Life Sciences Commons^™

Β-Cell Impairment And Clinically Meaningful Alterations In Glycemia In Obese Youth Across The Glucose Tolerance Spectrum, Joon Young Kim, Hala Tfayli, Fida Bacha, Sojung Lee, Nour Gebara, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background/aims: In obese youth, it is not clear what degree of β-cell impairment translates to glucose dysregulation commensurate with shifts from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes. We aimed to investigate the quantitative relationship between β-cell (clamp-measured disposition index [DI]) and OGTT glucose area under the curve (G-AUC) in obese youth across the spectrum of glucose tolerance.

Methods: Data from 152 youth (58 African-American [AA] and 94 American-White [AW]; 73 NGT, 48 IGT, and 31 type 2 diabetes) who completed a 3-h hyperinsulinemic (80 mu/m2/min)-euglycemic clamp, and a 2-h hyperglycemic (225 mg/dL) clamp …

Modeling Age-Dependent Developmental Changes In The Expression Of Genes Involved In Citrulline Synthesis Using Pig Enteroids, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Douglas G Burrin, Juan C Marini

Children’s Nutrition Research Center Staff Publications

metabolism of citrulline and arginine are well characterized. Enteroids, a novel ex-vivo model that recreates the three-dimensional structure of the intestinal crypt-villus unit, have shown to replicate molecular and physiological profiles of the intestinal segment from where they originated ("location memory").

Objective: The present study tested the hypothesis that enteroids recapitulate the developmental changes observed in vivo regarding citrulline production in pigs ("developmental memory").

Methods: Preterm (10- and 5-d preterm) and term pigs at birth, together with 7- and 35-d-old pigs were studied. Gene expression was measured in jejunal samples and in enteroids derived from this segment. Whole body citrulline …

Type 1 Doing Well: Pilot Feasibility And Acceptability Study Of A Strengths-Based Mhealth App For Parents Of Adolescents With Type 1 Diabetes, Marisa E Hilliard, Viena T Cao, Sahar S Eshtehardi, Charles G Minard, Rana Saber, Debbe Thompson, Lefkothea P Karaviti, Barbara J Anderson

Children’s Nutrition Research Center Staff Publications

Background: We evaluated the feasibility and acceptability of a pilot behavioral intervention delivered to parents of adolescents with type 1 diabetes (T1D) via mobile-friendly web app. The Type 1 Doing Well app aimed to promote supportive family diabetes management by helping parents recognize and reinforce teens' positive diabetes-related behaviors ("strengths").

Methods: Parents (n = 80, 74% recruitment) of adolescents (age range = 12-17 years, M = 15.3 ± 1.5 years, 59% female, 56% insulin pump, M hemoglobin A1c (HbA1c) = 9.0% ± 2.1%) were randomized 2:1 to intervention or control (i.e., usual medical care with or without app) for …

Transcutaneous Energy Transmission: Can We Do It Now?, Yuriy Pya

The VAD Journal

The percutaneous driveline used in contemporary LVADs presents a continuous risk of infection for the duration of support. Minimizing infection in durable mechanical circulatory support systems requires total implantation of all components and energy transfer by means other than percutaneous drivelines. A novel coplanar energy transfer (CET) system, similar to the original transcutaneous energy transfer (TET) design, is unique by incorporating two large rings with coil-within-the-coil topology to ensure strong resonance power. The CET system consists of an internal integrated controller, a battery coupled with an internal thoracic coil ring, and the LVAD pump. External equipment includes a power transmission …

Proposals For Upper Limits Of Safe Intake For Methionine, Histidine, And Lysine In Healthy Humans, Luc Cynober, Dennis M Bier, Patrick Stover, Motoni Kadowaki, Sidney M Morris, Rajavel Elango, Miro Smriga

Children’s Nutrition Research Center Staff Publications

Based on research presented during the 10th Amino Acid Assessment Workshop, no observed adverse effect levels (NOAELs) for supplemental methionine at 46 mg/(kg·d) (∼3.2 g/d), for supplemental histidine at 8.0 g/d, and for supplemental lysine at 6.0 g/d have been proposed. These NOAELs are relevant to healthy adults and are applicable only to high-purity amino acids administered in fortified foods or dietary supplements. Because individuals are exposed to the above supplemental amino acids in the context of complex combinations of essential amino acids or individually in dietary supplements for various physiologic benefits, such as body fat reduction, skin conditioning, mental …

The Central Melanocortin System And Human Obesity, Yongjie Yang, Yong Xu

Children’s Nutrition Research Center Staff Publications

The prevalence of obesity and the associated comorbidities highlight the importance of understanding the regulation of energy homeostasis. The central melanocortin system plays a critical role in controlling body weight balance. Melanocortin neurons sense and integrate the neuronal and hormonal signals, and then send regulatory projections, releasing anorexigenic or orexigenic melanocortin neuropeptides, to downstream neurons to regulate the food intake and energy expenditure. This review summarizes the latest progress in our understanding of the role of the melanocortin pathway in energy homeostasis. We also review the advances in the identification of human genetic variants that cause obesity via mechanisms that …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Fat And Fat-Free Mass Index References In Children And Young Adults: Assessments Along Racial And Ethnic Lines, Roman J Shypailo, William W Wong

Children’s Nutrition Research Center Staff Publications

Background: Fat-free mass index (FFMI) and fat mass index (FMI) are superior to BMI and fat percentage in evaluating nutritional status. However, existing references fail to account for racial/ethnic differences in body composition among children.

Objectives: Our goal was to produce age-based normative references for FFMI and FMI in children for specific racial/ethnic groups.

Methods: Body composition, weight, and height were measured in 1122 normal healthy children aged 2-21 y. Bone mineral content measured by DXA, total body water by deuterium dilution, and total body potassium by whole-body γ counting were combined to calculate fat-free mass (FFM) and fat mass …

The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes.

Objective: This paper presents the rationale, implementation, …

Cellular And Circuit Properties Of Slow Oscillations In The Thalamic Reticular Nucleus, John O'Malley

Dissertations and Theses (Open Access)

During sleep, neurons in the thalamic reticular nucleus (TRN) generate distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory thalamic nuclei underlie the generation of sleep spindles, the mechanisms regulating slow (<1 >Hz) forms of thalamic oscillations are poorly understood. Under in vitro conditions, in the absence of synaptic inputs, TRN neurons can generate slow oscillations in a cell-intrinsic manner. Activation of postsynaptic Group 1 metabotropic glutamate receptors (mGluR) leads to long-lasting plateau potentials thought to be mediated by both T-type calcium currents and calcium-activated nonselective cation currents (I_CAN). However, the identity of …

Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li

Dissertations and Theses (Open Access)

In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …

Profound And Redundant Functions Of Arcuate Neurons In Obesity Development, Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qi Wu, Gang Shu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate GABAergic (GABA

Astrocytes Rescue Neuronal Health After Cisplatin Treatment Through Mitochondrial Transfer., Krystal English, Krystal English

Dissertations and Theses (Open Access)

Abstract

Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer.

Author: Krystal English

Advisory Professor: Dr. Cobi J. Heijnen, Ph.D.

Chemotherapy-induced cognitive impairments are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially, mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health.

We used an in vitro system in which astrocytes with Mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons or neuronal stem …

Identification Of Trim24 Domain Essentiality In Primary Trim24coe Carcinosarcoma Cell Lines, Cem Dede

Dissertations and Theses (Open Access)

Regulation of transcriptional control is a critical feature for organismal development and survival. Because of its effects on chromatin-controlled expression, disruptions of this delicately tuned mechanism are an important factor in development of tumorigenesis. Therefore, there is a growing interest in targeting these control mechanisms for their potential therapeutic values.

Our lab previously discovered the epigenetic regulator function of Tripartite motif protein 24 (TRIM24) through its H3K4me0 and H3K23ac dual histone signature reader function, its negative regulatory effect on the p53 tumor suppressor, in addition to its shown oncogenic driving capacity on immortalized mammary epithelial cells when overexpressed. Although TRIM24 …

Aging Lowers Pex5 Levels In Cortical Neurons In Male And Female Mouse Brains, Ndidi-Ese Uzor

Dissertations and Theses (Open Access)

Peroxisomes are small organelles with critical functions: lipid synthesis, breakdown of reactive oxygen species by antioxidant enzymes, and amino acid degradation. In the brain, peroxisomal lipids make up the myelin sheath. Brain peroxisomal dysfunction leads to lipid disruption or neurological consequences if key peroxisomal proteins are absent. Still, it is unclear how peroxisomes are affected in neurodegenerative diseases and in normal brain aging. This work examines peroxisomal markers in three settings: 1) in a neuronal and 2) animal model of Huntington disease (HD), where mutant huntingtin (mHtt), the causative protein in Huntington disease pathogenesis is expressed, and 3) in the …

Artificial Intron Technology To Generate Conditional Knock-Out Mice, Amber N. Thomas-Gordon

Dissertations and Theses (Open Access)

Genetic engineering has been re-shaped by the invention of new tools in modern biotechnology in a way that offers precision and efficiency in modifying the genome at a single nucleotide level and/or allowing precise control of gene expression. Such gene manipulation brings about significant findings and revelations in comprehending more about embryonic development, cellular and physiological functions, and disease pathology. Current methods used to produce conditional knockouts have limitations on conditional allele placement and modification varies among genes in different organisms. Thus, a system for generating conditional alleles with fidelity remains a challenge. My goal was to examine an approach …

Bringing Til Therapy Beyond Melanoma: Advancing The Treatment Of Advanced Pancreatic And Ovarian Cancers, Donald Sakellariou-Thompson

Dissertations and Theses (Open Access)

The success of checkpoint blockade immunotherapy (CBI) has reinvigorated the cancer therapy field, particularly for advanced melanoma which has doubled the survival rates compared to 20 years ago. However, there are many solid tumor types that are yet to receive substantial benefit from this groundbreaking therapy, two of which are pancreatic cancer (PDAC) and ovarian cancer (OvCa). As such, the 5-year survival rate for PDAC and OvCa stand at 9% and 28% respectively. Despite the lack of efficacy of CBI so far, there is still evidence for the role of immune control in these cancers as evidenced by presence of …

Modulating Avidity Of H8f4-Car By Regulation Of Expression Via Codon Modification, Rolando Vedia

Dissertations and Theses (Open Access)

Despite recent advances in the field of cancer immunotherapy and chimeric antigen receptor (CAR) therapies for the treatment of acute myeloid leukemia (AML), there is a need for more unique and innovative modalities to improve these therapies. Our group has extensively studied and demonstrated the potential of targeting the leukemia-associated antigen PR1 in the setting of AML. PR1 is an HLA-A2-restricted nonameric peptide derived from serine proteases neutrophil elastase and proteinase 3, is overexpressed on myeloid leukemia cells, and expressed at normal low levels in healthy hematopoietic cells. We have demonstrated efficacy in targeting PR1/HLA-A2 via the novel development of …

Investigating The Role Of Quaking In Antigen Uptake And Cross-Presentation By Dendritic Cells, Yating Li

Dissertations and Theses (Open Access)

Dendritic cells (DCs) are considered the most potent antigen presenting cells (APC) due to their superior capability of cross-presenting exogenous antigens to CD8⁺ T cell for strong adaptive immune responses. They internalize foreign antigens by phagocytosis, endocytosis or macropinocytosis, which are then processed in endosomal compartments and loaded onto MHC Class I molecules. However, the molecular mechanisms regulating exogenous antigen uptake and cross-presentation by DCs are not fully understood.

In this study, we discovered that an RNA-binding protein, Quaking (QKI) plays a pivotal role in antigen uptake by DCs. Our previous studies in neural stem cells and microglia have …

Mutations Within And Between Early Cell Division Proteins And Their Effects On Division Regulation In Escherichia Coli, Kara Schoenemann

Dissertations and Theses (Open Access)

Cell division is a highly regulated process that must coordinate multiple implicit activities in different locations in the cell simultaneously. E. coli utilizes a macromolecular machine known as the divisome to accomplish cytokinesis. Assembly of the divisome begins with the assembly of a simpler structure known as the proto-ring. The proto-ring consists mainly of three essential proteins: FtsZ and its membrane tethers FtsA and ZipA. In this work, I aimed to understand the early regulation of division in E. coli by investigating the structure/function relationships of the proto-ring proteins, as well as their interactions with one another and how these …

Elevated Cochlear Adenosine Causes Hearing Loss Via Adora2b Signaling, Jeanne Manalo

Dissertations and Theses (Open Access)

Over 538 million people in the world have been diagnosed with hearing loss (HL). Current treatments for the most common type of HL, sensorineural HL, are limited to hearing aids and cochlear implants with no FDA-drugs available. The hearing process demands an abundance of ATP and HL is often attributed to a disruption in this metabolic energy currency. Patients who lack adenosine deaminase (ADA), the enzyme that irreversibly metabolizes adenosine, have high levels of adenosine that yield severe health problems, including HL; however, the pathogenic mechanisms behind HL and adenosine remain elusive. Our lab has found a HL phenotype in …

Methods To Investigate Hyperthermia Induced By Tumor Treating Fields, Ruchi Singh

Dissertations and Theses (Open Access)

Tumor Treating Fields (TTFields) are an antineoplastic treatment delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. TTF’s is a non-invasive application of low-intensity (1-3 V/cm), intermediate-frequency (100-500 kHz) alternating electric fields. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis through the depolymerization of microtubules and interruption of the spindle structure leading to mitotic catastrophe and the formation of non-viable daughter cells. Tumor Treating fields do not stimulate nerves and muscle because of their high frequency, and do …

Putative Roles Of Cd200 In The Leukemogenesis And Immune Evasion Of Leukemia Stem Cells, Shelley Herbrich

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) stem cells (LSC) are capable of surviving current standard chemotherapy and are the likely source of deadly, relapsed disease. While stem cell transplant serves as proof-of-principle that AML LSCs can be eliminated by the immune system, the translation of existing immunotherapies to AML have been met with limited success. Consequently, understanding and exploiting the unique immune mechanisms of AML LSCs is critical. To identify novel immunotherapeutic targets, we sourced multiple large, publicly available datasets and identified CD200 as a potential stem-cell specific immune checkpoint in AML. We hypothesized that CD200 was a stem-cell specific mechanism of …

Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing, Alexander Davis

Dissertations and Theses (Open Access)

Tumor cells have heterogeneous genotypes, which drives progression and treatment resistance. Such genetic intratumor heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting data. Researchers lack methods to determine whether sufficiently many cells have been sampled from a tumor. In addition, there are no proven computational methods for determining the ploidy of a cell, a necessary step in the determination of copy number. In this work, software for calculating probabilities from …

Understanding Spatial Language In Radiology: Representation Framework, Annotation, And Spatial Relation Extraction From Chest X-Ray Reports Using Deep Learning, Surabhi Datta, Yuqi Si, Laritza Rodriguez, Sonya E Shooshan, Dina Demner-Fushman, Kirk Roberts

Faculty, Staff and Student Publications

Radiology reports contain a radiologist's interpretations of images, and these images frequently describe spatial relations. Important radiographic findings are mostly described in reference to an anatomical location through spatial prepositions. Such spatial relationships are also linked to various differential diagnoses and often described through uncertainty phrases. Structured representation of this clinically significant spatial information has the potential to be used in a variety of downstream clinical informatics applications. Our focus is to extract these spatial representations from the reports. For this, we first define a representation framework based on the Spatial Role Labeling (SpRL) scheme, which we refer to as …

Paraventricular Hypothalamus Mediates Diurnal Rhythm Of Metabolism, Eun Ran Kim, Yuanzhong Xu, Ryan M Cassidy, Yungang Lu, Yongjie Yang, Jinbin Tian, De-Pei Li, Rachel Van Drunen, Aleix Ribas-Latre, Zhao-Lin Cai, Mingshan Xue, Benjamin R Arenkiel, Kristin Eckel-Mahan, Yong Xu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening …

Disrupted Hypothalamic Crh Neuron Responsiveness Contributes To Diet-Induced Obesity, Canjun Zhu, Yuanzhong Xu, Zhiying Jiang, Jin Bin Tian, Ryan M Cassidy, Zhao-Lin Cai, Gang Shu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qingyan Jiang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both …

Parenteral Lipids Shape Gut Bile Acid Pools And Microbiota Profiles In The Prevention Of Cholestasis In Preterm Pigs, Lee Call, Tiffany Molina, Barbara Stoll, Greg Guthrie, Shaji Chacko, Jogchum Plat, Jason Robinson, Sen Lin, Caitlin Vonderohe, Mahmoud Mohammad, Dennis Kunichoff, Stephanie Cruz, Patricio Lau, Muralidhar Premkumar, Jon Nielsen, Zhengfeng Fang, Oluyinka Olutoye, Thomas Thymann, Robert Britton, Per Sangild, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, …

Covid-19 Testnorm: A Tool To Normalize Covid-19 Testing Names To Loinc Codes, Xiao Dong, Jianfu Li, Ekin Soysal, Jiang Bian, Scott L Duvall, Elizabeth Hanchrow, Hongfang Liu, Kristine E Lynch, Michael Matheny, Karthik Natarajan, Lucila Ohno-Machado, Serguei Pakhomov, Ruth Madeleine Reeves, Amy M Sitapati, Swapna Abhyankar, Theresa Cullen, Jami Deckard, Xiaoqian Jiang, Robert Murphy, Hua Xu

Faculty, Staff and Student Publications

Large observational data networks that leverage routine clinical practice data in electronic health records (EHRs) are critical resources for research on coronavirus disease 2019 (COVID-19). Data normalization is a key challenge for the secondary use of EHRs for COVID-19 research across institutions. In this study, we addressed the challenge of automating the normalization of COVID-19 diagnostic tests, which are critical data elements, but for which controlled terminology terms were published after clinical implementation. We developed a simple but effective rule-based tool called COVID-19 TestNorm to automatically normalize local COVID-19 testing names to standard LOINC (Logical Observation Identifiers Names and Codes) …

Alteration Of Iron Responsive Gene Expression In Arabidopsis Glutaredoxin S17 Loss Of Function Plants With Or Without Iron Stress, Ninghui Cheng, Han Yu, Xiaolan Rao, Sunghun Park, Erin L Connolly, Kendal D Hirschi, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Iron (Fe) is a mineral nutrient and a metal cofactor essential for plants. Iron limitation can have detrimental effects on plant growth and development, while excess iron inside plant cells leads to oxidative damage. As a result, plants have evolved complex regulatory networks to respond to fluctuations in cellular iron concentrations. The mechanisms that regulate these responses however, are not fully understood. Heterologous expression of an Arabidopsis thaliana monothiol glutaredoxin S17 (GRXS17) suppresses the over-accumulation of iron in the Saccharomyces cerevisiae Grx3/Grx4 mutant and disruption of GRXS17 causes plant sensitivity to exogenous oxidants and iron deficiency stress. GRXS17 may act …