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Sample records for 4a fig 4b

  1. Characterization of Dengue Virus NS4A and NS4B Protein Interaction

    PubMed Central

    Zou, Jing; Xie, Xuping; Wang, Qing-Yin; Dong, Hongping; Lee, Michelle Yueqi; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus replication is mediated by a membrane-associated replication complex where viral membrane proteins NS2A, NS2B, NS4A, and NS4B serve as the scaffold for the replication complex formation. Here, we used dengue virus serotype 2 (DENV-2) as a model to characterize viral NS4A-NS4B interaction. NS4A interacts with NS4B in virus-infected cells and in cells transiently expressing NS4A and NS4B in the absence of other viral proteins. Recombinant NS4A and NS4B proteins directly bind to each other with an estimated Kd (dissociation constant) of 50 nM. Amino acids 40 to 76 (spanning the first transmembrane domain, consisting of amino acids 50 to 73) of NS4A and amino acids 84 to 146 (also spanning the first transmembrane domain, consisting of amino acids 101 to 129) of NS4B are the determinants for NS4A-NS4B interaction. Nuclear magnetic resonance (NMR) analysis suggests that NS4A residues 17 to 80 form two amphipathic helices (helix α1, comprised of residues 17 to 32, and helix α2, comprised of residues 40 to 47) that associate with the cytosolic side of endoplasmic reticulum (ER) membrane and helix α3 (residues 52 to 75) that transverses the ER membrane. In addition, NMR analysis identified NS4A residues that may participate in the NS4A-NS4B interaction. Amino acid substitution of these NS4A residues exhibited distinct effects on viral replication. Three of the four NS4A mutations (L48A, T54A, and L60A) that affected the NS4A-NS4B interaction abolished or severely reduced viral replication; in contrast, two NS4A mutations (F71A and G75A) that did not affect NS4A-NS4B interaction had marginal effects on viral replication, demonstrating the biological relevance of the NS4A-NS4B interaction to DENV-2 replication. Taken together, the study has provided experimental evidence to argue that blocking the NS4A-NS4B interaction could be a potential antiviral approach. IMPORTANCE Flavivirus NS4A and NS4B proteins are essential components of the ER membrane

  2. Specificity of the hepatitis C virus NS3 serine protease: effects of substitutions at the 3/4A, 4A/4B, 4B/5A, and 5A/5B cleavage sites on polyprotein processing.

    PubMed Central

    Kolykhalov, A A; Agapov, E V; Rice, C M

    1994-01-01

    Cleavage at four sites (3/4A, 4A/4B, 4B/5A, and 5A/5B) in the hepatitis C virus polyprotein requires a viral serine protease activity residing in the N-terminal one-third of the NS3 protein. Sequence comparison of the residues flanking these cleavage sites reveals conserved features including an acidic residue (Asp or Glu) at the P6 position, a Cys or Thr residue at the P1 position, and a Ser or Ala residue at the P1' position. In this study, we used site-directed mutagenesis to assess the importance of these and other residues for NS3 protease-dependent cleavages. Substitutions at the P7 to P2' positions of the 4A/4B site had varied effects on cleavage efficiency. Only Arg at the P1 position or Pro at P1' substantially blocked processing at this site. Leu was tolerated at the P1 position, whereas five other substitutions allowed various degrees of cleavage. Substitutions with positively charged or other hydrophilic residues at the P7, P3, P2, and P2' positions did not reduce cleavage efficiency. Five substitutions examined at the P6 position allowed complete cleavage, demonstrating that an acidic residue at this position is not essential. Parallel results were obtained with substrates containing an active NS3 protease domain in cis or when the protease domain was supplied in trans. Selected substitutions blocking or inhibiting cleavage at the 4A/4B site were also examined at the 3/4A, 4B/5A, and 5A/5B sites. For a given substitution, a site-dependent gradient in the degree of inhibition was observed, with a 3/4A site being least sensitive to mutagenesis, followed by the 4A/4B, 4B/5A, and 5A/5B sites. In most cases, mutations abolishing cleavage at one site did not affect processing at the other serine protease-dependent sites. However, mutations at the 3/4A site which inhibited cleavage also interfered with processing at the 4B/5A site. Finally, during the course of these studies an additional NS3 protease-dependent cleavage site has been identified in the NS4B

  3. The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.

    PubMed

    Sullivan, Con; Charette, Jeremy; Catchen, Julian; Lage, Christopher R; Giasson, Gregory; Postlethwait, John H; Millard, Paul J; Kim, Carol H

    2009-11-01

    Mammalian immune responses to LPS exposure are typified by the robust induction of NF-kappaB and IFN-beta responses largely mediated by TLR4 signal transduction pathways. In contrast to mammals, Tlr4 signal transduction pathways in nontetrapods are not well understood. Comprehensive syntenic and phylogenetic analyses support our hypothesis that zebrafish tlr4a and tlr4b genes are paralogous rather than orthologous to human TLR4. Furthermore, we provide evidence to support our assertion that the in vivo responsiveness of zebrafish to LPS exposure is not mediated by Tlr4a and Tlr4b paralogs because they fail to respond to LPS stimulation in vitro. Zebrafish Tlr4a and Tlr4b paralogs were also unresponsive to heat-killed Escherichia coli and Legionella pneumophila. Using chimeric molecules in which portions of the zebrafish Tlr4 proteins were fused to portions of the mouse TLR4 protein, we show that the lack of responsiveness to LPS was most likely due to the inability of the extracellular portions of zebrafish Tlr4a and Tlr4b to recognize the molecule, rather than to changes in their capacities to transduce signals through their Toll/IL-1 receptor (TIR) domains. Taken together, these findings strongly support the notion that zebrafish tlr4a and tlr4b paralogs have evolved to provide alternative ligand specificities to the Tlr immune defense system in this species. These data demonstrate that intensive examination of gene histories when describing the Tlr proteins of basally diverging vertebrates is required to obtain fuller appreciation of the evolution of their function. These studies provide the first evidence for the functional evolution of a novel Tlr.

  4. Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B

    PubMed Central

    Hannah, Jeffrey

    2016-01-01

    The cullin 4 subfamily of genes includes CUL4A and CUL4B, which share a mostly identical amino acid sequence aside from the elongated N-terminal region in CUL4B. Both act as scaffolding proteins for modular cullin RING ligase 4 (CRL4) complexes which promote the ubiquitination of a variety of substrates. CRL4 function is vital to cells as loss of both genes or their shared substrate adaptor protein DDB1 halts proliferation and eventually leads to cell death. Due to their high structural similarity, CUL4A and CUL4B share a substantial overlap in function. However, in some cases, differences in subcellular localization, spatiotemporal expression patterns and stress-inducibility preclude functional compensation. In this review, we highlight the most essential functions of the CUL4 genes in: DNA repair and replication, chromatin-remodeling, cell cycle regulation, embryogenesis, hematopoiesis and spermatogenesis. CUL4 genes are also clinically relevant as dysregulation can contribute to the onset of cancer and CRL4 complexes are often hijacked by certain viruses to promote viral replication and survival. Also, mutations in CUL4B have been implicated in a subset of patients suffering from syndromic X-linked intellectual disability (AKA mental retardation). Interestingly, the antitumor effects of immunomodulatory drugs are caused by their binding to the CRL4CRBN complex and re-directing the E3 ligase towards the Ikaros transcription factors IKZF1 and IKZF3. Because of their influence over key cellular functions and relevance to human disease, CRL4s are considered promising targets for therapeutic intervention. PMID:26344709

  5. Cell surface trafficking of TLR1 is differentially regulated by the chaperones PRAT4A and PRAT4B.

    PubMed

    Hart, Bryan E; Tapping, Richard I

    2012-05-11

    The subcellular localization of Toll-like receptors (TLRs) is critical to their ability to function as innate immune sensors of microbial infection. We previously reported that an I602S polymorphism of human TLR1 is associated with aberrant trafficking of the receptor to the cell surface, loss of responses to TLR1 agonists, and differential susceptibility to diseases caused by pathogenic mycobacteria. Through an extensive analysis of receptor deletion and point mutants we have discovered that position 602 resides within a short 6 amino acid cytoplasmic region that is required for TLR1 surface expression. This short trafficking motif, in conjunction with the adjacent transmembrane domain, is sufficient to direct TLR1 to the cell surface. A serine at position 602 interrupts this trafficking motif and prevents cell surface expression of TLR1. Additionally, we have found that ER-resident TLR chaperones, PRAT4A and PRAT4B, act as positive and negative regulators of TLR1 surface trafficking, respectively. Importantly, either over-expression of PRAT4A or knock-down of PRAT4B rescues cell surface expression of the TLR1 602S variant. We also report that IFN-γ treatment of primary human monocytes derived from homozygous 602S individuals rescues TLR1 cell surface trafficking and cellular responses to soluble agonists. This event appears to be mediated by PRAT4A whose expression is strongly induced in human monocytes by IFN-γ. Collectively, these results provide a mechanism for the differential trafficking of TLR1 I602S variants, and highlight the distinct roles for PRAT4A and PRAT4B in the regulation of TLR1 surface expression.

  6. Monoclonal antipeptide antibodies against amino acid residues 1101-1106 of human C4 distinguish C4A from C4B.

    PubMed

    Reilly, B D; Levine, P; Rothbard, J; Skanes, V M

    1991-01-01

    Comparison of amino acid sequences of the alpha-chain fragment of human C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 in which the aspartic acid-histidine substitution at position 1106 may be related to the amide and ester bond forming properties of these molecules. Peptides containing twelve amino acid residues of the C4A- or C4B-specific sequences were synthesized and injected into female Balb/c mice. Serum from 2 mice, one immunized with the C4A-specific peptide and the other with the C4B-specific peptide, gave strong isotype-specific responses in an enzyme-linked immunosorbent assay against affinity-purified C4A3 and C4B2B1. Spleen cells from these mice were fused with the mouse myeloma SP2/0-Ag 14, and two cloned cell lines, AII-1 and BII-1, were established from hybrids. Enzyme-linked immunosorbent assay and western blotting of monoclonal antibodies AII-1 and BII-1 show that the former reacts with the C4A but not with the C4B alpha-chain and the latter with C4B but not with the C4A alpha-chain. Furthermore, immunoblotting of C4 allelic variants showed that AII-1 reacted with all C4A allotypes tested, including A6, A4, A3 and A2, whereas BII-1 reacted with all C4B allotypes tested, including B5, B3, B2, and B1.

  7. Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site.

    PubMed Central

    Lin, C; Amberg, S M; Chambers, T J; Rice, C M

    1993-01-01

    Flavivirus proteins are produced by co- and posttranslational proteolytic processing of a large polyprotein by both host- and virus-encoded proteinases. The viral serine proteinase, which consists of NS2B and NS3, is responsible for cleavage of at least four dibasic sites (2A/2B, 2B/3, 3/4A, and 4B/5) in the nonstructural region. Since the amino acid sequence preceding NS4B shares characteristics with signal peptides used for translocation of nascent polypeptides into the lumen of the endoplasmic reticulum, it has been proposed that cleavage at the 4A/4B site is mediated by a cellular signal peptidase. In this report, cell-free translation and in vivo transient expression assays were used to study processing in the NS4 region of the yellow fever virus polyprotein. With a construct which contained NS4B preceded by 17 residues constituting the putative signal peptide (sig4B), membrane-dependent cleavage at the 4A/4B site was demonstrated in vitro. Surprisingly, processing of NS4A-4B was not observed in cell-free translation studies, and in vivo expression of several yellow fever virus polyproteins revealed that the 4A/4B cleavage occurred only during coexpression of NS2B and the proteinase domain of NS3. Examination of mutant derivatives of the NS3 proteinase domain demonstrated that cleavage at the 4A/4B site correlated with expression of an active NS2B-3 proteinase. From these results, we propose a model in which the signalase cleavage generating the N terminus of NS4B requires a prior NS2B-3 proteinase-mediated cleavage at a novel site (called the 4A/2K site) which is conserved among flaviviruses and located 23 residues upstream of the signalase site. In support of this model, mutations at the 4A/4B signalase site did not eliminate processing in the NS4 region. In contrast, substitutions at the 4A/2K site, which were engineered to block NS2B-3 proteinase-mediated cleavage, eliminated signalase cleavage at the 4A/4B site. In addition, the size of the 3(502)-4A

  8. 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

  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. Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia

    PubMed Central

    Ko, Rose M.; Kim, Hyung-Gyoon; Wolff, Linda; Klug, Christopher A.

    2008-01-01

    Inactivation of p15Ink4b expression by promoter hypermethylation occurs in up to 80% of acute myeloid leukemia (AML) cases and is particularly common in the FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO translocation in 40% of cases. To establish whether the loss of p15Ink4b contributes to AML progression in association with RUNX1-ETO, we have expressed the RUNX1-ETO fusion protein from a retroviral vector in hematopoietic progenitor cells isolated from wild-type, p15Ink4b or p16Ink4a knockout bone marrow. Analysis of lethally irradiated recipient mice reconstituted with RUNX1-ETO-expressing cells showed that neither p15Ink4b or p16Ink4a loss significantly accelerated disease progression over the time period of one year post-transplantation. Loss of p15Ink4b alone resulted in increased myeloid progenitor cell frequencies in bone marrow by 10 months post-transplant and a 19-fold increase in the frequency of Lin-c-Kit+Sca-1+ (LKS) cells that was not associated with expansion of long-term reconstituting HSC. These results strongly suggest that p15Ink4b loss must be accompanied by additional oncogenic changes for RUNX1-ETO-associated AML to develop. PMID:18037485

  11. Complement components C2, C3, and C4 (C4A and C4B) and BF polymorphisms in populations of the Indian subcontinent.

    PubMed

    Ad'hiah, A H; Papiha, S S

    1996-10-01

    Genetic polymorphisms of the complement components (five loci: C2, C3, C4A, C4B, and BF) have been investigated in the Telugu-speaking Hindu population of Hyderabad, Andhra Pradesh, India, and the Bangali-speaking Muslim population of Dacca, Bangladesh. The available data are compared to understand the genetic variation of complement components in populations of the Indian subcontinent. The C3*F and BF*F alleles show wide frequency variations in different ethnic groups of India. The range of variation in the C3*F allele is intermediate between European whites and southeast Asian populations, whereas the BF*F allele places the Indian frequencies between European whites and African blacks. This is the first population study to investigate the C2 and C4 (C4A and C4B) polymorphisms in two distinct groups of the Indian subcontinent. For the C2 polymorphism only the C2*B variant allele was observed, and its frequency was slightly higher than in European populations. In both populations the C4A and C4B loci were highly polymorphic, with a high frequency of the null alleles C4A*QO and C4B*QO, which may account for the greater susceptibility to certain autoimmune diseases in populations of South Asia.

  12. eIF4B stimulates eIF4A ATPase and unwinding activities by direct interaction through its 7-repeats region.

    PubMed

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

    2017-01-02

    Eukaryotic translation initiation starts with binding of the eIF4F complex to the 5'-m(7)G cap of the mRNA. Recruitment of the 43S pre-initiation complex (PIC), formed by the 40S ribosomal subunit and other translation initiation factors, leads to formation of the 48S PIC that then scans the 5'-untranslated region (5'-UTR) toward the start codon. The eIF4F complex consists of eIF4E, the cap binding protein, eIF4A, a DEAD-box RNA helicase that is believed to unwind secondary structures in the 5'-UTR during scanning, and eIF4G, a scaffold protein that binds to both eIF4E and eIF4A. The ATPase and helicase activities of eIF4A are jointly stimulated by eIF4G and the translation initiation factor eIF4B. Yeast eIF4B mediates recruitment of the 43S PIC to the cap-bound eIF4F complex by interacting with the 40S subunit and possibly with eIF4A. However, a direct interaction between yeast eIF4A and eIF4B has not been demonstrated yet. Here we show that eIF4B binds to eIF4A in the presence of RNA and ADPNP, independent of the presence of eIF4G. A stretch of seven moderately conserved repeats, the r1-7 region, is responsible for complex formation, for modulation of the conformational energy landscape of eIF4A by eIF4B, and for stimulating the RNA-dependent ATPase- and ATP-dependent RNA unwinding activities of eIF4A. The isolated r1-7 region only slightly stimulates eIF4A conformational changes and activities, suggesting that communication of the repeats with other regions of eIF4B is required for full stimulation of eIF4A activity, for recruitment of the PIC to the mRNA and for translation initiation.

  13. Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis

    PubMed Central

    Li, Na; Zhang, Jun; Liao, Dan; Yang, Lu; Wang, Yingxiong; Hou, Shengping

    2017-01-01

    Although several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE. PMID:28205620

  14. The Function of HMG-Box Transcription Factors Sox4a and Sox4b in Zebrafish Bone Development and Homeostasis

    NASA Astrophysics Data System (ADS)

    Aceto, J.; Motte, P.; Martial, J. A.; Muller, M.

    2008-06-01

    In mammals, the Sox4 gene is involved in development of endocardial crests, the brain, the lung, teeth, gonads and lymphocytes. Recently, Sox4 was shown to control bone mass and mineralization in mice. In zebrafish, two homologs for the mammalian Sox4 are present, sox4a and sox4b. Here we investigate the function of the sox4a and sox4b genes in cartilage and bone development in zebrafish. Therefore, we focus our attention on the first bone structures to be formed, the head skeleton and more precisely the pharyngeal cartilage. We show that both genes are expressed in the pharyngeal region, albeit at different time points during development. Double in situ hybridization experiments are used to exactly define the particular tissues where they are expressed. Furthermore, microinjection experiments of antisense oligonucleotides are used to block translation of these specific genes and to define their precise function during cartilage and bone development.

  15. The plasma membrane Ca2+ pump isoform 4a differs from isoform 4b in the mechanism of calmodulin binding and activation kinetics: implications for Ca2+ signaling.

    PubMed

    Caride, Ariel J; Filoteo, Adelaida G; Penniston, John T; Strehler, Emanuel E

    2007-08-31

    The inhibition by the regulatory domain and the interaction with calmodulin (CaM) vary among plasma membrane calcium pump (PMCA) isoforms. To explore these differences, the kinetics of CaM effects on PMCA4a were investigated and compared with those of PMCA4b. The maximal apparent rate constant for CaM activation of PMCA4a was almost twice that for PMCA4b, whereas the rates of activation for both isoforms showed similar dependence on Ca2+. The inactivation of PMCA4a by CaM removal was also faster than for PMCA4b, and Ca2+ showed a much smaller effect (2- versus 30-fold modification). The rate constants of the individual steps that determine the overall rates were obtained from stopped-flow experiments in which binding of TA-CaM was observed by changes in its fluorescence. TA-CaM binds to two conformations of PMCA4a, an "open" conformation with high activity, and a "closed" one with lower activity. Compared with PMCA4b (Penheiter, A. R., Bajzer, Z., Filoteo, A. G., Thorogate, R., Török, K., and Caride, A. J. (2003) Biochemistry 41, 12115-12124), the model for PMCA4a predicts less inhibition in the closed form and a much faster equilibrium between the open and closed forms. Based on the available kinetic parameters, we determined the constants to fit the shape of a Ca2+ signal in PMCA4b-overexpressing Chinese hamster ovary cells. Using the constants for PMCA4a, and allowing small variations in parameters of other systems contributing to a Ca2+ signal, we then simulated the effect of PMCA4a on the shape of a Ca2+ signal in Chinese hamster ovary cells. The results reproduce the published data (Brini, M., Coletto, L., Pierobon, N., Kraev, N., Guerini, D., and Carafoli, E. (2003) J. Biol. Chem. 278, 24500-24508), and thereby demonstrate the importance of altered regulatory kinetics for the different functional properties of PMCA isoforms.

  16. 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.

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

    PubMed Central

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

    1990-01-01

    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 (ester vs. amide). 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. Images PMID:2395880

  18. 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

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

    PubMed

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

    2016-10-27

    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.

  20. Purification and characterization of two novel antimicrobial peptides Subpeptin JM4-A and Subpeptin JM4-B produced by Bacillus subtilis JM4.

    PubMed

    Wu, Shimei; Jia, Shifang; Sun, Dandan; Chen, Meiling; Chen, Xiuzhu; Zhong, Jin; Huan, Liandong

    2005-11-01

    An antimicrobial peptides-producing strain was isolated from soil and identified as Bacillus subtilis JM4 according to biochemical tests and 16S rDNA sequence analysis. The corresponding antimicrobial peptides were purified to homogeneity by ammonium sulfate precipitation, sequential SP-Sepharose Fast Flow, Sephadex G-25 and C18 reverse-phase chromatography, and in the final purification step, two active fractions were harvested, designated as Subpeptin JM4-A and Subpeptin JM4-B. The molecular weights, determined by mass spectrometry, were 1422.71 Da for Subpeptin JM4-A and 1422.65 Da for Subpeptin JM4-B, respectively. Amino acid sequencing showed that they differed from each other only at the seventh amino acid except for three unidentified residues, and the two peptides had no significant sequence homology to the known peptides in the database, indicating that they are two novel antimicrobial peptides. In addition, characteristic measurements indicated that both peptides had a relatively broad inhibitory spectrum and remained active over a wide pH and temperature range.

  1. Mutational analysis of genes p14ARF, p15INK4b, p16INK4a, and PTEN in human nervous system tumors.

    PubMed

    Almeida, L O; Custódio, A C; Araújo, J J; Rey, J A; Almeida, J R W; Santos, M J; Clara, C A; Casartelli, C

    2008-05-27

    Cancer is one of the most common and severe problems in clinical medicine, and nervous system tumors represent about 2% of the types of cancer. The central role of the nervous system in the maintenance of vital activities and the functional consequences of the loss of neurons can explain how severe brain cancers are. The cell cycle is a highly complex process, with a wide number of regulatory proteins involved, and such proteins can suffer alterations that transform normal cells into malignant ones. The INK4 family members (CDK inhibitors) are the cell cycle regulators that block the progression of the cycle through the R point, causing an arrest in G1 stage. The p14ARF (alternative reading frame) gene is a tumor suppressor that inhibits p53 degradation during the progression of the cell cycle. The PTEN gene is related to the induction of growth suppression through cell cycle arrest, to apoptosis and to the inhibition of cell adhesion and migration. The purpose of the present study was to assess the mutational state of the genes p14ARF, p15INK4b, p16INK4a, and PTEN in 64 human nervous system tumor samples. Homozygous deletions were found in exon 2 of the p15INK4b gene and exon 3 of the p16INK4a gene in two schwannomas. Three samples showed a guanine deletion (63 codon) which led to a loss of heterozygosity in the p15 gene, and no alterations could be seen in the PTEN gene. Although the group of patients was heterogeneous, our results are in accordance with other different studies that indicate that homozygous deletion and loss of heterozygosity in the INK4 family members are frequently observed in nervous system tumors.

  2. 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.

  3. A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor

    PubMed Central

    Zou, Gang; Puig-Basagoiti, Francesc; Zhang, Bo; Qing, Min; Chen, Liqiang; Pankiewicz, Krzysztof W.; Felczak, Krzysztof; Yuan, Zhiming; Shi, Pei-Yong

    2017-01-01

    Lycorine potently inhibits flaviviruses in cell culture. At 1.2-μM concentration, lycorine reduced viral titers of West Nile (WNV), dengue, and yellow fever viruses by 102- to 104-fold. However, the compound did not inhibit an alphavirus (Western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. The compound exerts its antiviral activity mainly through suppression of viral RNA replication. A Val→Met substitution at the 9th amino acid position of the viral 2K peptide (spanning the endoplasmic reticulum membrane between NS4A and NS4B proteins) confers WNV resistance to lycorine, through enhancement of viral RNA replication. Initial chemistry synthesis demonstrated that modifications of the two hydroxyl groups of lycorine can increase the compound’s potency, while reducing its cytotoxicity. Taken together, the results have established lycorine as a flavivirus inhibitor for antiviral development. The lycorine-resistance results demonstrate a direct role of the 2K peptide in flavivirus RNA synthesis. PMID:19062063

  4. Accidental Conical Intersections in Mixed Trimers of Potassium and Rubidium: a Vibronic Analysis of the 4^4B_2 and 3^4A_1 States

    NASA Astrophysics Data System (ADS)

    Hauser, A. W.; Auböck, G.; Callegari, C.; Ernst, W. E.

    2010-06-01

    We compare the 3^4A_1 and 4^4B_2 states of homonuclear and heteronuclear alkali trimers formed of potassium and rubidium. The Multireference Rayleigh Schrödinger Perturbation Theory of second order is applied to obtain the corresponding adiabatic potential energy surfaces. In the case of homonuclear trimers these pairs of states correspond to the two branches of the E×{}e Jahn-Teller distorted 2^4E^' state. For heteronuclear trimers, the vibrational modes Q_x and Q_y are no longer degenerate, but the two electronic states still show a conical intersection at obtuse (KRb_2) or acute (K_2Rb) isosceles geometries. Spectroscopic consequences of this situation are discussed, vibronic spectra are predicted and compared to LIF spectra obtained in helium droplet isolation spectroscopy experiments of our group. J. Nagl, G. Auböck, A.W. Hauser, O. Allard, C. Callegari and W.E. Ernst, Phys. Rev. Lett. 100, 063001 (2008) J. Nagl, G. Auböck, A.W. Hauser, O. Allard, C. Callegari and W.E. Ernst, J. Chem. Phys. 128, 154320 (2008)

  5. 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

  6. Gene Copy-Number Variations (CNVs) and Protein Levels of Complement C4A and C4B as Novel Biomarkers for Partial Disease Remissions in New-Onset Type 1 Diabetes Patients

    PubMed Central

    Kingery, Suzanne E.; Wu, Yee Ling; Zhou, Bi; Hoffman, Robert P.; Yu, C. Yung

    2014-01-01

    Objective To determine the roles of complement C4A and C4B gene CNVs and their plasma protein concentrations in residual insulin secretion and loss of pancreatic beta-cell function in new-onset type 1 diabetes patients. Methods We studied 34 patients of European ancestry with new-onset type 1 diabetes, aged between 3 and 17 years (10.7±3.45), at Nationwide Children's Hospital in Columbus, Ohio. Gene copy-number and size variations of complement C4A and C4B were determined by genomic Southern blot analyses. C4A and C4B protein phenotypes were elucidated by immunofixation and radial immunodiffusion. Two-digit HLA-DRB1 genotypes were determined by sequence-specific PCR. At 1 month and 9-month post diagnosis, stimulated C-peptide levels were measured after a standardized mixed-meal tolerance test. Results The diploid gene copy-numbers of C4A varied from 0 to 4, and those of C4B from 0 to 3. Patients with higher copy-number of C4A or higher C4A plasma protein concentrations at diagnosis had higher C-peptide levels at 1 month post diagnosis (p=0.008; p=0.008). When controlled by the Z-score of body-mass index, C4A copy-numbers, C4A protein concentrations, the age of disease-onset, the number of HLA-DR3 but not DR4 alleles were significant parameters in determining C-peptide levels. At 9-month post diagnosis, 42.3% of patients remained in partial remission, and these patients were characterized by lower total C4B copy-numbers or lower C4B protein concentrations (p=0.02, p=0.0004). Conclusions C4A appears to associate with the protection of residual beta-cell function in new-onset type 1 diabetes; C4B is correlated with the end of disease remission at 9-month post diagnosis. PMID:22151770

  7. Duplex unwinding and ATPase activities of the DEAD-box helicase eIF4A are coupled by eIF4G and eIF4B.

    PubMed

    Özeş, Ali R; Feoktistova, Kateryna; Avanzino, Brian C; Fraser, Christopher S

    2011-09-30

    Eukaryotic initiation factor (eIF) 4A is a DEAD-box helicase that stimulates translation initiation by unwinding mRNA secondary structure. The accessory proteins eIF4G, eIF4B, and eIF4H enhance the duplex unwinding activity of eIF4A, but the extent to which they modulate eIF4A activity is poorly understood. Here, we use real-time fluorescence assays to determine the kinetic parameters of duplex unwinding and ATP hydrolysis by these initiation factors. To ensure efficient duplex unwinding, eIF4B and eIF4G cooperatively activate the duplex unwinding activity of eIF4A. Our data reveal that eIF4H is much less efficient at stimulating eIF4A unwinding activity than eIF4B, implying that eIF4H is not able to completely substitute for eIF4B in duplex unwinding. By monitoring unwinding and ATPase assays under identical conditions, we demonstrate that eIF4B couples the ATP hydrolysis cycle of eIF4A with strand separation, thereby minimizing nonproductive unwinding events. Using duplex substrates with altered GC contents but similar predicted thermal stabilities, we further show that the rate of formation of productive unwinding complexes is strongly influenced by the local stability per base pair, in addition to the stability of the entire duplex. This finding explains how a change in the GC content of a hairpin is able to influence translation initiation while maintaining the overall predicted thermal stability.

  8. Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients

    PubMed Central

    Lahner, Edith; Brigatti, Cristina; Marzinotto, Ilaria; Carabotti, Marilia; Scalese, Giulia; Davidson, Howard W; Wenzlau, Janet M; Bosi, Emanuele; Piemonti, Lorenzo; Annibale, Bruno; Lampasona, Vito

    2017-01-01

    Objectives: Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls. Methods: One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies. Results: ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (P<0.0001). The area under the receiver-operating characteristic curve was 0.98 (95% CI 0.965–0.996) for ATP4A, and 0.99 (95% CI 0.979–1.000) for ATP4B, both higher as compared with that of EIA: 0.86 (95% CI 0.809–0.896), P<0.0001. Sensitivity-specificity were 100–89% for ATP4A and 100–90% for ATP4B assay. Compared with LIPS, EIA for parietal cell autoantibodies showed a lower sensitivity (72%, P<0.0001) at a similar specificity (92%, P=0.558). Conclusions: Positivity to both, ATP4A and ATP4B autoantibodies is closely associated with atrophic body gastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa. PMID:28102858

  9. 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.

  10. International Conference on Harmonisation; guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 4A on Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests General Chapter; availability. Notice.

    PubMed

    2009-04-08

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 4A: Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests General Chapter." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides the results of the ICH Q4B evaluation of the Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests General Chapter harmonized text from each of the three pharmacopoeias (United States, European, and Japanese) represented by the Pharmacopoeial Discussion Group (PDG). The guidance conveys recognition of the three pharmacopoeial methods by the three ICH regulatory regions and provides specific information regarding the recognition. The guidance is intended to recognize the interchangeability between the local regional pharmacopoeias, thus avoiding redundant testing in favor of a common testing strategy in each regulatory region. In the Federal Register of February 21, 2008 (73 FR 9575), FDA made available a guidance on the Q4B process entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions."

  11. 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.

  12. Conspirators in a capital crime: co-deletion of p18INK4c and p16INK4a/p14ARF/p15INK4b in glioblastoma multiforme.

    PubMed

    Solomon, David A; Kim, Jung-Sik; Jean, Walter; Waldman, Todd

    2008-11-01

    Glioblastoma multiforme (GBM) is one of the most dreaded cancer diagnoses due to its poor prognosis and the limited treatment options. Homozygous deletion of the p16(INK4a)/p14(ARF)/p15(INK4b) locus is among the most common genetic alterations in GBM. Two recent studies have shown that deletion and mutation of another INK4 family member, p18(INK4c), also drives the pathogenesis of GBM. This minireview will discuss the known roles for p18(INK4c) in the initiation and progression of cancer and suggest opportunities for future studies.

  13. Results of hydrologic tests and water-chemistry analyses, wells H-4A, H-4B, and H-4C, at the proposed waste isolation pilot plant site, southeastern New Mexico

    USGS Publications Warehouse

    Mercer, Jerry W.; Davis, Paul; Dennehy, K.F.; Goetz, C.L.

    1981-01-01

    Data were collected during hydrologic testing at wells H-4A, H-4B, and H-4C in the southern part of the proposed Waste Isolation Pilot Plant site in southeastern New Mexico. The three water-bearing zones tested, the Magenta and Culebra Dolomite Members of the Rustler Formation and the Rustler Formation-Salado Formation contact, yield water to wells at rates less than 0.9 gallon per minute. Throughout the testing, water-pressure response in the tested zone was monitored by a pressure transducer system. Shut-in and slug tests were conducted to acquire the data from which the following values were derived. Calculated transmissivities for the Magenta, Culebra and the Rustler-Salado contact at wells H-4A, H-4B, and H-4C were 0.06, 0.9, and 0.0006 foot squared per day respectively. Water samples from the Magenta and Culebra had dissolved-solids concentrations of 22,300 and 18,100 milligrams per liter, respectively. The major chemical constituents of ground-water samples from these two zones were sodium, chloride, and sulfate. Water samples from the Rustler-Salado contact had a dissolved-solids concentration of 322,000 milligrams per liter and magnesium, sodium, and chloride were the major constituents. Radium-226, a naturally occurring radioactive element, was present in samples from all three zones. (USGS)

  14. Species-specific but not genotype-specific primary and secondary isotype-specific NSP4 antibody responses in gnotobiotic calves and piglets infected with homologous host bovine (NSP4[A]) or porcine (NSP4[B]) rotavirus.

    PubMed

    Yuan, Lijuan; Honma, Shinjiro; Ishida, Shin-Ichi; Yan, Xiao-Yi; Kapikian, Albert Z; Hoshino, Yasutaka

    2004-12-05

    Using recombinant baculoviruses expressing rotavirus NSP4 [A], [B], [C], and [D] genotypes of bovine, porcine, human, simian, or murine origin, we analyzed serum antibody responses to NSP4s in gnotobiotic calves and piglets infected by the oral/alimentary or intraamniotic route with bovine (NSP4[A]) (Wyatt, R.G., Mebus, C.A., Yolken, R.H., Kalica, A.R., James, H.D., Jr., Kapikian, A.Z., Chanock, R.M., 1979. Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus. Science 203(4380), 548-550) or porcine (NSP4[B]) (Hoshino, Y., Saif, L.J., Sereno, M.M., Chanock, R.M., Kapikian, A.Z., 1988. Infection immunity of piglets to either VP3 or VP7 outer capsid protein confers resistance to challenge with a virulent rotavirus bearing the corresponding antigen. J. Virol. 62(3), 744-748) rotaviruses. Following primary infection and challenge with virulent rotaviruses, the animals developed higher or significantly higher antibody titers to homologous host homotypic NSP4s than to heterologous host homotypic or heterologous host heterotypic NSP4s, indicating that antibody responses were species specific rather than genotype specific. Antibody responses to NSP4s corresponded closely with the phylogenetic relationships of NSP4s within a species-specific region of amino acids (aa) 131-141. In contrast, NSP4 genotypes determined by amino acid full-length sequence identity predicted poorly their "serotypes". In piglets, antibodies to NSP4 induced by previous oral infection failed to confer protection against challenge from a porcine rotavirus bearing serotypically different VP4 and VP7 but essentially identical NSP4 to the porcine rotavirus in primary infection. Thus, in an approach to immunization with a live oral rotavirus vaccine, the NSP4 protein does not appear to play an important role in protection against rotavirus disease and infection.

  15. Deregulated E2F-1 blocks terminal differentiation and loss of leukemogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and p16(INK4A).

    PubMed

    Amanullah, A; Hoffman, B; Liebermann, D A

    2000-07-15

    The transcription factor E2F-1 has been postulated to play a crucial role in the control of cell cycle progression because of its ability to be bound and regulated by the retinoblastoma gene product (pRb). Exogenous expression of E2F-1, under growth restrictive conditions, was shown to result in p53-dependent programmed cell death. The consequences of deregulated expression of E2F-1 on terminal differentiation of hematopoietic cells in the absence of E2F-1-mediated apoptosis, as well as mechanistic insights into how deregulated E2F-1 may affect terminal differentiation, have not been established. The autonomously proliferating M1 myeloblastic leukemia cell line, which is null for p53 expression and can be induced by interleukin-6 (IL-6) to undergo terminal macrophage differentiation with concomitant loss of leukemogenicity, provides a particularly attractive model system to address these issues. Deregulated and continued expression of E2F-1 blocked the IL-6-induced terminal differentiation program at an early blast stage, giving rise to immature cells, which continued to proliferate without undergoing apoptosis and retained their leukemogenic phenotype. Although E2F-1 blocked IL-6-mediated terminal differentiation and its associated growth arrest, it did not prevent the rapid induction of both p15(INK4B) and p16(INK4A), inhibition of cdk4 kinase activity, and subsequent hypophosphorylation of pRb. The results obtained imply that genetic alterations that both impair p53 function and deregulate E2F-1 expression may render hematopoietic cells refractory to the induction of differentiation and are, thereby, likely to play a major role in the progression of leukemias. (Blood. 2000;96:475-482)

  16. 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.

  17. Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine.

    PubMed

    Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; Khan, Amir S; Sardesai, Niranjan Y; Welles, Seth L; Jacobson, Jeffrey M; Weiner, David B; Kutzler, Michele A

    2014-01-01

    Chronic HCV is a surreptitious disease currently affecting approximately 3% of the world's population that can lead to liver failure and cancer decades following initial infection. However, there are currently no vaccines available for the prevention of chronic HCV. From patients who acutely resolve HCV infection, it is apparent that a strong and broad cytotoxic T lymphocyte (CTL) response is important in HCV clearance. DNA vaccines are naked plasmid DNA molecules that encode pathogen antigens to induce a pathogen-specific immune response. They are inexpensive to produce and have an excellent safety profile in animals and humans. Additionally, DNA vaccines are able to induce strong CTL responses, making them well-suited for an HCV vaccine. We aimed to maximize vaccine recipients' opportunity to induce a broad T cell response with a novel antigenic sequence, multi-antigen vaccine strategy. We have generated DNA plasmids encoding consensus sequences of HCV genotypes 1a and 1b non-structural proteins NS3/4a, NS4b, NS5a, and NS5b. Rhesus macaques were used to study the immunogenicity of these constructs. Four animals were immunized 3 times, 6 weeks apart, at a dose of 1.0mg per antigen construct, as an intramuscular injection followed by in vivo electroporation, which greatly increases DNA uptake by local cells. Immune responses were measured 2 weeks post-immunization regimen (PIR) in immunized rhesus macaques and showed a broad response to multiple HCV nonstructural antigens, with up to 4680 spot-forming units per million peripheral blood mononuclear cells (PBMCs) as measured by Interferon-γ ELISpot. In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements. At the final study time point, 6 weeks PIR, HCV-specific CD45RA- memory-like T cells

  18. 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.

  19. Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)

    PubMed Central

    Zhang, Han-Ting; Huang, Ying; Masood, Anbrin; Stolinski, Lisa R; Li, Yunfeng; Zhang, Lei; Dlaboga, Daniel; Jin, S-L Catherine; Conti, Marco; O’Donnell, James M

    2009-01-01

    Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression- and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4B−/−). Immunoblot analysis revealed loss of PDE4B expression in the cerebral cortex and amygdala of PDE4B−/− mice. The reduction of PDE4B expression was accompanied by decreases in PDE4 activity in the brain regions of PDE4B−/− mice. Compared to PDE4B + / + littermates, PDE4B−/− mice displayed anxiogenic-like behavior, as evidenced by decreased head-dips and time spent in head-dipping in the holeboard test, reduced transitions and time on the light side in the light–dark transition test, and decreased initial exploration and rears in the open-field test. Consistent with anxiogenic-like behavior, PDE4B−/− mice displayed increased levels of plasma corticosterone. In addition, these mice also showed a modest increase in the proliferation of neuronal cells in the hippocampal dentate gyrus. In the forced-swim test, PDE4B−/− mice exhibited decreased immobility; however, this was not supported by the results from the tail-suspension test. PDE4B−/− mice did not display changes in memory, locomotor activity, or nociceptive responses. Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior PMID:17700644

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  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. Familial C4B Deficiency and Immune Complex Glomerulonephritis

    PubMed Central

    Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY

    2010-01-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617

  7. Familial C4B deficiency and immune complex glomerulonephritis.

    PubMed

    Soto, K; Wu, Y L; Ortiz, A; Aparício, S R; Yu, C Y

    2010-10-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Critical review of host specificity and its coevolutionary implications in the fig/fig-wasp mutualism

    PubMed Central

    Machado, Carlos A.; Robbins, Nancy; Gilbert, M. Thomas P.; Herre, Edward Allen

    2005-01-01

    Figs (Ficus spp., Moraceae) and their pollinating wasps (Agaonidae, Chalcidoidea) constitute perhaps the most tightly integrated pollination mutualism that is known. Figs are characterized by extraordinarily high global and local species diversity. It has been proposed that the diversification of this mutualism has occurred through strict-sense coadaptation and cospeciation between pairs of fig and wasp species that are associated in highly specific one-to-one relationships. However, existing studies cast doubt on the generality of this proposition. Here, we review our current knowledge of the evolutionary history of the fig/fig-wasp mutualism. We critically examine the idea that codivergence between figs and their pollinators has been dominated by strict-sense cospeciation. We present phylogenetic and population genetic data from neotropical fig and fig wasp species that suggest that a more accurate model for diversification in this mutualism is that of groups of genetically well defined wasp species coevolving with genetically less well defined (frequently hybridizing) groups of figs. Last, we use our results to assess previously proposed hypotheses on models of speciation in this mutualism. PMID:15851680

  14. 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

    2011-10-07

    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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23515979

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

    PubMed Central

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

    2016-01-01

    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 of Cul4a in mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4b germ cell-specific conditional knock-out (Cul4bVasa),as well as Cul4b global knock-out (Cul4bSox2) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4b led 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, Cul4bVasa 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, Cul4b global 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Structural Basis for the Design of Selective Phosphodiesterase 4B Inhibitors

    PubMed Central

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

    2014-01-01

    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

  4. 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

  5. 21 CFR 145.131 - Artificially sweetened canned figs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Artificially sweetened canned figs. 145.131... § 145.131 Artificially sweetened canned figs. (a) Artificially sweetened canned figs is the food which conforms to the definition and standard of identity prescribed for canned figs by § 145.130, except that...

  6. [Anaphylactic reaction to Ficus benjamina (weeping fig)].

    PubMed

    Werfel, S; Ruëff, F; Przybilla, B

    2001-10-01

    Ficus benjamina (weeping fig) is a widespread indoor ornamental plant. Allergens of Ficus benjamina are a well-known cause of IgE-mediated respiratory diseases. We treated a 32-year-old female who for 10 years had suffered from perennial rhinoconjunctivitis. When dusting her 2 meter high Ficus benjamina, she developed an anaphylactic reaction which resolved without sequelae. Skin prick testing revealed a strong immediate type reaction to a Ficus extract, the serum concentration of specific IgE-antibodies to Ficus was > 100 kU/I (CAP class 6). In view of these strong test reactions and the conclusive history, no challenge tests with Ficus allergens were performed. After removal of the Ficus plants which she had owned for 17 years and after thorough cleaning of her dwelling, the patient's symptoms of perennial rhinoconjunctivitis stopped. The patient also was sensitized to, but not allergic to natural rubber latex, which occurs frequently in Ficus allergy and probably is due to cross reactivity to allergens from both sources. As Ficus benjamina is an important source of indoor allergens, it should not be used in dwellings or work places.

  7. Host sanctions and pollinator cheating in the fig tree–fig wasp mutualism

    PubMed Central

    Jandér, K. Charlotte; Herre, Edward Allen

    2010-01-01

    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. PMID:20071379

  8. 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.

  9. 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.

  10. Nematodes Associated with Fig Wasps, Pegoscapus spp. (Agaonidae), and Syconia of Native Floridian Figs (Ficus spp.)

    PubMed Central

    Giblin-Davis, Robin M.; Center, Barbara J.; Nadel, Hannah; Frank, J. Howard; Ramírez B., William

    1995-01-01

    Syconia in successive developmental phases from Ficus laevigata Vahl (F. citrifolia Miller sensu DeWolf 1960) (Moraceae) and successive life stages of its fig wasp pollinator, Pegoscapus sp. (P. assuetus (Grandi) sensu Wiebes 1983) (Agaonidae) were dissected to elucidate their association with two undescribed species of nematodes. Parasitodiplogazter sp. (Diplogasteridae) are transported by female Pegoscapus sp. into the cavity of a phase B syconium as third-stage juveniles (J3), where they molt to the J4 stage and greatly increase in size in the hemocoel of the fig wasp after it begins to pollinate and oviposit in female florets. The J4 exit the wasp cadaver in a phase B or early phase C syconium, and molt to adults that mate and lay eggs. New J3 infect the next generation of female or male wasps as they emerge from their galls in phase D figs. Mated entomogenous females of Schistonchus sp. (Aphelenchoididae) are transported in the hemocoel of female wasps to the fig cavity of a phase B syconium. Female Schistonchus sp. exit the wasp and parasitize immature male florets causing an exudate, the development of hypertrophied epidermal cells of the anther filaments and anthers, and aberrations of the anther filament, anthers, and pollen. At least one generation of Schistonchus sp. occurs in the male florets. Entomogenous females appear at about the time that fig wasps molt to adults in their galls in late phase C syconia. Another Schistonchus sp. was recovered from females of P. mexicanus (Ashmead) (P. jimenezi (Grandi) sensu Wiebes 1983) and from the syconia of F. aurea Nuttall and appears to have a life cycle similar to that described for the Schistonchus sp. from F. laevigata. PMID:19277255

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. Effect of moisture content on textural attributes of dried figs

    NASA Astrophysics Data System (ADS)

    Ansari, Sara; Maftoon-Azad, Neda; Farahnaky, Asgar; Hosseini, Ebrahim; Badii, Fojan

    2014-10-01

    Due to their soft texture consumers prefer moist figs, which has motivated fig processors to increase the production of this product. However, as water enhances the browning reaction rate, moisture content optimisation of moist figs is very important. Processed figs must have suitable texture softness with browning kept to a minimum. The purpose of this study was to examine the effect of moisture content on the textural attributes of dried figs. Hardness, compression energy, gradient, gumminess and chewiness of fig samples decreased with moisture content exponentially, whereas the trend of springiness and cohesiveness with change of moisture content was nearly constant. Moreover, in the texture profile analysis plot of rehydrated figs, the presence of negative area is an indication of adhesiveness which was zero in control dried figs. The results of the texture profile analysis tests proved the existence of a critical moisture content of about 18.4%, above which no significant effect of moisture content on textural parameters was found. The glass-rubber transition results from differential scanning calorimeter may explain the different texture profile analysis attributes of dried figs compared with rehydrated figs.

  18. 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.

  19. Accelerated hepatocellular carcinoma development in CUL4B transgenic mice.

    PubMed

    Yuan, Jupeng; Jiang, Baichun; Zhang, Aizhen; Qian, Yanyan; Tan, Haining; Gao, Jiangang; Shao, Changshun; Gong, Yaoqin

    2015-06-20

    Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase (CRL4B) complex that functions in proteolysis and in epigenetic regulation. CUL4B possesses tumor-promoting properties and is markedly upregulated in many types of human cancers. To determine the role of CUL4B in liver tumorigenesis, we generated transgenic mice that expressed human CUL4B in livers and other tissues and evaluated the development of spontaneous and chemically-induced hepatocellular carcinomas. We observed that CUL4B transgenic mice spontaneously developed liver tumors at a high incidence at old ages and exhibited enhanced DEN-induced hepatocarcinogenesis. There was a high proliferation rate in the livers of CUL4B transgenic mice that was accompanied by increased levels of Cdk1, Cdk4 and cyclin D1 and decreased level of p16. The transgenic mice also exhibited increased compensatory proliferation after DEN-induced liver injury, which was accompanied by activation of Akt, Erk, p38 and NF-κB. We also found that Prdx3 was downregulated and that DEN induced a higher level of reactive oxygen species in the livers of transgenic mice. Together, our results demonstrate a critical role of CUL4B in hepatocarcinogenesis in mice.

  20. FIG4 regulates lysosome membrane homeostasis independent of phosphatase function.

    PubMed

    Bharadwaj, Rajnish; Cunningham, Kathleen M; Zhang, Ke; Lloyd, Thomas E

    2016-02-15

    FIG4 is a phosphoinositide phosphatase that is mutated in several diseases including Charcot-Marie-Tooth Disease 4J (CMT4J) and Yunis-Varon syndrome (YVS). To investigate the mechanism of disease pathogenesis, we generated Drosophila models of FIG4-related diseases. Fig4 null mutant animals are viable but exhibit marked enlargement of the lysosomal compartment in muscle cells and neurons, accompanied by an age-related decline in flight ability. Transgenic animals expressing Drosophila Fig4 missense mutations corresponding to human pathogenic mutations can partially rescue lysosomal expansion phenotypes, consistent with these mutations causing decreased FIG4 function. Interestingly, Fig4 mutations predicted to inactivate FIG4 phosphatase activity rescue lysosome expansion phenotypes, and mutations in the phosphoinositide (3) phosphate kinase Fab1 that performs the reverse enzymatic reaction also causes a lysosome expansion phenotype. Since FIG4 and FAB1 are present together in the same biochemical complex, these data are consistent with a model in which FIG4 serves a phosphatase-independent biosynthetic function that is essential for lysosomal membrane homeostasis. Lysosomal phenotypes are suppressed by genetic inhibition of Rab7 or the HOPS complex, demonstrating that FIG4 functions after endosome-to-lysosome fusion. Furthermore, disruption of the retromer complex, implicated in recycling from the lysosome to Golgi, does not lead to similar phenotypes as Fig4, suggesting that the lysosomal defects are not due to compromised retromer-mediated recycling of endolysosomal membranes. These data show that FIG4 plays a critical noncatalytic function in maintaining lysosomal membrane homeostasis, and that this function is disrupted by mutations that cause CMT4J and YVS.

  1. FIG4 regulates lysosome membrane homeostasis independent of phosphatase function

    PubMed Central

    Bharadwaj, Rajnish; Cunningham, Kathleen M.; Zhang, Ke; Lloyd, Thomas E.

    2016-01-01

    FIG4 is a phosphoinositide phosphatase that is mutated in several diseases including Charcot-Marie-Tooth Disease 4J (CMT4J) and Yunis-Varon syndrome (YVS). To investigate the mechanism of disease pathogenesis, we generated Drosophila models of FIG4-related diseases. Fig4 null mutant animals are viable but exhibit marked enlargement of the lysosomal compartment in muscle cells and neurons, accompanied by an age-related decline in flight ability. Transgenic animals expressing Drosophila Fig4 missense mutations corresponding to human pathogenic mutations can partially rescue lysosomal expansion phenotypes, consistent with these mutations causing decreased FIG4 function. Interestingly, Fig4 mutations predicted to inactivate FIG4 phosphatase activity rescue lysosome expansion phenotypes, and mutations in the phosphoinositide (3) phosphate kinase Fab1 that performs the reverse enzymatic reaction also causes a lysosome expansion phenotype. Since FIG4 and FAB1 are present together in the same biochemical complex, these data are consistent with a model in which FIG4 serves a phosphatase-independent biosynthetic function that is essential for lysosomal membrane homeostasis. Lysosomal phenotypes are suppressed by genetic inhibition of Rab7 or the HOPS complex, demonstrating that FIG4 functions after endosome-to-lysosome fusion. Furthermore, disruption of the retromer complex, implicated in recycling from the lysosome to Golgi, does not lead to similar phenotypes as Fig4, suggesting that the lysosomal defects are not due to compromised retromer-mediated recycling of endolysosomal membranes. These data show that FIG4 plays a critical noncatalytic function in maintaining lysosomal membrane homeostasis, and that this function is disrupted by mutations that cause CMT4J and YVS. PMID:26662798

  2. 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

  3. 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.

  4. 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.

  5. Variants in CUL4B are Associated with Cerebral Malformations

    PubMed Central

    Vulto-van Silfhout, Anneke T.; Nakagawa, Tadashi; Bahi-Buisson, Nadia; Haas, Stefan A.; Hu, Hao; Bienek, Melanie; Vissers, Lisenka E.L.M.; Gilissen, Christian; Tzschach, Andreas; Busche, Andreas; Müsebeck, Jörg; Rump, Patrick; Mathijssen, Inge B.; Avela, Kristiina; Somer, Mirja; Doagu, Fatma; Philips, Anju K.; Rauch, Anita; Baumer, Alessandra; Voesenek, Krysta; Poirier, Karine; Vigneron, Jacqueline; Amram, Daniel; Odent, Sylvie; Nawara, Magdalena; Obersztyn, Ewa; Lenart, Jacek; Charzewska, Agnieszka; Lebrun, Nicolas; Fischer, Ute; Nillesen, Willy M.; Yntema, Helger G.; Järvelä, Irma; Ropers, Hans-Hilger; de Vries, Bert B.A.; Brunner, Han G.; van Bokhoven, Hans; Raymond, F. Lucy; Willemsen, Michèl A.A.P.; Chelly, Jamel; Xiong, Yue; Barkovich, A. James; Kalscheuer, Vera M.; Kleefstra, Tjitske; de Brouwer, Arjan P.M.

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B. PMID:25385192

  6. Variants in CUL4B are associated with cerebral malformations.

    PubMed

    Vulto-van Silfhout, Anneke T; Nakagawa, Tadashi; Bahi-Buisson, Nadia; Haas, Stefan A; Hu, Hao; Bienek, Melanie; Vissers, Lisenka E L M; Gilissen, Christian; Tzschach, Andreas; Busche, Andreas; Müsebeck, Jörg; Rump, Patrick; Mathijssen, Inge B; Avela, Kristiina; Somer, Mirja; Doagu, Fatma; Philips, Anju K; Rauch, Anita; Baumer, Alessandra; Voesenek, Krysta; Poirier, Karine; Vigneron, Jacqueline; Amram, Daniel; Odent, Sylvie; Nawara, Magdalena; Obersztyn, Ewa; Lenart, Jacek; Charzewska, Agnieszka; Lebrun, Nicolas; Fischer, Ute; Nillesen, Willy M; Yntema, Helger G; Järvelä, Irma; Ropers, Hans-Hilger; de Vries, Bert B A; Brunner, Han G; van Bokhoven, Hans; Raymond, F Lucy; Willemsen, Michèl A A P; Chelly, Jamel; Xiong, Yue; Barkovich, A James; Kalscheuer, Vera M; Kleefstra, Tjitske; de Brouwer, Arjan P M

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B.

  7. 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.

  8. The early regulation of figs in the United States.

    PubMed

    Young, J H

    1999-01-01

    When the Food and Drugs Act became law in 1906, the commercial fig industry in California had just become established. Domestic figs began to compete with imported figs, especially from Turkey and Greece. Fig culture, both in the Near East and the American West, was beset by many threats, especially insect pests. The Bureau of Chemistry in the U.S. Department of Agriculture (USDA), enforcer of the 1906 law, undertook to protect consumers from spoiled figs from overseas and in interstate commerce. Simultaneously the USDA helped both domestic and Turkish growers to counter infestation. Through the State Department, sanitary controls in Smyrna were enhanced. Scientific experts from Agriculture educated American growers and packers in protective techniques. A high point of both legal actions and educational endeavors came in the late 1920s. In the 1930s, the state of California assumed the role of guiding inspection and helping dispose of substandard figs. World War II brought retrogression in fig quality, requiring a new corrective campaign by the Food and Drug Administration, successor to the Bureau of Chemistry, to prevent spoiled figs from reaching the market. By the 1950s, the need for such legal actions was rare.

  9. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 17 microsatellite loci. The collection showed considerable polymorphism with ...

  11. One fig to bind them all: host conservatism in a fig wasp community unraveled by cospeciation analyses among pollinating and nonpollinating fig wasps.

    PubMed

    Jousselin, Emmanuelle; van Noort, Simon; Berry, Vincent; Rasplus, Jean-Yves; Rønsted, Nina; Erasmus, J Christoff; Greeff, Jaco M

    2008-07-01

    The study of chalcid wasps that live within syconia of fig trees (Moraceae, Ficus), provides a unique opportunity to investigate the evolution of specialized communities of insects. By conducting cospeciation analyses between figs of section Galoglychia and some of their associated fig wasps, we show that, although host switches and duplication have evidently played a role in the construction of the current associations, the global picture is one of significant cospeciation throughout the evolution of these communities. Contrary to common belief, nonpollinating wasps are at least as constrained as pollinators by their host association in their diversification in this section. By adapting a randomization test in a supertree context, we further confirm that wasp phylogenies are significantly congruent with each other, and build a "wasp community" supertree that retrieves Galoglychia taxonomic subdivisions. Altogether, these results probably reflect wasp host specialization but also, to some extent, they might indicate that niche saturation within the fig prevents recurrent intrahost speciation and host switching. Finally, a comparison of ITS2 sequence divergence of cospeciating pairs of wasps suggests that the diversification of some pollinating and nonpollinating wasps of Galoglychia figs has been synchronous but that pollinating wasps exhibit a higher rate of molecular evolution.

  12. 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.

  13. 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...

  14. 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

  15. 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...

  16. Phosphorylation of mammalian initiation factor eIF-4B

    SciTech Connect

    Duncan, R.F.; Milburn, S.C.; Cooper, R.; Gould, K.; Hunter, T.; Hershey, J.W.B.

    1987-05-01

    The phosphorylation of initiation factors appears to be an important mechanism for regulating the rate of translation in mammalian cells. eIF-4B (80 kDa) purified from HeLa cells exhibits a complex array of 8 to 12 spots when analyzed by 2-dimensional isoelectric focusing - SDS polyacrylamide gel electrophoresis. A similar array of eIF-4B spots is seen when total lysate proteins are analyzed by immunoblotting with anti-eIF-4B antiserum or with antibodies affinity-purified from the most basic eIF-4B spot. The multiple forms of eIF-4B are due to phosphorylation, since all but the most basic spot are labeled with (/sup 32/P)phosphate in vivo and the action of alkaline phosphatase in vitro reduces the array to only two spots. Tryptic peptide maps of phosphopeptides from each of the various isoelectric variants of eIF-4B show a similar complexity, suggesting that a number of different sites are phosphorylated in a random order. When serum-deprived HeLa cells are treated with phorbol ester, both the protein synthesis rate and the extent of eIF-4B phosphorylation increase, suggesting that C kinase may be a regulator of translation. Purified C kinase phosphorylates a number of pure initiation factors in vitro, but eIF-4B is the strongest target protein. When pure eIF-4B is treated, the entire mass of eIF-4B is shifted to the most acidic spots, indicating very strong phosphorylation. Attempts are being made to detect differences in the in vitro activities of the non-phosphorylated and highly phosphorylated forms.

  17. Discriminative host sanctions in a fig-wasp mutualism.

    PubMed

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

    2014-05-01

    In some mutualisms, cooperation in symbionts is promoted by hosts sanctioning "cheats," who obtain benefits but fail to reciprocate. In fig-wasp mutualisms, agaonid wasps pollinate the trees (Ficus spp.), but are also exploitative by using some flowers as larval food. Ficus can sanction cheats that fail to pollinate by aborting some un-pollinated figs. However, in those un-pollinated figs retained by trees, cheats successfully reproduce. When this occurs, wasp broods are reduced, suggesting sanctions increase offspring mortality within un-pollinated figs. We investigated sanction mechanisms of abortion and larval mortality against wasp cheats in the monoecious Ficus racemosa by introducing into figs 1, 3, 5, 7, or 9 female wasps (foundresses) that were either all pollen-laden (P+) or all pollen-free (P-). The abortion rates of P- figs were highest (-60%) when single foundresses were present. Abortion declined with increased foundresses and ceased with seven or more wasps present, irrespective of pollination. In un-aborted figs, wasp fitness (mean offspring per foundress) declined as foundress number increased, especially in P- figs. Reduced broods in P- figs resulted from increased larval mortality of female offspring as foundress number increased, resulting in more male-biased sex ratios. Overall sanctions estimated from both abortion rates and reduced offspring production strengthened as the number of cheats increased. In a second experiment, we decoupled pollination from wasp oviposition by introducing one pollen-free foundress, followed 24 h later by seven pollen-laden ovipositor-excised wasps. Compared with P+ and P- single-foundress figs, delayed pollination resulted in intermediate larval mortality and wasp fitness, which concurred with patterns of female offspring production. We conclude that fig abortion reflects both pollinator numbers and pollen presence. Sanctions within P- figs initiate soon after oviposition and discriminate against female offspring

  18. Pollinating fig wasps: genetic consequences of island recolonization.

    PubMed

    Zavodna, Monika; Arens, Paul; Van Dijk, Peter J; Partomihardjo, Tukirin; Vosman, Ben; Van Damme, Jos M M

    2005-09-01

    The levels of genetic diversity and gene flow may influence the long-term persistence of populations. Using microsatellite markers, we investigated genetic diversity and genetic differentiation in island (Krakatau archipelago, Indonesia) and mainland (Java and Sumatra, Indonesia) populations of Liporrhopalum tentacularis and Ceratosolen bisulcatus, the fig wasp pollinators of two dioecious Ficus (fig tree) species. Genetic diversity in Krakatau archipelago populations was similar to that found on the mainland. Population differentiation between mainland coastal sites and the Krakatau islands was weak in both wasp species, indicating that the intervening 40 km across open sea may not be a barrier for wasp gene flow (dispersal) and colonization of the islands. Surprisingly, mainland populations of the fig waSPS may be more genetically isolated than the islands, as gene flow between populations on the Javan mainland differed between the two wasp species. Contrasting growth forms and relative 'immunity' to the effects of deforestation in their host fig trees may account for these differences.

  19. 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.

  20. 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

  1. Category 4b - A Regulatory Alternative to TMDLs

    EPA Pesticide Factsheets

    The paper describes the extent to which states have successfully employed TMDL alternatives to address impaired waters and assigned these waters to Category 4b, and includes several Washington State examples.

  2. 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.

  3. Nanog regulates primordial germ cell migration through Cxcr4b.

    PubMed

    Sánchez-Sánchez, Ana Virginia; Camp, Esther; Leal-Tassias, Aránzazu; Atkinson, Stuart P; Armstrong, Lyle; Díaz-Llopis, Manuel; Mullor, José L

    2010-09-01

    Gonadal development in vertebrates depends on the early determination of primordial germ cells (PGCs) and their correct migration to the sites where the gonads develop. Several genes have been implicated in PGC specification and migration in vertebrates. Additionally, some of the genes associated with pluripotency, such as Oct4 and Nanog, are expressed in PGCs and gonads, suggesting a role for these genes in maintaining pluripotency of the germ lineage, which may be considered the only cell type that perpetually maintains stemness properties. Here, we report that medaka Nanog (Ol-Nanog) is expressed in the developing PGCs. Depletion of Ol-Nanog protein causes aberrant migration of PGCs and inhibits expression of Cxcr4b in PGCs, where it normally serves as the receptor of Sdf1a to guide PGC migration. Moreover, chromatin immunoprecipitation analysis demonstrates that Ol-Nanog protein binds to the promoter region of Cxcr4b, suggesting a direct regulation of Cxcr4b by Ol-Nanog. Simultaneous overexpression of Cxcr4b mRNA and depletion of Ol-Nanog protein in PGCs rescues the migration defective phenotype induced by a loss of Ol-Nanog, whereas overexpression of Sdf1a, the ligand for Cxcr4b, does not restore proper PGC migration. These results indicate that Ol-Nanog mediates PGC migration by regulating Cxcr4b expression.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. A Genetic Interaction between Hepatitis C Virus NS4B and NS3 Is Important for RNA Replication▿

    PubMed Central

    Paredes, Anne M.; Blight, Keril J.

    2008-01-01

    Hepatitis C virus (HCV) nonstructural protein 4B (NS4B), a poorly characterized integral membrane protein, is thought to function as a scaffold for replication complex assembly; however, functional interactions with the other HCV nonstructural proteins within this complex have not been defined. We report that a Con1 chimeric subgenomic replicon containing the NS4B gene from the closely related H77 isolate is defective for RNA replication in a transient assay, suggesting that H77 NS4B is unable to productively interact with the Con1 replication machinery. The H77 NS4B sequences that proved detrimental for Con1 RNA replication resided in the predicted N- and C-terminal cytoplasmic domains as well as the central transmembrane region. Selection for Con1 derivatives that could utilize the entire H77 NS4B or hybrid Con1-H77 NS4B proteins yielded mutants containing single amino acid substitutions in NS3 and NS4A. The second-site mutations in NS3 partially restored the replication of Con1 chimeras containing the N-terminal or transmembrane domains of H77 NS4B. In contrast, the deleterious H77-specific sequences in the C terminus of NS4B, which mapped to a cluster of four amino acids, were completely suppressed by second-site substitutions in NS3. Collectively, these results provide the first evidence for a genetic interaction between NS4B and NS3 important for productive HCV RNA replication. PMID:18715921

  10. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... section are whole mature figs of the light or dark varieties that may be either peeled or unpeeled. (c)(1... words “Preserved Figs”, but there shall be no intervening written, printed, or graphic matter, and the... precede or follow such name without intervening written, printed, or graphic matter, except that...

  11. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... section are whole mature figs of the light or dark varieties that may be either peeled or unpeeled. (c)(1... words “Preserved Figs”, but there shall be no intervening written, printed, or graphic matter, and the... precede or follow such name without intervening written, printed, or graphic matter, except that...

  12. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... section are whole mature figs of the light or dark varieties that may be either peeled or unpeeled. (c)(1... words “Preserved Figs”, but there shall be no intervening written, printed, or graphic matter, and the... precede or follow such name without intervening written, printed, or graphic matter, except that...

  13. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... section are whole mature figs of the light or dark varieties that may be either peeled or unpeeled. (c)(1... words “Preserved Figs”, but there shall be no intervening written, printed, or graphic matter, and the... precede or follow such name without intervening written, printed, or graphic matter, except that...

  14. 21 CFR 145.134 - Canned preserved figs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... section are whole mature figs of the light or dark varieties that may be either peeled or unpeeled. (c)(1... words “Preserved Figs”, but there shall be no intervening written, printed, or graphic matter, and the... precede or follow such name without intervening written, printed, or graphic matter, except that...

  15. 21 CFR 145.131 - Artificially sweetened canned figs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Artificially sweetened canned figs. 145.131 Section 145.131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CANNED FRUITS Requirements for Specific Standardized Canned...

  16. 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.

  17. 21 CFR 145.131 - Artificially sweetened canned figs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... artificially sweetened food is subject to the requirements for label statement of ingredients used, as... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Artificially sweetened canned figs. 145.131 Section 145.131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  18. 21 CFR 145.131 - Artificially sweetened canned figs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... artificially sweetened food is subject to the requirements for label statement of ingredients used, as... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Artificially sweetened canned figs. 145.131 Section 145.131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  19. 21 CFR 145.131 - Artificially sweetened canned figs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... artificially sweetened food is subject to the requirements for label statement of ingredients used, as... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Artificially sweetened canned figs. 145.131 Section 145.131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

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

    PubMed Central

    Stover, Ed; Velasco, Dianne; Koehmstedt, Anne

    2010-01-01

    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 (HG/HT = 0.853; 85.3%) and the among groups within total component (GGT = 0.147) accounted for the remaining 14.7%, of which ~64% accounted for among groups within clusters (GGC = 0.094) and ~36% among clusters (GCT = 0.053). The analysis of molecular variance (AMOVA) showed approximately similar results with nearly 87% of variation within groups and ~10% among groups within clusters, and ~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 with widespread dispersal of cultivars with many synonyms

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. RAMONA-4B code for BWR systems analysis

    SciTech Connect

    Cheng, H.S.; Rohatgi, U.S.

    1996-12-31

    The RAMONA-4B code is a coupled thermal-hydraulic, 3D kinetics code for plant transient analyses of a complete Boiling Water Reactor (BWR) system including Reactor Pressure Vessel (RPV), Balance of Plant (BOP) and containment. The complete system representation enables an integrated and coupled systems analysis of a BWR without recourse to prescribed boundary conditions.

  7. Therapeutic effects of fig tree latex on bovine papillomatosis.

    PubMed

    Hemmatzadeh, F; Fatemi, A; Amini, F

    2003-12-01

    The effects of fig tree latex in treating teat papillomatosis in cow in comparison with salicylic acid were evaluated. For this purpose, 12 cows of 1-3 years of age (average 2.25) affected by teat papillomatosis were divided into three groups. In group A, four cows were treated by fig tree (Ficus carica) latex; in group B, four cows were treated with 10% salicylic acid solution and in group C, four cows were kept as control animals receiving no treatment. Animals in each treatment group received their treatment once every 5 days. In groups A and B, de-epithelialization and shrinking of the warts began from the fifth day of treatment and all the warts disappeared within 30 days. However, in the control group no changes in the number of warts were observed until day 15 but thereafter a number of warts disappeared spontaneously in some of the animals. Both salicylic acid and fig tree latex were evaluated as having similar therapeutic effects in treating teat papillomatosis in cow.

  8. 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.

  9. Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S.

    PubMed Central

    Dahlbäck, B

    1983-01-01

    C4b-binding protein was purified from human plasma in high yield by a simple procedure involving barium citrate adsorption and two subsequent chromatographic steps. Approx. 80% of plasma C4b-binding protein was adsorbed on the barium citrate, presumably because of its complex-formation with vitamin K-dependent protein S. The purified C4b-binding protein had a molecular weight of 570 000, as determined by ultracentrifugation, and was composed of about eight subunits (Mr approx. 70 000). Uncomplexed plasma C4b-binding protein was purified from the supernatant after barium citrate adsorption. On sodium dodecyl sulphate/polyacrylamide-gel electrophoresis in non-reducing conditions and on agarose-gel electrophoresis it appeared as a doublet, indicating two forms differing slightly from each other in molecular weight and net charge. The protein band with the higher molecular weight in the doublet corresponded to the C4b-binding protein purified from the barium citrate eluate. Complex-formation between protein S and C4b-binding protein was studied in plasma, and in a system with purified components, by an agarose-gel electrophoresis technique. Protein S was found to form a 1:1 complex with the higher-molecular-weight form of C4b-binding protein, whereas the lower-molecular-weight form of C4b-binding protein did not bind protein S. The KD for the C4b-binding protein-protein S interaction in a system with purified components was approx. 0.9 X 10(-7) M. Rates of association and dissociation at 37 degrees C were low, namely about 1 X 10(3) M-1 . S-1 and 1.8 X 10(-4)-4.5 X 10(-4) S-1 respectively. In human plasma free protein S and free higher-molecular-weight C4b-binding protein were in equilibrium with the C4b-binding protein-protein S complex. Approx. 40% of both proteins existed as free proteins. From equilibrium data in plasma a KD of about 0.7 X 10(-7) M was calculated for the C4b-binding protein-protein S interaction. Images Fig. 2. Fig. 3. PMID:6223625

  10. Amino acid residues 1101-1105 of the isotypic region of human C4B is important to the covalent binding activity of complement component C4.

    PubMed

    Reilly, B D; Levine, R P; Skanes, V M

    1991-11-01

    The C4A and C4B isotypes of human C4 show certain functional differences that stem from their relative preference for transacylation to amino (-NH2) vs hydroxyl (-OH) nucleophiles, respectively, on complement-activating surfaces. Comparison of amino acid sequences of the alpha-chain fragment of C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 are the only consistent structural difference between isotype, i.e., Pro, Cys, Pro, Val, Leu, Asp in C4A and Leu, Ser, Pro, Val Ile, His in C4B. These residues may be responsible either in part or entirely for properties associated with isotype. To examine the functional role of residues 1101-1106 in C4B-mediated hemolysis, whole serum or immunopurified human C4 with allotypes, A3B1, A3, B2B1, or B1 were preincubated in the presence or absence of an antipeptide mAb (BII-1) specific for amino acid residues 1101-1105 of C4B. Sensitized sheep E and C4-deficient guinea pig serum was then added and lysis measured by absorbance at 415 nm. Our results show lysis of antibody-sensitized sheep E is inhibited by antibody and C4B2B1, C4B1, or C4A3B1 but not antibody and C4A3. The interference of hemolysis by BII-1 could not be explained by inhibition of activation of C4B or inhibition of C3 or C5 convertase activity. Furthermore, results from uptake experiments show that BII-1 interferes with the covalent binding activity of C4B, indicating residues 1101-1105 play a role in the covalent binding reaction of C4B to the target E-antibody complex.

  11. Discovery of Dengue Virus NS4B Inhibitors

    PubMed Central

    Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

  12. 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.

  13. Characterization of Nuclear Localization Signal in the N Terminus of CUL4B and Its Essential Role in Cyclin E Degradation and Cell Cycle Progression*

    PubMed Central

    Zou, Yongxin; Mi, Jun; Cui, Jinpeng; Lu, Defen; Zhang, Xiyu; Guo, Chenhong; Gao, Guimin; Liu, Qiji; Chen, Bingxi; Shao, Changshun; Gong, Yaoqin

    2009-01-01

    CUL4A and CUL4B, which are derived from the same ancestor, CUL4, encode scaffold proteins that organize cullin-RING ubiquitin ligase (E3) complexes. Recent genetic studies have shown that germ line mutation in CUL4B can cause mental retardation, short stature, and other abnormalities in humans. CUL4A was observed to be overexpressed in breast and hepatocellular cancers, although no germ line mutation in human CUL4A has been reported. Although CUL4A has been known to be involved in a number of cellular processes, including DNA repair and cell cycle regulation, little is known about whether CUL4B has similar functions. In this report, we tested the functional importance of CUL4B in cell proliferation and characterized the nuclear localization signal (NLS) that is essential for its function. We found that RNA interference silencing of CUL4B led to an inhibition of cell proliferation and a prolonged S phase, due to the overaccumulation of cyclin E, a substrate targeted by CUL4B for ubiquitination. We showed that, unlike CUL4A and other cullins that carry their NLS in their C termini, NLS in CUL4B is located in its N terminus, between amino acid 37 and 40, KKRK. This NLS could bind to importin α1, α3, and α5. NLS-deleted CUL4B was distributed in cytoplasm and failed to promote cell proliferation. Therefore, the nuclear localization of CUL4B mediated by NLS is critical for its normal function in cell proliferation. PMID:19801544

  14. A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.

    PubMed Central

    Méthot, N; Song, M S; Sonenberg, N

    1996-01-01

    The binding of mRNA to the ribosome is mediated by eukaryotic initiation factors eukaryotic initiation factor 4F (eIF4F), eIF4B, eIF4A, and eIF3, eIF4F binds to the mRNA cap structure and, in combination with eIF4B, is believed to unwind the secondary structure in the 5' untranslated region to facilitate ribosome binding. eIF3 associates with the 40S ribosomal subunit prior to mRNA binding. eIF4B copurifies with eIF3 and eIF4F through several purification steps, suggesting the involvement of a multisubunit complex during translation initiation. To understand the mechanism by which eIF4B promotes 40S ribosome binding to the mRNA, we studied its interactions with partner proteins by using a filter overlay (protein-protein [far Western]) assay and the two-hybrid system. In this report, we show that eIF4B self-associates and also interacts directly with the p170 subunit of eIF3. A region rich in aspartic acid, arginine, tyrosine, and glycine, termed the DRYG domain, is sufficient for self-association of eIF4B, both in vitro and in vivo, and for interaction with the p170 subunit of eIF3. These experiments suggest that eIF4B participates in mRNA-ribosome binding by acting as an intermediary between the mRNA and eIF3, via a direct interaction with the p170 subunit of eIF3. PMID:8816444

  15. 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.

  16. Cytotoxicity of fig fruit latex against human cancer cells.

    PubMed

    Wang, Jing; Wang, Xiujie; Jiang, Shu; Lin, Ping; Zhang, Jie; Lu, Yanrong; Wang, Qi; Xiong, Zhujuan; Wu, Yaying; Ren, Jingjing; Yang, Hongliang

    2008-03-01

    Fig fruit latex (FFL) contains significant amounts of polyphenolic compounds and can serve as a source of antioxidants after human consumption. The purpose of this study is to confirm anticancer activity of FFL against human cancer cells and to further elucidate its mechanism of activity. Human glioblastoma, hepatocellular carcinoma, and normal liver cells were used for in vitro tests of FFL effects. Those tests included cytotoxicity, colony formation inhibition, Brdu incorporation, acridine orange/ethidium bromide (AO/EB) staining for apoptotic cells, cell cycle distribution through flow cytometry (FCM), and ADP-ribosyltransferase (NAD+; poly(ADP-ribose) polymerase)-like 1 (ADPERL1) mRNA expression through RT-PCR in response to FFL treatment. After FFL treatment, the proliferation, colony formation, and Brdu labeling indices of cancer cells decreased (P<0.05), while the AO/EB stained apoptotic cells increased (P<0.05). By FCM analysis, an increase of G(0)/G(1) phase cell population and decrease of S and G(2)/M phase cells were observed (P<0.01), while both ADPRTL1 mRNA expression and apoptotic indices increased (P<0.01). The findings in these studies suggested that FFL exhibited potent cytotoxicity in some human cancer cells with little effect in normal cells at certain concentration. The mechanism for such effects might be associated with the inhibition of DNA synthesis, induction of apoptosis, and cell cycle arrest of cancer cells.

  17. 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.

  18. SECONDARY ECLIPSE PHOTOMETRY OF WASP-4b WITH WARM SPITZER

    SciTech Connect

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

    2011-01-20

    We present photometry of the giant extrasolar planet WASP-4b at 3.6 and 4.5 {mu}m 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 {mu}m 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 2{sigma} upper limit on |ecos {omega}| of 0.0024, which constrains the range of tidal heating models that could explain this planet's inflated radius.

  19. Low-temperature brewing using yeast immobilized on dried figs.

    PubMed

    Bekatorou, A; Sarellas, A; Ternan, N G; Mallouchos, A; Komaitis, M; Koutinas, A A; Kanellaki, M

    2002-12-04

    Dried figs, following exhaustive extraction of their residual sugars with water, were used for immobilization of Saccharomyces cerevisiae AXAZ-1. The immobilized biocatalyst was used in repeated batch fermentations of glucose at 30 degrees C, where significant reduction of the fermentation time was observed, falling from 65 h in the first batch to 7 h after the sixth batch. Repeated fermentations of wort at room and low temperatures resulted in fermentation times that fell from 26 to 20 h and from 27 to 24 days at 18 and 3 degrees C, respectively. Ethanol and beer productivities were high, showing suitability of the biocatalyst for low-temperature brewing. Diacetyl concentrations were low (0.3-0.5 mg/L), and polyphenols were lower than in commercial products and decreased as the fermentation temperature was decreased (126-50 mg/L). Ethyl acetate concentrations increased from 53 to 88 mg/L as the temperature was decreased, while the concentration of amyl alcohols at 3 degrees C (58 mg/L) was lower than half of that at 18 degrees C (125 mg/L). The beers produced at the end of the main fermentation had a fine clarity and a special fruity figlike aroma and taste, distinct from commercial products and more intense than beers produced by cells immobilized on other food-grade supports (gluten pellets or delignified cellulosic materials). GC-MS analysis did not show significant differences in the qualitative composition of the aroma compounds of the beers produced by immobilized and free cells.

  20. Patterns of diversification of Afrotropical Otiteselline fig wasps: phylogenetic study reveals a double radiation across host figs and conservatism of host association.

    PubMed

    Jousselin, E; Van Noort, S; Rasplus, J-Y; Greeff, J M

    2006-01-01

    We studied the phylogenetic relationships of Otiteselline fig waSPS associated with Ficus in the Afrotropical region using rDNA sequences. African fig species usually host two species of Otiteselline fig waSPS. Phylogenetic analyses reveal that this pattern of association results from the radiation of two clades of waSPS superimposed on the fig system. Within each clade, wasp species generally cluster according to their host classification. The phylogenies of the two clades are also generally more congruent than expected by chance. Together these results suggest that Otiteselline wasp speciation is largely constrained by the diversification of their hosts. Finally, we show a difference in ovipositor length between the two Otiteselline species coexisting in the same Ficus species, which probably corresponds to ecological differences. The diversification of ecological niches within the fig is probably, with cospeciation, one of the key factors explaining the diversification and maintenance of species of parasites of the fig/pollinator system.

  1. 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

  2. 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.

  3. 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

  4. Electron photon verification calculations using MCNP4B

    SciTech Connect

    Gierga, D.P.; Adams, K.J.

    1998-07-01

    MCNP4B was released in February 1997 with significant enhancements to electron/photon transport methods. These enhancements have been verified against a wide range of published electron/photon experiments, spanning high energy bremsstrahlung production to electron transmission and reflection. Three sets of bremsstrahlung experiments were simulated. The first verification calculations for bremsstrahlung production used the experimental results in Faddegon for 15 MeV electrons incident on lead, aluminum, and beryllium targets. The calculated integrated bremsstrahlung yields, the bremsstrahlung energy spectra, and the mean energy of the bremsstrahlung beam were compared with experiment. The impact of several MCNP tally options and physics parameters was explored in detail. The second was the experiment of O`Dell which measured the bremsstrahlung spectra from 10 and 20.9 MeV electrons incident on a gold/tungsten target. The final set was a comparison of relative experimental spectra with calculated results for 9.66 MeV electrons incident on tungsten based on the experiment of Starfelt and Koch. The transmission experiments of Ebert were also studied, including comparisons of transmission coefficients for 10.2 MeV electrons incident on carbon, silver, and uranium foils. The agreement between experiment and simulation was usually within two standard deviations of the experimental and calculational errors.

  5. 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.

  6. The incidence and pattern of copollinator diversification in dioecious and monoecious figs

    PubMed Central

    Yang, Li-Yuan; Machado, Carlos A; Dang, Xiao-Dong; Peng, Yan-Qiong; Yang, Da-Rong; Zhang, Da-Yong; Liao, Wan-Jin

    2015-01-01

    Differences in breeding system are associated with correlated ecological and morphological changes in plants. In Ficus, dioecy and monoecy are strongly associated with different suites of traits (tree height, population density, fruiting frequency, pollinator dispersal ecology). Although approximately 30% of fig species are pollinated by multiple species of fig-pollinating wasps, it has been suggested that copollinators are rare in dioecious figs. Here, we test whether there is a connection between the fig breeding system and copollinator incidence and diversification by conducting a meta-analysis of molecular data from pollinators of 119 fig species that includes new data from 15 Asian fig species. We find that the incidence of copollinators is not significantly different between monoecious and dioecious Ficus. Surprisingly, while all copollinators in dioecious figs are sister taxa, only 32.1% in monoecious figs are sister taxa. We present hypotheses to explain those patterns and discuss their consequences on the evolution of this mutualism. PMID:25495152

  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. Reactivation of Lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells.

    PubMed

    Zou, Jianlong; Hu, Bo; Arpag, Sezgi; Yan, Qing; Hamilton, Audra; Zeng, Yuan-Shan; Vanoye, Carlos G; Li, Jun

    2015-04-29

    Loss of function of FIG4 leads to Charcot-Marie-Tooth disease Type 4J, Yunis-Varon syndrome, or an epilepsy syndrome. FIG4 is a phosphatase with its catalytic specificity toward 5'-phosphate of phosphatidylinositol-3,5-diphosphate (PI3,5P2). However, the loss of FIG4 decreases PI3,5P2 levels likely due to FIG4's dominant effect in scaffolding a PI3,5P2 synthetic protein complex. At the cellular level, all these diseases share similar pathology with abnormal lysosomal storage and neuronal degeneration. Mice with no FIG4 expression (Fig4(-/-)) recapitulate the pathology in humans with FIG4 deficiency. Using a flow cytometry technique that rapidly quantifies lysosome sizes, we detected an impaired lysosomal fission, but normal fusion, in Fig4(-/-) cells. The fission defect was associated with a robust increase of intralysosomal Ca(2+) in Fig4(-/-) cells, including FIG4-deficient neurons. This finding was consistent with a suppressed Ca(2+) efflux of lysosomes because the endogenous ligand of lysosomal Ca(2+) channel TRPML1 is PI3,5P2 that is deficient in Fig4(-/-) cells. We reactivated the TRPML1 channels by application of TRPML1 synthetic ligand, ML-SA1. This treatment reduced the intralysosomal Ca(2+) level and rescued abnormal lysosomal storage in Fig4(-/-) culture cells and ex vivo DRGs. Furthermore, we found that the suppressed Ca(2+) efflux in Fig4(-/-) culture cells and Fig4(-/-) mouse brains profoundly downregulated the expression/activity of dynamin-1, a GTPase known to scissor organelle membranes during fission. This downregulation made dynamin-1 unavailable for lysosomal fission. Together, our study revealed a novel mechanism explaining abnormal lysosomal storage in FIG4 deficiency. Synthetic ligands of the TRPML1 may become a potential therapy against diseases with FIG4 deficiency.

  9. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  10. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  11. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  12. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  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. 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.

  15. 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

  16. 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.

  17. Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities.

    PubMed

    Lopez, Sandra M; Hodgson, Myles C; Packianathan, Charles; Bingol-Ozakpinar, Ozlem; Uras, Fikriye; Rosen, Barry P; Agoulnik, Irina U

    2013-10-18

    The tumor suppressor INPP4B is an important regulator of phosphatidyl-inositol signaling in the cell. Reduced INPP4B expression is associated with poor outcomes for breast, prostate, and ovarian cancer patients. INPP4B contains a CX5R catalytic motif characteristic of dual-specificity phosphatases, such as PTEN. Lipid phosphatase activity of INPP4B has previously been described. In this report we show that INPP4B can dephosphorylate para-nitrophenyl phosphate (pNPP) and 6,8-difluoro-4-methylumbelliferyl (DiFMUP), synthetic phosphotyrosine analogs, suggesting that INPP4B has protein tyrosine phosphatase (PTP) activity. Using mutagenesis, we examined the functional role of specific amino acids within the INPP4B C842KSAKDR catalytic site. The K843M mutant displayed increased pNPP hydrolysis, the K846M mutant lost lipid phosphatase activity with no effect on PTP activity, and the D847E substitution ablated PTP activity and significantly reduced lipid phosphatase activity. Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and PTP activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation. Taken together our data identified key residues in the INPP4B catalytic domain associated with lipid and protein phosphatase activities and found a robust downstream target regulated by INPP4B but not PTEN.

  18. Deep mtDNA divergences indicate cryptic species in a fig-pollinating wasp

    PubMed Central

    Haine, Eleanor R; Martin, Joanne; Cook, James M

    2006-01-01

    Background Figs and fig-pollinating wasps are obligate mutualists that have coevolved for ca 90 million years. They have radiated together, but do not show strict cospeciation. In particular, it is now clear that many fig species host two wasp species, so there is more wasp speciation than fig speciation. However, little is known about how fig wasps speciate. Results We studied variation in 71 fig-pollinating wasps from across the large geographic range of Ficus rubiginosa in Australia. All wasps sampled belong to one morphological species (Pleistodontes imperialis), but we found four deep mtDNA clades that differed from each other by 9–17% nucleotides. As these genetic distances exceed those normally found within species and overlap those (10–26%) found between morphologically distinct Pleistodontes species, they strongly suggest cryptic fig wasp species. mtDNA clade diversity declines from all four present in Northern Queensland to just one in Sydney, near the southern range limit. However, at most sites multiple clades coexist and can be found in the same tree or even the same fig fruit and there is no evidence for parallel sub-division of the host fig species. Both mtDNA data and sequences from two nuclear genes support the monophyly of the "P. imperialis complex" relative to other Pleistodontes species, suggesting that fig wasp divergence has occurred without any host plant shift. Wasps in clade 3 were infected by a single strain (W1) of Wolbachia bacteria, while those in other clades carried a double infection (W2+W3) of two other strains. Conclusion Our study indicates that cryptic fig-pollinating wasp species have developed on a single host plant species, without the involvement of host plant shifts, or parallel host plant divergence. Despite extensive evidence for coevolution between figs and fig wasps, wasp speciation may not always be linked strongly with fig speciation. PMID:17040562

  19. 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.

  20. 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.

  1. 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.

  2. 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.

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

    PubMed

    Wu, Ray-Chang; Zeng, Yang; Pan, I-Wen; Wu, Mei-Yi

    2015-09-01

    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.

  4. 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.

  5. 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.

  6. 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.

  7. LAPTM4B: an oncogene in various solid tumors and its functions

    PubMed Central

    Meng, Y; Wang, L; Chen, D; Chang, Y; Zhang, M; XU, J-J; Zhou, R; Zhang, Q-Y

    2016-01-01

    The oncogene Lysosome-associated protein transmembrane-4β (LAPTM4B) gene was identified, and the polymorphism region in the 5′-UTR of this gene was certified to be associated with tumor susceptibility. LAPTM4B-35 protein was found to be highly expressed in various solid tumors and could be a poor prognosis marker. The functions of LAPTM4B in solid tumors were also explored. It is suggested that LAPTM4B could promote the proliferation of tumor cells, boost invasion and metastasis, resist apoptosis, initiate autophagy and assist drug resistance. PMID:27212036

  8. The transcription activity of heat shock factor 4b is regulated by FGF2.

    PubMed

    Hu, Yan-Zhong; Zhang, Jun; Li, Shulian; Wang, Chuan; Chu, Liujie; Zhang, Zhi; Ma, Zengyi; Wang, Mingli; Jiang, Qiying; Liu, Guangchao; Qi, Yijun; Ma, Yuanfang

    2013-02-01

    Heat shock factor 4b has been found to be closely associated with postnatal lens development. It expresses in postnatal lens epithelial and secondary fiber cells and controls the expression of small heat shock proteins which are important for lens homeostasis. However, the signal pathways underlying Hsf4b are still not completely understood. Here we present that Hsf4b transcription activity is regulated by FGF2 a key growth factor that is involved in regulating lens development at multiple stages. FGF2 can promote Hsf4b nuclear-translocation and the expression of Hsp25 and αB-crystallin, the key downstream targets of Hsf4b in the Hsf4b-reconstituted mouse hsf4-/- lens epithelial cells. Further study indicates that FGF2 can induce Hsf4b protein stabilization through ERK1/2-mediated posttranslational phosphorylation or sumoylation. Hsf4b can promote FGF2-induced morphology transition from lens epithelial cell to the fiber cell, and this morphology transition can be inhibited by ERK1/2 inhibitor U0126. Taken together, our data demonstrate that Hsf4b is a novel downstream transcription factor of FGF2, and its transcription activity is associated with FGF2-modulated lens epithelial cell-fiber cell transition.

  9. 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.

  10. Mapping the Interactions between the NS4B and NS3 Proteins of Dengue Virus

    PubMed Central

    Zou, Jing; Lee, Le Tian; Wang, Qing Yin; Xie, Xuping; Lu, Siyan; Yau, Yin Hoe; Yuan, Zhiming; Geifman Shochat, Susana; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus RNA synthesis is mediated by a multiprotein complex associated with the endoplasmic reticulum membrane, named the replication complex (RC). Within the flavivirus RC, NS4B, an integral membrane protein with a role in virulence and regulation of the innate immune response, binds to the NS3 protease-helicase. NS4B modulates the RNA helicase activity of NS3, but the molecular details of their interaction remain elusive. Here, we used dengue virus (DENV) to map the determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV-infected cells and cells coexpressing both proteins. Surface plasmon resonance demonstrated that subdomains 2 and 3 of the NS3 helicase region and the cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible, with a tendency to form a three-turn α-helix and two short β-strands. Upon binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B exhibited line broadening, suggesting a participation in the interaction. Sequence alignment showed that 4 of these 12 residues are strictly conserved across different flaviviruses. Mutagenesis analysis showed that three (Q134, G140, and N144) of the four evolutionarily conserved NS4B residues are essential for DENV replication. The mapping of the NS3/NS4B-interacting regions described here can assist the design of inhibitors that disrupt their interface for antiviral therapy. IMPORTANCE NS3 and NS4B are essential components of the flavivirus RC. Using DENV as a model, we mapped the interaction between the viral NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the cytoplasmic loop of NS4B are critical for the interaction. Functional analysis delineated residues within the NS4B cytoplasmic loop that are crucial for DENV replication. Our findings reveal

  11. 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...

  12. Asymmetric interaction and indeterminate fitness correlation between cooperative partners in the fig–fig wasp mutualism

    PubMed Central

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

    2011-01-01

    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. PMID:21490005

  13. 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

  14. 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

  15. Codivergence and multiple host species use by fig wasp populations of the Ficus pollination mutualism

    PubMed Central

    2012-01-01

    Background The interaction between insects and plants takes myriad forms in the generation of spectacular diversity. In this association a species host range is fundamental and often measured using an estimate of phylogenetic concordance between species. Pollinating fig wasps display extreme host species specificity, but the intraspecific variation in empirical accounts of host affiliation has previously been underestimated. In this investigation, lineage delimitation and codiversification tests are used to generate and discuss hypotheses elucidating on pollinating fig wasp associations with Ficus. Results Statistical parsimony and AMOVA revealed deep divergences at the COI locus within several pollinating fig wasp species that persist on the same host Ficus species. Changes in branching patterns estimated using the generalized mixed Yule coalescent test indicated lineage duplication on the same Ficus species. Conversely, Elisabethiella and Alfonsiella fig wasp species are able to reproduce on multiple, but closely related host fig species. Tree reconciliation tests indicate significant codiversification as well as significant incongruence between fig wasp and Ficus phylogenies. Conclusions The findings demonstrate more relaxed pollinating fig wasp host specificity than previously appreciated. Evolutionarily conservative host associations have been tempered by horizontal transfer and lineage duplication among closely related Ficus species. Independent and asynchronistic diversification of pollinating fig wasps is best explained by a combination of both sympatric and allopatric models of speciation. Pollinator host preference constraints permit reproduction on closely related Ficus species, but uncertainty of the frequency and duration of these associations requires better resolution. PMID:22214193

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  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. Host-specificity and coevolution among pollinating and nonpollinating New World fig wasps.

    PubMed

    Marussich, Wendy A; Machado, Carlos A

    2007-05-01

    Figs (Ficus spp., Moraceae) and their pollinating wasps (Hymenoptera, Agaonidae, Chalcidoidea) constitute a classic example of an obligate plant-pollinator mutualism, and have become an ideal system for addressing questions on coevolution, speciation, and the maintenance of mutualisms. In addition to pollinating wasps, figs host several types of nonpollinating, parasitic wasps from a diverse array of Chalcid subfamilies with varied natural histories and ecological strategies (e.g. competitors, gallers, and parasitoids). Although a few recent studies have addressed the question of codivergence between specific genera of pollinating and nonpollinating fig wasps, no study has addressed the history of divergence of a fig wasp community comprised of multiple genera of wasps associated with a large number of sympatric fig hosts. Here, we conduct phylogenetic analyses of mitochondrial DNA sequences (COI) using 411 individuals from 69 pollinating and nonpollinating fig wasp species to assess relationships within and between five genera of fig wasps (Pegoscapus, Idarnes, Heterandrium, Aepocerus, Physothorax) associated with 17 species of New World Urostigma figs from section Americana. We show that host-switching and multiple wasp species per host are ubiquitous across Neotropical nonpollinating wasp genera. In spite of these findings, cophylogenetic analyses (TREEMAP 1.0, TREEMAP 2.02beta, and parafit) reveal evidence of codivergence among fig wasps from different ecological guilds. Our findings further challenge the classical notion of strict-sense coevolution between figs and their associated wasps, and mirror conclusions from detailed molecular studies of other mutualisms that have revealed common patterns of diffuse coevolution and asymmetric specialization among the participants.

  4. Mutations in classical swine fever virus NS4B affect virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), a virus causing a severe disease in swine. Protein domain analysis of the predicted amino acid sequence of NS4B in highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Interleukin-1 receptor like domain (TIR...

  5. 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...

  6. 78 FR 63221 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... ICH Q4B evaluation of the Bacterial Endotoxins Test General Chapter harmonized text from each of...

  7. 76 FR 37129 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... ] availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... published ICH guidance, ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the...

  8. Atypical Listeria monocytogenes Serotype 4b strains harboring a lineage II-specific gene cassette

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes is the etiological agent of listeriosis, a severe foodborne illness. The population of L. monocytogenes is divided into four lineages (I-IV) and serotype 4b in lineage I has been involved in numerous outbreaks. Several serotype 4b epidemic-associated clonal groups (ECI, II, an...

  9. 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

  10. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition

    PubMed Central

    Bortnik, Svetlana; Choutka, Courtney; Horlings, Hugo M.; Leung, Samuel; Baker, Jennifer H.; Lebovitz, Chandra; Dragowska, Wieslawa H.; Go, Nancy E.; Bally, Marcel B.; Minchinton, Andrew I.; Gelmon, Karen A.; Gorski, Sharon M.

    2016-01-01

    Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies. PMID:27556700

  11. 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.

  12. [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.

  13. 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

  14. 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.

  15. 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.

  16. Fitness reduction for uncooperative fig wasps through reduced offspring size: a third component of host sanctions.

    PubMed

    Jandér, K C; Dafoe, A; Herre, E A

    2016-09-01

    Mutually beneficial interactions between two species-mutualisms-are ancient, diverse, and of fundamental ecological importance. Nonetheless, factors that prevent one partner from reaping the benefits of the interaction without paying the cost are still poorly understood. Fig trees and their unique pollinators, fig wasps, present a powerful model system for studying mutualism stability. Both partners depend completely on each other for reproduction, cooperation levels can be manipulated, and the resulting field-based fitness quantified. Previous work has shown that fig trees can impose two types of host sanctions that reduce the fitness of wasps that do not pollinate: (1) fig abortion, which kills all developing larvae, and (2) reduced number of wasp offspring in figs that are not aborted. Here we demonstrate a third component of host sanctions. Through manipulative field experiments, we show that for four of five studied species, offspring of pollen-free foundresses are only 50-90% the size of offspring of pollinating foundresses. We further show that in all four studied species, smaller wasps are less likely to reach and enter a flowering fig to become foundresses themselves. Therefore, the experimentally determined size reduction of offspring is estimated to cause an additional reduction of up to 80% in fitness for a pollen-free foundress. We determine that the size reduction of pollen-free offspring acts on the level of the entire fig fruit rather than on individual flowers. These results show that estimates of the fitness effect of host sanctions on uncooperative symbionts should consider not only offspring quantity but also offspring quality. We discuss implications beyond the fig tree-fig wasp mutualism.

  17. (4bS,8aS)-1-Isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octa­hydro­phenan­thren-2-yl acetate

    PubMed Central

    Oubabi, Radouane; Auhmani, Aziz; Ait Itto, My Youssef; Auhmani, Abdelwahed; Daran, Jean-Claude

    2014-01-01

    The hemisynthesis of the title compound, C22H32O2, was carried out through direct acetyl­ation reaction of the naturally occurring diterpene totarol [systematic name: (4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexa­hydro­phen­an­thren-2-ol]. The mol­ecule is built up from three fused six membered rings, one saturated and two unsaturated. The central unsaturated ring has a half-chair conformation, whereas the other unsaturated ring displays a chair conformation. The absolute configuration is deduced from the chemical pathway. The value of the Hooft parameter [−0.10 (6)] allowed this absolute configuration to be confirmed. PMID:24765017

  18. INPP4B is an oncogenic regulator in human colon cancer

    PubMed Central

    Guo, S T; Chi, M N; Yang, R H; Guo, X Y; Zan, L K; Wang, C Y; Xi, Y F; Jin, L; Croft, A; Tseng, H-Y; Yan, X G; Farrelly, M; Wang, F H; Lai, F; Wang, J F; Li, Y P; Ackland, S; Scott, R; Agoulnik, I U; Hondermarck, H; Thorne, R F; Liu, T; Zhang, X D; Jiang, C C

    2016-01-01

    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum- and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease. PMID:26411369

  19. Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival

    PubMed Central

    Wang, Yubao; Begley, Michael; Li, Qing; Huang, Hai-Tsang; Lako, Ana; Eck, Michael J.; Gray, Nathanael S.; Mitchison, Timothy J.; Cantley, Lewis C.; Zhao, Jean J.

    2016-01-01

    The protein kinase maternal and embryonic leucine zipper kinase (MELK) is critical for mitotic progression of cancer cells; however, its mechanisms of action remain largely unknown. By combined approaches of immunoprecipitation/mass spectrometry and peptide library profiling, we identified the eukaryotic translation initiation factor 4B (eIF4B) as a MELK-interacting protein during mitosis and a bona fide substrate of MELK. MELK phosphorylates eIF4B at Ser406, a modification found to be most robust in the mitotic phase of the cell cycle. We further show that the MELK–eIF4B signaling axis regulates protein synthesis during mitosis. Specifically, synthesis of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B. Inactivation of MELK or eIF4B results in reduced protein synthesis of MCL1, which, in turn, induces apoptotic cell death of cancer cells. Our study thus defines a MELK–eIF4B signaling axis that regulates protein synthesis during mitosis, and consequently influences cancer cell survival. PMID:27528663

  20. 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

  1. Heat capacity, resistivity, and angular dependent magnetization studies of single crystal Nd1+ϵFe4B4 for ϵ≈17

    DOE PAGES

    Conner, Benjamin S.; Susner, Michael A.; Lampen-Kelley, Paula; ...

    2017-04-04

    Advances in crystal growth have allowed for synthesis of large single crystals of Nd1+ϵFe4B4, a well-known phase with a modulated structure. As a result we are able to report heat capacity and resistivity measurements on a single crystal Nd1+ϵFe4B4 sample with a distribution of ϵ that skews towards the solubility limit of Nd near ϵ ≈ 17. Heat capacity measurements show evidence of crystal field splitting at temperatures higher than the long-range ferromagnetic Curie temperature. Heat capacity, resistivity, and magnetization measurements all confirm a Curie temperature of 7 K which is lower than previously reported values in the Nd1+ϵFe4B4 system.more » Here, we also perform measurements of the angular dependence of the magnetization and discover behavior associated with the magnetic anisotropy that is inconsistent with the simple description previously proposed.« less

  2. A C-terminal di-leucine motif controls plasma membrane expression of PMCA4b.

    PubMed

    Antalffy, Géza; Pászty, Katalin; Varga, Karolina; Hegedűs, Luca; Enyedi, Agnes; Padányi, Rita

    2013-12-01

    Recent evidences show that the localization of different plasma membrane Ca(2+) ATPases (PMCAs) is regulated in various complex, cell type-specific ways. Here we show that in low-density epithelial and endothelial cells PMCA4b localized mostly in intracellular compartments and its plasma membrane localization was enhanced upon increasing density of cells. In good correlation with the enhanced plasma membrane localization a significantly more efficient Ca(2+) clearance was observed in confluent versus non-confluent HeLa cell cultures expressing mCherry-PMCA4b. We analyzed the subcellular localization and function of various C-terminally truncated PMCA4b variants and found that a truncated mutant PMCA4b-ct24 was mostly intracellular while another mutant, PMCA4b-ct48, localized more to the plasma membrane, indicating that a protein sequence corresponding to amino acid residues 1158-1181 contained a signal responsible for the intracellular retention of PMCA4b in non-confluent cultures. Alteration of three leucines to alanines at positions 1167-1169 resulted in enhanced cell surface expression and an appropriate Ca(2+) transport activity of both wild type and truncated pumps, suggesting that the di-leucine-like motif (1167)LLL was crucial in targeting PMCA4b. Furthermore, upon loss of cell-cell contact by extracellular Ca(2+) removal, the wild-type pump was translocated to the early endosomal compartment. Targeting PMCA4b to early endosomes was diminished by the L(1167-69)A mutation, and the mutant pump accumulated in long tubular cytosolic structures. In summary, we report a di-leucine-like internalization signal at the C-tail of PMCA4b and suggest an internalization-mediated loss of function of the pump upon low degree of cell-cell contact.

  3. LAPTM4B Gene Expression and Polymorphism as Diagnostic Markers of Breast Cancer in Egyptian Patients

    PubMed Central

    Shaker, Olfat; Taha, Fatma; Salah, Maha; El-Marzouky, Mohamed

    2015-01-01

    Summary Background The aim of this study was to investigate the association between LAPTM4B gene polymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer. Methods This case control study was done on 88 breast cancer patients, 40 with fibroadenoma and 80 healthy subjects. Genotyping of the LAPTM4B polymorphism was determined by PCR. Serum LAPTM4B level was measured using ELISA. Results There was a significant difference in the (*1/2+ *2/2) genotypes in breast cancer patients (59.1) compared to the control subjects (43.8%) (P=0.047; OR=1.86; 95% CI =1.01–3.43). The frequency of the allele 2* of the LAPTM4B gene was significantly higher in breast cancer patients (36.4%) than in the control (25.6%) (p=0.034; OR=1.66; 95% CI =1.04–2.65). Genotypes (*1/2+*2/2) were significantly associated with the differential classification of TNM. Serum level of LAPTM4B was significantly higher in breast cancer patients than in control and fibroadenoma and in fibroadenoma patients than in control. In breast cancer patients, serum LAPTM4B was significantly higher in stage III and in large tumor size. Serum LAPTM4B was significantly higher in the cancer patients’ genotypes (*1/2+*2/2). Conclusions Genetic polymorphism of LAPTM4B is a potential risk factor for the development of breast cancer. Serum LAPTM4B may be used as a diagnostic and prognostic marker for breast cancer. PMID:28356847

  4. Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor

    PubMed Central

    Titus, David J.; Wilson, Nicole M.; Freund, Julie E.; Carballosa, Melissa M.; Sikah, Kevin E.; Furones, Concepcion; Dietrich, W. Dalton; Gurney, Mark E.

    2016-01-01

    Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague-Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task. Treatment with the PDE4B inhibitor significantly reversed the TBI-induced deficits in cue and contextual fear conditioning and water maze retention. To further understand the underlying mechanisms of these memory impairments, we examined hippocampal long-term potentiation (LTP). TBI resulted in a significant reduction in basal synaptic transmission and impaired expression of LTP. Treatment with the PDE4B inhibitor significantly reduced the deficits in basal synaptic transmission and rescued LTP expression. The PDE4B inhibitor reduced tumor necrosis factor-α levels and increased phosphorylated CREB levels after TBI, suggesting that this drug inhibited molecular pathways in the brain known to be regulated by PDE4B. These results suggest that a subtype-selective PDE4B inhibitor is a potential therapeutic to reverse chronic learning and memory dysfunction and deficits in hippocampal synaptic plasticity following TBI. SIGNIFICANCE STATEMENT Currently, there are an estimated 3.2–5.3 million individuals living with disabilities from traumatic brain injury (TBI) in the United States, and 8 of

  5. Convergent incidences of Wolbachia infection in fig wasp communities from two continents

    PubMed Central

    Haine, Eleanor R.; Cook, James M.

    2005-01-01

    Wide surveys suggest that Wolbachia bacteria infect ca. 20% of all insect species, but particular taxonomic or ecological groups may display significantly higher or lower incidences. We studied 61 fig wasp species in Australia and found the highest known incidence (67%) of infection in a targeted study of this nature. A comparable study in Panama reported a similar figure (59%), confirming the exceptionally high incidence of Wolbachia in fig wasps. Importantly, these are two independent estimates of Wolbachia incidence in fig wasp communities, because no host species, or even genera, are shared between localities. The high level of infection may reflect enhanced opportunities for horizontal transmission inside fig fruits. Although incidence was similar in Panama and Australia, the actual strains involved were different and region-specific. Local strains were shared by several host species, although there was often no obvious (direct) ecological link between two hosts with the same infection. PMID:15734697

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. [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.

  13. Two New Copper Borates with Mesoscale Cubic Supramolecular Cages Assembled from {Cu4 @B20 } Clusters.

    PubMed

    Wang, Jia-Jia; Wei, Qi; Yang, Bai-Feng; Yang, Guo-Yu

    2017-02-24

    Two new copper borates, namely H6 [(μ4 -O)Cu4 @B20 O32 (OH)8 ]⋅25 H2 O (1) and H6 [(μ4 -O)Cu4 @B20 O32 (OH)8 ]⋅34 H2 O⋅8 H3 BO3 (2), with 3D supramolecular framework have been made under solvothermal conditions, which built by novel cubic supramolecular cages with mesoscale cavities via the H-bondings. Interestingly, the cage is assembled by [(μ4 -O)Cu4 @B20 O32 (OH)8 ] ({Cu4 @B20 }) cluster units with different point-group symmetry. Owing to extra H3 BO3 molecules participated in building the supramolecular framework, 2 has a larger cubic cage size and higher non-framework volume, leading to the cage size extended to mesoporous size set as a version of ''1 plus".

  14. 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).

  15. Current Drug Discovery for Anti-hepatitis C Virus Targeting NS4B.

    PubMed

    Wang, Zhenya; Chen, Xinli; Wu, Chunli; Xu, Haiwei; Liu, Hongmin

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide epidemic disease. It is estimated that more than 170 million individuals are infected with HCV and with three to four million new cases each year. Many new direct-acting antiviral (DAA) agents that specifically target HCV NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant effect for the patient and for the market recently. The non-structural 4B (NS4B) protein, is among the least characterized of the HCV proteins. A variety of functions have been recognized for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. In order to maximize antiviral efficacy and prevent the emergence of resistance, novel NS4B inhibitors have been subjected to pharmacological studies. In this review, we discussed current understanding of the structure and function of NS4B, and novel drug discoveries targeting NS4B as anti-hepatitis C virus such as sulfonamide, piperidine, carboxamide, piperazinone and quinoline derivatives within the last three years.

  16. UBE4B targets phosphorylated p53 at serines 15 and 392 for degradation

    PubMed Central

    Du, Cheng; Wu, Hong; Leng, Roger P.

    2016-01-01

    Phosphorylation of p53 is a key mechanism responsible for the activation of its tumor suppressor functions in response to various stresses. In unstressed cells, p53 is rapidly turned over and is maintained at a low basal level. After DNA damage or other forms of cellular stress, the p53 level increases, and the protein becomes metabolically stable. However, the mechanism of phosphorylated p53 regulation is unclear. In this study, we studied the kinetics of UBE4B, Hdm2, Pirh2, Cop1 and CHIP induction in response to p53 activation. We show that UBE4B coimmunoprecipitates with phosphorylated p53 at serines 15 and 392. Notably, the affinity between UBE4B and Hdm2 is greatly decreased after DNA damage. Furthermore, we observe that UBE4B promotes endogenous phospho-p53(S15) and phospho-p53(S392) degradation in response to IR. We demonstrate that UBE4B and Hdm2 repress p53S15A, p53S392A, and p53-2A(S15A, S392A) functions, including p53-dependent transactivation and growth inhibition. Overall, our results reveal that UBE4B plays an important role in regulating phosphorylated p53 following DNA damage. PMID:26673821

  17. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity.

    PubMed

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-08-30

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition.

  18. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity

    PubMed Central

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-01-01

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition. PMID:27527864

  19. 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

  20. KDM4B is a master regulator of the estrogen receptor signalling cascade.

    PubMed

    Gaughan, Luke; Stockley, Jacqueline; Coffey, Kelly; O'Neill, Daniel; Jones, Dominic L; Wade, Mark; Wright, Jamie; Moore, Madeleine; Tse, Sandy; Rogerson, Lynsey; Robson, Craig N

    2013-08-01

    The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment.

  1. Identification of natural rubber and characterization of rubber biosynthetic activity in fig tree.

    PubMed

    Kang, H; Kang, M Y; Han, K H

    2000-07-01

    Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea as part of a survey of rubber producing plants. Fourier transform infrared and (13)C nuclear magnetic resonance analysis of samples prepared by successive extraction with acetone and benzene confirmed that the benzene-soluble residues are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was 0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that the molecular size of the natural rubber from fig tree is about 190 kD. Similar to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray), rubber biosynthesis in fig tree is tightly associated with rubber particles. The rubber transferase in rubber particles exhibited a higher affinity for farnesyl pyrophosphate than for isopentenyl pyrophosphate, with apparent K(m) values of 2.8 and 228 microM, respectively. Examination of latex serum from fig tree by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins of 25 and 48 kD in size, and several proteins with molecular mass below 20 and above 100 kD. Partial N-terminal amino acid sequencing and immunochemical analyses revealed that the 25- and 48-kD proteins were novel and not related to any other suggested rubber transferases. The effect of EDTA and Mg(2+) ion on in vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent metal ion present in the latex serum is an important factor in determining the different rubber biosynthetic activities in fig tree and rubber tree.

  2. Fruit characteristics and factors affecting fruit removal in a Panamanian community of strangler figs.

    PubMed

    Korine, C; Kalko, E K V; Herre, E A

    2000-06-01

    We describe fruiting characteristics for 12 species in a community of strangler figs (Moraceae: Urostigma) studied in Panama. We quantify diurnal and nocturnal removal rates and proportions of fruits removed, and relate them to the activities of the main dispersers of the figs: bats and birds. These results combined with previous studies show that there are clear differences between fig species with fruit that ripen red and those with fruit that remain green(ish). In the red-fruited species, the fruit are small, ripen asynchronously over relatively long periods, produce little scent, and are mainly taken during the day by birds. In contrast, in the green(ish)-fruited species, the fruits are larger, span a range of sizes, ripen relatively synchronously, produce very distinctive aromas, and are mainly taken at night by bats. This dichotomy in fruiting characteristics suggests coadaptive links between groups of dispersers and different species within the genus Ficus. All fig species produce a range of fruit crop sizes (10-155 fuits/m(2) canopy area) of which a high proportion were removed by seed dispersers (>80%). Removal rates (fruit removed per day) were positively correlated with crop size, suggesting that trees with large crop size attract more frugivores. Removal rates of green-fruited figs were significantly lower and persistence and abortion of ripe fruit were significant higher around full moon, apparently due to the reduced activity of bats. We further estimate the number of bats that are sustained by a tree fruit crop and account for the observed fruit removal. We then discuss the evidence for coadaptation between different groups of figs and their seed dispersers, Finally, we consider the conservation implications for figs as keystone resources in tropical forests.

  3. [Relationship between population variation of fig trees and environment in the tropical rainforests of Xishuangbanna].

    PubMed

    Yang, Darong; Peng, Yanqiong; Zhang, Guangming; Song, Qishi; Zhao, Tingzhou; Wang, Qiuyan

    2002-09-01

    The species diversity of the plant plays an important role in the ecological environment conservation. In the tropical rainforest of Xishuangbanna the biological diversity is extremely rich, and which is a key region used to biological diversity research. And the fig is a key plant species in the tropical rainforest. The research results about the relationship between the variation of the figs population and environment of the region were following: 1. There were 69 species, variants and subspecies Ficus plant that was known in the tropical rainforest of Xishuangbanna, thereinto there were 23 species and subspecies owned to the Urostigma, and the Pharmacosyea had four species; the Sycomorrus two species and subspecies; while the Ficus owned 41 species, subspecies and variants, then Xishuangbanna borne the most richness and diversity of fig species and numbers in China. 2. The distribution of the figs had intimate connection with the environment, and the species and the quantities showed the most richness in the tropical primary rainforest that was protected well and almost intact, where the figs were mainly to be arbors and giant arbors; and in the devastated stand and secondary forest dwarf arbors, shrubs, bushes and ligneous liana possessed the most in the fig species; while in such regions of tropical rainforest environment that have been destroyed seriously one proportion of the pioneer species of the figs were the main members. 3. Only the key colony of Ficus can be conserved in the tropical rainforest, can the whole ecological environment of the tropical rainforest be protected and rehabilitated, which was one of the important measures to realize it.

  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. eIF4B stimulates translation of long mRNAs with structured 5′ UTRs and low closed-loop potential but weak dependence on eIF4G

    PubMed Central

    Sen, Neelam Dabas; Zhou, Fujun; Harris, Michael S.; Ingolia, Nicholas T.

    2016-01-01

    DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. However, either eliminating eIF4B or inactivating eIF4A preferentially impacts mRNAs with longer, more structured 5′ untranslated regions (UTRs). These findings reveal an eIF4A-independent role for eIF4B in addition to its function as eIF4A cofactor in promoting PIC attachment or scanning on structured mRNAs. eIF4B, eIF4A, and Ded1 mutations also preferentially impair translation of longer mRNAs in a fashion mitigated by the ability to form closed-loop messenger ribonucleoprotein particles (mRNPs) via eIF4F–poly(A)-binding protein 1 (Pab1) association, suggesting cooperation between closed-loop assembly and eIF4B/helicase functions. Remarkably, depleting eukaryotic translation initiation factor 4G (eIF4G), the scaffold subunit of eukaryotic translation initiation factor 4F (eIF4F), preferentially impacts short mRNAs with strong closed-loop potential and unstructured 5′ UTRs, exactly the opposite features associated with hyperdependence on the eIF4B/helicases. We propose that short, highly efficient mRNAs preferentially depend on the stimulatory effects of eIF4G-dependent closed-loop assembly. PMID:27601676

  6. 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

  7. Aflatoxins in Turkish dried figs intended for export to the European Union.

    PubMed

    Senyuva, H Z; Gilbert, J; Ulken, U

    2007-04-01

    Dried figs for export from Turkey from crop years 2003 through 2006 were tested for aflatoxin B1 and total aflatoxins. For export to the European Union, consignments of 0.5 to 10 tonnes of dried figs were sampled according to European Commission regulations, and high-pressure liquid chromatography (HPLC) was used to determine concentrations of aflatoxins Bl, B2, G1, and G2. For each consignment of dried figs, a 30-kg sample (comprising 100 subsamples) was divided into three 10-kg subsamples, which were separately blended and analyzed with HPLC. This monitoring effort was conducted for figs from 2003, 2004, 2005, and up to June 2006, for a total of 10,396 30-kg samples (28,489 analyses). The incidence of contamination with aflatoxin B1 at higher than 2 ng/g was on average 0.6, 2.0, 4.0, and 2.4% for 2003, 2004, 2005, and up to June 2006, respectively, whereas contamination with total aflatoxins at higher than 4 ng/g was 2.6, 3.0, 5.1, and 2.7%. There was significant variability in contamination between replicate 1-kg samples, indicating small numbers of individual contaminated figs were probably responsible. There were also substantial differences in the relative proportions of aflatoxins B1, B2, G1, and G2 among samples, suggesting different contributing fungal sources.

  8. 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).

  9. 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.

  10. 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.

  11. 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.

  12. Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages

    PubMed Central

    Yang, Jing-Xing; Hsieh, Kou-Chou; Chen, Yi-Ling; Lee, Chien-Kuo; Conti, Marco; Chuang, Tsung-Hsien; Wu, Chin-Pyng; Jin, S.-L. Catherine

    2017-01-01

    Activation of TLR4 by lipopolysaccharide (LPS) induces both pro-inflammatory and anti-inflammatory cytokine production in macrophages. Type 4 phosphodiesterases (PDE4) are key cAMP-hydrolyzing enzymes, and PDE4 inhibitors are considered as immunosuppressors to various inflammatory responses. We demonstrate here that PDE4 inhibitors enhance the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) secretion in LPS-activated mouse peritoneal macrophages, and this response was regulated at the transcriptional level rather than an increased IL-1Ra mRNA stability. Studies with PDE4-deficient macrophages revealed that the IL-1Ra upregulation elicited by LPS alone is PKA-independent, whereas the rolipram-enhanced response was mediated by inhibition of only PDE4B, one of the three PDE4 isoforms expressed in macrophages, and it requires PKA but not Epac activity. However, both pathways activate CREB to induce IL-1Ra expression. PDE4B ablation also promoted STAT3 phosphorylation (Tyr705) to LPS stimulation, but this STAT3 activation is not entirely responsible for the IL-1Ra upregulation in PDE4B-deficient macrophages. In a model of LPS-induced sepsis, only PDE4B-deficient mice displayed an increased circulating IL-1Ra, suggesting a protective role of PDE4B inactivation in vivo. These findings demonstrate that PDE4B negatively modulates anti-inflammatory cytokine expression in innate immune cells, and selectively targeting PDE4B should retain the therapeutic benefits of nonselective PDE4 inhibitors. PMID:28383060

  13. The higher level of complexity of K-Ras4B activation at the membrane

    PubMed Central

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S.; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-01-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5′-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.—Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. PMID:26718888

  14. Radiation processing as a post-harvest quarantine control for raisins, dried figs and dried apricots

    NASA Astrophysics Data System (ADS)

    Cetinkaya, N.; Ozyardımci, B.; Denli, E.; Ic, E.

    2006-03-01

    The commercially packed samples of raisins, dried figs and dried apricots were irradiated using doses in the range of 0.5-1.0 kGy for disinfestation and 0.5-5.0 kGy for sensory analysis with the dose rate ranging from 1.44 to 1.92 kGy/h. Pests on dried fruits were evaluated after 0, 1, 2 and 3 months of storage for irradiated dried figs and 1, 3, 6 and 12 months of storage for raisins and dried apricots. Sensory analysis of dried figs, dried apricots and raisins were carried out after 0, 1, 3, 6 and 12 months of storage. The results indicated that radiation processing at low doses, (˜1.0 kGy) is an effective post-harvest treatment and quarantine control for these products with no adverse effects on sensory (marketing) attributes.

  15. Molecular approaches to identify cryptic species and polymorphic species within a complex community of fig wasps.

    PubMed

    Xiao, Jin-Hua; Wang, Ning-Xin; Li, Yan-Wei; Murphy, Robert W; Wan, Dong-Guang; Niu, Li-Ming; Hu, Hao-Yuan; Fu, Yue-Guan; Huang, Da-Wei

    2010-11-29

    Cryptic and polymorphic species can complicate traditional taxonomic research and both of these concerns are common in fig wasp communities. Species identification is very difficult, despite great effort and the ecological importance of fig wasps. Herein, we try to identify all chalcidoid wasp species hosted by one species of fig, using both morphological and molecular methods. We compare the efficiency of four different DNA regions and find that ITS2 is highly effective for species identification, while mitochondrial COI and Cytb regions appear less reliable, possibly due to the interference signals from either nuclear copies of mtDNA, i.e. NUMTs, or the effects of Wolbachia infections. The analyses suggest that combining multiple markers is the best choice for inferring species identifications as any one marker may be unsuitable in a given case.

  16. 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.

  17. Comparison of the Pharmacological Profiles of Selective PDE4B and PDE4D Inhibitors in the Central Nervous System

    PubMed Central

    Zhang, Chong; Xu, Ying; Zhang, Han-Ting; Gurney, Mark E.; O’Donnell, James M.

    2017-01-01

    Inhibition of cyclic AMP (cAMP)-specific phosphodiesterase 4 (PDE4) has been proposed as a potential treatment for a series of neuropsychological conditions such as depression, anxiety and memory loss. However, the specific involvement of each of the PDE4 subtypes (PDE4A, 4B and 4C) in different categories of behavior has yet to be elucidated. In the present study, we compared the possible pharmacological effects of PDE4B and PDE4D selective inhibitors, A-33 and D159687, in mediating neurological function in mice. Both compounds were equally potent in stimulating cAMP signaling in the mouse hippocampal cell line HT-22 leading to an increase in CREB phosphorylation. In contrast, A-33 and D159687 displayed distinct neuropharmacological effects in mouse behavioral tests. A-33 has an antidepressant-like profile as indicated by reduced immobility time in the forced swim and tail suspension tasks, as well as reduced latency to feed in the novelty suppressed feeding test. D159687, on the other hand, had a procognitive profile as it improved memory in the novel object recognition test but had no antidepressant or anxiolytic benefit. The present data suggests that inhibitors targeting specific subtypes of PDE4 may exhibit differential pharmacological effects and aid a more efficient pharmacotherapy towards neuropsychological conditions. PMID:28054669

  18. 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

  19. 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

  20. New occurrence of non-pollinating fig wasps (Hymenoptera: Chalcidoidea) in Ficus microcarpa in Brazil.

    PubMed

    Farache, Fernando H A; O, Vanessa T do; Pereira, Rodrigo A S

    2009-01-01

    Ficus microcarpa is an Asian fig tree that is ornamentally cultivated. The specific pollinator, Eupristina verticillata Waterston, and the non-pollinators Walkerella microcarpae Boucek and Philotrypesis emeryi Grandi, have been reported associated to F. microcarpa in Brazil. In here we report for the first time the occurrence of Odontofroggatia ishii Wiebes and Philotrypesis taiwanensis Chen et al in F. microcarpa in Brazil. Our results suggest that P. taiwanensis and O. ishii represent a recent influx of these wasps into Brazil. Considering that approximately 20 fig wasp species are associated with F. microcarpa in its native area, novel occurrences can be reported in the future in Brazil.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25906080

  2. 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

    2015-04-03

    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.

  3. Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches.

    PubMed

    Li, Jing; Zhou, Nan; Liu, Wen; Li, Jianzong; Feng, Yu; Wang, Xiaoyun; Wu, Chuanfang; Bao, Jinku

    2016-05-01

    cAMP, intracellular cyclic adenosine monophosphate, is a ubiquitous second messenger that plays a key role in many physiological processes. PDE4B which can reduce the cAMP level by hydrolyzing cAMP to 5'-AMP has become a therapeutic target for the treatment of human diseases such as respiratory disorders, inflammation diseases, neurological and psychiatric disorders. However, the use of currently available PDE4B inhibitors is restricted due to serious side effects caused by targeting PDE4D. Hence, we are attempting to find out subfamily-selective PDE4B inhibitors from natural products, using computer-aided approaches such as virtual screening, docking, and molecular dynamics simulation. Finally, four potential PDE4B-selective inhibitors (ZINC67912770, ZINC67912780, ZINC72320169, and ZINC28882432) were found. Compared to the reference drug (roflumilast), they scored better during the virtual screening process. Binding free energy for them was -317.51, -239.44, -215.52, and -165.77 kJ/mol, better than -129.05 kJ/mol of roflumilast. The pharmacophore model of the four candidate inhibitors comprised six features, including one hydrogen bond donor, four hydrogen bond acceptors, and one aromatic ring feature. It is expected that our study will pave the way for the design of potent PDE4B-selective inhibitors of new drugs to treat a wide variety of diseases such as asthma, COPD, psoriasis, depression, etc.

  4. 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.

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

    PubMed Central

    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

  6. 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.

  7. Wetting of microstructured alumina fabricated by epitaxial growth of Al4B2O9 whiskers

    NASA Astrophysics Data System (ADS)

    Wang, Yifeng; Feng, Jicai; Chen, Zhe; Song, Xiaoguo; Cao, Jian

    2015-12-01

    Topographical microstructures were fabricated on alumina by epitaxial growth of Al4B2O9 whiskers in air. The products were characterized via scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. The whiskers were found to grow along the [0 0 1] crystallographic direction, and the lattice mismatch between Al2O3 and Al4B2O9 was determined to be 0.03%. The wetting of the Al4B2O9-whisker-coated surfaces by Ag-36.7Cu-8.0Ti at.% alloy was studied. The time needed to reach the equilibrium stage reduced as the temperature increased, and the final contact angle for liquid alloy on the rough surface was 27° at 880 °C. The wetting dynamics of the whiskers coated surfaces was investigated. After wetting, a whisker-interconnected region was formed between alumina and the alloy.

  8. Alternative pathways for association and dissociation of the calmodulin-binding domain of plasma membrane Ca(2+)-ATPase isoform 4b (PMCA4b).

    PubMed

    Penniston, John T; Caride, Ariel J; Strehler, Emanuel E

    2012-08-24

    The calmodulin (CaM)-binding domain of isoform 4b of the plasma membrane Ca(2+) -ATPase (PMCA) pump is represented by peptide C28. CaM binds to either PMCA or C28 by a mechanism in which the primary anchor residue Trp-1093 binds to the C-terminal lobe of the extended CaM molecule, followed by collapse of CaM with the N-terminal lobe binding to the secondary anchor Phe-1110 (Juranic, N., Atanasova, E., Filoteo, A. G., Macura, S., Prendergast, F. G., Penniston, J. T., and Strehler, E. E. (2010) J. Biol. Chem. 285, 4015-4024). This is a relatively rapid reaction, with an apparent half-time of ~1 s. The dissociation of CaM from PMCA4b or C28 is much slower, with an overall half-time of ~10 min. Using targeted molecular dynamics, we now show that dissociation of Ca(2+)-CaM from C28 may occur by a pathway in which Trp-1093, although deeply embedded in a pocket in the C-terminal lobe of CaM, leaves first. The dissociation begins by relatively rapid release of Trp-1093, followed by very slow release of Phe-1110, removal of C28, and return of CaM to its conformation in the free state. Fluorescence measurements and molecular dynamics calculations concur in showing that this alternative path of release of the PMCA4b CaM-binding domain is quite different from that of binding. The intermediate of dissociation with exposed Trp-1093 has a long lifetime (minutes) and may keep the PMCA primed for activation.

  9. Identification of New ATG4B Inhibitors Based on a Novel High-Throughput Screening Platform.

    PubMed

    Xu, Danqing; Xu, Zhiheng; Han, Li; Liu, Cheng; Zhou, Zheng; Qiu, Zongxing; Lin, Xianfeng; Tang, Guozhi; Shen, Hong; Aebi, Johannes; Riemer, Claus; Kuhn, Bernd; Stahl, Martin; Mark, David; Qin, Ning; Ding, Haiyuan

    2017-04-01

    Autophagy is an evolutionarily conserved homeostasis process through which aggregated proteins or damaged organelles are enveloped in a double-membrane structure called an autophagosome and then digested in a lysosome-dependent manner. Growing evidence suggests that malfunction of autophagy contributes to the pathogenesis of a variety of diseases, including cancer, viral infection, and neurodegeneration. However, autophagy is a complicated process, and understanding of the relevance of autophagy to disease is limited by lack of specific and potent autophagy modulators. ATG4B, a Cys-protease that cleaves ATG8 family proteins, such as LC3B, is a key protein in autophagosome formation and maturation process. A novel time-resolved fluorescence resonance energy transfer (TR-FRET) assay measuring protease activity of ATG4B was developed, validated, and adapted into a high-throughput screening (HTS) format. HTS was then conducted with a Roche focus library of 57,000 compounds. After hit confirmation and a counterscreen to filter out fluorescence interference compounds, 267 hits were confirmed, constituting a hit rate of 0.49%. Furthermore, among 65 hits with an IC50 < 50 µM, one compound mimics the LC3 peptide substrate (-TFG-). Chemistry modification based on this particular hit gave preliminary structure activity relationship (SAR) resulting in a compound with a 10-fold increase in potency. This compound forms a stable covalent bond with Cys74 of ATG4B in a 1:1 ratio as demonstrated by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Furthermore, this compound displayed cellular ATG4B inhibition activity. Overall, the novel TR-FRET ATG4B protease assay plus counterscreen assay provides a robust platform to identify ATG4B inhibitors, which would help to elucidate the mechanism of the autophagy pathway and offer opportunities for drug discovery.

  10. Cross-reactivity between Ficus benjamina (weeping fig) and natural rubber latex.

    PubMed

    Brehler, R; Abrams, E; Sedlmayr, S

    1998-04-01

    The importance of hypersensitivity to Ficus allergens is reported. Cross-sensitization between fig (Ficus carica), weeping fig (F. benjamina [Fb]), and natural rubber latex (NRL) was confirmed by RAST inhibition. We performed skin prick tests with fresh Fb tree sap and NRL extracts in 346 consecutive patients and in 151 patients with immediate-type hypersensitivity to NRL. Total serum IgE and IgE antibodies to NRL and Ficus spp. were analyzed in sera. By the RAST-inhibition method, we studied cross-reactivity among latex, fig, and weeping fig. Sensitization to Fb was diagnosed in 23 of the 346 consecutive patients, and the simultaneous presence of latex-specific IgE was highly significant. Of 151 NRL-allergic patients, 35 were also sensitized to Fb. Cross-reacting IgE antibodies recognizing latex and Ficus allergens were demonstrated by RAST inhibition. The present study reinforces the importance of Fb as an indoor allergen. Cross-reacting IgE antibodies to NRL and Ficus spp. allergens are frequently found in the sera of atopic patients. Development of commercially available standardized extracts for skin tests is urgently necessary.

  11. 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

  12. 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

  13. 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

  14. 76 FR 14320 - Importation of Figs and Pomegranates From Chile Under a Systems Approach

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... pomegranates from Chile using mitigation measures other than fumigation with methyl bromide. DATES: We will... with methyl bromide. The Animal and Plant Health Inspection Service (APHIS) also received a request... fresh figs and pomegranates from Chile using mitigation measures other than fumigation with...

  15. Global focused identification of germplasm strategy (figs) application on Trifolium epens L.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trifolium repens L. is a legume species extensively used in grass pastures. Traits such as level of cyanogenic glucosides and flower production are important in breeding productive and nutritious varieties. The Focused Identification of Germplasm Strategy (FIGS) is an approach used to screen large g...

  16. Local coexistence and genetic isolation of three pollinator species on the same fig tree species.

    PubMed

    Sutton, T L; DeGabriel, J L; Riegler, M; Cook, J M

    2017-01-11

    Molecular tools increasingly reveal cryptic lineages and species that were previously unnoticed by traditional taxonomy. The discovery of cryptic species in sympatry prompts the question of how they coexist in the apparent absence of ecological divergence. However, this assumes first that the molecular taxonomy used to identify cryptic lineages delimits species boundaries accurately. This issue is important, because many diversity studies rely heavily or solely on data from mitochondrial DNA sequences for species delimitation, and several factors may lead to poor identification of species boundaries. We used a multilocus population genetics approach to show that three mtDNA-defined cryptic lineages of the fig wasp Pleistodontes imperialis Saunders, which pollinate Port Jackson figs (Ficus rubiginosa) in north-eastern Australia, represent reproductively isolated species. These species coexist locally, with about 13% of figs (where mating occurs) containing wasps from two or three species. However, there was no evidence for gene flow between them. Confirmed cases of coexisting cryptic species provide excellent opportunities for future studies of the ecological and evolutionary forces shaping both species coexistence and fig/pollinator coevolution.Heredity advance online publication, 11 January 2017; doi:10.1038/hdy.2016.125.

  17. 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.

  18. 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.

  19. Parasitoid fig-wasp evolutionary diversification and variation in ecological opportunity.

    PubMed

    McLeish, M J; van Noort, S; Tolley, K A

    2010-04-01

    Ecological processes are manifest in the evolution and form of phenotype diversity. The great abundance of parasitoid species has led to speculation whether rates of speciation and extinction are dependent on parasitoid diversity. If these factors are mutually exclusive, species diversity should fluctuate instead of remaining relatively constant over time. It is not known whether radiations constrained by coevolutionary interactions conform to density-dependent diversification processes. Here we test the prediction that parasitoid fig wasp diversification responds to changes in ecological opportunity and density-independent processes. A phylogenetic approach is used to estimate relative divergence times and infer diversification rate changes using gamma-statistics. Monte Carlo constant rates tests that accommodate incomplete sampling could not reject constant rates diversification. Parasitoid fig wasp diversification is consistent with a more complex explanation than density-dependent cladogenesis. The results suggest contemporary African parasitoid fig wasp diversity remains a legacy of an ancient ecological opportunity facilitated by fig tree diversification following the breakup of Pan-African forests and evolution of the savanna biome over the last 55 Ma and the more recent aridification of the African continent in the last 5 Ma. These results imply that amplified phenotypic differentiation of specialist insects coevolving with plants is coupled to evolutionarily infrequent changes in ecological opportunity.

  20. 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...

  1. Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses

    PubMed Central

    Wen, Yahong; Shu, Chang; Han, Qingxia; Konan, Kouacou V.; Li, Pingwei; Kao, C. Cheng

    2015-01-01

    ABSTRACT The cyclic dinucleotide 2′,3′-cGAMP can bind the adaptor protein STING (stimulator of interferon [IFN] genes) to activate the production of type I IFNs and proinflammatory cytokines. We found that cGAMP added to the culture medium could suppress the replication of the hepatitis C virus (HCV) genotype 1b strain Con1 subgenomic replicon in human hepatoma cells. Knockdown of STING expression diminished the inhibitory effect on replicon replication, while overexpression of STING enhanced the inhibitory effects of cGAMP. The addition of cGAMP into 1b/Con1 replicon cells significantly increased the expression of type I IFNs and antiviral interferon-stimulated genes. Unexpectedly, replication of the genotype 2a JFH1 replicon and infectious JFH1 virus was less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon. Using chimeric replicons, 2a NS4B was identified to confer resistance to cGAMP. Transient expression of 2a NS4B resulted in a pronounced inhibitory effect on STING-mediated beta IFN (IFN-β) reporter activation compared to that of 1b NS4B. 2a NS4B was found to suppress STING accumulation in a dose-dependent manner. The predicted transmembrane domain of 2a NS4B was required to inhibit STING accumulation. These results demonstrate a novel genotype-specific inhibition of the STING-mediated host antiviral immune response. IMPORTANCE The cyclic dinucleotide cGAMP was found to potently inhibit the replication of HCV genotype 1b Con1 replicon but was less effective for the 2a/JFH1 replicon and infectious JFH1 virus. The predicted transmembrane domain in 2a NS4B was shown to be responsible for the decreased sensitivity to cGAMP. The N terminus of NS4B has been reported to suppress STING-mediated signaling by disrupting the interaction of STING and TBK1 and/or MAVS. We show that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation. PMID:26468527

  2. Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection.

    PubMed

    Okamoto, Nobuhiko; Watanabe, Miki; Naruto, Takuya; Matsuda, Keiko; Kohmoto, Tomohiro; Saito, Masako; Masuda, Kiyoshi; Imoto, Issei

    2017-01-01

    Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B, thus diagnosing this patient with Cabezas syndrome.

  3. Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection

    PubMed Central

    Okamoto, Nobuhiko; Watanabe, Miki; Naruto, Takuya; Matsuda, Keiko; Kohmoto, Tomohiro; Saito, Masako; Masuda, Kiyoshi; Imoto, Issei

    2017-01-01

    Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B, thus diagnosing this patient with Cabezas syndrome. PMID:28144446

  4. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) .

    PubMed

    Bauer, Peter; Leshinsky-Silver, Esther; Blumkin, Lubov; Schlipf, Nina; Schröder, Christopher; Schicks, Julia; Lev, Dorit; Riess, Olaf; Lerman-Sagie, Tally; Schöls, Ludger

    2012-02-01

    We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis,intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

  5. Overview of the Lockheed Martin Compact Fusion Reactor (CFR) T4B Experiment

    NASA Astrophysics Data System (ADS)

    McGuire, Thomas

    2016-10-01

    The Lockheed Martin Compact Fusion Reactor (CFR) Program endeavors to quickly develop a compact fusion power plant with favorable commercial economics and military utility. The CFR uses a diamagnetic, high beta, magnetically encapsulated, linear ring cusp plasma confinement scheme. The goal of the T4B experiment is to demonstrate a suitable plasma target for heating experiments and to characterize the behavior of plasma sources in the CFR configuration. The design of the T4B experiment will be presented, including discussion of predicted behavior, plasma sources, heating mechanisms, diagnostics suite and relevant numerical modeling. ©2016 Lockheed Martin Corporation. All Rights Reserved.

  6. Loss of p15/Ink4b accompanies tumorigenesis triggered by complex DNA double-strand breaks

    PubMed Central

    Camacho, Cristel V.; Mukherjee, Bipasha; McEllin, Brian; Ding, Liang-Hao; Hu, Burong; Habib, Amyn A.; Xie, Xian-Jin; Nirodi, Chaitanya S.; Saha, Debabrata; Story, Michael D.; Balajee, Adayabalam S.; Bachoo, Robert M.; Boothman, David A.; Burma, Sandeep

    2010-01-01

    DNA double-strand breaks (DSBs) are the most deleterious lesion inflicted by ionizing radiation. Although DSBs are potentially carcinogenic, it is not clear whether complex DSBs that are refractory to repair are more potently tumorigenic compared with simple breaks that can be rapidly repaired, correctly or incorrectly, by mammalian cells. We previously demonstrated that complex DSBs induced by high-linear energy transfer (LET) Fe ions are repaired slowly and incompletely, whereas those induced by low-LET gamma rays are repaired efficiently by mammalian cells. To determine whether Fe-induced DSBs are more potently tumorigenic than gamma ray-induced breaks, we irradiated ‘sensitized’ murine astrocytes that were deficient in Ink4a and Arf tumor suppressors and injected the surviving cells subcutaneously into nude mice. Using this model system, we find that Fe ions are potently tumorigenic, generating tumors with significantly higher frequency and shorter latency compared with tumors generated by gamma rays. Tumor formation by Fe-irradiated cells is accompanied by rampant genomic instability and multiple genomic changes, the most interesting of which is loss of the p15/Ink4b tumor suppressor due to deletion of a chromosomal region harboring the CDKN2A and CDKN2B loci. The additional loss of p15/Ink4b in tumors derived from cells that are already deficient in p16/Ink4a bolsters the hypothesis that p15 plays an important role in tumor suppression, especially in the absence of p16. Indeed, we find that reexpression of p15 in tumor-derived cells significantly attenuates the tumorigenic potential of these cells, indicating that p15 loss may be a critical event in tumorigenesis triggered by complex DSBs. PMID:20663777

  7. 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.

  8. 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.

  9. [Knockdown of Larp4b in Lin(-) cells does not affect the colony forming ability of mouse hematopoietic cells].

    PubMed

    Wang, Xiao-Juan; Pang, Ya-Kun; Cheng, Hui; Dong, Fang; Liang, Hao-Yue; Zhang, Ying-Chi; Wang, Xiao-Min; Xu, Jing; Cheng, Tao; Yuan, Wei-Ping

    2013-06-01

    Larp4b is a member of the LARP family, which can interact with RNA and generally stimulate the translation of mRNA. Abnormal expression of Larp4b can be found in leukemia patients in our previous study. This study was purposed to detect the relative expression of Larp4b mRNA in different subpopulations of mouse hematopoietic cells, to construct lentivirus vector containing shLarp4b targeting mouse gene Larp4b and to explore its effects on mouse Lin(-) cells infected with shLarp4b by lentivirus. SF-LV-shLarP4b-EGFP and control vectors were constructed and two-plasmid lentivirus packing system was used to transfect 293T cells. After 48 h and 72 h, lentivirus SF-LV-shLarp4b-EGFP was harvested and was used to infect Lin(-) cells. After 48 h, EGFP(+) cells was sorted by flow cytometry (FCM). Meanwhile, semi-quantitative real time-PCR, AnnexinV-PE/7-AAD staining, PI staining and colony forming cell assay (CFC) were performed to determine the expression of Larp4b and its effect on the proliferation of hematopoietic progenitor cells. The results showed that Larp4b was highly expressed in myeloid cells. SF-LV-shLarp4b-EGFP was successfully constructed according to the restriction endonuclease digestion assay. RT-PCR confirmed that Larp4b was efficiently knockdown in mouse Lin(-) cells. The low expression of Larp4b did not affect the colony forming number, the apoptosis and cell cycle of Lin(-) cells. It is concluded that knockdown of Larp4b in mouse Lin(-) cells do not contribute to the colony forming ability and the growth of Lin(-) cells in vitro. This useful knockdown system will be used to study in vivo Larp4b in future.

  10. Intrathecal injection of phosphodiesterase 4B-specific siRNA attenuates neuropathic pain in rats with L5 spinal nerve ligation.

    PubMed

    Ji, Qing; Di, Yan; He, Xiaoyun; Liu, Qingzhen; Liu, Jian; Li, Weiyan; Zhang, Lidong

    2016-02-01

    Phosphodiesterase 4 (PDE4) is an adenosine cyclic 3,5-monophosphate-specific degradative enzyme, which is closely associated with the inflammatory response. Among its four subtypes (A-D), it remains unclear which one exerts suppressive effects on inflammation and reduces neuropathic pain. The present study aimed to examine the modulation of neuroinflammation by PDE4 subtypes in the spinal cord of a rat model of L5 spinal nerve ligation (SNL)-induced neuropathic pain. The expression levels of PDE4A-D were measured in the lumbar spinal cords of naïve rats. The rats were then divided into seven groups: The sham group (sham surgery + saline), the saline group (SNL + saline), the vehicle group (SNL + Lipofectamine® RNAiMAX), the mismatch small interfering (si)RNA group (SNL + mismatch siRNA), the PDE4A-siRNA group (SNL + PDE4A-siRNA), the PDE4B-siRNA group (SNL + PDE4B-siRNA) and the PDE4D-siRNA group (SNL + PDE4D-siRNA). In order to determine behavioral changes, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded. The mRNA and protein expression levels of PDE4s were also detected. Furthermore, the association between behavioral changes and individual subtypes of PDE4 were studied following intrathecal administration of PDE4A, B and D-specific siRNA. The expression levels of protein kinases, including phosphorylated-extracellular signal-regulated kinases (p-ERK), and inflammatory cytokines were measured, in order to explore the underlying mechanisms. Subtypes A, B and D, but not C, were detected in the naïve rats. After SNL, both MWT and TWL were reduced. The mRNA and protein expression levels of PDE4A, B and D were significantly upregulated after 2, 4, 6 and 8 days of SNL. Subtype-specific siRNA significantly suppressed the elevated expression levels; however, only rats treated with PDE4B siRNA exhibited improved MWT and TWL. Further analysis of the PDE4B siRNA-treated rats demonstrated that 8 days after SNL, the intensity of p

  11. 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...

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

    PubMed

    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.

  13. 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...

  14. 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

  15. PSD-95 mediates membrane clustering of the human plasma membrane Ca2+ pump isoform 4b.

    PubMed

    Padányi, Rita; Pászty, Katalin; Strehler, Emanuel E; Enyedi, Agnes

    2009-06-01

    Besides the control of global calcium changes, specific plasma membrane calcium ATPase (PMCA) isoforms are involved in the regulation of local calcium signals. Although local calcium signaling requires the confinement of signaling molecules into microdomains, little is known about the specific organization of PMCA molecules within the plasma membrane. Here we show that co-expression with the postsynaptic density-95 (PSD-95) scaffolding protein increased the plasma membrane expression of PMCA4b and redistributed the pump into clusters. The clustering of PMCA4b was fully dependent on the presence of its PDZ-binding sequence. Using the fluorescence recovery after photobleaching (FRAP) technique, we show that the lateral membrane mobility of the clustered PMCA4b is significantly lower than that of the non-clustered molecules. Disruption of the actin-based cytoskeleton by cytochalasin D resulted in increased cluster size. Our results suggest that PSD-95 promotes the formation of high-density PMCA4b microdomains in the plasma membrane and that the membrane cytoskeleton plays an important role in the regulation of this process.

  16. 75 FR 54153 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 11... guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions... Electrophoresis General Chapter harmonized text from each of the three pharmacopoeias (United States,...

  17. 75 FR 18509 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Texts for Use in the ICH Regions; Annex 10: Polyacrylamide Gel Electrophoresis General Chapter.'' The... ICH Q4B evaluation of the Polyacrylamide Gel Electrophoresis General Chapter harmonized text from...

  18. 75 FR 17148 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... Dissolution Test General Chapter harmonized text from each of the three pharmacopoeias (United...

  19. 75 FR 53973 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... Sieving General Chapter harmonized text from each of the three pharmacopoeias (United States,...

  20. 75 FR 17147 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... Friability General Chapter harmonized text from each of the three pharmacopoeias (United States,...

  1. 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.

  2. 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.

  3. 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.

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

    PubMed Central

    Wang, Qi; Jiang, Zi-Feng; Wang, Ning-xin; Niu, Li-ming; Li, Zi; Huang, Da-Wei

    2013-01-01

    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. PMID:24101987

  5. Suppressors of cancer cell proliferation from fig (Ficus carica) resin: isolation and structure elucidation.

    PubMed

    Rubnov, S; Kashman, Y; Rabinowitz, R; Schlesinger, M; Mechoulam, R

    2001-07-01

    A mixture of 6-O-acyl-beta-D-glucosyl-beta-sitosterols, the acyl moeity being primarily palmitoyl and linoleyl with minor amounts of stearyl and oleyl, has been isolated as a potent cytotoxic agent from fig (Ficuscarica) latex and soybeans. Identity was established by spectroscopic methods (NMR, MS) and confirmed by chemical synthesis. Both the natural and the synthetic compounds showed in vitro inhibitory effects on proliferation of various cancer cell lines.

  6. Surveillance study of hepatitis A virus RNA on fig and date samples.

    PubMed

    Boxman, Ingeborg L A; te Loeke, Nathalie A J M; Klunder, Kyara; Hägele, Geke; Jansen, Claudia C C

    2012-02-01

    A total of 91 fig and 185 date samples were analyzed by reverse transcription (RT) real-time PCR for the presence of hepatitis A virus (HAV) RNA. Two batches of dates tested positive, and the HAV RNA detected was genotyped as IA. These findings warrant further development of methods applicable to food which is consumed untreated and is exported from countries in which HAV is endemic.

  7. The Crystal Structure of Cytochrome P450 4B1 (CYP4B1) Monoxygenase Complexed with Octane Discloses Several Structural Adaptations for ω-Hydroxylation.

    PubMed

    Hsu, Mei-Hui; Baer, Brian R; Rettie, Allan E; Johnson, Eric F

    2017-02-06

    P450 family 4 fatty acid ω-hydroxylases preferentially oxygenate primary C-H bonds over adjacent, energetically favored secondary C-H bonds, but the mechanism explaining this intriguing preference is unclear. To this end, the structure of rabbit P450 4B1 complexed with its substrate octane was determined by X-ray crystallography to define features of the active site that contribute to a preference for ω-hydroxylation. The structure indicated that octane is bound in a narrow active site cavity that limits access of the secondary C-H bond to the reactive intermediate. A highly conserved sequence motif on helix I contributes to positioning the terminal carbon of octane for ω-hydroxylation. Glu-310 of this motif auto-catalytically forms an ester bond with the heme 5-methyl, and the immobilized E310 contributes to substrate positioning. The preference for ω-hydroxylation was decreased in a E310A mutant having a shorter side-chain, but overall rates of metabolism were retained. E310D and E310Q substitutions having longer side-chains exhibit lower overall rates, likely due to higher conformational entropy for these residues, but they retained high preferences for octane ω-hydroxylation. Sequence comparisons indicated that active-site residues constraining octane for ω-hydroxylation are conserved in family 4 P450s. Moreover, the heme 7-propionate is positioned in the active site and provides additional restraints on substrate binding. In conclusion, P450 4B1 exhibits structural adaptations for ω-hydroxylation that include changes in the conformation of the heme and changes in a highly conserved helix I motif that is associated with selective oxygenation of un-activated primary C-H bonds.

  8. Five Cases of Phytophotodermatitis Caused by Fig Leaves and Relevant Literature Review

    PubMed Central

    Son, Jin-Hwa; Jin, Hyunju; You, Hyang-Suk; Shim, Woo-Haing; Kim, Jeong-Min; Kim, Gun-Wook; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum

    2017-01-01

    Phytophotodermatitis is a condition caused by sequential exposure to photosensitizing substances present in plants followed by ultraviolet light. Several plants (e.g., limes, celery, fig, and wild parsnip) contain furocoumarin compounds (psoralens). It is important for dermatologists to be aware of phytophotodermatitis because it may be misdiagnosed as cellulitis, tinea, or allergic contact dermatitis. We present five patients with a sharply defined erythematous swollen patch with bullae on both feet. They described soaking their feet in a fig leaves decoction to treat their underlying dermatologic diseases. Within 24 hours, all patients had a burning sensation in their feet, and erythema and edema had developed on the feet dorsa with exception of the portion of the skin covered by the sandals. Histopathologic examinations revealed sub-epithelial blisters with intensive epidermal necrosis. Phytophotodermatitis was ultimately diagnosed and, after several days, the patients' skin lesions began to recover upon treatment with systemic and topical corticosteroids. Unfortunately, since there are no studies providing sufficient evidence on the benefits of fig leaves, they should be used with caution. PMID:28223753

  9. Conflict of interest in a mutualism: documenting the elusive fig wasp-seed trade-off

    PubMed Central

    Herre, E. A.; West, S. A.

    1997-01-01

    The generally accepted view that mutualisms represent reciprocal exploitations implies a greater or lesser degree of inherent tension between the partners. This view emphasizes the importance of identifying conflicts of interest between the partners, and then attempting to quantify the effects of factors that influence costs and benefits to each. The natural history of the speciose fig-fig wasp pollination mutualisms permits such measurements. However, previous attempts to document the presumed tensions, which are expected to result in a negative relationship between the production of viable seeds and pollinator wasp offspring, have met with mixed results, casting doubt on the existence of the conflict. Here, we present hierarchical analyses of 929 fruits sampled from 30 crops representing nine species of monoecious New World figs. These analyses control for the confounding influences of variation in (1) pollination intensity (numbers of foundress pollinators); (2) flower number per fruit; and (3) the proportion of those flowers that develop, on seed and wasp production, both among and within crops. We thereby show that a negative relationship between the production of viable seeds and wasps is, in fact, ubiquitous, thus documenting this underlying tension inherent in the mutualism. We suggest that complex interactions of variables that influence costs and benefits are likely to be a general property of most mutualistic systems.

  10. New insights into the phylogeny of fig pollinators using Bayesian analyses.

    PubMed

    Jiang, Zi-Feng; Huang, Da-Wei; Zhu, Chao-Dong; Zhen, Wen-Quan

    2006-02-01

    The interaction between figs and fig pollinators is one of the most species-specific mutualisms. Recently, phylogenies of both partners based on molecular data provided insights into a wide spectrum of co-evolutionary questions. However, for the phylogeny of fig pollinators, there are some discrepancies between different studies and left some relationships unresolved, especially for deep nodes. The phylogenetic uncertainties of pollinators prohibit our further understanding of the history of the mutualism. Here, we present phylogenetic analyses of a larger COI sequence dataset that includes previously published datasets and our sequences from 20 species using Bayesian method and maximum parsimony. The analyses using different methods share similar topologies. Bayesian analyses provide high level of confidence for most internal nodes in terms of posterior probability. This study also clarifies some discrepancies between previous studies. After rooting with Tetrapus, other pollinators split into two clades. Wiebesia and Blastophaga are at basal positions in respective clade. Ceratosolen is not monophyletic because Kradibia and Liporrhopalum fall inside this group. Three subgenera of Ceratosolen: subgen. Ceratosolen, subgen. Rothropus, and subgen. Strepitus are not supported. Therefore, Ceratosolen is suggested to be re-divided into three groups. Urostigma pollinators (including Dolichoris and Blastophaga psenes) are clustered together. The monophylies of Wiebesia, Blastophaga, Dolichoris are not supported in this analysis. This study also provides a new framework for re-evaluating character evolution and re-inspecting the definition of some genera.

  11. FigSum: automatically generating structured text summaries for figures in biomedical literature.

    PubMed

    Agarwal, Shashank; Yu, Hong

    2009-11-14

    Figures are frequently used in biomedical articles to support research findings; however, they are often difficult to comprehend based on their legends alone and information from the full-text articles is required to fully understand them. Previously, we found that the information associated with a single figure is distributed throughout the full-text article the figure appears in. Here, we develop and evaluate a figure summarization system - FigSum, which aggregates this scattered information to improve figure comprehension. For each figure in an article, FigSum generates a structured text summary comprising one sentence from each of the four rhetorical categories - Introduction, Methods, Results and Discussion (IMRaD). The IMRaD category of sentences is predicted by an automated machine learning classifier. Our evaluation shows that FigSum captures 53% of the sentences in the gold standard summaries annotated by biomedical scientists and achieves an average ROUGE-1 score of 0.70, which is higher than a baseline system.

  12. Wind-borne insects mediate directional pollen transfer between desert fig trees 160 kilometers apart

    PubMed Central

    Ahmed, Sophia; Compton, Stephen G.; Butlin, Roger K.; Gilmartin, Philip M.

    2009-01-01

    The question of how far pollen can move between plants has implications for topics as diverse as habitat fragmentation, conservation management, and the containment of genetically modified crops. The monoecious African fig tree Ficus sycomorus L. relies on the small, short-lived, night-flying, host-specific fig wasp Ceratosolen arabicus Mayr for pollination. We used microsatellite markers to characterize a geographically isolated riparian population of F. sycomorus growing along the Ugab River in the Namib Desert, Namibia, together with paternity analysis of seedlings from known mothers, to map pollen movement within this population. In this way we tracked insect movements between individually recognizable trees by means of their pollen cargo and documented the movement of C. arabicus between known trees separated by more than 160 km, with a mean distance for confirmed successful pollination events of 88.6 km. The predominant observed movement of pollinators was in a westerly direction, toward the sea, reflecting seasonal nighttime wind direction and the wind-borne dispersal of fig wasps. Our results suggest the existence of an extensive panmictic population of trees that are well suited to overcome the effects of geographical isolation. PMID:19910534

  13. 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.

  14. 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.

  15. Five Cases of Phytophotodermatitis Caused by Fig Leaves and Relevant Literature Review.

    PubMed

    Son, Jin-Hwa; Jin, Hyunju; You, Hyang-Suk; Shim, Woo-Haing; Kim, Jeong-Min; Kim, Gun-Wook; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Byung-Soo

    2017-02-01

    Phytophotodermatitis is a condition caused by sequential exposure to photosensitizing substances present in plants followed by ultraviolet light. Several plants (e.g., limes, celery, fig, and wild parsnip) contain furocoumarin compounds (psoralens). It is important for dermatologists to be aware of phytophotodermatitis because it may be misdiagnosed as cellulitis, tinea, or allergic contact dermatitis. We present five patients with a sharply defined erythematous swollen patch with bullae on both feet. They described soaking their feet in a fig leaves decoction to treat their underlying dermatologic diseases. Within 24 hours, all patients had a burning sensation in their feet, and erythema and edema had developed on the feet dorsa with exception of the portion of the skin covered by the sandals. Histopathologic examinations revealed sub-epithelial blisters with intensive epidermal necrosis. Phytophotodermatitis was ultimately diagnosed and, after several days, the patients' skin lesions began to recover upon treatment with systemic and topical corticosteroids. Unfortunately, since there are no studies providing sufficient evidence on the benefits of fig leaves, they should be used with caution.

  16. Wind-borne insects mediate directional pollen transfer between desert fig trees 160 kilometers apart.

    PubMed

    Ahmed, Sophia; Compton, Stephen G; Butlin, Roger K; Gilmartin, Philip M

    2009-12-01

    The question of how far pollen can move between plants has implications for topics as diverse as habitat fragmentation, conservation management, and the containment of genetically modified crops. The monoecious African fig tree Ficus sycomorus L. relies on the small, short-lived, night-flying, host-specific fig wasp Ceratosolen arabicus Mayr for pollination. We used microsatellite markers to characterize a geographically isolated riparian population of F. sycomorus growing along the Ugab River in the Namib Desert, Namibia, together with paternity analysis of seedlings from known mothers, to map pollen movement within this population. In this way we tracked insect movements between individually recognizable trees by means of their pollen cargo and documented the movement of C. arabicus between known trees separated by more than 160 km, with a mean distance for confirmed successful pollination events of 88.6 km. The predominant observed movement of pollinators was in a westerly direction, toward the sea, reflecting seasonal nighttime wind direction and the wind-borne dispersal of fig wasps. Our results suggest the existence of an extensive panmictic population of trees that are well suited to overcome the effects of geographical isolation.

  17. Premature Attraction of Pollinators to Inaccessible Figs of Ficus altissima: A Search for Ecological and Evolutionary Consequences

    PubMed Central

    Zhang, Yuan; Peng, Yan-Qiong; Compton, Stephen G.; Yang, Da-Rong

    2014-01-01

    Adult life spans of only one or two days characterise life cycles of the fig wasps (Agaonidae) that pollinate fig trees (Ficus spp., Moraceae). Selection is expected to favour traits that maximise the value of the timing of encounters between such mutualistic partners, and fig wasps are usually only attracted to their hosts by species- and developmental-stage specific volatiles released from figs at the time when they are ready to be entered, oviposited in and pollinated. We found that Ficus altissima is exceptional, because it has persistent tight-fitting bud covers that prevent its Eupristina altissima pollinator (and a second species of ‘cheater’ agaonid) from entering its figs for several days after they start to be attracted. We examined the consequences of delayed entry for the figs and fig wasps and tested whether delayed entry has been selected to increase adult longevity. We found that older pollinators produced fewer and smaller offspring, but seed production was more efficient. Pollinator offspring ratios also varied depending on the age of figs they entered. The two agaonids from F. altissima lived slightly longer than six congeners associated with typical figs, but this was explainable by their larger body sizes. Delayed entry generates reproductive costs, especially for the pollinator. This opens an interesting perspective on the coevolution of figs and their pollinators and on the nature of mutualistic interactions in general. PMID:24466217

  18. Development and characterization of a replicon-based phenotypic assay for assessing HCV NS4B from clinical isolates.

    PubMed

    Rajyaguru, Sonal; Yang, Huiling; Martin, Ross; Miller, Michael D; Mo, Hongmei

    2013-11-01

    The hepatitis C virus (HCV) NS4B inhibitors have shown potent inhibition of HCV replication in vitro. To assess the effect of viral diversity on the susceptibility to NS4B inhibitors, genotype (GT)-specific GT1a and GT1b replicon shuttle vectors were designed and created for cloning HCV NS4B genes from clinical isolates. For the GT1b NS4B shuttle vector, the S2204I adaptive mutation was introduced in NS5A to improve replication due to the replacement of the K1846T adaptive mutation in NS4B with NS4B from the clinical isolates. In addition to the adaptive mutations, a newly identified Huh-7 cell line, Huh-7-1C, which is highly permissive for both GT1a and GT1b replication, was used to further enhance the replication levels. HCV NS4B gene from clinical isolates was amplified and inserted into the corresponding GT1a and GT1b modified lab strain chimeric replicons. GT1a and GT1b chimeric replicons expressing diverse NS4B genes from corresponding subtypes of clinical isolates replicated at highly efficient levels for phenotypic analysis. Due to natural variation in their amino acid residues in NS4B, these isolates displayed varying drug susceptibilities to an NS4B inhibitor. In mixed populations with wild-type, the sensitivity of resistance detection of NS4B resistant mutants H94R and V105M was between 20% and 80%. The chimeric shuttle vectors can be used to characterize the activity of antiviral drugs targeting NS4B from diverse natural clinical isolates and aid in the development of novel compounds against HCV NS4B.

  19. 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.

  20. Qatar Exoplanet Survey : Qatar-3b, Qatar-4b, and Qatar-5b

    NASA Astrophysics Data System (ADS)

    Alsubai, Khalid; Mislis, Dimitris; Tsvetanov, Zlatan I.; Latham, David W.; Bieryla, Allyson; Buchhave, Lars A.; Esquerdo, Gilbert A.; Bramich, D. M.; Pyrzas, Stylianos; Vilchez, Nicolas P. E.; Mancini, Luigi; Southworth, John; Evans, Daniel F.; Henning, Thomas; Ciceri, Simona

    2017-04-01

    We report the discovery of Qatar-3b, Qatar-4b, and Qatar-5b, three new transiting planets identified by the Qatar Exoplanet Survey. The three planets belong to the hot Jupiter family, with orbital periods of {P}{{Q}3{{b}}} = 2.50792 days, {P}{{Q}4{{b}}} = 1.80539 days, and {P}{{Q}5{{b}}} = 2.87923 days. Follow-up spectroscopic observations reveal the masses of the planets to be {M}{{Q}3{{b}}} = 4.31 ± 0.47 {M}{{J}}, {M}{{Q}4{{b}}} = 6.10 ± 0.54 {M}{{J}}, and {M}{{Q}5{{b}}} = 4.32 ± 0.18 {M}{{J}}, while model fits to the transit light curves yield radii of {R}{{Q}3{{b}}} = 1.096 ± 0.14 {R}{{J}}, {R}{{Q}4{{b}}} = 1.135 ± 0.11 {R}{{J}}, and {R}{{Q}5{{b}}} = 1.107 ± 0.064 {R}{{J}}. The host stars are low-mass main sequence stars with masses and radii M Q3 = 1.145 ± 0.064 M ⊙, M Q4 = 0.896 ± 0.048 M ⊙, M Q5 = 1.128 ± 0.056 M ⊙ and R Q3 = 1.272 ± 0.14 R ⊙, R Q4 = 0.849 ± 0.063 R ⊙, and R Q5 = 1.076 ± 0.051 R ⊙ for Qatar-3, 4, and 5 respectively. The V magnitudes of the three host stars are V Q3 = 12.88, V Q4 = 13.60, and V Q5 = 12.82. All three new planets can be classified as heavy hot Jupiters (M > 4 M J).

  1. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

    PubMed

    Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong

    2016-09-21

    Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever.

  2. Molecular docking NS4B of DENV 1-4 with known bioactive phyto-chemicals

    PubMed Central

    Paul, Anubrata; Vibhuti, Arpana; Raj, Samuel

    2016-01-01

    Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS4B is a target for designing specific antivirals due to its importance in viral replication. Medicinal plants have been a savior for dengue virus as they consist of a class of phytochemicals having anti-viral activity and can pose a new approach ofstrong drug against viruses. The present study analyzes the activity of compounds against NS4B of DENV (1-4) serotypes. In this study Catechin, Cianidanol, Epicatechin, Eupatoretin, Glabranin, Laurifolin, DL-Catechin, astherapeutic agents were filtered by using Lipinski rule’s five and the drug-likeness property of these agents were used for assessment of pharmacological properties. The molecular docking results presented the 2-D structures of bioactive complex, which interacted with especially conserved residues of target domains. Interestingly, we find the Catechin, Laurifolin, Cianidanol have highest binding energy against NS4B in DENV-1,2,4 which is evident by the formation of more hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results revealed that the bioactive compound, especially Catechin has significant anti-dengue activities. In addition, this study may be helpful in further experimental investigations. PMID:28149049

  3. 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.

  4. 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.

  5. Inhibition of HCV replication by humanized-single domain transbodies to NS4B.

    PubMed

    Glab-Ampai, Kittirat; Malik, Aijaz Ahmad; Chulanetra, Monrat; Thanongsaksrikul, Jeeraphong; Thueng-In, Kanyarat; Srimanote, Potjanee; Tongtawe, Pongsri; Chaicumpa, Wanpen

    2016-08-05

    NS4B of hepatitis C virus (HCV) initiates membrane web formation, binds RNA and other HCV proteins for viral replication complex (RC) formation, hydrolyses NTP, and inhibits innate anti-viral immunity. Thus, NS4B is an attractive target of a novel anti-HCV agent. In this study, humanized-nanobodies (VHs/VHHs) that bound to recombinant NS4B were produced by means of phage display technology. The nanobodies were linked molecularly to a cell penetrating peptide, penetratin (PEN), for making them cell penetrable (become transbodies). Human hepatic (Huh7) cells transfected with HCV JFH1-RNA that were treated with transbodies from four Escherichia coli clones (PEN-VHH7, PEN-VHH9, PEN-VH33, and PEN-VH43) had significant reduction of HCV RNA amounts in their culture fluids and intracellularly when compared to the transfected cells treated with control transbody and medium alone. The results were supported by the HCV foci assay. The transbody treated-transfected cells also had upregulation of the studied innate cytokine genes, IRF3, IFNβ and IL-28b. The transbodies have high potential for testing further as a novel anti-HCV agent, either alone, adjunct of existing anti-HCV agents/remedies, or in combination with their cognates specific to other HCV enzymes/proteins.

  6. (4R,4aS,4bS,7R,10aR)-4-Hy­droxy-4a,7-dimethyl-2-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-deca­hydro­phenanthren-1-one

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Machado, André T. Lousada; Brocksom, Timothy J.; Ferreira, M. Lúcia; Tiekink, Edward R. T.

    2011-01-01

    In the title compound, C19H28O2, the A ring adopts a chair conformation, and each of the B and C rings adopts a distorted half-chair conformation with the methine C atom in the CH2C(H)C(=O) residue, common to both rings, lying 0.6397 (19) and 0.6328 (18) Å out of the approximate plane defined by the remaining five C atoms (r.m.s. deviations = 0.0791 and 0.0901 Å for rings B and C, respectively). Helical supra­molecular chains along the a axis mediated by hy­droxy–carbonyl O—H⋯O hydrogen bonds feature in the crystal packing. PMID:22220138

  7. (4R*,4aS*,4bS*,5R*,10aR*)-4-Hy­droxy-4a,5-dimethyl-2-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-deca­hydro­phenan­thren-1-one

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Machado, André T. Lousada; Brocksom, Timothy J.; Ferreira, M. Lúcia; Tiekink, Edward R. T.

    2011-01-01

    In the title compound, C19H28O2, the A ring adopts a chair conformation. Both the B and C rings adopt envelope conformations with the C atoms common to both rings and adjacent to the carbonyl and hydroxyl groups, respectively, lying 0.604 (3) and 0.634 (3) Å out of the mean planes defined by the remaining five C atoms of rings B and C, respectively (r.m.s. deviations = 0.0100 and 0.0157 Å, respectively). The formation of linear supra­molecular C(7) chains along the a axis mediated by hy­droxy-O—H⋯O(carbon­yl) hydrogen bonds is the most prominent feature of the crystal packing. PMID:22199834

  8. 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

  9. Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy

    PubMed Central

    Vaccari, Ilaria; Carbone, Antonietta; Previtali, Stefano Carlo; Mironova, Yevgeniya A.; Alberizzi, Valeria; Noseda, Roberta; Rivellini, Cristina; Bianchi, Francesca; Del Carro, Ubaldo; D'Antonio, Maurizio; Lenk, Guy M.; Wrabetz, Lawrence; Giger, Roman J.; Meisler, Miriam H.; Bolino, Alessandra

    2015-01-01

    Mutations of FIG4 are responsible for Yunis-Varón syndrome, familial epilepsy with polymicrogyria, and Charcot-Marie-Tooth type 4J neuropathy (CMT4J). Although loss of the FIG4 phospholipid phosphatase consistently causes decreased PtdIns(3,5)P2 levels, cell-specific sensitivity to partial loss of FIG4 function may differentiate FIG4-associated disorders. CMT4J is an autosomal recessive neuropathy characterized by severe demyelination and axonal loss in human, with both motor and sensory involvement. However, it is unclear whether FIG4 has cell autonomous roles in both motor neurons and Schwann cells, and how loss of FIG4/PtdIns(3,5)P2-mediated functions contribute to the pathogenesis of CMT4J. Here, we report that mice with conditional inactivation of Fig4 in motor neurons display neuronal and axonal degeneration. In contrast, conditional inactivation of Fig4 in Schwann cells causes demyelination and defects in autophagy-mediated degradation. Moreover, Fig4-regulated endolysosomal trafficking in Schwann cells is essential for myelin biogenesis during development and for proper regeneration/remyelination after injury. Our data suggest that impaired endolysosomal trafficking in both motor neurons and Schwann cells contributes to CMT4J neuropathy. PMID:25187576

  10. Yunis-Varón Syndrome Is Caused by Mutations in FIG4, Encoding a Phosphoinositide Phosphatase

    PubMed Central

    Campeau, Philippe M.; Lenk, Guy M.; Lu, James T.; Bae, Yangjin; Burrage, Lindsay; Turnpenny, Peter; Román Corona-Rivera, Jorge; Morandi, Lucia; Mora, Marina; Reutter, Heiko; Vulto-van Silfhout, Anneke T.; Faivre, Laurence; Haan, Eric; Gibbs, Richard A.; Meisler, Miriam H.; Lee, Brendan H.

    2013-01-01

    Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of FIG4 in affected individuals from three unrelated families. FIG4 encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P2 levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of Fig4-null mouse fibroblasts. Homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarged vacuoles in neurons. We demonstrate that Fig4-null mice also have small skeletons with reduced trabecular bone volume and cortical thickness and that cultured osteoblasts accumulate large vacuoles. Our findings demonstrate that homozygosity or compound heterozygosity for null mutations of FIG4 is responsible for YVS, the most severe known human phenotype caused by defective phosphoinositide metabolism. In contrast, in Charcot-Marie-Tooth disease type 4J (also caused by FIG4 mutations), one of the FIG4 alleles is hypomorphic and disease is limited to the peripheral nervous system. This genotype-phenotype correlation demonstrates that absence of FIG4 activity leads to central nervous system dysfunction and extensive skeletal anomalies. Our results describe a role for PI(3,5)P2 signaling in skeletal development and maintenance. PMID:23623387

  11. Efficient transformation and regeneration of fig (Ficus carica L.) via somatic embryogenesis.

    PubMed

    Soliman, Hemaid Ibrahim; Gabr, Mahdia; Abdallah, Naglaa A

    2010-01-01

    Fig is one of the most important fruit trees in Egypt. It used to constitute the major source of income for the inhabitants of the western north coast of Egypt. Since 1993 fig cultivations were threatened by a number of factors including virus, insect and mite infections. An efficient system for regeneration and transformation of the common fig Ficus carica L. cultivar Sultani (fresh consumption) was required to conserve fig cultivation in the area. The effect of different combinations of BA and NAA/2,4-D and kinetin on callus formation from leaf segments were studied. Results showed that the best medium for callus formation was MS supplemented with 2.0 mg/l 2,4-D and 0.2 mg/l kinetin. The best plantlet differentiation was obtained at concentrations of 30 mg/l 2iP and 7 mg/l TDZ with 0.25 mg/l NAA (with a regeneration efficiency of 83 and 79%, respectively). On the other hand, the obtained callus failed to induce organogenesis on media containing a combination of BA and kinetin. The highest shoot formation percentage (89%) was obtained when using 2 mg/l TDZ and 4 mg/l 2iP. The highest percentage of shoots forming roots (95%) was obtained when using MS medium supplemented with 1.0 mg/l IBA. Explants were transformed using Agrobacterium and microprojectile bombardment using the plasmid pISV2678 which harbors the gus-intron and bar genes. Results showed that the highest transformation efficiency using the Agrobacterium (17.5%) was obtained when explants were co-cultivated with the bacteria for 30 min. The highest transformation efficiency recorded using the microprojectile bombardment (12%) was obtained with 2.0 μg DNA per shot at 1,100 psi and a distance of 6 cm repeated twice. The transgenic nature of regenerated plants was confirmed by PCR analysis, histochemical GUS assay and leaf painting assay.

  12. Vacuolar protein sorting 4B regulates apoptosis of intestinal epithelial cells via p38 MAPK in Crohn's disease.

    PubMed

    Zhang, Dongmei; Wang, Liang; Yan, Lijun; Miao, Xianjing; Gong, Chen; Xiao, Min; Ni, Runzhou; Tang, Qiyun

    2015-02-01

    Vacuolar protein sorting 4B (VPS4B), a member of ATPase family proteins, reportedly possesses multiple biological functions, such as regulating the development of breast cancer and non-small-cell lung cancer, participating in Parkinson's disease, and modulating neuronal apoptosis after cerebral ischemia. However, its expression and potential functions in Crohn's disease (CD) has not been understood. In this study, we reported for the first time that VPS4B was over-expressed in intestinal epithelial cell (IECs) of patients with CD. In TNBS-induced mouse colitis models, we observed the up-regulation of VPS4B was accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and phosphorylated p38 in colitis IECs. Co-localization of VPS4B and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of VPS4B in IEC apoptosis. Employing the TNF-α-treated HT29 cells as an in vitro IEC apoptosis model, we confirmed the positive correlation of VPS4B with caspase-dependent cellular apoptosis. Knocking VPS4B down by siRNA significantly alleviated TNF-α-induced p38 phosphorylation and cellular apoptosis in HT29 cells. Taken together, our findings suggested that VPS4B may facilitate the IEC apoptosis in CD via p38 MAPK signaling pathway.

  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 Central

    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. PMID:24223925

  15. 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.

  16. 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.

  17. 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.

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

    PubMed Central

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

    2008-01-01

    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

  19. 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%.

  20. INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas

    PubMed Central

    Wilmott, James S.; Guo, Xiang Yun; Yan, Xu Guang; Wang, Chun Yan; Liu, Xiao Ying; Jin, Lei; Tseng, Hsin-Yi; Liu, Tao; Croft, Amanda; Hondermarck, Hubert; Scolyer, Richard A.; Jiang, Chen Chen; Zhang, Xu Dong

    2015-01-01

    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates PI3K/Akt signalling and has a tumour suppressive role in some types of cancers. However, we have found that it is upregulated in a subset of melanomas. Here we report that INPP4B can function as an oncogenic driver through activation of serum- and glucocorticoid-regulated kinase 3 (SGK3) in melanoma. While INPP4B knockdown inhibited melanoma cell proliferation and retarded melanoma xenograft growth, overexpression of INPP4B enhanced melanoma cell and melanocyte proliferation and triggered anchorage-independent growth of melanocytes. Noticeably, INPP4B-mediated melanoma cell proliferation was not related to activation of Akt, but was mediated by SGK3. Upregulation of INPP4B in melanoma cells was associated with loss of miRNA (miR)-494 and/or miR-599 due to gene copy number reduction. Indeed, overexpression of miR-494 or miR-599 downregulated INPP4B, reduced SGK3 activation, and inhibited melanoma cell proliferation, whereas introduction of anti-miR-494 or anti-miR-599 upregulated INPP4B, enhanced SGK3 activation, and promoted melanoma cell proliferation. Collectively, these results identify upregulation of INPP4B as an oncogenic mechanism through activation of SGK3 in a subset of melanomas, with implications for targeting INPP4B and restoring miR-494 and miR-599 as novel approaches in the treatment of melanomas with high INPP4B expression. PMID:26573229

  1. 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

  2. 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.

  3. 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.

  4. 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 with respect to fresh baby kiwi fruit grown in Chile. The analyses evaluate the risks associated...

  5. Natural enemies managing the invasion of the Fig whitefly, Singhiella simplex (Hemiptera: Aleyrodidae), infesting a Ficus benjamina hedge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fig whitefly, Singhiella simplex (Singh) is a recent invasive species that has become a major pest in Florida feeding on Ficus shrubs and trees. A pilot study was conducted on a weeping fig, Ficus benjamina shrub hedge to determine the efficacy and compatibility of a biopesticide (PFR 97™=Isaria...

  6. 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.

  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.

  8. 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.

  9. 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

  10. Synergistic interactions between PDE4B and GSK-3: DISC1 mutant mice.

    PubMed

    Lipina, Tatiana V; Wang, Min; Liu, Fang; Roder, John C

    2012-03-01

    Disrupted-In-Schizophrenia-1 (DISC1) is a strong genetic risk factor associated with psychiatric disorders. Two distinct mutations in the second exon of the DISC1 gene (Q31L and L100P) lead to either depression- or schizophrenia-like behavior in mice. Both phosphodiesterase-4B (PDE4B) and glycogen synthase kinase-3 (GSK-3) have common binding sites on N-terminal region of DISC1 and are implicated into etiology of schizophrenia and depression. It is not known if PDE4B and GSK-3 could converge signals in the cell via DISC1 at the same time. The purpose of the present study was to assess whether rolipram (PDE4 inhibitor) might synergize with TDZD-8 (GSK-3 blocker) to produce antipsychotic effects at low doses on the DISC1-L100P genetic model. Indeed, combined treatment of DISC1-L100P mice with rolipram (0.1 mg/kg) and TDZD-8 (2.5 mg/kg) in sub-threshold doses corrected their Pre-Pulse Inhibition (PPI) deficit and hyperactivity, without any side effects at these doses. We have suggested that rolipram-induced increase of cAMP level might influence GSK-3 function and, hence the efficacy of TDZD-8. Our second goal was to estimate how DISC1-Q31L with reduced PDE4B activity, and therefore mimicking rolipram-induced conditions, could alter pharmacological response to TDZD-8, GSK-3 activity and its interaction with DISC1. DISC1-Q31L mutants showed increased sensitivity to GSK-3 inhibitor compare to DISC1-L100P mice. TDZD-8 (2.5 mg/kg) was able to correct PPI deficit, reduce immobility in the forced swim test (FST) and increased social motivation/novelty. In parallel, biochemical analysis revealed significantly reduced binding of GSK-3 to the mutated DISC1-Q31L and increased enzymatic activity of GSK-3. Taken together, genetic variations in DISC1 influence formation of biochemical complex with PDE4 and GSK-3 and strength the possibility of synergistic interactions between these proteins.

  11. 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.

  12. 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

  13. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis in the United States, 2003-2008

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes can cause severe foodborne disease (listeriosis). Serotype 4b strains have resulted in numerous outbreaks, repeatedly involving three epidemic clones (ECI, ECII, and ECIa). Little is known about population structure of L. monocytogenes serotype 4b from sporadic listeriosis, ev...

  14. 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

    ... 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 Use... evaluation of the Bacterial Endotoxins Test General Chapter harmonized text from each of the...

  15. Identification of RAN1 orthologue associated with sex determination through whole genome sequencing analysis in fig (Ficus carica L.).

    PubMed

    Mori, Kazuki; Shirasawa, Kenta; Nogata, Hitoshi; Hirata, Chiharu; Tashiro, Kosuke; Habu, Tsuyoshi; Kim, Sangwan; Himeno, Shuichi; Kuhara, Satoru; Ikegami, Hidetoshi

    2017-01-25

    With the aim of identifying sex determinants of fig, we generated the first draft genome sequence of fig and conducted the subsequent analyses. Linkage analysis with a high-density genetic map established by a restriction-site associated sequencing technique, and genome-wide association study followed by whole-genome resequencing analysis identified two missense mutations in RESPONSIVE-TO-ANTAGONIST1 (RAN1) orthologue encoding copper-transporting ATPase completely associated with sex phenotypes of investigated figs. This result suggests that RAN1 is a possible sex determinant candidate in the fig genome. The genomic resources and genetic findings obtained in this study can contribute to general understanding of Ficus species and provide an insight into fig's and plant's sex determination system.

  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. Complete nucleotide sequence of a novel strain of fig fleck-associated virus from China.

    PubMed

    He, Zhen; Mijit, Mahmut; Li, Shifang; Zhang, Zhixiang

    2017-04-01

    The complete nucleotide sequence of fig fleck-associated virus from Xinjiang Uygur Autonomous Region of China (FFkaV-CN) was determined. The 6,723-nucleotide-long viral genome, excluding a terminal poly(A) tail, contains three open reading frames (ORFs). Pairwise comparisons showed that FFkaV-CN shares 83% and 92% sequence identity with FFkaV-Italy based on the complete genomic sequence and CP aa sequence, respectively, slightly higher than the species demarcation criterion for the genus Maculavirus. Phylogenetic analysis showed that FFkaV-CN and FFkaV-Italy clustered into one group. These results indicate that FFkaV-CN is a novel strain of FFkaV with a genome organization somewhat different from what was reported for FFkaV-Italy.

  18. 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.

  19. 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

  20. The plasma membrane Ca(2+) pump PMCA4b inhibits the migratory and metastatic activity of BRAF mutant melanoma cells.

    PubMed

    Hegedũs, Luca; Garay, Tamás; Molnár, Eszter; Varga, Karolina; Bilecz, Ágnes; Török, Szilvia; Padányi, Rita; Pászty, Katalin; Wolf, Matthias; Grusch, Michael; Kállay, Enikõ; Döme, Balázs; Berger, Walter; Hegedũs, Balázs; Enyedi, Agnes

    2016-11-04

    Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca(2+) signaling is a well-known regulator of tumor progression, the crosstalk between Ca(2+) signaling and the Ras-BRAF-MEK-ERK pathway is much less explored. Here we show that in BRAF mutant melanoma cells the abundance of the plasma membrane Ca(2+) ATPase isoform 4b (PMCA4b, ATP2B4) is low at baseline but markedly elevated by treatment with the mutant BRAF specific inhibitor vemurafenib. In line with these findings gene expression microarray data also shows decreased PMCA4b expression in cutaneous melanoma when compared to benign nevi. The MEK inhibitor selumetinib-similarly to that of the BRAF-specific inhibitor-also increases PMCA4b levels in both BRAF and NRAS mutant melanoma cells suggesting that the MAPK pathway is involved in the regulation of PMCA4b expression. The increased abundance of PMCA4b in the plasma membrane enhances [Ca(2+) ]i clearance from cells after Ca(2+) entry. Moreover we show that both vemurafenib treatment and PMCA4b overexpression induce marked inhibition of migration of BRAF mutant melanoma cells. Importantly, reduced migration of PMCA4b expressing BRAF mutant cells is associated with a marked decrease in their metastatic potential in vivo. Taken together, our data reveal an important crosstalk between Ca(2+) signaling and the MAPK pathway through the regulation of PMCA4b expression and suggest that PMCA4b is a previously unrecognized metastasis suppressor.

  1. LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.

    PubMed

    Küspert, Maritta; Murakawa, Yasuhiro; Schäffler, Katrin; Vanselow, Jens T; Wolf, Elmar; Juranek, Stefan; Schlosser, Andreas; Landthaler, Markus; Fischer, Utz

    2015-07-01

    mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting "mRNP code" determines the fate of any given mRNA and thus controlling gene expression at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA-binding proteins characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown previously direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3' UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B-binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability.

  2. The electron and energy transfer between oligothiophenes and thieno[3,4-b]thiophene units

    NASA Astrophysics Data System (ADS)

    Szarko, Jodi; Guo, Jianchang; Liang, Yongye; Rolczynski, Brian; Yu, Luping; Chen, Lin X.

    2008-08-01

    In a recent study, it has been shown that organic photovoltaic (OPV) solar cells consisting of polymers with certain stoichiometric ratios of alkyl thiophene:thieno[3,4-b]thiophene monomeric units in random sequences, when combined with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), may have potentials for creating more efficient devices. Such a potential enhancement is mainly due to the light harvesting in most of the visible and near infrared region by these low band-gap polymers. However, very little is known about the photoinduced energy/electron transfer and transport within these copolymers. It is important to understand both the ultrafast interactions between these two monomeric units when they are linked in the copolymers and their interactions with the electron acceptor PCBM in order to determine the transport mechanisms in these systems, and then to create the architectures that optimize electronic transport properties. Therefore, three oligomer molecules have been synthesized to model the local interactions in the copolymers, each of which consists of a thieno[3,4-b] thiophene derivative at its center linked with two alkyl oligothiophene side units. The alkyl oligothiophene units for the three molecules are 2, 4, or 8 units in length. By performing transient absorption and fluorescence upconversion measurements, the nature of the early exciton diffusion and energy transfer between these different units is elucidated.

  3. Geopotential Model Improvement Using POCM_4B Dynamic Ocean Topography Information: PGM2000A

    NASA Technical Reports Server (NTRS)

    Pavlis, N. K.; Chinn, D. S.; Cox, C. M.; Lemoine, Frank G.; Smith, David E. (Technical Monitor)

    2000-01-01

    The two-year mean (1993-1994) Dynamic Ocean Topography (DOT) field implied by the POCM_4B circulation model was used to develop normal equations for DOT, in a surface spherical harmonic representation. These normal equations were combined with normal equations from satellite tracking data, surface gravity data, and altimeter data from TOPEX/Poseidon and ERS-1. Several least-squares combination solutions were developed in this fashion, by varying parameters such as the maximum degree of the estimated DOT and the relative weights of the different data. The solutions were evaluated in terms of orbit fit residuals, GPS/Leveling-derived undulations, and independent DOT information from in situ WOCE hydrographic data. An optimal solution was developed in this fashion which was originally presented at the 1998 EGS meeting in Nice, France. This model, designated here PGM2000A, maintains the orbit and land geoid modeling performance of EGM96, while improving its marine geoid modeling capability. In addition, PGM2000A's error spectrum is considerably more realistic than those of other contemporary gravitational models and agrees well with the error spectrum of EGM96. We will present the development and evaluation of PGM2000A, with particular emphasis on the weighting of the DOT information implied by POCM_4B. We will also present an inter-comparison of PGM2000A with the GRIM5-C1 and TEG-4 models. Directions for future work and problematic areas will be identified.

  4. 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

  5. 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

  6. 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.

  7. Effects of ingestion by neotropical bats on germination parameters of native free-standing and strangler figs (Ficus sp., Moraceae).

    PubMed

    Heer, Katrin; Albrecht, Larissa; Kalko, Elisabeth K V

    2010-06-01

    Fruit-eating animals can influence the germination success of seeds through transportation and handling. We experimentally tested the contribution of ingestion by the common fruit-eating bat, Artibeus jamaicensis (Phyllostomidae, Chiroptera), to the percentage and rate of seed germination of figs (Ficus, Moraceae), which are considered keystone species for many frugivores. We collected fruits from three species of native free-standing figs (subgenus Pharmacosycea: F. insipida, F. maxima and F. yoponensis) and three species of native strangler figs (subgenus Urostigma: F. nymphiifolia, F. obtusifolia and F. popenoei) on Barro Colorado Island, Panama. The germination success of seeds removed from fruit pulp either manually or by ingestion was very high (>92%), while seeds that were not removed from fruit pulp were destroyed by fast-growing fungi within a few days. The dynamics of seed germination were not influenced by ingestion, but differed between the two subgenera of figs. In free-standing figs, germination started significantly earlier (5.3 +/- 0.7 days) than in strangler figs (8.6 +/- 1.4 days). Furthermore, strangler seeds were covered with a sticky coating and their seedlings developed cotyledons faster than fine roots, in contrast to free-standing figs that showed the opposite pattern. Our results demonstrate that the germination of fig seeds is positively influenced by passage through the gut of A. jamaicensis. Furthermore, free-standing and strangler figs revealed differences in germination parameters that might be adaptive with respect to the suitability of microsites such as tree fall gaps or host trees for establishment.

  8. 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

  9. 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.

  10. Inhibitor screening and enzymatic activity determination for autophagy target Atg4B using a gel electrophoresis-based assay.

    PubMed

    Cleenewerck, Matthias; Grootaert, Mandy O J; Gladysz, Rafaela; Adriaenssens, Yves; Roelandt, Ria; Joossens, Jurgen; Lambeir, Anne-Marie; De Meyer, Guido R Y; Declercq, Wim; Augustyns, Koen; Martinet, Wim; Van der Veken, Pieter

    2016-11-10

    Atg4B is a cysteine hydrolase that plays a key role in autophagy. Although it has been proposed as an attractive drug target, inhibitor discovery has proven highly challenging. The absence of a standardized, easily implementable enzyme activity/inhibition assay for Atg4B most likely contributes to this situation. Therefore, three different assay types for Atg4B activity/inhibition quantification were first compared: (1) an approach using fluorogenic Atg4B-substrates, (2) an in-gel densitometric quantification assay and (3) a thermal shift protocol. The gel-based approach showed the most promising results and was validated for screening of potential Atg4B inhibitors. A set of 8 literature inhibitors was included. Remarkably, in our hands only 2 literature references were found to have measurable Atg4B affinity. Furthermore, a fragment library (n = 182) was tested for Atg4B inhibition. One library member showed inhibition at high micromolar concentration and was found fit for further, fragment-based inhibitor design.

  11. 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.

  12. HATS-4b: A Dense Hot Jupiter Transiting a Super Metal-rich G star

    NASA Astrophysics Data System (ADS)

    Jordán, Andrés; Brahm, Rafael; Bakos, G. Á.; Bayliss, D.; Penev, K.; Hartman, J. D.; Zhou, G.; Mancini, L.; Mohler-Fischer, M.; Ciceri, S.; Sato, B.; Csubry, Z.; Rabus, M.; Suc, V.; Espinoza, N.; Bhatti, W.; de Val-Borro, M.; Buchhave, L.; Csák, B.; Henning, T.; Schmidt, B.; Tan, T. G.; Noyes, R. W.; Béky, B.; Butler, R. P.; Shectman, S.; Crane, J.; Thompson, I.; Williams, A.; Martin, R.; Contreras, C.; Lázár, J.; Papp, I.; Sári, P.

    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 Mp ≈ 1.32 M Jup, radius of Rp ≈ 1.02 R Jup, and density of ρ p = 1.55 ± 0.16 g cm-3 ≈1.24 ρJup. The host star has a mass of 1.00 M ⊙, a radius of 0.92 R ⊙, 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 J and is thus likely to have a significant content of heavy elements of the order of 75 M ⊕. 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. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institut für Astronomie (MPIA), and the Australian National University (ANU). The station at Las Campanas Observatory (LCO) of the Carnegie Institution is operated by PU in conjunction with collaborators at the Pontificia Universidad Católica de Chile, the station at the High Energy Spectroscopic Survey site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. This paper includes data gathered with the 6.5 m Magellan Telescopes located at LCO, Chile. Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan, and on observations made with the MPG/ESO 2.2 m Telescope at the ESO Observatory in La Silla. This paper uses observations obtained with facilities of the Las Cumbres Observatory Global Telescope.

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

    PubMed

    Schmidt, Eva M; Wiek, Constanze; 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.

  14. 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

  15. 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.

  16. Hexadecanedionic acid-sepharose 4B: A new tool for preparation of albumin-depleted plasma.

    PubMed

    Soskic, Vukic; Schwall, Gerhard; Nyakatura, Elke; Poznanovic, Slobodan; Stegmann, Werner; Schrattenholz, Andre

    2006-12-01

    Serum and plasma are the major sources of human material for clinical molecular diagnostics and drug discovery. However, due to the high abundance of some proteins, of which serum albumin (SA) is most prominent, lower-abundance proteins often remain undetectable in proteomic analysis of these body fluids. We have used hexadecanedionic acid (HDA) immobilized to Sepharose 4B to develop an affinity resin that is effective in the removal of SA from plasma. Two-dimensional gel analysis of the SA-depleted samples shows a significant enhancement of the low-abundance proteins and highly specific capture of serum albumin. The HDA resin shows better performance in terms of specificity than dye-based resins.

  17. [A novel pyridazino-fused ring system: synthesis of pyridazino[3,4-b]diazepam].

    PubMed

    Károlyházy, L; Horváth, G; Mátyus, P

    2001-08-01

    As an analogue of pyridazino-fused ring systems with pharmacological activities, the novel pyridazinol[3,4-b][1,5]diazepine ring system was prepared. The synthetic pathway includes three steps from 4 5-(N-benzyl-N-3-hydroxypropyl)amino derivative which is easily available through nucleophilic substitution reaction of the known 4,5-dichloro-2-methyl-6-nitro-3(2H)-pyridazinone (2) with N-benzyl-N-(3-hydroxypropyl)amine. In the first step, compound 4 was treated with thionyl chloride to give the chloropropyl derivative 5. In the second step, a Bechamp reduction was carried out with Fe in acetic acid to obtain the amino compound 6, and finally the ring closure reaction of 6 was performed in N,N-dimethylformamide in the presence of potassium carbonate at 110 degrees C for 40 hours. In this way the bicyclic compound 7 could be isolated in 48% yield.

  18. Low-energy Be4+/B5+ - H2 cross sections

    NASA Astrophysics Data System (ADS)

    Saha, Bidhan

    2000-06-01

    Single electron capture cross sections from molecular hydrogen by Be4+/B5+ have been calculated using the Molecular Orbital formalism in the semiclassical close-coupling scheme. The important interactions leading to state selective charge transfer are confined at large internuclear seperation. We have found that freezing the molecular details of the target turns out to be a convenient strategy [1]. In our investigation we treat H2 as a pseudo-atom with ionization potential 16.1 eV. The results will be presented in the conference. This work is supported by Research Corporation, NSF CREST and Army High Performance Computing Research. [1] A. Kumar and B C Saha, Phys Rev A 59,1273 (1999).

  19. 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

  20. Identification of RAN1 orthologue associated with sex determination through whole genome sequencing analysis in fig (Ficus carica L.)

    PubMed Central

    Mori, Kazuki; Shirasawa, Kenta; Nogata, Hitoshi; Hirata, Chiharu; Tashiro, Kosuke; Habu, Tsuyoshi; Kim, Sangwan; Himeno, Shuichi; Kuhara, Satoru; Ikegami, Hidetoshi

    2017-01-01

    With the aim of identifying sex determinants of fig, we generated the first draft genome sequence of fig and conducted the subsequent analyses. Linkage analysis with a high-density genetic map established by a restriction-site associated sequencing technique, and genome-wide association study followed by whole-genome resequencing analysis identified two missense mutations in RESPONSIVE-TO-ANTAGONIST1 (RAN1) orthologue encoding copper-transporting ATPase completely associated with sex phenotypes of investigated figs. This result suggests that RAN1 is a possible sex determinant candidate in the fig genome. The genomic resources and genetic findings obtained in this study can contribute to general understanding of Ficus species and provide an insight into fig’s and plant’s sex determination system. PMID:28120935

  1. Cul4A is essential for spermatogenesis and male fertility.

    PubMed

    Kopanja, Dragana; Roy, Nilotpal; Stoyanova, Tanya; Hess, Rex A; Bagchi, Srilata; Raychaudhuri, Pradip

    2011-04-15

    The mammalian Cul4 genes, Cul4A and Cul4B, encode the scaffold components of the cullin-based E3 ubiquitin ligases. The two Cul4 genes are functionally redundant. Recent study indicated that mice expressing a truncated CUL4A that fails to interact with its functional partner ROC1 exhibit no developmental phenotype. We generated a Cul4A-/- strain lacking exons 4-8 that does not express any detectable truncated protein. In this strain, the male mice are infertile and exhibit severe deficiencies in spermatogenesis. The primary spermatocytes are deficient in progression through late prophase I, a time point when expression of the X-linked Cul4B gene is silenced due to meiotic sex chromosome inactivation. Testes of the Cul4A-/- mice exhibit extensive apoptosis. Interestingly, the pachytene spermatocytes exhibit persistent double stranded breaks, suggesting a deficiency in homologous recombination. Also, we find that CUL4A localizes to the double stranded breaks generated in pre-pachytene spermatocytes. The observations identify a novel function of CUL4A in meiotic recombination and demonstrate an essential role of CUL4A in spermatogenesis.

  2. Serum reactivity to other indoor ficus plants in patients with allergy to weeping fig (Ficus benjamina).

    PubMed

    Axelsson, I G; Johansson, S G; Larsson, P H; Zetterström, O

    1991-02-01

    Ornamental plants have long been used for indoor decoration. An example is the india rubber tree (Ficus elastica). With the increased popularity of green plants, both in private homes and public premises, small-leaf species, such as weeping fig or Ficus benjamina (Fb), have become widely used. Exposure to dust from Fb may cause sensitization and allergic airway symptoms, which among occupationally exposed plant keepers occur both in atopics and non-atopics. The serum reactivity to sap extracts from Fb and seven other indoor plants of the genus Ficus were investigated with RAST and a RAST inhibition technique, using sera from 12 atopic subjects and 12 plant keepers, sensitized to Fb. The allergenic similarity between the different extracts was found to be extensive. The specific IgE antibodies with the highest concentrations in serum were those against Fb and its variegate form, "star light", with decreasing values for the other species, especially those with larger leaves. The binding of IgE antibodies to the other Ficus RAST discs could be completely inhibited by extract of Fb. These reactions were probably due to cross-reactivity. Sensitization is believed to occur by inhalation of allergen-enriched dust, emanating from the leaves of the plants. The high allergenic potency of the species with many small leaves may be due to their large total leaf area.

  3. A Role for Parasites in Stabilising the Fig-Pollinator Mutualism

    PubMed Central

    Dunn, Derek W; Segar, Simon T; Ridley, Jo; Chan, Ruth; Crozier, Ross H; Yu, Douglas W; Cook, James M

    2008-01-01

    Mutualisms are interspecific interactions in which both players benefit. Explaining their maintenance is problematic, because cheaters should outcompete cooperative conspecifics, leading to mutualism instability. Monoecious figs (Ficus) are pollinated by host-specific wasps (Agaonidae), whose larvae gall ovules in their “fruits” (syconia). Female pollinating wasps oviposit directly into Ficus ovules from inside the receptive syconium. Across Ficus species, there is a widely documented segregation of pollinator galls in inner ovules and seeds in outer ovules. This pattern suggests that wasps avoid, or are prevented from ovipositing into, outer ovules, and this results in mutualism stability. However, the mechanisms preventing wasps from exploiting outer ovules remain unknown. We report that in Ficus rubiginosa, offspring in outer ovules are vulnerable to attack by parasitic wasps that oviposit from outside the syconium. Parasitism risk decreases towards the centre of the syconium, where inner ovules provide enemy-free space for pollinator offspring. We suggest that the resulting gradient in offspring viability is likely to contribute to selection on pollinators to avoid outer ovules, and by forcing wasps to focus on a subset of ovules, reduces their galling rates. This previously unidentified mechanism may therefore contribute to mutualism persistence independent of additional factors that invoke plant defences against pollinator oviposition, or physiological constraints on pollinators that prevent oviposition in all available ovules. PMID:18336072

  4. 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.

  5. 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.

  6. 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.

  7. A role for parasites in stabilising the fig-pollinator mutualism.

    PubMed

    Dunn, Derek W; Segar, Simon T; Ridley, Jo; Chan, Ruth; Crozier, Ross H; Yu, Douglas W; Cook, James M

    2008-03-11

    Mutualisms are interspecific interactions in which both players benefit. Explaining their maintenance is problematic, because cheaters should outcompete cooperative conspecifics, leading to mutualism instability. Monoecious figs (Ficus) are pollinated by host-specific wasps (Agaonidae), whose larvae gall ovules in their "fruits" (syconia). Female pollinating wasps oviposit directly into Ficus ovules from inside the receptive syconium. Across Ficus species, there is a widely documented segregation of pollinator galls in inner ovules and seeds in outer ovules. This pattern suggests that wasps avoid, or are prevented from ovipositing into, outer ovules, and this results in mutualism stability. However, the mechanisms preventing wasps from exploiting outer ovules remain unknown. We report that in Ficus rubiginosa, offspring in outer ovules are vulnerable to attack by parasitic wasps that oviposit from outside the syconium. Parasitism risk decreases towards the centre of the syconium, where inner ovules provide enemy-free space for pollinator offspring. We suggest that the resulting gradient in offspring viability is likely to contribute to selection on pollinators to avoid outer ovules, and by forcing wasps to focus on a subset of ovules, reduces their galling rates. This previously unidentified mechanism may therefore contribute to mutualism persistence independent of additional factors that invoke plant defences against pollinator oviposition, or physiological constraints on pollinators that prevent oviposition in all available ovules.

  8. 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

  9. Traditional agroecosystems as conservatories and incubators of cultivated plant varietal diversity: the case of fig (Ficus carica L.) in Morocco

    PubMed Central

    2010-01-01

    Background Traditional agroecosystems are known to host both large crop species diversity and high within crop genetic diversity. In a context of global change, this diversity may be needed to feed the world. Are these agroecosystems museums (i.e. large core collections) or cradles of diversity? We investigated this question for a clonally propagated plant, fig (Ficus carica), within its native range, in Morocco, but as far away as possible from supposed centers of domestication. Results Fig varieties were locally numerous. They were found to be mainly highly local and corresponded to clones propagated vegetatively. Nevertheless these clones were often sufficiently old to have accumulated somatic mutations for selected traits (fig skin color) and at neutral loci (microsatellite markers). Further the pattern of spatial genetic structure was similar to the pattern expected in natural population for a mutation/drift/migration model at equilibrium, with homogeneous levels of local genetic diversity throughout Moroccan traditional agroecosystems. Conclusions We conclude that traditional agroecosystems constitue active incubators of varietal diversity even for clonally propagated crop species, and even when varieties correspond to clones that are often old. As only female fig is cultivated, wild fig and cultivated fig probably constitute a single evolutionary unit within these traditional agroecosystems. Core collections, however useful, are museums and hence cannot serve the same functions as traditional agroecosystems. PMID:20167055

  10. 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.

  11. 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

    ... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 13: Bulk Density and Tapped Density...

  12. Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Marchi, E; Barbanti, M; Lefebvre, P

    1990-04-01

    In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.

  13. Relationship between LAPTM4B Gene Polymorphism and Prognosis of Patients following Tumor Resection for Colorectal and Esophageal Cancers

    PubMed Central

    Xing, Xiaofang; Du, Hong; Zhou, Chunlian; Zhang, Qingyun; Hao, Chunyi; Wen, Xianzi; Ji, Jiafu

    2016-01-01

    Background Lysosome-associated transmembrane-4 beta (LAPTM4B) is an oncogene that participates tumorgenesis in a variety of human solid tumors, and it has two alleles named as LAPTM4B*1 and *2. The present study aimed to identify the association of LAPTM4B genotype with clinicopathological features and prognosis in colorectal and esophageal cancer patients. Method Genotypes of LAPTM4B were determined by PCR in 167 colon cancer cases (72 patients in a discovery cohort and 95 patients in a testing cohort), 160 rectal cancer cases and 164 esophageal cancer cases. Association between the LAPTM4B gene polymorphism and clinicopathological variables was calculated by Chi-square test or Fisher’s exact test. Patient survival differences were calculated by the Kaplan-Meier method. Prognostic factors were determined with Log-rank test and Cox regression model. Results LAPTM4B *1/1 was more frequently detected in colon cancer patients with lymph node metastasis and TNM III+IV stages in total colon cancer (discovery + testing cohorts). LAPTM4B *2/2 decreased in recurrent patients in total colon cancer patients (P = 0.045). Kaplan-Meier survival curves and Log-rank test showed that LAPTM4B*1 was correlated with shorter overall survival (OS) in discovery and testing cohorts of colon cancer (P = 0.0254 and 0.0292, respectively), but not in rectal and esophageal cancer cases (P = 0.7669 and 0.9356, respectively). Multivariate analysis showed that LAPTM4B genotype was an independent prognostic factor for OS in total colon cancer [P = 0.004, hazard ratio (HR) = 0.432; 95% confidence interval (CI) = 0.243–0.768], but not in rectal and esophageal cancers (P = 0.791, HR = 1.073, 95% CI = 0.638–1.804 and 0.998, HR = 1.000, 95% CI = 0.663–1.530, respectively). Conclusion These findings suggested that LAPTM4B allele *1 was a risk factor associated with poor prognosis in patients with colon cancer, but not in patients with rectal or esophageal cancers. LAPTM4B genotype status might

  14. Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404.

    PubMed

    van Cleef, Koen W R; Overheul, Gijs J; Thomassen, Michael C; Marjakangas, Jenni M; van Rij, Ronald P

    2016-04-01

    Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development.

  15. 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

  16. 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

  17. 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.

  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. Intramolecular cycloaddition reactions of furo[3,4-b]indoles for alkaloid synthesis.

    PubMed

    Padwa, Albert; Zou, Yan; Cheng, Bo; Li, Hao; Downer-Riley, Nadale; Straub, Christopher S

    2014-04-04

    Model studies dealing with the Cu(II)- or Rh(II)-catalyzed carbenoid cyclization/cycloaddition cascade of several α-diazo indolo amido esters have been carried out as an approach to the alkaloid scandine. The Cu(II)-catalyzed reaction of an α-diazo indolo diester that contains a tethered oxa-pentenyl side chain was found to give rise to a reactive benzo[c]furan which undergoes a subsequent [4 + 2]-cycloaddition across the tethered π-bond. The reaction proceeds by the initial generation of a copper carbenoid intermediate which cyclizes onto the adjacent carbonyl group to give a reactive benzo[c]furan which in certain cases can be isolated. Disappointingly, the analogous reaction with the related amido indolo ester failed to take place, even when the tethered π-bond contained an electron-withdrawing carbomethoxy group. It would seem that the geometric requirements for the intramolecular cycloaddition of the furo[3,4-b]indole system with the tethered π-bond imposes distinct restrictions upon the bond angles of the reacting centers to prevent the cycloaddition reaction from occurring. However, the incorporation of another carbonyl group on the nitrogen atom of the tethered alkenyl diazo amido indolo ester seemingly provides better orbital overlap between the reacting π-systems and allows the desired cycloaddition reaction to occur.

  1. Nucleocapsid Protein from Fig Mosaic Virus Forms Cytoplasmic Agglomerates That Are Hauled by Endoplasmic Reticulum Streaming

    PubMed Central

    Ishikawa, Kazuya; Miura, Chihiro; Maejima, Kensaku; Komatsu, Ken; Hashimoto, Masayoshi; Tomomitsu, Tatsuya; Fukuoka, Misato; Yusa, Akira; Yamaji, Yasuyuki

    2014-01-01

    ABSTRACT Although many studies have demonstrated intracellular movement of viral proteins or viral replication complexes, little is known about the mechanisms of their motility. In this study, we analyzed the localization and motility of the nucleocapsid protein (NP) of Fig mosaic virus (FMV), a negative-strand RNA virus belonging to the recently established genus Emaravirus. Electron microscopy of FMV-infected cells using immunogold labeling showed that NPs formed cytoplasmic agglomerates that were predominantly enveloped by the endoplasmic reticulum (ER) membrane, while nonenveloped NP agglomerates also localized along the ER. Likewise, transiently expressed NPs formed agglomerates, designated NP bodies (NBs), in close proximity to the ER, as was the case in FMV-infected cells. Subcellular fractionation and electron microscopic analyses of NP-expressing cells revealed that NBs localized in the cytoplasm. Furthermore, we found that NBs moved rapidly with the streaming of the ER in an actomyosin-dependent manner. Brefeldin A treatment at a high concentration to disturb the ER network configuration induced aberrant accumulation of NBs in the perinuclear region, indicating that the ER network configuration is related to NB localization. Dominant negative inhibition of the class XI myosins, XI-1, XI-2, and XI-K, affected both ER streaming and NB movement in a similar pattern. Taken together, these results showed that NBs localize in the cytoplasm but in close proximity to the ER membrane to form enveloped particles and that this causes passive movements of cytoplasmic NBs by ER streaming. IMPORTANCE Intracellular trafficking is a primary and essential step for the cell-to-cell movement of viruses. To date, many studies have demonstrated the rapid intracellular movement of viral factors but have failed to provide evidence for the mechanism or biological significance of this motility. Here, we observed that agglomerates of nucleocapsid protein (NP) moved rapidly

  2. Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML.

    PubMed

    Rijal, Sewa; Fleming, Shaun; Cummings, Nik; Rynkiewicz, Natalie K; Ooms, Lisa M; Nguyen, Nhu-Y N; Teh, Tse-Chieh; Avery, Sharon; McManus, Julie F; Papenfuss, Anthony T; McLean, Catriona; Guthridge, Mark A; Mitchell, Christina A; Wei, Andrew H

    2015-04-30

    Phosphoinositide signaling regulates diverse cellular functions. Phosphoinositide-3 kinase (PI3K) generates PtdIns(3,4,5)P3 and PtdIns(3,4)P2, leading to the activation of proliferative and anti-apoptotic signaling pathways. Termination of phosphoinositide signaling requires hydrolysis of inositol ring phosphate groups through the actions of PtdIns(3,4,5)P3 3-phosphatase (PTEN), PtdIns(3,4,5)P3 5-phosphatases (eg, SHIP), and PtdIns(3,4)P2 4-phosphatases (eg, INPP4B). The biological relevance of most of these phosphoinositide phosphatases in acute myeloid leukemia (AML) remains poorly understood. Mass spectrometry-based gene expression profiling of 3-, 4- and 5-phosphatases in human AML revealed significant overexpression of INPP4B. Analysis of an expanded panel of 205 AML cases at diagnosis revealed INPP4B overexpression in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B conferred leukemic resistance to cytosine arabinoside (ara-C), daunorubicin, and etoposide. Expression of a phosphatase inert variant (INPP4B C842A) failed to abrogate resistance of AML cells to chemotherapy in vitro or in vivo. In contrast, targeted suppression of endogenously overexpressed INPP4B by RNA interference sensitized AML cell lines and primary AML to chemotherapy. These findings demonstrate a previously unsuspected and clinically relevant role for INPP4B gain of function as a mediator of chemoresistance and poor survival outcome in AML independent of its phosphoinositide phosphatase function.

  3. 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.

  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. COI and ITS2 sequences delimit species, reveal cryptic taxa and host specificity of fig-associated Sycophila (Hymenoptera, Eurytomidae).

    PubMed

    Li, Yanwei; Zhou, Xin; Feng, Gui; Hu, Haoyuan; Niu, Liming; Hebert, Paul D N; Huang, Dawei

    2010-01-01

    Although the genus Sycophila has broad host preferences, some species are specifically associated with figs as nonpollinator wasps. Because of their sexual dimorphism, morphological plasticity, cryptic mating behaviour and poorly known biology, species identifications are often uncertain. It is particularly difficult to match conspecific females and males. In this study, we employed two molecular markers, mitochondrial COI and nuclear ITS2, to identify Sycophila from six Chinese fig species. Morphological studies revealed 25 female and male morphs, while sequence results for both genes were consistent in supporting the presence of 15 species, of which 13 were host specialists and two used dual hosts. A single species of Sycophila was respectively found on four fig species, but six species were isolated from Ficus benjamina and a same number was reared from Ficus microcarpa. Sequence results revealed three male morphs in one species and detected two species that were overlooked by morphological analysis.

  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. The interaction between the hepatitis C proteins NS4B and NS5A is involved in viral replication.

    PubMed

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S; Hirschberg, Koret; Sklan, Ella H

    2015-01-15

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B-NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits.

  8. UBE4B protein couples ubiquitination and sorting machineries to enable epidermal growth factor receptor (EGFR) degradation.

    PubMed

    Sirisaengtaksin, Natalie; Gireud, Monica; Yan, Qing; Kubota, Yoshihisa; Meza, Denisse; Waymire, Jack C; Zage, Peter E; Bean, Andrew J

    2014-01-31

    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.

  9. The caspase-3 cleavage product of the plasma membrane Ca2+-ATPase 4b is activated and appropriately targeted.

    PubMed

    Pászty, Katalin; Antalffy, Géza; Penheiter, Alan R; Homolya, László; Padányi, Rita; Iliás, Attila; Filoteo, Adelaida G; Penniston, John T; Enyedi, Agnes

    2005-11-01

    The calmodulin-activated transporter hPMCA4 (human plasma membrane Ca2+-ATPase isoform 4) is a target for cleavage by caspase-3 during apoptosis. We have demonstrated that caspase-3 generates a 120 kDa fragment of this pump which lacks the complete autoinhibitory sequence [Paszty, Verma, Padanyi, Filoteo, Penniston and Enyedi (2002) J. Biol. Chem. 277, 6822-6829]. In the present study we analysed further the characteristics of the fragment of hPMCA4b produced by caspase-3. We did this by overexpressing the caspase-3 cleavage product of hPMCA4b in COS-7 and MDCKII (Madin-Darby canine kidney II) cells. This technique made it possible to clearly define the properties of this fragment, and we showed that it is constitutively active, as it forms a phosphoenzyme intermediate and has high Ca2+ transport activity in the absence of calmodulin. When this fragment of hPMCA4b was stably expressed in MDCKII cell clones, it was targeted without degradation to the basolateral plasma membrane. In summary, our studies emphasize that the caspase-3 cleavage product of hPMCA4b is constitutively active, and that the C-terminus is not required for proper targeting of hPMCA4b to the plasma membrane. Also, for the first time, we have generated cell clones that stably express a constitutively active PMCA.

  10. 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.

  11. Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication.

    PubMed

    Vidotto, Alessandra; Morais, Ana T S; Ribeiro, Milene R; Pacca, Carolina C; Terzian, Ana C B; Gil, Laura H V G; Mohana-Borges, Ronaldo; Gallay, Philippe; Nogueira, Mauricio L

    2017-04-07

    Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in cells treated with both inhibitors using reporter BHK-21-rep-YFV17D-LucNeoIres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction.

  12. 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

  13. The FIGS (Focused Identification of Germplasm Strategy) Approach Identifies Traits Related to Drought Adaptation in Vicia faba Genetic Resources

    PubMed Central

    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. PMID:23667581

  14. Thieno[3,4-b]thiophene-Based Novel Small-Molecule Optoelectronic Materials.

    PubMed

    Zhang, Cheng; Zhu, Xiaozhang

    2017-04-04

    Because of the tailorable photoelectric properties derived from judicious molecular design and large-area and low-temperature processability especially on flexible substrates, design and synthesis of new organic π-functional materials is always a central topic in the field of organic optoelectronics, which siginificantly contributed to the development of high-performance optoelectronic devices such as organic photovoltaics (OPVs), organic field-effect transistors (OFETs), and organic light-emitting diodes (OLEDs). Compared with polymers, small molecules with well-defined molecular structures benefit the establishment of structure-property relationships, which may provide valuable guidelines for the design of new optoelectronic materials to further promote the device performance. New building blocks are essential for the construction of optoelectronic materials. As is well recognized, thiophene-based functional materials have played an indispensable role in the development of organic optoelectronics. Compared with six-membered benzene, five-membered thiophene shows weaker aromaticity and lower steric hindrance and may provide extra sulfur-sulfur interactions in solid state. Among various thiophene building blocks, thieno[3,4-b]thiophene (TbT) is an asymmetric fused bithiophene containing four functionalization positions, in which the proaromatic thiophene can effectively stabilize the quinoidal resonance of the aromatic thiophene. Thus, TbT exhibits a unique characteristic of quinoid-resonance effect that is powerful to modulate electronic structures. Although the application of TbT in polymer donor materials represented by PTB-7 has achieved a great success, its application in small-molecule optoelectronic materials is almost an untouched field. In this Account, we summerize the rational design of a series of TbT-based small-molecule optoelectronic materials designed and optimized by quinoid-resonance effect, regiochemistry, and side-chain engineering and

  15. 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.

  16. Skin Involvement and Breast Cancer: Are T4B Lesions of All Sizes Created Equal?

    PubMed Central

    Silverman, Diana; Ruth, Karen; Sigurdson, Elin R.; Egleston, Brian L.; Goldstein, Lori J.; Wong, Yu-Ning; Boraas, Marcia; Bleicher, Richard J.

    2014-01-01

    Background Nonmetastatic non-inflammatory invasive breast cancers having skin involvement (SI) are classified as T4b, regardless of size. This study evaluated disease specific survival (DSS) to determine whether size should be considered for these lesions, rather than grouping them all into Stage III. Study Design Surveillance Epidemiology and End Results data linked to Medicare claims were reviewed. SI and nonSI tumors were reclassified using AJCC 7th Edition groupings using tumor size and nodal involvement alone without considering SI (neostage). DSS was adjusted for demographics, histology and treatment using competing risk methods with propensity score-based weighting and bootstrap standard errors. Results Among 924 SI patients diagnosed between 1992 and 2005, tumors were 0.1–2.0, 2.1–5.0, and >5.0 cm in 11.6%, 51.1%, and 37.3% of cases, respectively. There were no nodal metastases in 22.3%, 1–3 positive nodes in 31.7%, 4–9 positive in 28.6% and ≥10 positive in 17.4% of cases. For SI patients, adjusted 5-year DSS was 95.8% [95%CI: 95.6–96.0] for neostage I, declining progressively to 36.4% [95%CI: 33.8–39.2] for neostage IIIC patients. Adjusted 5-year DSS for SI and nonSI tumors (n=66,185) was similar for neostage I, IIA, and IIB, and markedly lower for IIIA and IIIC. Adjusted DSS for SI IIIA was similar to nonSI IIIC. Conclusions Noninflammatory SI breast cancers have widely varied DSS that differs by tumor size and nodal involvement, and therefore should not all be stage III. SI should be subordinate to T and N groupings to classify SI with nonSI lesions having similar prognoses. PMID:25026875

  17. Geographic and taxonomic distribution of a positive interaction: ant-tended homopterans indirectly benefit figs across southern Africa.

    PubMed

    Cushman, J Hall; Compton, Stephen G; Zachariades, Costas; Ware, Anthony B; Nefdt, Rory J C; Rashbrook, Vanessa K

    1998-09-01

    Although species pairs and assemblages often occur across geographic regions, ecologists know very little about the outcome of their interactions on such large spatial scales. Here, we assess the geographic distribution and taxonomic diversity of a positive interaction involving ant-tended homopterans and fig trees in the genus Ficus. Previous experimental studies at a few locations in South Africa indicated that Ficus sur indirectly benefited from the presence of a homopteran (Hilda patruelis) because it attracted ants (primarily Pheidole megacephala) that reduced the effects of both pre-dispersal ovule gallers and parasitoids of pollinating wasps. Based on this work, we evaluated three conditions that must be met in order to support the hypothesis that this indirect interaction involves many fig species and occurs throughout much of southern Africa and Madagascar. Data on 429 trees distributed among five countries indicated that 20 of 38 Ficus species, and 46% of all trees sampled, had ants on their figs. Members of the Sycomorus subgenus were significantly more likely to attract ants than those in the Urostigma subgenus, and ant-colonization levels on these species were significantly greater than for Urostigma species. On average, each ant-occupied F.sur tree had 37% of its fig crop colonized by ants, whereas the value was 24% for other Ficus species. H. patruelis was the most common source for attracting ants, although figs were also attacked by a range of other ant-tended homopterans. P. megacephala was significantly more common on figs than other ant species, being present on 58% of sampled trees. Ant densities commonly exceeded 4.5 per fig, which a field experiment indicated was sufficient to provide protection from ovule gallers and parasitoids of pollinators. Forty-nine percent of all colonized F. sur trees sampled had ant densities equal to or greater than 4.5 per fig, whereas this value was 23% for other Ficus species. We conclude that there is

  18. UBE4B Levels Are Correlated with Clinical Outcomes in Neuroblastoma Patients and with Altered Neuroblastoma Cell Proliferation and Sensitivity to EGFR Inhibitors

    PubMed Central

    Zage, Peter E.; Sirisaengtaksin, Natalie; Liu, Yin; Gireud, Monica; Brown, Brandon S.; Palla, Shana; Richards, Kristen N.; Hughes, Dennis P.M.; Bean, Andrew J.

    2012-01-01

    Background The UBE4B gene, located on chromosome 1p36, encodes a ubiquitin ligase that interacts with Hrs, a protein involved in EGFR trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. We have analyzed the roles of UBE4B in the outcomes of neuroblastoma patients and in neuroblastoma tumor cell proliferation, EGFR trafficking, and response to EGFR inhibition. Methods We examined the association of UBE4B expression with neuroblastoma patient survival using available microarray datasets. We measured UBE4B and EGFR protein levels in patient tumor samples and EGFR degradation rates in neuroblastoma cell lines and analyzed the effects of UBE4B on neuroblastoma tumor cell growth. The effects of the EGFR inhibitor cetuximab were examined in neuroblastoma cells expressing wild-type and mutant UBE4B. Results Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma. UBE4B overexpression reduced neuroblastoma tumor cell proliferation, and UBE4B expression was inversely related to EGFR expression in patient tumor samples. EGFR degradation rates correlated with cellular UBE4B levels. Enhanced expression of catalytically active UBE4B resulted in reduced sensitivity to EGFR inhibition. Conclusions We have demonstrated associations between UBE4B expression and neuroblastoma patient outcomes and between UBE4B and EGFR expression in neuroblastoma tumor samples. Moreover, levels of UBE4B influenced neuroblastoma tumor cell proliferation, EGFR degradation, and response to EGFR inhibition. These results suggest UBE4B-mediated GFR trafficking may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions, and that UBE4B expression may be a marker that can predict responses of neuroblastoma tumors to treatment. PMID:22990745

  19. 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

  20. Local Outbreak of Listeria monocytogenes Serotype 4b Sequence Type 6 Due to Contaminated Meat Pâté.

    PubMed

    Althaus, Denise; Jermini, Marco; Giannini, Petra; Martinetti, Gladys; Reinholz, Danuta; Nüesch-Inderbinen, Magdalena; Lehner, Angelika; Stephan, Roger

    2017-04-01

    In January and February 2016, five cases of confirmed and two cases of probable infection due to Listeria monocytogenes serotype 4b, sequence type (ST) 6 belonging to a single pulsed-field gel electrophoresis pulsotype pattern were registered in a region of southern Switzerland. L. monocytogenes was detected in blood samples (four cases) and pleural fluid (one case). Furthermore, L. monocytogenes 4b ST6 was detected in a stool sample of an asymptomatic person exposed to a common food. Forthwith, the food safety authority and a local gourmet meat producer reported L. monocytogenes contamination of meat pâté. Analysis of further food and environmental samples from the premises of the producer yielded isolates matching the clinical strains and confirmed the presence of L. monocytogenes 4b ST6 in the mincing machine as the cause of the food contamination.

  1. (4aS,4bR,7R,10aS)-3,7-Dimethyl-10a-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-deca­hydro­phenanthrene-1,4-dione

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Machado, André T. Lousada; Brocksom, Timothy J.; Ferreira, M. Lúcia; Tiekink, Edward R. T.

    2011-01-01

    In the title compound, C19H26O2, the A ring adopts a chair conformation, whereas the B and C rings both adopt distorted half-chair conformations with the quaternary C atom common to both rings lying 0.577 (3) and 0.648 (3) Å out of the approximate plane defined by the remaining five C atoms (r.m.s. deviations = 0.1386 and 0.1156 Å) for the B and C rings, respectively. Mol­ecules are assembled in the crystal through C—H⋯O inter­actions involving both carbonyl O atoms, which lead to supra­molecular chains aligned along the b axis. PMID:22199712

  2. Upregulation of LAPTM4B-35 promotes malignant transformation and tumorigenesis in L02 human liver cell line.

    PubMed

    Li, Li; Shan, Yi; Yang, Hua; Zhang, Sha; Lin, Ming; Zhu, Ping; Chen, Xin-Yu; Yi, Jing; McNutt, Michael A; Shao, Gen-Ze; Zhou, Rou-Li

    2011-07-01

    Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in China. We have previously demonstrated that LAPTM4B-35, encoded by lysosomal protein transmembrane 4 beta gene, is overexpressed in over 80% of HCCs and is a novel-independent prognostic factor for metastasis, recurrence, and postoperative survival in HCC. In this study, we investigated the role of LAPTM4B-35 in malignant transformation and tumorigenesis using L02 cells, a cell line originated from human normal liver cells. Our data show that replication-deficient adenovirus vector-mediated upregulation of LAPTM4B-35 promotes anchorage-independent proliferation and resistance to adriamycin-induced apoptosis. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included the activation of phosphoinositide 3-kinases (PI3K)/serine/threonine protein kinase B (PKB/AKT)/bcl-xL/bcl-2-associated death promoter homolog (Bad) signaling pathway, inhibition of caspase-3 activation, upregulation of Bcl-2, and downregulation of Bax. In addition, upregulation of LAPTM4B-35 in L02 cells resulted in tumorigenesis in 100% (6/6) of inoculated nude mice and accelerated the death of mice with xenografts in vivo. In conclusion, LAPTM4B-35 promotes malignant transformation and tumorigenesis in human liver L02 cell line through promotion of deregulated proliferation and inhibition of apoptosis. These findings suggest that overexpression of LAPTM4B-35 may play a critical role in hepatocarcinogenesis and therefore, may be a therapeutic target for HCC.

  3. 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.

  4. Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404

    PubMed Central

    van Cleef, Koen W. R.; Overheul, Gijs J.; Thomassen, Michael C.; Marjakangas, Jenni M.

    2016-01-01

    Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development. PMID:26856827

  5. Kepler-4b: A Hot Neptune-Like Planet of a G0 Star Near Main-Sequence Turnoff

    DTIC Science & Technology

    2010-04-20

    70 80 90. 100 Planetary Mass (Earth Masses) 1 2 3 4 5 6 7 R ad iu s (E ar th R ad ii) Kepler-4b Uranus Neptune GJ 436b Baraffe Z=0.5, NI, 7Gyr HAT...have masses and radii equal to or larger than those of Neptune and Uranus . The most important differences between the three exoplanets are their host...in Neptune or Uranus ). Nevertheless, we can state with a measure of confidence that there are no possible interior models for Kepler-4b with no H/He

  6. The Development of a Degree 360 Expansion of the Dynamic Ocean Topography of the POCM_4B Global Circulation Model

    NASA Technical Reports Server (NTRS)

    Rapp, Richard H.

    1998-01-01

    This paper documents the development of a degree 360 expansion of the dynamic ocean topography (DOT) of the POCM_4B ocean circulation model. The principles and software used that led to the final model are described. A key principle was the development of interpolated DOT values into land areas to avoid discontinuities at or near the land/ocean interface. The power spectrum of the POCM_4B is also presented with comparisons made between orthonormal (ON) and spherical harmonic magnitudes to degree 24. A merged file of ON and SH computed degree variances is proposed for applications where the DOT power spectrum from low to high (360) degrees is needed.

  7. 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.

  8. 76 FR 18511 - Notice of Decision To Issue Permits for the Importation of Fresh Figs From Chile into the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ... figs in the recommended treatment may not kill eggs of the insects of concern because eggs would most... specify a particular insect of concern, the pest ] risk assessment identified Mediterranean fruit fly... tolerance of Mediterranean fruit fly relative to other target insects, including mites. As we...

  9. 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.

  10. Traditional nutritional analyses of figs overestimates intake of most nutrient fractions: a study of ficus perforata consumed by howler monkeys (Alouatta palliata mexicana).

    PubMed

    Urquiza-Haas, Tania; Serio-Silva, Juan Carlos; Hernández-Salazar, Laura Teresa

    2008-05-01

    There continue to remain uncertainty concerning the nutritional importance of figs (Ficus spp.) in the primate diet. Although studies have been performed on the nutritional analysis of fig pulp and seed fractions separately, there has not been an attempt to quantify the contribution of animal matter within figs. Here we report nutritional values of figs (Ficus perforata) (Urostigma) consumed by a troop of howler monkeys (Alouatta palliata mexicana). Separate nutritional assays were performed on the pulp, seed, and animal fraction. Whole-fig analyses significantly exaggerate the concentrations of all nutrients (lipids especially) as seeds, which represent a large proportion of the fig (45%), cannot be digested. Animal matter only represents 1% of the fig, and augments fig protein and lipid content by 0.44 and 0.30%, respectively. This represents the 11 and 9% of the fraction available for digestion. Differences in fig consumption were observed between age and sex classes (P=0.04) and periods of the day (P=0.001); females consumed more figs than males and the highest consumption of figs was observed in the afternoon. F. perforata figs may be an important component of the howler monkeys diet owing to their high content of water and calcium.

  11. Heat shock factor-4 (HSF-4a) is a repressor of HSF-1 mediated transcription.

    PubMed

    Zhang, Y; Frejtag, W; Dai, R; Mivechi, N F

    2001-01-01

    Heat shock transcription factors (HSFs) regulate the expression of heat shock proteins and other molecular chaperones that are involved in cellular processes from higher order assembly to protein degradation and apoptosis. Among the human HSFs, HSF-4 is expressed as at least two splice variants. One isoform (HSF-4b) possesses a transcriptional activation domain, but this region is absent in the other isoform (HSF-4a). We have recently shown that the HSF-4a isoform represses basal transcription from heterologous promoters both in vitro and in vivo. Here we show that HSF-4a and HSF-4b have dramatically different effects on HSF-1-containing nuclear bodies, which form after heat shock. While the expression of HSF-4b colocalizes with nuclear granules, the expression of HSF-4a prevents their formation. In addition, there is a concurrent reduction of HSF-1 in the nucleus, and there is reduction in its DNA binding activity and in HSE-dependent transcription of a reporter gene. To better understand the mechanism by which HSF-4a represses transcription, we inducibly expressed HSF-4a in cells and found that HSF-4a binds to the heat shock element (HSE) during attenuation of the heat shock response. Thus HSF-4a is an active repressor of HSF-1-mediated transcription. This repressor function makes the HSF-4a isoform unique within the HSF family.

  12. Transiting exoplanets from the CoRoT space mission. V. CoRoT-Exo-4b: stellar and planetary parameters

    NASA Astrophysics Data System (ADS)

    Moutou, C.; Bruntt, H.; Guillot, T.; Shporer, A.; Guenther, E.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barbieri, M.; Barge, P.; Benz, W.; Bordé, P.; Bouchy, F.; Deeg, H. J.; de La Reza, R.; Deleuil, M.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gillon, M.; Gondoin, P.; Hatzes, A.; Hébrard, G.; Jorda, L.; Kabath, P.; Lammer, H.; Léger, A.; Llebaria, A.; Loeillet, B.; Magain, P.; Mayor, M.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Rouan, D.; Schneider, J.; Udry, S.; Wuchterl, G.

    2008-09-01

    Aims: The CoRoT satellite has announced its fourth transiting planet (Aigrain et al. 2008, A&A, 488, L43) with space photometry. We describe and analyse complementary observations of this system performed to establish the planetary nature of the transiting body and to estimate the fundamental parameters of the planet and its parent star. Methods: We have analysed high precision radial-velocity data, ground-based photometry, and high signal-to-noise ratio spectroscopy. Results: The parent star CoRoT-Exo-4 (2MASS 06484671-0040219) is a late F-type star of mass of 1.16 M⊙ and radius of 1.17 R⊙. The planet has a circular orbit with a period of 9.20205 d. The planet radius is 1.19 R_Jup and the mass is 0.72 M_Jup. It is a gas-giant planet with a “normal” internal structure of mainly H and He. CoRoT-Exo-4b has the second longest period of the known transiting planets. It is an important discovery since it occupies an empty area in the mass-period diagram of transiting exoplanets. Based on observations obtained with CoRoT, a space project operated by the French Space Agency, CNES, with participation of the Science Programme of ESA, ESTEC/RSSD, Austria, Belgium, Brazil, Germany and Spain; and on observations made with the SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07B.MOUT), and the HARPS spectrograph at ESO La Silla Observatory (079.C-0127/F). Table 2 and Fig. 5 are only available in electronic form at http://www.aanda.org

  13. Egr-1 regulates irradiation-induced autophagy through Atg4B to promote radioresistance in hepatocellular carcinoma cells

    PubMed Central

    Peng, W-x; Wan, Y-y; Gong, A-h; Ge, L; Jin, J; Xu, M; Wu, C-y

    2017-01-01

    Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) revealed that Egr-1 binds to the Atg4B promoter to upregulate its expression in HCC cells. Suppression of Egr-1 function by dominant-negative Egr-1 dampens IR-induced autophagy, cell migration, and increases cell sensitivity to radiotherapy. Together, these results suggest that Egr-1 contributes to HCC radioresistance through directly upregulating target gene Atg4B, which may serve as a protective mechanism by preferential activation of the autophagy. PMID:28134935

  14. Near-Zero Thermal Expansion and High Ultraviolet Transparency in a Borate Crystal of Zn4 B6 O13.

    PubMed

    Jiang, Xingxing; Molokeev, Maxim S; Gong, Pifu; Yang, Yi; Wang, Wei; Wang, Shuaihua; Wu, Shaofan; Wang, Yingxia; Huang, Rongjin; Li, Laifeng; Wu, Yicheng; Xing, Xianran; Lin, Zheshuai

    2016-09-01

    Intrinsic isotropic near-zero thermal expansion is discovered in borate crystal Zn4 B6 O13 with high transparency in the ultraviolet region. First-principles calculations demonstrate that the very low thermal expansion originates mainly from the invariability of the solid [B24 O48 ] truncated octahedra that are fixed by the [Zn4 O13 ] clusters in the ZBO structure.

  15. 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...

  16. Increased expression of plasma membrane Ca(2+)ATPase 4b in platelets from hypertensives: a new sign of abnormal thrombopoiesis?

    PubMed

    Dally, Saoussen; Chaabane, Chiraz; Corvazier, Elisabeth; Bredoux, Raymonde; Bobe, Regis; Ftouhi, Bochra; Slimane, Hedia; Raies, Aly; Enouf, Jocelyne

    2007-11-01

    Platelet Ca(2+) homeostasis is controlled by a multi-Ca(2+)ATPase system including two PMCA (plasma membrane Ca(2+)ATPase) and seven SERCA (sarco/endoplasmic reticulum Ca(2+)ATPase) isoforms. Previous studies have shown similar platelet Ca(2+) abnormalities in diabetic and hypertensive patients, including an increase in intracellular [Ca(2+)](I), a possible modulation of PMCA activity and increased PMCA tyrosine phosphorylation. Very recently, we found that platelets from diabetic patients also exhibited increased PMCA4b expression. In the present study we looked for further similarities between diabetic and hypertensive patients. We first confirmed a decrease in Ca(2+)ATPase activity (mean 55 + 7%) in mixed platelet membranes isolated from 10 patients with hypertension compared with those from 10 healthy controls. In addition, the decreased Ca(2+)ATPase activity correlated with the DBP of the different patients, as expected for PMCA activity. Second, we performed a pilot study of six hypertensives to examine their expressions of PMCA and SERCA mRNA and proteins. Like the diabetic patients, 100% of hypertensives were found to present a major increase in PMCA4b expression (mean value of 218 +/- 21%). We thus determined that platelets from diabetic and hypertensive patients showed similar increased PMCA4b isoform. Since increased PMCA4b expression was recently found to be associated with a perturbation of megakaryocytopoiesis, these findings may also point to an abnormality in platelet maturation in hypertension.

  17. 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

    ... 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 General... General Chapter harmonized text from each of the three pharmacopoeias (United States, European,...

  18. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication

    PubMed Central

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S.; Hirschberg, Koret; Sklan, Ella H.

    2015-01-01

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B–NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits. PMID:25462354

  19. KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels

    PubMed Central

    Choi, Ji-Young; Yoon, Sang-Sun; Kim, Sang-Eun; Ahn Jo, Sangmee

    2017-01-01

    Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression. Inhibition of G9a and EZH2, histone methyltransferases responsible for methylation at H3K9 and H3K27, respectively as well as G9a overexpression demonstrated the involvement of G9a in TNF-α-induced ICAM1 expression and leukocyte adhesion and transmigration. A specific role for KDM4B, a histone demethylase targeting H3K9me2, in TNF-α-induced ICAM1 upregulation was validated with siRNA. Moreover, treating mice with a KDM4 inhibitor ML324 blocked TNF-α-mediated neutrophil adhesion. Similarly, TNF-α-induced VCAM1 expression was suppressed by G9a overexpression and KDM4B knockdown. Collectively, we demonstrated that modification of H3K9me2 by G9a and KDM4B regulates expression of vascular adhesion molecules, and that depletion of these proteins or KDM4B reduces inflammation-induced leukocyte extravasation. Thus, blocking ICAM1 or KDM4B could offer a novel therapeutic opportunity treating brain diseases. PMID:28327608

  20. Role of irradiation in the green synthesis of silver nanoparticles mediated by fig (Ficus carica) leaf extract.

    PubMed

    Ulug, Bulent; Haluk Turkdemir, M; Cicek, Ahmet; Mete, Ahmet

    2015-01-25

    Biosynthesis of silver nanoparticles in an aqueous mixture of fig (Ficus carica) leaf extract and AgNO3 solution exposed to a set of irradiances at different wavelengths are studied. Nanoparticle formation for irradiances between 6.5 mW/cm(2) and 13.3 mW/cm(2) in the 330-550 nm wavelength range is investigated and the results are compared to those of the nanoparticles synthesized in the dark and under direct sunlight. Ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy, along with particle size analysis and transmission electron microscopy are employed for the characterization of samples and extracts. Irradiance is found to have profound influence on the reduction rates. However, size and spherical shape of the nanoparticles are persistent, irrespective of irradiance and wavelength. Irradiance is discussed to influence the particle formation and aggregation rates through the formation of free radicals in the fig extract.

  1. Sirovena Bouček (Pteromalidae: Pireninae), a new member of the fig wasp community associated with Ficus microcarpa (Moraceae).

    PubMed

    Li, Zi; Xiao, Hui; Huang, Da-Wei

    2013-01-01

    Sirovena Bouček (Chalcidoidea: Pteromalidae, Pireninae) was known only from females of its type species, S. stigma Bouček, 1988. Males and host associations were both unknown. Both sexes of a second species of Sirovena, S. costallifera sp. nov., reared from Ficus microcarpa L. (Moraceae) in Yunnan, China, are described based on morphological characters and mitochondrial COI sequences. The males of S. costallifera show sexual dimorphism in body coloration, structure of the antennae and notauli, and body sculpture. Reliable host records of Pireninae are Cecidomyiidae (Diptera). Because midges also parasitize some figs, we speculate that S. costallifera is a parasitoid of some cecidomyiid midge that attacks fig syconia. A key to differentiate the two species is provided.

  2. 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

    2016-07-14

    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.

  3. 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.

  4. Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.

    PubMed

    Dennis, Michael D; Jefferson, Leonard S; Kimball, Scot R

    2012-12-14

    Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.

  5. 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.

  6. CRL4B interacts with and coordinates the SIN3A-HDAC complex to repress CDKN1A and drive cell cycle progression.

    PubMed

    Ji, Qinghong; Hu, Huili; Yang, Fan; Yuan, Jupeng; Yang, Yang; Jiang, Liangqian; Qian, Yanyan; Jiang, Baichun; Zou, Yongxin; Wang, Yan; Shao, Changshun; Gong, Yaoqin

    2014-11-01

    CUL4B, a scaffold protein that assembles the CRL4B ubiquitin ligase complex, participates in the regulation of a broad spectrum of biological processes. Here, we demonstrate a crucial role of CUL4B in driving cell cycle progression. We show that loss of CUL4B results in a significant reduction in cell proliferation and causes G1 cell cycle arrest, accompanied by the upregulation of the cyclin-dependent kinase (CDK) inhibitors (CKIs) p21 and p57 (encoded by CDKN1A and CDKN1C, respectively). Strikingly, CUL4B was found to negatively regulate the function of p21 through transcriptional repression, but not through proteolysis. Furthermore, we demonstrate that CRL4B and SIN3A-HDAC complexes interact with each other and co-occupy the CDKN1A and CDKN1C promoters. Lack of CUL4B led to a decreased retention of SIN3A-HDAC components and increased levels of acetylated H3 and H4. Interestingly, the ubiquitylation function of CRL4B is not required for the stable retention of SIN3A-HDAC on the promoters of target genes. Thus, in addition to directly contributing to epigenetic silencing by catalyzing H2AK119 monoubiquitylation, CRL4B also facilitates the deacetylation function of SIN3A-HDAC. Our findings reveal a coordinated action between CRL4B and SIN3A-HDAC complexes in transcriptional repression.

  7. 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.

  8. Neutrons Flux Distributions of the Pu-Be Source and its Simulation by the MCNP-4B Code

    NASA Astrophysics Data System (ADS)

    Faghihi, F.; Mehdizadeh, S.; Hadad, K.

    Neutron Fluence rate of a low intense Pu-Be source is measured by Neutron Activation Analysis (NAA) of 197Au foils. Also, the neutron fluence rate distribution versus energy is calculated using the MCNP-4B code based on ENDF/B-V library. Theoretical simulation as well as our experimental performance are a new experience for Iranians to make reliability with the code for further researches. In our theoretical investigation, an isotropic Pu-Be source with cylindrical volume distribution is simulated and relative neutron fluence rate versus energy is calculated using MCNP-4B code. Variation of the fast and also thermal neutrons fluence rate, which are measured by NAA method and MCNP code, are compared.

  9. The calculated magnetic, electronic and thermodynamic properties of Ce3Co29Si4B10 compound

    NASA Astrophysics Data System (ADS)

    Huo, Jin-Rong; Wang, Xiao-Xu; Hu, Yao-Wen; Zhang, Guo-Hua; Cheng, Hai-Xia; Li, Lu; Qian, Ping

    2016-05-01

    The magnetic moment, lattice parameter and atom fraction coordinates for Ce3Co29Si4B10 are calculated by the first-principles GGA+U method, and the results indicate that the calculated and experimental values are basically accordant when U=2.6 eV. We study the interaction effect and orbital hybridization between Co and Ce atoms. The projected density of states at U=2.6 eV which provided by Co-2c, Ce-2b and Ce-4d sites are contrasted with else U values. Meanwhile the electron density of states for different sites and the distance between various atoms are exhibited. In addition, the thermodynamic properties of Ce3Co29Si4B10 are evaluated by using a series of interatomic pair potentials.

  10. 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.

  11. FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex

    PubMed Central

    Sjögren, Benita; Swaney, Steven; Neubig, Richard R.

    2015-01-01

    The ubiquitin-proteasome system for protein degradation plays a major role in regulating cell function and many signaling proteins are tightly controlled by this mechanism. Among these, Regulator of G Protein Signaling 2 (RGS2) is a target for rapid proteasomal degradation, however, the specific enzymes involved are not known. Using a genomic siRNA screening approach, we identified a novel E3 ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1 (DDB1) and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation. While the more typical F-box partners CUL1 and Skp1 can bind FBXO44, that E3 ligase complex does not bind RGS2 and is not involved in RGS2 degradation. These observations define an unexpected DDB1/CUL4B-containing FBXO44 E3 ligase complex. Pharmacological targeting of this mechanism provides a novel therapeutic approach to hypertension, anxiety, and other diseases associated with RGS2 dysregulation. PMID:25970626

  12. An improved method for expression and purification of functional human Ca(2+) transporter PMCA4b in Saccharomyces cerevisiae.

    PubMed

    Corbacho, Isaac; García-Prieto, Francisco F; Hinojosa, Ara E; Berrocal, María; Mata, Ana M

    2016-04-01

    Human plasma membrane calcium ATPases (PMCAs) are highly regulated transporters responsible for the extrusion of calcium out of the cell. Since calcium homeostasis is implicated in several diseases and neurodegenerative disorders, understanding PMCAs activity is crucial. One of the major hindrances is the availability of these proteins for functional and structural analysis. Here, using the yeast Saccharomyces cerevisiae system, we show a new and enhanced method for the expression of the full-length human PMCA isoform 4b (hPMCA4b) and a truncated form lacking its auto-inhibitory domain. We have also improved a method for the purification of the native isoform by calmodulin-agarose affinity chromatography, and developed a new method to purify the truncated isoform by glutathione-Sepharose affinity chromatography. One of the most relevant features of this work is that, when compared to PMCAs purification from pig brain, our method provides a pure single isoform instead of a mixture of isoforms, essential for fine-tuning the activity of PMCA4b. Another relevant feature is that the method described in this work has a superior yield of protein than previously established methods to purify PMCA proteins expressed in yeasts.

  13. SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer

    PubMed Central

    Bon, Emeline; Driffort, Virginie; Gradek, Frédéric; Martinez-Caceres, Carlos; Anchelin, Monique; Pelegrin, Pablo; Cayuela, Maria-Luisa; Marionneau-Lambot, Séverine; Oullier, Thibauld; Guibon, Roseline; Fromont, Gaëlle; Gutierrez-Pajares, Jorge L.; Domingo, Isabelle; Piver, Eric; Moreau, Alain; Burlaud-Gaillard, Julien; Frank, Philippe G.; Chevalier, Stéphan; Besson, Pierre; Roger, Sébastien

    2016-01-01

    The development of metastases largely relies on the capacity of cancer cells to invade extracellular matrices (ECM) using two invasion modes termed ‘mesenchymal' and ‘amoeboid', with possible transitions between these modes. Here we show that the SCN4B gene, encoding for the β4 protein, initially characterized as an auxiliary subunit of voltage-gated sodium channels (NaV) in excitable tissues, is expressed in normal epithelial cells and that reduced β4 protein levels in breast cancer biopsies correlate with high-grade primary and metastatic tumours. In cancer cells, reducing β4 expression increases RhoA activity, potentiates cell migration and invasiveness, primary tumour growth and metastatic spreading, by promoting the acquisition of an amoeboid–mesenchymal hybrid phenotype. This hyperactivated migration is independent of NaV and is prevented by overexpression of the intracellular C-terminus of β4. Conversely, SCN4B overexpression reduces cancer cell invasiveness and tumour progression, indicating that SCN4B/β4 represents a metastasis-suppressor gene. PMID:27917859

  14. Magnetic phase transformations and superconductivity in Dy0.8Y0.2Rh4B4

    NASA Astrophysics Data System (ADS)

    Dmitriev, V. M.; Zaleskiĭ, A.; Khlybov, E. P.; Rybal'Chenko, L. F.; Khristenko, E. V.; Ishchenko, L. A.; Terekhov, A. V.; Kostyleva, I. E.; Lachenkov, S. A.

    2008-11-01

    The results of experimental studies of the magnetic and the superconducting properties of the compound Dy0.8Y0.2Rh4B4 with tetragonal body-centered crystal structure of the perovskite type (LuRu4B4) are presented. It is shown that the compound undergoes a paramagnet-ferrimagnet phase transition at the Curie temperature TC≈30.5K and its magnetic compensation temperature Tcomp≈17K. According to resistance measurements, the compound becomes a ferrimagnetic superconductor at Tconset≈5.9K which undergoes a ferrimagnet-antiferromagnet phase transition at TN≈2.7K while still remaining a superconductor. The specific heat exhibits a sharp maximum at this temperature. Point-contact Andreev reflection spectroscopy is used to measure the temperature and field dependences of the order parameter Δ(T ,H) and the temperature dependence of the upper critical field Hc2(T ). The dependences obtained differ radically from those generally accepted for conventional superconductors. The results obtained are discussed in connection with the possibility of triplet pairing in Dy0.8Y0.2Rh4B4.

  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

    2013-06-03

    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. 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

  17. Two C-terminal variants of NBC4, a new member of the sodium bicarbonate cotransporter family: cloning, characterization, and localization.

    PubMed

    Pushkin, A; Abuladze, N; Newman, D; Lee, I; Xu, G; Kurtz, I

    2000-07-01

    We report the cloning, characterization, and chromosomal assignment of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC4. The NBC4 gene was mapped to chromosome 2p13 and is a new candidate gene for Alstrom syndrome. Two variants of the transporter have been isolated from human testis and heart, which differ in their C termini. NBC4a encodes a 1137-residue polypeptide and is widely expressed in various tissues, including liver, testis, and spleen. NBC4b is identical to NBC4a except that it has a 16-nucleotide insert, creating a C-terminal frame shift. NBC4b encodes a 1074-residue polypeptide and is highly expressed in heart. Amino acids 1-1046 are common to both NBC4 variants. NBC4a has two protein-interacting domains that are lacking in NBC4b: a proline-rich sequence, PPPSVIKIP (amino acids 1102-1110), and a consensus PDZ-interacting domain, SYSL (1134-1137). NBC4b lacks the stretch of charged residues present in the C terminus of NBC4a and other members of the NBC family. Unlike other members of the NBC family, both NBC4a and NBC4b have a unique glycine-rich region (amino acids 440-469). In comparison with other members of the bicarbonate transport superfamily, NBC4a and NBC4b are most similar structurally to the electrogenic sodium bicarbonate cotransporters (NBC1).

  18. 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.

  19. 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.

  20. 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.

  1. Redescription of the fig wasp genus Sycophilodes Joseph (Chalcidoidea: Pteromalidae: Epichrysomallinae) with description of a new species from India.

    PubMed

    Pramanik, Achintya; Dey, Debjani

    2014-07-18

    Sycophilodes Joseph is a non-pollinating fig wasp genus so far reported only from Ficus benghalensis L. The genus Sycophilodes is revised with redescription of the male and the first description of the female of its only currently included species, S. moniliformis. A second species, Sycophilodes uluberiaensis Pramanik & Dey sp. nov. is described. Available keys are modified and supplemented to facilitate identification of Sycophilodes and a key for distinguishing both sexes of the two included species is presented. All type specimens are deposited in the National Pusa Collection, IARI, New Delhi.

  2. 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.

  3. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease▿

    PubMed Central

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-01-01

    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. PMID:21507982

  4. Isolation and structure of ciguatoxin-4A, a new ciguatoxin precursor, from cultures of dinoflagellate Gambierdiscus toxicus and parrotfish Scarus gibbus.

    PubMed

    Satake, M; Ishibashi, Y; Legrand, A M; Yasumoto, T

    1996-12-01

    A new ciguatoxin congener, ciguatoxin-4A (CTX4A), was isolated from cultures of marine dinoflagellate Gambierdiscus toxicus, and its structure was elucidated to be 52-epiciguatoxin-4B on the basis of spectroscopic data. Chromatographic and spectral comparisons indicated that CTX4A was identical with a structurally unelucidated congener known as scaritoxin or SG1.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Selective resource allocation may promote a sex ratio in pollinator fig wasps more beneficial for the host tree.

    PubMed

    Li, Zhao-Tian; Peng, Yan-Qiong; Wen, Xiao-Lan; Jandér, K Charlotte

    2016-10-12

    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.

  10. 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.

  11. Giant magnetic coercivity in YNi4B-type SmNi3TB (T=Mn-Cu) solid solutions

    NASA Astrophysics Data System (ADS)

    Yao, Jinlei; Yan, Chang; Yapaskurt, V. O.; Morozkin, A. V.

    2016-12-01

    The effects of transition metal substitution for Ni on the magnetic properties of the YNi4B-type SmNi4B via SmNi3TB (T=Mn, Fe, Co, Cu) solid solutions have been investigated. SmNi4B, SmNi3MnB, SmNi3FeB, SmNi3CoB and SmNi3CuB show ferromagnetic ordering at 40 K, 210 K, 322 K, 90 K and 57 K and field sensitive metamagnetic-like transitions at 15 K, 100 K, 185 K, 55 K and 15 K in a magnetic field of 10 kOe, respectively. The magnetocaloric effects of SmNi3TB (T=Mn-Cu) were calculated in terms of isothermal magnetic entropy change (ΔSm). The magnetic entropy ΔSm reaches value of -0.94 J/kg K at 40 K for SmNi4B, -1.5 J/kg K at 205 K for SmNi3MnB, -0.54 J/kg K at 320 K for SmNi3FeB, -0.49 J/kg K at 90 K for SmNi3CoB and -0.54 J/kg K at 60 K for SmNi3CuB in field change of 0-50 kOe around the Curie temperature. They show positive ΔSm of +0.71 J/kg K at ~10 K for SmNi4B, +1.69 J/kg K at 30 K for SmNi3MnB, +0.89 J/kg K at 110 K for SmNi3FeB, +1.08 J/kg K at 25 K for SmNi3CoB and +1.12 J/kg K at 10 K for SmNi3CuB in field change of 0-50 kOe around the low temperature metamagnetic-like transition. Below the field induced transition temperature (change of magnetic structure), SmNi3TB (T=Mn-Cu) exhibits giant magnetic coercivity of 74 kOe at 5 K for SmNi4B, 69 kOe at 20 K (90 kOe at 10 K) for SmNi3MnB, 77 kOe at 60 K for SmNi3FeB, 88 kOe at 20 K for SmNi3CoB and 52 kOe at 5 K for SmNi3CuB.

  12. Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo.

    PubMed

    Hsu, Iawen; Yeh, Chiuan-Ren; Slavin, Spencer; Miyamoto, Hiroshi; Netto, George J; Tsai, Yu-Chieh; Muyan, Mesut; Wu, Xue-Ru; Messing, Edward M; Guancial, Elizabeth A; Yeh, Shuyuan

    2014-09-15

    Clinical reports show males have a higher bladder cancer (BCa) incidence than females. The sexual difference of BCa occurrence suggests that estrogen and its receptors may affect BCa development. Estrogen receptor alpha (ERα) is the classic receptor to convey estrogen signaling, however, the function of ERα in BCa development remains largely unknown. To understand the in vivo role of ERα in BCa development, we generated total and urothelial specific ERα knockout mice (ERαKO) and used the pre- carcinogen BBN to induce BCa. Earlier reports showed that ERα promotes breast and ovarian cancers in females. Surprisingly and of clinical importance, our results showed that ERα inhibits BCa development and loss of the ERα gene results in an earlier onset and higher incidence of BBN-induced in vivo mouse BCa. Supportively, carcinogen induced malignant transformation ability was reduced in ERα expressing urothelial cells as compared to ERα negative cells. Mechanism studies suggest that ERα could control the expression of INPP4B to reduce AKT activity and consequently reduce BCa cell growth. In addition, IHC staining of clinical sample analyses show that INPP4B expression, in correlation with reduced ERα, is significantly reduced in human BCa specimens. Together, this is the first report using the in vivo cre-loxP gene knockout mouse model to characterize ERα roles in BCa development. Our studies provide multiple in vitro cell studies and in vivo animal model data as well as human BCa tissue analyses to prove ERα plays a protective role in BCa initiation and growth at least partly via modulating the INPP4B/Akt pathway.

  13. First report of severe parainfluenza virus 4B and rhinovirus C coinfection in a liver transplant recipient treated with immunoglobulin.

    PubMed

    Sridhar, Siddharth; Luk, Hayes K H; Lau, Susanna K P; Woo, Patrick C Y

    2014-12-01

    We describe the first reported case of severe pneumonia due to coinfection by parainfluenza virus type 4B and rhinovirus C in a liver transplant recipient. The patient responded promptly to intravenous immunoglobulin and timely infection control measures prevented spreading of the infections. This report highlights respiratory viral coinfections as a possible cause of severe morbidity in transplant recipients and the importance of efficient molecular diagnostic technologies with major impact on clinical practice in a transplant center. It also describes a potential therapeutic strategy for such patients.

  14. Developing VUV spectroscopy for protein folding and material luminescence on beamline 4B8 at the Beijing Synchrotron Radiation Facility.

    PubMed

    Tao, Ye; Huang, Yan; Gao, Zhenghua; Zhuang, Hao; Zhou, Aiyu; Tan, Yinglei; Li, Daowu; Sun, Shuaishuai

    2009-11-01

    The new 4B8 beamline provides UV-VUV light in the wavelength range from 360 to 120 nm. It uniquely enables two kinds of spectroscopy measurements: synchrotron radiation circular dichroism spectroscopy and VUV excited fluorescence spectroscopy. The former is mainly used in protein secondary structure studies, and the latter in VUV excited luminescent materials research. Remote access to fluorescence measurement has been realised and users can collect data online. Besides steady-state measurements, fluorescence lifetime measurements have been established using the time domain method, while a laser-induced temperature jump is under development for protein folding dynamics using circular dichroism as a probe.

  15. ATG4B contains a C-terminal LIR motif important for binding and efficient cleavage of mammalian orthologs of yeast Atg8.

    PubMed

    Skytte Rasmussen, Mads; Mouilleron, Stéphane; Kumar Shrestha, Birendra; Wirth, Martina; Lee, Rebecca; Bowitz Larsen, Kenneth; Abudu Princely, Yakubu; O'Reilly, Nicola; Sjøttem, Eva; Tooze, Sharon A; Lamark, Trond; Johansen, Terje

    2017-02-15

    The cysteine protease ATG4B cleaves off one or more C-terminal residues of the inactive proform of proteins of the ortholog and paralog LC3 and GABARAP subfamilies of yeast Atg8 to expose a C-terminal glycine that is conjugated to phosphatidylethanolamine during autophagosome formation. We show that ATG4B contains a C-terminal LC3-interacting region (LIR) motif important for efficient binding to and cleavage of LC3 and GABARAP proteins. We solved the crystal structures of the GABARAPL1-ATG4B C-terminal LIR complex. Analyses of the structures and in vitro binding assays, using specific point mutants, clearly showed that the ATG4B LIR binds via electrostatic-, aromatic HP1 and hydrophobic HP2 pocket interactions. Both these interactions and the catalytic site-substrate interaction contribute to binding between LC3s or GABARAPs and ATG4B. We also reveal an unexpected role for ATG4B in stabilizing the unlipidated forms of GABARAP and GABARAPL1. In mouse embryonic fibroblast (MEF) atg4b knockout cells, GABARAP and GABARAPL1 were unstable and degraded by the proteasome. Strikingly, the LIR motif of ATG4B was required for stabilization of the unlipidated forms of GABARAP and GABARAPL1 in cells.

  16. 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

  17. 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... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General prohibition