Digital Commons Network^™

Ultrafiltration Rate And Incident Atrial Fibrillation Among Older Individuals Initiating Hemodialysis, Jennifer E Flythe, Sai Liu, Maria E Montez-Rath, Wolfgang C Winkelmayer, Tara I Chang

Faculty, Staff and Students Publications

BACKGROUND: Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients.

METHODS: We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67 years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) …

Breastfeeding And Risk Of Overweight In Childhood And Beyond: A Systematic Review With Emphasis On Sibling-Pair And Intervention Studies, Kathryn G Dewey, Darcy Güngör, Sharon M Donovan, Emily M Madan, Sudha Venkatramanan, Teresa A Davis, Ronald E Kleinman, Elsie M Taveras, Regan L Bailey, Rachel Novotny, Nancy Terry, Gisela Butera, Julie Obbagy, Janet De Jesus, Eve Stoody

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Breastfeeding is associated with a lower risk of subsequent overweight or obesity, but it is uncertain whether this is a causal relation because most studies have not adequately reduced risk of bias due to confounding.

OBJECTIVES: The aim of this review was to examine whether 1) ever compared with never consuming human milk and 2) different durations of human milk consumption among infants fed human milk are related to later risk of overweight or obesity, with emphasis on sibling-pair and intervention studies.

METHODS: The 2020 Dietary Guidelines Advisory Committee, together with the Nutrition Evidence Systematic Review team, conducted a …

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, 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 J A Camps, Graeme L Close, Jamie A Cooper, Sai K Das, Richard Cooper, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije 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 K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa 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 U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Dale A Schoeller, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

Identification Of An Atp/P2x7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness, Xiaomei Kong, William C Bennett, Corey M Jania, Kelly D Chason, Zachary German, Jennifer Adouli, Samuel D Budney, Brandon T Oby, Catharina Van Heusden, Eduardo R Lazarowski, Ilona Jaspers, Scott H Randell, Barry A Hedgespeth, Glenn Cruse, Xiaoyang Hua, Stephen A Schworer, Gregory J Smith, Samir Np Kelada, Stephen L Tilley

Faculty, Staff and Student Publications

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast …

Apathy Is Not Associated With A Panel Of Biomarkers In Older Adults With Hiv Disease, Steven Paul Woods, Jennifer L Thompson, Michelle A Babicz, Lokesh Shahani, Gabriela Delevati Colpo, Natalia P Rocha, Erin E Morgan, Antonio L Teixeira

Faculty, Staff and Student Publications

OBJECTIVE: Apathy is prevalent in HIV disease and can significantly impact personal well-being; however, little is known about its neurobiological substrates in persons with HIV (PWH) disease.

METHODS: This cross-sectional, correlational study examined the association between apathy and several plasma biomarkers (tumor necrosis factor alpha, kynurenine, tryptophan, quinolinic acid, brain-derived neurotrophic factor, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau at position threonine 181) in 109 PWH and 30 seronegative participants ages 50 and older. Apathy was measured with a composite score derived from subscales of the Frontal Systems Behavior Scale and the Profile of Mood States.

RESULTS: …

Feasibility Of A Sensor-Controlled Digital Game For Heart Failure Self-Management: Randomized Controlled Trial, Kavita Radhakrishnan, Christine Julien, Tom Baranowski, Matthew O'Hair, Grace Lee, Atami Sagna De Main, Catherine Allen, Bindu Viswanathan, Edison Thomaz, Miyong Kim

Faculty, Staff and Students Publications

BACKGROUND: Poor self-management of heart failure (HF) contributes to devastating health consequences. Our innovative sensor-controlled digital game (SCDG) integrates data from sensors to trigger game rewards, progress, and feedback based on the real-time behaviors of individuals with HF.

OBJECTIVE: The aim of this study is to compare daily weight monitoring and physical activity behavior adherence by older adults using an SCDG intervention versus a sensors-only intervention in a feasibility randomized controlled trial.

METHODS: English-speaking adults with HF aged 55 years or older who owned a smartphone and could walk unassisted were recruited from Texas and Oklahoma from November 2019 to …

Dna Methylation At A Nutritionally Sensitive Region Of The Pax8 Gene Is Associated With Thyroid Volume And Function In Gambian Children, Toby Candler, Noah J Kessler, Chathura J Gunasekara, Kate A Ward, Philip James, Eleonora Laritsky, Maria S Baker, Roger Dyer, Rajavel Elango, David Jeffries, Robert A Waterland, Sophie E Moore, Marian Ludgate, Andrew M Prentice, Matt J Silver

Children’s Nutrition Research Center Staff Publications

PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and PAX8 gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that PAX8 hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range. Free T4 was associated with a decrease in DXA-derived body fat and bone mineral density. Furthermore, offspring PAX8 methylation was associated with periconceptional maternal nutrition, and …

Surgical Treatment Of Valvular Heart Disease In Nigeria: A 6-Year Experience, Ikechukwu A Nwafor, John C Eze, Maureen N Nwafor

The Texas Heart Institute Journal

Surgical treatment of valvular heart disease in Nigeria, the most populous country in sub-Saharan Africa, is adversely affected by socioeconomic factors such as poverty and ignorance. To evaluate our experience in this context, we identified all patients who underwent surgery for acquired or congenital valvular heart disease at our Nigerian center from February 2013 through January 2019. We collected data from their medical records, including patient age and sex, pathophysiologic causes and types of valvular disease, surgical treatment, and outcomes. Ninety-three patients (43 males [46.2%]; mean age, 38.9 ± 10.0 yr [range, 11–80 yr]) underwent surgical treatment of a total …

Left Ventricular Ballooning Patterns In Recurrent Takotsubo Cardiomyopathy: A Systematic Review And Meta-Analysis Of Reported Cases, Ravi Korabathina, Jamie Porcadas, Kevin E Kip, Puja R Korabathina, Andrew D Rosenthal, Peter Wassmer

The Texas Heart Institute Journal

Recurrent takotsubo cardiomyopathy (TTC) and the clinical profiles and outcomes of patients have not been fully evaluated, nor has the effect of left ventricular ballooning pattern. After searching the medical literature for reports of patients with recurrent TTC, we identified 84 articles with 101 case descriptions. We divided the cases into those with only apical left ventricular ballooning patterns at recurrence (typical, n=60), and those with at least one midventricular or basal ballooning pattern (atypical, n=41). We then compared their clinical profiles and outcomes.

The groups were similar in terms of baseline demographic characteristics, presence and types of triggers, use …

Mitophagy In Depression: Pathophysiology And Treatment Targets, Ashutosh Tripathi, Giselli Scaini, Tatiana Barichello, João Quevedo, Anilkumar Pillai

Faculty, Staff and Student Publications

Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS) production and cell-free mitochondrial DNA (mtDNA) release, leading to increased inflammation. Mitophagy is a vital pathway, which selectively removes defective mitochondria through the process of autophagy. Thus, an impairment in the mitophagy pathway might trigger the gradual accumulation of defective mitochondria. Accumulating evidence suggest that inflammation and mitochondrial dysfunction are linked to the pathogenesis of depression. In this article, we have reviewed the role of impaired mitophagy as a contributing factor in depression pathophysiology. Further, we have discussed the potential …

Analysis Of Covid-19 Infection And Mortality Among Patients With Psychiatric Disorders, 2020, Antonio L Teixeira, Trudy Millard Krause, Lopita Ghosh, Lokesh Shahani, Rodrigo Machado-Vieira, Scott D Lane, Eric Boerwinkle, Jair C Soares

Faculty, Staff and Student Publications

IMPORTANCE: People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19.

OBJECTIVE: To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested …

Hop2 Interacts With The Transcription Factor Cebpα And Suppresses Adipocyte Differentiation, Tonghui Lin, Yang Zhang, Tingting Zhang, Rita A Steckler, Xiangli Yang

Faculty, Staff and Student Publications

CCAAT enhancer binding protein (CEBP) transcription factors (TFs) are known to promote adipocyte differentiation; however, suppressors of CEBP TFs have not been reported thus far. Here, we find that homologous chromosome pairing protein 2 (Hop2) functions as an inhibitor for the TF CEBPα. We found that Hop2 mRNA is highly and specifically expressed in adipose tissue, and that ectopic Hop2 expression suppresses reporter activity induced by CEBP as revealed by DNA transfection. Recombinant and ectopically expressed Hop2 was shown to interact with CEBPα in pull-down and coimmunoprecipitation assays, and interaction between endogenous Hop2 and CEBPα was observed in the nuclei …

Positron Emission Tomography In The Covid-19 Pandemic Era, Chentao Jin, Xiaoyun Luo, Shufang Qian, Kai Zhang, Yuanxue Gao, Rui Zhou, Peili Cen, Zhoujiao Xu, Hong Zhang, Mei Tian

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of …

Citalopram For Treatment Of Cocaine Use Disorder: A Bayesian Drop-The-Loser Randomized Clinical Trial, Robert Suchting, Charles E Green, Constanza De Dios, Jessica Vincent, F Gerard Moeller, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose.

METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits …

Revisiting The Controversy: The Role Of Fungi In Chronic Rhinosinusitis, Matthew A Tyler, Kent Lam, Michael J Marino, William C Yao, Isaac Schmale, Martin J Citardi, Amber U Luong

Faculty, Staff and Student Publications

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial.

Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a Type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have …

Ckb Inhibits Epithelial-Mesenchymal Transition And Prostate Cancer Progression By Sequestering And Inhibiting Akt Activation, Zheng Wang, Mohit Hulsurkar, Lijuan Zhuo, Jinbang Xu, Han Yang, Samira Naderinezhad, Lin Wang, Guoliang Zhang, Nanping Ai, Linna Li, Jeffrey T Chang, Songlin Zhang, Ladan Fazli, Chad J Creighton, Fang Bai, Michael M Ittmann, Martin E Gleave, Wenliang Li

Faculty, Staff and Students Publications

Epithelial-mesenchymal transition (EMT) contributes to tumor invasion, metastasis and drug resistance. AKT activation is key in a number of cellular processes. While many positive regulators for either EMT or AKT activation have been reported, few negative regulators are established. Through kinase cDNA screen, we identified brain-type creatine kinase (CKB or BCK) as a potent suppressor for both. As a ubiquitously expressed kinase in normal tissues, CKB is significantly downregulated in several solid cancer types. Lower CKB expression is significantly associated with worse prognosis. Phenotypically, CKB overexpression suppresses, while its silencing promotes, EMT and cell migration, xenograft tumor growth and metastasis …

Mortality, Kidney Failure, And Hospitalization Among Medicare Beneficiaries With Ckd And Pulmonary Hypertension, Sankar D Navaneethan, Carl P Walther, L Parker Gregg, Shweta Bansal, Wolfgang C Winkelmayer, Vijay Nambi, Jingbo Niu

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis.

STUDY DESIGN: Retrospective, observational study using a matched cohort design.

SETTING & PARTICIPANTS: Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016).

PREDICTOR: Presence of pulmonary hypertension.

OUTCOME: Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization.

ANALYTICAL …

Patient Characteristics And Outcomes Of Type 2 Myocardial Infarction During Heart Failure Hospitalizations In The United States, Salik Nazir, Abdul Mannan Khan Minhas, Ishan S Kamat, Robert W Ariss, George V Moukarbel, Juan Carlos Plana Gomez, Savitri Fedson, Ajith Nair, Biykem Bozkurt, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Type 2 myocardial infarction (MI) is increasingly diagnosed in patients with heart failure (HF). A paucity of data exists pertinent to the contemporary prevalence and impact of type 2 MI in patients with HF. We studied the patient profiles and the prognostic impact of type 2 MI on outcomes of HF hospitalizations.

METHODS: The Nationwide Readmission Database 2018 was queried for patients with HF hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between both cohorts were compared.

RESULTS: Of 1,072,674 primary HF hospitalizations included in the study, 28,813 (2.7%) had type 2 …

Drivers Of Transcriptional Variance In Human Intestinal Epithelial Organoids, Zachary K Criss, Nobel Bhasin, Sara C Di Rienzi, Anubama Rajan, Kali Deans-Fielder, Ganesh Swaminathan, Nabiollah Kamyabi, Xi-Lei Zeng, Harsha Doddapaneni, Vipin K Menon, Deepavali Chakravarti, Clarissa Estrella, Xiaomin Yu, Ketki Patil, Joseph F Petrosino, James C Fleet, Michael P Verzi, Sylvia Christakos, Michael A Helmrath, Sumimasa Arimura, Ronald A Depinho, Robert A Britton, Anthony W Maresso, K Jane Grande-Allen, Sarah E Blutt, Sue E Crawford, Mary K Estes, Sasirekha Ramani, Noah F Shroyer

Faculty, Staff and Students Publications

Human intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the human intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. RNA-sequencing datasets from 276 experiments performed on 37 human enteroid and colonoid lines from 29 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and gene set enrichment analysis (GSEA) were used to identify differentially expressed genes and enriched pathways. PERMANOVA, Pearson's correlation, and dendrogram analysis of the data originally indicated …

Comparison Of Culture With Antibiogram To Next-Generation Sequencing Using Bacterial Isolates And Formalin-Fixed, Paraffin-Embedded Gastric Biopsies, Kristina G Hulten, Robert M Genta, Ira N Kalfus, Yi Zhou, Hongjun Zhang, David Y Graham

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies.

METHODS: H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics.

RESULTS: Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, …

Clinical Outcomes Of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia In A County Hospital System, Effrosyni Apostolidou, Curtis Lachowiez, Harinder S Juneja, Wei Qiao, Onyebuchi Ononogbu, Courtney Nicole Miller-Chism, Mark Udden, Hilary Ma, Martha Pritchett Mims

Faculty, Staff and Student Publications

BACKGROUND: Major advances in the treatment of acute lymphoblastic leukemia (ALL) over the past decade have resulted in 5-year overall survival (OS) rates of 80% in mature B cell ALL, 50% in precursor B cell ALL, 50% to 60% in T cell ALL, and 60% to 70% in Philadelphia chromosome-positive (Ph+) ALL, as reported in studies from large, specialized centers. However, many patients treated in the community have limited access to novel therapies and stem cell transplantation (HSCT).

PATIENTS AND METHODS: The purpose of this retrospective cohort analysis was to evaluate the clinical outcomes of patients ≥ 16 years with …

Glycogen Storage Disease Type Ia: Current Management Options, Burden And Unmet Needs, Terry G J Derks, David F Rodriguez-Buritica, Ayesha Ahmad, Foekje De Boer, María L Couce, Sarah C Grünert, Philippe Labrune, Nerea López Maldonado, Carolina Fischinger Moura De Souza, Rebecca Riba-Wolman, Alessandro Rossi, Heather Saavedra, Rupal Naik Gupta, Vassili Valayannopoulos, John Mitchell

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists …

Replication Stress Response Defects Are Associated With Response To Immune Checkpoint Blockade In Nonhypermutated Cancers, Daniel J Mcgrail, Patrick G Pilié, Hui Dai, Truong Nguyen Anh Lam, Yulong Liang, Leonie Voorwerk, Marleen Kok, Xiang H-F Zhang, Jeffrey M Rosen, Amy B Heimberger, Christine B Peterson, Eric Jonasch, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Treatment with immune checkpoint blockade (ICB) has resulted in durable responses for a subset of patients with cancer, with predictive biomarkers for ICB response originally identified largely in the context of hypermutated cancers. Although recent clinical data have demonstrated clinical responses to ICB in certain patients with nonhypermutated cancers, previously established ICB response biomarkers have failed to accurately identify which of these patients may benefit from ICB. Here, we demonstrated that a replication stress response (RSR) defect gene expression signature, but not other proposed biomarkers, is associated with ICB response in 12 independent cohorts of patients with nonhypermutated cancer across …

Energy Compensation And Adiposity In Humans, Vincent Careau, Lewis G Halsey, Herman Pontzer, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Sai Krupa Das, Richard Cooper, Lara R Dugas, Simon D Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije 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 K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa 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, John J Reilly, 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 U Loechl, Amy H Luke, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, William W Wong, Yosuke Yamada, John R Speakman, Iaea Dlw Database Group

Children’s Nutrition Research Center Staff Publications

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.

Super-Resolution Microscopy Reveals Photoreceptor-Specific Subciliary Location And Function Of Ciliopathy-Associated Protein Cep290, Valencia L Potter, Abigail R Moye, Michael A Robichaux, Theodore G Wensel

Faculty, Staff and Students Publications

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout …

Simultaneous Monitoring Cytoplasmic Calcium Ion And Cell Surface Phosphatidylserine In The Necrotic Touch Neurons Of Caenorhabditis Elegans, Yoshitaka Furuta, Zheng Zhou

Faculty, Staff and Students Publications

Calcium ions trigger many cellular events, including the release of neurotransmitters at the synaptic terminal and excitotoxic cell death. Recently, we have discovered that a transient increase in the level of cytoplasmic Ca2+ triggers the exposure of phosphatidylserine (PS) on the surfaces of necrotic cells in the nematode Caenorhabditis elegans. PS serves as an “eat me” signal that attracts engulfing cells to engulf and degrade necrotic cells. During the above study, we developed a microscopic imaging protocol for real-time monitoring the levels of cytoplasmic Ca2+ and cell surface PS in Caenorhabditis elegans touch neurons. Previously, Ca2+ dynamics was monitored …

Precision Food Parenting: A Proposed Conceptual Model And Research Agenda, Tom Baranowski, Debbe Thompson, Sheryl O Hughes, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Precision medicine, nutrition and behavioral interventions are attempting to move beyond the specification of therapies applied to groups, since some people benefit, some do not and some are harmed by the same therapy. Instead, precision therapies are attempting to employ diverse sets of data to individualize or tailor interventions to optimize the benefits for the receiving individuals. The benefits to be achieved are mostly in the distant future, but the research needs to start now. While precision pediatric nutrition will combine diverse demographic, behavioral and biological variables to specify the optimal foods a child should eat to optimize health, precision …

A Selective Antibiotic For Lyme Disease, Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S Polikanov, Cecily A Freliech, Julie E Mccarthy, Diane G Edmondson, Steven J Norris, Anthony D'Onofrio, Linden T Hu, Helen I Zgurskaya, Kim Lewis

Faculty, Staff and Student Publications

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining …

Norovirus Protease Structure And Antivirals Development, Boyang Zhao, Liya Hu, Yongcheng Song, Ketki Patil, Sasirekha Ramani, Robert L Atmar, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is an excellent target for developing small-molecule inhibitors. The current strategy for developing HuNoV protease inhibitors is by targeting the enzyme's active site and designing inhibitors that bind to the substrate-binding pockets located near the active site. However, subtle differential conformational flexibility in response to the different substrates in the polyprotein and structural differences in the active site and …

Free-Floating Immunostaining Of Mouse Brains, Longlong Tu, Nan Zhang, Kristine M Conde, Jonathan C Bean, Chunmei Wang, Yong Xu

Children’s Nutrition Research Center Staff Publications

Immunohistochemical staining of mouse brains is a routine technique commonly used in neuroscience to investigate central mechanisms underlying the regulation of energy metabolism and other neurobiological processes. However, the quality, reliability, and reproducibility of brain histology results may vary among laboratories. For each staining experiment, it is necessary to optimize the key procedures based on differences in species, tissues, targeted proteins, and the working conditions of the reagents. This paper demonstrates a reliable workflow in detail, including intra-aortic perfusion, brain sectioning, free-floating immunostaining, tissue mounting, and imaging, which can be followed easily by researchers in this field.

Also discussed are …