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102. CRISPR-Generated Nrf2a Loss- and Gain-of-Function Mutants Facilitate Mechanistic Analysis of Chemical Oxidative Stress-Mediated Toxicity in Zebrafish

Author

Mills, Margaret G., primary, Ramsden, Richard, additional, Ma, Eva Y., additional, Corrales, Jone, additional, Kristofco, Lauren A., additional, Steele, W. Baylor, additional, Saari, Gavin N., additional, Melnikov, Fjodor, additional, Kostal, Jakub, additional, Kavanagh, Terrance J., additional, Zimmerman, Julie B., additional, Voutchkova-Kostal, Adelina M., additional, Brooks, Bryan W., additional, Coish, Philip, additional, Anastas, Paul T., additional, and Gallagher, Evan, additional

Published
2019
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103. Toward Less Hazardous Industrial Compounds: Coupling Quantum Mechanical Computations, Biomarker Responses, and Behavioral Profiles To Identify Bioactivity of SN2 Electrophiles in Alternative Vertebrate Models

Author

Steele, W. Baylor, primary, Kristofco, Lauren A., additional, Corrales, Jone, additional, Saari, Gavin N., additional, Corcoran, Eric J., additional, Hill, Bridgett N., additional, Mills, Margaret G., additional, Gallagher, Evan, additional, Kavanagh, Terrance J., additional, Melnikov, Fjodor, additional, Zimmerman, Julie B., additional, Voutchkova-Kostal, Adelina, additional, Anastas, Paul T., additional, Kostal, Jakub, additional, and Brooks, Bryan W., additional

Published
2019
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105. The scent marking behaviour of the brown hyaena Hyaena brunnea

Author

Mills, M.G.L, Gorman, M.L, and Mills, Margaret E.J.

Abstract

The deposition onto grass stalks of two distinct, strongsmelling substances produced in the anal scent pouch, is the most common form of scent marking in the brown hyaena (Hyaena brunnea). It is called pasting. The behaviour associated with pasting is described, as is the related functional anatomy of the scent pouch. The dispersion pattern of pastings within a group territory and the rate of marking in different parts of the territory were ascertained by direct observations on radio collared hyaenas. The data were analysed by the computer programs SYMAP and SYMVU which graphically display the data as a three dimensional map. Brown hyaenas leave most pastings in those areas in which they spend most time. This is in the central part of the territory. When they visit the boundaries, however, the frequency of pasting increases. GLC analyses of the pastings from two known individuals show distinct differences in the relative concentrations of the many compounds in the pastings of each. Behavioural observations show that the hyaenas are able to recognize different individuals' pastings. Pasting could function to inform group members of each other's movements as well as to inform outsiders that the territory is occupied.

Published
2017

107. The safer chemical design game. Gamification of green chemistry and safer chemical design concepts for high school and undergraduate students

Author

Mellor, Karolina E., primary, Coish, Philip, additional, Brooks, Bryan W., additional, Gallagher, Evan P., additional, Mills, Margaret, additional, Kavanagh, Terrance J., additional, Simcox, Nancy, additional, Lasker, Grace A., additional, Botta, Dianne, additional, Voutchkova-Kostal, Adelina, additional, Kostal, Jakub, additional, Mullins, Melissa L., additional, Nesmith, Suzanne M., additional, Corrales, Jone, additional, Kristofco, Lauren, additional, Saari, Gavin, additional, Steele, W. Baylor, additional, Melnikov, Fjodor, additional, Zimmerman, Julie B., additional, and Anastas, Paul T., additional

Published
2018
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114. Coffee and Coffeehouses

Author

Mills, Margaret A.

Subjects
Coffee and Coffeehouses (Book) -- Book reviews, Books -- Book reviews, Anthropology/archeology/folklore
Published
1990

115. Evolution of schooling behavior in threespine sticklebacks is shaped by the Eda gene

Author

Mills, Margaret G, Greenwood, Anna K, Wark, Abigail R, Peichel, Catherine, and Archambeault, Sophie Louise

Subjects
570 Life sciences, biology
Abstract

Despite longstanding interest in the genetic mechanisms that underlie behavioral evolution, very few genes that underlie naturally occurring variation in behavior between individuals or species are known, particularly in vertebrates. Here, we build on our previous forward genetic mapping experiments and use transgenic approaches to identify Ectodysplasin as a gene that causes differences in schooling behavior between wild populations of threespine stickleback (Gasterosteus aculeatus) fish. This work provides rare insight into the proximate mechanisms that have shaped the evolution of vertebrate behavior.

Published
2016
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118. The Molecular Design Research Network

Author

Coish, Philip, primary, Brooks, Bryan W, additional, Gallagher, Evan P, additional, Mills, Margaret, additional, Kavanagh, Terrance J, additional, Simcox, Nancy, additional, Lasker, Grace A, additional, Botta, Dianne, additional, Schmuck, Stephanie C, additional, Voutchkova-Kostal, Adelina, additional, Kostal, Jakub, additional, Mullins, Melissa L, additional, Nesmith, Suzanne M, additional, Mellor, Karolina E, additional, Corrales, Jone, additional, Kristofco, Lauren A, additional, Saari, Gavin N, additional, Steele, Baylor, additional, Shen, Longzhu Q, additional, Melnikov, Fjodor, additional, Zimmerman, Julie B, additional, and Anastas, Paul T, additional

Published
2017
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121. Dementia and guardianship: challenges in social work practice in a health care setting

Author

Mills, Margaret

Subjects
Capacity, Neoliberalism, Postmodernism, Adult guardianship, Dementia, Social constructionism
Abstract

This thesis critically examines social work practice in complex and disputed situations where an alternative legal decision-maker is perceived as necessary for a person with dementia. Australia has unique adult guardianship legislation and social workers are actively engaged in the process in a variety of ways, such as weighing the benefits against the possible harm and lodging applications. Yet within the profession this is an area where there is very little research. The purpose of this study is therefore to enable social workers to better understand the dynamics involved in adult guardianship proceedings for a person with dementia and provide knowledge that can be used for more effective practice. The theoretical approach is to use perspectives from social constructionism, with the links which can be made to modernism and postmodernism being taken into account. Five research case studies were investigated drawing from the caseload of social workers in an aged care service at a large metropolitan hospital in Australia. A thematic network analysis of the findings showed that the research case studies are constantly evolving, where different players participate by bringing their own perspectives, and in this process alliances are formed which reflect underlying dynamics of power. There are many diverse and contested issues, such as varied understandings of dementia and capacity and differing constructions of the notions of risk, protection and responsibility. The implications for social work practice are that in a contemporary health and welfare context social work is well placed to make an important contribution through its traditional roles of negotiation, interpretation and mediation between those who have discursive rights and those who do not.

Published
2015

123. Toward the Design of Less Hazardous Chemicals: Exploring Comparative Oxidative Stress in Two Common Animal Models

Author

Corrales, Jone, primary, Kristofco, Lauren A., additional, Steele, W. Baylor, additional, Saari, Gavin N., additional, Kostal, Jakub, additional, Williams, E. Spencer, additional, Mills, Margaret, additional, Gallagher, Evan P., additional, Kavanagh, Terrance J., additional, Simcox, Nancy, additional, Shen, Longzhu Q., additional, Melnikov, Fjodor, additional, Zimmerman, Julie B., additional, Voutchkova-Kostal, Adelina M., additional, Anastas, Paul T., additional, and Brooks, Bryan W., additional

Published
2016
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127. CRISPR-Generated Nrf2a Loss- and Gain-of-Function Mutants Facilitate Mechanistic Analysis of Chemical Oxidative Stress-Mediated Toxicity in Zebrafish

Author

Mills, Margaret G., Ramsden, Richard, Ma, Eva Y., Corrales, Jone, Kristofco, Lauren A., Steele, W. Baylor, Saari, Gavin N., Melnikov, Fjodor, Kostal, Jakub, Kavanagh, Terrance J., Zimmerman, Julie B., Voutchkova-Kostal, Adelina M., Brooks, Bryan W., Coish, Philip, Anastas, Paul T., and Gallagher, Evan

Abstract

The transcription factor Nrf2a induces a cellular antioxidant response and provides protection against chemical-induced oxidative stress, as well as playing a critical role in development and disease. Zebrafish are a powerful model to study the role of Nrf2a in these processes but have been limited by reliance on transient gene knockdown techniques or mutants with only partial functional alteration. We developed several lines of zebrafish carrying different null (loss of function, LOF) or hyperactive (gain of function, GOF) mutations to facilitate our understanding of the Nrf2a pathway in protecting against oxidative stress. The mutants confirmed Nrf2a dependence for induction of the antioxidant genes gclc, gstp, prdx1, and gpx1aand identified a role for Nrf2a in the baseline expression of these genes, as well as for sod1. Specifically, the 4-fold induction of gstpby tert-butyl hydroperoxide (tBHP) in wild type fish was abolished in LOF mutants. In addition, baseline gstpexpression in GOF mutants increased by 12.6-fold and in LOF mutants was 0.8-fold relative to wild type. Nrf2a LOF mutants showed increased sensitivity to the acute toxicity of cumene hydroperoxide (CHP) and tBHP throughout the first 4 days of development. Conversely, GOF mutants were less sensitive to CHP toxicity during the first 4 days of development and were protected against the toxicity of both hydroperoxides after 4 dpf. Neither gain nor loss of Nrf2a modulated the toxicity of R-(−)-carvone (CAR), despite the ability of this compound to potently induce Nrf2a-dependent antioxidant genes. Similar to other species, GOF zebrafish mutants exhibited significant growth and survival defects. In summary, these new genetic tools can be used to facilitate the identification of downstream gene targets of Nrf2a, better define the role of Nrf2a in the toxicity of environmental chemicals, and further the study of diseases involving altered Nrf2a function.

Published
2020
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128. Toward Less Hazardous Industrial Compounds: Coupling Quantum Mechanical Computations, Biomarker Responses, and Behavioral Profiles To Identify Bioactivity of SN2 Electrophiles in Alternative Vertebrate Models

Author

Steele, W. Baylor, Kristofco, Lauren A., Corrales, Jone, Saari, Gavin N., Corcoran, Eric J., Hill, Bridgett N., Mills, Margaret G., Gallagher, Evan, Kavanagh, Terrance J., Melnikov, Fjodor, Zimmerman, Julie B., Voutchkova-Kostal, Adelina, Anastas, Paul T., Kostal, Jakub, and Brooks, Bryan W.

Abstract

Sustainable molecular design of less hazardous chemicals promises to reduce risks to public health and the environment. Computational chemistry modeling coupled with alternative toxicology models (e.g., larval fish) present unique high-throughput opportunities to understand structural characteristics eliciting adverse outcomes. Numerous environmental contaminants with reactive properties can elicit oxidative stress, an important toxicological response associated with diverse adverse outcomes (i.e., cancer, diabetes, neurodegenerative disorders, etc.). We examined a common chemical mechanism (bimolecular nucleophilic substitution (SN2)) associated with oxidative stress using property-based computational modeling coupled with acute (mortality) and sublethal (glutathione, photomotor behavior) responses in the zebrafish (Danio rerio) and the fathead minnow (Pimephales promelas) models to identify whether relationships exist among biological responses and molecular attributes of industrial chemicals. Following standardized methods, embryonic zebrafish and larval fathead minnows were exposed separately to eight different SN2 compounds for 96 h. Acute and sublethal responses were compared to computationally derived in silico chemical descriptors. Specifically, frontier molecular orbital energies were significantly related to acute LC50values and photomotor response (PMR) no observed effect concentrations (NOECs) in both fathead minnow and zebrafish. This reactivity index, LC50values, and PMR NOECs were also significantly related to whole body glutathione (GSH) levels, suggesting that acute and chronic toxicity results from protein adduct formation for SN2 electrophiles. Shared refractory locomotor response patterns among study compounds and two alternative vertebrate models appear informative of electrophilic properties associated with oxidative stress for SN2 chemicals. Electrophilic parameters derived from frontier molecular orbitals were predictive of experimental in vivo acute and sublethal toxicity. These observations provide important implications for identifying and designing less hazardous industrial chemicals with reduced potential to elicit oxidative stress through bimolecular nucleophilic substitution.

Published
2020
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132. Female Education as a Theme in the Novels of Charlotte Brontë.

Author

Mills, Margaret

Subjects
*EDUCATION in literature, *WOMEN'S education, *WOMEN in literature, *ENGLISH women's writings, *GENDER inequality, *HISTORY
Abstract

In her novels, Charlotte Brontë challenges the experiences of women in education, class, marriage and employment. It is not surprising that female education had a prominent part to play in her novels: two of them have their main setting within a school, and the protagonist is employed as teacher, governess or tutor. Although Charlotte’s preoccupation with teaching as a career and with the means by which a woman could achieve that role reflects her own life experience, it is incorrect to assume that she wrote about these matters simply because this was familiar territory for her. Education, and particularly the education of women, was an issue of growing importance in the eighteenth and nineteenth centuries. My paper outlines some significant educational issues at the time Charlotte was writing — the function of teaching and learning and the curricula content for male and female education — and considers the connection in her novels between education and power imbalance between the sexes. [ABSTRACT FROM PUBLISHER]

Published
2018
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139. Dementia and Guardianship: Challenges in Social Work Practice.

Author

Mills, Margaret

Subjects
*DECISION making, *DEMENTIA, *GUARDIAN & ward, *INTERVIEWING, *RESEARCH methodology, *CASE studies, *QUESTIONNAIRES, *SOCIAL services, *SOCIAL workers, *QUALITATIVE research, *PROFESSIONAL practice, *FINANCIAL management, *SOCIAL constructionism, *THEMATIC analysis, *DATA analysis software
Abstract

Decision-making within the context of dementia can be an uncertain and problematic process. This study critically examined challenges in social work practice in instances where a legal alternative decision-maker through guardianship proceedings was perceived as necessary. Theoretical perspectives from social constructionism underpinned the research. Five qualitative case studies were investigated. A thematic network analysis showed that the situations were constantly evolving and different players participated by bringing their own perspectives. In this process alliances were formed that reflected underlying dynamics of power. Contested issues included varied understandings of dementia and capacity, and differing constructions of risk, protection, and responsibility. The implications for practice are discussed with social work being well placed to make an important contribution through its traditional roles of negotiation, interpretation, and mediation between those who have discursive rights and those who do not. Ethical reasoning as a basis for decision-making was also of significance. [ABSTRACT FROM AUTHOR]

Published
2017
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141. Genetic Architecture of Variation in the Lateral Line Sensory System of Threespine Sticklebacks

Author

Wark, Abigail R, primary, Mills, Margaret G, additional, Dang, Lam-Ha, additional, Chan, Yingguang Frank, additional, Jones, Felicity C, additional, Brady, Shannon D, additional, Absher, Devin M, additional, Grimwood, Jane, additional, Schmutz, Jeremy, additional, Myers, Richard M, additional, Kingsley, David M, additional, and Peichel, Catherine L, additional

Published
2012
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143. Evaluation and clinical validation of monkeypox (mpox) virus real-time PCR assays.

Author

Mills, Margaret G., Juergens, Kate B., Gov, Jolene P., McCormick, Carter J., Sampoleo, Reigran, Kachikis, Alisa, Amory, John K., Fang, Ferric C., Pérez-Osorio, Ailyn C., Lieberman, Nicole A.P., and Greninger, Alexander L.

Subjects
*MONKEYPOX, *VIRAL DNA, *ARTIFICIAL chromosomes, *CEREBROSPINAL fluid, *SALIVA, *VACCINIA
Abstract

• MPXV qPCR assays targeting G2R and F3L have limits of detection at 66 copies/mL for virus in VTM. • MPXV-G2R gives slightly lower Ct values than F3L, likely based on presence of additional gene copies in MPXV genome. • MPXV-F3L detects MXPV in 14 different specimen types. In spring of 2022, an outbreak of monkeypox (mpox) spread worldwide. Here, we describe performance characteristics of monkeypox virus (MPXV)-specific and pan-orthopoxvirus qPCR assays for clinical use. We validated probe-based qPCR assays targeting MPXV-specific loci F3L and G2R (genes MPXVgp052/OPG065 and MPXVgp002 and gp190/OPG002, respectively) and a pan-orthopoxvirus assay targeting the E9L locus (MPXVgp057/OPG071). Clinical samples and synthetic controls were extracted using the Roche MP96 or Promega Maxwell 48 instrument. qPCR was performed on the AB7500 thermocycler. Synthetic control DNA and high concentration clinical samples were quantified by droplet PCR. Cross-reactivity was evaluated for camelpox and cowpox genomic DNA, vaccinia culture supernatant, and HSV- and VZV-positive clinical specimens. We also tested the performance of the F3L assay using dry swabs, Aptima vaginal and rectal swabs, nasopharyngeal, rectal, and oral swabs, cerebrospinal fluid, plasma, serum, whole blood, breastmilk, urine, saliva, and semen. The MPXV-F3L assay is reproducible at a limit of detection (LoD) of 65.6 copies/mL of viral DNA in viral transport medium/universal transport medium (VTM/UTM), or 3.3 copies/PCR reaction. No cross-reactivity with herpesviruses or other poxviruses was observed. MPXV-F3L detects MPXV DNA in alternative specimen types, with an LoD ranging between 260-1000 copies/mL, or 5.7-10 copies/PCR reaction. In clinical swab VTM specimens, MPXV-F3L and MPXV-G2R assays outperformed OPXV-E9L by an average of 2.4 and 2.8 Cts, respectively. MPXV-G2R outperformed MPXV-F3L by 0.4 Cts, consistent with presence of two copies of G2R present in labile inverted terminal repeats (ITRs) of MPXV genome. MPXV is readily detected by qPCR using three clinically validated assays. [ABSTRACT FROM AUTHOR]

Published
2023
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144. Author Correction: Mutations in viral nucleocapsid protein and endoRNase are discovered to associate with COVID19 hospitalization risk.

Author

Zhao, Lue Ping, Roychoudhury, Pavitra, Gilbert, Peter, Schiffer, Joshua, Lybrand, Terry P., Payne, Thomas H., Randhawa, April, Thiebaud, Sara, Mills, Margaret, Greninger, Alex, Pyo, Chul-Woo, Wang, Ruihan, Li, Renyu, Thomas, Alexander, Norris, Brandon, Nelson, Wyatt C., Jerome, Keith R., and Geraghty, Daniel E.

Subjects
VIRAL mutation, VIRAL proteins, COVID-19, VIRAL genomes, HOSPITAL care
Abstract

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-04376-4, published online 24 January 2022 The original version of this Article contained an error in Figure 1, where an old version of the figure was mistakenly submitted for publication. These authors contributed equally: Lue Ping Zhao and Pavitra Roychoudhury. [Extracted from the article]

Published
2022
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