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1. Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case–control study

Author

Tait, Luke, primary, Staniaszek, Lydia E., additional, Galizia, Elizabeth, additional, Martin‐Lopez, David, additional, Walker, Matthew C., additional, Azeez, Al Anzari Abdul, additional, Meiklejohn, Kay, additional, Allen, David, additional, Price, Chris, additional, Georgiou, Sophie, additional, Bagary, Manny, additional, Khalsa, Sakh, additional, Manfredonia, Francesco, additional, Tittensor, Phil, additional, Lawthom, Charlotte, additional, Howes, Benjamin B., additional, Shankar, Rohit, additional, Terry, John R., additional, and Woldman, Wessel, additional

Published
2024
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2. Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

Author

Del Bene, Victor A, primary, Martin, Roy C., additional, Brinkerhoff, Sarah A., additional, Olson, Joseph W., additional, Nelson, Matthew J., additional, Marotta, Dario, additional, Gonzalez, Christopher L., additional, Mills, Kelly A., additional, Kamath, Vidyulata, additional, Cutter, Gary, additional, Hurt, Chris P., additional, Wade, Melissa, additional, Robinson, Frank G., additional, Bentley, J. Nicole, additional, Guthrie, Barton L., additional, Knight, Robert T., additional, and Walker, Harrison C., additional

Published
2024
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4. A high‐throughput analysis of high‐resolution X‐ray CT images of stems of olive and citrus plants resistant and susceptible to Xylella fastidiosa

Author

Walker, Nancy C., Ruiz, Siul A., Ferreira, Talita R., Coletta‐Filho, Helvecio D., Le Houx, James, McKay Fletcher, Daniel, White, Steven M., Roose, Tiina, Walker, Nancy C., Ruiz, Siul A., Ferreira, Talita R., Coletta‐Filho, Helvecio D., Le Houx, James, McKay Fletcher, Daniel, White, Steven M., and Roose, Tiina

Abstract

The bacterial plant pathogen Xylella fastidiosa causes disease in several globally important crops. However, some cultivars harbour reduced bacterial loads and express few symptoms. Evidence considering plant species in isolation suggests xylem structure influences cultivar susceptibility to X. fastidiosa. We test this theory more broadly by analysing high-resolution synchrotron X-ray computed tomography of healthy and infected plant vasculature from two taxonomic groups containing susceptible and resistant varieties: two citrus cultivars (sweet orange cv. Pera, tangor cv. Murcott) and two olive cultivars (Koroneiki, Leccino). Results found the susceptible plants had more vessels than resistant ones, which could promote within-host pathogen spread. However, features associated with resistance were not shared by citrus and olive. While xylem vessels in resistant citrus stems had comparable diameters to those in susceptible plants, resistant olives had narrower vessels that could limit biofilm spread. And while differences among olive cultivars were not detected, results suggest greater vascular connectivity in resistant compared to susceptible citrus plants. We hypothesize that this provides alternate flow paths for sustaining hydraulic functionality under infection. In summary, this work elucidates different physiological resistance mechanisms between two taxonomic groups, while supporting the existence of an intertaxonomical metric that could speed up the identification of candidate-resistant plants.

Published
2024

6. Exploring the dynamics of the 2022 mpox outbreak in Canada

Author

Milwid, Rachael M., primary, Li, Michael, additional, Fazil, Aamir, additional, Maheu‐Giroux, Mathieu, additional, Doyle, Carla M., additional, Xia, Yiqing, additional, Cox, Joseph, additional, Grace, Daniel, additional, Dvorakova, Milada, additional, Walker, Steven C., additional, Mishra, Sharmistha, additional, and Ogden, Nicholas H., additional

Published
2023
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14. The impact of xylem geometry on olive cultivar resistance to Xylella fastidiosa: an image‐based study

Author

Walker, Nancy C., White, Steven M., McKay Fletcher, Dan, Ruiz, Siul A., Rankin, Kathryn E., De Stradis, Angelo, Saponari, Maria, Williams, Katherine A., Petroselli, Chiara, Roose, Tiina, Walker, Nancy C., White, Steven M., McKay Fletcher, Dan, Ruiz, Siul A., Rankin, Kathryn E., De Stradis, Angelo, Saponari, Maria, Williams, Katherine A., Petroselli, Chiara, and Roose, Tiina

Abstract

Xylella fastidiosa is a xylem-limited plant pathogen infecting many crops globally and is the cause of the recent olive disease epidemic in Italy. One strategy proposed to mitigate losses is to replant susceptible crops with resistant varieties. Several genetic, biochemical and biophysical traits are associated to X. fastidiosa disease resistance. However, mechanisms underpinning resistance are poorly understood. We hypothesize that the susceptibility of olive cultivars to infection will correlate to xylem vessel diameters, with narrower vessels being resistant to air embolisms and having slower flow rates limiting pathogen spread. To test this, we scanned stems from four olive cultivars of varying susceptibility to X. fastidiosa using X-ray computed tomography. Scans were processed by a bespoke methodology that segmented vessels, facilitating diameter measurements. Though significant differences were not found comparing stem-average vessel section diameters among cultivars, they were found when comparing diameter distributions. Moreover, the measurements indicated that although vessel diameter distributions may play a role regarding the resistance of Leccino, it is unlikely they do for FS17. Considering Young–Laplace and Hagen–Poiseuille equations, we inferred differences in embolism susceptibility and hydraulic conductivity of the vasculature. Our results suggest susceptible cultivars, having a greater proportion of larger vessels, are more vulnerable to air embolisms. In addition, results suggest that under certain pressure conditions, functional vasculature in susceptible cultivars could be subject to greater stresses than in resistant cultivars. These results support investigation into xylem morphological screening to help inform olive replanting. Furthermore, our framework could test the relevance of xylem geometry to disease resistance in other crops.

Published
2023

16. Altered lateralization of the cingulum in deployment‐related traumatic brain injury: An ENIGMA military‐relevant brain injury study

Author

Dennis, Emily L., primary, Newsome, Mary R., additional, Lindsey, Hannah M., additional, Adamson, Maheen, additional, Austin, Tara A., additional, Disner, Seth G., additional, Eapen, Blessen C., additional, Esopenko, Carrie, additional, Franz, Carol E., additional, Geuze, Elbert, additional, Haswell, Courtney, additional, Hinds, Sidney R., additional, Hodges, Cooper B., additional, Irimia, Andrei, additional, Kenney, Kimbra, additional, Koerte, Inga K., additional, Kremen, William S., additional, Levin, Harvey S., additional, Morey, Rajendra A., additional, Ollinger, John, additional, Rowland, Jared A., additional, Scheibel, Randall S., additional, Shenton, Martha E., additional, Sullivan, Danielle R., additional, Talbert, Leah D., additional, Thomopoulos, Sophia I., additional, Troyanskaya, Maya, additional, Walker, William C., additional, Wang, Xin, additional, Ware, Ashley L., additional, Werner, John Kent, additional, Williams, Wright, additional, Thompson, Paul M., additional, Tate, David F., additional, and Wilde, Elisabeth A., additional

Published
2022
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20. Identification of neoantigens in oesophageal adenocarcinoma

Author

Nicholas, Ben, primary, Bailey, Alistair, additional, McCann, Katy J., additional, Wood, Oliver, additional, Walker, Robert C., additional, Parker, Robert, additional, Ternette, Nicola, additional, Elliott, Tim, additional, Underwood, Tim J., additional, Johnson, Peter, additional, and Skipp, Paul, additional

Published
2022
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23. Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer

Author

Doan, Coleen, primary, Aouizerat, Bradley E., additional, Ye, Yi, additional, Dang, Dongmin, additional, Asam, Kesava, additional, Bhattacharya, Aditi, additional, Howard, Timothy, additional, Patel, Yogin K., additional, Viet, Dan T., additional, Figueroa, Johnny D., additional, Zhong, Jiang F., additional, Thomas, Carissa M., additional, Morlandt, Anthony B., additional, Yu, Gary, additional, Callahan, Nicholas F., additional, Allen, Clint T., additional, Grandhi, Anupama, additional, Herford, Alan S., additional, Walker, Paul C., additional, Nguyen, Khanh, additional, Kidd, Stephanie C., additional, Lee, Steve C., additional, Inman, Jared C., additional, Slater, Jason M., additional, and Viet, Chi T., additional

Published
2022
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24. The effect of carbamazepine on bone structure and strength in control and osteogenesis imperfecta (Col1a2 +/p.G610C) mice

Author

Blank, Martha, primary, McGregor, Narelle E., additional, Rowley, Lynn, additional, Kung, Louise H. W., additional, Crimeen‐Irwin, Blessing, additional, Poulton, Ingrid J., additional, Walker, Emma C., additional, Gooi, Jonathan H., additional, Lamandé, Shireen R., additional, Sims, Natalie A., additional, and Bateman, John F., additional

Published
2022
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25. Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia

Author

Olson, Joseph W., primary, Nakhmani, Arie, additional, Irwin, Zachary T., additional, Edwards, Lloyd J., additional, Gonzalez, Christopher L., additional, Wade, Melissa H., additional, Black, Sarah D., additional, Awad, Mohammad Z., additional, Kuhman, Daniel J., additional, Hurt, Christopher P., additional, Guthrie, Bart L., additional, and Walker, Harrison C., additional

Published
2022
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26. Virtual Pharmacophore Screening Identifies Small‐Molecule Inhibitors of the Rev1‐CT/RIR Protein–Protein Interaction

Author

Massachusetts Institute of Technology. Department of Biology, Dash, Radha C., Ozen, Zuleyha, McCarthy, Kaitlyn R., Chatterjee, Nimrat, Harris, Cynthia A., Rizzo, Alessandro A., Walker, Graham C., Korzhnev, Dmitry M., Hadden, M. Kyle, Massachusetts Institute of Technology. Department of Biology, Dash, Radha C., Ozen, Zuleyha, McCarthy, Kaitlyn R., Chatterjee, Nimrat, Harris, Cynthia A., Rizzo, Alessandro A., Walker, Graham C., Korzhnev, Dmitry M., and Hadden, M. Kyle

Abstract

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Translesion synthesis (TLS) has emerged as a mechanism through which several forms of cancer develop acquired resistance to first-line genotoxic chemotherapies by allowing replication to continue in the presence of damaged DNA. Small molecules that inhibit TLS hold promise as a novel class of anticancer agents that can serve to enhance the efficacy of these front-line therapies. We previously used a structure-based rational design approach to identify the phenazopyridine scaffold as an inhibitor of TLS that functions by disrupting the protein–protein interaction (PPI) between the C-terminal domain of the TLS DNA polymerase Rev1 (Rev1-CT) and the Rev1 interacting regions (RIR) of other TLS DNA polymerases. To continue the identification of small molecules that disrupt the Rev1-CT/RIR PPI, we generated a pharmacophore model based on the phenazopyridine scaffold and used it in a structure-based virtual screen. In vitro analysis of promising hits identified several new chemotypes with the ability to disrupt this key TLS PPI. In addition, several of these compounds were found to enhance the efficacy of cisplatin in cultured cells, highlighting their anti-TLS potential.

Published
2022

27. Neuropsychological Functioning in Primary Dystonia: Updated and Expanded Multidomain Meta‐Analysis

Author

Aita, Stephen L., primary, Del Bene, Victor A., additional, Marotta, Dario A., additional, Pizer, Jasmin H., additional, Hawley, Nanako A., additional, Niccolai, Lindsay, additional, Walker, Harrison C., additional, Gerstenecker, Adam, additional, Martin, Roy C., additional, Clay, Olivio J., additional, Crowe, Michael, additional, Triebel, Kristen L., additional, and Hill, Benjamin D., additional

Published
2022
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33. Engineering bacteriocin-mediated resistance against the plant pathogen Pseudomonas syringae

Author

Rooney, William M, Grinter, Rhys W, Correia, Annapaula, Parkhill, Julian, Walker, Daniel C, Milner, Joel J, Grinter, Rhys W [0000-0002-8195-5348], Parkhill, Julian [0000-0002-7069-5958], Walker, Daniel C [0000-0002-4206-2942], Milner, Joel J [0000-0003-3702-4295], and Apollo - University of Cambridge Repository

Subjects
disease resistance antimicrobial peptide, Bacteriocins, Solanum lycopersicum, fungi, Arabidopsis, food and beverages, putidacin L1, Humans, Pseudomonas syringae, tobacco, transgenic, Disease Resistance, Plant Diseases
Abstract

The plant pathogen, Pseudomonas syringae (Ps), together with related Ps species, infects and attacks a wide range of agronomically important crops, including tomato, kiwifruit, pepper, olive and soybean, causing economic losses. Currently, chemicals and introduced resistance genes are used to protect plants against these pathogens but have limited success and may have adverse environmental impacts. Consequently, there is a pressing need to develop alternative strategies to combat bacterial disease in crops. One such strategy involves using narrow-spectrum protein antibiotics (so-called bacteriocins), which diverse bacteria use to compete against closely related species. Here, we demonstrate that one bacteriocin, putidacin L1 (PL1), can be expressed in an active form at high levels in Arabidopsis and in Nicotiana benthamiana in planta to provide effective resistance against diverse pathovars of Ps. Furthermore, we find that Ps strains that mutate to acquire tolerance to PL1 lose their O-antigen, exhibit reduced motility and still cannot induce disease symptoms in PL1-transgenic Arabidopsis. Our results provide proof-of-principle that the transgene-mediated expression of a bacteriocin in planta can provide effective disease resistance to bacterial pathogens. Thus, the expression of bacteriocins in crops might offer an effective strategy for managing bacterial disease, in the same way that the genetic modification of crops to express insecticidal proteins has proven to be an extremely successful strategy for pest management. Crucially, nearly all genera of bacteria, including many plant pathogenic species, produce bacteriocins, providing an extensive source of these antimicrobial agents.

Published
2020

37. Virtual Pharmacophore Screening Identifies Small‐Molecule Inhibitors of the Rev1‐CT/RIR Protein–Protein Interaction

Author

Dash, Radha C, Ozen, Zuleyha, McCarthy, Kaitlyn R, Chatterjee, Nimrat, Harris, Cynthia A, Rizzo, Alessandro A, Walker, Graham C, Korzhnev, Dmitry M, Hadden, M Kyle, Dash, Radha C, Ozen, Zuleyha, McCarthy, Kaitlyn R, Chatterjee, Nimrat, Harris, Cynthia A, Rizzo, Alessandro A, Walker, Graham C, Korzhnev, Dmitry M, and Hadden, M Kyle

Abstract

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Translesion synthesis (TLS) has emerged as a mechanism through which several forms of cancer develop acquired resistance to first-line genotoxic chemotherapies by allowing replication to continue in the presence of damaged DNA. Small molecules that inhibit TLS hold promise as a novel class of anticancer agents that can serve to enhance the efficacy of these front-line therapies. We previously used a structure-based rational design approach to identify the phenazopyridine scaffold as an inhibitor of TLS that functions by disrupting the protein–protein interaction (PPI) between the C-terminal domain of the TLS DNA polymerase Rev1 (Rev1-CT) and the Rev1 interacting regions (RIR) of other TLS DNA polymerases. To continue the identification of small molecules that disrupt the Rev1-CT/RIR PPI, we generated a pharmacophore model based on the phenazopyridine scaffold and used it in a structure-based virtual screen. In vitro analysis of promising hits identified several new chemotypes with the ability to disrupt this key TLS PPI. In addition, several of these compounds were found to enhance the efficacy of cisplatin in cultured cells, highlighting their anti-TLS potential.

Published
2021

38. Subcortical short‐term plasticity elicited by deep brain stimulation

Author

Awad, Mohammad Z., primary, Vaden, Ryan J., additional, Irwin, Zachary T., additional, Gonzalez, Christopher L., additional, Black, Sarah, additional, Nakhmani, Arie, additional, Jaeger, Byron C., additional, Bentley, J. Nicole, additional, Guthrie, Barton L., additional, and Walker, Harrison C., additional

Published
2021
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41. Engineering bacteriocin-mediated resistance against the plant pathogen Pseudomonas syringae

Author

Rooney, William M., Grinter, Rhys W., Correia, Annapaula, Walker, Daniel C., and Milner, Joel J.

Subjects
fungi, food and beverages
Abstract

The plant pathogen, Pseudomonas syringae (Ps), together with related Ps species, infect and attack a wide range of agronomically important crops, including tomato, kiwifruit, pepper, olive and soybean, causing economic losses. Currently, chemicals and introduced resistance genes are used to protect plants against these pathogens but have limited success and may have adverse environmental impacts. Consequently, there is a pressing need to develop alternative strategies to combat bacterial disease in crops. One such strategy involves using narrow‐spectrum protein antibiotics (so‐called bacteriocins), which diverse bacteria use to compete against closely related species. Here, we demonstrate that one bacteriocin, putidacin L1 (PL1), can be expressed in an active form at high levels in Arabidopsis and in Nicotiana benthamiana in planta to provide effective resistance against diverse pathovars of Ps. Furthermore, we find that Ps strains that mutate to acquire tolerance to PL1 lose their O‐antigen, exhibit reduced motility, and still cannot induce disease symptoms in PL1‐transgenic Arabidopsis. Our results provide proof‐of‐principle that the transgene‐mediated expression of a bacteriocin in planta can provide effective disease resistance to bacterial pathogens. Thus, the expression of bacteriocins in crops might offer an effective strategy for managing bacterial disease, in the same way that the genetic modification of crops to express insecticidal proteins has proven to be an extremely successful strategy for pest management. Crucially, nearly all genera of bacteria, including many plant pathogenic species, produce bacteriocins, providing an extensive source of these antimicrobial agents.

Published
2020

44. Client Experience with the Ontario Birth Center Demonstration Project

Author

Reszel, Jessica, primary, Weiss, Deborah, additional, Darling, Elizabeth K., additional, Sidney, Dana, additional, Van Wagner, Vicki, additional, Soderstrom, Bobbi, additional, Rogers, Judy, additional, Holmberg, Vivian, additional, Peterson, Wendy E., additional, Khan, Bushra M., additional, Walker, Mark C., additional, and Sprague, Ann E., additional

Published
2020
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50. Baseline neuropsychological profiles in prion disease predict survival time

Author

Sundaram, Saranya E., primary, Staffaroni, Adam M., additional, Walker, Nicole C., additional, Casaletto, Kaitlin B., additional, Casey, Megan, additional, Golubjatnikov, Aili, additional, Metcalf, Stacy, additional, O’Leary, Kelly, additional, Wong, Katherine, additional, Benisano, Kendra, additional, Forner, Sven, additional, Gonzalez Catalan, Marta, additional, Allen, Isabel E., additional, Rosen, Howard J., additional, Kramer, Joel H., additional, and Geschwind, Michael D., additional

Published
2020
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