8,455 results on '"Mortimer, P."'
Search Results
152. What Makes Work Meaningful?
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Mortimer, Samuel A.
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- 2023
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153. The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study
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Ben Knox-Brown, Jaymini Patel, James Potts, Rana Ahmed, Althea Aquart-Stewart, Cristina Barbara, A. Sonia Buist, Hamid Hacene Cherkaski, Meriam Denguezli, Mohammed Elbiaze, Gregory E. Erhabor, Frits M. E. Franssen, Mohammed Al Ghobain, Thorarinn Gislason, Christer Janson, Ali Kocabaş, David Mannino, Guy Marks, Kevin Mortimer, Asaad Ahmed Nafees, Daniel Obaseki, Stefanni Nonna M. Paraguas, Li Cher Loh, Abdul Rashid, Sundeep Salvi, Terence Seemungal, Michael Studnicka, Wan C. Tan, Emiel F. M. Wouters, Hazim Abozid, Alexander Mueller, Peter Burney, and Andre F. S. Amaral
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Spirometry ,Small airways obstruction ,Symptoms ,Cardiovascular disease ,Quality of life ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. Methods Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). Results Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. Conclusion Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.
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- 2023
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154. A chimeric antigen receptor-based cellular safeguard mechanism for selective in vivo depletion of engineered T cells
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Mortimer Svec, Sarah Dötsch, Linda Warmuth, Manuel Trebo, Simon Fräßle, Stanley R. Riddell, Ulrich Jäger, Elvira D’Ippolito, and Dirk H. Busch
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chimeric antigen receptor ,safeguard mechanism ,side effects ,on-target/off-tumor ,B cell aplasia 2 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Adoptive immunotherapy based on chimeric antigen receptor (CAR)-engineered T cells has exhibited impressive clinical efficacy in treating B-cell malignancies. However, the potency of CAR-T cells carriethe potential for significant on-target/off-tumor toxicities when target antigens are shared with healthy cells, necessitating the development of complementary safety measures. In this context, there is a need to selectively eliminate therapeutically administered CAR-T cells, especially to revert long-term CAR-T cell-related side effects. To address this, we have developed an effective cellular-based safety mechanism to specifically target and eliminate the transferred CAR-T cells. As proof-of-principle, we have designed a secondary CAR (anti-CAR CAR) capable of recognizing a short peptide sequence (Strep-tag II) incorporated into the hinge domain of an anti-CD19 CAR. In in vitro experiments, these anti-CAR CAR-T cells have demonstrated antigen-specific cytokine release and cytotoxicity when co-cultured with anti-CD19 CAR-T cells. Moreover, in both immunocompromised and immunocompetent mice, we observed the successful depletion of anti-CD19 CAR-T cells when administered concurrently with anti-CAR CAR-T cells. We have also demonstrated the efficacy of this safeguard mechanism in a clinically relevant animal model of B-cell aplasia induced by CD19 CAR treatment, where this side effect was reversed upon anti-CAR CAR-T cells infusion. Notably, efficient B-cell recovery occurred even in the absence of any pre-conditioning regimens prior anti-CAR CAR-T cells transfer, thus enhancing its practical applicability. In summary, we developed a robust cellular safeguard system for selective in vivo elimination of engineered T cells, offering a promising solution to address CAR-T cell-related on-target/off-tumor toxicities.
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- 2024
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155. Screening for post-TB lung disease at TB treatment completion: Are symptoms sufficient?
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Jamilah Meghji, Vester Gunsaru, Beatrice Chinoko, Elizabeth Joekes, Ndaziona P K Banda, Nicola Marozva, Jamie Rylance, Stephen B Squire, Kevin Mortimer, and Maia Lesosky
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Public aspects of medicine ,RA1-1270 - Abstract
Pulmonary TB survivors face a high burden of post-TB lung disease (PTLD) after TB treatment completion. In this secondary data analysis we investigate the performance of parameters measured at TB treatment completion in predicting morbidity over the subsequent year, to inform programmatic approaches to PTLD screening in low-resource settings. Cohort data from urban Blantyre, Malawi were used to construct regression models for five morbidity outcomes (chronic respiratory symptoms or functional limitation, ongoing health seeking, spirometry decline, self-reported financial impact of TB disease, and death) in the year after PTB treatment, using three modelling approaches: logistic regression; penalised regression with pre-selected predictors; elastic net penalised regression using the full parent dataset. Predictors included demographic, clinical, symptom, spirometry and chest x-ray variables. The predictive performance of models were examined using the area under the receiver-operator curve (ROC AUC) values. Key predictors were identified, and their positive and negative predictive values (NPV) determined. The presence of respiratory symptoms at TB treatment completion was the strongest predictor of morbidity outcomes. TB survivors reporting breathlessness had higher odds of spirometry decline (aOR 20.5, 95%CI:3-199.1), health seeking (aOR 10.2, 2.4-50), and symptoms or functional limitation at 1-year (aOR 16.7, 3.3-133.4). Those reporting activity limitation were more likely to report symptoms or functional limitation at 1-year (aOR 4.2, 1.8-10.3), or severe financial impact of TB disease (aOR2.3, 1.0-5.0). Models were not significantly improved by including spirometry or imaging parameters. ROC AUCs were between 0.65-0.77 for the morbidity outcomes. Activity limitation at treatment completion had a NPV value of 78-98% for adverse outcomes. Our data suggest that whilst challenging to predict the development of post-TB morbidity, the use of symptom screening tools at TB treatment completion to prioritise post-TB care should be explored. We identified little benefit from the additional use of spirometry or CXR imaging.
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- 2024
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156. Evolutionary computation for adaptive quantum device design
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Mortimer, Luke, Estarellas, Marta P., Spiller, Timothy P., and D'Amico, Irene
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Quantum Physics - Abstract
As Noisy Intermediate-Scale Quantum (NISQ) devices grow in number of qubits, determining good or even adequate parameter configurations for a given application, or for device calibration, becomes a cumbersome task. An evolutionary algorithm is presented here which allows for the automatic tuning of the parameters of any arrangement of coupled qubits, to perform a given task with high fidelity. The algorithm's use is exemplified with the generation of schemes for the distribution of quantum states and the design of multi-qubit gates. The algorithm is demonstrated to converge very rapidly, yielding unforeseeable designs of quantum devices that perform their required tasks with excellent fidelities. Given these promising results, practical scalability and application versatility, the approach has the potential to become a powerful technique to aid the design and calibration of NISQ devices., Comment: 11 pages, 15 figures (including the Supporting Information, which has been included to the end of the paper)
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- 2020
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157. An Automated, Cost-Effective Optical System for Accelerated Anti-microbial Susceptibility Testing (AST) using Deep Learning
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Brown, Calvin, Tseng, Derek, Larkin, Paige M. K., Realegeno, Susan, Mortimer, Leanne, Subramonian, Arjun, Di Carlo, Dino, Garner, Omai B., and Ozcan, Aydogan
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Quantitative Biology - Quantitative Methods ,Physics - Applied Physics ,Physics - Instrumentation and Detectors ,Physics - Medical Physics - Abstract
Antimicrobial susceptibility testing (AST) is a standard clinical procedure used to quantify antimicrobial resistance (AMR). Currently, the gold standard method requires incubation for 18-24 h and subsequent inspection for growth by a trained medical technologist. We demonstrate an automated, cost-effective optical system that delivers early AST results, minimizing incubation time and eliminating human errors, while remaining compatible with standard phenotypic assay workflow. The system is composed of cost-effective components and eliminates the need for optomechanical scanning. A neural network processes the captured optical intensity information from an array of fiber optic cables to determine whether bacterial growth has occurred in each well of a 96-well microplate. When the system was blindly tested on isolates from 33 patients with Staphylococcus aureus infections, 95.03% of all the wells containing growth were correctly identified using our neural network, with an average of 5.72 h of incubation time required to identify growth. 90% of all wells (growth and no-growth) were correctly classified after 7 h, and 95% after 10.5 h. Our deep learning-based optical system met the FDA-defined criteria for essential and categorical agreements for all 14 antibiotics tested after an average of 6.13 h and 6.98 h, respectively. Furthermore, our system met the FDA criteria for major and very major error rates for 11 of 12 possible drugs after an average of 4.02 h, and 9 of 13 possible drugs after an average of 9.39 h, respectively. This system could enable faster, inexpensive, automated AST, especially in resource limited settings, helping to mitigate the rise of global AMR., Comment: 13 Pages, 6 Figures, 1 Table
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- 2020
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158. Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya
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Jennifer K Quint, Jonathan Fuld, Angela Obasi, Sean Semple, Ruaraidh Dobson, Kevin Mortimer, Maia Lesosky, Jeremiah Chakaya, Cindy M Gray, Graham Devereux, Richard Kiplimo, Fred Orina, Helen Meme, Evans Amukoye, Cressida Bowyer, Amos Ndombi, Sarah E West, and Lindsey Zurba
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Medicine ,Diseases of the respiratory system ,RC705-779 - Abstract
Background In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.Methods Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child’s immunisation booklet containing records of birth weight and serial weights in the first year.Results 2373 children participated, 52% girls, median age (IQR), 10 years (8–13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms ‘wheeze in the last 12 months’; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and ‘trouble breathing’ 3.18 (95% CI 2.27 to 4.45), p
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- 2023
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159. Profound and selective lymphopaenia in primary lymphatic anomaly patients demonstrates the significance of lymphatic-lymphocyte interactions
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Julian Pearce, Linda Hadcocks, Sahar Mansour, Malou van Zanten, Steve Jeffery, Kristiana Gordon, Pia Ostergaard, Peter Mortimer, and Derek C. Macallan
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lymphatic diseases ,lymphoedema ,lymphopaenia ,cellulitis ,lymphangiectasia ,lymphocyte subsets ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionThe lymphatic system has a pivotal role in immune homeostasis. To better understand this, we investigated the impact of Primary Lymphatic Anomalies (PLA) on lymphocyte numbers and phenotype.MethodsThe study comprised (i) a retrospective cohort: 177 PLA subjects from the National Primary Lymphatic Anomaly Register with clinical and laboratory data, and (ii) a prospective cohort: 28 patients with PLA and 20 healthy controls. Patients were subdivided using established phenotypic diagnostic categories and grouped into simplex (localised tissue involvement only) and systemic (involvement of central lymphatics). Further grouping variables included genital involvement and the likelihood of co-existent intestinal lymphangiectasia. Haematology laboratory parameters were analysed in both cohorts. In the prospective cohort, prospective blood samples were analysed by flow cytometry for markers of proliferation, differentiation, activation, skin-homing, and for regulatory (CD4+Foxp3+) T cells (Treg).ResultsIn patients with PLA, lymphopaenia was frequent (22% of subjects), affected primarily the CD4+ T cell subset, and was more severe in subjects with systemic versus simplex patterns of disease (36% vs 9% for lymphopaenia; 70% vs 33% for CD4+ cells). B cells, NK cells and monocytes were better conserved (except in GATA2 deficiency characterised by monocytopaenia). Genital oedema and likelihood of concomitant intestinal lymphangiectasia independently predicted CD4+ T cell depletion. Analysing CD4+ and CD8+ T cells by differentiation markers revealed disproportionate depletion of naïve cells, with a skewing towards a more differentiated effector profile. Systemic PLA conditions were associated with: increased expression of Ki67, indicative of recent cell division, in naïve CD4+, but not CD8+ T cells; increased levels of activation in CD4+, but not CD8+ T cells; and an increased proportion of Treg. Skin-homing marker (CCR10, CLA and CCR4) expression was reduced in some patients with simplex phenotypes.DiscussionPatients with PLA who have dysfunctional lymphatics have a selective reduction in circulating lymphocytes which preferentially depletes naïve CD4+ T cells. The presence of systemic disease, genital oedema, and intestinal lymphangiectasia independently predict CD4 lymphopaenia. The association of this depletion with immune activation and increased circulating Tregs suggests lymphatic-lymphocyte interactions and local inflammatory changes are pivotal in driving immunopathology.
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- 2023
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160. 233 Repolarizing M2 to M1 macrophages using chimeric antigen receptors (CAR) for solid tumors
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Rachel Morris, Michael Boyer, Michelle Townsend, Timothy Phares, Adam Blaszczak, Rachel Garlick, Kenneth Katschke, Gaju Shrestha, Ashlin Cowger, Taylor Brindley, McCall Jensen, Audrey Meade, Tony Mortimer, and Kim O’Neill
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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161. 635 A phase 1, first in human (FIH) study of autologous macrophages engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants (pts) with HER2 overexpressing solid tumors
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Yuan Yuan, Michael Klichinsky, Saar Gill, Melissa Johnson, Thomas Condamine, Jennifer Specht, Richard T Maziarz, Kim Reiss, Debora Barton, Daniel Cushing, Joanne Mortimer, Paula R Pohlmann, E Claire Dees, Naoto Ueno, Mathew Angelos, Ramona F Swaby, and Yara Abdou
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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162. Second-generation antipsychotics and metabolic syndrome: a role for mitochondria
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Katherine R. H. Mortimer, Mohammed Zia Ul Haq Katshu, and Lisa Chakrabarti
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antipsychotics ,psychosis ,mitochondria ,energy metabolism ,metabolic syndrome ,Psychiatry ,RC435-571 - Abstract
Psychosis is a known risk factor for developing metabolic syndrome (MetS). The risk is even greater in patients who are taking second-generation antipsychotics (SGAs). SGAs exacerbate metabolic abnormalities and lead to a 3-fold increased risk of severe weight gain, type 2 diabetes, and cardiovascular disease in patients. Mitochondrial dysfunction is a hallmark of MetS. Mitochondria process glucose and fatty acids into ATP. If these processes are impaired, it can result in dyslipidaemia, hyperglycaemia and an imbalance between nutrient input and energy output. This leads to increased adiposity, insulin resistance and atherosclerosis. It is unclear how SGAs induce MetS and how mitochondria might be involved in this process. It has been found that SGAs impair cellular glucose uptake in liver, dysregulating glucose and fatty acid metabolism which leads to an accumulation of glucose and/or lipids and an increase reactive oxygen species (ROS) which target mitochondrial proteins. This affects complexes of the electron transport chain (ETC) to reduce mitochondrial respiration. While there is a suggestion that SGAs may interact with a variety of processes that disrupt mitochondrial function, some of the results are conflicting, and a clear picture of how SGAs interact with mitochondria in different cell types has not yet emerged. Here, we outline the current evidence showing how SGAs may trigger mitochondrial dysfunction and lead to the development of MetS.
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- 2023
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163. Reprogramming sphingolipid glycosylation is required for endosymbiont persistence in Medicago truncatula.
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Moore, William M, Chan, Candace, Ishikawa, Toshiki, Rennie, Emilie A, Wipf, Heidi M-L, Benites, Veronica, Kawai-Yamada, Maki, Mortimer, Jenny C, and Scheller, Henrik V
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GIPC ,Medicago truncatula ,Rhizophagus irregularis ,Sinorhizobium meliloti ,glycosyltransferase ,sphingolipid ,symbiosis ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Developmental Biology - Abstract
Plant endosymbiosis relies on the development of specialized membranes that encapsulate the endosymbiont and facilitate nutrient exchange. However, the identity and function of lipids within these membrane interfaces is largely unknown. Here, we identify GLUCOSAMINE INOSITOL PHOSPHORYLCERAMIDE TRANSFERASE1 (GINT1) as a sphingolipid glycosyltransferase highly expressed in Medicago truncatula root nodules and roots colonized by arbuscular mycorrhizal (AM) fungi and further demonstrate that this enzyme functions in the synthesis of N-acetyl-glucosamine-decorated glycosyl inositol phosphoryl ceramides (GIPCs) in planta. MtGINT1 expression was developmentally regulated in symbiotic tissues associated with the development of symbiosome and periarbuscular membranes. RNAi silencing of MtGINT1 did not affect overall root growth but strongly impaired nodulation and AM symbiosis, resulting in the senescence of symbiosomes and arbuscules. Our results indicate that, although M. truncatula root sphingolipidome predominantly consists of hexose-decorated GIPCs, local reprogramming of GIPC glycosylation by MtGINT1 is required for the persistence of endosymbionts within the plant cell.
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- 2021
164. Metabolic syndrome risk components and mortality after triple‐negative breast cancer diagnosis in postmenopausal women in the Women's Health Initiative
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Yuan, Yuan, Pan, Kathy, Mortimer, Joanne, Chlebowski, Rowan T, Luo, Juhua, Yan, Jessica E, Yost, Susan E, Kroenke, Candyce H, Adams‐Campbell, Lucile, Nassir, Rami, Sun, Yangbo, Shadyab, Aladdin H, Vitolins, Mara Z, Saquib, Nazmus, Wild, Robert A, Manson, JoAnn E, and Nelson, Rebecca A
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Nutrition ,Aging ,Clinical Research ,Breast Cancer ,Cancer ,Prevention ,Good Health and Well Being ,Female ,Humans ,Metabolic Syndrome ,Postmenopause ,Risk Factors ,Triple Negative Breast Neoplasms ,Women's Health ,metabolic syndrome ,postmenopausal women ,risk factors ,triple-negative breast cancer ,Women's Health Initiative ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Public health - Abstract
BackgroundTriple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women's Health Initiative.MethodsFive hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status.ResultsOf the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components.ConclusionsPostmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death.
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- 2021
165. Sphingolipid biosynthesis modulates plasmodesmal ultrastructure and phloem unloading
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Yan, Dawei, Yadav, Shri, Paterlini, Andrea, Nicolas, William, Belevich, Ilya, Grison, Magali, Vaten, Anne, Karami, Leila, El-Showk, Sedeer, Lee, Jung-Youn, Murawska, Gosia, Mortimer, Jenny, Knoblauch, Michael, Jokitalo, Eija, Markham, Jonathan, Bayer, Emmanuelle, and Helariutta, Ykä
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Quantitative Biology - Subcellular Processes - Abstract
During phloem unloading, multiple cell-to-cell transport events move organic substances to the root meristem. Although the primary unloading event from the sieve elements to the phloem pole pericycle has been characterized to some extent, little is known about post-sieve element unloading. Here, we report a novel gene, PHLOEM UNLOADING MODULATOR (PLM), in the absence of which plasmodesmata-mediated symplastic transport through the phloem pole pericycle--endodermis interface is specifically enhanced. Increased unloading is attributable to a defect in the formation of the endoplasmic reticulum--plasma membrane tethers during plasmodesmal morphogenesis, resulting in the majority of pores lacking a visible cytoplasmic sleeve. PLM encodes a putative enzyme required for the biosynthesis of sphingolipids with very-long-chain fatty acid. Taken together, our results indicate that post-sieve element unloading involves sphingolipid metabolism, which affects plasmodesmal ultrastructure. They also raise the question of how and why plasmodesmata with no cytoplasmic sleeve facilitate molecular trafficking., Comment: Nature Plants, Nature Publishing Group, In press
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- 2019
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166. The Arabidopsis thaliana nucleotide sugar transporter GONST2 is a functional homolog of GONST1.
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Jing, Beibei, Ishikawa, Toshiki, Soltis, Nicole, Inada, Noriko, Liang, Yan, Murawska, Gosia, Fang, Lin, Andeberhan, Fekadu, Pidatala, Ramana, Yu, Xiaolan, Baidoo, Edward, Kawai-Yamada, Maki, Loque, Dominique, Kliebenstein, Daniel J, Dupree, Paul, and Mortimer, Jenny C
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Arabidopsis thaliana ,Botrytis cinerea ,GIPC ,Golovinomyces orontii ,cell wall ,sphingolipid ,transporter - Abstract
Glycosylinositolphosphorylceramides (GIPCs) are the predominant lipid in the outer leaflet of the plasma membrane. Characterized GIPC glycosylation mutants have severe or lethal plant phenotypes. However, the function of the glycosylation is unclear. Previously, we characterized Arabidopsis thaliana GONST1 and showed that it was a nucleotide sugar transporter which provides GDP-mannose for GIPC glycosylation. gonst1 has a severe growth phenotype, as well as a constitutive defense response. Here, we characterize a mutant in GONST1's closest homolog, GONST2. The gonst2-1 allele has a minor change to GIPC headgroup glycosylation. Like other reported GIPC glycosylation mutants, gonst1-1gonst2-1 has reduced cellulose, a cell wall polymer that is synthesized at the plasma membrane. The gonst2-1 allele has increased resistance to a biotrophic pathogen Golovinomyces orontii but not the necrotrophic pathogen Botrytis cinerea. Expression of GONST2 under the GONST1 promoter can rescue the gonst1 phenotype, indicating that GONST2 has a similar function to GONST1 in providing GDP-D-Man for GIPC mannosylation.
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- 2021
167. Nanotechnology to advance CRISPR-Cas genetic engineering of plants.
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Demirer, Gozde, Silva, Tallyta, Jackson, Christopher, Thomas, Jason, W Ehrhardt, David, Rhee, Seung, Landry, Markita, and Mortimer, Jennifer
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CRISPR-Cas Systems ,Gene Editing ,Genome ,Plant ,Nanotechnology ,Plants ,Genetically Modified - Abstract
CRISPR-Cas genetic engineering of plants holds tremendous potential for providing food security, battling biotic and abiotic crop stresses caused by climate change, and for environmental remediation and sustainability. Since the discovery of CRISPR-Cas technology, its usefulness has been demonstrated widely, including for genome editing in plants. Despite the revolutionary nature of genome-editing tools and the notable progress that these tools have enabled in plant genetic engineering, there remain many challenges for CRISPR applications in plant biotechnology. Nanomaterials could address some of the most critical challenges of CRISPR genome editing in plants through improvements in cargo delivery, species independence, germline transformation and gene editing efficiency. This Perspective identifies major barriers preventing CRISPR-mediated plant genetic engineering from reaching its full potential, and discusses ways that nanoparticle technologies can lower or eliminate these barriers. We also describe advances that are needed in nanotechnology to facilitate and accelerate plant genome editing. Timely advancement of the application of CRISPR technologies in plant engineering is crucial for our ability to feed and sustain the growing human population under a changing global climate.
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- 2021
168. Are Methanol-Derived Foliar Methyl Acetate Emissions a Tracer of Acetate-Mediated Drought Survival in Plants?
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Dewhirst, Rebecca A, Lei, Joseph, Afseth, Cassandra A, Castanha, Cristina, Wistrom, Christina M, Mortimer, Jenny C, and Jardine, Kolby J
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acetate fermentation ,acetylation ,biogenic ,methanol ,volatile organic compound - Abstract
Upregulation of acetate fermentation in plants has recently been described as an evolutionarily conserved drought survival strategy, with the amount of acetate produced directly correlating to survival. However, destructive measurements are required to evaluate acetate-linked drought responses, limiting the temporal and spatial scales that can be studied. Here, 13C-labeling studies with poplar (Populus trichocarpa) branches confirmed that methyl acetate is produced in plants from the acetate-linked acetylation of methanol. Methyl acetate emissions from detached leaves were strongly stimulated during desiccation, with total emissions decreasing with the leaf developmental stage. In addition, diurnal methyl acetate emissions from whole physiologically active poplar branches increased as a function of temperature, and light-dark transitions resulted in significant emission bursts lasting several hours. During experimental drought treatments of potted poplar saplings, light-dark methyl acetate emission bursts were eliminated while strong enhancements in methyl acetate emissions lasting > 6 days were observed with their initiation coinciding with the suppression of transpiration and photosynthesis. The results suggest that methyl acetate emissions represent a novel non-invasive tracer of acetate-mediated temperature and drought survival response in plants. The findings may have important implications for the future understanding of acetate-mediated drought responses to transcription, cellular metabolism, and hormone signaling, as well as its associated changes in carbon cycling and water use from individual plants to whole ecosystems.
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- 2021
169. Neuroprotective actions of a fatty acid nitroalkene in Parkinson’s disease
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Roberto Di Maio, Matthew T. Keeney, Veronika Cechova, Amanda Mortimer, Ahssan Sekandari, Pascal Rowart, J. Timothy Greenamyre, Bruce A. Freeman, and Marco Fazzari
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract To date there are no therapeutic strategies that limit the progression of Parkinson’s disease (PD). The mechanisms underlying PD-related nigrostriatal neurodegeneration remain incompletely understood, with multiple factors modulating the course of PD pathogenesis. This includes Nrf2-dependent gene expression, oxidative stress, α-synuclein pathology, mitochondrial dysfunction, and neuroinflammation. In vitro and sub-acute in vivo rotenone rat models of PD were used to evaluate the neuroprotective potential of a clinically-safe, multi-target metabolic and inflammatory modulator, the electrophilic fatty acid nitroalkene 10-nitro-oleic acid (10-NO2-OA). In N27-A dopaminergic cells and in the substantia nigra pars compacta of rats, 10-NO2-OA activated Nrf2-regulated gene expression and inhibited NOX2 and LRRK2 hyperactivation, oxidative stress, microglial activation, α-synuclein modification, and downstream mitochondrial import impairment. These data reveal broad neuroprotective actions of 10-NO2-OA in a sub-acute model of PD and motivate more chronic studies in rodents and primates.
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- 2023
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170. GLORIA - A globally representative hyperspectral in situ dataset for optical sensing of water quality
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Moritz K. Lehmann, Daniela Gurlin, Nima Pahlevan, Krista Alikas, Ted Conroy, Janet Anstee, Sundarabalan V. Balasubramanian, Cláudio C. F. Barbosa, Caren Binding, Astrid Bracher, Mariano Bresciani, Ashley Burtner, Zhigang Cao, Arnold G. Dekker, Courtney Di Vittorio, Nathan Drayson, Reagan M. Errera, Virginia Fernandez, Dariusz Ficek, Cédric G. Fichot, Peter Gege, Claudia Giardino, Anatoly A. Gitelson, Steven R. Greb, Hayden Henderson, Hiroto Higa, Abolfazl Irani Rahaghi, Cédric Jamet, Dalin Jiang, Thomas Jordan, Kersti Kangro, Jeremy A. Kravitz, Arne S. Kristoffersen, Raphael Kudela, Lin Li, Martin Ligi, Hubert Loisel, Steven Lohrenz, Ronghua Ma, Daniel A. Maciel, Tim J. Malthus, Bunkei Matsushita, Mark Matthews, Camille Minaudo, Deepak R. Mishra, Sachidananda Mishra, Tim Moore, Wesley J. Moses, Hà Nguyễn, Evlyn M. L. M. Novo, Stéfani Novoa, Daniel Odermatt, David M. O’Donnell, Leif G. Olmanson, Michael Ondrusek, Natascha Oppelt, Sylvain Ouillon, Waterloo Pereira Filho, Stefan Plattner, Antonio Ruiz Verdú, Salem I. Salem, John F. Schalles, Stefan G. H. Simis, Eko Siswanto, Brandon Smith, Ian Somlai-Schweiger, Mariana A. Soppa, Evangelos Spyrakos, Elinor Tessin, Hendrik J. van der Woerd, Andrea Vander Woude, Ryan A. Vandermeulen, Vincent Vantrepotte, Marcel R. Wernand, Mortimer Werther, Kyana Young, and Linwei Yue
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Science - Abstract
Abstract The development of algorithms for remote sensing of water quality (RSWQ) requires a large amount of in situ data to account for the bio-geo-optical diversity of inland and coastal waters. The GLObal Reflectance community dataset for Imaging and optical sensing of Aquatic environments (GLORIA) includes 7,572 curated hyperspectral remote sensing reflectance measurements at 1 nm intervals within the 350 to 900 nm wavelength range. In addition, at least one co-located water quality measurement of chlorophyll a, total suspended solids, absorption by dissolved substances, and Secchi depth, is provided. The data were contributed by researchers affiliated with 59 institutions worldwide and come from 450 different water bodies, making GLORIA the de-facto state of knowledge of in situ coastal and inland aquatic optical diversity. Each measurement is documented with comprehensive methodological details, allowing users to evaluate fitness-for-purpose, and providing a reference for practitioners planning similar measurements. We provide open and free access to this dataset with the goal of enabling scientific and technological advancement towards operational regional and global RSWQ monitoring.
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- 2023
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171. Implementing spatially and temporally varying snow densities into the GlobSnow snow water equivalent retrieval
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P. Venäläinen, K. Luojus, C. Mortimer, J. Lemmetyinen, J. Pulliainen, M. Takala, M. Moisander, and L. Zschenderlein
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Environmental sciences ,GE1-350 ,Geology ,QE1-996.5 - Abstract
Snow water equivalent (SWE) is a valuable characteristic of snow cover, and it can be estimated using passive spaceborne radiometer measurements. The radiometer-based GlobSnow SWE retrieval methodology, which assimilates weather station snow depth observations into the retrieval, has improved the reliability and accuracy of SWE retrieval when compared to stand-alone radiometer SWE retrievals. To further improve the GlobSnow SWE retrieval methodology, we investigate implementing spatially and temporally varying snow densities into the retrieval procedure. Thus far, the GlobSnow SWE retrieval has used a constant snow density throughout the retrieval despite differing locations, snow depth, or time of winter. This constant snow density is a known source of inaccuracy in the retrieval. Four different versions of spatially and temporally varying snow densities are tested over a 10-year period (2000–2009). These versions use two different spatial interpolation techniques: ordinary Kriging interpolation and inverse distance weighted regression (IDWR). All versions were found to improve the SWE retrieval compared to the baseline GlobSnow v3.0 product, although differences between versions are small. Overall, the best results were obtained by implementing IDWR-interpolated densities into the algorithm, which reduced RMSE (root mean square error) and MAE (mean absolute error) by about 4 mm (8 % improvement) and 5 mm (16 % improvement) when compared to the baseline GlobSnow product, respectively. Furthermore, implementing varying snow densities into the SWE retrieval improves the magnitude and seasonal evolution of the Northern Hemisphere snow mass estimate compared to the baseline product and a product post-processed with varying snow densities.
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- 2023
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172. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update
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Mark L. Levy, Leonard B. Bacharier, Eric Bateman, Louis-Philippe Boulet, Chris Brightling, Roland Buhl, Guy Brusselle, Alvaro A. Cruz, Jeffrey M. Drazen, Liesbeth Duijts, Louise Fleming, Hiromasa Inoue, Fanny W. S. Ko, Jerry A. Krishnan, Kevin Mortimer, Paulo M. Pitrez, Aziz Sheikh, Arzu Yorgancıoğlu, and Helen K. Reddel
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Diseases of the respiratory system ,RC705-779 - Abstract
Abstract The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with “mild” asthma) as combination ICS–formoterol taken as needed for symptom relief. For patients with moderate–severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS–formoterol. Asthma treatment is not “one size fits all”; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.
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- 2023
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173. Efficacy of mindfulness and goal setting interventions for increasing resilience and reducing smoking in lower socio-economic groups: randomised controlled trial protocol
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Reece De Zylva, Elissa Mortimer, Emma Miller, George Tsourtos, Sharon Lawn, Carlene Wilson, Jonathan Karnon, Richard Woodman, and Paul Ward
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Smoking cessation ,Socioeconomic status ,RCT ,Resilience ,Mindfulness ,Goal setting ,Medicine (General) ,R5-920 ,Social pathology. Social and public welfare. Criminology ,HV1-9960 - Abstract
Abstract Background Smoking and resulting health problems disproportionately impact low socioeconomic status (SES) individuals. Building resilience presents an approach to ‘closing the gap’. Mindfulness-based interventions and setting realistic goals are preferred in low socioeconomic communities. We aim to test if these interventions, delivered online and consolidated with peer support offered via ex-smokers, are successful in promoting smoking cessation and resilience. Our conceptualisation of resilience encompasses the inner capacity/skills and external resources (e.g., social support) which smokers utilise to bounce back from adversity. We include a process evaluation of barriers/facilitators to interventions and cost-effectiveness analysis (from health system perspective). Methods We plan a four-arm parallel 12-month RCT with a 6-month follow-up to test the efficacy of three group-based interventions each followed by peer support. Arm 1: mindfulness-integrated cognitive behavioural therapy; Arm 2: mindfulness training; Arm 3: setting realistic goals; Arm 4: active control group directed to quit services. All interventions will be administered online. Participants are adult smokers in Australia (N = 812) who have an average weekly household income less than $457AUD or receive welfare benefits. Group-based interventions will occur over 6 months, followed by 6 months of forum-based peer support. Primary outcome: self-reported 14-day period prevalence of smoking abstinence at 6 months, with remote biochemical verification of saliva cotinine (
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- 2023
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174. Molecular Mechanisms of Nanomaterial-Bacterial Interactions Revealed by Omics—The Role of Nanomaterial Effect Level
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Mortimer, Monika, Wang, Ying, and Holden, Patricia A
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Biomedical and Clinical Sciences ,Engineering ,Medical Biochemistry and Metabolomics ,Medical Biotechnology ,Nanotechnology ,Bioengineering ,Biotechnology ,2.2 Factors relating to the physical environment ,Aetiology ,Infection ,engineered nanomaterials ,bacteria ,pathways ,transcriptomic ,proteomic ,metabolomic ,Other Biological Sciences ,Biomedical Engineering ,Industrial biotechnology ,Medical biotechnology ,Biomedical engineering - Abstract
Nanotechnology is employed across a wide range of antibacterial applications in clinical settings, food, pharmaceutical and textile industries, water treatment and consumer goods. Depending on type and concentration, engineered nanomaterials (ENMs) can also benefit bacteria in myriad contexts including within the human body, in biotechnology, environmental bioremediation, wastewater treatment, and agriculture. However, to realize the full potential of nanotechnology across broad applications, it is necessary to understand conditions and mechanisms of detrimental or beneficial effects of ENMs to bacteria. To study ENM effects, bacterial population growth or viability are commonly assessed. However, such endpoints alone may be insufficiently sensitive to fully probe ENM effects on bacterial physiology. To reveal more thoroughly how bacteria respond to ENMs, molecular-level omics methods such as transcriptomics, proteomics, and metabolomics are required. Because omics methods are increasingly utilized, a body of literature exists from which to synthesize state-of-the-art knowledge. Here we review relevant literature regarding ENM impacts on bacterial cellular pathways obtained by transcriptomic, proteomic, and metabolomic analyses across three growth and viability effect levels: inhibitory, sub-inhibitory or stimulatory. As indicated by our analysis, a wider range of pathways are affected in bacteria at sub-inhibitory vs. inhibitory ENM effect levels, underscoring the importance of ENM exposure concentration in elucidating ENM mechanisms of action and interpreting omics results. In addition, challenges and future research directions of applying omics approaches in studying bacterial-ENM interactions are discussed.
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- 2021
175. Vision, challenges and opportunities for a Plant Cell Atlas
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Ahmed, Jahed, Alaba, Oluwafemi, Ameen, Gazala, Arora, Vaishali, Arteaga-Vazquez, Mario A, Arun, Alok, Bailey-Serres, Julia, Bartley, Laura E, Bassel, George W, Bergmann, Dominique C, Bertolini, Edoardo, Bhati, Kaushal Kumar, Blanco-Touriñán, Noel, Briggs, Steven P, Brumos, Javier, Buer, Benjamin, Burlaocot, Adrien, Cervantes-Pérez, Sergio Alan, Chen, Sixue, Contreras-Moreira, Bruno, CORPAS, Francisco J, Cruz-Ramirez, Alfredo, Cuevas-Velazquez, Cesar L, Cuperus, Josh T, David, Lisa I, de Folter, Stefan, Denolf, Peter H, Ding, Pingtao, Dwyer, William P, Evans, Matthew MS, George, Nancy, Handakumbura, Pubudu P, Harrison, Maria J, Haswell, Elizabeth S, Herath, Venura, Jiao, Yuling, Jinkerson, Robert E, John, Uwe, Joshi, Sanjay, Joshi, Abhishek, Joubert, Lydia-Marie, Katam, Ramesh, Kaur, Harmanpreet, Kazachkova, Yana, Raju, Sunil K Kenchanmane, Khan, Mather A, Khangura, Rajdeep, Kumar, Ajay, Kumar, Arun, Kumar, Pankaj, Kumar, Pradeep, Lavania, Dhruv, Lew, Tedrick Thomas Salim, Lewsey, Mathew G, Lin, Chien-Yuan, Liu, Dianyi, Liu, Le, Liu, Tie, Lokdarshi, Ansul, Luong, Ai My, Macaulay, Iain C, Mahmud, Sakil, Mähönen, Ari Pekka, Malukani, Kamal Kumar, Marand, Alexandre P, Martin, Carly A, McWhite, Claire D, Mehta, Devang, Martín, Miguel Miñambres, Mortimer, Jenny C, Nikolov, Lachezar A, Nobori, Tatsuya, Nolan, Trevor M, Ogden, Aaron J, Otegui, Marisa S, Ott, Mark-Christoph, Palma, José M, Paul, Puneet, Rehman, Atique U, Romera-Branchat, Maida, Romero, Luis C, Roth, Ronelle, Sah, Saroj K, Shahan, Rachel, Solanki, Shyam, Song, Bao-Hua, Sozzani, Rosangela, Stacey, Gary, Stepanova, Anna N, Taylor, Nicolas L, Tello-Ruiz, Marcela K, Tran, Tuan M, Tripathi, Rajiv Kumar, Vadde, Batthula Vijaya Lakshmi Vadde, Varga, Tamas, Vidovic, Marija, Walley, Justin W, Wang, Zhiyong, Weizbauer, Renate A, and Whelan, James
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Plant Biology ,Biological Sciences ,Agriculture ,Chlamydomonas reinhardtii ,Chloroplasts ,Computational Biology ,Image Processing ,Computer-Assisted ,Plant Cells ,Plant Development ,Plants ,Zea mays ,Plant Cell Atlas Consortium ,4D imaging ,A. thaliana ,Plant Cell Atlas ,cell biology ,chlamydomonas reinhardtii ,location-to-function ,maize ,science forum ,single-cell omics ,translational research ,Biochemistry and Cell Biology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.
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- 2021
176. The TaCslA12 gene expressed in the wheat grain endosperm synthesizes wheat-like mannan when expressed in yeast and Arabidopsis.
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Verhertbruggen, Yves, Bouder, Axelle, Vigouroux, Jacqueline, Alvarado, Camille, Geairon, Audrey, Guillon, Fabienne, Wilkinson, Mark D, Stritt, Fabian, Pauly, Markus, Lee, Mi Yeon, Mortimer, Jenny C, Scheller, Henrik V, Mitchell, Rowan AC, Voiniciuc, Cătălin, Saulnier, Luc, and Chateigner-Boutin, Anne-Laure
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Saccharomyces cerevisiae ,Plants ,Genetically Modified ,Arabidopsis ,Triticum ,Tobacco ,Mannans ,Genes ,Plant ,Endosperm ,Edible Grain ,Cell walls ,Developing endosperm ,Heterologous expression ,Mannan ,Wheat grain ,Plant Biology ,Crop and Pasture Production ,Plant Biology & Botany - Abstract
Mannan is a class of cell wall polysaccharides widespread in the plant kingdom. Mannan structure and properties vary according to species and organ. The cell walls of cereal grains have been extensively studied due to their role in cereal processing and to their beneficial effect on human health as dietary fiber. Recently, we showed that mannan in wheat (Triticum aestivum) grain endosperm has a linear structure of β-1,4-linked mannose residues. The aim of this work was to study the biosynthesis and function of wheat grain mannan. We showed that mannan is deposited in the endosperm early during grain development, and we identified candidate mannan biosynthetic genes expressed in the endosperm. The functional study in wheat was unsuccessful therefore our best candidate genes were expressed in heterologous systems. The endosperm-specificTaCslA12 gene expressed in Pichia pastoris and in an Arabidopsis thaliana mutant depleted in glucomannan led to the production of wheat-like linear mannan lacking glucose residues and with moderate acetylation. Therefore, this gene encodes a mannan synthase and is likely responsible for the synthesis of wheat endosperm mannan.
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- 2021
177. Biophysical analysis of the plant-specific GIPC sphingolipids reveals multiple modes of membrane regulation
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Cassim, Adiilah Mamode, Navon, Yotam, Gao, Yu, Decossas, Marion, Fouillen, Laetitia, Grélard, Axelle, Nagano, Minoru, Lambert, Olivier, Bahammou, Delphine, Van Delft, Pierre, Maneta-Peyret, Lilly, Simon-Plas, Françoise, Heux, Laurent, Jean, Bruno, Fragneto, Giovanna, Mortimer, Jenny C, Deleu, Magali, Lins, Laurence, and Mongrand, Sébastien
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Biochemistry and Cell Biology ,Chemical Sciences ,Biological Sciences ,Biophysics ,Cell Membrane ,Plants ,Polysaccharides ,Species Specificity ,Sphingolipids ,GIPC ,Langmuir monolayer ,cryo-EM ,modeling ,neutron reflectivity ,phytosterol ,plasma membrane ,solid-state NMR ,sphingolipids ,ζ-potential ,Medical and Health Sciences ,Biochemistry & Molecular Biology ,Biological sciences ,Biomedical and clinical sciences ,Chemical sciences - Abstract
The plant plasma membrane (PM) is an essential barrier between the cell and the external environment, controlling signal perception and transmission. It consists of an asymmetrical lipid bilayer made up of three different lipid classes: sphingolipids, sterols, and phospholipids. The glycosyl inositol phosphoryl ceramides (GIPCs), representing up to 40% of total sphingolipids, are assumed to be almost exclusively in the outer leaflet of the PM. However, their biological role and properties are poorly defined. In this study, we investigated the role of GIPCs in membrane organization. Because GIPCs are not commercially available, we developed a protocol to extract and isolate GIPC-enriched fractions from eudicots (cauliflower and tobacco) and monocots (leek and rice). Lipidomic analysis confirmed the presence of trihydroxylated long chain bases and 2-hydroxylated very long-chain fatty acids up to 26 carbon atoms. The glycan head groups of the GIPCs from monocots and dicots were analyzed by gas chromatograph-mass spectrometry, revealing different sugar moieties. Multiple biophysics tools, namely Langmuir monolayer, ζ-Potential, light scattering, neutron reflectivity, solid state 2H-NMR, and molecular modeling, were used to investigate the physical properties of the GIPCs, as well as their interaction with free and conjugated phytosterols. We showed that GIPCs increase the thickness and electronegativity of model membranes, interact differentially with the different phytosterols species, and regulate the gel-to-fluid phase transition during temperature variations. These results unveil the multiple roles played by GIPCs in the plant PM.
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- 2021
178. Biophysical analysis of the plant-specific GIPC sphingolipids reveals multiple modes of membrane regulation.
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Mamode Cassim, Adiilah, Navon, Yotam, Gao, Yu, Decossas, Marion, Fouillen, Laetitia, Grélard, Axelle, Nagano, Minoru, Lambert, Olivier, Bahammou, Delphine, Van Delft, Pierre, Maneta-Peyret, Lilly, Simon-Plas, Françoise, Heux, Laurent, Jean, Bruno, Fragneto, Giovanna, Mortimer, Jenny C, Deleu, Magali, Lins, Laurence, and Mongrand, Sébastien
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Cell Membrane ,Plants ,Polysaccharides ,Sphingolipids ,Biophysics ,Species Specificity ,GIPC ,Langmuir monolayer ,cryo-EM ,modeling ,neutron reflectivity ,phytosterol ,plasma membrane ,solid-state NMR ,sphingolipids ,ζ-potential ,Biochemistry & Molecular Biology ,Chemical Sciences ,Biological Sciences ,Medical and Health Sciences - Abstract
The plant plasma membrane (PM) is an essential barrier between the cell and the external environment, controlling signal perception and transmission. It consists of an asymmetrical lipid bilayer made up of three different lipid classes: sphingolipids, sterols, and phospholipids. The glycosyl inositol phosphoryl ceramides (GIPCs), representing up to 40% of total sphingolipids, are assumed to be almost exclusively in the outer leaflet of the PM. However, their biological role and properties are poorly defined. In this study, we investigated the role of GIPCs in membrane organization. Because GIPCs are not commercially available, we developed a protocol to extract and isolate GIPC-enriched fractions from eudicots (cauliflower and tobacco) and monocots (leek and rice). Lipidomic analysis confirmed the presence of trihydroxylated long chain bases and 2-hydroxylated very long-chain fatty acids up to 26 carbon atoms. The glycan head groups of the GIPCs from monocots and dicots were analyzed by gas chromatograph-mass spectrometry, revealing different sugar moieties. Multiple biophysics tools, namely Langmuir monolayer, ζ-Potential, light scattering, neutron reflectivity, solid state 2H-NMR, and molecular modeling, were used to investigate the physical properties of the GIPCs, as well as their interaction with free and conjugated phytosterols. We showed that GIPCs increase the thickness and electronegativity of model membranes, interact differentially with the different phytosterols species, and regulate the gel-to-fluid phase transition during temperature variations. These results unveil the multiple roles played by GIPCs in the plant PM.
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- 2021
179. Investigating the Effectiveness of Anonymous Online Peer Feedback in Translation Technology Teaching
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Sha, Lu, Wang, Xiangling, Ma, Shuya, and Mortimer, Thomas Anthony
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Online peer feedback has been regarded as an effective way to promote collaborative learning in the teaching of translation technology. But there is limited research about decreasing the negative influence of social factors such as peer pressure, favouritism, and face-saving in the process. Therefore, the present study examined the effects of anonymous online peer feedback (AOPF) on students' translation performance, feedback quality, self-efficacy and perceptions in translation technology teaching. A total of 60 Chinese postgraduate students from a translation technology training course participated in this study, and they were then randomly assigned into either the anonymous or identified group. Results indicated that AOPF was a practical approach to improving translation performance. The content analysis showed that the anonymous group provided more cognitive and metacognitive feedback messages in terms of feedback quality. In addition, students in the anonymous group felt more comfortable giving in-depth suggestions for peer work. However, there was no significant difference in affective feedback messages between the two groups. Furthermore, results from the questionnaires revealed that anonymity in online peer feedback could improve the students' self-efficacy and learning satisfaction. These findings can give insights for trainers to facilitate practical peer assessment activities in translation technology training.
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- 2022
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180. Teacher Self-Perception as a Pedagogical STEM Content Expert and Its Influence on Classroom Practice
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Mortimer, Emily
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Providing a positive atmosphere for growth in STEM can elevate female middle school students towards seeing themselves succeeding even through short-term failures and cognitive dissonance. Yet, through negative gendered discourses, females can be easily persuaded against the challenging curriculum of STEM and move down a path of least resistance. A teacher confident in their content and proficient in their pedagogy is one that can provide a role model showing students how to push forward even when things get complicated. This study aims to understand how female middle school teachers in a mid-western American city self-identify as pedagogical content experts in STEM and how their identities influence their practices in the classroom. Grounded in the theoretical framework of poststructural feminism, this study works to uncover how teachers consistently navigate and transcend the gendered cultural norms that impact how they identify as pedagogical STEM content experts. The case study methodology was used to study the gendered discourses, with four cases representing one female middle school teacher. Upon completion of each case analysis, case and cross-case analyses were used to identify the tension and juxtaposition between cases. Upon analysis, the most noteworthy takeaway from this study was the continued presence of gendered norms and contradictions towards self-identifying as an expert. Highlighting the teacher's gendered and socially displaced role, the terms expert and teacher continued to be viewed as opposing identities. Numerous times, each participant described expertise in both content and pedagogy but refused to self-identify as a pedagogical STEM content expert in the interviews, focus groups, or writings. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
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- 2022
181. Identifying transcription factors that reduce wood recalcitrance and improve enzymatic degradation of xylem cell wall in Populus.
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Hori, Chiaki, Takata, Naoki, Lam, Pui Ying, Tobimatsu, Yuki, Nagano, Soichiro, Mortimer, Jenny C, and Cullen, Dan
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Cell Wall ,Populus ,Plant Proteins ,Transcription Factors ,Gene Expression Regulation ,Enzymologic ,Gene Expression Regulation ,Plant ,Wood ,Gene Expression Regulation ,Enzymologic ,Plant - Abstract
Developing an efficient deconstruction step of woody biomass for biorefinery has been drawing considerable attention since its xylem cell walls display highly recalcitrance nature. Here, we explored transcriptional factors (TFs) that reduce wood recalcitrance and improve saccharification efficiency in Populus species. First, 33 TF genes up-regulated during poplar wood formation were selected as potential regulators of xylem cell wall structure. The transgenic hybrid aspens (Populus tremula × Populus tremuloides) overexpressing each selected TF gene were screened for in vitro enzymatic saccharification. Of these, four transgenic seedlings overexpressing previously uncharacterized TF genes increased total glucan hydrolysis on average compared to control. The best performing lines overexpressing Pt × tERF123 and Pt × tZHD14 were further grown to form mature xylem in the greenhouse. Notably, the xylem cell walls exhibited significantly increased total xylan hydrolysis as well as initial hydrolysis rates of glucan. The increased saccharification of Pt × tERF123-overexpressing lines could reflect the improved balance of cell wall components, i.e., high cellulose and low xylan and lignin content, which could be caused by upregulation of cellulose synthase genes upon the expression of Pt × tERF123. Overall, we successfully identified Pt × tERF123 and Pt × tZHD14 as effective targets for reducing cell wall recalcitrance and improving the enzymatic degradation of woody plant biomass.
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- 2020
182. Variation in sugarcane biomass composition and enzymatic saccharification of leaves, internodes and roots.
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Mason, Patrick J, Furtado, Agnelo, Marquardt, Annelie, Hodgson-Kratky, Katrina, Hoang, Nam V, Botha, Frederik C, Papa, Gabriella, Mortimer, Jenny C, Simmons, Blake, and Henry, Robert J
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Carbon partitioning ,Cell wall ,Compositional analysis ,Soluble sugars ,Sugarcane ,Sugarcane (saccharum spp ,hybrids) ,Chemical Engineering ,Industrial Biotechnology - Abstract
BackgroundThe composition of biomass determines its suitability for different applications within a biorefinery system. The proportion of the major biomass fractions (sugar, cellulose, hemicellulose and lignin) may vary in different sugarcane genotypes and growth environments and different parts of the plant. This study investigated the composition of mature and immature internodes, roots and mature leaves of sugarcane.ResultsInternodes were found to have a significantly larger alcohol-soluble component than leaves and roots. The primary difference between the immature and mature internodes was the ratio of soluble sugars. In mature tissues, sucrose content was significantly higher, whereas in immature internodal tissues there was lower sucrose and heightened concentrations of reducing sugars. Carbon (C) partitioning in leaf tissues was characterised by low levels of soluble components and high "other" and cell wall fractions. Root tissue had low ratios of soluble fractions relative to their cell wall contents, indicating a lack of storage of soluble carbon. There was no significant difference in the ratio of the major cell wall fractions between the major organ types. Characterisation of individual non-cellulosic monomers indicated leaf and root tissues had significantly higher arabinose and galactose fractions. Significantly larger proportions of syringyl lignin compounds and the hydroxycinnamic compound, p-coumaric acid were observed in mature internodal tissues compared to the other tissue types. Tissue-specific differences in composition were shown to greatly affect the recalcitrance of the cell wall to enzymatic saccharification.ConclusionsOverall, this study displayed clear evidence of the differential partitioning of C throughout the sugarcane plant in specific organs. These organ-specific differences have major implications in their utility as a bioproduct feedstock. For example, the inclusion of trash (leaves) with the culms (internodes) may alter processing efficiency.
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- 2020
183. Agrobacterium-mediated transient transformation of sorghum leaves for accelerating functional genomics and genome editing studies
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Sharma, Rita, Liang, Yan, Lee, Mi Yeon, Pidatala, Venkataramana R, Mortimer, Jenny C, and Scheller, Henrik V
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Biomedical and Clinical Sciences ,Biotechnology ,Genetics ,Generic health relevance ,Agrobacterium tumefaciens ,CRISPR-Cas Systems ,Gene Editing ,Genome ,Plant ,Genomics ,Green Fluorescent Proteins ,Plant Leaves ,Plants ,Genetically Modified ,Protoplasts ,RNA ,Guide ,CRISPR-Cas Systems ,Reproducibility of Results ,Sorghum ,Nicotiana ,Transformation ,Genetic ,Agrobacterium ,CRISPR ,sgRNA ,Transformation ,Transient ,Biochemistry and Cell Biology ,Other Medical and Health Sciences ,Bioinformatics ,Biomedical and clinical sciences - Abstract
ObjectivesSorghum is one of the most recalcitrant species for transformation. Considering the time and effort required for stable transformation in sorghum, establishing a transient system to screen the efficiency and full functionality of vector constructs is highly desirable.ResultsHere, we report an Agrobacterium-mediated transient transformation assay with intact sorghum leaves using green fluorescent protein as marker. It also provides a good monocot alternative to tobacco and protoplast assays with a direct, native and more reliable system for testing single guide RNA (sgRNA) expression construct efficiency. Given the simplicity and ease of transformation, high reproducibility, and ability to test large constructs, this method can be widely adopted to speed up functional genomic and genome editing studies.
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- 2020
184. A grass-specific cellulose-xylan interaction dominates in sorghum secondary cell walls.
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Gao, Yu, Lipton, Andrew S, Wittmer, Yuuki, Murray, Dylan T, and Mortimer, Jenny C
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Cell Wall ,Arabidopsis ,Sorghum ,Plant Stems ,Carbon Isotopes ,Cellulose ,Xylans ,Nuclear Magnetic Resonance ,Biomolecular ,Species Specificity ,Models ,Biological ,Xylem ,Models ,Biological ,Nuclear Magnetic Resonance ,Biomolecular - Abstract
Sorghum (Sorghum bicolor L. Moench) is a promising source of lignocellulosic biomass for the production of renewable fuels and chemicals, as well as for forage. Understanding secondary cell wall architecture is key to understanding recalcitrance i.e. identifying features which prevent the efficient conversion of complex biomass to simple carbon units. Here, we use multi-dimensional magic angle spinning solid-state NMR to characterize the sorghum secondary cell wall. We show that xylan is mainly in a three-fold screw conformation due to dense arabinosyl substitutions, with close proximity to cellulose. We also show that sorghum secondary cell walls present a high ratio of amorphous to crystalline cellulose as compared to dicots. We propose a model of sorghum cell wall architecture which is dominated by interactions between three-fold screw xylan and amorphous cellulose. This work will aid the design of low-recalcitrance biomass crops, a requirement for a sustainable bioeconomy.
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- 2020
185. No evidence for transient transformation via pollen magnetofection in several monocot species.
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Vejlupkova, Zuzana, Warman, Cedar, Sharma, Rita, Scheller, Henrik Vibe, Mortimer, Jenny C, and Fowler, John E
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Plants ,Genetically Modified ,Pollen ,Magnetite Nanoparticles ,Gene Editing ,Plants ,Genetically Modified - Published
- 2020
186. Evaluation of frameworks proposed as protective of antimicrobial resistance propagation in the environment
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Mortimer, Monika, Winchell, Alyssa, and Holden, Patricia A
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Environmental Sciences ,Pollution and Contamination ,Antimicrobial Resistance ,Anti-Bacterial Agents ,Drug Resistance ,Bacterial ,Environmental Monitoring ,Humans ,Risk Assessment ,Rivers ,United States ,Water Pollutants ,Chemical ,Antimicrobial resistance ,Surface waters ,PNEC ,Antibiotic concentrations ,Environment ,Human health - Abstract
Antimicrobial resistance (AMR) in the environment is a globally concerning issue. This study sought to improve the understanding of human health risks from an environmental AMR proliferation perspective. Surface water concentrations of 11 most used antibiotics in the United States were simulated for the Columbia and Sacramento River watersheds using the Pharmaceutical Assessment and Transport Evaluation (PhATE) model. The predicted environmental concentrations (PECs) and literature-reported measured environmental concentrations (MECs) of antibiotics were compared to the predicted no effect concentrations (PNECs) of three frameworks proposed as protective of AMR selection. For all of the studied antibiotics, PECs (except for moxifloxacin, a 4th generation fluoroquinolone), and at least one published MEC, were above the safe limit proposed by at least one of the three frameworks. The results indicate that a variety of different antibiotics with different mechanisms of action and physico-chemical properties are likely in environmental compartments at or above the concentrations currently proposed as safe from an AMR proliferation perspective. Understanding environmental occurrence of antibiotics is important for assessing environmental exposures and, when compared to PNECs for resistance selection, can-either alone or in combination with other methods- more specifically indicate where there are potential risks of AMR proliferation.
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- 2020
187. Erythematous capillary-lymphatic malformations mimicking blood vascular anomalies
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René Hägerling, Malou Van Zanten, Rose Yinghan Behncke, Sascha Ulferts, Nils R. Hansmeier, Bruno Märkl, Christian Witzel, Bernard Ho, Vaughan Keeley, Katie Riches, Sahar Mansour, Kristiana Gordon, Pia Ostergaard, and Peter S. Mortimer
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Angiogenesis ,Cell biology ,Medicine - Abstract
Superficial erythematous cutaneous vascular malformations are assumed to be blood vascular in origin, but cutaneous lymphatic malformations can contain blood and appear red. Management may be different and so an accurate diagnosis is important. Cutaneous malformations were investigated through 2D histology and 3D whole-mount histology. Two lesions were clinically considered as port-wine birthmarks and another 3 lesions as erythematous telangiectasias. The aims were (i) to demonstrate that cutaneous erythematous malformations including telangiectasia can represent a lymphatic phenotype, (ii) to determine if lesions represent expanded but otherwise normal or malformed lymphatics, and (iii) to determine if the presence of erythrocytes explained the red color. Microscopy revealed all lesions as lymphatic structures. Port-wine birthmarks proved to be cystic lesions, with nonuniform lymphatic marker expression and a disconnected lymphatic network suggesting a lymphatic malformation. Erythematous telangiectasias represented expanded but nonmalformed lymphatics. Blood within lymphatics appeared to explain the color. Blood-lymphatic shunts could be detected in the erythematous telangiectasia. In conclusion, erythematous cutaneous capillary lesions may be lymphatic in origin but clinically indistinguishable from blood vascular malformations. Biopsy is advised for correct phenotyping and management. Erythrocytes are the likely explanation for color accessing lymphatics through lympho-venous shunts.
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- 2023
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188. Improving the lives of ethnically diverse family carers and people living with dementia using digital media resources – Protocol for the Draw-Care randomised controlled trial
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Antonia Thodis, Thu-Ha Dang, Josefine Antoniades, Andrew S. Gilbert, Tuan Nguyen, Danijela Hlis, Mary Gurgone, Briony Dow, Claudia Cooper, Lily-Dongxia Xiao, Nilmini Wickramasinghe, Nalika Ulapane, Mathew Varghese, Santosh Loganathan, Joanne Enticott, Duncan Mortimer, and Bianca Brijnath
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Objectives Ethnically diverse family carers of people living with dementia (hereafter carers and people with dementia) experience more psychological distress than other carers. To reduce this inequality, culturally adapted, multilingual, evidence-based practical assistance is needed. This paper details the Draw-Care study protocol including a randomised control trial (RCT) to test the effectiveness of a digital intervention comprising a multilingual website, virtual assistant, animated films, and information, on the lives of carers and people with dementia in Australia. Methods The Draw-Care intervention will be evaluated in a 12-week active waitlist parallel design RCT with 194 carers from Arabic, Cantonese, Greek, Hindi, Italian, Mandarin, Spanish, Tamil, and Vietnamese-speaking language groups. Our intervention was based on the World Health Organization's (WHO) iSupport Lite online carer support messages and was co-designed with carers, people with dementia, service providers, and clinicians. Culturally adapted multilingual digital resources were created in nine languages and English. Results In Phase I (2022), six co-design workshops with stakeholders and interviews with people with dementia informed the development of the intervention which will be trialled and evaluated in Phases II and III (2023 and 2024). Conclusions Digital media content is a novel approach to providing cost-effective access to health care information. This study protocol details the three study phases including the RCT of a co-designed, culturally adapted, multilingual, digital intervention for carers and people with dementia to advance the evidence in dementia and digital healthcare research and help meet the needs of carers and people with dementia in Australia and globally.
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- 2023
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189. Inflammation-related proteins as biomarkers of treatment-related behavioral symptoms: A longitudinal study of breast cancer patients and age-matched controls
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Sunita K. Patel, Elizabeth C. Breen, I. Benjamin Paz, Laura Kruper, Joanne Mortimer, F. Lennie Wong, Smita Bhatia, Michael R. Irwin, and Carolyn E. Behrendt
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Behavioral symptoms in breast cancer (BC) survivors have been attributed to cancer treatment and resulting inflammation. However, studies linking behavioral symptoms to BC treatment have observed patients only after some treatment. Our prospective study with pre-treatment baseline investigates post-treatment changes in inflammation-related biomarkers and whether those changes correlate with changes in symptoms. Methods: Participants were postmenopausal women, newly-diagnosed with stage 0–3 BC before any treatment (n = 173 “patients”), and age-matched women without cancer (n = 77 “controls”), who were assessed on plasma markers [soluble tumor necrosis factor receptor type 2 (sTNF-RII), interleukin (IL)-6, IL-1 receptor antagonist (IL-1RA), C-reactive protein (CRP)]) and symptoms (Physical Functioning, Pain, Attention/concentration, Perceived Cognitive Problems, Fatigue, Sleep Insufficiency, Depression). Participants were assessed again 1 month, 1 year, and 2 years after completing primary treatment or similar interval in controls. Generalized linear mixed models tested 4 treatments (surgery alone or with chemotherapy, radiation, or both) for association with change per marker. Joint models tested change per marker for association with change per symptom. Models considered demographic, socioeconomic, and clinical covariates. False Discovery Rate method controlled risk of error from multiple hypotheses. Results: At one month post-completion of treatment, sTNF-RII and IL-6 were elevated by all BC treatments, as were IL-1RA and CRP after surgery alone (all, p
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- 2023
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190. Insights into the mechanisms involved in the fungal degradation of plastics
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Eyalira Jacob Okal, Gui Heng, Ephie A. Magige, Sehroon Khan, Shixi Wu, Zhiqiang Ge, Tianfu Zhang, Peter E. Mortimer, and Jianchu Xu
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Plastic biodegradation ,Pre-treatment ,Enzyme hydrolysis ,Prooxidants ,Molecular mechanisms ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
Fungi are considered among the most efficient microbial degraders of plastics, as they produce salient enzymes and can survive on recalcitrant compounds with limited nutrients. In recent years, studies have reported numerous species of fungi that can degrade different types of plastics, yet there remain many gaps in our understanding of the processes involved in biodegradation. In addition, many unknowns need to be resolved regarding the fungal enzymes responsible for plastic fragmentation and the regulatory mechanisms which fungi use to hydrolyse, assimilate and mineralize synthetic plastics. This review aims to detail the main methods used in plastic hydrolysis by fungi, key enzymatic and molecular mechanisms, chemical agents that enhance the enzymatic breakdown of plastics, and viable industrial applications. Considering that polymers such as lignin, bioplastics, phenolics, and other petroleum-based compounds exhibit closely related characteristics in terms of hydrophobicity and structure, and are degraded by similar fungal enzymes as plastics, we have reasoned that genes that have been reported to regulate the biodegradation of these compounds or their homologs could equally be involved in the regulation of plastic degrading enzymes in fungi. Thus, this review highlights and provides insight into some of the most likely regulatory mechanisms by which fungi degrade plastics, target enzymes, genes, and transcription factors involved in the process, as well as key limitations to industrial upscaling of plastic biodegradation and biological approaches that can be employed to overcome these challenges.
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- 2023
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191. A Review of Teachers and Teaching On Stage and On Screen
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Amy Mortimer
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pedagogues ,identity ,artistic representation ,Arts in general ,NX1-820 - Abstract
This piece is a review of Teachers and Teaching on Stage and on Screen: Dramatic Depictions, edited by Diane Conrad and Monica Prendergast (2019). Mortimer’s personal poetic response opens the review to honour her artistic ways of knowing and responding to the content. The book’s contributing authors, all educators, provide diverse cultural, social, and socio-economic perspectives and insights into how teachers and teaching are represented in film and on stage. Conrad and Prendergast’s book invites a range of audiences (from pre-service teachers to academics) to reflect on dramatic depictions of teachers and to use them to deepen understandings of the complexities of teaching, schooling, and students—and, if readers are teachers themselves, to examine their own practice.
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- 2023
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192. Mycobacterium abscessus skin and soft tissue infection following autologous fat grafting in Kurdistan treated with an antibiotic combination including Imipenem-Relebactam and Rifabutin
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Alison J. Beech, Sharon E. Weinberg, Alice E. Mortimer, Fiona Lynch, James Bedford, and Giorgio Calisti
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Mycobacterium abscessus ,Rapid growing mycobacterium ,Cosmetic tourism ,Imipenem-relebactam ,Rifabutin ,Multi-drug resistance ,Diseases of the respiratory system ,RC705-779 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Medical tourism is becoming increasingly popular. The most popularly sought operations are cosmetic procedures. With the increase in cosmetic tourism, it is unsurprising that there has also been a rise in skin and soft tissue infections caused by nontuberculous mycobacteria (NTM); in particular by the rapidly growing mycobacteria species.Here we provide a case of a 35 year-old woman who presented after autologous fat grafting with multiple painful, violaceous, and purulent nodules on her arms, legs, and breasts. Infection was found to be due to Mycobacterium abscessus. She was successfully treated with azithromycin, clofazimine, rifabutin, amikacin, imipenem-cilastatin-relebactam (Recarbrio™) and imipenem-cilastatin. This is the first described case of a M. abscessus infection successfully treated using this combination.
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- 2023
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193. Supply Cost and Life-Cycle Greenhouse Gas Footprint of Dry and Ensiled Biomass Sorghum for Biofuel Production
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Baral, Nawa Raj, Dahlberg, Jeff, Putnam, Daniel, Mortimer, Jenny C, and Scown, Corinne D
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Chemical Engineering ,Analytical Chemistry ,Engineering ,Chemical Sciences ,Responsible Consumption and Production ,bioenergy ,silage ,sorghum ,biomass ,technoeconomic analysis ,life-cycle assessment ,greenhouse gas emissions ,Environmental Science and Management ,Analytical chemistry ,Chemical engineering - Abstract
Biomass sorghum is a promising feedstock for cellulosic biorefineries because of its high yield and drought tolerance. However, the difficulty of effectively drying sorghum in some regions means that it may require different handling than previously studied grassy feedstocks. This study compares the delivered cost and life-cycle greenhouse gas (GHG) footprint of field drying and baling, module storage (wrapped, densely packed biomass), pelletizing, and ensiling. Ensiling has not been widely considered for use in bioenergy production. For farms within 66 km of the biorefinery, ensiled biomass is of the lowest cost and GHG strategy despite additional cost and energy demand for hauling wet biomass. Field drying and baling, if feasible, is the most cost-effective option for sorghum between 66 km and 104 km, beyond which pellets are preferable. A 2000 bone-dry-metric ton (bdt)/day biorefinery can source sorghum with 18 bdt/ha yield cultivated on 5% of surrounding land at costs ranging from $122 (silage) to $167 (pellets)/bdt and a life-cycle GHG footprint of 111 (silage) to 179 kg CO2e/bdt (pellets). With 28 bdt/ha biomass yield, 10% cultivation of surrounding land, and low fertilizer application, costs can range from $66 (silage) to $85 (pellets)/ bdt and GHG footprint of 43 (silage) to 96 kg CO2e (pellets)/bdt.
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- 2020
194. Impact of abiotic stress on the regulation of cell wall biosynthesis in Populus trichocarpa
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Hori, Chiaki, Yu, Xiang, Mortimer, Jenny C, Sano, Ryosuke, Matsumoto, Tomoko, Kikuchi, Jun, Demura, Taku, and Ohtani, Misato
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Plant Biology ,Biological Sciences ,Genetics ,abiotic stress ,monolignol biosynthesis ,poplar ,secondary cell wall ,Biotechnology - Abstract
Growth of biomass for lignocellulosic biofuels and biomaterials may take place on land unsuitable for foods, meaning the biomass plants are exposed to increased abiotic stresses. Thus, the understanding how this affects biomass composition and quality is important for downstream bioprocessing. Here, we analyzed the effect of drought and salt stress on cell wall biosynthesis in young shoots and xylem tissues of Populus trichocarpa using transcriptomic and biochemical methods. Following exposure to abiotic stress, stem tissues reduced vessel sizes, and young shoots increased xylem formation. Compositional analyses revealed a reduction in the total amount of cell wall polysaccharides. In contrast, the total lignin amount was unchanged, while the ratio of S/G lignin was significantly decreased in young shoots. Consistent with these observations, transcriptome analyses show that the expression of a subset of cell wall-related genes is tightly regulated by drought and salt stresses. In particular, the expression of a part of genes encoding key enzymes for S-lignin biosynthesis, caffeic acid O-methyltransferase and ferulate 5-hydroxylase, was decreased, suggesting the lower S/G ratio could be partly attributed to the down-regulation of these genes. Together, our data identifies a transcriptional abiotic stress response strategy in poplar, which results in adaptive changes to the plant cell wall.
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- 2020
195. Understanding the effects of Covid-19 through a life course lens
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Settersten, Richard A, Bernardi, Laura, Härkönen, Juho, Antonucci, Toni C, Dykstra, Pearl A, Heckhausen, Jutta, Kuh, Diana, Mayer, Karl Ulrich, Moen, Phyllis, Mortimer, Jeylan T, Mulder, Clara H, Smeeding, Timothy M, van der Lippe, Tanja, Hagestad, Gunhild O, Kohli, Martin, Levy, René, Schoon, Ingrid, and Thomson, Elizabeth
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Human Society ,Demography ,Behavioral and Social Science ,Good Health and Well Being ,coronavirus disease 2019 ,life transitions ,life trajectories ,life domains ,age ,generation ,cohort ,social change ,social inequality ,Sociology - Abstract
The Covid-19 pandemic is shaking fundamental assumptions about the human life course in societies around the world. In this essay, we draw on our collective expertise to illustrate how a life course perspective can make critical contributions to understanding the pandemic's effects on individuals, families, and populations. We explore the pandemic's implications for the organization and experience of life transitions and trajectories within and across central domains: health, personal control and planning, social relationships and family, education, work and careers, and migration and mobility. We consider both the life course implications of being infected by the Covid-19 virus or attached to someone who has; and being affected by the pandemic's social, economic, cultural, and psychological consequences. It is our goal to offer some programmatic observations on which life course research and policies can build as the pandemic's short- and long-term consequences unfold.
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- 2020
196. Pneumonia and Exposure to Household Air Pollution in Children Under the Age of 5 Years in Rural Malawi Findings From the Cooking and Pneumonia Study
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Mortimer, Kevin, Lesosky, Maia, Semple, Sean, Malava, Jullita, Katundu, Cynthia, Crampin, Amelia, Wang, Duolao, Weston, William, Pope, Dan, Havens, Deborah, Gordon, Stephen B, and Balmes, John
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Pneumonia ,Prevention ,Climate-Related Exposures and Conditions ,Clinical Research ,Pneumonia & Influenza ,Pediatric ,Clinical Trials and Supportive Activities ,Health Effects of Indoor Air Pollution ,Lung ,Health Effects of Household Energy Combustion ,Aetiology ,2.2 Factors relating to the physical environment ,Respiratory ,Age Factors ,Air Pollution ,Indoor ,Carbon Monoxide ,Child ,Preschool ,Cluster Analysis ,Cooking ,Female ,Humans ,Incidence ,Infant ,Malawi ,Male ,Particulate Matter ,Rural Health ,cookstove ,household air pollution ,pneumonia ,Clinical Sciences ,Respiratory System - Abstract
BackgroundExposure to household air pollution is associated with an increased risk of pneumonia in children in low- and middle-income countries; however, exposure-response data are limited, and there are uncertainties around the extent to which biomass-fueled cookstoves can reduce these exposures.Research questionWhat is the association between exposure to household air pollution and pneumonia in children under the age of 5 years in rural Malawi and what are the effects of a biomass-fueled cookstove intervention on personal exposure to household air pollution?Study design and methodsWe measured personal exposure to carbon monoxide (CO; 48 hours of continuous measurement and transcutaneous carboxyhemoglobin) every 6 months in children who participated in a cluster-randomized controlled trial of a cleaner burning biomass-fueled cookstove intervention to prevent pneumonia in children under the age of 5 years in rural Malawi (the Cooking And Pneumonia Study). Exposure-response and multivariable analyses were done.ResultsWe recruited 1805 (928 intervention; 877 control) children (mean age, 25.6 months; 50.6% female). We found no evidence of an association between exposure to CO (incident rate ratio, 1.0; 95% CI, 0.967 to 1.014; P = .53) or carboxyhemoglobin (incident rate ratio, 1.00; 95% CI, 0.993 to 1.003; P = .41) in children who experienced pneumonia vs those who did not. Median exposure to CO in the intervention and control groups was was 0.34 (interquartile range, 0.15 to 0.81) and 0.37 parts per million (interquartile range, 0.15 toa 0.97), respectively. The group difference in means was 0.46 (95% CI, -0.95 to 0.012; P = .06).InterpretationExposure to CO in our population was low with no association seen between exposure to CO and pneumonia incidence and no effect of the Cooking And Pneumonia Study intervention on these exposures. These findings suggest that CO may not be an appropriate measure of household air pollution exposure in settings such as rural Malawi and that there is a need to develop ways to measure particulate matter exposures directly in young children instead.Clinical trial registrationISRCTN59448623.
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- 2020
197. Do Cell Wall Esters Facilitate Forest Response to Climate?
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Dewhirst, Rebecca A, Mortimer, Jenny C, and Jardine, Kolby J
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Plant Biology ,Biological Sciences ,Climate Action ,Atmosphere ,Carbon Dioxide ,Cell Wall ,Climate Change ,Ecosystem ,Esters ,Forests ,Ecology ,Crop and Pasture Production ,Plant Biology & Botany ,Plant biology - Abstract
Terrestrial ecosystem dynamics are strongly modified by stresses associated with climate change, impacting plant growth and development, mortality, and ecological succession. Here we highlight the potential role of plant cell wall esters to link changes in cell wall structure and function with biosphere-atmosphere fluxes of methanol, acetic acid, carbon dioxide (CO2), and water (H2O).
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- 2020
198. Use of HER2-Directed Therapy in Metastatic Breast Cancer and How Community Physicians Collaborate to Improve Care.
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Mortimer, Joanne, Kruper, Laura, Cianfrocca, Mary, Lavasani, Sayeh, Liu, Sariah, Tank-Patel, Niki, Sedrak, Mina, Smith, Wade, Stewart, Daphne, Waisman, James, Yeon, Christina, Wang, Tina, and Yuan, Yuan
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HER2-directed therapy ,breast cancer ,community ,research - Abstract
The development of new HER2-directed therapies has resulted in a significant prolongation of survival for women with metastatic HER2-positive breast cancer. Discoveries in the laboratory inform clinical trials which are the basis for improving the standard of care and are also the backbone for quality improvement. Clinical trials can be completed more rapidly by expanding trial enrollment to community sites. In this article we review some of the challenges in treating metastatic breast cancer with HER2-directed therapies and our strategies for incorporating our community partners into the research network.
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- 2020
199. Synthesis and Function of Complex Sphingolipid Glycosylation.
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Mortimer, Jenny C and Scheller, Henrik Vibe
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GIPC ,glycosylinositol phosphorylceramide ,phytoglycolipid ,plasma membrane ,Ecology ,Plant Biology ,Crop and Pasture Production ,Plant Biology & Botany - Abstract
Glycosylinositol phosphorylceramides (GIPCs) constitute an important class of plasma-membrane lipids in plants. The complex glycan headgroups of GIPCs vary between plant species and tissues. Recent studies have shown that the structure of the glycan headgroup is important for plant development, abiotic stress tolerance, and interactions with pathogenic and symbiotic microorganisms.
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- 2020
200. Accumulation of high-value bioproducts in planta can improve the economics of advanced biofuels
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Yang, Minliang, Baral, Nawa Raj, Simmons, Blake A, Mortimer, Jenny C, Shih, Patrick M, and Scown, Corinne D
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Biological Sciences ,Industrial Biotechnology ,Biofuels ,Biomass ,Costs and Cost Analysis ,Crops ,Agricultural ,in planta accumulation ,bioproduct ,technoeconomic analysis ,bioenergy crop ,biofuel - Abstract
Coproduction of high-value bioproducts at biorefineries is a key factor in making biofuels more cost-competitive. One strategy for generating coproducts is to directly engineer bioenergy crops to accumulate bioproducts in planta that can be fractionated and recovered at biorefineries. Here, we develop quantitative insights into the relationship between bioproduct market value and target accumulation rates by investigating a set of industrially relevant compounds already extracted from plant sources with a wide range of market prices and applications, including $100/kg (artemisinin). These compounds are used to identify a range of mass fraction thresholds required to achieve net economic benefits for biorefineries and the additional amounts needed to reach a target $2.50/gal biofuel selling price, using cellulosic ethanol production as a test case. Bioproduct market prices and recovery costs determine the accumulation threshold; we find that moderate- to high-value compounds (i.e., cannabidiol and artemisinin) offer net economic benefits at accumulation rates of just 0.01% dry weight (dwt) to 0.02 dwt%. Lower-value compounds, including limonene, latex, and PHB, require at least an order-of-magnitude greater accumulation to overcome additional extraction and recovery costs (0.3 to 1.2 dwt%). We also find that a diversified approach is critical. For example, global artemisinin demand could be met with fewer than 10 biorefineries, while global demand for latex is equivalent to nearly 180 facilities. Our results provide a roadmap for future plant metabolic engineering efforts aimed at increasing the value derived from bioenergy crops.
- Published
- 2020
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