Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Small Bowel Obstruction In Postpartum Vaginal Delivery Due To Prior Abdominal Adhesions Case Report, Liubin Yang, Lydia Kao

Children’s Nutrition Research Center Staff Publications

Intestinal obstruction rarely occurs after uncomplicated vaginal deliveries. Here, we present a case of a multiparous woman with a history of prior appendectomy presenting with generalized, nonspecific abdominal pain that was out of proportion to exam findings. Initial abdominal X-ray was nonspecific, and subsequent computed tomography (CT) abdomen showed closed small bowel obstruction requiring surgical repair. We present a case of intestinal obstruction occurring within 24 hours of uncomplicated vaginal delivery with a risk factor of a prior appendectomy surgery and the use of CT abdomen and pelvis to expedite diagnose.

Functional And Technical Outcomes In Acute Ischemic Stroke Patients With Hyperdense Middle Cerebral Artery Sign Treated With Endovascular Thrombectomy, Yimin Chen, Francesco Diana, Mohammad Mofatteh, Sijie Zhou, Juanmei Chen, Zhou Huang, Weijuan Wu, Yajie Yang, Zhiyi Zeng, Weijian Zhang, Ziqi Ouyang, Thanh N Nguyen, Shuiquan Yang, José Fidel Baizabal-Carvallo, Xuxing Liao

Children’s Nutrition Research Center Staff Publications

Background and objective: The hyperdense middle cerebral artery sign (HMCAS) is observed in a proportion of patients with acute ischemic stroke (AIS). This sign reflects the presence of an intravascular thrombus rich in red blood cells. Several studies have demonstrated that HMCAS increases the risk of poor outcomes in AIS patients treated with IV thrombolysis or no reperfusion therapy; however, whether HMCAS predicts a poor outcome in patients treated with endovascular thrombectomy (EVT) is less clear. We aimed to evaluate the functional outcome by the modified Rankin scale (mRS) at 90 days and technical challenges in patients with HMCAS undergoing …

Commentary: Effect Evaluation Of Sahtak Bi Sahnak, A Lebanese Secondary School-Based Nutrition Intervention: A Cluster Randomised Trial, Abu Bakkar Siddique, Andrew W Brown, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger

Williams Honors College, Honors Research Projects

I made endospanin 1 knockout (KO) zebrafish to examine its effects on lipid and bone metabolism. Endospanin 1, or leptin receptor overlapping transcript (leprot), is a cytosolic protein linked to the protein hormone leptin that influences the trafficking of leptin receptors to the plasma membrane of cells. Genes for endospanin and tyrosinase (a pigmentation enzyme) were targeted via a microinjection of guide RNAs and CRISPR Cas9 into zebrafish embryos at 2-4 cell stages. I was able to disrupt the endospanin 1 gene (based upon the disruption of tyrosinase), but very few mutant zebrafish fully developed into adults. Only low KO …

Advancements In Glycogen Detection And Spatial Profiling Reveals A New Therapeutic Path For Ewing Sarcoma: A Non-Traditional Glycogen Storage Disease, Lyndsay E. A. Young

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the primary glucose storage carbohydrate in mammals, and it is synthesized in most tissues. As glycogen architecture modulates its role in metabolism, it is essential to accurately evaluate and quantify glycogen, glycogen phosphate, and chain length of glucose monomers. Simultaneous quantitation of glycogen architecture is challenging. This work describes a highly-sensitive method for the detection of both glycogen-derived glucose and glucose-phosphate esters utilizing gas-chromatography coupled mass spectrometry (GCMS). We then integrated this glycogen quantitation workflow into a routinely utilized metabolomics-based assay. The work presented describes a workflow for the normalization of polar metabolites utilizing amino acids derived from …

Support Their Sleep: Enhancing Nurses' Knowledge And Implementation Of Non-Pharmacological Sleep Protocols To Improve Patient Rest, Recovery, And Reduce Cognitive Impairment., David C. Barry

Master's Theses and Capstones

Background: Sleep and rest play an influential role in promoting recovery and healing in humans. Hospitalized patients are at risk for altered sleep from hospitalization, illness, and stimulation from a hospital environment. Non-pharmacologic interventions preformed by nurses can help to improve sleep and sleep environment for patients.

Local problem: There was no protocol or available information regarding patient sleep promotion for nurses to references when caring for patients.

Methods: Nurses in the microsystem (n=8) were administered a pre/post questionnaire containing Likert scales and a short quiz containing knowledge-based questions. Questionnaires were distributed to nurses prior to and after …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Attitudes Toward Implicit Bias Among Ncaa Medical Support Staff, B J. Warner, A P. Jacobsen, M Decker, S A. Cage

Clinical Practice in Athletic Training

Introduction: Implicit biases are unconscious attitudes, emotions, or stereotypes that have the potential to negatively affect behaviors, actions, and decisions. Recent research has shown that healthcare workers do not provide equitable care to patients from different demographics. When patients are receiving different levels of care, there is a potential for different patient-related outcomes. One of their first steps in many implicit bias interventions for healthcare professionals is identifying one’s implicit bias. The purpose of this study was to describe the attitudes toward implicit bias among non-athletic training healthcare professionals who provide care to collegiate student-athletes. Methods: An electronic survey was …

Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu

Faculty, Staff and Student Publications

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in …

Chronic Restraint Stress Impairs Voluntary Wheel Running But Has No Effect On Food-Motivated Behavior In Mice, Kiersten Scott, Thien Trong Phan, Nabila Boukelmoune, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed …

Low Ferritin Count In Female Collegiate Soccer Player Presents As Concussion, E N. Nelson, T D. Pitcock, M K. Knoblauch, L J. Harrison

Clinical Practice in Athletic Training

Background: Women’s soccer leads the National Collegiate Athletic Association for having the highest number of concussions in female sports. Common symptoms of concussion can include light headedness, headaches, and dizziness, but these symptoms are not exclusive to concussions. Female athletes may experience nutritional deficits that can lead to a wide range of symptoms mimicking those commonly experienced with a concussion such as headaches, dizziness, and fatigue. The patient in this case is a 21- year-old female soccer athlete who presented with sensitivity to light, light headedness, nausea, and fatigue after experiencing repeated ‘headers’ as well as a collision during a …

Editorial: Metabolic Regulation Under Oxidative Stress In Cancer, Elavarasan Subramani, Abishai Dominic, Pratip K Bhattacharya, Daniel E Frigo, Ilya Bederman, Ali Vaziri-Gohar

Faculty, Staff and Student Publications

Oxidative stress has emerged as a key component of cancer metabolism that impacts multiple facets of tumor biology (1). Recent studies have shed light on the complex interplay of cellular redox and its impact on molecular mechanisms that govern metabolic reprogramming under oxidative stress (2, 3). It is well established that altered glucose metabolism exhibited by tumor cells leads to an enormous oxidative burden through various metabolic routes (4, 5). What is less known but remains a great interest to the field is whether elevated oxidative stress has a causal role in …

Comparison Of Two Lipid Emulsions On The Incidence Of Parenteral Nutrition Associated Cholestasis In Neonates, Joy Greenberg, Mamta Naik, John Chapman, Allison Davidson, Essam Imseis

Faculty, Staff and Student Publications

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE.

METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were …

Effect Of Stretch And Release On Myofascial Stem Cell Function In Vitro: A Putative Model To Understand The Molecular Benefits Of The Myofascial Release (Mfr) Technique, Ben Smith, Shahn Notta, Debasis Mondal

Research Day

Despite the beneficial effects of osteopathic manipulative techniques (OMT), there is a lack of in vitro models to understand the molecular mechanisms associated with these time-tested therapies. The Myofascial Release (MFR) technique is a non-invasive approach that involves passive stretching, hold and release, of the soft tissue to achieve myofascial homeostasis. Tissue-resident mesenchymal stem cells (MSC) can regulate the myofascial microenvironment by altering their secreted factors following stretch and release. Therefore, we initiated studies to develop an in vitro model to investigate the possible effects of stretch and release on MSC function, i.e. proliferation and differentiation capabilities, and changes in …

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Relationship Between Reproductive And Bone Biomarkers And Osteoarthritis In Zoo Asian (Elephas Maximus) And African (Loxodonta Africana) Elephants, Daniella E Chusyd, Janine L Brown, Lilian Golzarri-Arroyo, Stephanie L Dickinson, Virginia B Kraus, Jessica Siegal-Willott, Timothy M Griffin, Janet L Huebner, Katie L Edwards, David B Allison, Steven N Austad

Children’s Nutrition Research Center Staff Publications

Osteoarthritis (OA) is common in zoo Asian (Elephas maximus) and African (Loxodonta africana) elephants. This study investigated the relationship between confirmed or suspected OA with ovarian cyclicity, gonadotropins, progestagens, luteinizing hormone (LH), follicular stimulating hormone (FSH), and collagen type I (CTX-I) in zoo elephants. In Asian elephants, odds of having confirmed or suspected OA decreased with cycling (OR = 0.22, P = 0.016; OR = 0.29, P = 0.020, respectively), however, not when adjusted for age (odds ratio [OR] = 0.31, P = 0.112; OR = 0.58, P = 0.369, respectively). In African elephants, none of …

Conditioning On Parental Mating Types Can Reduce Necessary Assumptions For Mendelian Randomization, Keisuke Ejima, Nianjun Liu, Luis Miguel Mestre, Gustavo De Los Campos, David B Allison

Children’s Nutrition Research Center Staff Publications

Mendelian randomization (MR) has become a common tool used in epidemiological studies. However, when confounding variables are correlated with the instrumental variable (in this case, a genetic/variant/marker), the estimation can remain biased even with MR. We propose conditioning on parental mating types (a function of parental genotypes) in MR to eliminate the need for one set of assumptions, thereby plausibly reducing such bias. We illustrate a situation in which the instrumental variable and confounding variables are correlated using two unlinked diallelic genetic loci: one, an instrumental variable and the other, a confounding variable. Assortative mating or population admixture can create …

Editorial: Non-Coding Genome And Endocrinology: From Bench To Bedside, Radu Pirlog, Kinga Nemeth, George Adrian Calin

Faculty, Staff and Student Publications

No abstract provided.

A Conserved Oxalyl-Coenzyme A Decarboxylase In Oxalate Catabolism, Ninghui Cheng, Vincent Paris, Xiaolan Rao, Xiaoqiang Wang, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in multiple physiological problems. Such problems include a disruption of membrane integrity, mitochondrial function, metal chelation, and free radical formation. Recent work suggests that a CoA-dependent pathway of oxalate catabolism plays a critical role in regulating tissue oxalate concentrations in plants. Although this CoA-dependent pathway of oxalate catabolism is important, large gaps in our knowledge of the enzymes catalyzing each step remain. Evidence that an oxalyl-CoA decarboxylase (OXC) catalyzes the second step in this pathway, accelerating the …

Clinical Significance Of Glycolytic Metabolic Activity In Hepatocellular Carcinoma, Joann Jung, Sowon Park, Yeonwoo Jang, Sung-Hwan Lee, Yun Seong Jeong, Sun Young Yim, Ju-Seog Lee

Faculty, Staff and Student Publications

High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (n = 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor …

Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Christine U Vohwinkel, Nana Burns, Ethan Coit, Xiaoyi Yuan, Eszter K Vladar, Christina Sul, Eric P Schmidt, Peter Carmeliet, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during …

Does Receiving A Sars-Cov-2 Antibody Test Result Change Covid-19 Protective Behaviors? Testing Risk Compensation In Undergraduate Students With A Randomized Controlled Trial, Christina Ludema, Molly S Rosenberg, Jonathan T Macy, Sina Kianersi, Maya Luetke, Chen Chen, Lilian Golzarri-Arroyo, Erin Ables, Kevin Maki, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Risk compensation, or matching behavior to a perceived level of acceptable risk, can blunt the effectiveness of public health interventions. One area of possible risk compensation during the SARS-CoV-2 pandemic is antibody testing. While antibody tests are imperfect measures of immunity, results may influence risk perception and individual preventive actions. We conducted a randomized control trial to assess whether receiving antibody test results changed SARS-CoV-2 protective behaviors.

Purpose: Assess whether objective information about antibody status, particularly for those who are antibody negative and likely still susceptible to SARS-CoV-2 infection, increases protective behaviors. Secondarily, assess whether a positive antibody test …

The Role Of Lncrnas In The Tumor Microenvironment And Immunotherapy Of Melanoma, Wencheng Zhou, Xuewen Xu, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs …

Evaluation Of Recombinant Live-Attenuated Respiratory Syncytial Virus (Rsv) Vaccines Rsv/Δns2/Δ1313/I1314l And Rsv/276 In Rsv-Seronegative Children, Coleen K Cunningham, Ruth A Karron, Petronella Muresan, Matthew S Kelly, Elizabeth J Mcfarland, Charlotte Perlowski, Jennifer Libous, Jennifer Oliva, Patrick Jean-Philippe, Jack Moye, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Benjamin Johnston, Ellen G Chadwick, Mikhaela Cielo, Mary Paul, Jaime G Deville, Mariam Aziz, Lijuan Yang, Cindy Luongo, Peter L Collins, Ursula J Buchholz, International Maternal Pediatric Adolescent Aids Clinical Trials (Impaact) 2018 Study Team

Children’s Nutrition Research Center Staff Publications

Background: This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.

Methods: RSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.

Results: Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more …

The Rheumatoid Arthritis Drug Auranofin Lowers Leptin Levels And Exerts Antidiabetic Effects In Obese Mice, Aaron R Cox, Peter M Masschelin, Pradip K Saha, Jessica B Felix, Robert Sharp, Zeqin Lian, Yan Xia, Natasha Chernis, David A Bader, Kang Ho Kim, Xin Li, Jun Yoshino, Xin Li, Gang Li, Zheng Sun, Huaizhu Wu, Cristian Coarfa, David D Moore, Samuel Klein, Kai Sun, Sean M Hartig

Faculty, Staff and Student Publications

Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and coincides with type 2 diabetes mellitus (T2DM). However, pharmacological targeting of inflammation lacks durable therapeutic effects in insulin-resistant conditions. Through a computational screen, we discovered that the FDA-approved rheumatoid arthritis drug auranofin improved insulin sensitivity and normalized obesity-associated abnormalities, including hepatic steatosis and hyperinsulinemia in mouse models of T2DM. We also discovered that auranofin accumulation in WAT depleted inflammatory responses to a high-fat diet without altering body composition in obese wild-type mice. Surprisingly, elevated leptin levels and blunted beta-adrenergic receptor activity achieved by leptin receptor deletion abolished the antidiabetic …

Expression Of P-Stat3 And C-Myc Correlates With P2-Hnf4Α Expression In Nonalcoholic Fatty Liver Disease (Nafld), Mamoun Younes, Lin Zhang, Baharan Fekry, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

We studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 …

Modulation Of Sirtuins During Monolayer Chondrocyte Culture Influences Cartilage Regeneration Upon Transfer To A 3d Culture Environment, Hannah K Heywood, Stephen D Thorpe, Renos M Jeropoulos, Paul W Caton, David A Lee

Faculty, Staff and Student Publications

This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine. When subjected to osmolarity and glucose concentrations representative of the in vivo niche, freshly isolated bovine chondrocytes exhibited increases in SIRT1 but not SIRT3 gene expression. Replicating methods adopted for the in vitro monolayer expansion of chondrocytes for cartilage regenerative therapies, we …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …