732 results on '"Nixon, B."'
Search Results
2. PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma
- Author
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Duchatel, RJ, Jackson, ER, Parackal, SG, Kiltschewskij, D, Findlay, IJ, Mannan, A, Staudt, DE, Thomas, BC, Germon, ZP, Laternser, S, Kearney, PS, Jamaluddin, MFB, Douglas, AM, Beitaki, T, McEwen, HP, Persson, ML, Hocke, EA, Jain, V, Aksu, M, Manning, EE, Murray, HC, Verrills, NM, Sun, CX, Daniel, P, Vilain, RE, Skerrett-Byrne, DA, Nixon, B, Hua, S, de Bock, CE ; https://orcid.org/0000-0001-5182-8535, Colino-Sanguino, Y, Valdes-Mora, F, Tsoli, M ; https://orcid.org/0000-0003-1155-0510, Ziegler, DS ; https://orcid.org/0000-0001-7451-7916, Cairns, MJ, Raabe, EH, Vitanza, NA, Hulleman, E, Phoenix, TN, Koschmann, C, Alvaro, F, Dayas, CV, Tinkle, CL, Wheeler, H, Whittle, JR, Eisenstat, DD, Firestein, R, Mueller, S, Valvi, S, Hansford, JR, Ashley, DM, Gregory, SG, Kilburn, LB, Nazarian, J, Cain, JE, Dun, MD, Valdes Mora, Fatima ; https://orcid.org/0000-0001-7490-0114, Duchatel, RJ, Jackson, ER, Parackal, SG, Kiltschewskij, D, Findlay, IJ, Mannan, A, Staudt, DE, Thomas, BC, Germon, ZP, Laternser, S, Kearney, PS, Jamaluddin, MFB, Douglas, AM, Beitaki, T, McEwen, HP, Persson, ML, Hocke, EA, Jain, V, Aksu, M, Manning, EE, Murray, HC, Verrills, NM, Sun, CX, Daniel, P, Vilain, RE, Skerrett-Byrne, DA, Nixon, B, Hua, S, de Bock, CE ; https://orcid.org/0000-0001-5182-8535, Colino-Sanguino, Y, Valdes-Mora, F, Tsoli, M ; https://orcid.org/0000-0003-1155-0510, Ziegler, DS ; https://orcid.org/0000-0001-7451-7916, Cairns, MJ, Raabe, EH, Vitanza, NA, Hulleman, E, Phoenix, TN, Koschmann, C, Alvaro, F, Dayas, CV, Tinkle, CL, Wheeler, H, Whittle, JR, Eisenstat, DD, Firestein, R, Mueller, S, Valvi, S, Hansford, JR, Ashley, DM, Gregory, SG, Kilburn, LB, Nazarian, J, Cain, JE, Dun, MD, and Valdes Mora, Fatima ; https://orcid.org/0000-0001-7490-0114 more...
- Abstract
Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy. more...
- Published
- 2024
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3. Building an Understanding of Proteostasis in Reproductive Cells: The Impact of Reactive Carbonyl Species on Protein Fate
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Smyth, SP, Nixon, B, Skerrett-Byrne, DA, Burke, ND, Bromfield, EG, Smyth, SP, Nixon, B, Skerrett-Byrne, DA, Burke, ND, and Bromfield, EG
- Abstract
Significance: Stringent regulation of protein homeostasis pathways, under both physiological and pathological conditions, is necessary for the maintenance of proteome fidelity and optimal cell functioning. However, when challenged by endogenous or exogenous stressors, these proteostasis pathways can become dysregulated with detrimental consequences for protein fate, cell survival, and overall organism health. Most notably, there are numerous somatic pathologies associated with a loss of proteostatic regulation, including neurodegenerative disorders, type 2 diabetes, and some cancers. Recent Advances: Lipid oxidation-derived reactive carbonyl species (RCS), such as 4-hydroxynonenal (4HNE) and malondialdehyde, are relatively underappreciated purveyors of proteostatic dysregulation, which elicit their effects via the nonenzymatic post-translational modification of proteins. Emerging evidence suggests that a subset of germline proteins can serve as substrates for 4HNE modification. Among these, prevalent targets include succinate dehydrogenase, heat shock protein A2 and A-kinase anchor protein 4, all of which are intrinsically associated with fertility. Critical Issues: Despite growing knowledge in this field, the RCS adductomes of spermatozoa and oocytes are yet to be comprehensively investigated. Furthermore, the manner by which RCS-mediated adduction impacts protein fate and drives cellular responses, such as protein aggregation, requires further examination in the germline. Given that RCS-protein adduction has been attributed a role in infertility, there has been sparked research investment into strategies to prevent lipid peroxidation in germ cells. Future Directions: An increased depth of knowledge regarding the mechanisms and substrates of RCS-mediated protein modification in reproductive cells may reveal important targets for the development of novel therapies to improve fertility and pregnancy outcomes for future generations. more...
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- 2024
4. Understanding the Structural Ballet of Cellulose Formation – Using CryoEM to Reveal the Role of Protein Flexibility on Higher-order Oligomer Formation, Glucan Catalysis, and Cellulose Microfibril Extrusion.
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Massenburg, Lynnicia, O'Neill, Hugh, Nixon, B Tracy, and Williams, Alexis N
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- 2024
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5. Prolonged Chilled Preservation and Preliminary Investigations of Energy Production of Koala (Phascolarctos cinereus) Spermatozoa
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Schultz, B., primary, Hulse, L., additional, Nicolson, V., additional, Larkin, R., additional, Bromfield, E., additional, Nixon, B., additional, and Johnston, S., additional
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- 2021
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6. Synthesis and Self-Assembly of Cellulose Microfibrils from Reconstituted Cellulose Synthase
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Cho, Sung Hyun, Purushotham, Pallinti, Fang, Chao, Maranas, Cassandra, Díaz-Moreno, Sara M., Bulone, Vincent, Zimmer, Jochen, Kumar, Manish, and Nixon, B. Tracy
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- 2017
7. Science and Science‐Enabling Activities of the SHERLOC and WATSON Imaging Systems in Jezero Crater, Mars
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Wogsland, B. V., primary, Minitti, M. E., additional, Kah, L. C., additional, Yingst, R. A., additional, Abbey, W., additional, Bhartia, R., additional, Beegle, L., additional, Bleefeld, B. L., additional, Cardarelli, E. L., additional, Conrad, P. G., additional, Edgett, K., additional, Hickman‐Lewis, K., additional, Hugget, J., additional, Imbeah, S., additional, Kennedy, M. R., additional, Lee, C., additional, Nixon, B. E., additional, Núñez, J. I., additional, Pascuzzo, A., additional, Robinson, M., additional, Sanchez‐Vahamonde, C. Rodriguez, additional, Scheller, E., additional, Sharma, S., additional, Siljeström, S., additional, Steadman, K., additional, Winchell, K., additional, and Ravine, Michael A., additional more...
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- 2023
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8. Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety
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Fennell, K. A., Busby, R. G. G., Li, S., Bodden, C., Stanger, S. J., Nixon, B., Short, A. K., Hannan, A. J., and Pang, T. Y.
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- 2020
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9. Non-coding RNA in Spermatogenesis and Epididymal Maturation
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Holt, J. E., Stanger, S. J., Nixon, B., McLaughlin, E. A., COHEN, IRUN, Series editor, Lajtha, Abel, Series editor, Lambris, John, Series editor, Paoletti, Rodolfo, Series editor, Wilhelm, Dagmar, editor, and Bernard, Pascal, editor more...
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- 2016
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10. Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology
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Aitken, R.J., Muscio, L., Whiting, S., Connaughton, H.S., Fraser, B.A., Nixon, B., Smith, N.D., and De Iuliis, G.N.
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- 2016
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11. A single heterologously expressed plant cellulose synthase isoform is sufficient for cellulose microfibril formation in vitro
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Purushotham, Pallinti, Cho, Sung Hyun, Díaz-Moreno, Sara M., Kumar, Manish, Nixon, B. Tracy, Bulone, Vincent, and Zimmer, Jochen
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- 2016
12. Blockade of ROS production inhibits oncogenic signaling in acute myeloid leukemia and amplifies response to precision therapies.
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Germon, ZP, Sillar, JR, Mannan, A, Duchatel, RJ, Staudt, D, Murray, HC, Findlay, IJ, Jackson, ER, McEwen, HP, Douglas, AM, McLachlan, T, Schjenken, JE, Skerrett-Byrne, DA, Huang, H, Melo-Braga, MN, Plank, MW, Alvaro, F, Chamberlain, J, De Iuliis, G, Aitken, RJ, Nixon, B, Wei, AH, Enjeti, AK, Huang, Y, Lock, RB, Larsen, MR, Lee, H, Vaghjiani, V, Cain, JE, de Bock, CE, Verrills, NM, Dun, MD, Germon, ZP, Sillar, JR, Mannan, A, Duchatel, RJ, Staudt, D, Murray, HC, Findlay, IJ, Jackson, ER, McEwen, HP, Douglas, AM, McLachlan, T, Schjenken, JE, Skerrett-Byrne, DA, Huang, H, Melo-Braga, MN, Plank, MW, Alvaro, F, Chamberlain, J, De Iuliis, G, Aitken, RJ, Nixon, B, Wei, AH, Enjeti, AK, Huang, Y, Lock, RB, Larsen, MR, Lee, H, Vaghjiani, V, Cain, JE, de Bock, CE, Verrills, NM, and Dun, MD more...
- Abstract
Mutations in the type III receptor tyrosine kinase FLT3 are frequent in patients with acute myeloid leukemia (AML) and are associated with a poor prognosis. AML is characterized by the overproduction of reactive oxygen species (ROS), which can induce cysteine oxidation in redox-sensitive signaling proteins. Here, we sought to characterize the specific pathways affected by ROS in AML by assessing oncogenic signaling in primary AML samples. The oxidation or phosphorylation of signaling proteins that mediate growth and proliferation was increased in samples from patient subtypes with FLT3 mutations. These samples also showed increases in the oxidation of proteins in the ROS-producing Rac/NADPH oxidase-2 (NOX2) complex. Inhibition of NOX2 increased the apoptosis of FLT3-mutant AML cells in response to FLT3 inhibitors. NOX2 inhibition also reduced the phosphorylation and cysteine oxidation of FLT3 in patient-derived xenograft mouse models, suggesting that decreased oxidative stress reduces the oncogenic signaling of FLT3. In mice grafted with FLT3 mutant AML cells, treatment with a NOX2 inhibitor reduced the number of circulating cancer cells, and combining FLT3 and NOX2 inhibitors increased survival to a greater extent than either treatment alone. Together, these data raise the possibility that combining NOX2 and FLT3 inhibitors could improve the treatment of FLT3 mutant AML. more...
- Published
- 2023
13. Linking physico‐chemical parameters and macroinvertebrates for water quality assessment of Kakamega and the East Usambara montane ecosystems in Kenya.
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Ndungu, Joseph G., Marubu, Rose M., Ochola, John B., Onyimbo, Nixon B., Sevgan, Subramanian, Muriuki, Caroline W., Komu, Kalist E., and Gikungu, Mary W.
- Abstract
Copyright of African Journal of Ecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2024
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14. Advancing Rhodobacter sphaeroides as a platform for expression of functional membrane proteins
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Erbakan, Mustafa, Curtis, Brandon S., Nixon, B. Tracy, Kumar, Manish, and Curtis, Wayne R.
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- 2015
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15. A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers
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Vandavasi, Venu Gopal, Putnam, Daniel K., Zhang, Qiu, Petridis, Loukas, Heller, William T., Nixon, B. Tracy, Haigler, Candace H., Kalluri, Udaya, Coates, Leighton, Langan, Paul, Smith, Jeremy C., Meiler, Jens, and O'Neill, Hugh more...
- Published
- 2016
16. A general mechanism for transcription bubble nucleation in bacteria
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Mueller, Andreas U., primary, Chen, James, additional, Wu, Mengyu, additional, Chiu, Courtney, additional, Nixon, B. Tracy, additional, Campbell, Elizabeth A., additional, and Darst, Seth A., additional more...
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- 2023
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17. Abstract 1208: Structure determination of moss PpCesA5 cellulose synthase trimer
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Massenburg, Lynnicia, primary, Nixon, B. Tracy, additional, and O'Neill, Hugh, additional
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- 2023
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18. 74MO HERIZON overall survival results: A study of IMU-131, a HER2 targeting peptide vaccine, plus standard of care chemotherapy in patients with HER2 overexpressing metastatic or advanced gastric/GEJ cancer
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Maglakelidze, M., primary, Ryspayeva, D., additional, Andric, Z.G., additional, Petrovic, Z., additional, Bulat, I.V., additional, Nikolic, I.V., additional, Chawla, T., additional, Nagarkar, R., additional, Wiedermann, U., additional, Blumenstein, B.A., additional, Chong, L.M.O., additional, Ede, N.J., additional, Nixon, B., additional, and Good, A.J., additional more...
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- 2022
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19. Opening and Closing of the Bacterial RNA Polymerase Clamp
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Chakraborty, Anirban, Wang, Dongye, Ebright, Yon W., Korlann, You, Kortkhonjia, Ekaterine, Kim, Taiho, Chowdhury, Saikat, Wigneshweraraj, Sivaramesh, Irschik, Herbert, Jansen, Rolf, Nixon, B. Tracy, Knight, Jennifer, Weiss, Shimon, and Ebright, Richard H. more...
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- 2012
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20. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress
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Sobinoff, A.P., Pye, V., Nixon, B., Roman, S.D., and McLaughlin, E.A.
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- 2012
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21. P1.15-08 Phase 1: IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy as Monotherapy or in Combination with Atezolizumab, in Adults with Non-Small Cell Lung Cancer
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Richardson, G.E., primary, Park, J.J., additional, Boyer, M.J., additional, Gutierrez, M., additional, Carbone, D.P., additional, Savvides, P., additional, Kaumaya, P., additional, Bekaii-Saab, T.S., additional, Phan, T.G., additional, Chong, L.M.O., additional, Cha, S., additional, Ede, N., additional, Nixon, B., additional, Withana, N.P., additional, and Good, A.J., additional more...
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- 2022
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22. Evidence for Plant-Conserved Region Mediated Trimeric CESAs in Plant Cellulose Synthase Complexes
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Du, Juan, primary, Vandavasi, Venu Gopal, additional, Molloy, Kelly R., additional, Yang, Hui, additional, Massenburg, Lynnicia N., additional, Singh, Abhishek, additional, Kwansa, Albert L., additional, Yingling, Yaroslava G., additional, O’Neill, Hugh, additional, Chait, Brian T., additional, Kumar, Manish, additional, and Nixon, B. Tracy, additional more...
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- 2022
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23. 1421P Final results of the phase II trial of HER-Vaxx, a B-cell peptide-based vaccine plus standard care of chemotherapy in patients with HER2-overexpressing advanced gastric cancer - (HERIZON)
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Tobias, J., Kundi, M., Garner-Spitzer, E., Zielinski, C.C., Maglakelidze, M., Andric, Z.G., Petrovic, Z., Nikolic, I.V., Ryspayeva, D., Bulat, I.V., Nagarkar, R., Chawla, T., Chong, L.O., Nixon, B., Yavrom, S., Ede, N.J., and Wiedermann, U. more...
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- 2024
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24. Assessment of the Emerging Threat Posed by Perfluoroalkyl and Polyfluoroalkyl Substances to Male Reproduction in Humans
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Calvert, L, Green, MP, De Iuliis, GN, Dun, MD, Turner, BD, Clarke, BO, Eamens, AL, Roman, SD, Nixon, B, Calvert, L, Green, MP, De Iuliis, GN, Dun, MD, Turner, BD, Clarke, BO, Eamens, AL, Roman, SD, and Nixon, B more...
- Abstract
Per-fluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of synthetic fluorinated chemicals used widely in industry and consumer products. Due to their extensive use and chemical stability, PFAS are ubiquitous environmental contaminants and as such, form an emerging risk factor for male reproductive health. The long half-lives of PFAS is of particular concern as the propensity to accumulate in biological systems prolong the time taken for excretion, taking years in many cases. Accordingly, there is mounting evidence supporting a negative association between PFAS exposure and an array of human health conditions. However, inconsistencies among epidemiological and experimental findings have hindered the ability to definitively link negative reproductive outcomes to specific PFAS exposure. This situation highlights the requirement for further investigation and the identification of reliable biological models that can inform health risks, allowing sensitive assessment of the spectrum of effects of PFAS exposure on humans. Here, we review the literature on the biological effects of PFAS exposure, with a specific focus on male reproduction, owing to its utility as a sentinel marker of general health. Indeed, male infertility has increasingly been shown to serve as an early indicator of a range of co-morbidities such as coronary, inflammatory, and metabolic diseases. It follows that adverse associations have been established between PFAS exposure and the incidence of testicular dysfunction, including pathologies such as testicular cancer and a reduction in semen quality. We also give consideration to the mechanisms that render the male reproductive tract vulnerable to PFAS mediated damage, and discuss novel remediation strategies to mitigate the negative impact of PFAS contamination and/or to ameliorate the PFAS load of exposed individuals. more...
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- 2022
25. Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos
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Denbeigh, J. M., Nixon, B. A., Lee, J. J. Y., Jerkic, M., Marsden, P. A., Letarte, M., Puri, M. C., and Foster, F. S.
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- 2015
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26. Non-coding RNA in Spermatogenesis and Epididymal Maturation
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Holt, J. E., primary, Stanger, S. J., additional, Nixon, B., additional, and McLaughlin, E. A., additional
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- 2015
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27. Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 AAA+ ATPase for Remodeling Bacterial RNA Polymerase
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Chen, Baoyu, Sysoeva, Tatyana A., Chowdhury, Saikat, Guo, Liang, De Carlo, Sacha, Hanson, Jeffrey A., Yang, Haw, and Nixon, B. Tracy
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- 2010
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28. Structure of In Vitro-Synthesized Cellulose Fibrils Viewed by Cryo-Electron Tomography and 13C Natural-Abundance Dynamic Nuclear Polarization Solid-State NMR
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Deligey, Fabien, primary, Frank, Mark A., additional, Cho, Sung Hyun, additional, Kirui, Alex, additional, Mentink-Vigier, Frederic, additional, Swulius, Matthew T., additional, Nixon, B. Tracy, additional, and Wang, Tuo, additional more...
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- 2022
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29. Decreased dose of radiation to dogs during acquisition of elbow radiographs using draped shielding
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Nemanic, S., Nixon, B. K., Francis, R. A., Farmer, R. H., Harlan, D. L., and Baltzer, W. I.
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- 2015
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30. Coupling σ Factor Conformation to RNA Polymerase Reorganisation for DNA Melting
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Burrows, Patricia C., Joly, Nicolas, Cannon, Wendy V., Cámara, Beatriz P., Rappas, Mathieu, Zhang, Xiaodong, Dawes, Kathleen, Nixon, B. Tracy, Wigneshweraraj, Siva R., and Buck, Martin
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- 2009
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31. Two-Component Regulatory Systems Responsive to Environmental Stimuli Share Strongly Conserved Domains with the Nitrogen Assimilation Regulatory Genes ntrB and ntrC
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Nixon, B. Tracy, Ronson, Clive W., and Ausubel, Frederick M.
- Published
- 1986
32. Growth Hormone Promotes the Differentiation of Myoblasts and Preadipocytes Generated by Azacytidine Treatment of 10T 1/2 Cells
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Nixon, B. Tracy and Green, Howard
- Published
- 1984
33. Induction of Single-Strand DNA Breaks in Human Cells by H2 O2 Formed in Near-uv (Black Light)-Irradiated Medium
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Wang, R. J., Ananthaswamy, H. N., Nixon, B. T., Hartman, P. S., and Eisenstark, A.
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- 1980
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34. Identification of Hydrogen Peroxide as a Photoproduct Toxic to Human Cells in Tissue-Culture Medium Irradiated with "Daylight" Fluorescent Light
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Wang, Richard J. and Nixon, B. Tracy
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- 1978
35. Time-resolved proteomic profiling of cigarette smoke-induced experimental chronic obstructive pulmonary disease
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Skerrett-Byrne, DA, Bromfield, EG, Murray, HC, Jamaluddin, MFB, Jarnicki, AG, Fricker, M, Essilfie, AT, Jones, B, Haw, TJ, Hampsey, D, Anderson, AL, Nixon, B, Scott, RJ, Wark, PAB, Dun, MD, and Hansbro, PM more...
- Subjects
Proteomics ,Disease Models, Animal ,Mice ,Pulmonary Disease, Chronic Obstructive ,Smoke ,Respiratory System ,Smoking ,Animals ,sense organs ,Lung ,11 Medical and Health Sciences - Abstract
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis. METHODS: We employed quantitative label-based proteomics to map the changes in the lung tissue proteome of cigarette smoke-induced experimental COPD that is induced over 8 weeks and progresses over 12 weeks. RESULTS: Quantification of 7324 proteins enabled the tracking of changes to the proteome. Alterations in protein expression profiles occurred in the induction phase, with 18 and 16 protein changes at 4- and 6-week time points, compared to age-matched controls, respectively. Strikingly, 269 proteins had altered expression after 8 weeks when the hallmark pathological features of human COPD emerge, but this dropped to 27 changes at 12 weeks with disease progression. Differentially expressed proteins were validated using other mouse and human COPD bronchial biopsy samples. Major changes in RNA biosynthesis (heterogeneous nuclear ribonucleoproteins C1/C2 [HNRNPC] and RNA-binding protein Musashi homologue 2 [MSI2]) and modulators of inflammatory responses (S100A1) were notable. Mitochondrial dysfunction and changes in oxidative stress proteins also occurred. CONCLUSION: We provide a detailed proteomic profile, identifying proteins associated with the pathogenesis and disease progression of COPD establishing a platform to develop effective new treatment strategies. more...
- Published
- 2021
36. Phase transitions in the assembly of multivalent signalling proteins
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Li, Pilong, Banjade, Sudeep, Cheng, Hui-Chun, Kim, Soyeon, Chen, Baoyu, Guo, Liang, Llaguno, Marc, Hollingsworth, Javoris V., King, David S., Banani, Salman F., Russo, Paul S., Jiang, Qiu-Xing, Nixon, B. Tracy, and Rosen, Michael K. more...
- Subjects
Physiological aspects ,Research ,Properties ,Phosphorylation -- Physiological aspects ,Wiskott-Aldrich syndrome ,Protein research ,Phase transitions (Physics) -- Research ,Macromolecules -- Properties ,Phosphotransferases -- Properties ,Phase transformations (Statistical physics) -- Research - Abstract
Covalent and non-covalent interactions between multivalent small molecules are central elements of classical polymer chemistry and physics and of supramolecular chemistry (2-4). These fields have produced theories and experimental demonstrations [...], Cells are organized on length scales ranging from angstrom to micrometres. However, the mechanisms by which angstrom-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin (1), the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology. more...
- Published
- 2012
37. Effects of 4-nonylphenol and 17α-ethynylestradiol exposure in the Sydney rock oyster, Saccostrea glomerata: Vitellogenin induction and gonadal development
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Andrew, M.N., Dunstan, R.H., O’Connor, W.A., Van Zwieten, L., Nixon, B., and MacFarlane, G.R.
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- 2008
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38. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities
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Bennetts, L.E., De Iuliis, G.N., Nixon, B., Kime, M., Zelski, K., McVicar, C.M., Lewis, S.E., and Aitken, R.J.
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- 2008
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39. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, H, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K, Boehme, K, Brenneisen, P, Brown, J, Dalrymple, B, Harvey, D, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, M, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, O, Kauppila, J, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, 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M., Jean-Quartier C., Jeon S. -M., Jia Y., Jutzeler C., Kalatzis P., Karim M., Karsay K., Keitel A., Kempe A., Keown J. R., Khoo C. M., Khwaja N., Kievit R. A., Kosanic S., Koutoukidis D. A., Kramer P., Kumar D., Kirag N., Lanza G., Le T. D., Leem J. W., Leightley D., Leite A., Lercher L., Li Y., Lim R., Lima L. R. A., Lin L., Ling T., Liu Y., Liu Z., Lu Y., Lum F. M., Luo H., Machhi J., Macleod A., Macwan I., Madala H. R., Madani N., de Maio N., Makowiecki K., Mallinson D. J., Margelyte R., Maria C., Markonis Y., Marsili L., Mavoa S., McWilliams L., Megersa M., Souto-Maior C., Menichetti J., Mercieca-Bebber R., Miller J. J., Minde D. -P. M., Minges A., Mishra E., Mishra V. R., Moores C., Morrice N., Moskalensky A. E., Navarin N., Negera E., Nolet P., Nordberg A., Norden R., Nowicki J. P., Olova N., Olszewski P., Onzima R., Pan C. -L., Park C., Park D. I., Park S., Patil C. D., Pedro S. A., Perry S. R., Peter J., Peterson B. M., Pezzuolo A., Pozdnyakov I., Qian S., Qin L., Rafe A., Raote I., Raza A., Rebl H., Refai O., Regan T., Richa T., Richardson M. F., Robinson K. R., Rossoni L., Rouet R., Safaei S., Schneeberger P. H. H., Schwotzer D., Sebastian A., Selinski J., Seltmann S., Sha F., Shalev N., Shang J. -L., Singer J., Singh M., Smith T., Solomon-Moore E., Song L., Soraggi S., Stanley R., Steckhan N., Strobl F., Subissi L., Supriyanto I., Surve C. R., Suzuki T., Syme C., Sorelius K., Tang Y., Tantawy M., Tennakoon S., Teseo S., Toelzer C., Tomov N., Tovar M., Tran L., Tripathi S., Tuladhar A. M., Ukubuiwe A. C., Ung C. O. L., Valgepea K., Vatanparast H., Vidal A., Wang Q., Watari R., Webster R., Wei J., Wibowo D., Wingenbach T. S. H., Xavier R. M., Xiao S., Xiong P., Xu S., Yao R., Yao W., Yin Q., Zaitsu M., Zeineb Z., Zhan X. -Y., Zhang R., Zhang W., Zheng S., Zhou B., Ahmad H., Akinwumi S. A., Albery G. F., Alhowimel A., Ali J., Alshehri M., Alsuhaibani M., Anikin A., Azubuike S. O., Bach-Mortensen A., Baltiansky L., Bartas M., Belachew K. Y., Bhardwaj V., Binder K., Bland N. S., Boah M., Bullen B., Calabro G. E., Callahan T. J., Cao B., Chalmers K., Chang W., Che Z., Chen A. T. Y., Chen Z., Choi Y., Chowdhury M. A. K., Christensen M. R., Cooke R. S. C., Cottini M., Covington N. V., Cunningham C., Delarocque J., Devos L., Dhar A. R., Ding K. -F., Dong K., Dong Z., Dreyer N., Ekstrand C., Fardet T., Feleke B. E., Feurer T., Freitas A., Gao T., Giganti F., Grabowski P., Guerra-Mora J. R., Guo C., Guo X., Gupta H., He S., Heijne M., Heinemann S., Hogrebe A., Huang Z., Iskander-Rizk S., Iyer L. M., Jahan Y., James A. S., Joel E., Joffroy B., Jegousse C., Kambondo G., Karnati P., Kaya C., Ke A., Kelly D., Kickert R., Kidibule P. E., Kieselmann J. P., Kim H. J., Kitazawa T., Lamberts A., Liang H., Linn S. N., Litfin T., Liusuo W., Lygirou V., Mahato A. K., Mai Z. -M., Major R. W., Mali S., Mallis P., Mao W., Marvin-Dowle K., Mason L. D., Merideth B., Merino-Plaza M. 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- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. more...
- Published
- 2019
40. 1367TiP IMPRINTER: An open label, multi-center, dose escalation/expansion, phase I study of IMU-201 (PD1-Vaxx), a B-cell immunotherapy, in adults with non-small cell lung cancer
- Author
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Laeufle, R., primary, Richardson, G., additional, Park, J.J.W., additional, Gutierrez, M., additional, Boyer, M., additional, Carbone, D., additional, Savvides, P., additional, Bekaii-Saab, T., additional, Kaumaya, P., additional, Phan, T., additional, Ede, N., additional, Chong, L., additional, Nixon, B., additional, and Good, A., additional more...
- Published
- 2021
- Full Text
- View/download PDF
41. P-159 HERIZON: Phase 2 part of the IMU-131 HER2/neu vaccine plus chemotherapy study randomized in patients with HER2/NEU overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction
- Author
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Maglakelidze, M., primary, Ryspayenva, D., additional, Bulat, I., additional, Andric, Z., additional, Nikolic, I., additional, Chawla, T., additional, Choudhary, V., additional, Venkata, G., additional, Radosavljevic, D., additional, Petrovic, Z., additional, Wiedermann, U., additional, Chong, L., additional, Laeufle, R., additional, Ede, N., additional, Nixon, B., additional, and Good, A., additional more...
- Published
- 2021
- Full Text
- View/download PDF
42. New insights into the molecular mechanisms of sperm-egg interaction
- Author
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Nixon, B., Aitken, R. J., and McLaughlin, E. A.
- Published
- 2007
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43. 1536P HERIZON: A phase II study of HER-Vaxx (IMU-131), a HER2-targeting peptide vaccine plus standard of care chemotherapy in patients with HER2+ advanced stomach cancer - Dose-dependent anti-cancer antibodies correlating with improved clinical outcome
- Author
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Tobias, J., Kundi, M., Garner-Spitzer, E., Zielinski, C., Maglakelidze, M., Andric, Z.G., Petrovic, Z., Nagarkar, R., Chawla, T., Chong, L.O., Nixon, B., Yavrom, S., Ede, N., and Wiedermann, U.
- Published
- 2023
- Full Text
- View/download PDF
44. Assessment of the Emerging Threat Posed by Perfluoroalkyl and Polyfluoroalkyl Substances to Male Reproduction in Humans.
- Author
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Calvert, L, Green, MP, De Iuliis, GN, Dun, MD, Turner, BD, Clarke, BO, Eamens, AL, Roman, SD, Nixon, B, Calvert, L, Green, MP, De Iuliis, GN, Dun, MD, Turner, BD, Clarke, BO, Eamens, AL, Roman, SD, and Nixon, B more...
- Abstract
Per-fluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of synthetic fluorinated chemicals used widely in industry and consumer products. Due to their extensive use and chemical stability, PFAS are ubiquitous environmental contaminants and as such, form an emerging risk factor for male reproductive health. The long half-lives of PFAS is of particular concern as the propensity to accumulate in biological systems prolong the time taken for excretion, taking years in many cases. Accordingly, there is mounting evidence supporting a negative association between PFAS exposure and an array of human health conditions. However, inconsistencies among epidemiological and experimental findings have hindered the ability to definitively link negative reproductive outcomes to specific PFAS exposure. This situation highlights the requirement for further investigation and the identification of reliable biological models that can inform health risks, allowing sensitive assessment of the spectrum of effects of PFAS exposure on humans. Here, we review the literature on the biological effects of PFAS exposure, with a specific focus on male reproduction, owing to its utility as a sentinel marker of general health. Indeed, male infertility has increasingly been shown to serve as an early indicator of a range of co-morbidities such as coronary, inflammatory, and metabolic diseases. It follows that adverse associations have been established between PFAS exposure and the incidence of testicular dysfunction, including pathologies such as testicular cancer and a reduction in semen quality. We also give consideration to the mechanisms that render the male reproductive tract vulnerable to PFAS mediated damage, and discuss novel remediation strategies to mitigate the negative impact of PFAS contamination and/or to ameliorate the PFAS load of exposed individuals. more...
- Published
- 2021
45. Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia
- Author
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Murray, HC, Enjeti, AK, Kahl, RGS, Flanagan, HM, Sillar, J, Skerrett-Byrne, DA, Al Mazi, JG, Au, GG, de Bock, CE ; https://orcid.org/0000-0001-5182-8535, Evans, K, Smith, ND, Anderson, A, Nixon, B, Lock, RB ; https://orcid.org/0000-0002-3436-9071, Larsen, MR, Verrills, NM, Dun, MD, Murray, HC, Enjeti, AK, Kahl, RGS, Flanagan, HM, Sillar, J, Skerrett-Byrne, DA, Al Mazi, JG, Au, GG, de Bock, CE ; https://orcid.org/0000-0001-5182-8535, Evans, K, Smith, ND, Anderson, A, Nixon, B, Lock, RB ; https://orcid.org/0000-0002-3436-9071, Larsen, MR, Verrills, NM, and Dun, MD more...
- Published
- 2021
46. Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development
- Author
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Trigg, NA, Skerrett-Byrne, DA, Xavier, MJ, Zhou, W, Anderson, AL, Stanger, SJ, Katen, AL, De Iuliis, GN, Dun, MD, Roman, SD, Eamens, AL, Nixon, B, Trigg, NA, Skerrett-Byrne, DA, Xavier, MJ, Zhou, W, Anderson, AL, Stanger, SJ, Katen, AL, De Iuliis, GN, Dun, MD, Roman, SD, Eamens, AL, and Nixon, B more...
- Abstract
Paternal exposure to environmental stressors elicits distinct changes to the sperm sncRNA profile, modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the reproductive toxicant acrylamide. Furthermore, we trace the differential accumulation of acrylamide-responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure alters the abundance of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identify extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa and dysregulated gene expression during early embryonic development following fertilization by acrylamide-exposed spermatozoa. These data provide mechanistic links to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos. more...
- Published
- 2021
47. A novel role for milk fat globule-EGF factor 8 protein (MFGE8) in the mediation of mouse sperm-extracellular vesicle interactions
- Author
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Trigg, NA, Stanger, SJ, Zhou, W, Skerrett-Byrne, DA, Sipila, P, Dun, MD, Eamens, AL, De Iuliis, GN, Bromfield, EG, Roman, SD, Nixon, B, Trigg, NA, Stanger, SJ, Zhou, W, Skerrett-Byrne, DA, Sipila, P, Dun, MD, Eamens, AL, De Iuliis, GN, Bromfield, EG, Roman, SD, and Nixon, B more...
- Abstract
Spermatozoa transition to functional maturity as they are conveyed through the epididymis, a highly specialized region of the male excurrent duct system. Owing to their transcriptionally and translationally inert state, this transformation into fertilization competent cells is driven by complex mechanisms of intercellular communication with the secretory epithelium that delineates the epididymal tubule. Chief among these mechanisms are the release of extracellular vesicles (EV), which have been implicated in the exchange of varied macromolecular cargo with spermatozoa. Here, we describe the optimization of a tractable cell culture model to study the mechanistic basis of sperm-extracellular vesicle interactions. In tandem with receptor inhibition strategies, our data demonstrate the importance of milk fat globule-EGF factor 8 (MFGE8) protein in mediating the efficient exchange of macromolecular EV cargo with mouse spermatozoa; with the MFGE8 integrin-binding Arg-Gly-Asp (RGD) tripeptide motif identified as being of particular importance. Specifically, complementary strategies involving MFGE8 RGD domain ablation, competitive RGD-peptide inhibition and antibody-masking of alpha V integrin receptors, all significantly inhibited the uptake and redistribution of EV-delivered proteins into immature mouse spermatozoa. These collective data implicate the MFGE8 ligand and its cognate integrin receptor in the mediation of the EV interactions that underpin sperm maturation. more...
- Published
- 2021
48. ATP Ground- and Transition States of Bacterial Enhancer Binding AAA+ ATPases Support Complex Formation with Their Target Protein, σ54
- Author
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Chen, Baoyu, Doucleff, Michaeleen, Wemmer, David E., De Carlo, Sacha, Huang, Hector H., Nogales, Eva, Hoover, Timothy R., Kondrashkina, Elena, Guo, Liang, and Nixon, B. Tracy
- Published
- 2007
- Full Text
- View/download PDF
49. Structural Basis of DNA Recognition by the Alternative Sigma-factor, σ54
- Author
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Doucleff, Michaeleen, Pelton, Jeffrey G., Lee, Peter S., Nixon, B. Tracy, and Wemmer, David E.
- Published
- 2007
- Full Text
- View/download PDF
50. The structural basis for regulated assembly and function of the transcriptional activator NtrC
- Author
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De Carlo, Sacha, Baoyu Chen, Hoover, Timothy R., Kondrashkina, Elena, Nogales, Eva, and Nixon, B. Tracy
- Subjects
Hydrolysis -- Research ,Genetic transcription -- Research ,Protein C -- Chemical properties ,DNA-ligand interactions -- Research ,Biological sciences - Abstract
X-ray solution scattering and electron microscopy structures of the activated, full-length nitrogen regulatory protein C (NtrC) is reported, showing a novel mechanism for regulation of AAA+ ATPase assembly via the juxtaposition of the receiver domains and ATPase ring. Accompanying the hydrolysis cycle that is required for transcriptional activation, major order-disorder changes in the GAFTGA loops involved in the sigma(super 54) binding as well as in the DNA-binding domains are observed. more...
- Published
- 2006
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