@article{haverroth_gobble_bradley_harris-gilliam_fischer_williams_long_sozzani_2024, title={The Black American experience: Answering the global challenge of broadening participation in STEM/agriculture}, volume={1}, ISSN={["1532-298X"]}, url={https://doi.org/10.1093/plcell/koae002}, DOI={10.1093/plcell/koae002}, journal={PLANT CELL}, author={Haverroth, Eduardo and Gobble, Mariah and Bradley, Latosha and Harris-Gilliam, Kailyn and Fischer, Alicia and Williams, Cranos and Long, Terri and Sozzani, Rosangela}, year={2024}, month={Jan} }
 @article{schmittling_muhammad_haque_long_williams_2023, title={Cellular clarity: a logistic regression approach to identify root epidermal regulators of iron deficiency response}, volume={24}, ISSN={["1471-2164"]}, DOI={10.1186/s12864-023-09714-6}, abstractNote={Abstract
                Background
                Plants respond to stress through highly tuned regulatory networks. While prior works identified master regulators of iron deficiency responses in A. thaliana from whole-root data, identifying regulators that act at the cellular level is critical to a more comprehensive understanding of iron homeostasis. Within the root epidermis complex molecular mechanisms that facilitate iron reduction and uptake from the rhizosphere are known to be regulated by bHLH transcriptional regulators. However, many questions remain about the regulatory mechanisms that control these responses, and how they may integrate with developmental processes within the epidermis. Here, we use transcriptional profiling to gain insight into root epidermis-specific regulatory processes.
              
                Results
                Set comparisons of differentially expressed genes (DEGs) between whole root and epidermis transcript measurements identified differences in magnitude and timing of organ-level vs. epidermis-specific responses. Utilizing a unique sampling method combined with a mutual information metric across time-lagged and non-time-lagged windows, we identified relationships between clusters of functionally relevant differentially expressed genes suggesting that developmental regulatory processes may act upstream of well-known Fe-specific responses. By integrating static data (DNA motif information) with time-series transcriptomic data and employing machine learning approaches, specifically logistic regression models with LASSO, we also identified putative motifs that served as crucial features for predicting differentially expressed genes. Twenty-eight transcription factors (TFs) known to bind to these motifs were not differentially expressed, indicating that these TFs may be regulated post-transcriptionally or post-translationally. Notably, many of these TFs also play a role in root development and general stress response.
              
                Conclusions
                This work uncovered key differences in -Fe response identified using whole root data vs. cell-specific root epidermal data. Machine learning approaches combined with additional static data identified putative regulators of -Fe response that would not have been identified solely through transcriptomic profiles and reveal how developmental and general stress responses within the epidermis may act upstream of more specialized -Fe responses for Fe uptake.
              }, number={1}, journal={BMC GENOMICS}, author={Schmittling, Selene R. and Muhammad, Durreshahwar and Haque, Samiul and Long, Terri A. and Williams, Cranos M.}, year={2023}, month={Oct} }
 @article{choi_hyeon_lee_long_hwang_hwang_2022, title={BTS Is a Negative Regulator for the Cellular Energy Level and the Expression of Energy Metabolism-Related Genes Encoded by Two Organellar Genomes in Leaf Tissues}, volume={4}, ISSN={["0219-1032"]}, url={https://doi.org/10.14348/molcells.2022.2029}, DOI={10.14348/molcells.2022.2029}, abstractNote={E3 ligase BRUTUS (BTS), a putative iron sensor, is expressed in both root and shoot tissues in seedlings of Arabidopsis thaliana. The role of BTS in root tissues has been well established. However, its role in shoot tissues has been scarcely studied. Comparative transcriptome analysis with shoot and root tissues revealed that BTS is involved in regulating energy metabolism by modulating expression of mitochondrial and chloroplast genes in shoot tissues. Moreover, in shoot tissues of bts-1 plants, levels of ADP and ATP and the ratio of ADP/ATP were greatly increased with a concomitant decrease in levels of soluble sugar and starch. The decreased starch level in bts-1 shoot tissues was restored to the level of shoot tissues of wild-type plants upon vanadate treatment. Through this study, we expand the role of BTS to regulation of energy metabolism in the shoot in addition to its role of iron deficiency response in roots.}, journal={MOLECULES AND CELLS}, publisher={Korean Society for Molecular and Cellular Biology}, author={Choi, Bongsoo and Hyeon, Do Young and Lee, Juhun and Long, Terri A. and Hwang, Daehee and Hwang, Inhwan}, year={2022}, month={Apr} }
 @article{muhammad_clark_haque_williams_sozzani_long_2022, title={POPEYE intercellular localization mediates cell-specific iron deficiency responses}, volume={8}, ISSN={["1532-2548"]}, url={https://doi.org/10.1093/plphys/kiac357}, DOI={10.1093/plphys/kiac357}, abstractNote={Abstract
               Plants must tightly regulate iron (Fe) sensing, acquisition, transport, mobilization, and storage to ensure sufficient levels of this essential micronutrient. POPEYE (PYE) is an iron responsive transcription factor that positively regulates the iron deficiency response, while also repressing genes essential for maintaining iron homeostasis. However, little is known about how PYE plays such contradictory roles. Under iron-deficient conditions, pPYE:GFP accumulates in the root pericycle while pPYE:PYE–GFP is localized to the nucleus in all Arabidopsis (Arabidopsis thaliana) root cells, suggesting that PYE may have cell-specific dynamics and functions. Using scanning fluorescence correlation spectroscopy and cell-specific promoters, we found that PYE–GFP moves between different cells and that the tendency for movement corresponds with transcript abundance. While localization to the cortex, endodermis, and vasculature is required to manage changes in iron availability, vasculature and endodermis localization of PYE–GFP protein exacerbated pye-1 defects and elicited a host of transcriptional changes that are detrimental to iron mobilization. Our findings indicate that PYE acts as a positive regulator of iron deficiency response by regulating iron bioavailability differentially across cells, which may trigger iron uptake from the surrounding rhizosphere and impact root energy metabolism.}, journal={PLANT PHYSIOLOGY}, publisher={Oxford University Press (OUP)}, author={Muhammad, DurreShahwar and Clark, Natalie M. and Haque, Samiul and Williams, Cranos M. and Sozzani, Rosangela and Long, Terri A.}, year={2022}, month={Aug} }
 @article{broeck_spurney_fisher_schwartz_clark_nguyen_madison_gobble_long_sozzani_2021, title={A hybrid model connecting regulatory interactions with stem cell divisions in the root}, volume={2}, url={https://doi.org/10.1017/qpb.2021.1}, DOI={10.1017/qpb.2021.1}, abstractNote={Abstract
	  Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.}, journal={Quantitative Plant Biology}, publisher={Cambridge University Press (CUP)}, author={Broeck, Lisa Van and Spurney, Ryan J. and Fisher, Adam P. and Schwartz, Michael and Clark, Natalie M. and Nguyen, Thomas T. and Madison, Imani and Gobble, Mariah and Long, Terri and Sozzani, Rosangela}, year={2021} }
 @article{friesner_colon-carmona_schnoes_stepanova_mason_macintosh_ullah_baxter_callis_sierra-cajas_et al._2021, title={Broadening the impact of plant science through innovative, integrative, and inclusive outreach}, volume={5}, ISSN={["2475-4455"]}, url={http://dx.doi.org/10.1002/pld3.316}, DOI={10.1002/pld3.316}, abstractNote={AbstractPopulation growth and climate change will impact food security and potentially exacerbate the environmental toll that agriculture has taken on our planet. These existential concerns demand that a passionate, interdisciplinary, and diverse community of plant science professionals is trained during the 21st century. Furthermore, societal trends that question the importance of science and expert knowledge highlight the need to better communicate the value of rigorous fundamental scientific exploration. Engaging students and the general public in the wonder of plants, and science in general, requires renewed efforts that take advantage of advances in technology and new models of funding and knowledge dissemination. In November 2018, funded by the National Science Foundation through the Arabidopsis Research and Training for the 21st century (ART 21) research coordination network, a symposium and workshop were held that included a diverse panel of students, scientists, educators, and administrators from across the US. The purpose of the workshop was to re‐envision how outreach programs are funded, evaluated, acknowledged, and shared within the plant science community. One key objective was to generate a roadmap for future efforts. We hope that this document will serve as such, by providing a comprehensive resource for students and young faculty interested in developing effective outreach programs. We also anticipate that this document will guide the formation of community partnerships to scale up currently successful outreach programs, and lead to the design of future programs that effectively engage with a more diverse student body and citizenry.}, number={4}, journal={PLANT DIRECT}, publisher={Wiley}, author={Friesner, Joanna and Colon-Carmona, Adan and Schnoes, Alexandra M. and Stepanova, Anna and Mason, Grace Alex and Macintosh, Gustavo C. and Ullah, Hemayat and Baxter, Ivan and Callis, Judy and Sierra-Cajas, Kimberly and et al.}, year={2021}, month={Apr} }
 @misc{hodgens_akpa_long_2021, title={Solving the puzzle of Fe homeostasis by integrating molecular, mathematical, and societal models}, volume={64}, ISSN={["1879-0356"]}, url={https://doi.org/10.1016/j.pbi.2021.102149}, DOI={10.1016/j.pbi.2021.102149}, abstractNote={To ensure optimal utilization and bioavailability, iron uptake, transport, subcellular localization, and assimilation are tightly regulated in plants. Herein, we examine recent advances in our understanding of cellular responses to Fe deficiency. We then use intracellular mechanisms of Fe homeostasis to discuss how formalizing cell biology knowledge via a mathematical model can advance discovery even when quantitative data is limited. Using simulation-based inference to identify plausible systems mechanisms that conform to known emergent phenotypes can yield novel, testable hypotheses to guide targeted experiments. However, this approach relies on the accurate encoding of domain-expert knowledge in exploratory mathematical models. We argue that this would be facilitated by fostering more "systems thinking" life scientists and that diversifying your research team may be a practical path to achieve that goal.}, journal={CURRENT OPINION IN PLANT BIOLOGY}, publisher={Elsevier BV}, author={Hodgens, Charles and Akpa, Belinda S. and Long, Terri A.}, year={2021}, month={Dec} }
 @inbook{buckner_madison_melvin_long_sozzani_williams_2020, title={BioVision Tracker: A semi-automated image analysis software for spatiotemporal gene expression tracking in Arabidopsis thaliana}, volume={160}, ISBN={9780128215333}, ISSN={0091-679X}, url={http://dx.doi.org/10.1016/bs.mcb.2020.04.017}, DOI={10.1016/bs.mcb.2020.04.017}, abstractNote={Fluorescence microscopy can produce large quantities of data that reveal the spatiotemporal behavior of gene expression at the cellular level in plants. Automated or semi-automated image analysis methods are required to extract data from these images. These data are helpful in revealing spatial and/or temporal-dependent processes that influence development in the meristematic region of plant roots. Tracking spatiotemporal gene expression in the meristem requires the processing of multiple microscopy imaging channels (one channel used to image root geometry which serves as a reference for relating locations within the root, and one or more channels used to image fluorescent gene expression signals). Many automated image analysis methods rely on the staining of cell walls with fluorescent dyes to capture cellular geometry and overall root geometry. However, in long time-course imaging experiments, dyes may fade which hinders spatial assessment in image analysis. Here, we describe a procedure for analyzing 3D microscopy images to track spatiotemporal gene expression signals using the MATLAB-based BioVision Tracker software. This software requires either a fluorescence image or a brightfield image to analyze root geometry and a fluorescence image to capture and track temporal changes in gene expression.}, booktitle={Methods in Cell Biology}, publisher={Elsevier}, author={Buckner, Eli and Madison, Imani and Melvin, Charles and Long, Terri and Sozzani, Rosangela and Williams, Cranos}, year={2020}, pages={419–436} }
 @article{tong_madison_long_williams_2020, title={Computational solutions for modeling and controlling plant response to abiotic stresses: a review with focus on iron deficiency}, volume={57}, url={https://doi.org/10.1016/j.pbi.2020.05.006}, DOI={10.1016/j.pbi.2020.05.006}, abstractNote={Computational solutions enable plant scientists to model protein-mediated stress responses and characterize novel gene functions that coordinate responses to a variety of abiotic stress conditions. Recently, density functional theory was used to study proteins active sites and elucidate enzyme conversion mechanisms involved in iron deficiency responsive signaling pathways. Computational approaches for protein homology modeling and the kinetic modeling of signaling pathways have also resolved the identity and function in proteins involved in iron deficiency signaling pathways. Significant changes in gene relationships under other stress conditions, such as heat or drought stress, have been recently identified using differential network analysis, suggesting that stress tolerance is achieved through asynchronous control. Moreover, the increasing development and use of statistical modeling and systematic modeling of transcriptomic data have provided significant insight into the gene regulatory mechanisms associated with abiotic stress responses. These types of in silico approaches have facilitated the plant science community's future goals of developing multi-scale models of responses to iron deficiency stress and other abiotic stress conditions.}, journal={Current Opinion in Plant Biology}, publisher={Elsevier BV}, author={Tong, Haonan and Madison, Imani and Long, Terri A and Williams, Cranos M}, year={2020}, month={Oct}, pages={8–15} }
 @article{broeck_spurney_fisher_schwartz_clark_nguyen_madison_gobble_long_sozzani_2020, title={Exchange of molecular and cellular information: a hybrid model that integrates stem cell divisions and key regulatory interactions}, url={https://doi.org/10.1101/2020.11.30.404426}, DOI={10.1101/2020.11.30.404426}, abstractNote={AbstractStem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WOX5 and SHR, regulate divisions in the root stem cell niche (SCN). However, how these proteins coordinately function to establish systemic behavior is not well understood. We propose a non-cell autonomous role for WOX5 in the CEI and identify a regulator, AN3/GIF1, that coordinates CEI divisions. Here we show with a multiscale hybrid model integrating ODEs and agent-based modeling that QC and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behavior, which led us to predict cell-type-specific expression dynamics of SHR, SCR, WOX5, AN3, and CYCD6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.Thumbnail image}, author={Broeck, Lisa Van and Spurney, Ryan J. and Fisher, Adam P. and Schwartz, Michael and Clark, Natalie M. and Nguyen, Thomas T. and Madison, Imani and Gobble, Mariah and Long, Terri and Sozzani, Rosangela}, year={2020}, month={Dec} }
 @article{herlihy_long_mcdowell_2020, title={Iron homeostasis and plant immune responses: Recent insights and translational implications}, volume={295}, url={https://doi.org/10.1074/jbc.REV120.010856}, DOI={10.1074/jbc.REV120.010856}, abstractNote={Iron metabolism and the plant immune system are both critical for plant vigor in natural ecosystems and for reliable agricultural productivity. Mechanistic studies of plant iron home-ostasis and plant immunity have traditionally been carried out in isolation from each other; however, our growing understanding of both processes has uncovered significant connections. For example, iron plays a critical role in the generation of reactive oxygen intermediates during immunity and has been recently implicated as a critical factor for immune-initiated cell death via ferroptosis. Moreover, plant iron stress triggers immune activation, suggesting that sensing of iron depletion is a mechanism by which plants recognize a pathogen threat. The iron deficiency response engages hormone signaling sectors that are also utilized for plant immune signaling, providing a probable explanation for iron-immunity cross-talk. Finally, interference with iron acquisition by pathogens might be a critical component of the immune response. Efforts to address the global burden of iron deficiency–related anemia have focused on classical breeding and transgenic approaches to develop crops biofortified for iron content. However, our improved mechanistic understanding of plant iron metabolism suggests that such alterations could promote or impede plant immunity, depending on the nature of the alteration and the virulence strategy of the pathogen. Effects of iron biofortification on disease resistance should be evaluated while developing plants for iron biofortification.}, number={39}, journal={Journal of Biological Chemistry}, publisher={Elsevier BV}, author={Herlihy, John H. and Long, Terri A. and McDowell, John M.}, year={2020}, month={Sep}, pages={13444–13457} }
 @inbook{madison_melvin_buckner_williams_sozzani_long_2020, title={MAGIC: Live imaging of cellular division in plant seedlings using lightsheet microscopy}, volume={160}, ISBN={9780128215333}, ISSN={0091-679X}, url={http://dx.doi.org/10.1016/bs.mcb.2020.04.004}, DOI={10.1016/bs.mcb.2020.04.004}, abstractNote={Imaging technologies have been used to understand plant genetic and developmental processes, from the dynamics of gene expression to tissue and organ morphogenesis. Although the field has advanced incredibly in recent years, gaps remain in identifying fine and dynamic spatiotemporal intervals of target processes, such as changes to gene expression in response to abiotic stresses. Lightsheet microscopy is a valuable tool for such studies due to its ability to perform long-term imaging at fine intervals of time and at low photo-toxicity of live vertically oriented seedlings. In this chapter, we describe a detailed method for preparing and imaging Arabidopsis thaliana seedlings for lightsheet microscopy via a Multi-Sample Imaging Growth Chamber (MAGIC), which allows simultaneous imaging of at least four samples. This method opens new avenues for acquiring imaging data at a high temporal resolution, which can be eventually probed to identify key regulatory time points and any spatial dependencies of target developmental processes.}, booktitle={Methods in Cell Biology}, publisher={Elsevier}, author={Madison, Imani and Melvin, Charles and Buckner, Eli and Williams, Cranos and Sozzani, Rosangela and Long, Terri}, year={2020}, pages={405–418} }
 @article{buckner_madison_chou_matthiadis_melvin_sozzani_williams_long_2019, title={Automated Imaging, Tracking, and Analytics Pipeline for Differentiating Environmental Effects on Root Meristematic Cell Division}, volume={10}, ISSN={1664-462X}, url={http://dx.doi.org/10.3389/fpls.2019.01487}, DOI={10.3389/fpls.2019.01487}, abstractNote={Exposure of plants to abiotic stresses, whether individually or in combination, triggers dynamic changes to gene regulation. These responses induce distinct changes in phenotypic characteristics, enabling the plant to adapt to changing environments. For example, iron deficiency and heat stress have been shown to alter root development by reducing primary root growth and reducing cell proliferation, respectively. Currently, identifying the dynamic temporal coordination of genetic responses to combined abiotic stresses remains a bottleneck. This is, in part, due to an inability to isolate specific intervals in developmental time where differential activity in plant stress responses plays a critical role. Here, we observed that iron deficiency, in combination with temporary heat stress, suppresses the expression of iron deficiency-responsive pPYE::LUC (POPEYE::luciferase) and pBTS::LUC (BRUTUS::luciferase) reporter genes. Moreover, root growth was suppressed less under combined iron deficiency and heat stress than under either single stress condition. To further explore the interaction between pathways, we also created a computer vision pipeline to extract, analyze, and compare high-dimensional dynamic spatial and temporal cellular data in response to heat and iron deficiency stress conditions at high temporal resolution. Specifically, we used fluorescence light sheet microscopy to image Arabidopsis thaliana roots expressing CYCB1;1:GFP, a marker for cell entry into mitosis, every 20 min for 24 h exposed to either iron sufficiency, iron deficiency, heat stress, or combined iron deficiency and heat stress. Our pipeline extracted spatiotemporal metrics from these time-course data. These metrics showed that the persistency and timing of CYCB1;1:GFP signal were uniquely different under combined iron deficiency and heat stress conditions versus the single stress conditions. These metrics also indicated that the spatiotemporal characteristics of the CYCB1;1:GFP signal under combined stress were more dissimilar to the control response than the response seen under iron deficiency for the majority of the 24-h experiment. Moreover, the combined stress response was less dissimilar to the control than the response seen under heat stress. This indicated that pathways activated when the plant is exposed to both iron deficiency and heat stress affected CYCB1;1:GFP spatiotemporal function antagonistically}, journal={Frontiers in Plant Science}, publisher={Frontiers Media SA}, author={Buckner, Eli and Madison, Imani and Chou, Hsuan and Matthiadis, Anna and Melvin, Charles E. and Sozzani, Rosangela and Williams, Cranos and Long, Terri A.}, year={2019}, month={Nov} }
 @article{koryachko_matthiadis_haque_muhammad_ducoste_tuck_long_williams_2019, title={Dynamic modelling of the iron deficiency modulated transcriptome response in Arabidopsis thaliana roots}, volume={1}, ISSN={2517-5025}, url={http://dx.doi.org/10.1093/insilicoplants/diz005}, DOI={10.1093/insilicoplants/diz005}, abstractNote={The iron deficiency response in plants is a complex biological process with a host of influencing factors. The ability to precisely modulate this process at the transcriptome level would enable genetic manipulations allowing plants to survive in nutritionally poor soils and accumulate increased iron content in edible tissues. Despite the collected experimental data describing different aspects of the iron deficiency response in plants, no attempts have been made towards aggregating this information into a descriptive and predictive model of gene expression changes over time. We formulated and trained a dynamic model of the iron deficiency induced transcriptional response in Arabidopsis thaliana. Gene activity dynamics were modelled with a set of ordinary differential equations that contain biologically tractable parameters. The trained model was able to capture and account for a significant difference in mRNA decay rates under iron sufficient and iron deficient conditions, approximate the expression behaviour of currently unknown gene regulators, unveil potential synergistic effects between the modulating transcription factors and predict the effect of double regulator mutants. The presented modelling approach illustrates a framework for experimental design, data analysis and information aggregation in an effort to gain a deeper understanding of various aspects of a biological process of interest.}, number={1}, journal={in silico Plants}, publisher={Oxford University Press (OUP)}, author={Koryachko, Alexandr and Matthiadis, Anna and Haque, Samiul and Muhammad, Durreshahwar and Ducoste, Joel J and Tuck, James M and Long, Terri A and Williams, Cranos M}, year={2019}, month={Jan} }
 @misc{rodriguez-celma_chou_kobayashi_long_balk_2019, title={Hemerythrin E3 Ubiquitin Ligases as Negative Regulators of Iron Homeostasis in Plants}, volume={10}, ISSN={["1664-462X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85062388289&partnerID=MN8TOARS}, DOI={10.3389/fpls.2019.00098}, abstractNote={Iron (Fe) is an essential nutrient for plants, but at the same time its redox properties can make it a dangerous toxin inside living cells. Homeostasis between uptake, use and storage of Fe must be maintained at all times. A small family of unique hemerythrin E3 ubiquitin ligases found in green algae and plants play an important role in avoiding toxic Fe overload, acting as negative regulators of Fe homeostasis. Protein interaction data showed that they target specific transcription factors for degradation by the 26S proteasome. It is thought that the activity of the E3 ubiquitin ligases is controlled by Fe binding to the N-terminal hemerythrin motifs. Here, we discuss what we have learned so far from studies on the HRZ (Hemerythrin RING Zinc finger) proteins in rice, the homologous BTS (BRUTUS) and root-specific BTSL (BRUTUS-LIKE) in Arabidopsis. A mechanistic model is proposed to help focus future research questions towards a full understanding of the regulatory role of these proteins in Fe homeostasis in plants.}, journal={FRONTIERS IN PLANT SCIENCE}, author={Rodriguez-Celma, Jorge and Chou, Hsuan and Kobayashi, Takanori and Long, Terri A. and Balk, Janneke}, year={2019}, month={Feb} }
 @misc{mendoza-cózatl_gokul_carelse_jobe_long_keyster_kopriva_2019, title={Keep talking: crosstalk between iron and sulfur networks fine-tunes growth and development to promote survival under iron limitation}, volume={70}, ISSN={["1460-2431"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85071636551&partnerID=MN8TOARS}, DOI={10.1093/jxb/erz290}, abstractNote={Abstract
               Plants are capable of synthesizing all the molecules necessary to complete their life cycle from minerals, water, and light. This plasticity, however, comes at a high energetic cost and therefore plants need to regulate their economy and allocate resources accordingly. Iron–sulfur (Fe–S) clusters are at the center of photosynthesis, respiration, amino acid, and DNA metabolism. Fe–S clusters are extraordinary catalysts, but their main components (Fe2+ and S2−) are highly reactive and potentially toxic. To prevent toxicity, plants have evolved mechanisms to regulate the uptake, storage, and assimilation of Fe and S. Recent advances have been made in understanding the cellular economy of Fe and S metabolism individually, and growing evidence suggests that there is dynamic crosstalk between Fe and S networks. In this review, we summarize and discuss recent literature on Fe sensing, allocation, use efficiency, and, when pertinent, its relationship to S metabolism. Our future perspectives include a discussion about the open questions and challenges ahead and how the plant nutrition field can come together to approach these questions in a cohesive and more efficient way.}, number={16}, journal={JOURNAL OF EXPERIMENTAL BOTANY}, author={Mendoza-Cózatl, D.G. and Gokul, A. and Carelse, M.F. and Jobe, T.O. and Long, T.A. and Keyster, M. and Kopriva, S.}, year={2019}, month={Aug}, pages={4197–4210} }
 @article{selote_matthiadis_gillikin_sato_long_2018, title={The E3 ligase BRUTUS facilitates degradation of VOZ1/2 transcription factors}, volume={41}, ISSN={["1365-3040"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85050368197&partnerID=MN8TOARS}, DOI={10.1111/pce.13363}, abstractNote={AbstractBRUTUS (BTS) is an iron binding E3 ligase that has been shown to bind to and influence the accumulation of target basic helix‐loop‐helix transcription factors through 26S proteasome‐mediated degradation in Arabidopsis thaliana. Vascular Plant One‐Zinc finger 1 (VOZ1) and Vascular plant One‐Zinc finger 2 (VOZ2) are NAM, ATAF1/2 and CUC2 (NAC) domain transcription factors that negatively regulate drought and cold stress responses in plants and have previously been shown to be degraded via the 26S proteasome. However, the mechanism that initializes this degradation is unknown. Here, we show that BTS interacts with VOZ1 and VOZ2 and that the presence of the BTS RING domain is essential for these interactions. Through cell‐free degradation and immunodetection analyses, we demonstrate that BTS facilitates the degradation of Vascular plant One‐Zinc finger 1/2 (VOZ1/2) protein in the nucleus particularly under drought and cold stress conditions. In addition to its known role in controlling the iron‐deficiency response in plants, here, we report that BTS may play a role in drought and possibly other abiotic stress responses by facilitating the degradation of transcription factors, VOZ1/2.}, number={10}, journal={PLANT CELL AND ENVIRONMENT}, publisher={Wiley}, author={Selote, Devarshi and Matthiadis, Anna and Gillikin, Jeffrey W. and Sato, Masa H. and Long, Terri A.}, year={2018}, month={Oct}, pages={2463–2474} }
 @article{samira_li_kliebenstein_li_davis_gillikin_long_2018, title={The bHLH transcription factor ILR3 modulates multiple stress responses in Arabidopsis}, volume={97}, ISSN={0167-4412 1573-5028}, url={http://dx.doi.org/10.1007/S11103-018-0735-8}, DOI={10.1007/s11103-018-0735-8}, abstractNote={ILR3 and PYE function in a regulatory network that modulates GLS accumulation under iron deficiency. The molecular processes involved in the cross talk between iron (Fe) homeostasis and other metabolic processes in plants are poorly understood. In Arabidopsis thaliana the transcription factor IAA-LEUCINE RESISTANT3 (ILR3) regulates iron deficiency response, aliphatic glucosinolate (GLS) biosynthesis and pathogen response. ILR3 is also known to interact with its homolog, POPEYE (PYE), which also plays a role in Fe response. However, little is known about how ILR3 regulates such diverse processes, particularly, via its interaction with PYE. Since GLS are produced as part of a defense mechanism against wounding pathogens, we examined pILR3::β-GLUCURONIDASE expression and found that Fe deficiency enhances the wound-induced expression of ILR3 in roots and that ILR3 is induced in response to the wounding pathogen, sugarbeet root cyst nematode (Heterodera schachtii). We also examined the expression pattern of genes involved in Fe homeostasis and aliphatic GLS biosynthesis in pye-1, ilr3-2 and pye-1xilr3-2 (pxi) mutants and found that ILR3 and PYE differentially regulate the expression of genes involved these processes under Fe deficiency. We measured GLS levels and sugarbeet root cyst nematode infection rates under varying Fe conditions, and found that long-chain GLS levels are elevated in ilr3-2 and pxi mutants. This increase in long-chain GLS accumulation is correlated with elevated nematode resistance in ilr3-2 and pxi mutants in the absence of Fe. Our findings suggest that ILR3 and PYE function in a regulatory network that controls wounding pathogen response in plant roots by modulating GLS accumulation under iron deficiency.}, number={4-5}, journal={Plant Molecular Biology}, publisher={Springer Science and Business Media LLC}, author={Samira, Rozalynne and Li, Baohua and Kliebenstein, Daniel and Li, Chunying and Davis, Eric and Gillikin, Jeffrey W. and Long, Terri A.}, year={2018}, month={Jun}, pages={297–309} }
 @article{matthiadis_long_2016, title={Further insight into BRUTUS domain composition and functionality}, volume={11}, ISSN={["1559-2324"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84986575665&partnerID=MN8TOARS}, DOI={10.1080/15592324.2016.1204508}, abstractNote={ABSTRACT BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis.}, number={8}, journal={PLANT SIGNALING & BEHAVIOR}, author={Matthiadis, Anna and Long, Terri A.}, year={2016} }
 @misc{muhammad_schmittling_williams_long_2017, title={More than meets the eye: Emergent properties of transcription factors networks in Arabidopsis}, volume={1860}, ISSN={["0006-3002"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84995470767&partnerID=MN8TOARS}, DOI={10.1016/j.bbagrm.2016.07.017}, abstractNote={Uncovering and mathematically modeling Transcription Factor Networks (TFNs) are the first steps in engineering plants with traits that are better equipped to respond to changing environments. Although several plant TFNs are well known, the framework for systematically modeling complex characteristics such as switch-like behavior, oscillations, and homeostasis that emerge from them remain elusive. This review highlights literature that provides, in part, experimental and computational techniques for characterizing TFNs. This review also outlines methodologies that have been used to mathematically model the dynamic characteristics of TFNs. We present several examples of TFNs in plants that are involved in developmental and stress response. In several cases, advanced algorithms capture or quantify emergent properties that serve as the basis for robustness and adaptability in plant responses. Increasing the use of mathematical approaches will shed new light on these regulatory properties that control plant growth and development, leading to mathematical models that predict plant behavior. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.}, number={1}, journal={BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS}, author={Muhammad, Durreshahwar and Schmittling, Selene and Williams, Cranos and Long, Terri A.}, year={2017}, month={Jan}, pages={64–74} }
 @article{koryachko_matthiadis_muhammad_foret_brady_ducoste_tuck_long_williams_2015, title={Clustering and Differential Alignment Algorithm: Identification of Early Stage Regulators in the Arabidopsis thaliana Iron Deficiency Response}, volume={10}, ISSN={["1932-6203"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84943338816&partnerID=MN8TOARS}, DOI={10.1371/journal.pone.0136591}, abstractNote={Time course transcriptome datasets are commonly used to predict key gene regulators associated with stress responses and to explore gene functionality. Techniques developed to extract causal relationships between genes from high throughput time course expression data are limited by low signal levels coupled with noise and sparseness in time points. We deal with these limitations by proposing the Cluster and Differential Alignment Algorithm (CDAA). This algorithm was designed to process transcriptome data by first grouping genes based on stages of activity and then using similarities in gene expression to predict influential connections between individual genes. Regulatory relationships are assigned based on pairwise alignment scores generated using the expression patterns of two genes and some inferred delay between the regulator and the observed activity of the target. We applied the CDAA to an iron deficiency time course microarray dataset to identify regulators that influence 7 target transcription factors known to participate in the Arabidopsis thaliana iron deficiency response. The algorithm predicted that 7 regulators previously unlinked to iron homeostasis influence the expression of these known transcription factors. We validated over half of predicted influential relationships using qRT-PCR expression analysis in mutant backgrounds. One predicted regulator-target relationship was shown to be a direct binding interaction according to yeast one-hybrid (Y1H) analysis. These results serve as a proof of concept emphasizing the utility of the CDAA for identifying unknown or missing nodes in regulatory cascades, providing the fundamental knowledge needed for constructing predictive gene regulatory networks. We propose that this tool can be used successfully for similar time course datasets to extract additional information and infer reliable regulatory connections for individual genes.}, number={8}, journal={PLOS ONE}, author={Koryachko, Alexandr and Matthiadis, Anna and Muhammad, Durreshahwar and Foret, Jessica and Brady, Siobhan M. and Ducoste, Joel J. and Tuck, James and Long, Terri A. and Williams, Cranos}, year={2015}, month={Aug} }
 @article{koryachko_matthiadis_ducoste_tuck_long_williams_2015, title={Computational approaches to identify regulators of plant stress response using high-throughput gene expression data}, volume={3-4}, ISSN={2214-6628}, url={http://dx.doi.org/10.1016/J.CPB.2015.04.001}, DOI={10.1016/j.cpb.2015.04.001}, abstractNote={Insight into biological stress regulatory pathways can be derived from high-throughput transcriptomic data using computational algorithms. These algorithms can be integrated into a computational approach to provide specific testable predictions that answer biological questions of interest. This review conceptually organizes a wide variety of developed algorithms into a classification system based on desired type of output predictions. This classification is then used as a structure to describe completed approaches in the literature, with a focus on project goals, overall path of implemented algorithms, and biological insight gained. These algorithms and approaches are introduced mainly in the context of research on the model plant species Arabidopsis thaliana under stress conditions, though the nature of computational techniques makes these approaches easily applicable to a wide range of species, data types, and conditions.}, journal={Current Plant Biology}, publisher={Elsevier BV}, author={Koryachko, Alexandr and Matthiadis, Anna and Ducoste, Joel J. and Tuck, James and Long, Terri A. and Williams, Cranos}, year={2015}, month={Sep}, pages={20–29} }
 @article{martinez-trujillo_mendez-bravo_ortiz-castro_hernandez-madrigal_ibarra-laclette_ruiz-herrera_long_cervantes_herrera-estrella_lopez-bucio_et al._2014, title={Chromate alters root system architecture and activates expression of genes involved in iron homeostasis and signaling in Arabidopsis thaliana}, volume={86}, ISSN={["1573-5028"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84906088354&partnerID=MN8TOARS}, DOI={10.1007/s11103-014-0210-0}, abstractNote={Soil contamination by hexavalent chromium [Cr(VI) or chromate] due to anthropogenic activities has become an increasingly important environmental problem. To date few studies have been performed to elucidate the signaling networks involved on adaptive responses to (CrVI) toxicity in plants. In this work, we report that depending upon its concentration, Cr(VI) alters in different ways the architecture of the root system in Arabidopsis thaliana seedlings. Low concentrations of Cr (20-40 µM) promoted primary root growth, while concentrations higher than 60 µM Cr repressed growth and increased formation of root hairs, lateral root primordia and adventitious roots. We analyzed global gene expression changes in seedlings grown in media supplied with 20 or 140 µM Cr. The level of 731 transcripts was significantly modified in response to Cr treatment with only five genes common to both Cr concentrations. Interestingly, 23 genes related to iron (Fe) acquisition were up-regulated including IRT1, YSL2, FRO5, BHLH100, BHLH101 and BHLH039 and the master controllers of Fe deficiency responses PYE and BTS were specifically activated in pericycle cells. It was also found that increasing concentration of Cr in the plant correlated with a decrease in Fe content, but increased both acidification of the rhizosphere and activity of the ferric chelate reductase. Supply of Fe to Cr-treated Arabidopsis allowed primary root to resume growth and alleviated toxicity symptoms, indicating that Fe nutrition is a major target of Cr stress in plants. Our results show that low Cr levels are beneficial to plants and that toxic Cr concentrations activate a low-Fe rescue system.}, number={1-2}, journal={PLANT MOLECULAR BIOLOGY}, author={Martinez-Trujillo, M. and Mendez-Bravo, A. and Ortiz-Castro, R. and Hernandez-Madrigal, F. and Ibarra-Laclette, E. and Ruiz-Herrera, L. F. and Long, Terri A. and Cervantes, C. and Herrera-Estrella, L. and Lopez-Bucio, J. and et al.}, year={2014}, month={Sep}, pages={35–50} }
 @misc{gonzalez-guerrero_matthiadis_saez_long_2014, title={Fixating on metals: new insights into the role of metals in nodulation and symbiotic nitrogen fixation}, volume={5}, ISSN={["1664-462X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84901021951&partnerID=MN8TOARS}, DOI={10.3389/fpls.2014.00045}, abstractNote={Symbiotic nitrogen fixation is one of the most promising and immediate alternatives to the overuse of polluting nitrogen fertilizers for improving plant nutrition. At the core of this process are a number of metalloproteins that catalyze and provide energy for the conversion of atmospheric nitrogen to ammonia, eliminate free radicals produced by this process, and create the microaerobic conditions required by these reactions. In legumes, metal cofactors are provided to endosymbiotic rhizobia within root nodule cortical cells. However, low metal bioavailability is prevalent in most soils types, resulting in widespread plant metal deficiency and decreased nitrogen fixation capabilities. As a result, renewed efforts have been undertaken to identify the mechanisms governing metal delivery from soil to the rhizobia, and to determine how metals are used in the nodule and how they are recycled once the nodule is no longer functional. This effort is being aided by improved legume molecular biology tools (genome projects, mutant collections, and transformation methods), in addition to state-of-the-art metal visualization systems.}, number={FEB}, journal={FRONTIERS IN PLANT SCIENCE}, author={Gonzalez-Guerrero, Manuel and Matthiadis, Anna and Saez, Angela and Long, Terri A.}, year={2014}, month={Feb} }
 @article{selote_samira_matthiadis_gillikin_long_2015, title={Iron-Binding E3 Ligase Mediates Iron Response in Plants by Targeting Basic Helix-Loop-Helix Transcription Factors}, volume={167}, ISSN={["1532-2548"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84920141665&partnerID=MN8TOARS}, DOI={10.1104/pp.114.250837}, abstractNote={AbstractIron uptake and metabolism are tightly regulated in both plants and animals. In Arabidopsis (Arabidopsis thaliana), BRUTUS (BTS), which contains three hemerythrin (HHE) domains and a Really Interesting New Gene (RING) domain, interacts with basic helix-loop-helix transcription factors that are capable of forming heterodimers with POPEYE (PYE), a positive regulator of the iron deficiency response. BTS has been shown to have E3 ligase capacity and to play a role in root growth, rhizosphere acidification, and iron reductase activity in response to iron deprivation. To further characterize the function of this protein, we examined the expression pattern of recombinant ProBTS::β-GLUCURONIDASE and found that it is expressed in developing embryos and other reproductive tissues, corresponding with its apparent role in reproductive growth and development. Our findings also indicate that the interactions between BTS and PYE-like (PYEL) basic helix-loop-helix transcription factors occur within the nucleus and are dependent on the presence of the RING domain. We provide evidence that BTS facilitates 26S proteasome-mediated degradation of PYEL proteins in the absence of iron. We also determined that, upon binding iron at the HHE domains, BTS is destabilized and that this destabilization relies on specific residues within the HHE domains. This study reveals an important and unique mechanism for plant iron homeostasis whereby an E3 ubiquitin ligase may posttranslationally control components of the transcriptional regulatory network involved in the iron deficiency response.}, number={1}, journal={PLANT PHYSIOLOGY}, author={Selote, Devarshi and Samira, Rozalynne and Matthiadis, Anna and Gillikin, Jeffrey W. and Long, Terri A.}, year={2015}, month={Jan}, pages={273-+} }
 @article{sugimoto_okegawa_tohri_long_covert_hisabori_shikanai_2013, title={A Single Amino Acid Alteration in PGR5 Confers Resistance to Antimycin A in Cyclic Electron Transport around PSI}, volume={54}, url={http://dx.doi.org/10.1093/pcp/pct098}, DOI={10.1093/pcp/pct098}, abstractNote={In Arabidopsis thaliana, the main route of cyclic electron transport around PSI is sensitive to antimycin A, but the site of inhibition has not been clarified. We discovered that ferredoxin-dependent plastoquinone reduction in ruptured chloroplasts was less sensitive to antimycin A in Arabidopsis that overaccumulated PGR5 (PROTON GRADIENT REGULATION 5) originating from Pinus taeda (PtPGR5) than that in the wild type. Consistent with this in vitro observation, infiltration of antimycin A reduced PSII yields and the non-photochemical quenching (NPQ) of Chl fluorescence in wild-type leaves but not in leaves accumulating PtPGR5. There are eight amino acid differences between PGR5 of Arabidopsis (AtPGR5) and PtPGR5 in their mature forms. To determine the site conferring antimycin A resistance, a series of AtPGR5 and PtPGR5 variants was introduced into the Arabidopsis pgr5 mutant. We determined that the presence of lysine rather than valine at the third amino acid position was necessary and sufficient for resistance to antimycin A. High levels of resistance to antimycin A required overaccumulation of PtPGR5 in ruptured chloroplasts, suggesting that PtPGR5 is partly resistant to antimycin A. In contrast, PSII yield was almost fully resistant to antimycin A in leaves accumulating endogenous levels of PtPGR5 or AtPGR5 V3K that had lysine instead of valine at the third position. NPQ was also dramatically recovered in leaves of these lines. These results imply that partial recovery of PSI cyclic electron transport is sufficient for maintaining redox homeostasis in photosynthesis. Our discovery suggests that antimycin A inhibits the function of PGR5 or proteins localized close to PGR5.}, number={9}, journal={Plant and Cell Physiology}, author={Sugimoto, K. and Okegawa, Y. and Tohri, A. and Long, T.A. and Covert, S.F. and Hisabori, T. and Shikanai, T.}, year={2013}, month={Sep}, pages={1525–1534} }
 @misc{samira_stallmann_massenburg_long_2013, title={Ironing out the issues: Integrated approaches to understanding iron homeostasis in plants}, volume={210}, ISSN={["0168-9452"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84880395733&partnerID=MN8TOARS}, DOI={10.1016/j.plantsci.2013.06.004}, abstractNote={Plants initialize responses to environmental changes at all levels, from signaling to translation and beyond. Such is the case for fluctuations in the availability of iron (Fe), one of the most critical micronutrients for plants. The results of these responses are physiological and morphological changes that lead to increased iron uptake from the rhizosphere, and recycling and reallocation of Fe, which must be properly localized within specific cells and cellular compartment for use. The use of reductionist approaches, in combination with in vivo and in situ Fe localization tools, has been able to shed light on critical signaling molecules, transcriptional regulators, transporters and other proteins involved in Fe homeostasis. Recent advances in elemental distribution and speciation analysis now enable detection and measurement of Fe and other elements at resolutions never seen before. Moreover, increasing use of systems biology approaches provide a substantially broader perspective of how Fe availability affects processes at many levels. This review highlights the latest in vivo and in situ iron localization approaches and some of the recent advances in understanding mechanisms that control Fe translocation. A broad perspective of how Fe localization data might one day be integrated with large-scale data to create models for Fe homeostasis is presented.}, journal={PLANT SCIENCE}, author={Samira, Rozalynne and Stallmann, Anna and Massenburg, Lynnicia N. and Long, Terri A.}, year={2013}, month={Sep}, pages={250–259} }
 @article{long_2011, title={Many needles in a haystack: cell-type specific abiotic stress responses}, volume={14}, ISSN={1369-5266}, url={http://dx.doi.org/10.1016/j.pbi.2011.04.005}, DOI={10.1016/j.pbi.2011.04.005}, abstractNote={Plants react to abiotic stress with a number of physiological, biochemical, and developmental alterations. These responses include changes in signaling components, gene transcription, non-coding RNAs, proteins, and metabolites that occur in a cell-type and tissue-specific manner. Recent advances in cell-type specifically isolating protoplasts and nuclei from plants, extracting mRNA from targeted cells, and whole-genome transcriptional profiling have enabled scientists to gain insight into how cells and tissues respond transcriptionally to abiotic stress. Continued technological advances in profiling the proteomes, metabolomes, and other biological components of specific cells will continue to broaden our understanding of plant stress responses.}, number={3}, journal={Current Opinion in Plant Biology}, publisher={Elsevier BV}, author={Long, Terri A}, year={2011}, month={Jun}, pages={325–331} }
 @article{long_tsukagoshi_busch_lahner_salt_benfey_2010, title={The bHLH Transcription Factor POPEYE Regulates Response to Iron Deficiency in Arabidopsis Roots}, volume={22}, url={http://dx.doi.org/10.1105/tpc.110.074096}, DOI={10.1105/tpc.110.074096}, abstractNote={AbstractGlobal population increases and climate change underscore the need for better comprehension of how plants acquire and process nutrients such as iron. Using cell type–specific transcriptional profiling, we identified a pericycle-specific iron deficiency response and a bHLH transcription factor, POPEYE (PYE), that may play an important role in this response. Functional analysis of PYE suggests that it positively regulates growth and development under iron-deficient conditions. Chromatin immunoprecipitation-on-chip analysis and transcriptional profiling reveal that PYE helps maintain iron homeostasis by regulating the expression of known iron homeostasis genes and other genes involved in transcription, development, and stress response. PYE interacts with PYE homologs, including IAA–Leu Resistant3 (ILR3), another bHLH transcription factor that is involved in metal ion homeostasis. Moreover, ILR3 interacts with a third protein, BRUTUS (BTS), a putative E3 ligase protein, with metal ion binding and DNA binding domains, which negatively regulates the response to iron deficiency. PYE and BTS expression is also tightly coregulated. We propose that interactions among PYE, PYE homologs, and BTS are important for maintaining iron homeostasis under low iron conditions.}, number={7}, journal={The Plant Cell}, author={Long, T.A. and Tsukagoshi, H. and Busch, W. and Lahner, B. and Salt, D.E. and Benfey, P.N.}, year={2010}, month={Jul}, pages={2219–2236} }
 @article{benfey_cui_twigg_long_iyer-pascuzzi_tsukagoshi_sozzani_jackson_van norman_moreno-risueno_2009, title={Development rooted in interwoven networks}, volume={331}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2009.05.012}, DOI={10.1016/j.ydbio.2009.05.012}, abstractNote={Freshwater planarians appear to utilize inductive signals to specify their germ cell lineage: germ cells are believed to form post-embryonically from the pluripotent somatic stem cells, known as neoblasts. Previously, we identified a planarian homolog of nanos (Smed-nanos) and demonstrated by RNA interference (RNAi) that this gene is required for the development, maintenance, and regeneration of planarian germ cells. We have performed microarray analyses to compare gene expression profiles between planarians with early germ cells and those without them. We identified ∼300 genes that are significantly down-regulated in animals lacking early germ cells. This data set contains genes implicated in germ cell development in other organisms, conserved genes not yet reported to have germ cell-related functions, and novel genes. Analysis using putative domain functions (Clusters of Orthologous Groups) suggested diverse molecular functions, including cytoskeletal components, metabolism, RNA processing and modification, transcription, as well as signal transduction. Top hits have been validated by in situ hybridization. Functional analyses of these genes via RNA interference are being carried out. Thus far, we have identified several genes that, when knocked down by RNAi, cause various defects in germ cell development, including: impaired testes development; loss of spermatogonial stem cells; meiotic failure; and defects in sperm elongation. This work will contribute to our knowledge of conserved regulators of germ cell differentiation. (Supported by NIH-NICHD R01-HD043403.)}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Benfey, Philip N. and Cui, Hongchang and Twigg, Richard and Long, Terri and Iyer-Pascuzzi, Anjali and Tsukagoshi, Hironaka and Sozzani, Rosangela and Jackson, Terry and Van Norman, Jaimie and Moreno-Risueno, Miguel}, year={2009}, month={Jul}, pages={386} }
 @article{dinneny_long_wang_jung_mace_pointer_barron_brady_schiefelbein_benfey_2008, title={Cell Identity Mediates the Response of Arabidopsis Roots to Abiotic Stress}, volume={320}, url={http://dx.doi.org/10.1126/science.1153795}, DOI={10.1126/science.1153795}, abstractNote={
            Little is known about the way developmental cues affect how cells interpret their environment. We characterized the transcriptional response to high salinity of different cell layers and developmental stages of the
            Arabidopsis
            root and found that transcriptional responses are highly constrained by developmental parameters. These transcriptional changes lead to the differential regulation of specific biological functions in subsets of cell layers, several of which correspond to observable physiological changes. We showed that known stress pathways primarily control semiubiquitous responses and used mutants that disrupt epidermal patterning to reveal cell-layer–specific and inter–cell-layer effects. By performing a similar analysis using iron deprivation, we identified common cell-type–specific stress responses and revealed the crucial role the environment plays in defining the transcriptional outcome of cell-fate decisions.
          }, number={5878}, journal={Science}, author={Dinneny, J.R. and Long, T.A. and Wang, J.Y. and Jung, J.W. and Mace, D. and Pointer, S. and Barron, C. and Brady, S.M. and Schiefelbein, J. and Benfey, P.N.}, year={2008}, month={May}, pages={942–945} }
 @article{long_okegawa_shikanai_schmidt_covert_2008, title={Conserved role of PROTON GRADIENT REGULATION 5 in the regulation of PSI cyclic electron transport}, volume={228}, ISSN={0032-0935 1432-2048}, url={http://dx.doi.org/10.1007/s00425-008-0789-y}, DOI={10.1007/s00425-008-0789-y}, abstractNote={There are at least two photosynthetic cyclic electron transport (CET) pathways in most C(3) plants: the NAD(P)H dehydrogenase (NDH)-dependent pathway and a pathway dependent upon putative ferredoxin:plastoquinone oxidoreductase (FQR) activity. While the NDH complex has been identified, and shown to play a role in photosynthesis, especially under stress conditions, less is known about the machinery of FQR-dependent CET. Recent studies indicate that FQR-dependent CET is dependent upon PGR5, a small protein of unknown function. In a previous study we found that overexpression of PGR5 causes alterations in growth and development associated with decreased chloroplast development and a transient increase in nonphotochemical quenching (NPQ) after the shift from dark to light. In the current study we examine the spatiotemporal expression pattern of PGR5, and the effects of overexpression of PGR5 in Arabidopsis under a host of light and stress conditions. To investigate the conserved function of PGR5, we cloned PGR5 from a species which apparently lacks NDH, loblolly pine, and overexpressed it in Arabidopsis. Although greening of cotyledons was severely delayed in overexpressing lines under low light, mature plants survived exposure to high light and drought stress better than wild-type. In addition, PSI was more resistant to high light in the PGR5 overexpressors than in wild-type plants, while PSII was more sensitive to this stress. These complex responses corresponded to alterations in linear and cyclic electron transfer, suggesting that over-accumulation of PGR5 induces pleiotropic effects, probably via elevated CET. We conclude that PGR5 has a developmentally-regulated, conserved role in mediating CET.}, number={6}, journal={Planta}, publisher={Springer Science and Business Media LLC}, author={Long, Terri A. and Okegawa, Yuki and Shikanai, Toshiharu and Schmidt, Gregory W. and Covert, Sarah F.}, year={2008}, month={Jul}, pages={907–918} }
 @article{long_brady_benfey_2008, title={Systems Approaches to Identifying Gene Regulatory Networks in Plants}, volume={24}, url={http://dx.doi.org/10.1146/annurev.cellbio.24.110707.175408}, DOI={10.1146/annurev.cellbio.24.110707.175408}, abstractNote={ Complex gene regulatory networks are composed of genes, noncoding RNAs, proteins, metabolites, and signaling components. The availability of genome-wide mutagenesis libraries; large-scale transcriptome, proteome, and metabalome data sets; and new high-throughput methods that uncover protein interactions underscores the need for mathematical modeling techniques that better enable scientists to synthesize these large amounts of information and to understand the properties of these biological systems. Systems biology approaches can allow researchers to move beyond a reductionist approach and to both integrate and comprehend the interactions of multiple components within these systems. Descriptive and mathematical models for gene regulatory networks can reveal emergent properties of these plant systems. This review highlights methods that researchers are using to obtain large-scale data sets, and examples of gene regulatory networks modeled with these data. Emergent properties revealed by the use of these network models and perspectives on the future of systems biology are discussed. }, journal={Annual Review of Cell and Developmental Biology}, author={Long, T.A. and Brady, S.M. and Benfey, P.N.}, year={2008}, month={Nov}, pages={81–103} }
 @article{okegawa_long_iwano_takayama_kobayashi_covert_shikanai_2007, title={A Balanced PGR5 Level is Required for Chloroplast Development and Optimum Operation of Cyclic Electron Transport Around Photosystem I}, volume={48}, url={http://dx.doi.org/10.1093/pcp/pcm116}, DOI={10.1093/pcp/pcm116}, abstractNote={PSI cyclic electron transport contributes markedly to photosynthesis and photoprotection in flowering plants. Although the thylakoid protein PGR5 (Proton Gradient Regulation 5) has been shown to be essential for the main route of PSI cyclic electron transport, its exact function remains unclear. In transgenic Arabidopsis plants overaccumulating PGR5 in the thylakoid membrane, chloroplast development was delayed, especially in the cotyledons. Although photosynthetic electron transport was not affected during steady-state photosynthesis, a high level of non-photochemical quenching (NPQ) was transiently induced after a shift of light conditions. This phenotype was explained by elevated activity of PSI cyclic electron transport, which was monitored in an in vitro system using ruptured chloroplasts, and also in leaves. The effect of overaccumulation of PGR5 was specific to the antimycin A-sensitive pathway of PSI cyclic electron transport but not to the NAD(P)H dehydrogenase (NDH) pathway. We propose that a balanced PGR5 level is required for efficient regulation of the rate of antimycin A-sensitive PSI cyclic electron transport, although the rate of PSI cyclic electron transport is probably also regulated by other factors during steady-state photosynthesis.}, number={10}, journal={Plant and Cell Physiology}, author={Okegawa, Y. and Long, T.A. and Iwano, M. and Takayama, S. and Kobayashi, Y. and Covert, S.F. and Shikanai, T.}, year={2007}, month={Aug}, pages={1462–1471} }
 @article{long_benfey_2006, title={Transcription factors and hormones: new insights into plant cell differentiation}, volume={18}, ISSN={0955-0674}, url={http://dx.doi.org/10.1016/j.ceb.2006.09.004}, DOI={10.1016/j.ceb.2006.09.004}, abstractNote={Plant development is a continuous process, mainly due to the presence of stem cell niches within the root and shoot. The interplay between a host of transcription factors determines whether the cells within the meristem maintain their stem cell state, differentiate into leaves or form secondary meristems, which develop into shoots and flowers. Several recent studies provide new insight into how transcription factors and phytohormones interact within meristems to control cell proliferation and differentiation.}, number={6}, journal={Current Opinion in Cell Biology}, publisher={Elsevier BV}, author={Long, Terri A and Benfey, Philip N}, year={2006}, month={Dec}, pages={710–714} }
 @article{brady_long_benfey_2006, title={Unraveling the Dynamic Transcriptome}, volume={18}, url={http://dx.doi.org/10.1105/tpc.105.037572}, DOI={10.1105/tpc.105.037572}, abstractNote={The advent of large-scale transcriptional profiling techniques signalled a new age in biology. Instead of understanding the expression and action of single genes, the field of transcriptomics allows for the examination of whole transcriptome changes across a variety of biological conditions. These}, number={9}, journal={The Plant Cell}, author={Brady, S.M. and Long, T.A. and Benfey, P.N.}, year={2006}, month={Sep}, pages={2101–2111} }
 @article{mcdowell_dhandaydham_long_aarts_goff_holub_dangl_1998, title={Intragenic Recombination and Diversifying Selection Contribute to the Evolution of Downy Mildew Resistance at the RPP8 Locus of Arabidopsis}, volume={10}, url={http://dx.doi.org/10.1105/tpc.10.11.1861}, DOI={10.1105/tpc.10.11.1861}, abstractNote={Pathogen resistance (R) genes of the NBS-LRR class (for nucleotide binding site and leucine-rich repeat) are found in many plant species and confer resistance to a diverse spectrum of pathogens. Little is known about the mechanisms that drive NBS-LRR gene evolution in the host–pathogen arms race. We cloned the RPP8 gene (for resistance to Peronospora parasitica) and compared the structure of alleles at this locus in resistant Landsberg erecta (Ler-0) and susceptible Columbia (Col-0) accessions. RPP8-Ler encodes an NBS-LRR protein with a putative N-terminal leucine zipper and is more closely related to previously cloned R genes that confer resistance to bacterial pathogens than it is to other known RPP genes. The RPP8 haplotype in Ler-0 contains the functional RPP8-Ler gene and a nonfunctional homolog, RPH8A. In contrast, the rpp8 locus in Col-0 contains a single chimeric gene, which was likely derived from unequal crossing over between RPP8-Ler and RPH8A ancestors within a Ler-like haplotype. Sequence divergence among RPP8 family members has been accelerated by positive selection on the putative ligand binding region in the LRRs. These observations indicate that NBS-LRR molecular evolution is driven by the same mechanisms that promote rapid sequence diversification among other genes involved in non-self-recognition.}, number={11}, journal={The Plant Cell}, author={McDowell, J.M. and Dhandaydham, M. and Long, T.A. and Aarts, M.G.M. and Goff, S. and Holub, E.B. and Dangl, J.L.}, year={1998}, month={Nov}, pages={1861–1874} }