. One step ahead: a parasitoid disperses farther and forms a wider geographic population than its fig wasp host.

    PubMed

    Sutton, Timothy L; Riegler, Markus; Cook, James M

    2016-02-01

    The structure of populations across landscapes influences the dynamics of their interactions with other species. Understanding the geographic structure of populations can thus shed light on the potential for interacting species to co-evolve. Host-parasitoid interactions are widespread in nature and also represent a significant force in the evolution of plant-insect interactions. However, there have been few comparisons of population structure between an insect host and its parasitoid. We used microsatellite markers to analyse the population genetic structure of Pleistodontes imperialis sp. 1, a fig-pollinating wasp of Port Jackson fig (Ficus rubiginosa), and its main parasitoid, Sycoscapter sp. A, in eastern Australia. Besides exploring this host-parasitoid system, our study also constitutes, to our knowledge, the first study of population structure in a nonpollinating fig wasp species. We collected matched samples of pollinators and parasitoids at several sites in two regions separated by up to 2000 km. We found that pollinators occupying the two regions represent distinct populations, but, in contrast, parasitoids formed a single population across the wide geographic range sampled. We observed genetic isolation by distance for each species, but found consistently lower FST and RST values between sites for parasitoids compared with pollinators. Previous studies have indicated that pollinators of monoecious figs can disperse over very long distances, and we provide the first genetic evidence that their parasitoids may disperse as far, if not farther. The contrasting geographic population structures of host and parasitoid highlight the potential for geographic mosaics in this important symbiotic system.

  19. Limited collaborative study of an optional method for the isolation of light filth from fig and fruit paste.

    PubMed

    Kvenberg, J E; Eisenberg, W V; King, A C

    1975-05-01

    The present official first action method for the isolation of light filth from fig and fruit paste, 44.083(a), occasionally yields excessive plant debris on filter papers, which causes difficulty in effectively counting insect filth. The proposed method provides the option of an additional flotation of trapped off material in a Corning percolator. This revision has been adopted as official first action as an alternative to 44.083(a). PMID:1141170

  20. Propagation of Some Local Fig (Ficus carica L.) Cultivars by Hardwood Cuttings under the Field Conditions in Tunisia.

    PubMed

    Aljane, Fateh; Nahdi, Sabrine

    2014-01-01

    This research was carried out in Southeast of Tunisia in 2009 and 2010, in order to study the propagation of six (Ficus carica L.) cultivars by using hardwood cuttings under the field conditions. The effect of the cultivars and the type of buds, shoots age, shoots length, and shoots diameter were recorded. Ten cuttings per cultivar and/or cutting types with three replications were planted in rooting unit. Percentage of root emergence and six morphological parameters of young fig plants were measured. Results showed that the responses of cuttings as fig nursery plants presented a high variability among the five cultivars. The most widely varied characters were % root emergence (RE) and cumulative growth of young plant (CG). The first one ranged from 10% to 90%, the second varied within 32 and 112 cm. Concerning the ''BITHER" cultivar, 6 cutting types with different age, length, and diameter were evaluated. Results showed a great variation in % of root emergence (0-90%), length of nursery plant (3-77 cm), and number of roots/nursery plant (0-29 roots). The present research showed that the hardwood cutting of local fig cultivars can be propagated under field conditions in Southeast of Tunisia.

  1. Alternative promoters of gene MAGE4a

    SciTech Connect

    De Plaen, E.; Naerhuyzen, B.; De Smet, C.

    1997-03-01

    Gene MAGE-4 (HGMW-approved symbol MAGE4) is expressed in several types of tumors, but not in normal tissues, except testis and placenta. The 5{prime} end of this gene contains eight homologous exons spread over a 5.8-kb region. These exons are alternatively spliced to a unique second exon and a unique third exon, which encodes a protein of 317 amino acids. The analysis of transcripts found in testis, placenta, and a sarcoma cell line showed that each of the alternative first exons is used in at least one of these tissues. Various regions of the promoter of the fifth alternative exon (1.5) were cloned in a luciferase reporter plasmid, and the constructs were transfected in a sarcoma cell line that expresses MAGE-4. Two Ets motifs located between positions -70 and -29 relative to the transcription start site were found to drive 55% of the promoter activity. A region containing an Sp1 consensus binding site located upstream of the two Ets motifs was found to be responsible for 44% of the transcriptional activity. MAGE-4a promoters 1.4 and 1.6, which also contain the Sp1 and the two Ets binding motifs, supported a level of transcription comparable to that of promoter 1.5, whereas promoter 1.1, which contains only one Ets binding site, was sixfold less active. In line with observations made with gene MAGE-1 (HGMW-approved symbol MAGE1), we found that promoter 1.5 stimulated a high level of transcription in a melanoma cell line that does not express MAGE-4. This suggests that the tumor-specific expression of MAGE genes is not determined by the presence of specific transcription factors. 26 refs., 7 figs., 2 tabs.

  2. Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome.

    PubMed

    Chong, Chan Eng; Lim, Kue Peng; Gan, Chai Phei; Marsh, Christina A; Zain, Rosnah Binti; Abraham, Mannil Thomas; Prime, Stephen S; Teo, Soo-Hwang; Silvio Gutkind, J; Patel, Vyomesh; Cheong, Sok Ching

    2012-08-01

    MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC. PMID:22459352

  3. Stringent Regulation of Complement Lectin Pathway C3/C5 Convertase By C4b-Binding Protein (C4bp)

    PubMed Central

    Rawal, Nenoo; Rajagopalan, Rema; Salvi, Veena P.

    2009-01-01

    The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (EMan) was examined. While the C4BP concentration for inhibiting 50% (IC50) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.05 nM), ∼3- and 41-fold more was required to inhibit assembly of the C5 convertase on zymosan (2.81 nM) and EMan (42.66 nM). No difference in binding interactions between C4BP and surface-bound C4b alone or in complex with C3b was observed. Increasing the C4b density on zymosan (14,000-431,000 C4b/Zym) increased the number of C4b bound per C4BP from 2.87 to 8.23 indicating that at high C4b density all seven α-chains of C4BP are engaged in C4b-binding. In contrast, the number of C4b bound per C4BP remained constant (3.79 ± 0.60) when the C4b density on EMan was increased. The data also show that C4BP regulates assembly and decay of the lectin pathway C3/C5 convertase more stringently than the classical pathway C3/C5 convertase because of a ∼7 to 13-fold greater affinity for C4b deposited via the lectin pathway than the classical pathway. C4BP thus regulates efficiently the four times greater potential of the lectin pathway than the classical pathway in generating the C3/C5 convertase and hence production of pro-inflammatory products, which are required to fight infections but occasionally cause pathological inflammatory reactions. PMID:19660812

  4. Cullin 4B is recruited to tristetraprolin-containing messenger ribonucleoproteins and regulates TNF-α mRNA polysome loading.

    PubMed

    Pfeiffer, Jason R; Brooks, Seth A

    2012-02-15

    TNF-α is a central mediator of inflammation and critical for host response to infection and injury. TNF-α biosynthesis is controlled by transcriptional and posttranscriptional mechanisms allowing for rapid, transient production. Tristetraprolin (TTP) is an AU-rich element binding protein that regulates the stability of the TNF-α mRNA. Using a screen to identify TTP-interacting proteins, we identified Cullin 4B (Cul4B), a scaffolding component of the Cullin ring finger ligase family of ubiquitin E3 ligases. Short hairpin RNA knockdown of Cul4B results in a significant reduction in TNF-α protein and mRNA in LPS-stimulated mouse macrophage RAW264.7 cells as well as a reduction in TTP protein. TNF-α message t(1/2) was reduced from 69 to 33 min in LPS-stimulated cells. TNF-3' untranslated region luciferase assays utilizing wild-type and mutant TTP-AA (S52A, S178A) indicate that TTP function is enhanced in Cul4B short hairpin RNA cells. Importantly, the fold induction of TNF-α mRNA polysome loading in response to LPS stimulation is reduced by Cul4B knockdown. Cul4B is present on the polysomes and colocalizes with TTP to exosomes and processing bodies, which are sites of mRNA decay. We conclude that Cul4B licenses the TTP-containing TNF-α messenger ribonucleoprotein for loading onto polysomes, and reduction of Cul4B expression shunts the messenger ribonucleoproteins into the degradative pathway.

  5. Interferon-dependent engagement of eukaryotic initiation factor 4B via S6 kinase (S6K)- and ribosomal protein S6K-mediated signals.

    PubMed

    Kroczynska, Barbara; Kaur, Surinder; Katsoulidis, Efstratios; Majchrzak-Kita, Beata; Sassano, Antonella; Kozma, Sara C; Fish, Eleanor N; Platanias, Leonidas C

    2009-05-01

    Although the roles of Jak-Stat pathways in type I and II interferon (IFN)-dependent transcriptional regulation are well established, the precise mechanisms of mRNA translation for IFN-sensitive genes remain to be defined. We examined the effects of IFNs on the phosphorylation/activation of eukaryotic translation initiation factor 4B (eIF4B). Our data show that eIF4B is phosphorylated on Ser422 during treatment of sensitive cells with alpha IFN (IFN-alpha) or IFN-gamma. Such phosphorylation is regulated, in a cell type-specific manner, by either the p70 S6 kinase (S6K) or the p90 ribosomal protein S6K (RSK) and results in enhanced interaction of the protein with eIF3A (p170/eIF3A) and increased associated ATPase activity. Our data also demonstrate that IFN-inducible eIF4B activity and IFN-stimulated gene 15 protein (ISG15) or IFN-gamma-inducible chemokine CXCL-10 protein expression are diminished in S6k1/S6k2 double-knockout mouse embryonic fibroblasts. In addition, IFN-alpha-inducible ISG15 protein expression is blocked by eIF4B or eIF3A knockdown, establishing a requirement for these proteins in mRNA translation/protein expression by IFNs. Importantly, the generation of IFN-dependent growth inhibitory effects on primitive leukemic progenitors is dependent on activation of the S6K/eIF4B or RSK/eIF4B pathway. Taken together, our findings establish critical roles for S6K and RSK in the induction of IFN-dependent biological effects and define a key regulatory role for eIF4B as a common mediator and integrator of IFN-generated signals from these kinases. PMID:19289497

  6. CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility.

    PubMed

    Aravindan, Rolands G; Fomin, Victor P; Naik, Ulhas P; Modelski, Mark J; Naik, Meghna U; Galileo, Deni S; Duncan, Randall L; Martin-Deleon, Patricia A

    2012-08-01

    Deletion of the highly conserved gene for the major Ca(2+) efflux pump, Plasma membrane calcium/calmodulin-dependent ATPase 4b (Pmca4b), in the mouse leads to loss of progressive and hyperactivated sperm motility and infertility. Here we first demonstrate that compared to wild-type (WT), Junctional adhesion molecule-A (Jam-A) null sperm, previously shown to have motility defects and an abnormal mitochondrial phenotype reminiscent of that seen in Pmca4b nulls, exhibit reduced (P < 0.001) ATP levels, significantly (P < 0.001) greater cytosolic Ca(2+) concentration ([Ca(2+) ](c)) and ∼10-fold higher mitochondrial sequestration, indicating Ca(2+) overload. Investigating the mechanism involved, we used co-immunoprecipitation studies to show that CASK (Ca(2+) /calmodulin-dependent serine kinase), identified for the first time on the sperm flagellum where it co-localizes with both PMCA4b and JAM-A on the proximal principal piece, acts as a common interacting partner of both. Importantly, CASK binds alternatively and non-synergistically with each of these molecules via its single PDZ (PDS-95/Dlg/ZO-1) domain to either inhibit or promote efflux. In the absence of CASK-JAM-A interaction in Jam-A null sperm, CASK-PMCA4b interaction is increased, resulting in inhibition of PMCA4b's enzymatic activity, consequent Ca(2+) accumulation, and a ∼6-fold over-expression of constitutively ATP-utilizing CASK, compared to WT. Thus, CASK negatively regulates PMCA4b by directly binding to it and JAM-A positively regulates it indirectly through CASK. The decreased motility is likely due to the collateral net deficit in ATP observed in nulls. Our data indicate that Ca(2+) homeostasis in sperm is maintained by the relative ratios of CASK-PMCA4b and CASK-JAM-A interactions.

  7. Enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome P450 4B1: applications for prodrug-activating gene therapy.

    PubMed

    Steffens, S; Frank, S; Fischer, U; Heuser, C; Meyer, K L; Dobberstein, K U; Rainov, N G; Kramm, C M

    2000-05-01

    To monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (EGFP) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (HSV-tk) and rabbit cytochrome P450 4B1 (cyp4b1). Expression of the resulting fusion proteins, TK-EGFP and 4B1-EGFP, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol. Ganciclovir and 4-ipomeanol sensitivity was comparable with that achieved with the native HSV-TK and CYP4B1 proteins. As shown by fluorescence microscopy, TK-EGFP was expressed predominantly intranuclearly, whereas 4B1-EGFP was detectable in the cytoplasm, thereby displaying the orthotopic subcellular distribution of the corresponding native enzymes. The fluorescence intensity correlated well with the corresponding prodrug sensitivity, as shown by fluorescence-activated cell sorter analysis. EGFP expression was also used for the selection of stably HSV-tk-transduced cells by flow cytometric cell sorting. Resulting cell populations showed a homogeneity of fluorescence intensity similar to single-cell clones after antibiotic selection. In conclusion, tk-egfp and 4b1-egfp fusion genes are valuable tools for monitoring prodrug-activating gene therapy in living cells. EGFP fusion genes/proteins provide a simple and reproducible means for the detection, selection, and characterization of cells expressing enzyme genes for prodrug activation.

  8. LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation

    PubMed Central

    Tan, Xiaojun; Sun, Yue; Thapa, Narendra; Liao, Yihan; Hedman, Andrew C; Anderson, Richard A

    2015-01-01

    Lysosomal degradation is essential for the termination of EGF-stimulated EGF receptor (EGFR) signaling. This requires EGFR sorting to the intraluminal vesicles (ILVs) of multi-vesicular endosomes (MVEs). Cytosolic proteins including the ESCRT machineries are key regulators of EGFR intraluminal sorting, but roles for endosomal transmembrane proteins in receptor sorting are poorly defined. Here, we show that LAPTM4B, an endosomal transmembrane oncoprotein, inhibits EGF-induced EGFR intraluminal sorting and lysosomal degradation, leading to enhanced and prolonged EGFR signaling. LAPTM4B blocks EGFR sorting by promoting ubiquitination of Hrs (an ESCRT-0 subunit), which inhibits the Hrs association with ubiquitinated EGFR. This is counteracted by the endosomal PIP kinase, PIPKIγi5, which directly binds LAPTM4B and neutralizes the inhibitory function of LAPTM4B in EGFR sorting by generating PtdIns(4,5)P2 and recruiting SNX5. PtdIns(4,5)P2 and SNX5 function together to protect Hrs from ubiquitination, thereby promoting EGFR intraluminal sorting. These results reveal an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2 signaling, and the ESCRT complex and define a mechanism by which the oncoprotein LAPTM4B can transform cells and promote tumor progression. PMID:25588945

  9. Molecular Basis for the Association of Human E4B U Box Ubiquitin Ligase with E2-Conjugating Enzymes UbcH5c and Ubc4

    SciTech Connect

    Benirschke, Robert C.; Thompson, James R.; Nominé, Yves; Wasielewski, Emeric; Juranić, Nenad; Macura, Slobodan; Hatakeyama, Shigetsugu; Nakayama, Keiichi I.; Botuyan, Maria Victoria; Mer, Georges

    2010-09-07

    Human E4B, also called UFD2a, is a U box-containing protein that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor. E4B is thought to participate in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. The U box domain is an anchor site for E2 ubiquitin-conjugating enzymes, but little is known of the binding mechanism. Using X-ray crystallography and NMR spectroscopy, we determined the structures of E4B U box free and bound to UbcH5c and Ubc4 E2s. Whereas previously characterized U box domains are homodimeric, we show that E4B U box is a monomer stabilized by a network of hydrogen bonds identified from scalar coupling measurements. These structural studies, complemented by calorimetry- and NMR-based binding assays, suggest an allosteric regulation of UbcH5c and Ubc4 by E4B U box and provide a molecular basis to understand how the ubiquitylation machinery involving E4B assembles.

  10. Knockdown of the Drosophila FIG4 induces deficient locomotive behavior, shortening of motor neuron, axonal targeting aberration, reduction of life span and defects in eye development.

    PubMed

    Kyotani, Akane; Azuma, Yumiko; Yamamoto, Itaru; Yoshida, Hideki; Mizuta, Ikuko; Mizuno, Toshiki; Nakagawa, Masanori; Tokuda, Takahiko; Yamaguchi, Masamitsu

    2016-03-01

    Mutations in Factor-Induced-Gene 4 (FIG4) gene have been identified in Charcot-Marie-Tooth disease type 4J (CMT4J), Yunis-Varon syndrome and epilepsy with polymicrogyria. FIG4 protein regulates a cellular abundance of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a signaling lipid on the cytosolic surface of membranes of the late endosomal compartment. PI(3,5)P2 is required for retrograde membrane trafficking from lysosomal and late endosomal compartments to the Golgi. However, it is still unknown how the neurodegeneration that occurs in these diseases is related to the loss of FIG4 function. Drosophila has CG17840 (dFIG4) as a human FIG4 homolog. Here we specifically knocked down dFIG4 in various tissues, and investigated their phenotypes. Neuron-specific knockdown of dFIG4 resulted in axonal targeting aberrations of photoreceptor neurons, shortened presynaptic terminals of motor neurons in 3rd instar larvae and reduced climbing ability in adulthood and life span. Fat body-specific knockdown of dFIG4 resulted in enlarged lysosomes in cells that were detected by staining with LysoTracker. In addition, eye imaginal disk-specific knockdown of dFIG4 disrupted differentiation of pupal ommatidial cell types, such as cone cells and pigment cells, suggesting an additional role of dFIG4 during eye development.

  11. Knockdown of the Drosophila FIG4 induces deficient locomotive behavior, shortening of motor neuron, axonal targeting aberration, reduction of life span and defects in eye development.

    PubMed

    Kyotani, Akane; Azuma, Yumiko; Yamamoto, Itaru; Yoshida, Hideki; Mizuta, Ikuko; Mizuno, Toshiki; Nakagawa, Masanori; Tokuda, Takahiko; Yamaguchi, Masamitsu

    2016-03-01

    Mutations in Factor-Induced-Gene 4 (FIG4) gene have been identified in Charcot-Marie-Tooth disease type 4J (CMT4J), Yunis-Varon syndrome and epilepsy with polymicrogyria. FIG4 protein regulates a cellular abundance of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a signaling lipid on the cytosolic surface of membranes of the late endosomal compartment. PI(3,5)P2 is required for retrograde membrane trafficking from lysosomal and late endosomal compartments to the Golgi. However, it is still unknown how the neurodegeneration that occurs in these diseases is related to the loss of FIG4 function. Drosophila has CG17840 (dFIG4) as a human FIG4 homolog. Here we specifically knocked down dFIG4 in various tissues, and investigated their phenotypes. Neuron-specific knockdown of dFIG4 resulted in axonal targeting aberrations of photoreceptor neurons, shortened presynaptic terminals of motor neurons in 3rd instar larvae and reduced climbing ability in adulthood and life span. Fat body-specific knockdown of dFIG4 resulted in enlarged lysosomes in cells that were detected by staining with LysoTracker. In addition, eye imaginal disk-specific knockdown of dFIG4 disrupted differentiation of pupal ommatidial cell types, such as cone cells and pigment cells, suggesting an additional role of dFIG4 during eye development. PMID:26708557

  12. The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice

    SciTech Connect

    Plowman, Sarah J.; Arends, Mark J.; Brownstein, David G.; Luo Feijun; Devenney, Paul S.; Rose, Lorraine; Ritchie, Ann-Marie; Berry, Rachel L.; Harrison, David J.; Hooper, Martin L.; Patek, Charles E. . E-mail: Charles.Patek@ed.ac.uk

    2006-01-01

    Ras proteins function as molecular switches in signal transduction pathways, and, here, we examined the effects of the K-ras4A and 4B splice variants on cell function by comparing wild-type embryonic stem (ES) cells with K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} (exon 4A knock-out) ES cells which express K-ras4B only and K-ras {sup -/-} (exons 1-3 knock-out) ES cells which express neither splice variant, and intestinal epithelium from wild-type and K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} mice. RT-qPCR analysis found that K-ras4B expression was reduced in K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells but unaffected in small intestine. K-Ras deficiency did not affect ES cell growth, and K-Ras4A deficiency did not affect intestinal epithelial proliferation. K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} and K-ras {sup -/-} ES cells showed a reduced capacity for differentiation following LIF withdrawal, and K-ras {sup -/-} cells were least differentiated. K-Ras4A deficiency inhibited etoposide-induced apoptosis in ES cells and intestinal epithelial cells. However, K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells were more resistant to etoposide-induced apoptosis than K-ras {sup -/-} cells. The results indicate that (1) K-Ras4A promotes apoptosis while K-Ras4B inhibits it, and (2) K-Ras4B, and possibly K-Ras4A, promotes differentiation. The findings raise the possibility that alteration of the K-Ras4A/4B isoform ratio modulates tumorigenesis by differentially affecting stem cell survival and/or differentiation. However, K-Ras4A deficiency did not affect life expectancy or spontaneous overall tumor incidence in aging mice.

  13. C/EBPβ-LAP*/LAP Expression Is Mediated by RSK/eIF4B-Dependent Signalling and Boosted by Increased Protein Stability in Models of Monocytic Differentiation

    PubMed Central

    Christmann, Martin; Friesenhagen, Judith; Westphal, Andreas; Pietsch, Daniel; Brand, Korbinian

    2015-01-01

    The transcription factor C/EBPβ plays a key role in monocytic differentiation and inflammation. Its small isoform LIP is associated with proliferation at early premonocytic developmental stages and regulated via mTOR-dependent signalling. During later stages of (pre)monocytic differentiation there is a considerable increase in the large C/EBPβ isoforms LAP*/LAP which inhibit proliferation thus supporting terminal differentiation. Here, we showed in different models of monocytic differentiation that this dramatic increase in the LAP*/LAP protein and LAP/LIP ratio was accompanied by an only modest/retarded mRNA increase suggesting an important role for (post)translational mechanisms. We found that LAP*/LAP formation was induced via MEK/RSK-dependent cascades, whereas mTOR/S6K1 were not involved. Remarkably, LAP*/LAP expression was dependent on phosphorylated eIF4B, an acceleratory protein of RNA helicase eIF4A. PKR inhibition reduced the expression of eIF4B and C/EBPβ in an eIF2α-independent manner. Furthermore, under our conditions a marked stabilisation of LAP*/LAP protein occurred, accompanied by reduced chymotrypsin-like proteasome/calpain activities and increased calpastatin levels. Our study elucidates new signalling pathways inducing LAP*/LAP expression and indicates new alternative PKR functions in monocytes. The switch from mTOR- to RSK-mediated signalling to orchestrate eIF4B-dependent LAP*/LAP translation, accompanied by increased protein stability but only small mRNA changes, may be a prototypical example for the regulation of protein expression during selected processes of differentiation/proliferation. PMID:26646662

  14. Genetic and physiological data suggest demographic and adaptive responses in complex interactions between populations of figs (Ficus pumila) and their pollinating wasps (Wiebesia pumilae).

    PubMed

    Wang, Hurng-Yi; Hsieh, Chia-Hung; Huang, Chin-Gi; Kong, Siu-Wah; Chang, Hsiao-Chi; Lee, Ho-Huei; Wang, Wei-Kuang; Chen, Shih-Lun; Tzeng, Hsy-Yu; Wu, Wen-Jer

    2013-07-01

    To study interactions between host figs and their pollinating wasps and the influence of climatic change on their genetic structures, we sequenced cytoplasmic and nuclear genes and genotyped nuclear microsatellite loci from two varieties of Ficus pumila, the widespread creeping fig and endemic jelly fig, and from their pollinating wasps, Wiebesia pumilae, found in Taiwan and on nearby offshore islands. Great divergence in the mitochondrial cytochrome c oxidase subunit I (mtCOI) with no genetic admixture in nuclear markers indicated that creeping- and jelly-fig wasps are genetically distinct. Compared with creeping-fig wasps, jelly-fig wasps also showed better resistance under cold (20 °C) than warm (25 and 30 °C) conditions in a survival test, indicating their adaptation to a cold environment, which may have facilitated population expansion during the ice age as shown by a nuclear intron and 10 microsatellite loci. An excess of amino acid divergence and a pattern of too many rare mtCOI variants of jelly-fig wasps as revealed by computer simulations and neutrality tests implied the effect of positive selection, which we hypothesize was associated with the cold-adaptation process. Chloroplast DNA of the two fig plants was completely segregated, with signs of genetic admixture in nuclear markers. As creeping- and jelly-fig wasps can pollinate creeping figs, occasional gene flow between the two figs is thus possible. Therefore, it is suggested that pollinating wasps may be playing an active role in driving introgression between different types of host fig.

  15. Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection.

    PubMed

    Ngampasutadol, Jutamas; Ram, Sanjay; Blom, Anna M; Jarva, Hanna; Jerse, Ann E; Lien, Egil; Goguen, Jon; Gulati, Sunita; Rice, Peter A

    2005-11-22

    Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease that is restricted to humans. Complement forms a key arm of the innate immune system that combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por) molecules to bind the classical pathway of complement down-regulatory protein C4b-binding protein (C4bp) to evade killing by human complement. Strains of N. gonorrhoeae that resisted killing by human serum complement were killed by serum from rodent, lagomorph, and primate species, which cannot be readily infected experimentally with this organism and whose C4bp molecules did not bind to N. gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can infect virtually all mammals, bound species-specific C4bp and uniformly resisted serum complement-mediated killing by these species. Serum resistance of gonococci was restored in these sera by human C4bp. An exception was serotype Por1B-bearing gonococcal strains that previously had been used successfully in a chimpanzee model of gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee C4bp and resisted killing by chimpanzee serum, providing insight into the host restriction of gonorrhea and addressing why Por1B strains, but not Por1A strains, have been successful in experimental chimpanzee infection. Our findings may lead to the development of better animal models for gonorrhea and may also have implications in the choice of complement sources to evaluate neisserial vaccine candidates.

  16. Complement inhibitor C4b-binding protein-friend or foe in the innate immune system?

    PubMed

    Blom, Anna M; Villoutreix, Bruno O; Dahlbäck, Björn

    2004-04-01

    The complement system constitutes an important component of the defence against foreign organisms, functioning both in innate and adaptive immune systems. It is potentially harmful also to the own organism and is therefore tightly regulated by a number of membrane-bound and soluble factors. C4b-binding protein (C4BP) is a potent circulating soluble inhibitor of the classical and lectin pathways of complement. In recent years, the relationships between the structure of C4BP and its functions have been elucidated using a combination of computer-based molecular analysis and recombinant DNA technologies. Moreover, two novel functions have recently been ascribed to C4BP. One is the ability of C4BP to localize complement regulatory activity to the surface of apoptotic cells via its interaction with the membrane-binding vitamin K-dependent protein S. The other is the ability of C4BP to act as a survival factor for B cells due to an interaction with CD40. The complement regulatory activity of C4BP is not only beneficial because it is also explored by pathogens such as Neisseria gonorrhoeae, Bordetella pertussis, Streptococcus pyogenes, Escherichia coli K1, and Candida albicans, that bind C4BP to their surfaces. This contributes to the serum resistance and the pathogenicity of these bacteria. In this review, the structural requirements and functional importance of the interactions between C4BP and its various ligands are discussed.

  17. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-08-02

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  18. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-01-01

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  19. Sharp green electroluminescence from 1H-pyrazolo[3,4-b]quinoline-based light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Tao, Y. T.; Balasubramaniam, E.; Danel, A.; Jarosz, B.; Tomasik, P.

    2000-09-01

    A multilayer organic light-emitting diode was fabricated using a fluorescent compound {6-N,N-diethylamino-1-methyl-3-phenyl-1H-pyrazolo[3,4-b]quinoline} (PAQ-NEt2) doped into the hole-transporting layer of NPB {4,4'-bis[N-(1-naphthyl-1-)-N-phenyl-amino]-biphenyl}, with the TPBI {2,2',2″-(1,3,5-phenylene)tris[1-phenyl-1H-benzimidazole]} as an electrontransporting material. At 16% PAQ-NEt2 doping concentration, the device gave a sharp, bright, and efficient green electroluminescence (EL) peaked at around 530 nm. The full width at half maximum of the EL is 60 nm, which is 60% of the green emission from typical NPB/AlQ [where AlQ=tris(8-hydroxyquinoline) aluminum] device. For the same concentration, a maximum luminance of 37 000 cd/m2 was obtained at 10.0 V and the maximum power, luminescence, and external quantum efficiencies were obtained 4.2 lm/W, 6.0 cd/A, and 1.6%, respectively, at 5.0 V.

  20. Purification of beef-heart cytochrome c oxidase by hydrophobic interaction chromatography on octyl-Sepharose CL-4B.

    PubMed

    Rosén, S

    1978-04-12

    1. Hydrophobic interaction chromatography on Octyl-Sepharose CL-4B is used as a new and simple method for the preparation of large amounts of beef-heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). 2. The method involves only one cycle of (NH4)2SO4 fractionation before the material is applied to the column. After washing with 10% cholate and 1.5% Tween 80, elution of the enzyme is accomplished with 1% Triton X-100. 3. The enzyme so prepared contains about 10 nmol heme alpha/mg protein and about 0.2% phospholipid. 4. Characterization of the enzyme has been made with optical and EPR spectroscopy and polyacrylamide gel electrophoresis. The preparation appears by these criteria to be at least as good as other purified enzyme preparations. 5. The turnover rate at infinite cytochrome c concentration in 0.1 M sodium phosphate buffer and 0.5% Tween 80 at pH 6.1 is 80 s-1 per functional unit of the enzyme. A more than three-fold activation could be obtained by the addition of phosphatidylcholine at neutral pH.

  1. Heterodyne coherent detection of WDM PDM-QPSK signals with spectral efficiency of 4b/s/Hz.

    PubMed

    Li, Xinying; Dong, Ze; Yu, Jianjun; Yu, Jianguo; Chi, Nan

    2013-04-01

    We experimentally demonstrate heterodyne coherent detection of 8 × 112-Gb/s ultra-density wavelength-division-multiplexing (WDM) polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) signal after 1120-km single-mode fiber-28 (SMF-28) transmission. The spectral efficiency (SE) is 4b/s/Hz. It is the first time to realize WDM signal transmission with high SE by adopting heterodyne coherent detection. At the heterodyne coherent receiver, intermediate frequency (IF) down conversion is realized in digital frequency domain after analog-to-digital conversion. A digital post filter and 1-bit maximum likelihood sequence estimation (MLSE) adopted after carrier phase estimation (CPE) in the conventional digital-signal-processing (DSP) process is used to suppress the enhanced noise and crosstalk as well as overcome the filtering effects. The bit-error ratio (BER) for all channels is under the forward-error-correction (FEC) limit of 3.8 × 10(-3) after 1120-km SMF-28 transmission.

  2. Heterodyne detection and transmission of 60-Gbaud PDM-QPSK signal with SE of 4b/s/Hz.

    PubMed

    Li, Xinying; Xiao, Jiangnan; Yu, Jianjun

    2014-04-21

    We experimentally demonstrate 8 × 240-Gb/s super-Nyquist wavelength-division-multiplexing (WDM) polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) signal transmission on a 50-GHz grid with a net spectral efficiency (SE) of 4b/s/Hz adopting hardware-efficient simplified heterodyne detection. 9-ary quadrature-amplitude-modulation-like (9QAM-like) processing based on multi-modulus blind equalization (MMBE) is adopted to reduce analog-to-digital converter (ADC) bandwidth requirement and improve receiver sensitivity. The transmission distance at the soft-decision forward-error-correction (SD-FEC) threshold of 2 × 10(-2) is 2 × 420 km based on digital post filtering while largely extended to over 5 × 420 km based on 9QAM-like processing, which well illustrates 9QAM-like processing is more efficient for heterodyne coherent WDM system. Moreover, only two ADC channels are needed for simplified heterodyne detection of one 60-Gbaud PDM-QPSK WDM channel, and thus only one commercial oscilloscope (OSC) with two input ports can work well for each WDM channel.

  3. Ammonia Inhibition of Plasmid pRmeGR4a Conjugal Transfer between Rhizobium meliloti Strains

    PubMed Central

    Herrera-Cervera, J. A.; Olivares, J.; Sanjuan, J.

    1996-01-01

    We have examined nutritional factors influencing conjugal transfer of the two nonsymbiotic large plasmids, pRmeGR4a and pRmeGR4b, of Rhizobium meliloti GR4. To monitor transfer, each plasmid was tagged with a different antibiotic resistance marker. Transfer of plasmid pRmeGR4b was dependent upon the presence of plasmid pRmeGR4a on the same donor cell. Transconjugants for pRmeGR4b were obtained at frequencies 5-to 10-fold higher than transconjugants carrying both plasmids, indicating that mobilization of pRmeGR4b by pRmeGR4a probably occurred in trans. Conjugal transfer of the tagged plasmids between R. meliloti strains was tested on minimal medium supplemented with single amino acids, nitrate, or ammonium as the single nitrogen source. A higher number of transconjugants was obtained when glutamate was the only nitrogen source, whereas conjugation was virtually undetectable on ammonium. No relationship was found between donor or recipient growth rate and plasmid transfer rate on a given nitrogen source. Furthermore, in media containing both glutamate and ammonium as nitrogen sources, transfer was reduced almost 100-fold compared with that in media containing glutamate alone. Inhibition was readily detected at 2.5 mM or higher concentrations of either ammonium chloride or ammonium sulfate and appeared to be specific for exogenously supplied ammonium. Inhibition of conjugal transfer between R. meliloti strains by ammonium was only observed for rhizobial plasmids, not for a heterologous plasmid such as RP4. Apparently, ammonium did not affect the plasmid-encoded transfer machinery, as it had no influence on rhizobial plasmid transfer from R. meliloti to Agrobacterium tumefaciens. The effect of ammonium seemed to take place on R. meliloti recipient cells, thereby reducing the efficiency of plasmid conjugation, probably by affecting mating pair formation or stabilization. PMID:16535284

  4. Some pollinators are more equal than others: Factors influencing pollen loads and seed set capacity of two actively and passively pollinating fig wasps

    NASA Astrophysics Data System (ADS)

    Kjellberg, Finn; Suleman, Nazia; Raja, Shazia; Tayou, Abelouahad; Hossaert-McKey, Martine; Compton, Stephen G.

    2014-05-01

    The nursery pollination system of fig trees (Ficus) results in the plants providing resources for pollinator fig wasp larvae as part of their male reproductive investment, with selection determining relative investment into pollinating wasps and the pollen they carry. The small size of Ficus pollen suggests that the quantities of pollen transported by individual wasps often limits male reproductive success. We assessed variation in fig wasp pollen loads and its influence on seed production in actively pollinated (Ficus montana) and passively pollinated (Ficus carica) dioecious fig trees.

  5. Downregulation of ROS-FIG inhibits cell proliferation, colony‑formation, cell cycle progression, migration and invasion, while inducing apoptosis in intrahepatic cholangiocarcinoma cells.

    PubMed

    Deng, Gang; Hu, Chenghuan; Zhu, Lei; Huang, Feizhou; Huang, Wei; Xu, Hongbo; Nie, Wanpin

    2014-09-01

    Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with poor responsiveness to existing drug therapies. Therefore, novel treatment strategies against ICC are required to improve survival. The aim of this study was to demonstrate the role of fused-in-glioblastoma-c-ros-oncogene1 (FIG-ROS) fusion gene in ICC. ROS was positively expressed in ICC tissues and HUCCT1 cells. Plasmids expressing ROS- and FIG-specific shRNAs were constructed and transfected into HUCCT1 cells. The results showed that single transfection of ROS- or FIG-specific shRNA inhibited HUCCT1 cell proliferation, colony formation, cell cycle progression, migration and invasion, while inducing apoptosis. Moreover, the co-inhibition of ROS- and FIG-specific shRNA exhibited stronger effects on HUCCT1 cell proliferation, apoptosis, colony formation, cell cycle progression, migration and invasion, when compared to single inhibition of ROS and FIG. Furthermore, findings of this study suggested that the AKT signaling pathway was involved in the ROS-FIG-mediated biological processes of HUCCT1 cells. In summary, the results suggest that FIG-ROS plays an oncogenic role in ICC. Additionally, ROS1-6290 and FIG-363 segments may become effective therapeutic targets for ICC harboring ROS-FIG fusion protein.

  6. Selective resource allocation may promote a sex ratio in pollinator fig wasps more beneficial for the host tree

    PubMed Central

    Li, Zhao-Tian; Peng, Yan-Qiong; Wen, Xiao-Lan; Jandér, K. Charlotte

    2016-01-01

    Mutualisms play a key role in most ecosystems, yet the mechanisms that prevent overexploitation of the mutualistic relationship are still poorly understood. In the mutualism between fig trees and their pollinating wasps both partners depend on each other. Fig trees benefit from female wasps that disperse their pollen, whereas wasps frequently benefit from a higher ratio of male offspring. Here we use manipulative field experiments to address whether host trees (Ficus racemosa) can influence the offspring sex ratio of the pollinator wasp. We controlled wasp matings; virgin wasps can lay only male eggs. We found that virgin foundress wasps had fewer offspring than mated foundresses. This was not caused by virgin wasps having a shorter lifespan, or laying fewer eggs. Instead, male wasp larvae were more likely to die during development. Additionally, male eggs were deposited in flowers of equal style length to those of female eggs, yet emerged from galls with shorter pedicels than those of female wasps. We suggest that male larvae are either allocated less resources by the tree, or are less able to attract resources, during development. If the tree orchestrates this difference it would promote a more female-biased wasp brood, thus increasing the tree’s fitness. PMID:27731351

  7. Whole exome sequencing identifies three recessive FIG4 mutations in an apparently dominant pedigree with Charcot-Marie-Tooth disease.

    PubMed

    Menezes, Manoj P; Waddell, Leigh; Lenk, Guy M; Kaur, Simranpreet; MacArthur, Daniel G; Meisler, Miriam H; Clarke, Nigel F

    2014-08-01

    Charcot-Marie-Tooth disease (CMT) is genetically heterogeneous and classification based on motor nerve conduction velocity and inheritance is used to direct genetic testing. With the less common genetic forms of CMT, identifying the causative genetic mutation by Sanger sequencing of individual genes can be time-consuming and costly. Next-generation sequencing technologies show promise for clinical testing in diseases where a similar phenotype is caused by different genes. We report the unusual occurrence of CMT4J, caused by mutations in FIG4, in a apparently dominant pedigree. The affected proband and her mother exhibit different disease severities associated with different combinations of compound heterozygous FIG4 mutations, identified by whole exome sequencing. The proband was also shown to carry a de novo nonsense mutation in the dystrophin gene, which may contribute to her more severe phenotype. This study is a cautionary reminder that in families with two generations affected, explanations other than dominant inheritance are possible, such as recessive inheritance due to three mutations segregating in the family. It also emphasises the advantages of next-generation sequencing approaches that screen multiple CMT genes at once for patients in whom the common genes have been excluded.

  8. Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer's disease.

    PubMed

    Essa, Musthafa Mohamed; Subash, Selvaraju; Akbar, Mohammed; Al-Adawi, Samir; Guillemin, Gilles J

    2015-01-01

    Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. The APPsw/Tg2576 mice exhibit age-related deterioration in memory and learning as well as amyloid-beta (Aβ) accumulation, and this mouse strain is considered an effective model for studying the mechanism of accelerated brain aging and senescence. The present study was aimed to investigate the beneficial effects of dietary supplements pomegranate, figs, or the dates on suppressing inflammatory cytokines in APPsw/Tg2576 mice. Changes in the plasma cytokines and Aβ, ATP, and inflammatory cytokines were investigated in the brain of transgenic mice. Significantly enhanced levels of inflammatory cytokines IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, TNF-α and Eotaxin activity were decreased by administration of the diet supplements containing pomegranates, figs, or dates. In addition, putative delays in the formation of senile plaques, as indicated by a decreasing tendency of brain Aβ1-40 and Aβ1-42 contents, were observed. Thus, novel results mediated by reducing inflammatory cytokines during aging may represent one mechanism by which these supplements exert their beneficial effects against neurodegenerative diseases such as AD.

  9. Pectinesterase Inhibitor from Jelly Fig (Ficus awkeotsang Makino) Achene Inhibits Surface Antigen Expression by Human Hepatitis B Virus

    PubMed Central

    Huang, Yu-Chuen; Jiang, Chii-Ming; Chen, Yu-Jen; Chen, Yu-Yawn

    2013-01-01

    Pectinesterase inhibitor (PEI) isolated from jelly fig (Ficus awkeotsang Makino) is an edible component of a popular drink consumed in Asia. Hepatitis B virus (HBV) infection is prevalent in Asia, and current treatments for HBV infection need improvement. This study aimed to evaluate the effect of PEI on the surface antigen expression by HBV (HBsAg). Human hepatoma cell lines Hep3B and Huh7 served as in vitro models for assessing the cytotoxicity and HBsAg expression. A culture of primary hepatocytes cultured from mice served as the normal counterpart. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. HBsAg expression was evaluated by measuring HBsAg secretion into the culture medium using an enzyme-linked immunosorbent assay. The results showed that PEI did not affect the viability of the human hepatoma cell lines or primary mouse hepatocytes. PEI inhibited the expression of HBsAg in hepatoma cell lines harboring endogenous (Hep3B) and integrated (Huh7) HBV genomes in a concentration- and time-dependent manner, thus implicating a universal activity against HBV gene expression. In conclusion, it suggests that PEI from jelly fig inhibits the expression of human HBsAg in host cells without toxic effects on normal primary hepatocytes. PMID:24302965

  10. Identification, purification and characterization of a novel collagenolytic serine protease from fig (Ficus carica var. Brown Turkey) latex.

    PubMed

    Raskovic, Brankica; Bozovic, Olga; Prodanovic, Radivoje; Niketic, Vesna; Polovic, Natalija

    2014-12-01

    A novel collagenolytic serine protease was identified and then purified (along with ficin) to apparent homogeneity from the latex of fig (Ficus carica, var. Brown Turkey) by two step chromatographic procedure using gel and covalent chromatography. The enzyme is a monomeric protein of molecular mass of 41 ± 9 kDa as estimated by analytical gel filtration chromatography. It is an acidic protein with a pI value of approximately 5 and optimal activity at pH 8.0-8.5 and temperature 60°C. The enzymatic activity was strongly inhibited by PMSF and Pefabloc SC, indicating that the enzyme is a serine protease. The enzyme showed specificity towards gelatin and collagen (215 GDU/mg and 24.8 CDU/mg, respectively) and non-specific protease activity (0.18 U/mg against casein). The enzyme was stable and retained full activity over a broad range of pH and temperature. The fig latex collagenolytic protease is potentially useful as a non-microbial enzyme with collagenolytic activity for various applications in the fields of biochemistry, biotechnology and medicine. PMID:24982021

  11. Pectinesterase Inhibitor from Jelly Fig (Ficus awkeotsang Makino) Achene Inhibits Surface Antigen Expression by Human Hepatitis B Virus.

    PubMed

    Huang, Yu-Chuen; Jiang, Chii-Ming; Chen, Yu-Jen; Chen, Yu-Yawn

    2013-01-01

    Pectinesterase inhibitor (PEI) isolated from jelly fig (Ficus awkeotsang Makino) is an edible component of a popular drink consumed in Asia. Hepatitis B virus (HBV) infection is prevalent in Asia, and current treatments for HBV infection need improvement. This study aimed to evaluate the effect of PEI on the surface antigen expression by HBV (HBsAg). Human hepatoma cell lines Hep3B and Huh7 served as in vitro models for assessing the cytotoxicity and HBsAg expression. A culture of primary hepatocytes cultured from mice served as the normal counterpart. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. HBsAg expression was evaluated by measuring HBsAg secretion into the culture medium using an enzyme-linked immunosorbent assay. The results showed that PEI did not affect the viability of the human hepatoma cell lines or primary mouse hepatocytes. PEI inhibited the expression of HBsAg in hepatoma cell lines harboring endogenous (Hep3B) and integrated (Huh7) HBV genomes in a concentration- and time-dependent manner, thus implicating a universal activity against HBV gene expression. In conclusion, it suggests that PEI from jelly fig inhibits the expression of human HBsAg in host cells without toxic effects on normal primary hepatocytes. PMID:24302965

  12. Identification, purification and characterization of a novel collagenolytic serine protease from fig (Ficus carica var. Brown Turkey) latex.

    PubMed

    Raskovic, Brankica; Bozovic, Olga; Prodanovic, Radivoje; Niketic, Vesna; Polovic, Natalija

    2014-12-01

    A novel collagenolytic serine protease was identified and then purified (along with ficin) to apparent homogeneity from the latex of fig (Ficus carica, var. Brown Turkey) by two step chromatographic procedure using gel and covalent chromatography. The enzyme is a monomeric protein of molecular mass of 41 ± 9 kDa as estimated by analytical gel filtration chromatography. It is an acidic protein with a pI value of approximately 5 and optimal activity at pH 8.0-8.5 and temperature 60°C. The enzymatic activity was strongly inhibited by PMSF and Pefabloc SC, indicating that the enzyme is a serine protease. The enzyme showed specificity towards gelatin and collagen (215 GDU/mg and 24.8 CDU/mg, respectively) and non-specific protease activity (0.18 U/mg against casein). The enzyme was stable and retained full activity over a broad range of pH and temperature. The fig latex collagenolytic protease is potentially useful as a non-microbial enzyme with collagenolytic activity for various applications in the fields of biochemistry, biotechnology and medicine.

  13. A West Nile virus NS4B-P38G mutant strain induces cell intrinsic innate cytokine responses in human monocytic and macrophage cells

    PubMed Central

    Xie, Guorui; Luo, Huanle; Tian, Bing; Mann, Brian; Bao, Xiaoyong; McBride, Jere; Tesh, Robert; Barrett, Alan D; Wang, Tian

    2015-01-01

    Previous studies have shown that an attenuated West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant induces stronger innate and adaptive immune responses than wild-type WNV in mice, which has important applications to vaccine development. To investigate the mechanism of immunogenicity, we characterized WNV NS4B-P38G mutant infection in two human cell lines--THP-1 cells and THP-1 macrophages. Although the NS4B-P38G mutant produced more viral RNA than the parental WNV NY99 in both cell types, there was no detectable infectious virus in the supernatant of either cell type. Nonetheless, the attenuated mutant boosted higher innate cytokine responses than virulent parental WNV NY99 in these cells. The NS4B-P38G mutant infection of THP-1 cells led to more diverse and robust innate cytokine responses than that seen in THP-1 macrophages, which were mediated by toll-like receptor (TLR)7 and retinoic acid-inducible gene 1(RIG-I) signaling pathways. Overall, these results suggest that a defective viral life cycle during NS4B-P38G mutant infection in human monocytic and macrophage cells leads to more potent cell intrinsic innate cytokine responses. PMID:25562791

  14. MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B.

    PubMed

    Li, Lei; Ma, Hui-Qiang

    2015-08-01

    There is increasing evidence to suggest that microRNAs (miRNAs; miRs) are involved in the development of oral squamous cell carcinoma (OSCC). miR-216a has been identified as being involved in tumorigenesis, however, the mechanisms of miR-216a in various types of cancer, either as a tumor suppressor or as an oncogenic miRNA, and the specific regulatory role of miR-216a in OSCC remain to be elucidated. The present study demonstrated that the expression of miR-216a was significantly reduced in OSCC tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, colony formation, migration and invasion of the OSCC cells. In addition, eukaryotic translation initiation factor 4B (EIF4B) was identified as a direct target of miR-216a, which was observed to be upregulated in the OSCC tissues. Furthermore, overexpression of EIF4B significantly attenuated the antitumor effect of miR-216a, and a negative correlation was observed between miR-216a and EIF4B in the OSCC tissues. Taken together, these findings indicated that miR-216a has a suppressive role in OSCC cells by directly targeting EIF4B, and may function as a potential prognostic biomarker and novel therapeutic target.

  15. Optimized human CYP4B1 in combination with the alkylator prodrug 4-ipomeanol serves as a novel suicide gene system for adoptive T-cell therapies.

    PubMed

    Roellecke, K; Virts, E L; Einholz, R; Edson, K Z; Altvater, B; Rossig, C; von Laer, D; Scheckenbach, K; Wagenmann, M; Reinhardt, D; Kramm, C M; Rettie, A E; Wiek, C; Hanenberg, H

    2016-07-01

    Engineering autologous or allogeneic T cells to express a suicide gene can control potential toxicity in adoptive T-cell therapies. We recently reported the development of a novel human suicide gene system that is based on an orphan human cytochrome P450 enzyme, CYP4B1, and the naturally occurring alkylator prodrug 4-ipomeanol. The goal of this study was to systematically develop a clinically applicable self-inactivating lentiviral vector for efficient co-expression of CYP4B1 as an ER-located protein with two distinct types of cell surface proteins, either MACS selection genes for donor lymphocyte infusions after allogeneic stem cell transplantation or chimeric antigen receptors for retargeting primary T cells. The U3 region of the myeloproliferative sarcoma virus in combination with the T2A site was found to drive high-level expression of our CYP4B1 mutant with truncated CD34 or CD271 as MACS suitable selection markers. This lentiviral vector backbone was also well suited for co-expression of CYP4B1 with a codon-optimized CD19 chimeric antigen receptor (CAR) construct. Finally, 4-ipomeanol efficiently induced apoptosis in primary T cells that co-express mutant CYP4B1 and the divergently located MACS selection and CAR genes. In conclusion, we here developed a clinically suited lentiviral vector that supports high-level co-expression of cell surface proteins with a potent novel human suicide gene. PMID:27092941

  16. Farnesylated and methylated KRAS4b: high yield production of protein suitable for biophysical studies of prenylated protein-lipid interactions

    PubMed Central

    Gillette, William K.; Esposito, Dominic; Abreu Blanco, Maria; Alexander, Patrick; Bindu, Lakshman; Bittner, Cammi; Chertov, Oleg; Frank, Peter H.; Grose, Carissa; Jones, Jane E.; Meng, Zhaojing; Perkins, Shelley; Van, Que; Ghirlando, Rodolfo; Fivash, Matthew; Nissley, Dwight V.; McCormick, Frank; Holderfield, Matthew; Stephen, Andrew G.

    2015-01-01

    Prenylated proteins play key roles in several human diseases including cancer, atherosclerosis and Alzheimer’s disease. KRAS4b, which is frequently mutated in pancreatic, colon and lung cancers, is processed by farnesylation, proteolytic cleavage and carboxymethylation at the C-terminus. Plasma membrane localization of KRAS4b requires this processing as does KRAS4b-dependent RAF kinase activation. Previous attempts to produce modified KRAS have relied on protein engineering approaches or in vitro farnesylation of bacterially expressed KRAS protein. The proteins produced by these methods do not accurately replicate the mature KRAS protein found in mammalian cells and the protein yield is typically low. We describe a protocol that yields 5–10 mg/L highly purified, farnesylated, and methylated KRAS4b from insect cells. Farnesylated and methylated KRAS4b is fully active in hydrolyzing GTP, binds RAF-RBD on lipid Nanodiscs and interacts with the known farnesyl-binding protein PDEδ. PMID:26522388

  17. Phylogeny and evolution of life-history strategies in the Sycophaginae non-pollinating fig wasps (Hymenoptera, Chalcidoidea)

    PubMed Central

    2011-01-01

    Background Non-pollinating Sycophaginae (Hymenoptera, Chalcidoidea) form small communities within Urostigma and Sycomorus fig trees. The species show differences in galling habits and exhibit apterous, winged or dimorphic males. The large gall inducers oviposit early in syconium development and lay few eggs; the small gall inducers lay more eggs soon after pollination; the ostiolar gall-inducers enter the syconium to oviposit and the cleptoparasites oviposit in galls induced by other fig wasps. The systematics of the group remains unclear and only one phylogeny based on limited sampling has been published to date. Here we present an expanded phylogeny for sycophagine fig wasps including about 1.5 times the number of described species. We sequenced mitochondrial and nuclear markers (4.2 kb) on 73 species and 145 individuals and conducted maximum likelihood and Bayesian phylogenetic analyses. We then used this phylogeny to reconstruct the evolution of Sycophaginae life-history strategies and test if the presence of winged males and small brood size may be correlated. Results The resulting trees are well resolved and strongly supported. With the exception of Apocrytophagus, which is paraphyletic with respect to Sycophaga, all genera are monophyletic. The Sycophaginae are divided into three clades: (i) Eukoebelea; (ii) Pseudidarnes, Anidarnes and Conidarnes and (iii) Apocryptophagus, Sycophaga and Idarnes. The ancestral states for galling habits and male morphology remain ambiguous and our reconstructions show that the two traits are evolutionary labile. Conclusions The three main clades could be considered as tribes and we list some morphological characters that define them. The same biologies re-evolved several times independently, which make Sycophaginae an interesting model to test predictions on what factors will canalize the evolution of a particular biology. The ostiolar gall-inducers are the only monophyletic group. In 15 Myr, they evolved several morphological

  18. A switch from mutualist to exploiter is reflected in smaller egg loads and increased larval mortalities in a 'cheater' fig wasp

    NASA Astrophysics Data System (ADS)

    Zhao, Jiang-Bo; Peng, Yan-Qiong; Quinnell, Rupert J.; Compton, Stephen G.; Yang, Da-Rong

    2014-05-01

    The interaction between the hundreds of Ficus species and their specific pollinating fig wasps (Agaonidae) presents a striking example of mutualism. Foundress fig wasps pollinate fig flowers, but also lay their eggs in (and gall) some of them. Only two cases of cheating fig wasps (that fail to pollinate) have been reported, from two continents, suggesting that there is a cost to abandoning pollination. Reasons for the rarity of cheating are a major question in fig biology, because persistence of the mutualism depends on fig wasps continuing to pollinate. A cost in terms of reduced reproductive success among cheaters could be one explanation. Here we compare the behavior and reproduction of an undescribed Eupristina sp., a cheater that coexists with the pollinator Eupristina altissima on Ficus altissima in southern China. Adult females of both species fought with conspecifics when they were seeking entry through the ostiole into receptive figs, but there was no fighting with heterospecifics. Despite a similar body size, female pollinators contained more eggs than female cheaters. Pollinators and cheaters produced similar number of galls, and although almost twice as many flowers were galled in figs entered by two compared to one foundress, larval mortality was greatly increased when two foundresses were present. Larval mortality was also significantly higher for cheaters compared to pollinators, independent of the number of foundresses. Ovules galled by the cheater were thus significantly less likely to result in adult offspring, suggesting that there are significant costs associated with abandoning the mutualism.

  19. Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression.

    PubMed Central

    Barba, G; Rittner, C; Schneider, P M

    1993-01-01

    The fourth component of the human complement system (C4) is coded for by two genes, C4A and C4B, located within the MHC. Null alleles of C4 (C4Q0) are defined by the absence of C4 protein in plasma. These null alleles are due either to large gene deletions or to nonexpression of the respective genes. In a previous study, evidence was obtained for nonexpressed defective genes at the C4A locus, and for gene conversion at the C4B locus. To further characterize the molecular basis of these non-expressed C4A genes, we selected nine pairs of PCR primers from flanking genomic intron sequences to amplify all 41 exons from individuals with a defective C4A gene. The amplified products were subjected to single-stranded conformation polymorphism (SSCP) analysis to detect possible mutations. PCR products exhibiting a variation in the SSCP pattern were sequenced directly. In 10 of 12 individuals studied, we detected a 2-bp insertion in exon 29 leading to nonexpression due to the creation of a termination codon, which was observed in linkage to the haplotype HLA-B60-DR6 in seven cases. In one of the other two individuals without this mutation, evidence was obtained for gene conversion to the C4B isotype. The genetic basis of C4A nonexpression in the second individual is not yet known and will be subject to further analysis. Images PMID:8473511

  20. Flavonoid content in leaf extracts of the fig (Ficus carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.).

    PubMed

    Vaya, Jacob; Mahmood, Saeed

    2006-01-01

    The total flavonoid content of leaf extracts (70% ethanol) from fig (Ficus carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.) plants were determined by using reverse phase high-performance liquid chromatography (HPLC)-and analyzed by UV/VIS array and electrospray ionization (ESI)-mass spectrometry (MS) detectors. As a base for comparison, flavonoid type and level were also determined in extracts from soybeans and grape seeds. It was found that the major flavonoids in Ficus are quercetin and luteolin, with a total of 631 and 681 mg/kg extract, respectively. In Ceratonia leaves, nine different flavonoids were detected. The major one was myricetin (1486 mg/kg extract), with a similar level in Pistacia (1331 mg/kg extract, myricetin). The present study is the first to report the presence of the isoflavone genistein in the Pistacia leaf, which was discovered to consist of about a third of the genistein level detected in soybean.

  1. Comparative gas exchange characteristics of potted, glasshouse-grown almond, apple, fig, grape, olive, peach and Asian pear

    USGS Publications Warehouse

    Higgins, S.S.; Larsen, F.E.; Bendel, R.B.; Radamaker, G.K.; Bassman, J.H.; Bidlake, W.R.; Wir, A.A.

    1992-01-01

    Net photosynthesis (Pn), dark respiration (Rd), transpirational flux density (TFD) and leaf conductance (kl) on glasshouse-grown plants of almond, apple, fig, grape, olive, peach and Asian pear were examined under various laboratory environmental conditions. Grape and almond had the highest light-saturated photosynthetic rates, greater than 20 ??mol CO2 m-2 s-1. Apple had the lowest temperature optimum for Pn, 20??C. Almond had the highest Rd rate between 10 and 50??C, but grape had the highest Q10 for respiration, a value of 2.5. Apple, olive and grape stomata were most sensitive to the leaf-to-air vapor pressure difference. Apple had the greatest sensitivity of Pn to the vapor pressure difference. ?? 1992.

  2. Ficus religiosa L. figs--a potential herbal adjuvant to phenytoin for improved management of epilepsy and associated behavioral comorbidities.

    PubMed

    Singh, Paramdeep; Singh, Damanpreet; Goel, Rajesh Kumar

    2014-12-01

    Oxidative stress, together with mitochondrial dysfunction, has been reported to be involved in the pathogenesis of epileptogenesis and its associated comorbidities. Phytoflavonoids have shown numerous beneficial ameliorative effects on different neurological disorders by virtue of their antioxidant effect. The present study investigated the effect of flavonoid-rich ethyl acetate fraction of the crude fig extract of Ficus religiosa in combination with phenytoin on seizure severity, depressive behavior, and cognitive deficit in pentylenetetrazol (PTZ)-kindled mice. The flavonoid-rich ethyl acetate fraction of the crude fig extract was found to show significant antioxidant potential in various in vitro free radical scavenging assays. Combined treatment of this fraction (2.5, 5, and 10 mg/kg; i.p.) along with a subeffective dose of phenytoin (15 mg/kg; i.p.) in postkindled animals once daily for fifteen days showed a dose-dependent decrease in the seizure severity score, a decreased number of mistakes, increased step-down latency in passive shock avoidance paradigm, and decreased immobility time in the tail suspension test in comparison with the phenytoin only-treated group. Biochemical investigations of the brain tissue showed amelioration of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, and reduced catalase and acetylcholinesterase (AChE) activities, thereby indicating suppression of oxidative stress. In conclusion, the results of the present study showed the protective effect of the flavonoid-rich fraction of F. religiosa along with a subeffective dose of phenytoin in PTZ-kindling-associated cognitive deficit and depressive behavior with complete suppression of seizures through reduction of oxidative stress, supporting the the need for clinical evaluation of the supplementation of phytoflavonoids along with antiepileptic drugs (AEDs) for management of epilepsy and its psychiatric and cognitive comorbidities. PMID:25461211

  3. Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones.

    PubMed

    Arvieux, J; Yssel, H; Colomb, M G

    1988-10-01

    The effect of complement fragments C3b and C4b, on the triggering of antigen-specific human T-cell clones by Epstein-Barr virus-transformed human lymphoblastoid B cells (LCL) when these fragments are covalently coupled to the antigen tetanus toxin (TT) is described. TT was chemically cross-linked to purified C3b [(TT-C3b)n], C4b [(TT-C4b)n] or bovine serum albumin [(TT-BSA)n] as a control. T-cell activation was quantified by tritiated thymidine incorporation and 51Cr release. (TT-C3b)n and (TT-C4b)n induced proliferative responses comparable to (TT-BSA)n but at 18-25 and 4-6 lower concentrations, respectively. This enhancing effect required the covalent cross-linking of the complement fragments to the antigen and involved intracellular processing of the latter by LCL. Antigen presentation was similarly enhanced when measuring the cytotoxic activity of a helper T-cell clone against LCL previously pulsed with (TT-C3b)n or (TT-C4b)n compared with (TT-BSA)n. Binding studies, carried out on LCL using TT radiolabelled with 125I before cross-linking, indicated that (TT-C3b)n and (TT-C4b)n gave three- to four-fold more binding than (TT-BSA)n. Addition of antibodies against CR1 and CR2 or proteolytic removal of these complement receptors with trypsin inhibited by about 60% the enhancing effect of TT-bound C3b and C4b in both binding and functional assays. These results indicate that binding of C3b or C4b to antigen enhances antigen-specific proliferative and cytotoxic responses of T cells by targeting opsonized antigen onto complement receptors CR1 and CR2 of LCL. The putative significance of these findings in terms of regulation of immune responses by complement is discussed.

  4. Instability due to a two recirculation pump trip in a BWR using RAMONA-4B computer code with 3D neutron kinetics

    SciTech Connect

    Cheng, H.S.; Rohatgi, U.S.

    1993-06-01

    An investigation was made of the potential for thermal-hydraulic instabilities coupled to neutronic feedback in a BWR due to a two recirculation pump trip event using the RAMONA-4B computer code with 3D neutron kinetics. It is concluded that a high-power (100%) and low-flow (75%) initial condition would most likely lead to in-phase density wave oscillations after the tripping of both recirculation pumps, and that RAMONA-4B is capable of predicting such thermal-hydraulic instabilities coupled to neutronic feedback in BWR and in SBWR.

  5. Synthesis of new 9-glycosyl-4,9-dihydropyrano [3,4-b]indole-1(3H)-ones as antibacterial agents.

    PubMed

    Kassab, Shaymaa E; Hegazy, Gehan H; Eid, Nahed M; Amin, Kamelia M; El-Gendy, Adel A

    2011-11-01

    A series of new 9-glycosyl-4,9-dihydropyrano[3,4-b]indole-1(3H)-ones 3 was synthesized in moderate to low yields. 4,9-Dihydropyrano[3,4-b]indole-1(3H)-ones (1) were coupled with different acetobromoglycopyranoses 2 in refluxing toluene in the presence of silver oxide to afford one coupling product of the respective N-glycosides. α-L-Arabinopyranosides 3j and 3m were the most active glycosides among the tested compounds against certain Gram positive and Gram negative bacterial strains.

  6. An analysis of the deformation approach to calculation of the life of hydrogen impregnated 1Kh16N4B steel in low-cycle fatigue

    SciTech Connect

    Litvin, V.V.; Anan'evskii, V.A.; Mints, A.I.

    1986-01-01

    This paper presents the results of experimental investigations and an analysis of the applicability of the deformation approach for calculation of the life of 1Kh16N4B steel in low-cycle fatigue. Hydrogen impregnation was done with use of cathodic polarization in a special cell with a polarization current density of 35 mA/cm/sup 2/ for 60 min. The test results are presented, and it can be seen that the influence of hydrogen absorption significantly changes the life of 1Kh16N4B steel, but the Coffin-Kavomoto criterion does not give satisfactory results.

  7. Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones.

    PubMed

    Arvieux, J; Yssel, H; Colomb, M G

    1988-10-01

    The effect of complement fragments C3b and C4b, on the triggering of antigen-specific human T-cell clones by Epstein-Barr virus-transformed human lymphoblastoid B cells (LCL) when these fragments are covalently coupled to the antigen tetanus toxin (TT) is described. TT was chemically cross-linked to purified C3b [(TT-C3b)n], C4b [(TT-C4b)n] or bovine serum albumin [(TT-BSA)n] as a control. T-cell activation was quantified by tritiated thymidine incorporation and 51Cr release. (TT-C3b)n and (TT-C4b)n induced proliferative responses comparable to (TT-BSA)n but at 18-25 and 4-6 lower concentrations, respectively. This enhancing effect required the covalent cross-linking of the complement fragments to the antigen and involved intracellular processing of the latter by LCL. Antigen presentation was similarly enhanced when measuring the cytotoxic activity of a helper T-cell clone against LCL previously pulsed with (TT-C3b)n or (TT-C4b)n compared with (TT-BSA)n. Binding studies, carried out on LCL using TT radiolabelled with 125I before cross-linking, indicated that (TT-C3b)n and (TT-C4b)n gave three- to four-fold more binding than (TT-BSA)n. Addition of antibodies against CR1 and CR2 or proteolytic removal of these complement receptors with trypsin inhibited by about 60% the enhancing effect of TT-bound C3b and C4b in both binding and functional assays. These results indicate that binding of C3b or C4b to antigen enhances antigen-specific proliferative and cytotoxic responses of T cells by targeting opsonized antigen onto complement receptors CR1 and CR2 of LCL. The putative significance of these findings in terms of regulation of immune responses by complement is discussed. PMID:2973431

  8. Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats

    SciTech Connect

    Chen, Xiang-Qi; Chen, Liang-Long Fan, Lin; Fang, Jun; Chen, Zhao-Yang; Li, Wei-Wei

    2014-04-25

    Highlights: • BFGF exists only in the cytoplasm of live cells. • BFGF cannot be secreted into the extracellular space to promote cell growth. • We combine the secretion-promoting signal peptide of FGF4. • We successfully modified BMSCs with the fused genes of FGF4-bFGF. • We promoted the therapeutic effects of transplanted BMSCs in myocardial infarction. - Abstract: The aim of this study was to investigate whether the modification of bone marrow-derived mesenchymal stem cells (BMSCs) with the fused FGF4 (fibroblast growth factor 4)-bFGF (basic fibroblast growth factor) gene could improve the expression and secretion of BFGF, and increase the efficacies in repairing infarcted myocardium. We used In-Fusion technique to construct recombinant lentiviral vectors containing the individual gene of bFGF, enhanced green fluorescent protein (EGFP), or genes of FGF4-bFGF and EGFP, and then transfected these lentiviruses into rat BMSCs. We conducted an in vitro experiment to compare the secretion of bFGF in BMSCs infected by these lentiviruses and also examined their therapeutic effects in the treatment of myocardial infraction in a rodent study. Sixty rats were tested in the following five conditions: Group-SHAM received only sham operation as controls; Group-AMI received only injection of placebo PBS buffer; Group-BMSC, Group-bFGF and Group-FGF4-bFGF received implantation of BMSCs with empty lentivirus, bFGF lentivirus, and FGF4-bFGF lentivirus, respectively. Our results found out that the transplanted FGF4-bFGF BMSCs had the highest survival rate, and also the highest myocardial expression of bFGF and microvascular density as evidenced by Western blotting and immunohistochemistry, respectively. As compared to other groups, the Group-FGF4-BFGF rats had the lowest myocardial fibrotic fraction, and the highest left ventricular ejection fraction. These results suggest that the modification of BMSCs with the FGF4-bFGF fused gene can not only increase the expression of

  9. Induced overexpression of OCT4A in human embryonic stem cells increases cloning efficiency.

    PubMed

    Tsai, Steven C; Chang, David F; Hong, Chang-Mu; Xia, Ping; Senadheera, Dinithi; Trump, Lisa; Mishra, Suparna; Lutzko, Carolyn

    2014-06-15

    Our knowledge of the molecular mechanisms underlying human embryonic stem cell (hESC) self-renewal and differentiation is incomplete. The level of octamer-binding transcription factor 4 (Oct4), a critical regulator of pluripotency, is precisely controlled in mouse embryonic stem cells. However, studies of human OCT4 are often confounded by the presence of three isoforms and six expressed pseudogenes, which has complicated the interpretation of results. Using an inducible lentiviral overexpression and knockdown system to manipulate OCT4A above or below physiological levels, we specifically examine the functional role of the OCT4A isoform in hESC. (We also designed and generated a comparable series of vectors, which were not functional, for the overexpression and knockdown of OCT4B.) We show that specific knockdown of OCT4A results in hESC differentiation, as indicated by morphology changes, cell surface antigen expression, and upregulation of ectodermal genes. In contrast, inducible overexpression of OCT4A in hESC leads to a transient instability of the hESC phenotype, as indicated by changes in morphology, cell surface antigen expression, and transcriptional profile, that returns to baseline within 5 days. Interestingly, sustained expression of OCT4A past 5 days enhances hESC cloning efficiency, suggesting that higher levels of OCT4A can support self-renewal. Overall, our results indicate that high levels of OCT4A increase hESC cloning efficiency and do not induce differentiation (whereas OCT4B expression cannot be induced in hESC), highlighting the importance of isoform-specific studies in a stable and inducible expression system for human OCT4. Additionally, we demonstrate the utility of an efficient method for conditional gene expression in hESC.

  10. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    PubMed

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  11. Complete Genome Sequences of Two Listeria monocytogenes Serovars, 1/2a and 4b, Isolated from Dairy Products in Brazil

    PubMed Central

    Campos, Fabrício Souza; Mariot, Roberta Fogliatto; Prichula, Janira; de Moura, Tiane Martin; Frazzon, Ana Paula Guedes

    2015-01-01

    Listeria monocytogenes is the foodborne pathogen responsible for a bacterial infection called listeriosis. Here, we present the whole-genome sequences of two L. monocytogenes serovars, 1/2a and 4b, which are considered the most prevalent in food processing plants and listeriosis outbreaks, respectively. PMID:26679596

  12. PARAQUAT TOLERANCE3 Is an E3 Ligase That Switches off Activated Oxidative Response by Targeting Histone-Modifying PROTEIN METHYLTRANSFERASE4b

    PubMed Central

    Du, Jin; Zhao, Tao-Lan; Wang, Peng-Fei; Zhao, Ping-Xia; Xie, Qi; Cao, Xiao-Feng; Xiang, Cheng-Bin

    2016-01-01

    Oxidative stress is unavoidable for aerobic organisms. When abiotic and biotic stresses are encountered, oxidative damage could occur in cells. To avoid this damage, defense mechanisms must be timely and efficiently modulated. While the response to oxidative stress has been extensively studied in plants, little is known about how the activated response is switched off when oxidative stress is diminished. By studying Arabidopsis mutant paraquat tolerance3, we identified the genetic locus PARAQUAT TOLERANCE3 (PQT3) as a major negative regulator of oxidative stress tolerance. PQT3, encoding an E3 ubiquitin ligase, is rapidly down-regulated by oxidative stress. PQT3 has E3 ubiquitin ligase activity in ubiquitination assay. Subsequently, we identified PRMT4b as a PQT3-interacting protein. By histone methylation, PRMT4b upregulates the expression of APX1 and GPX1, encoding two key enzymes against oxidative stress. On the other hand, PRMT4b is recognized by PQT3 for targeted degradation via 26S proteasome. Therefore, we have identified PQT3 as an E3 ligase that acts as a negative regulator of activated response to oxidative stress and found that histone modification by PRMT4b at APX1 and GPX1 loci plays an important role in oxidative stress tolerance. PMID:27676073

  13. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome.

    PubMed

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-02-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

  14. Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.

    PubMed

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-10-01

    Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases.

  15. Synergistic effects of sodium chloride, Glucose, and temperature on biofilm formation by Listeria monocytogenes serotype 1/2a and 4b strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biofilm formation by Listeria monocytogenes is generally associated with its persistence in the food processing environment. Serotype 1/2a strains make up more than 50% of the total isolates recovered from food and environment, while serotype 4b strains are most often associated with major outbreaks...

  16. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome

    PubMed Central

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-01-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome. PMID:24781758

  17. Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.

    PubMed

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-10-01

    Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases. PMID:25462154

  18. Flaviviral NS4b, chameleon and jack‐in‐the‐box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention

    PubMed Central

    Zmurko, Joanna; Dallmeier, Kai

    2015-01-01

    Summary Dengue virus and other flaviviruses such as the yellow fever, West Nile, and Japanese encephalitis viruses are emerging vector‐borne human pathogens that affect annually more than 100 million individuals and that may cause debilitating and potentially fatal hemorrhagic and encephalitic diseases. Currently, there are no specific antiviral drugs for the treatment of flavivirus‐associated disease. A better understanding of the flavivirus–host interactions during the different events of the flaviviral life cycle may be essential when developing novel antiviral strategies. The flaviviral non‐structural protein 4b (NS4b) appears to play an important role in flaviviral replication by facilitating the formation of the viral replication complexes and in counteracting innate immune responses such as the following: (i) type I IFN signaling; (ii) RNA interference; (iii) formation of stress granules; and (iv) the unfolded protein response. Intriguingly, NS4b has recently been shown to constitute an excellent target for the selective inhibition of flavivirus replication. We here review the current knowledge on NS4b. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:25828437

  19. Draft Genome Sequences of Listeria monocytogenes Serotype 4b Strains 944 and 2993 and Serotype 1/2c Strains 198 and 2932

    PubMed Central

    Casey, Aidan; Fox, Edward M.; Leong, Dara; Gahan, Cormac G. M.; Jordan, Kieran

    2016-01-01

    Listeria monocytogenes is a foodborne pathogen and the causative agent of listeriosis among humans and animals. The draft genome sequences of L. monocytogenes serotype 4b strains 944 and 2993 and serotype 1/2c strains 198 and 2932 are reported here. PMID:27257200

  20. Identification of A Novel SBF2 Frameshift Mutation in Charcot–Marie–Tooth Disease Type 4B2 Using Whole-exome Sequencing

    PubMed Central

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-01-01

    Charcot–Marie–Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient’s condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases. PMID:25462154

  1. A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways.

    PubMed

    Xie, Guorui; Welte, Thomas; Wang, Jia; Whiteman, Melissa C; Wicker, Jason A; Saxena, Vandana; Cong, Yingzi; Barrett, Alan D T; Wang, Tian

    2013-08-28

    Prior work shows that an attenuated West Nile virus (WNV), the nonstructural (NS)4B-P38G mutant infection in mice induced strong immune responses and protected host from subsequent lethal wild-type WNV infection. Here, we investigated NS4B-P38G mutant infection in myeloid differentiation factor 88-deficient (MyD88(-/-)) and Toll-like receptor 7-deficient (TLR7(-/-)) mice and found they had enhanced susceptibility compared to wild-type mice. Both groups had lower WNV-specific IgM response and reduced effector T cell functions. Dendritic cells (DCs) also exhibited a reduced maturation and impaired antigen-presenting functions compared to wild-type DCs. Moreover, infection with NS4B-P38G mutant in TLR7(-/-) and MyD88(-/-) mice provided full and partial protection respectively from subsequent challenge with lethal wild-type WNV. There were reduced T cell responses in MyD88(-/-) and interleukin-1 receptor deficient (IL-1R(-/-)) mice during secondary challenge with wild-type WNV. In contrast, TLR7(-/-) mice displayed normal T cell functions. Collectively, these results suggest that TLR7-dependent MyD88 signaling is required for T cell priming during NS4B-P38G mutant infection, whereas the TLR7-independent MyD88 signaling pathways are involved in memory T cell development, which may contribute to host protection during secondary challenge with wild-type WNV. PMID:23845800

  2. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis Cases in the United States from 2003 to 2008

    PubMed Central

    Ward, Todd J.; Graves, Lewis M.; Tarr, Cheryl L.; Siletzky, Robin M.; Kathariou, Sophia

    2014-01-01

    Listeria monocytogenes can cause severe food-borne disease (listeriosis). Numerous outbreaks have involved three serotype 4b epidemic clones (ECs): ECI, ECII, and ECIa. However, little is known about the population structure of L. monocytogenes serotype 4b from sporadic listeriosis in the United States, even though most cases of human listeriosis are in fact sporadic. Here we analyzed 136 serotype 4b isolates from sporadic cases in the United States, 2003 to 2008, utilizing multiple tools including multilocus genotyping, pulsed-field gel electrophoresis, and sequence analysis of the inlAB locus. ECI, ECII, and ECIa were frequently encountered (32, 17, and 7%, respectively). However, annually 30 to 68% of isolates were outside these ECs, and several novel clonal groups were identified. An estimated 33 and 17% of the isolates, mostly among the ECs, were resistant to cadmium and arsenic, respectively, but resistance to benzalkonium chloride was uncommon (3%) among the sporadic isolates. The frequency of clonal groups fluctuated within the 6-year study period, without consistent trends. However, on several occasions, temporal clusters of isolates with indistinguishable genotypes were detected, suggesting the possibility of hidden multistate outbreaks. Our analysis suggests a complex population structure of serotype 4b L. monocytogenes from sporadic disease, with important contributions by ECs and several novel clonal groups. Continuous monitoring will be needed to assess long-term trends in clonality patterns and population struct