Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Human Milk Cortisol Is Associated With Infant Temperament, Katherine R. Grey, Elyssia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

The implications of the biologically active elements in milk for the mammalian infant are largely unknown. Animal models demonstrate that transmission of glucocorticoids through milk influences behavior and modifies brain development in offspring. The aim of this study was to determine the relation between human milk cortisol levels and temperament of the breastfed infant. Fifty-two mother and infant pairs participated when the infants were three-months old. Milk cortisol levels were assessed and each mother completed the Infant Behavior Questionnaire (IBQ), a widely used parent-report measure of infant temperament. Analyses revealed a positive association between milk cortisol and the negative affectivity …

Methods For Quantifying T Cell Receptor Binding Affinities And Thermodynamics, Kurt H. Piepenbrink, Brian E. Gloor, Kathryn M. Armstrong, Brian M. Baker

Food for Health: Publications

αβ T cell receptors (TCRs) recognize peptide antigens bound and presented by class I or class II major histocompatibility complex (MHC) proteins. Recognition of a peptide/MHC complex is required for initiation and propagation of a cellular immune response, as well as the development and maintenance of the T cell repertoire. Here we discuss methods to quantify the affinities and thermodynamics of interactions between soluble ectodomains of TCRs and their peptide/MHC ligands, focusing on titration calorimetry, surface plasmon resonance, and fluorescence anisotropy. As TCRs typically bind ligand with weak-to-moderate affinities, we focus the discussion on means to enhance the accuracy and …

Interaction Between Lubricants Containing Phosphate Ester Additives And Stainless Steels, David W. Johnson, Matthew Bachus, John E. Hils

Chemistry Faculty Publications

One way to improve fuel efficiency in today’s jet aircraft engines is to create an environment for higher operating temperatures and speeds. New and improved lubricants and bearing materials must be developed to remain stable in these elevated operating temperatures. Three lubricants, with varying amounts of tricresyl phosphate added as an anti-wear/extreme pressure additive were tested on two different stainless steels at varying temperatures ranging from 300 °C to 350 °C in vacuum. Significant decomposition of the lubricant base-stocks and the phosphate ester additive did occur in most of the trials resulting in the formation of carboxylic acids and phenols. …

Novel Therapeutic Targets Identified By High-Throughput Technologies For Triple-Negative Breast Cancer, Christine Shiang

Dissertations and Theses (Open Access)

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to …

Cinacalcet As Adjunctive Therapy For Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets., Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism from inadequate calcium absorption in the gut, is the underlying pathophysiology for rachitic changes in hereditary vitamin D-resistant rickets (HVDRR). We describe a novel use of Cinacalcet to treat a child with HVDRR in whom conventional modes of therapy had to be discontinued. Cinacalcet therapy with high-dose oral calcium effectively normalized the metabolic abnormalities and bone condition. The relative ease of administration of the calcimimetic as a once- or twice-daily oral preparation, compared with traditional intravenous calcium administration, should encourage its move to the frontline of treatment of the disorder.

Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose

Food for Health: Publications

Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and …

Fiber-Free White Flour With Fructose Offers A Better Model Of Metabolic Syndrome, Faridah Amin, Anwar Hassan Gilani

Department of Biological & Biomedical Sciences

BACKGROUND: The metabolic syndrome (MS) is a combination of metabolic abnormalities that lead to an increased risk of cardiovascular diseases. Due to its rising incidence and demanding life-long use of multiple drugs, there is a growing interest in testing and developing new allopathic, complementary and alternative therapies for controlling or curing disorders of MS. The discovery of new therapeutic modalities requires animal models of disease and currently available models have limitations. Developing an appropriate animal model for MS to achieve various therapeutic targets remains a challenge and this study aims to develop a rat model which closely depicts MS in …

The Healthy Incentive For Pre-Schools (Hip) Project: The Development, Validation, Evaluation And Implementation Of An Healthy Incentive Scheme In The Irish Full Day Care Pre-School Setting., Charlotte Johnston Molloy

Doctoral

While many children are now cared for outside the home, inadequate nutrition and physical activity practices in pre-schools have been reported. This study aimed to develop a validated nutrition and health related evaluation tool and an education information resource for pre-schools, and determine whether their use can promote improved food service and nutrition and physical activity practices in this setting. Following a pilot phase undertaken in Co. Wicklow (n 12), pre-schools providing a full day care service in the Midland Area of Ireland were invited to participate in the study (n, 100). Direct observation was used to collect data (food …

Control Of Candida Albicans Metabolism And Biofilm Formation By Pseudomonas Aeruginosa Phenazines, Diana K. Morales, Nora Grahl, Chinweike Okegbe, Lars E. P. Dietrich, Nicholas J. Jacobs, Deborah A. Hogan

Dartmouth Scholarship

Candidaalbicanshasdevelopmentalprogramsthatgoverntransitionsbetweenyeastandfilamentousmorphologies and between unattached and biofilm lifestyles. Here, we report that filamentation, intercellular adherence, and biofilm develop- ment were inhibited during interactions between Candida albicans and Pseudomonas aeruginosa through the action of P. aeruginosa-produced phenazines. While phenazines are toxic to C. albicans at millimolar concentrations, we found that lower concentrations of any of three different phenazines (pyocyanin, phenazine methosulfate, and phenazine-1-carboxylate) allowed growth but affected the development of C. albicans wrinkled colony biofilms and inhibited the fungal yeast-to-filament transition. Phenazines impaired C. albicans growth on nonfermentable carbon sources and led to increased production of fer- mentation products (ethanol, glycerol, and …

Offspring And Maternal Health Benefits Of Exercise During Pregnancy, Lindsay G. Carter

Theses and Dissertations--Nutritional Sciences

Maternal lifestyle and nutrient intake during pregnancy can have long-lasting effects on the health of offspring as well as the mother. This dissertation focuses on the impact of maternal exercise during pregnancy on offspring insulin sensitivity and glucose uptake and the maternal effects of exercise during pregnancy.

The first aim of this dissertation was to investigate if exercise prior to and during pregnancy and nursing would improve glucose uptake and insulin sensitivity in mice and rats. In both mice and rats, it was concluded that maternal exercise could enhance whole-body insulin sensitivity and increase glucose uptake into skeletal muscle and …

An Investigation Of Perinatal Polychlorinated Biphenyl Exposure On Body Composition And Glucose Homeostasis, Cetewayo S. Rashid

Theses and Dissertations--Nutritional Sciences

Recent advancements have uncovered environmental contributions to obesity and diabetes etiology. In fact, perinatal malnutrition resulting in low birth weight (LBW) has been shown to correlate with later life obesity and impaired glucose tolerance in aged offspring. LBW can result from a myriad of developmental perturbations including macronutrient restriction, hypoxia, maternal stress and toxin exposure.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that bioaccumulate in the food chain resulting in dietary exposure in humans. Maternal and cord blood PCB levels are inversely associated with birth weight, and recent studies indicate that perinatal exposures to PCBs contribute to gender-specific obesity development …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …

Development And Validation Of A Predictive Model Of Acute Glucose Response To Exercise In Individuals With Type 2 Diabetes, Bryan S. Gibson, Sheri R. Colberg, Paul Poirier, Denise Maria Martins Vancea, Jason Jones, Robin Marcus

Human Movement Studies & Special Education Faculty Publications

Background: Our purpose was to develop and test a predictive model of the acute glucose response to exercise in individuals with type 2 diabetes.

Design and methods: Data from three previous exercise studies (56 subjects, 488 exercise sessions) were combined and used as a development dataset. A mixed-effects Least Absolute Shrinkage Selection Operator (LASSO) was used to select predictors among 12 potential predictors. Tests of the relative importance of each predictor were conducted using the Lindemann Merenda and Gold (LMG) algorithm. Model structure was tested using likelihood ratio tests. Model accuracy in the development dataset was assessed by leave-one-out cross-validation. …

Coplanar Pcb-Induced Inflammation And Dietary Interventions, Katryn Elizabeth Eske

Theses and Dissertations--Nutritional Sciences

Diseases, such as cardiovascular disease (CVD), are linked to chronic low levels of inflammation. This inflamed state is the product of risk factors including exposure to environmental pollutants, such as polychlorinated biphenyls (PCBs), which are correlated with increased risk for CVD and diabetes. In response to this health risk, our research addresses the mechanisms by which coplanar PCBs elicit an inflammatory response and the mitigation of PCB-induced inflammation through dietary intervention using docosahexaenoic acid (DHA), an omega-3 lipid. Investigators from the University of Kentucky Engineering Department are developing remediation technologies that detoxify PCBs through dechlorination. We studied the cellular toxicity …

Preparation Of Phosphonoterephthalic Acids Via Palladium-Catalyzed Coupling Of Aromatic Iodoesters, Nathaniel Ivan, Vladimir Benin, Alexander Morgan

Chemistry Faculty Publications

The current article reports in detail the preparation of two phosphonoterephthalic acids: 2-phosphonoterephthalic acid (1) and 2,5-diphosphonoterephthalic acid (2). Efficient, scalable syntheses have been developed for both compounds based on Pd-catalyzed coupling reactions of iodinated terephthalate esters. Phosphonoterephthalic acids are potentially useful as flame-retardant additives or as monomers for the construction of acid-pendant polymer chains.

Reaction Between Polyol-Esters And Phosphate Esters In The Presence Of Metal Carbides, David W. Johnson, Carolyn Iacullo, John E. Hils

Chemistry Faculty Publications

The reaction of metal carbides with polyol esters found in aerospace lubricants and phosphate esters commonly used as additives was investigated. Carbides were of particular interest since modern materials under consideration at high temperature bearings have surfaces that are primarily metal carbides. Vanadium and chromium carbide were found to react with the ester and phosphate ester by a transesterification reaction, producing an alkyl phosphate which is less stable than the aromatic phosphate esters. In the process, the metal carbide is converted to the metal phosphate and metal polyphosphate, evidenced by the infrared and Raman spectra of the solid residue and …

The Role Of Dairy Products And Milk In Adolescent Obesity: Evidence From Hong Kong’S ‘‘Children Of 1997’’ Birth Cohort, Shi Lin Lin, Marie Tarrant, Lai Ling Hui, Man Ki Kwok, Tai Hing Lam, Gabriel M. Leung, Mary Schooling

Publications and Research

Background
Observational studies, mainly from Western populations, suggest dairy consumption is inversely associated with adiposity. However, in these populations the intake range is limited and both diet and obesity may share social patterning. Evidence from non-Western developed settings with different social patterning, is valuable in distinguishing whether observed associations are biologically mediated or socially confounded.

Objective
To examine the associations of milk or other dairy product consumption with adolescent obesity.

Methods
We used multivariable linear regression models to examine the associations of milk or other dairy product consumption, obtained from a food frequency questionnaire, at 11 years with body mass …

Development And Validation Of Sunlight Exposure Measurement Questionnaire (Sem-Q) For Use In Adult Population Residing In Pakistan, Quratulain Humayun, Romaina Iqbal, Iqbal Azam, Aysha Habib Khan, Amna Rehana Siddiqui, Naila Baig Ansari

Department of Pathology and Laboratory Medicine

Background: Vitamin D deficiency has been identified as a major public health problem worldwide. Sunlight is the main source of vitamin D and its measurement using dosimeters is expensive and difficult for use in population-based studies. Hence, the aim of this study was to develop and validate questionnaires to assess sunlight exposure in healthy individuals residing in Karachi, Pakistan.

Methods: Two questionnaires with seven important items for sunlight exposure assessment were developed. Fifty four healthy adults were enrolled based on their reported sunlight exposure (high = 17, moderate = 18, low = 19) from Aga Khan University, Karachi. Over four …

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Biochemistry and Microbiology

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …

Eating Behaviors Of Older Adults Participating In Government-Sponsored Programs With Different Demographic Backgrounds, Yeon Bai, Shahla M. Wunderlich, Joseph Brusca, Johnson-Austin Marti, Michelle O'Malley

Department of Nutrition and Food Studies Scholarship and Creative Works

The purpose of this study was to determine the food behaviors of nutritionally high-risk seniors as a function of their racial background, gender, marital status, and education level. A total of 69 seniors were identified to be at high nutritional risk using the Nutrition Screening Initiative (NSI) checklist. A supplemental questionnaire (SQ) was created to examine the risk factors in relation to the participant’s demographic background. Key results indicated that Asians practiced healthy food behaviors and women were more likely to eat alone (p≤0.05). Married participants (90.9%) were most likely to consume 2 meals or more each day. College educated …

Gut Microbiome Composition Is Linked To Whole Grain-Induced Immunological Improvements, Ines Martinez, James M. Lattimer, Kelcie L. Hubach, Jennifer A. Case, Junyi Yang, Casey G. Weber, Julie A. Louk, Devin J. Rose, Gayaneh Kyureghian, Daniel A. Peterson, Mark D. Haub, Jens Walter

Food for Health: Publications

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on …

Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman

Chemistry Faculty Publications

The reaction of an isomeric mixture of the methyl perfluoroalkyl ether, C4F9OCH3 (Novec-7100), in the presence of isopropyl alcohol (IPA) and/or water has been studied by measuring the rate of product formation using an ion-selective electrode (ISE) for fluoride ion, Karl Fisher coulometric titrations for water, and 1H and 19F NMR spectroscopy for product identification and rate studies. The results showed the methyl perfluoroalkyl ether to be very stable with products forming at the rate of ∼1 ppm per year at a laboratory temperature of 20 °C. Measurements over the temperature range of 6° to 100 °C were made on …

The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun

Dissertations and Theses (Open Access)

Plasma low-density lipoprotein (LDL) levels are positively correlated with the incidence of coronary artery disease. In the circulation, the plasma LDL clearance is mainly achieved by the uptake via LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered gene, playing an important role in LDL metabolism. Gain-of-function mutations of PCSK9 lead to hypercholesterolemia and loss-of-function mutations of PCSK9 are associated with decrease of LDL cholesterol. The effects of PCSK9 on cholesterol levels are the consequence of a strong interaction between the catalytic domain of PCSK9 and epidermal growth factor-like repeat A (EGF-A) domain of …

Metabolic Regulation Of Mtor Activation And Endoplasmic Reticulum Stress In The Heart, Shiraj Sen

Dissertations and Theses (Open Access)

When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin

Dissertations and Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …

Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang

MIIR Faculty Research

Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, …

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …

The Role Of Vascular Endothelial Growth Factor At The Blood-Brain Barrier In Diabetes, Aileen J. Marcelo

Theses, Dissertations and Capstones

Diabetes is a risk factor for stroke and vascular dementia. Clinical studies using gadolinium-magnetic resonance imaging techniques have shown diabetic patients exhibit a permeability increase at the blood-brain barrier (BBB) (Starr et al, 2003). The BBB, a vascular interface at the level of brain microvascular vessels, functions to provide nutrients and oxygen from the peripheral circulation, mediates waste efflux from the brain, and protects the brain from toxins. These functions are due to the presence of tight junction proteins. Animal studies have shown increased BBB permeability is due to a decrease in these proteins (Hawkins et al, 2007). Based on …

Effects Of Adipocyte Deficiency Of Angiotensin Type 1a Receptors In Models Of Obesity And Hypercholesterolemia, Kelly Anne Putnam

Theses and Dissertations--Nutritional Sciences

Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a …