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3. Cardiac remodelling following myocardial infarction and the cardioprotective efficacy of adrenergic stimulation against reperfusion injury in healthy and failing hearts

Author

Young, Megan E., Caputo, Massimo, and Suleiman, Saadeh

Abstract

Introduction: Following myocardial infarction (MI) a process of adverse cardiac remodelling occurs leading to impaired function and eventually heart failure. Improving understanding of cardiac remodelling progression will aid in identifying targets for therapeutic intervention. Additionally, there is a need to design cardioprotective interventions against ischemia reperfusion (I/R) injury in failing hearts. Strategies targeting the adrenergic receptor (AR) signalling pathways are cardioprotective, whether such interventions are protective in the failing heart or in combination with cardioplegic arrest is not presently known. Methods: MI was induced in Wistar rats by occlusion of the left anterior descending coronary artery. Animals were recovered for 3-days, 2-weeks, or 4 weeks. Cardiac function was assessed by echocardiography. Blood and tissue samples were collected for metabolomics, histology, electron microscopy (EM) and proteomics. Cardioprotection against I/R injury was assessed ex-vivo in healthy and failing hearts. Pre-conditioning drugs targeting AR pathways were given prior to I/R, with or without cardioplegic arrest. Results: Functional impairment was evident at 3-days, with further deterioration at later time-points. Cardiomyocyte loss alongside increased collagen deposition occurred over-time in the infarct area, with subtle changes in remote areas. EM showed a time-dependent increase in telocytes within the extracellular matrix of the infarcted area. There were extensive cardiac proteome changes during early remodelling which markedly decreased during the later stages. Interestingly, there were changes in cardiac proteome and blood metabolites in response to sham surgery. Targeting the α1A-ARs conferred protection against I/R injury in healthy and failing hearts. Targeting β-ARs pathways provided additional protection to cardioplegic arrest, the underlying mechanism(s) involving modulation of the mitochondrial permeability transition pore. Conclusion: This work comprehensively characterised the cardiac remodelling process over-time following MI, providing new insights into disease progression. It has also shown the potential of targeting AR pathways to protect the heart against I/R injury as occurs in cardiac surgery.

Published
2023

7. Control of Unsaturation in De Novo Fatty Acid Biosynthesis by FabA

Author

Bartholow, Thomas G, Sztain, Terra, Young, Megan A, Lee, D John, Davis, Tony D, Abagyan, Ruben, and Burkart, Michael D

Subjects
Acyl Carrier Protein, Escherichia coli, Fatty Acid Synthase, Type II, Fatty Acids, Fatty Acids, Unsaturated, Hydro-Lyases, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology
Abstract

Carrier protein-dependent biosynthesis provides a thiotemplated format for the production of natural products. Within these pathways, many reactions display exquisite substrate selectivity, a regulatory framework proposed to be controlled by protein-protein interactions (PPIs). In Escherichia coli, unsaturated fatty acids are generated within the de novo fatty acid synthase by a chain length-specific interaction between the acyl carrier protein AcpP and the isomerizing dehydratase FabA. To evaluate PPI-based control of reactivity, interactions of FabA with AcpP bearing multiple sequestered substrates were analyzed through NMR titration and guided high-resolution docking. Through a combination of quantitative binding constants, residue-specific perturbation analysis, and high-resolution docking, a model for substrate control via PPIs has been developed. The in silico results illuminate the mechanism of FabA substrate selectivity and provide a structural rationale with atomic detail. Helix III positioning in AcpP communicates sequestered chain length identity recognized by FabA, demonstrating a powerful strategy to regulate activity by allosteric control. These studies broadly illuminate carrier protein-dependent pathways and offer an important consideration for future inhibitor design and pathway engineering.

Published
2022

9. Epidemiology of cardiovascular disease and its risk factors among refugees and asylum seekers: Systematic review and meta-analysis

Author

Al-Rousan, Tala, AlHeresh, Rawan, Saadi, Altaf, El-Sabrout, Hannah, Young, Megan, Benmarhnia, Tarik, Han, Benjamin H, and Alshawabkeh, Laith

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, Prevention, Good Health and Well Being, Refugees, CVD, Stroke, Displaced, Migrants, Risk factors, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThis is the first systematic review and meta-analysis assessing cardiovascular disease incidence and risk factors among refugees and asylum seekers.Methods and resultsPubMed, PsycINFO, CINAHL, and Embase databases were searched for studies in English from January 1, 1977, to March 8, 2020. Inclusion criteria were (1) observation of refugee history in participants; (2) diagnosis of CVD (coronary artery disease, heart failure, stroke, or CVD mortality) and risk factors (hypertension, diabetes, tobacco use, hyperlipidemia, obesity, psychosocial factors); (3) assessment of effect size and spread, (4) adjustment for sex; and (5) comparison with non-refugee migrants or natives. Data were extracted and evaluated by multiple reviewers for study quality. Of the 1158 screened articles, Participants from 7 studies (0.6%) involving 116.989 refugees living in Denmark, Sweden, and the United States were included in the systematic review, of which three studies synthesized the quantitative analyses. A fixed-effects model was created to pool the effect sizes of included studies. The pooled incidence of CVD in refugees was 1.71 (95% CI: 1.03, 2.83) compared with non-refugee counterparts. Pyschosocial factors were associated with increased risk of CVD in refugees but evidence on CVD risk factors varied by nativity and duration since resettlement.ConclusionsRefugee experience is an independent risk factor for CVD. Robust research on CVD in displaced populations is needed to improve the quality of evidence, clinical and preventive care, and address health equity in this marginalized population globally.

Published
2022

10. Nutrient and Trace Element Contributions from Drained Islands in the Sacramento–San Joaquin Delta, California

Author

Richardson, Christina M., Fackrell, Joseph K., Kraus, Tamara E. C., Young, Megan, and Paytan, Adina

Subjects
Drainage water quality, agricultural drainage, return flow, diversions, Delta island groundwater, nitrogen, phosphorous, metals
Abstract

Inventorying nutrient and trace element sources in the Sacramento-San Joaquin Delta (the Delta) is critical to understanding how changes—including alterations to point source inputs such as upgrades to the Sacramento Regional Wastewater Treatment Plant (SRWTP) and landscape-scale changes related to wetland restoration—may alter the Delta’s water quality. While island drains are a ubiquitous feature of the Delta, limited data exist to evaluate island drainage mass fluxes in this system. To better constrain inputs from island drains, we measured monthly discharge along with nutrient and trace element concentrations in island drainage on three Delta islands and surrounding rivers from June 2017 to September 2018. These data were used to calculate island-level fluxes and then upscaled to estimate Delta-wide contributions from island drains. Based on these results, we present (1) new estimates of gross and net nutrient and trace element fluxes from Delta island drains, and (2) concomitant N stable isotope data to improve our understanding of island N cycling. Over 60% of nearly all island drainage gross nutrient and trace element loads occurred in winter and spring. Upscaled island drainage net annual total nitrogen (TN), total dissolved nitrogen (TDN), and NH4+ loads comprised an estimated 9%, 7%, and 4%, respectively, of annual inputs to this system in 2018, before the SRWTP upgrade. Under a post-upgrade scenario, we estimated net annual island drainage TDN contributions to increase to 11% and NH4+ contributions to 45% of total Delta inputs as the SRWTP NH4+ load diminished to near zero. Our results suggest that island drainage is a measurable N source that has likely become increasingly important now that the SRWTP upgrade is complete. With over 200 potential active outfalls, these inputs may affect aquatic biogeochemical cycling in many regions of the Delta, especially in areas with long residence times.

Published
2022

11. Curricular Reform in Serious Illness Communication and Palliative Care: Using Medical Students’ Voices to Guide Change

Author

Reidy, Jennifer A., Brizzi, Kate, Chan, Stephanie H., Day, Hollis, Epstein, Scott K., Fischer, Melissa, Garg, Priya S., Gosline, Anna, Jaramillo, Carolina, Livne, Emma, Mitchell, Suzanne, Morgan, Sarah, Olmsted, Molly W., Stebbins, Patricia, Stumpf, Isabella, Vesel, Tamara, Yeh, Irene M., Young, Megan E., and Goldman, Roberta E.

Published
2024
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12. Protein–protein interaction based substrate control in the E. coli octanoic acid transferase, LipB

Author

Bartholow, Thomas G, Sztain, Terra, Young, Megan A, Davis, Tony D, Abagyan, Ruben, and Burkart, Michael D

Subjects
Infection
Abstract

Lipoic acid is an essential cofactor produced in all organisms by diverting octanoic acid derived as an intermediate of type II fatty acid biosynthesis. In bacteria, octanoic acid is transferred from the acyl carrier protein (ACP) to the lipoylated target protein by the octanoyltransferase LipB. LipB has a well-documented substrate selectivity, indicating a mechanism of octanoic acid recognition. The present study reveals the precise protein-protein interactions (PPIs) responsible for this selectivity in Escherichia coli through a combination of solution-state protein NMR titration with high-resolution docking of the experimentally examined substrates. We examine the structural changes of substrate-bound ACP and determine the precise geometry of the LipB interface. Thermodynamic effects from varying substrates were observed by NMR, and steric occlusion of docked models indicates how LipB interprets proper substrate identity via allosteric binding. This study provides a model for elucidating how substrate identity is transferred through the ACP structure to regulate activity in octanoyl transferases.

Published
2021

14. Decoding allosteric regulation by the acyl carrier protein

Author

Sztain, Terra, Bartholow, Thomas G, Lee, D John, Casalino, Lorenzo, Mitchell, Andrew, Young, Megan A, Wang, Jianing, McCammon, J Andrew, and Burkart, Michael D

Subjects
Biochemistry and Cell Biology, Biological Sciences, Underpinning research, 1.1 Normal biological development and functioning, Acyl Carrier Protein, Allosteric Regulation, Amino Acid Sequence, Escherichia coli, Escherichia coli Proteins, Magnetic Resonance Spectroscopy, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Conformation, Protein Interaction Domains and Motifs, Protein Interaction Maps, acyl carrier protein, nuclear magnetic resonance, molecular dynamics, chain flipping
Abstract

Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Płoskoń et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)-dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products.

Published
2021

19. Elucidation of transient protein-protein interactions within carrier protein-dependent biosynthesis.

Author

Bartholow, Thomas G, Sztain, Terra, Patel, Ashay, Lee, D John, Young, Megan A, Abagyan, Ruben, and Burkart, Michael D

Abstract

Fatty acid biosynthesis (FAB) is an essential and highly conserved metabolic pathway. In bacteria, this process is mediated by an elaborate network of protein•protein interactions (PPIs) involving a small, dynamic acyl carrier protein that interacts with dozens of other partner proteins (PPs). These PPIs have remained poorly characterized due to their dynamic and transient nature. Using a combination of solution-phase NMR spectroscopy and protein-protein docking simulations, we report a comprehensive residue-by-residue comparison of the PPIs formed during FAB in Escherichia coli. This technique describes and compares the molecular basis of six discrete binding events responsible for E. coli FAB and offers insights into a method to characterize these events and those in related carrier protein-dependent pathways.

Published
2021

20. Targeting Communication Effectiveness in Adults Who Stutter: A Preliminary Study

Author

Byrd, Courtney T., Coalson, Geoffrey A., and Young, Megan M.

Abstract

The purpose of this study was to examine the benefits of a treatment approach for adults who stutter that focuses on core communication competencies rather than attempt to modify speech fluency. Eleven adults who stutter completed a 12-week treatment program at The Arthur M. Blank Center for Stuttering Education and Research. Pre- and posttreatment measures included (a) self-reported cognitive and affective aspects of stuttering (Overall Assessment of the Speaker's Experience of Stuttering [OASES], Self-Perceived Communication Competence [SPCC], Devereux Adult Resilience Survey [DARS], and Self-Compassion Scale [SCS]) and (b) ratings of 9 core communication competencies by an unfamiliar clinician blind to pre/posttreatment status. Participants reported significant mitigation of the adverse impact of stuttering (OASES) and greater resilience (DARS) after treatment. Participants also demonstrated significant gains in 8 of the 9 clinician-perceived communication competencies. Lower pretreatment stuttering frequencies were not significantly associated with posttreatment gains in clinician-perceived communication competencies. Preliminary findings suggest that, similar to findings for children and adolescents who stutter in previous studies, significant psychosocial and communicative benefit can be obtained for adults who stutter following treatment designed to focus on communication effectiveness rather than fluency, and that these gains are not contingent on the participants' stuttering frequency prior to enrollment.

Published
2022
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21. (p)ppGpp and c-di-AMP Homeostasis Is Controlled by CbpB in Listeria monocytogenes.

Author

Peterson, Bret N, Young, Megan KM, Luo, Shukun, Wang, Jeffrey, Whiteley, Aaron T, Woodward, Joshua J, Tong, Liang, Wang, Jue D, and Portnoy, Daniel A

Subjects
Animals, Mice, Listeria monocytogenes, Bacterial Proteins, Dinucleoside Phosphates, Guanosine Pentaphosphate, Signal Transduction, Second Messenger Systems, Gene Expression Regulation, Bacterial, Protein Binding, Homeostasis, bacteria, cyclic dinucleotide, stringent response, Prevention, Digestive Diseases, Genetics, Infectious Diseases, Emerging Infectious Diseases, 1.1 Normal biological development and functioning, Microbiology
Abstract

The facultative intracellular pathogen Listeria monocytogenes, like many related Firmicutes, uses the nucleotide second messenger cyclic di-AMP (c-di-AMP) to adapt to changes in nutrient availability, osmotic stress, and the presence of cell wall-acting antibiotics. In rich medium, c-di-AMP is essential; however, mutations in cbpB, the gene encoding c-di-AMP binding protein B, suppress essentiality. In this study, we identified that the reason for cbpB-dependent essentiality is through induction of the stringent response by RelA. RelA is a bifunctional RelA/SpoT homolog (RSH) that modulates levels of (p)ppGpp, a secondary messenger that orchestrates the stringent response through multiple allosteric interactions. We performed a forward genetic suppressor screen on bacteria lacking c-di-AMP to identify genomic mutations that rescued growth while cbpB was constitutively expressed and identified mutations in the synthetase domain of RelA. The synthetase domain of RelA was also identified as an interacting partner of CbpB in a yeast-2-hybrid screen. Biochemical analyses confirmed that free CbpB activates RelA while c-di-AMP inhibits its activation. We solved the crystal structure of CbpB bound and unbound to c-di-AMP and provide insight into the region important for c-di-AMP binding and RelA activation. The results of this study show that CbpB completes a homeostatic regulatory circuit between c-di-AMP and (p)ppGpp in Listeria monocytogenes IMPORTANCE Bacteria must efficiently maintain homeostasis of essential molecules to survive in the environment. We found that the levels of c-di-AMP and (p)ppGpp, two nucleotide second messengers that are highly conserved throughout the microbial world, coexist in a homeostatic loop in the facultative intracellular pathogen Listeria monocytogenes Here, we found that cyclic di-AMP binding protein B (CbpB) acts as a c-di-AMP sensor that promotes the synthesis of (p)ppGpp by binding to RelA when c-di-AMP levels are low. Addition of c-di-AMP prevented RelA activation by binding and sequestering CbpB. Previous studies showed that (p)ppGpp binds and inhibits c-di-AMP phosphodiesterases, resulting in an increase in c-di-AMP. This pathway is controlled via direct enzymatic regulation and indicates an additional mechanism of ribosome-independent stringent activation.

Published
2020

23. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Author

Gornet, Jean-Marc, Beaugerie, Laurent, Shaji, Sebastian, Peyrin-Biroulet, Laurent, Reimund, Jean-Marie, Hebuterne, Xavier, Amiot, Aurélien, Armelao, Franco, Blanc, Pierre, Papi, Claudio, De Chambrun, Guillaume Pineton, Roblin, Xavier, Chu, Karmiris, Konstantinos, Shariq, Sohail, Viazis, Nikolaos, Limdi, Jimmy, Eder H, Piotr, Michalopoulos, Georgios, Bell, Andrew, Biancone, Livia, Dewitte, Marie, Mazhar, Zia, Franchimont, Denis, Nancey, Stephane, Macaigne, Gilles, Principi, Maria Beatrice, Fumery, Mathurin, Parkes, Gareth, Valats, Jean-Christophe, Doherty, Glen, Bouguen, Guillaume, Molnar, Tamás, Tsai, Hersin, Gangi, Mohsin, Pedersen, Natalia, Heluwaert, Frédéric, Shenderey, Richard, Zeissig, Sebastian, Butterworth, Jeffrey, Castiglione, Fabiana, Corless, Lynsey, Zallot, Camille, Baert, Filip, Singh, Salil, Sonwalkar, Sunil, Clayton, Elizabeth, Rahier, Jean-François, Vani, Deven, Bellaiche, Guy, De Vos, Martine, Kirchgesner, Julien, Kopylov, Uri, Lobaton, Triana, Locher, Christophe, Mantzaris, Gerassimos, Abouda, George, Smith, Katie, Sprakes, Michael, Theodoropoulou, Angeliki, Wesley, Emma, Bonnet, Joëlle, Elphick, David, Gilletta, Cyrielle, Gordon, John, Laharie, David, Nakad, Antoine, Orlando, Ambrogio, Dubois, Patrick, Hasselblatt, Peter, Michiels, Christophe, Preston, Cathryn, Staicu, Anca, Vuitton, Lucine, Kaassis, Mehdi, Speight, Ally, Ghosh, Deb, Löwenberg, Mark, Mathieu, Nicolas, Pelletier, Anne-Laure, Phillips, Anne, Magro, Fernando, Altwegg, Romain, Avni, Irit, biron, Landy, Jonathon, Nachury, Maria, Shenoy, Achuth, Trang, Caroline, Abitbol, Vered, Bamias, Georgios, Farkas, Klaudia, Maaser, Christian, Shitrit, Ariella, Siegmund, Britta, Filippi, Jérôme, O'morain, Colm, Yanai, Henit, Costes, Laurent, Hobday, David, Szepes, Zoltán, Calabrese, Emma, Dallal, Helen, Fung, Michael, Ramadas, Arvind, Baburajan, Bijay, Koss, Konrad, Barberis, Christophe, Buisson, Anthony, Amil, Morgane, Balestrieri, Paola, Johnson, Matthew, Tzouvala, Maria, Viennot, Stéphanie, Nagy, Ferenc, Thompson, Nick, Alric, Laurent, Samuel, Sunil, Bourrier, Anne, Chanteloup, Elise, Del Tedesco, Emilie, Harbord, Marcus, Lobo, Alan, Myers, Sally, Pollok, Richard, Ahmad, Tariq, Chaudhary, Rakesh, Karakoidas, Christos, Soliman, Ashraf, Stefanescu, Carmen, Theocharis, Georgios, Branden, Stijn Vanden, Beltran, Belén, Bouhnik, Yoram, Bourreille, Arnaud, Branco, Joana, Colleypriest, Ben, Eliakim, Rami, Knight, Paul, O'toole, Aoibhlinn, Robles, Virgina, Triantafyllou, Konstantinos, Bosca, Marta Maia, Lambrecht, Guy, Mosquera, Lucia Marquez, Panter, Simon, Pappa, Aikaterini, Simon, Marion, Sivaji, Ganesh, Bellanger, Christophe, Belle, Arthur, Borruel, Natalia, Egan, Laurence, Peeters, Harald, Sharpstone, Daniel, Arasaradnam, Ramesh, Benitez, José Manuel, Dahlerup, Jens Frederik, Giouleme, Olga, Gisbert, Javier P., Helwig, Ulf, Minguez, Miguel, Tsironi, Eftychia, Variola, Angela, Allen, Patrick, Boivineau, Lucille, Cole, Andy, Dib, Nina, Gomollon, Fernando, Johnston, Richard, Katsanos, Konstantinos, Kennedy, Nick, Kiszka-Kanowitz, Marianne, Marin-Jimenez, Ignacio, Miheller, Pál, Nos, Pilar, Saraj, Othman, Vinter-Jensen, Lars, Zittan, Eran, Baudry, Clotilde, Calvet, Xavier, Cazelles-Boudier, Marie-Christine, Coenegrachts, Jean-Louis, Cullen, Garret, Daperno, Marco, Dhar, Anjan, Gerard, Romain, Jensen, Nanna, Maharshak, Nitsan, Mcalindon, Mark, Mcloughlin, Simon, Parkes, Miles, Patel, Kamal, Peixoto, Armando, Polymeros, Dimitrios, Portela, Francisco, Rocca, Rodolfo, Seksik, Philippe, Subramanian, Sreedhar, Tennenbaum, Ruth, Atreya, Raja, Bachmann, Oliver, Berger, Arthur, Bor, Renáta, Buckley, Maire, Carpio, Daniel, Chaparro, María, Costa, Francesco, Domenech, Eugeni, Esteve, Maria, Foley, Stephen, Guardiola, Jordi, Koutroubakis, Ioannis, Kuehbacher, Tanja, Landman, Cécilia, Lavagna, Alessandro, Manceñido, Noemí, Mañosa, Míriam, Martín-Arranz, Maria Dolores, Plastaras, Laurianne, Scribano, Maria Lia, Sengupta, Subhasish, Teich, Nils, Tran-Minh, My-Linh, Zampeli, Evanthia, Amininejad, Leila, Arroyo, Teresa, Attar, Alain, Backman, Ann-Sofie, Bálint, Anita, Beckly, John, Ben Horin, Shomron, Bernardo, Sónia, Caillo, Ludovic, Caron, Bénédicte, Shanika de Silva, María, FábiáN, Anna, Fiorino, Gionata, Gutierrez, Ana, Lahat, Adi, Masmoudi, Mohamed, Mendolaro, Marco, Muls, Vinciane, Poullenot, Florian, Probert, Christopher, Reenaers, Catherine, Rutka, Mariann, Sarwari, Zaman, Sayer, Joanne, Sicilia, Beatriz, Sousa, Helena, van Kemseke, Catherine, Zabana, Yamile, Astegiano, Marco, Banim, Paul, Bettenworth, Dominik, Boualit, Médina, Brodersen, Jacob Broder, Christidou, Angeliki, Cooney, Rachel, Pinto, João Cortez, Cravo, Portugal Marília, Cremer, Anneline, Danese, Silvio, di Sabatino, Antonio, Fallingborg, Jan, Ferronato, Antonio, Planella, Esther Garcia, Gupta, Sanjay, Halfvarson, Jonas, Israeli, Eran, Kestenbaum, Samantha, Larsen, Lone, Macken, Elisabeth, Mathou, Nicoletta, Milassin, Ágnes, Pofelski, Joanna, Ricci, Chiara, Rodriguez-Moranta, Francisco, Schmidt-Lauber, Martin, Shaw, Ian, Soares, Marta, Soliman, Heithem, Triantos, Christos, Zografos, Konstantinos, Agrawal, Anurag, Armuzzi, Alessandro, Aubourg, Alexandre, Acosta, Manuel Barreiro-de, Barrio, Jesús, Bergemalm, Daniel, Bermejo, Fernando, Bodini, Giorgia, Bohr, Johan, Bossuyt, Peter, Christodoulou, Dimitrios, Claessens, Christophe, Collins, Paul, de Francisco, Ruth, Garcia, Santiago, Georgopoulos, Sotirios, Goutorbe, Felix, Kalantzis, Chrisostomos, Kourikou, Anastasia, Mace, Vincent, Malamut, Georgia, Ministro, Paula, Larmurier, Isabelle Nion, Ricart, Elena, Serrero, Mélanie, Sheridan, Juliette, Weimers, Petra, Andersen, Vibeke, Arroja, Bruno, Bokemeyer, Bernd, Bujanda, Luis, Degand, Thibault, Eriksson, Carl, Garceau, Cécile, Glerup, Henning, Goren, Idan, Jackson, Lucina, Koch, Stéphane, Mesonero, Francisco, Ordas, Ingrid, Riviere, Pauline, Saibeni, Simone, Soares, João, Tavernier, Noémie, Theede, Klaus, Ungar, Bella, Bästlein, Elke, Gasbarrini, Antonio, Protopapas, Andreas, Reindl, Wolfgang, Bossa, Fabrizio, Hart, Ailsa, Heil, Franz-Josef, O'Connor, Anthony, Oldenburg, Bas, Pastorelli, Luca, Stephen patchett, Ramakrishnan, Subramaniam, de Caestecker, John, Echarri, Ana, Kevans, David, Büning, Jürgen, Coelho, Rosa, Jansen, Jeroen, Koslowski, Benjamin, Wells, Christopher, Ceballos, Daniel, König, Ingrid, Padmanabhan, Hari, Patani, Timi, Qureshi, Raheel, Zagorowicz, Edyta, Allez, Matthieu, Archavlis, Emmanouil, Bonnet, Delphine, Guidi, Luisa, Mcnamara, Deirdre, Vernia, Piero, Weidenhiller, Michael, Alon, Lang, Boysen, Trine, Delattre, Charlotte, Farrell, Richard, Krüger, Rolf-Achim, Paupard, Thierry, Vind, Ida, Caprioli, Flavio, Gancho, Vladimir, Quentin, Vincent, Avidan, Benjamin, D’Haens, Geert, Mccarthy, Jane, Snook, Jonathon, Soufleris, Konstantinos, Zerbib, Frank, Carter, Dan, Depla, Annekatrien, Eisenbach, Thomas, Fries, Walter, Grammatikos, Nikolaos, Ilegems, Saskia, Lopez-Sanroman, Antonio, Moreau, Jacques, Riegler, Gabriele, Rietdijk, Svend, Rocha, Marta, Rosa, Isabelle, Ryan, Barbara, Yeremenko, Yelena, Boruchowicz, Arnaud, Damião, Filipe, Laoudi, Foteini, Lügering, Andreas, Macarri, Giampiero, Thomopoulos, Konstantinos, Barros, Luísa, Blixt, Thomas, Garros, Aurélien, Khorrami, Sam, Sokol, Harry, Sturm, Andreas, Livovsky, Dan, Maul, Jochen, Miks, Heinrich, Papadopoulos, Vasileios, Schmidt, Carsten, Snir, Yifat, Svenningsen, Lise, Ahmed, Wafaa, Broitman, Yelena, Cuillerier, Emmanuel, Kant, Prashant, Leyden, Jan, Lichtenstein, Lev, Lopes, Susana, Martineau, Chloé, Mulcahy, Hugh, Schweitzer, Axel, Van Schaik, Fiona, Banai, Hagar, Danion, Pauline, Dulery, Charlotte, Fidder, Herma, Gay, Claire, Hagege, Hervé, Harnois, Florence, Jørgensen, Søren Peter, Müller-Ziehm, Jens, Oikonomou, Michail, Palmela, Carolina, Schulze/Röske, Jörg, Smith, Mark, Thurm, Tamar, Bresso, Francesca, Brixi, Hedia, Jones, John, Macmathuna, Padraig, Painchart, Claire, Ron, Yulia, Vester-Andersen, Marianne, Alexandrino, Gonçalo, Börner, Norbert, Cardoso, Mariana, Chagas, Cristina, Dignaß, Axel, Dotan, Iris, Hedin, Charlotte, Karatzas, Pantelis, Kasapidis, Panagiotis, Palatka, Károly, Sakizlis, Georgios, Wilson, Ana, Bosanko, Nick, Caldeira, Paulo, Gagniere, Charlotte, Libier, Louise, Meunier, Camille, Moog, Gero, Pasquion, Audrey, Pica, Roberta, Akbar, Ayesha, Arab, Nadia, Cadiot, Guillaume, Carvalho, João, Charpignon, Claire, Fellermann, Laus, Fishman, Sigal, Fraser, Gerald, Gluck, Nathan, Hoesl, Mark, Kierkus, Jarosław, Klopocka, Maria, Arranz, Eduardo Martin, Menchen, Luis, Nikolaus, Susanna, Petrache, Anca, Ponsioen, Cyriel, Riestra, Sabino, Robledo, Pilar, Rodriguez, Cristina, Samer, Misheal, Tischer, Matthias, Wypych, Joanna, Baudon, Julien, Bezzio, Cristina, Boschetti, Gilles, Burisch, Johan, Creed, Tom, Demarzo, Maria Giulia, Festa, Stefano, Figueroa, Andrés, Julsgaard, Mette, Navarro, Pablo, Perez-Galindo, Pablo, Rouillon, Cléa, Sablich, Emanuele, Tosca, Joan, Vidon, Mathias, Vidon, Marine, Vitte, René-Louis, Wampach, Anne, Baumann, Cédric, Urmes, Isabelle Clerc, Rousseau, Hélène, Borie, Marc, Uzzan, Mathieu, Chatten, Kelly, Peter, Rimmer, Tariq, Iqbal, Cossignani, Marta, Cañete, Fiorella, Holvoet, Tom, Krasz, Susanne, Dias, Sandra, Abalia, Hadas, Abaza, Aziza, Abramovich, Gal, Ackzell, Ingrid, Adams, Carol, Addleton, Catherine, Alfambra, Erika, Algaba, Alicia, Allcock, Clare, Allison, Joanna, Amouriaux, Karine, Anderson, Julie, Anderson, Emma, Appelmans, Saskia, Armstrong, Lisa, Atkins, Stacey, Attaran-Bandarabadi, Masoumeh, Bailey, Yvonne, Bardot, Stephanie, Beck, Natasha, Bennett, Lillie, Bergfeld, Jonathan Phil, Berkane, Ramdane, Boey, Hanne, Bowlas, Louise, Bradley-Potts, Joanne, Brear, Tracy, Bretlander-Peters, Nicole, Brown, Ellen, Brown, Johanna, Buckingham, Elizabeth, Buellens, Katrien, Bull, Rhian, Burke, Maura, Burns, Leighanne, Burton, Julie, Bwalya, Agness, Cabanas, Karine, Callaghan, Muriel, Camou, Océane, Campbell, Debbie, Capoferro, Elvira, Carnahan, Mandy, Carnio, Cornelia, Carter, Anne, Clack, Concetta Casali, Chedouba, Leïla, Cipriano, Bessie, Claeys, Sophie, Closset, Manon, Coban, Dilek, Cococcia, Sara, Coe, Carolann, Cole, Helen, Collet, Emilie, Collins, Kayleigh, Combes, Isabelle, Connor, Emma, Constantin, Kathryn, Cooke, Susan, Cornet, Nathanaëlle, Corrihons, Estelle, Corsino, Pilar, Cortaville, Rosie, Cotterill, Donna, Cowton, Amanda, Cox, Harriet, Cripps, Viktoria, Crowder, Amanda, Cukier, Tzufit, Daniel, Amelia, Dawe, Chris, de Haan, Jose, Croix, Rosanna de la, Dejonckheere, Evva, Villanegro, Juan Delare, Delaval, Guillaume, Delliponti, Mariangela, Delommez, Aude, Detry, Emilie, Dhanaratne, Melanie, Galan, Laura Diez, Dodel, Marie, Dooks, Emma, Du Cheyron, Joseph, Duane, Linda, Vulgo Cochran, Jennifer Dulling, Dyer, Simona, Dymond, Harvey, Ekblad, Charlotte, Elliott, Kerry, Emmerson, Ingrid, Eugene-Jolchine, Irène, Fleming, Lorna, Fletcher, Eve, Ford, Sarah, Forshaw, Greg, Foulds, Angela, Francois, Caroline, Fuge, Nicole, Gafni, Gal, Ganon, Miri, Nuñez, Olga Garcia, Ramirez, Laura Garcia, Gelder, Sophie, Gettkowski, Raimonda, Gilardi, Daniela, Giuffrida, Paolo, Gobert, Vincent, Godden, Jo, Godwin, Nuala, Goulden, Kay, Graham, Sharon, Green, Charlotte, Green, Marie, Gueye, Aboubakar, Guler, Tuba, Gustavsson, Ida, Hadjisavvas, Helena, Hammonds, Fiona, Hantzi, Christina, Hauke, Marion, Haydock, Julie, Hayes, Orla, Nislev, Lizette Helbo, Hochstodter, Jessica, Hogg, Ashleigh, Hölbing, Manuela, Holland, Maureen, Holsbergen, Maartje, Howard, Linda, Hoyda, Aviya, Hull, Robert, Irish, Jane, Jackson, Wendy, Janssen, Wendy, Jeffrey, Lesley, Jourdan, Sofia, Jutrowska, Izabela, Kaniel, Chava, Karezos, Theofilos, Kelly, Niamh, Kelly, Jessica, Kennedy, Mary, Kennedy, Una, Kibaru, Joyce, Kirkman, Gemma, Klaproth, Janine, Kneese, Corinna, Koch, Andrea, Kokke, Kathleen, Koppelow, Martha, Krause, Sabine, Krauspe, Sabine, Kwakkenbos, Petra, Labarile, Nunzia, Lang, Hannah, Lassailly, Marianne, Leconte, Martine, Lepczynski, Linda, Levell, Emma, Levhar, Nina, Lindhort, Kerstin, Lisle, Jessica, Cauce, Beatriz Lopez, Lorenz, Gabriele, Lovati, Ambra, Lowry, Tracey, Lund, Margareta, Vorderbrügge, Anne Lutz, Maansson, Suzanne, Madapathage, Videsheka, Cheviakoff, Maelys, Magness, Alison, Manley, Orla, Manyoni, Catherine, Marg, Ingke, Marra, Antonella, Martins, Carole, Massella, Arianna, Mathias, Aurore, Mervyn, Danielle, Minsart, Charlotte, Mitchell, Sally, Monks, Kathleen, Montero, Mélanie, Moore, Alson, Moser, Maren, Moss, Alison, Mullen, Angela, Murciano, M. Francisca, Naylor, Deanna, Nehus, Ansgar, Nicholson, Anne, Nöding, Sarah, Nolan, Sinead, Nörenberg, Janet, Northcott, Clare, O'Connell, Jim, O’Kelly, Alison, Orbach-Zingboim, Noam, Orobitg, Judit, Otieno, Charlene, Owen, Charlotte, Patch, Sarah, Pauker, Maor, Pauli, Renate, Pearson, Harriet, Peggy, Falgon, Petit, Séverine, Petrissans, Christine, Piergallini, Simona, Pippard, Lucy, Pitt, Laura, Pócsik, Gabriella, Poher, Yoann, Pomes, Chloé, Pritchard, Lucy, Puchades, Laura, Quaid, Sheena, Rana, Aleem, Raynard, Dana, Reilly, Mykla, Reinert, Sonja, Reinknecht, Manuela, Renner, Baerbel, Reynolds, Rob, Rizzuto, Giulia, Robinson, Matthew, Robrechts, Joke, Rodriguez, Eva M., Rosenblum, Efrat, Russel, Tamlyn, Sadare, Ibiyemi, Salama, Noa, Schakel, Toos, Schauer, Anja, Schiavoni, Elisa, Shaw, Caroline, Shelton, Sarah, Sicart, Virginie, Siouville, Elodie, Smith, Orla, Soude, Théo, Stephenson, Sophie, Stephenson, Elaine, Steppe, Marjan, Sterkx, An, Stickley, Jo, Sugrue, Kathleen, Swietec, Natalia, Tasiaux, Charlotte, Thamu, Bhavneet, Thomas, Susane, Tobi, Ogwa, Touabi, Kahina, Tovi, Shifra, Tregonning, Julie, Turchini, Laura, Unkhoff, Julia, Unruh, Olesya, Uzun, Nurcan, Van Aert, Frauke, Bergh, Sandrine Vanden, Vandenbroucke, Louise, Vansteenkiste, Laura, Vardit, Shay, Vergriete, Valentin, Walker, Elaine, Warner, Eleanor, Watchorn, Olivia, Watson, Ekaterina, Wauthier, Marie-Claire, Weetman, Belgium Maria, Weston, Margaret, West-Petroschka, Wiebke, Wienecke, Susann, Wierling, Kerstin, Wiestler, Miriam, Wilcox, Rebecca, Wilhelmsen, Elva, Williams, Angharad, Williamson, Georgina, Wilson, Deborah, Wistance, Kate, Wortmann, Nicolas, Wurie, Subie, Yadgar, Karin, Young, Gail, Young, Megan, Aucouturier, Julien, Bertin, Marie- Jo, Bougrine, Hasnae, Coisnon, Marie, Defrance, Antoine, Gutierrez, Kati, Harouz, Amel, Jerber, Laure, Khlifi, Aida, Kirati, Amina, Liworo, Nasaladjine, Logoltat, Maude, Mailhat, Charlotte, M'Bayi, Chancely, Medane, Yasmina, Merkhoufa, Dalal, Elhad, Saouda Mohamed, Monthe, Bertille, Moyon, Fanny, Rabiega, Pascaline, Sekela, Jennifer, Thilloy, Charlotte, Hamamouche, Naima, Partisotti, Frederic, Blandin, Patrick, Mokhtari, Hocine, Coutard, Laure, and Doherty, Glen A.

Published
2023
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24. Periodic Properties Illustrated by CH[subscript 3]NH[subscript 3]Pb(I[subscript 1-'x'Br'x')[subscript 3] Solid Solution Perovskite Semiconductors

Author

Lisensky, George C., Dauzvardis, Fabian, and Young, Megan M. K.

Abstract

For solid solutions with the same arrangement of atoms, the size of a unit cell depends on the size of the atoms in the unit cell. The distance between nuclei also helps determine how strongly electrons are held, which changes the band gap energy. Samples of semiconductor CH[subscript 3]NH[subscript3]Pb(I[subscript 1-"x"Br"x")[subscript 3] solid solutions were prepared; the unit cell size was measured by powder X-ray diffraction, and the band gap energy was measured by visible absorption spectroscopy. This use of a material with significant research and technological implications for solar cells illustrates the periodic properties relationship between composition, atomic size, and electron energy levels.

Published
2021
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27. Human influence on the 2021 British Columbia floods

Author

Gillett, Nathan P., Cannon, Alex J., Malinina, Elizaveta, Schnorbus, Markus, Anslow, Faron, Sun, Qiaohong, Kirchmeier-Young, Megan, Zwiers, Francis, Seiler, Christian, Zhang, Xuebin, Flato, Greg, Wan, Hui, Li, Guilong, and Castellan, Armel

Published
2022
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28. Comparison of Anti‐Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight‐Based Dosing of Polyvalent Immunoglobulin.

Author

Young, Megan K, Ng, Shu‐Kay, Faddy, Helen M, and Nimmo, Graeme R

Subjects
*INTRAVENOUS immunoglobulins, *VIRAL antibodies, *DATA analysis, *HEPATITIS A, *FISHER exact test, *TREATMENT effectiveness, *RANDOMIZED controlled trials, *DESCRIPTIVE statistics, *MANN Whitney U Test, *CHI-squared test, *STATISTICS, *DATA analysis software
Abstract

This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post‐exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight). Quantitative serial serum hepatitis A antibody concentrations were measured at baseline and then on days 1, 3, 7, 28, and 50. Fifteen participants completed the trial. Serum hepatitis A antibody concentrations were not different between the study groups at any time point. Pharmacokinetic parameters estimated from participant data were not different between the study groups. The hepatitis A antibody level of all participants exceeded 10 mIU/mL at day 50. While no difference between dosing regimens was found in this study, further research should examine dosing at the lower limit of current Australian recommendations before making policy decisions. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential.

Author

Patel, Aaran H., Koysombat, Kanyada, Pierret, Aureliane, Young, Megan, Comninos, Alexander N., Dhillo, Waljit S., and Abbara, Ali

Subjects
KISSPEPTIN neurons, BONE health, KISSPEPTINS, PULSE generators, GONADOTROPIN releasing hormone
Abstract

Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin‐releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss—often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Natural Variation in the Multidrug Efflux Pump SGE1 Underlies Ionic Liquid Tolerance in Yeast

Author

Higgins, Douglas A, Young, Megan KM, Tremaine, Mary, Sardi, Maria, Fletcher, Jenna M, Agnew, Margaret, Liu, Lisa, Dickinson, Quinn, Peris, David, Wrobel, Russell L, Hittinger, Chris Todd, Gasch, Audrey P, Singer, Steven W, Simmons, Blake A, Landick, Robert, Thelen, Michael P, and Sato, Trey K

Subjects
Microbiology, Biological Sciences, Genetics, Industrial Biotechnology, Human Genome, Biotechnology, Drug Tolerance, Genetic Variation, Imidazoles, Ionic Liquids, Membrane Proteins, Membrane Transport Proteins, Phenotype, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, yeast, ionic liquid, natural variation, major facilitator superfamily, biofuels, toxin tolerance, Developmental Biology, Biochemistry and cell biology
Abstract

Imidazolium ionic liquids (IILs) have a range of biotechnological applications, including as pretreatment solvents that extract cellulose from plant biomass for microbial fermentation into sustainable bioenergy. However, residual levels of IILs, such as 1-ethyl-3-methylimidazolium chloride ([C2C1im]Cl), are toxic to biofuel-producing microbes, including the yeast Saccharomyces cerevisiae. S. cerevisiae strains isolated from diverse ecological niches differ in genomic sequence and in phenotypes potentially beneficial for industrial applications, including tolerance to inhibitory compounds present in hydrolyzed plant feedstocks. We evaluated >100 genome-sequenced S. cerevisiae strains for tolerance to [C2C1im]Cl and identified one strain with exceptional tolerance. By screening a library of genomic DNA fragments from the [C2C1im]Cl-tolerant strain for improved IIL tolerance, we identified SGE1, which encodes a plasma membrane multidrug efflux pump, and a previously uncharacterized gene that we named ionic liquid tolerance 1 (ILT1), which encodes a predicted membrane protein. Analyses of SGE1 sequences from our panel of S. cerevisiae strains together with growth phenotypes implicated two single nucleotide polymorphisms (SNPs) that associated with IIL tolerance and sensitivity. We confirmed these phenotypic effects by transferring the SGE1 SNPs into a [C2C1im]Cl-sensitive yeast strain using CRISPR/Cas9 genome editing. Further studies indicated that these SNPs affect Sge1 protein stability and cell surface localization, influencing the amount of toxic IILs that cells can pump out of the cytoplasm. Our results highlight the general potential for discovering useful biotechnological functions from untapped natural sequence variation and provide functional insight into emergent SGE1 alleles with reduced capacities to protect against IIL toxicity.

Published
2018

34. Reversal of congenital hypogonadotrophic hypogonadism (CHH) in a woman with a heterozygous inactivating variant in GnRHR gene

Author

W, Nyunt Sandhi, primary, Phylactou, Maria, additional, Koysombat, Kanyada, additional, Tsoutsouki, Jovanna, additional, C, Yeung Arthur, additional, Young, Megan, additional, Newman, Anastasia, additional, N, Comninos Alexander, additional, Mamoojee, Yaasir, additional, Pitteloud, Nelly, additional, Quinton, Richard, additional, S, Dhillo Waljit, additional, and Abbara, Ali, additional

Published
2024
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37. Kisspeptin as a test of hypothalamic function in women presenting with oligo / amenorrhoea

Author

Patel, Bijal, primary, Abbara, Ali, additional, Yeung, Arthur, additional, Phylactou, Maria, additional, Tsoutsouki, Jovanna, additional, Koysombat, Kanyada, additional, Young, Megan, additional, Nyunt, Sandhi, additional, Qayum, Ambreen, additional, Patel, Aaran, additional, Zielinska, Agata, additional, Omar, Yusra, additional, Eng, Pei, additional, Mills, Edouard G, additional, Hanassab, Simon, additional, Webber, Lisa, additional, Jayasena, Channa, additional, Tan, Tricia, additional, Quinton, Richard, additional, Clarke, Sophie, additional, Comninos, Alexander, additional, and Dhillo, Waljit, additional

Published
2024
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38. Endocrine responses to kisspeptin in an unusual case of kallmann syndrome with unilateral anosmia

Author

Tsoutsouki, Jovanna, primary, N, Comninos Alexander, additional, Phylactou, Maria, additional, Patel, Bijal, additional, Mills, Edouard, additional, Young, Megan, additional, Yeung, Arthur, additional, Koysombat, Kanyada, additional, Modi, Manish, additional, Papadopoulou, Deborah, additional, Howard, Sasha, additional, S, Dhillo Waljit, additional, and Abbara, Ali, additional

Published
2024
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43. Chapter 1 From Precarious Work to Sustainable Livelihoods

Author

Carr, Stuart, Hodgetts, Darrin J., Hopner, Veronica, and Young, Megan

Subjects
"Stuart C. Carr, Veronica Hopner, Darrin J. Hodgetts, Megan Young, Livelihoods, Precarious, Sustainable, Tackling, Work"
Abstract

This volume further anchors often abstracted, global ideas like “universal decent work” within local situations, everyday work practices, and lived experiences. Relatedly, a historical strength of I/O psychology has been its focus on the diversity of sociocultural values and norms in the workplace, including at national, organizational, and individual levels (for a review, see Carr, 2013). This chapter builds on, but also constructively away from, those foundations. Specifically, this chapter—like the contributions that follow—adds to these sociocultural considerations. We do so by including diversities associated with the various socioeconomic situations of different groups that are omnipresent at the hard edges of the wage, work security, and wellbeing spectra (Carr, 2023). Finally, this chapter and book take a deep dive into “who” has been systematically excluded from decent work in the past, and how they might be systemically included in our collective and sustainable futures.

Published
2024
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