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The Influence Of Tas2r38 Bitter Taste Gene Polymorphisms On Obesity Risk In Three Racially Diverse Groups, Chaowanee Chupeerach, Pradtana Tapanee, Nattira On-Nom, Piya Temviriyanukul, Boonrat Chantong, Nicole Reeder, Grace A. Adegoye, Terezie Tolar-Peterson

BioMedicine

Objectives: Bitter taste perception affects food preference, eating behavior, and nutrient intake. The purpose of this study was to investigate the contribution of bitter taste gene polymorphisms to body fatness as measured by percentage of body fat.

Method: Three common single nucleotide polymorphisms (SNPs) of the TAS2R38 gene which result in amino acid changes in the protein (A49P, V262A, and I296V), were studied in three racially diverse groups: European Americans n=313, African Americans n=109, and Asians n=234.

Results: The allele frequencies of the three SNPs were similar to previous studies. The rare haplotypes, AAI and AAV, were found in high …

Konjac Glucomannan Polysaccharide And Inulin Oligosaccharide Ameliorate Dextran Sodium Sulfate-Induced Colitis And Alterations In Fecal Microbiota And Short-Chain Fatty Acids In C57bl/6j Mice, Chih-Hsuan Changchien, Cheng-Hsin Wang, Hsiao-Ling Chen

BioMedicine

Background: Konjac glucomannan polysaccharide (KGM), inulin oligosaccharide (inulin) and their mixture has been shown to modulate the gut-associated lymphoid tissue immunity.

Aims: The present study was mainly to determine effects of a low-level (2% w/w) KGM and inulin and their combination on dextran sodium sulfate (DSS)-induced colitis. We also determine the potential mechanisms mediating these effects of dietary fibers.

Methods: C57BL/6J mice (6 weeks of age, eight per group) were randomly assigned to consume one of the following diets: control (DSS group) or control diet supplemented with 2% (w/w) of KGM (KGM group), 2% (w/w) of inulin oligosaccharide (degree of …

A Cancer Ubiquitome Landscape Identifies Metabolic Reprogramming As Target Of Parkin Tumor Suppression, Ekta Agarwal, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Jagadish C Ghosh, Lucia Languino, Valentina Vaira, David W Speicher, Dario C Altieri

Department of Cancer Biology Faculty Papers

Changes in metabolism that affect mitochondrial and glycolytic networks are hallmarks of cancer, but their impact in disease is still elusive. Using global proteomics and ubiquitome screens, we now show that Parkin, an E3 ubiquitin ligase and key effector of mitophagy altered in Parkinson's disease, shuts off mitochondrial dynamics and inhibits the non-oxidative phase of the pentose phosphate pathway. This blocks tumor cell movements, creates metabolic and oxidative stress, and inhibits primary and metastatic tumor growth. Uniformly down-regulated in cancer patients, Parkin tumor suppression requires its E3 ligase function, is reversed by antioxidants, and is independent of mitophagy. These data …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

2021 Scas Annual Meeting Program And Bulletin

Journal of the South Carolina Academy of Science

No abstract provided.

The Effect Of Qualitative Versus Quantitative Nutritional Education On The Eating Habits Of Female High School Athletes, Brantley Aycock

Journal of the South Carolina Academy of Science

No abstract provided.

The Effect Of Poverty Levels And Minority Percentages On Lead Content In South Carolina Midlands School Drinking Water, Kathleen L. Barfield

Journal of the South Carolina Academy of Science

No abstract provided.

Exploring The Effect Of Metal Chelating Properties Of Hylocereus Undatus, Artocarpus Heterophyllus, And Rubus Idaeus On The Lifespan Of Caenorhabditis Elegans: Potential Ace Inhibitors, Evelyn Plakal

Journal of the South Carolina Academy of Science

No abstract provided.

Elevated Lipid Oxidation Is Associated With Exceeding Gestational Weight Gain Recommendations And Increased Neonatal Anthropometrics: A Cross-Sectional Analysis, Jill M. Maples, Samantha F. Ehrlich, Nikki B. Zite, Kevin J. Pearson, W. Todd Cade, Courtney J. Riedinger, Maire M. Blankenship, Rachel A. Tinius

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Deviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG and neonatal outcomes. The purpose of this study was to explore the potential link between maternal lipid oxidation rate, GWG, and neonatal anthropometric outcomes.

METHODS: Women (N = 32) with a lean pre-pregnancy BMI were recruited during late pregnancy and substrate metabolism was assessed using indirect calorimetry, before and after consumption of a high-fat meal. GWG was categorized as follows: inadequate, adequate, or excess. Shortly …

Dermatitis Herpetiformis: An Update On Diagnosis, Disease Monitoring, And Management, Christopher N Nguyen, Soo-Jung Kim

Faculty, Staff and Students Publications

Dermatitis herpetiformis (DH), Duhring disease, is caused by gluten sensitivity and affects 11.2 to 75.3 per 100,000 people in the United States and Europe with an incidence of 0.4 to 3.5 per 100,000 people per year. DH is characterized by a symmetrical blistering rash on the extensor surfaces with severe pruritus. The diagnosis continues to be made primarily by pathognomonic findings on histopathology, especially direct immunofluorescence (DIF). Recently, anti-epidermal transglutaminase (TG3) antibodies have shown to be a primary diagnostic serology, while anti-tissue transglutaminase (TG2) and other autoantibodies may be used to support the diagnosis and for disease monitoring. Newly diagnosed …

Correcting For Sparsity And Interdependence In Glycomics By Accounting For Glycan Biosynthesis, Bokan Bao, Benjamin P Kellman, Austin W T Chiang, Yujie Zhang, James T Sorrentino, Austin K York, Mahmoud A Mohammad, Morey W Haymond, Lars Bode, Nathan E Lewis

Children’s Nutrition Research Center Staff Publications

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps. Furthermore, the overlap of measured glycans can be low across samples. We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power. …

Proof Of Concept: The Use Of Renal Biomarkers In Critically Ill Pediatric Patients For Therapeutic Drug Monitoring, Christopher Lee Shaffer

Theses & Dissertations

Acute kidney injury (AKI) is a serious and common complication in critically ill pediatric patients. The incidence of pediatric AKI continues to increase, especially in patients who undergo surgical correction of congenital heart defects. Serum creatinine and urine output are the most commonly used tools to assess renal function, with international guidelines standardizing AKI-definitions based upon these parameters. However, changes in serum creatinine can occur 24 hours or later after a renal insult event, delaying the diagnosis and potential interventions to reverse injury. It is critical to identify endogenous renal biomarkers within the pediatric population that are both timely and …

Daily Energy Expenditure Through The Human Life Course, Herman Pontzer, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marjije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Teresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at …

Thermal Properties Of 18f-Fdg Uptake And Imaging In Positron Emission Tomography Scans Of Cancerous Cells, Carleigh R. Eagle

PANDION: The Osprey Journal of Research and Ideas

Positron Emission Tomography (PET) scans can utilize a radioactive tracer, in this case 2-deoxy2-[fluorine-18] fluoro-D-glucose (¹⁸F-FDG), to visualize malignant tumors in cancer patients. The uptake was compared to glucose to understand the difference in thermal properties, which contribute to the ability to image the cancerous cells. The uptake of ¹⁸F-FDG by cancer cells and the imaging process of positron emission tomography were reviewed from a thermodynamic perspective. Gastrointestinal and neurological imaging techniques were reviewed to understand the role of PET imaging in different areas of the human body.

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer

Faculty, Staff and Students Publications

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma …

Simple Energy Balance Or Microbiome For Childhood Obesity Prevention?, Tom Baranowski, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Obesity prevention interventions generally have either not worked or had effects inadequate to mitigate the problem. They have been predicated on the simple energy balance model, which has been severely questioned by biological scientists. Numerous other etiological mechanisms have been proposed, including the intestinal microbiome, which has been related to childhood obesity in numerous ways. Public health research is needed in regard to diet and the microbiome, which hopefully will lead to effective child obesity prevention.

Monogenic Diabetes In Youth With Presumed Type 2 Diabetes: Results From The Progress In Diabetes Genetics In Youth (Prodigy) Collaboration, Jennifer N Todd, Jeffrey W Kleinberger, Haichen Zhang, Shylaja Srinivasan, Sherida E Tollefsen, Lynne L Levitsky, Lorraine E Levitt Katz, Jeanie B Tryggestad, Fida Bacha, Giuseppina Imperatore, Jean M Lawrence, Catherine Pihoker, Jasmin Divers, Jason Flannick, Dana Dabelea, Jose C Florez, Toni I Pollin

Children’s Nutrition Research Center Staff Publications

Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.

Research design and methods: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic …

A Noncoding Rna Modulator Potentiates Phenylalanine Metabolism In Mice, Yajuan Li, Zhi Tan, Yaohua Zhang, Zhao Zhang, Qingsong Hu, Ke Liang, Yao Jun, Youqiong Ye, Yi-Chuan Li, Chunlai Li, Lan Liao, Jianming Xu, Zhen Xing, Yinghong Pan, Sujash S Chatterjee, Tina K Nguyen, Heidi Hsiao, Sergey D Egranov, Nagireddy Putluri, Cristian Coarfa, David H Hawke, Preethi H Gunaratne, Kuang-Lei Tsai, Leng Han, Mien-Chie Hung, George A Calin, Fares Namour, Jean-Louis Guéant, Ania C Muntau, Nenad Blau, V Reid Sutton, Manuel Schiff, François Feillet, Shuxing Zhang, Chunru Lin, Liuqing Yang

Faculty, Staff and Students Publications

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that …

Testing The Effects Of Two Field-To-Fork Programs On The Nutritional Outcomes Of Elementary School Students From Diverse And Lower-Income Communities, Kimberly R. Hartson, Kristi M. King, Carol O'Neal, Aishia Brown, Toluwanimi Olajuyigbe, Shakeyrah Elmore, Angelique Perez

Faculty and Staff Scholarship

The purpose of this quasi-experimental study was to evaluate the effects of two farm-to-school programs, specifically the Field-to-Fork Multi-visit Program (N  =  264) and the Field-to-Fork After-school Club (N  =  56), on nutritional outcomes of elementary school students (third to fifth grade) from urban, diverse, and lower-income communities. Data were collected via self-report surveys measuring: (a) knowledge of recommendations for daily fruit and vegetable intake; (b) fruit and vegetable consumption; (c) knowledge of cooking a healthy recipe using vegetables; and (d) desire for farm fresh foods at school. Statistical analyses included McNemar’s and Wilcoxon signed rank tests. The …

Family-Based Obesity Prevention Interventions Among Hispanic Children And Families: A Scoping Review, Erica G Soltero, Armando Peña, Veronica Gonzalez, Edith Hernandez, Guisela Mackey, Chishinga Callender, Jayna M Dave, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

This scoping review examined intervention and sample characteristics of family-based obesity prevention interventions among Hispanic youth. This review also examined the degree to which existing interventions were culturally-adapted, acknowledged social determinants of health (SDoH), and collaborated with community stakeholders. A comprehensive search across Medline Ovid, Embase, Scopus, PsycInfo, and Pubmed was used to identify 13 studies primarily based in the U.S. (92.3%). Data was extracted by two independent reviewers. Most used a randomized control trial design (69.2%), a behavior change theory (84.6%), and reported moderate to high (≥70%) retention (69.2%). Studies targeted improvements in physical activity (69.2%) and fruit and …

A Machine Learning Case-Control Classifier For Schizophrenia Based On Dna Methylation In Blood, Chathura J Gunasekara, Eilis Hannon, Harry Mackay, Cristian Coarfa, Andrew Mcquillin, David St Clair, Jonathan Mill, Robert A Waterland

Children’s Nutrition Research Center Staff Publications

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

Graduate Theses/Dissertations

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Gestational Weight Gain In 4 Low- And Middle-Income Countries And Associations With Birth Outcomes: A Secondary Analysis Of The Women First Trial., Melissa S Bauserman, Carla M Bann, K Michael Hambidge, Ana L Garces, Lester Figueroa, Jamie L Westcott, Jackie K Patterson, Elizabeth M Mcclure, Vanessa R Thorsten, Sumera Ali Aziz, Sarah Saleem, Robert L Goldenberg, Richard Derman, Veena Herekar, Manjunath Somannavar, Marion W Koso-Thomas, Adrien L Lokangaka, Antoinette K Tshefu, Nancy F Krebs, Carl L Bose, Shivaprasad Goudar, Sangappa Dhaded, Bhalchandra Kodkany, Omrana Pasha, Abhik Das, Menachem Miodovnik, N K Raju Tonse

Global Health Articles

BACKGROUND: Adequate gestational weight gain (GWG) is essential for healthy fetal growth. However, in low- and middle-income countries, where malnutrition is prevalent, little information is available about GWG and how it might be modified by nutritional status and interventions.

OBJECTIVE: We describe GWG and its associations with fetal growth and birth outcomes. We also examined the extent to which prepregnancy BMI, and preconception and early weight gain modify GWG, and its effects on fetal growth.

METHODS: This was a secondary analysis of the Women First Trial, including 2331 women within the Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan, …

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey N. Thompson, Yan Yan, Tobyn Branck, Jeremy E. Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% …

Pedsql™ Gastroparesis Symptoms Module Domain And Item Development: Qualitative Methods, James W Varni, Robert J Shulman, Mariella M Self, Liz Febo-Rodriguez, Heather Charron, Kent Williams, Sam Nurko, Rachel L Rosen, Bruno P Chumpitazi

Children’s Nutrition Research Center Staff Publications

Objectives: Like adults, children suffer from gastroparesis; however, there are currently no validated instruments to determine the impact of gastroparesis in pediatric patients. The objective of this study was to develop the items and domains to support the content validity of the new Pediatric Quality of Life Inventory (PedsQL™) Gastroparesis Symptoms Module.

Methods: Patients were recruited from the National Institute of Diabetes and Digestive and Kidney Diseases Pediatric Gastroparesis Registry. The qualitative methods involved an iterative process comprising a literature review of existing questionnaires and gastroparesis clinical research, an expert review panel of pediatric gastroenterologists who provided feedback on the …

Recommendations For The Use Of The Veggie Meter® For Spectroscopy-Based Skin Carotenoid Measurements In The Research Setting, Marcela D Radtke, Mykaela Poe, Jodi Stookey, Stephanie Jilcott Pitts, Nancy E Moran, Matthew J Landry, Lewis P Rubin, Virginia C Stage, Rachel E Scherr

Children’s Nutrition Research Center Staff Publications

Carotenoids are a class of phytochemical compounds found in a variety of fruits and vegetables (F/V) and, therefore, are commonly used as a biomarker for F/V intake. The Veggie Meter® is a noninvasive research-grade instrument that detects and quantifies carotenoids in the skin. To determine current practices and examine variability among users, a survey was administered to researchers using the device (n = 19, response rate = 35.8%) and variation in anatomical site preparation, calibration, number of measurements, measurement site, and documentation was observed. A protocol was developed in partnership with Veggie Meter® users to outline the preparation, calibration, …

Metabolomics Profiling Of Patients With A-Β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis, Farook Jahoor, Jean W Hsu, Paras B Mehta, Kelly R Keene, Ruchi Gaba, Surya Narayan Mulukutla, Eunice Caducoy, W Frank Peacock, Sanjeet G Patel, Rasmus Bennet, Ake Lernmark, Ashok Balasubramanyam

Faculty, Staff and Students Publications

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as …

Thioredoxin Reductase Is A Major Regulator Of Metabolism In Leukemia Cells, Sheelarani Karunanithi, Ruifu Liu, Yongchun Hou, Giancarlo Gonzalez, Natasha Oldford, Anne Jessica Roe, Nethrie Idipilly, Kalpana Gupta, Chandra Sekhar Amara, Satwikreddy Putluri, Grace Kyueun Lee, Juan Valentin-Goyco, Lindsay Stetson, Stephen A Moreton, Vasanta Putluri, Shyam M Kavuri, Yogen Saunthararajah, Marcos De Lima, Gregory P Tochtrop, Nagireddy Putluri, David N Wald

Faculty, Staff and Students Publications

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for …