105 research outputs found

    Patriarchal Negotiations: Women, Writing and Religion 1640-1660

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    PhDWomen were prominent in the Lollard movement in the fifteenth century, but it is only in the mid-seventeenth century that women begin to produce theological texts which contribute to the controversy over popular religious expression and women's part in religious culture. After 1640 women began to publish on a number of theological issues and in a wide range of genres: prose polemic, prophecy, autobiography and spiritual meditation. Subject to widespread criticism, they quickly had to fashion a rhetoric of justification with which to defend their intervention in print and pacify male critics. This thesis shows that they achieved this in two ways: by producing a literature which complied with the expectations of masculine theological culture and by manipulating these assumptions so as to create space for a female symbolic language of piety. They developed a literary self-consciousness which depends on the idea of subjectivity as a gendered experience and they often resisted their detractors by valorising denigrated forms of female subjectivity and pursuing theological conclusions irrespective of normative ideas of gender. Women did not engage in theological debate in isolation, however. They often intervened as committed members of religious sects and thus deserve to be read as representatives of corporate and communal theologies. In contrast to earlier studies which have sought to recover neglected women writers as early feminists, without reading their work historically, this thesis seeks to uncover the social and the theological rather than the authorial origin of much early modem women's writing and to measure its engagement with early modem debates on women and religious culture. It seeks to challenge the increasingly dominant view of early modem women writers which invests them with too modem an authorial presence, by reconstituting the seventeenth-century debates which gave rise to their work and by bringing modem French feminist perspectives to bear on a period largely untouched by theoretical approaches to literature. To this end it proceeds by way of several close readings of women who wrote as women and as Baptists, Independents, Levellers, Presbyterians and Quakers

    The Effect of Collectivism on Union Attitudes and Beliefs

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    Researchers have attempted to understand the unionization process by examining the variables surrounding an individual’s decision to vote for a union. Despite the linkage of an individual’s attitude towards unions and the individual’s propensity to vote for a union, there has been little research which attempts to understand which personality constructs might be predictive of general attitudes towards unions. Using causal modeling techniques, we investigated the effect of collectivism on general union attitudes and union instrumentality beliefs with a sample of workers from the Southeastern United States. It was found that a more collectivist orientation is positively associated with beliefs about, and feelings towards, unions. Ancillary analyses revealed that African Americans held greater union favorability attitudes and greater positive beliefs about union instrumentality relative to Caucasians, though a more collectivist nature among African Americans did not explain these findings. It was also revealed that females had a more positive general attitude towards unions and were marginally more positive regarding the effects of unions on specific issues as compared to males

    Evolutionary and therapeutic consequences of phenotypic heterogeneity in microbial populations

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    The historical notion of a microbial population has been of a clonal population of identical swimming planktonic cells in a laboratory flask. As the field has advanced, we have grown to appreciate the immense diversity in microbial behaviors, from their propensity to grow in dense surface-attached communities as a biofilm, to the consequences of social dilemmas between cells, to their ability to form spores able to survive nearly any environmental insult. However, the historically biased view of the clonal microbial population still persists – even when a rare phenotype is investigated, the focus simply shifts to that narrower focal population - and this bias can lead to some of the broader questions relating to the consequences of phenotypic diversity within populations to be overlooked. This work seeks to address this gap by investigating the evolutionary causes and consequences of phenotypic heterogeneity, with a focus on clinically relevant phenotypes. We first develop and experimentally validate a theoretical model describing the evolution of a microbial population faced with a trade-off between survival and fecundity phenotypes (e.g. biofilm and planktonic cells), which suggests that simultaneous investment in both types maximizes lineage fitness in heterogeneous environments. This model helps to inform the experimental studies in the following chapters. We find that biofilm-mediated phenotypic resistance to antibiotics is evolutionarily labile, and responsive to antibiotic dose and whether biofilm or planktonic cells are passaged. We also show that persistence in E. coli is age-independent, supporting the current hypothesis of stochastic metabolic fluctuations as the cause of this rare phenotype. Finally, we explore phenotypic variation across a library of natural isolates of P. aeruginosa, and find few organizing principles among key phenotypes related to virulence. Together these results suggest that phenotypic heterogeneity is a crucial component in the ecology and evolution of microbial populations, and directly affects pressing applied concerns such as the antibiotic resistance crisis

    Nutrient Sensing by Tas1R Proteins is Required for Normal Bone Resorption

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    Current therapies for low bone mass consist of inhibiting osteoclast activity or increasing the PTH or Wnt signaling pathways. These approaches have significant drawbacks that limit their use in specific patient populations and/or negatively impact patient compliance with therapy. Developing improved therapies requires diversifying our understanding of the mechanisms underlying postnatal bone remodeling by examining lesser-known signaling pathways. One such pathway is the taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors, which participates in monitoring energy and nutrient status. Previous work reported that global deletion of TAS1R member 3 (TAS1R3), which is a bi-functional protein that recognizes amino acids or sweet molecules when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively, leads to increased cortical bone mass. Here, we corroborate the increased thickness of cortical bone in Tas1R3 knockout mice and confirm that Tas1R3 is expressed in the bone environment. Quantification of serum bone turnover markers indicate that this phenotype is likely due to uncoupled bone remodeling, with levels of the bone resorption marker CTx being reduced greater than 60% in Tas1R3 mutant mice; no changes were observed in levels of the bone formation marker PINP. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and RAW264.7 cells following RANKL-mediated differentiation. These findings suggest that osteoclast function and/or differentiation may be altered in the absence of Tas1R3 expression. To test this, we quantified bone-specific expression of Rankl and determined the Rankl:Opg ratio; no differences were observed between control and Tas1R3 knockout mice in these analyses. In vitro studies examining further downstream effectors of TAS1R2:3 in response to saccharin and receptor antagonist gurmarin are currently underway. Collectively, our findings provide the first demonstration that nutrient monitoring by TAS1R3 is essential for normal bone resorption in vivo

    Roles and Programming of Arabidopsis ARGONAUTE Proteins during Turnip Mosaic Virus Infection

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    [EN] In eukaryotes, ARGONAUTE proteins (AGOs) associate with microRNAs (miRNAs), short interfering RNAs (siRNAs), and other classes of small RNAs to regulate target RNA or target loci. Viral infection in plants induces a potent and highly specific antiviral RNA silencing response characterized by the formation of virus-derived siRNAs. Arabidopsis thaliana has ten AGO genes of which AGO1, AGO2, and AGO7 have been shown to play roles in antiviral defense. A genetic analysis was used to identify and characterize the roles of AGO proteins in antiviral defense against Turnip mosaic virus (TuMV) in Arabidopsis. AGO1, AGO2 and AGO10 promoted anti-TuMV defense in a modular way in various organs, with AGO2 providing a prominent antiviral role in leaves. AGO5, AGO7 and AGO10 had minor effects in leaves. AGO1 and AGO10 had overlapping antiviral functions in inflorescence tissues after systemic movement of the virus, although the roles of AGO1 and AGO10 accounted for only a minor amount of the overall antiviral activity. By combining AGO protein immunoprecipitation with high-throughput sequencing of associated small RNAs, AGO2, AGO10, and to a lesser extent AGO1 were shown to associate with siRNAs derived from silencing suppressor (HC-Pro)-deficient TuMV-AS9, but not with siRNAs derived from wild-type TuMV. Co-immunoprecipitation and small RNA sequencing revealed that viral siRNAs broadly associated with wild-type HC-Pro during TuMV infection. These results support the hypothesis that suppression of antiviral silencing during TuMV infection, at least in part, occurs through sequestration of virus-derived siRNAs away from antiviral AGO proteins by HC-Pro. These findings indicate that distinct AGO proteins function as antiviral modules, and provide a molecular explanation for the silencing suppressor activity of HC-Pro.National Institutes of Health (www.nih.gov) grant AI43288 to JCC. National Science Foundation (www.nsf.gov) grant MCB-0956526 to JCC. Helen Hay Whitney (www.hhwf.org) Post-Doctoral fellowship (F-972) to HGR. USDA AFRI NIFA (www.csrees.usda.gov) Postdoctoral Fellowship (MOW-2012-01361) to NF. NSF (www.nsf.gov) Graduate Research Fellowship (DGE-1143954) to JSH Japan Society for the Promotion of Science (www.jsps.go.jp) Postdoctoral Fellowship to AT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Garcia-Ruiz, H.; Carbonell, A.; Hoyer, JS.; Fahlgren, N.; Gilbert, KB.; Takeda, A.; Giampetruzzi, A.... (2015). Roles and Programming of Arabidopsis ARGONAUTE Proteins during Turnip Mosaic Virus Infection. 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The Polerovirus Silencing Suppressor P0 Targets ARGONAUTE Proteins for Degradation. Current Biology, 17(18), 1609-1614. doi:10.1016/j.cub.2007.08.039Bortolamiol, D., Pazhouhandeh, M., Marrocco, K., Genschik, P., & Ziegler-Graff, V. (2007). The Polerovirus F Box Protein P0 Targets ARGONAUTE1 to Suppress RNA Silencing. Current Biology, 17(18), 1615-1621. doi:10.1016/j.cub.2007.07.061Csorba, T., Lózsa, R., Hutvágner, G., & Burgyán, J. (2010). Polerovirus protein P0 prevents the assembly of small RNA-containing RISC complexes and leads to degradation of ARGONAUTE1. The Plant Journal, 62(3), 463-472. doi:10.1111/j.1365-313x.2010.04163.xDerrien, B., Baumberger, N., Schepetilnikov, M., Viotti, C., De Cillia, J., Ziegler-Graff, V., … Genschik, P. (2012). Degradation of the antiviral component ARGONAUTE1 by the autophagy pathway. Proceedings of the National Academy of Sciences, 109(39), 15942-15946. doi:10.1073/pnas.1209487109Zhang, X., Yuan, Y.-R., Pei, Y., Lin, S.-S., Tuschl, T., Patel, D. J., & Chua, N.-H. (2006). Cucumber mosaic virus-encoded 2b suppressor inhibits Arabidopsis Argonaute1 cleavage activity to counter plant defense. Genes & Development, 20(23), 3255-3268. doi:10.1101/gad.1495506Giner, A., Lakatos, L., García-Chapa, M., López-Moya, J. J., & Burgyán, J. (2010). Viral Protein Inhibits RISC Activity by Argonaute Binding through Conserved WG/GW Motifs. PLoS Pathogens, 6(7), e1000996. doi:10.1371/journal.ppat.1000996Nakahara, K. S., & Masuta, C. (2014). Interaction between viral RNA silencing suppressors and host factors in plant immunity. Current Opinion in Plant Biology, 20, 88-95. doi:10.1016/j.pbi.2014.05.004Garcia-Ruiz, H., Takeda, A., Chapman, E. J., Sullivan, C. M., Fahlgren, N., Brempelis, K. J., & Carrington, J. C. (2010). Arabidopsis RNA-Dependent RNA Polymerases and Dicer-Like Proteins in Antiviral Defense and Small Interfering RNA Biogenesis during Turnip Mosaic Virus Infection  . The Plant Cell, 22(2), 481-496. doi:10.1105/tpc.109.073056Vaucheret, H. (2008). Plant ARGONAUTES. Trends in Plant Science, 13(7), 350-358. doi:10.1016/j.tplants.2008.04.007Morel, J.-B., Godon, C., Mourrain, P., Béclin, C., Boutet, S., Feuerbach, F., … Vaucheret, H. (2002). Fertile Hypomorphic ARGONAUTE (ago1) Mutants Impaired in Post-Transcriptional Gene Silencing and Virus Resistance. The Plant Cell, 14(3), 629-639. doi:10.1105/tpc.010358Harvey, J. J. W., Lewsey, M. G., Patel, K., Westwood, J., Heimstädt, S., Carr, J. P., & Baulcombe, D. C. (2011). An Antiviral Defense Role of AGO2 in Plants. PLoS ONE, 6(1), e14639. doi:10.1371/journal.pone.0014639Zhang, X., Zhang, X., Singh, J., Li, D., & Qu, F. (2012). Temperature-Dependent Survival of Turnip Crinkle Virus-Infected Arabidopsis Plants Relies on an RNA Silencing-Based Defense That Requires DCL2, AGO2, and HEN1. Journal of Virology, 86(12), 6847-6854. doi:10.1128/jvi.00497-12Wang, X.-B., Jovel, J., Udomporn, P., Wang, Y., Wu, Q., Li, W.-X., … Ding, S.-W. (2011). The 21-Nucleotide, but Not 22-Nucleotide, Viral Secondary Small Interfering RNAs Direct Potent Antiviral Defense by Two Cooperative Argonautes in Arabidopsis thaliana    . The Plant Cell, 23(4), 1625-1638. doi:10.1105/tpc.110.082305Dzianott, A., Sztuba-Solińska, J., & Bujarski, J. J. (2012). Mutations in the Antiviral RNAi Defense Pathway Modify Brome mosaic virus RNA Recombinant Profiles. Molecular Plant-Microbe Interactions®, 25(1), 97-106. doi:10.1094/mpmi-05-11-0137Carbonell, A., Fahlgren, N., Garcia-Ruiz, H., Gilbert, K. B., Montgomery, T. A., Nguyen, T., … Carrington, J. C. (2012). Functional Analysis of Three Arabidopsis ARGONAUTES Using Slicer-Defective Mutants  . The Plant Cell, 24(9), 3613-3629. doi:10.1105/tpc.112.099945Takeda, A., Iwasaki, S., Watanabe, T., Utsumi, M., & Watanabe, Y. (2008). The Mechanism Selecting the Guide Strand from Small RNA Duplexes is Different Among Argonaute Proteins. Plant and Cell Physiology, 49(4), 493-500. doi:10.1093/pcp/pcn043Azevedo, J., Garcia, D., Pontier, D., Ohnesorge, S., Yu, A., Garcia, S., … Voinnet, O. (2010). Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein. Genes & Development, 24(9), 904-915. doi:10.1101/gad.1908710Wei, W., Ba, Z., Gao, M., Wu, Y., Ma, Y., Amiard, S., … Qi, Y. (2012). A Role for Small RNAs in DNA Double-Strand Break Repair. Cell, 149(1), 101-112. doi:10.1016/j.cell.2012.03.002Zhang, X., Zhao, H., Gao, S., Wang, W.-C., Katiyar-Agarwal, S., Huang, H.-D., … Jin, H. (2011). Arabidopsis Argonaute 2 Regulates Innate Immunity via miRNA393∗-Mediated Silencing of a Golgi-Localized SNARE Gene, MEMB12. Molecular Cell, 42(3), 356-366. doi:10.1016/j.molcel.2011.04.010Zhu, H., Hu, F., Wang, R., Zhou, X., Sze, S.-H., Liou, L. W., … Zhang, X. (2011). Arabidopsis Argonaute10 Specifically Sequesters miR166/165 to Regulate Shoot Apical Meristem Development. Cell, 145(2), 242-256. doi:10.1016/j.cell.2011.03.024Mallory, A. C., Hinze, A., Tucker, M. R., Bouché, N., Gasciolli, V., Elmayan, T., … Laux, T. (2009). Redundant and Specific Roles of the ARGONAUTE Proteins AGO1 and ZLL in Development and Small RNA-Directed Gene Silencing. PLoS Genetics, 5(9), e1000646. doi:10.1371/journal.pgen.1000646Kasschau, K. D., Cronin, S., & Carrington, J. C. (1997). Genome Amplification and Long-Distance Movement Functions Associated with the Central Domain of Tobacco Etch Potyvirus Helper Component–Proteinase. Virology, 228(2), 251-262. doi:10.1006/viro.1996.8368Lakatos, L., Csorba, T., Pantaleo, V., Chapman, E. J., Carrington, J. C., Liu, Y.-P., … Burgyán, J. (2006). Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors. The EMBO Journal, 25(12), 2768-2780. doi:10.1038/sj.emboj.7601164Mallory, A. C., Reinhart, B. J., Bartel, D., Vance, V. B., & Bowman, L. H. (2002). A viral suppressor of RNA silencing differentially regulates the accumulation of short interfering RNAs and micro-RNAs in tobacco. Proceedings of the National Academy of Sciences, 99(23), 15228-15233. doi:10.1073/pnas.232434999Chapman, E. J. (2004). Viral RNA silencing suppressors inhibit the microRNA pathway at an intermediate step. Genes & Development, 18(10), 1179-1186. doi:10.1101/gad.1201204Kasschau, K. D., Xie, Z., Allen, E., Llave, C., Chapman, E. J., Krizan, K. A., & Carrington, J. C. (2003). P1/HC-Pro, a Viral Suppressor of RNA Silencing, Interferes with Arabidopsis Development and miRNA Function. Developmental Cell, 4(2), 205-217. doi:10.1016/s1534-5807(03)00025-xSchott, G., Mari-Ordonez, A., Himber, C., Alioua, A., Voinnet, O., & Dunoyer, P. (2012). Differential effects of viral silencing suppressors on siRNA and miRNA loading support the existence of two distinct cellular pools of ARGONAUTE1. The EMBO Journal, 31(11), 2553-2565. doi:10.1038/emboj.2012.92Shiboleth, Y. M., Haronsky, E., Leibman, D., Arazi, T., Wassenegger, M., Whitham, S. A., … Gal-On, A. (2007). The Conserved FRNK Box in HC-Pro, a Plant Viral Suppressor of Gene Silencing, Is Required for Small RNA Binding and Mediates Symptom Development. Journal of Virology, 81(23), 13135-13148. doi:10.1128/jvi.01031-07Endres, M. W., Gregory, B. D., Gao, Z., Foreman, A. W., Mlotshwa, S., Ge, X., … Vance, V. (2010). Two Plant Viral Suppressors of Silencing Require the Ethylene-Inducible Host Transcription Factor RAV2 to Block RNA Silencing. PLoS Pathogens, 6(1), e1000729. doi:10.1371/journal.ppat.1000729Ala-Poikela, M., Goytia, E., Haikonen, T., Rajamäki, M.-L., & Valkonen, J. P. T. (2011). Helper Component Proteinase of the Genus Potyvirus Is an Interaction Partner of Translation Initiation Factors eIF(iso)4E and eIF4E and Contains a 4E Binding Motif. 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HC-Pro silencing suppressor significantly alters the gene expression profile in tobacco leaves and flowers. BMC Plant Biology, 11(1), 68. doi:10.1186/1471-2229-11-68Lellis, A. D., Kasschau, K. D., Whitham, S. A., & Carrington, J. C. (2002). Loss-of-Susceptibility Mutants of Arabidopsis thaliana Reveal an Essential Role for eIF(iso)4E during Potyvirus Infection. Current Biology, 12(12), 1046-1051. doi:10.1016/s0960-9822(02)00898-9Montgomery, T. A., Howell, M. D., Cuperus, J. T., Li, D., Hansen, J. E., Alexander, A. L., … Carrington, J. C. (2008). Specificity of ARGONAUTE7-miR390 Interaction and Dual Functionality in TAS3 Trans-Acting siRNA Formation. Cell, 133(1), 128-141. doi:10.1016/j.cell.2008.02.033Mi, S., Cai, T., Hu, Y., Chen, Y., Hodges, E., Ni, F., … Qi, Y. (2008). Sorting of Small RNAs into Arabidopsis Argonaute Complexes Is Directed by the 5′ Terminal Nucleotide. 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