Dietetics and Clinical Nutrition Commons^™

Identification Of Dietary Supplements Associated With Blood Metabolites In The Hispanic Community Health Study/Study Of Latinos Cohort Study, Robert C Kaplan, Jessica S Williams-Nguyen, Yuhan Huang, Yasmin Mossavar-Rahmani, Bing Yu, Eric Boerwinkle, Marc D Gellman, Martha Daviglus, Aisha Chilcoat, Linda Van Horn, Kim Faurot, Qibin Qi, Heather Greenlee

Faculty, Staff and Student Publications

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements.

OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk.

METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites …

The Inherited Intestinal Microbiota From Myeloid-Specific Zip8ko Mice Impairs Pulmonary Host Defense Against Pneumococcal Pneumonia, Derrick R. Samuelson, Deandra R. Smith, Kelly C. Cunningham, Sabah Haq, Daniel N. Villageliú, Christi Christi Ellis, Niaz Bahar Chowdhury, Amanda E. Ramer-Tait, Jeff Price, Daren L. Knoell

Food for Health: Publications

Intestinal dysbiosis increases susceptibility to infection through the alteration of metabolic profiles, which increases morbidity. Zinc (Zn) homeostasis in mammals is tightly regulated by 24 Zn transporters. ZIP8 is unique in that it is required by myeloid cells to maintain proper host defense against bacterial pneumonia. In addition, a frequently occurring ZIP8 defective variant (SLC39A8 rs13107325) is strongly associated with inflammation-based disorders and bacterial infection. In this study, we developed a novel model to study the effects of ZIP8-mediated intestinal dysbiosis on pulmonary host defense independent of the genetic effects. Cecal microbial communities from a myeloid-specific Zip8 knockout mouse …

Survey Of Nutrition Education Among Medical Students, Michael P. Duggan, Anahita T. Kodali, Zach A. Panton, Shannon M. Smith, Grant J. Riew, Jack F. Donaghue, Gregory A. Leya, Logan G. Briggs

Journal of Wellness

Introduction: The current literature regarding both specific interventions and the current level of nutrition education in the United States is scarce. The purpose of this paper is to provide medical student perspectives on both the degree and necessity of nutrition education during medical school.

Methods: Medicine in Motion (MM) is a non-profit student-run organization founded in 2018 that aims to address burnout in medicine through physical activity, community service, and philanthropy. MM issued a survey to nine of its chapters in January 2021 to assess a range of topics including burnout, physical activity, and nutrition education.

Results: Of 5500 invited …

Identification Of A Gabaergic Neural Circuit Governing Leptin Signaling Deficiency-Induced Obesity, Yong Han, Yang He, Lauren Harris, Yong Xu, Qi Wu

Faculty, Staff and Students Publications

The hormone leptin is known to robustly suppress food intake by acting upon the leptin receptor (LepR) signaling system residing within the agouti-related protein (AgRP) neurons of the hypothalamus. However, clinical studies indicate that leptin is undesirable as a therapeutic regiment for obesity, which is at least partly attributed to the poorly understood complex secondary structure and key signaling mechanism of the leptin-responsive neural circuit. Here, we show that the LepR-expressing portal neurons send GABAergic projections to a cohort of α3-GABAA receptor expressing neurons within the dorsomedial hypothalamic nucleus (DMH) for the control of leptin-mediated obesity phenotype. We identified the …

Health Consequences Of Low Energy Availability In Females And Their Underlying Physiological Mechanisms, Grace Parry

Senior Honors Theses

Low energy availability (LEA) is a state in which energy intake is insufficient to support energy expenditure while maintaining energy balance, which has been shown to result in gastrointestinal distress, immunosuppression, reduced metabolic rate, menstrual dysfunction, diminished bone health, and impaired cardiovascular function in females. Alterations to the microbiome and mucosal lining may propagate gastrointestinal complaints and compromised immune function associated with LEA. The pathophysiology of LEA is otherwise largely driven by hormonal adaptations. Diminished production of thyroid hormones is known to contribute to reduced metabolic rate. Decreases in leptin and insulin and increases in ghrelin disrupt reproductive function through …

The Effect Of A Pharmaceutical Ghrelin Agonist On Lifespan In C57bl/6j Male Mice: A Controlled Experiment, Kathryn A Kaiser, Inga Kadish, Thomas Van Groen, Daniel L Smith, Stephanie Dickinson, Beate Henschel, Erik S Parker, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

Interventions for animal lifespan extension like caloric restriction (CR) have identified physiologic and biochemical pathways related to hunger and energy-sensing status as possible contributors, but mechanisms have not been fully elucidated. Prior studies using ghrelin agonists show greater food intake but no effect on lifespan in rodent models. This experiment in male C57BL/6J mice tested the influence of ghrelin agonism for perceived hunger, in the absence of CR, on longevity. Mice aged 4 weeks were allowed to acclimate for 2 weeks prior to being assigned (N = 60/group). Prior to lights off daily (12:12 cycle), animals were fed a ghrelin …

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive To Change In Carotenoid Intake In A 6-Week Randomized Controlled Feeding Trial In A Racially/Ethnically Diverse Sample, Stephanie Jilcott Pitts, Nancy E Moran, Melissa N Laska, Qiang Wu, Lisa Harnack, Stacey Moe, Pamela Carr-Manthe, Elizabeth Gates, Jocelyn Chang, Yusuf Zaidi, Abigail Gelineau, Lauren Berg, Neal E Craft

Children’s Nutrition Research Center Staff Publications

Background: Reflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter-assessed skin carotenoid score change is responsive to changes in carotenoid intake.

Objectives: This study aimed to evaluate Veggie Meter-assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial.

Methods: …

Effect Of The Physical Fibrillated Sweet Potato (Ipomoea Batatas) Stem On The Plant-Based Patty Analogues, Suyoon Lee, You Young Lee, Yang Kim, Seung Hwan Ham, Min Gyu Lee, Jungwoo Hahn, Young Jin Choi

Faculty, Staff and Student Publications

In this study, a dietary fiber extracted from sweet potato stems (Ipomoea batatas, PS) was evaluated for its ability to improve the quality of vegetable patty analogues. A patty analogues containing 0–50 wt% dietary fiber were prepared to analyze the utilized dietary fiber's performance. To evaluate the manufactured patty analogues, texture profile analysis, color analysis, emulsion stability, and microstructural analysis were conducted. As the PS increased, the hardness decreased, while the total expressible fluids tended to increase. The color analysis revealed that the a* value, which represents red, declined as the PS content increased, and heterogeneous colors showed …

Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device …

Soybean Gmsaul1, A Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely Through Repressing The Activation Of Gmmpk3, Jun-Mei Li, Mei-Yan Ye, Chaofeng Wang, Xiao-Han Ma, Ni-Ni Wu, Chen-Li Zhong, Yanjun Zhang, Ninghui Cheng, Paul A Nakata, Lirong Zeng, Jian-Zhong Liu

Faculty, Staff and Students Publications

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, …

Scurvy, Abnormal Mri, And Gelatinous Bone Marrow In An Adolescent With Avoidant Restrictive Food Intake Disorder, Ginny Claire Kim, Asha M Davidson, Rebecca M Beyda, Mona A Eissa

Faculty, Staff and Student Publications

BACKGROUND: Although medical literature describes pediatric scurvy as "rare", a growing number of case reports suggests otherwise. Patients often undergo costly and unnecessary workup due to unfamiliarity with the presentation of scurvy. This case report further supports the small yet growing literature documenting scurvy and its manifestations in patients with eating disorders.

CASE PRESENTATION: A 15-year-old female presented to the emergency department with bilateral knee and ankle swelling and pain in the setting of chronic lower limb rash and BMI of 16.3. For years, she had restricted her diet to carbohydrates. Exam showed perifollicular petechial hemorrhagic rash with corkscrew hairs, …

Use Of Dual Genomic Sequencing To Screen Mitochondrial Diseases In Pediatrics: A Retrospective Analysis, Teng-Hui Wu, Jing Peng, Li Yang, Yan-Hui Chen, Xiu-Lan Lu, Jiao-Tian Huang, Jie-Yu You, Wen-Xian Ou-Yang, Yue-Yu Sun, Yi-Nan Xue, Xiao Mao, Hui-Ming Yan, Rong-Na Ren, Jing Xie, Zhi-Heng Chen, Victor-Wei Zhang, Gui-Zhen Lyu, Fang He

Children’s Nutrition Research Center Staff Publications

Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged <  18 years) who underwent dual genomic sequencing were enrolled in this retrospective multicentre study. We evaluated the mitochondrial disease criteria (MDC) and molecular diagnostic yield of dual genomic sequencing. Causative variants were identified in 177 out of 503 (35.2%) patients using dual genomic sequencing. Forty-six patients (9.1%) had mitochondria-related variants, including 25 patients with nuclear DNA (nDNA) variants, 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (MT-ND6 and POLG; MT-ND5 and RARS2; MT-TL1 and NARS2; MT-CO2 and NDUFS1; MT-CYB and SMARCA2; and CHRNA4 and MT-CO3). Based on the MDC, 15.2% of the patients with mitochondria-related variants were classified as "unlikely to have mitochondrial disorder". Moreover, 4.5% of the patients with non-mitochondria-related variants and 1.43% with negative genetic tests, were classified as "probably having mitochondrial disorder". Dual genomic sequencing in suspected MDs provided a more comprehensive and accurate diagnosis for pediatric patients, especially for patients with dual genomic variants.

Child Weight Status: The Role Of Feeding Styles And Highly Motivated Eating In Children, Maria A Papaioannou, Thomas G Power, Teresia M O'Connor, Jennifer O Fisher, Nilda E Micheli, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

Although parental feeding plays an important role in child eating and weight status, high food motivation among children may also be a factor shaping how feeding impacts child weight. This study explored whether individual differences in preschool children’s food motivation interacted with mothers’ feeding styles in predicting subsequent child weight status. Participants included 129 Hispanic Head Start mother/child dyads. Data were collected at ages 4–5 years (Time 1) and 7–9 (Time 3). Staff measured heights/weights and observed children in an eating in the absence of hunger task. Mothers reported on feeding styles/practices and children’s eating behaviors. A principal components analysis …

Child Weight Status: The Role Of Feeding Styles And Highly Motivated Eating In Children, Maria A Papaioannou, Thomas G Power, Teresia M O'Connor, Jennifer O Fisher, Nilda E Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Although parental feeding plays an important role in child eating and weight status, high food motivation among children may also be a factor shaping how feeding impacts child weight. This study explored whether individual differences in preschool children’s food motivation interacted with mothers’ feeding styles in predicting subsequent child weight status. Participants included 129 Hispanic Head Start mother/child dyads. Data were collected at ages 4–5 years (Time 1) and 7–9 (Time 3). Staff measured heights/weights and observed children in an eating in the absence of hunger task. Mothers reported on feeding styles/practices and children’s eating behaviors. A principal components analysis …

Validation Of The Entrainment Signal Regularity Index And Associations With Children’S Changes In Bmi, Jennette P Moreno, Kevin M Hannay, Amy R Goetz, Olivia Walch, Philip Cheng

Children’s Nutrition Research Center Staff Publications

Objective: This study examined the validity of a novel metric of circadian health, the Entrainment Signal Regularity Index (ESRI), and its relationship to changes in BMI during the school year and summer.

Methods: In a longitudinal observational data set, this study examined the relationship between ESRI score and children's (n = 119, 5- to 8-year-olds) sleep and physical activity levels during the school year and summer, differences in ESRI score during the school year and summer, and the association of ESRI score during the school year and summer with changes in BMI across those time periods.

Results: The ESRI score …

Asprosin Promotes Feeding Through Sk Channel-Dependent Activation Of Agrp Neurons, Bing Feng, Hesong Liu, Ila Mishra, Clemens Duerrschmid, Peiyu Gao, Pingwen Xu, Chunmei Wang, Yanlin He

Faculty, Staff and Students Publications

Asprosin, a recently identified adipokine, activates agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARH) via binding to protein tyrosine phosphatase receptor δ (Ptprd) to increase food intake. However, the intracellular mechanisms responsible for asprosin/Ptprd-mediated activation of AgRPARH neurons remain unknown. Here, we demonstrate that the small-conductance calcium-activated potassium (SK) channel is required for the stimulatory effects of asprosin/Ptprd on AgRPARH neurons. Specifically, we found that deficiency or elevation of circulating asprosin increased or decreased the SK current in AgRPARH neurons, respectively. AgRPARH-specific deletion of SK3 (an SK channel subtype highly expressed in AgRPARH neurons) blocked asprosin-induced …

Promoting Health Equity: Identifying Parent And Child Reactions To A Culturally-Grounded Obesity Prevention Program Specifically Designed For Black Girls Using Community-Engaged Research, Haley Allen, Chishinga Callender, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

The Butterfly Girls (BFG) Study is a culturally and developmentally appropriate online obesity prevention program for 8-10-year-old Black girls designed with key stakeholders in the Black community. This multi-methods investigation, conducted with parent-child dyads who participated in an outcome evaluation of the intervention, aimed to understand parent and child reactions to the program. We were particularly interested in understanding perceptions regarding its cultural and developmental appropriateness, relevance and acceptability. Program participation and survey data (demographics, parent and child write-in comments on process evaluation surveys) were analyzed. Participation data demonstrated high adherence in treatment and comparison groups. Descriptive statistics were calculated …

Tracking The Evolution Of Esophageal Squamous Cell Carcinoma Under Dynamic Immune Selection By Multi-Omics Sequencing, Sijia Cui, Nicholas Mcgranahan, Jing Gao, Peng Chen, Wei Jiang, Lingrong Yang, Li Ma, Junfang Liao, Tian Xie, Congying Xie, Tariq Enver, Shixiu Wu

Children’s Nutrition Research Center Staff Publications

Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, …

Dual-Specificity Phosphatases 22-Deficient T Cells Contribute To The Pathogenesis Of Ankylosing Spondylitis, Ming-Han Chen, Huai-Chia Chuang, Yi-Chen Yeh, Chung-Tei Chou, Tse-Hua Tan

Children’s Nutrition Research Center Staff Publications

Background: Dual-specificity phosphatases (DUSPs) can dephosphorylate both tyrosine and serine/threonine residues of their substrates and regulate T cell-mediated immunity and autoimmunity. The aim of this study was to investigate the potential roles of DUSPs in ankylosing spondylitis (AS).

Methods: Sixty AS patients and 45 healthy controls were enrolled in this study. Associations of gene expression of 23 DUSPs in peripheral T cells with inflammatory cytokine gene expression and disease activity of AS were analyzed. Finally, we investigated whether the characteristics of AS are developed in DUSP-knockout mice.

Results: The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in peripheral …

Biosynthesis Of Chlorophyll And Other Isoprenoids In The Plastid Of Red Grape Berry Skins, António Teixeira, Henrique Noronha, Sarah Frusciante, Gianfranco Diretto, Hernâni Gerós

Faculty, Staff and Student Publications

Despite current knowledge showing that fruits like tomato and grape berries accumulate different components of the light reactions and Calvin cycle, the role of green tissues in fruits is not yet fully understood. In mature tomato fruits, chlorophylls are degraded and replaced by carotenoids through the conversion of chloroplasts in chromoplasts, while in red grape berries, chloroplasts persist at maturity and chlorophylls are masked by anthocyanins. To study isoprenoid and lipid metabolism in grape skin chloroplasts, metabolites of enriched organelle fractions were analyzed by high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and the expression of key genes was evaluated by real-time …

How Much Did It Cost To Develop And Implement An Ehealth Intervention For A Minority Children Population That Overlapped With The Covid-19 Pandemic?, Alexandra Monashefsky, Dar Alon, Tom Baranowski, Tiago V Barreira, Kelly A Chiu, Amy Fleischman, Melanie C Green, Shirley Huang, Ronald C Samuels, Caio Victor Sousa, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions.

Objectives: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19.

Methods: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs.

Results: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant …

Randomized Controlled Trial Of A Novel Lifestyle Intervention Used With Or Without Meal Replacements In Work Sites, Sai Krupa Das, Rachel E Silver, Taylor A Vail, Meghan K Chin, Caroline M Blanchard, Stephanie L Dickinson, Xiwei Chen, Lisa Ceglia, Edward Saltzman, David B Allison, Susan B Roberts

Children’s Nutrition Research Center Staff Publications

Objective: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting.

Methods: Twelve work sites were randomized to an 18-month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6-month wait-listed control (n = 4). Participants were employees …

Diabetes Of Unclear Type In An Adolescent Boy With Multiple Islet-Cell Autoantibody Positivity Successfully Managed With Glucagon-Like Peptide-1 Receptor Agonist Alone: A Case Report, Olivia Z B Ginnard, Maria J Redondo, Sarah K Lyons

Children’s Nutrition Research Center Staff Publications

Diabetes classification has traditionally considered type 1 and type 2 diabetes as 2 separate entities with different pathogenic mechanisms. However, clinicians and researchers see increasingly more exceptions to this conventional paradigm, leading to a concept of mixed phenotypes in diabetes classification. Herein we report the case of an adolescent with unclear diabetes type due to the presence of obesity, robust endogenous insulin production, multiple islet autoantibody positivity and severe hyperglycemia at diabetes diagnosis that has been successfully treated with liraglutide therapy alone. Our case report highlights the difficulty of diabetes classification and subsequent need for personalized medicine with regard to …

How Much Did It Cost To Develop And Implement An Ehealth Intervention For A Minority Children Population That Overlapped With The Covid-19 Pandemic?, Alexandra Monashefsky, Dar Alon, Tom Baranowski, Tiago V Barreira, Kelly A Chiu, Amy Fleischman, Melanie C Green, Shirley Huang, Ronald C Samuels, Caio Victor Sousa, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions.

Objectives: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19.

Methods: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs.

Results: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant …

Association Of Lifestyle Behaviors With Non-Alcoholic Fatty Liver Disease And Advanced Fibrosis Detected By Transient Elastography Among Hispanic/Latinos Adults In The Us, Natalia I Heredia, Xiaotao Zhang, Maya Balakrishnan, Jessica P Hwang, Aaron P Thrift

Faculty, Staff and Students Publications

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease, with the highest prevalence observed in the U.S. among Hispanic/Latino adults. While physical activity and dietary behaviors have established protective associations with NAFLD and its severity, these associations have not been well-characterized in Hispanic/Latino adults. The purpose of this study was to assess the association of lifestyle behaviors with NAFLD and advanced fibrosis in US Hispanic/Latino adults.

DESIGN: We selected all Hispanic/Latino adults from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). NAFLD was defined as CAP ≥285 dB/m, and advanced fibrosis as liver stiffness measurements ≥8.6 …

Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson

Faculty, Staff and Students Publications

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.

METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification …

Structure Of The Lysosomal Mtorc1-Tfeb-Rag-Ragulator Megacomplex, Zhicheng Cui, Gennaro Napolitano, Mariana E G De Araujo, Alessandra Esposito, Jlenia Monfregola, Lukas A Huber, Andrea Ballabio, James H Hurley

Duncan NRI Faculty and Staff Publications

The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy1. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1)2–5 is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN6,7. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the ‘megacomplex’. Two full Rag–Ragulator complexes …

Brain Nuclear Receptors And Cardiovascular Function, Mengjie Wang, Yongjie Yang, Yong Xu

Faculty, Staff and Students Publications

Brain-heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which …

Pgc-1Α Senses The Cbc Of Pre-Mrna To Dictate The Fate Of Promoter-Proximally Paused Rnapii, Xavier Rambout, Hana Cho, Roméo Blanc, Qing Lyu, Joseph M Miano, Joe V Chakkalakal, Geoffrey M Nelson, Hari K Yalamanchili, Karen Adelman, Lynne E Maquat

Children’s Nutrition Research Center Staff Publications

PGC-1α is well established as a metazoan transcriptional coactivator of cellular adaptation in response to stress. However, the mechanisms by which PGC-1α activates gene transcription are incompletely understood. Here, we report that PGC-1α serves as a scaffold protein that physically and functionally connects the DNA-binding protein estrogen-related receptor α (ERRα), cap-binding protein 80 (CBP80), and Mediator to overcome promoter-proximal pausing of RNAPII and transcriptionally activate stress-response genes. We show that PGC-1α promotes pausing release in a two-arm mechanism (1) by recruiting the positive transcription elongation factor b (P-TEFb) and (2) by outcompeting the premature transcription termination complex Integrator. Using mice …

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …