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Human Islets Expressing Hnf1a Variant Have Defective Beta Cell Transcriptional Regulatory Networks, Rachana Haliyur, Sambra D. Redick, David M. Harlan, Alvin C. Powers 2019 Vanderbilt University

Human Islets Expressing Hnf1a Variant Have Defective Beta Cell Transcriptional Regulatory Networks, Rachana Haliyur, Sambra D. Redick, David M. Harlan, Alvin C. Powers

Open Access Articles

Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained beta cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1alpha (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction ...


Associations Between Income, Acculturation, Country Of Origin, And Type Ii Diabetes Among African Immigrants To Ontario, Canada, Girma Aman Goshe 2019 Walden University

Associations Between Income, Acculturation, Country Of Origin, And Type Ii Diabetes Among African Immigrants To Ontario, Canada, Girma Aman Goshe

Walden Dissertations and Doctoral Studies

Diabetes has become a longstanding public health challenge around the world. Over the last 3 decades, the number of people with Type II diabetes (T2DM) has grown to an epidemic level in Canada. Prior research indicated African immigrants residing in Ontario, Canada experienced a 2â??4 times higher prevalence of T2DM than Canadian-born individuals. The social determinants of health theoretical framework guided this study assessing the relationship of the risk factors with T2DM. A quantitative, cross-sectional design was employed using the 2007â??2014 Canadian Community Health Survey data. The random sample included 1,526 African immigrants residing in Ontario, Canada ...


Of Course, Humans Are Not Unique!, Bernard Wallner 2019 University of Vienna

Of Course, Humans Are Not Unique!, Bernard Wallner

Animal Sentience

This commentary focuses on the question of the uniqueness of humans in comparison to other species and on the false assumption that single arguments support logical conclusions. Comparative analysis of genetic data in humans and nonhuman primates regarding the dopaminergic system of the subcortical mesolimbic reward system highlights homologous traits shared and modified by the process of evolution. Such an analytical approach is more relevant than claims of uniqueness.


Measuring The Impact Of A Weeklong Fall Break On Stress Physiology In First Year Engineering Students, Ayesha Khan, Heather Poole, Elliott A. Beaton 2018 McMaster University

Measuring The Impact Of A Weeklong Fall Break On Stress Physiology In First Year Engineering Students, Ayesha Khan, Heather Poole, Elliott A. Beaton

The Canadian Journal for the Scholarship of Teaching and Learning

Canadian post-secondary institutions are increasingly introducing a fall break into their term calendars, with the stated goal of reducing student stress and improving academic success. We conducted a pilot study around the time of this fall break during which we collected saliva samples to measure the ratio of two metabolic hormones (cortisol and dehydroepiandrosterone (DHEA)) from first-year male engineering students in order to document possible changes in their stress levels before and after the break. Participants self-identified a particular day in the week prior to the break that they considered to be most stressful, followed by a day in the ...


Targeting Neuropeptides To Bone Fractures For Accelerated Healing, Nicholas A. Young, Jeffery J. Nielsen, Philip S. Low 2018 Purdue University

Targeting Neuropeptides To Bone Fractures For Accelerated Healing, Nicholas A. Young, Jeffery J. Nielsen, Philip S. Low

The Summer Undergraduate Research Fellowship (SURF) Symposium

In patients over the age of 65 especially, bone fractures represent a significant disease burden. Non-invasive drug therapies are not available for bone fractures which represents a problem for this population. Vasoactive intestinal peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), two neuromodulator peptides in the glucagon superfamily, have demonstrated positive regulation of osteoblast proliferation and activity. Using acidic oligopeptides, we have developed ligands that target to and accumulate at fracture sites. These targeting ligands can be synthesized in sequence with bone anabolic peptides to minimize off target effects and increase potency at the fracture site to create safer and ...


Anril: A Lncrna At The Cdkn2a/B Locus With Roles In Cancer And Metabolic Disease, Yahui Kong, Chih-Heng Hsieh, Laura C. Alonso 2018 University of Massachusetts Medical School

Anril: A Lncrna At The Cdkn2a/B Locus With Roles In Cancer And Metabolic Disease, Yahui Kong, Chih-Heng Hsieh, Laura C. Alonso

Open Access Articles

The CDKN2A/B genomic locus is associated with risk of human cancers and metabolic disease. Although the locus contains several important protein-coding genes, studies suggest disease roles for a lesser-known antisense lncRNA encoded at this locus, called ANRIL. ANRIL is a complex gene containing at least 21 exons in simians, with many reported linear and circular isoforms. Like other genes, abundance of ANRIL is regulated by epigenetics, classic transcription regulation, splicing, and post-transcriptional influences such as RNA stability and microRNAs. Known molecular functions of ANRIL include in cis and in trans gene regulation through chromatin modification complexes, and influence over ...


Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Donald A. Morgan, Kamal Rahmouni, Michael P. Czech 2018 University of Massachusetts Medical School

Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Donald A. Morgan, Kamal Rahmouni, Michael P. Czech

Open Access Articles

OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT).

METHODS AND RESULTS: Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This ...


Regulation Of Juvenile Hormone Synthesis By 20-Hydroxyecdysone In The Yellow-Fever Mosquito, Aedes Aegypti, Maria Areiza 2018 Florida International University

Regulation Of Juvenile Hormone Synthesis By 20-Hydroxyecdysone In The Yellow-Fever Mosquito, Aedes Aegypti, Maria Areiza

FIU Electronic Theses and Dissertations

In Aedes aegypti, development and reproduction are regulated by juvenile hormone III (JH). This master regulatory hormone is synthesized by the corpora allata (CA), a pair of endocrine glands with neural connections to the brain. JH titers are largely determined by the rate of biosynthetic activity of the CA and are regulated by inhibitory and stimulatory factors. Like JH, the ecdysteroid 20-hydroxyecdysone (20E) is a key hormonal regulator and has been proposed as an allatoregulator in other insects. However, its part in the regulation of JH biosynthesis of mosquitoes was unknown. The specific aims of this dissertation were to (1 ...


The Singing Voice During The First Two Years Of Testosterone Therapy: Working With The Trans Or Gender Queer Voice, Tessa M. Romano 2018 University of Colorado Boulder

The Singing Voice During The First Two Years Of Testosterone Therapy: Working With The Trans Or Gender Queer Voice, Tessa M. Romano

Voice and Opera Graduate Theses & Dissertations

In order to better serve singers who identify as trans men or gender queer, voice teachers must understand the vocal effects of hormone replacement therapy, specifically that of testosterone therapy. Testosterone therapy is the only type of hormone replacement therapy that permanently changes the voice and eventually results in a full octave drop or more of a person’s spoken fundamental frequency. Due to such a dramatic shift, the voice change process can be turbulent.

This dissertation is designed to educate both cis gender voice teachers and trans and gender queer singers on the process of vocal change during the ...


The Effect Of Ethanol On Skeletal Muscle Endocrine Function And The Novel Myokines Myonectin And Irisin, Kendra Hagood 2018 East Tennessee State University

The Effect Of Ethanol On Skeletal Muscle Endocrine Function And The Novel Myokines Myonectin And Irisin, Kendra Hagood

Electronic Theses and Dissertations

Excessive alcohol consumption is a leading cause of death and disability globally and can lead to diseases such as alcoholic skeletal myopathy. Skeletal muscle is the largest organ in the human body and functions to regulate whole-body energy homeostasis. Additionally, skeletal muscle can function as an endocrine organ via secretion of myokines. Two myokines, myonectin and irisin, present a wide range of effects upon metabolism, inflammation, and tissue survival- signaling. We hypothesized that chronic alcohol consumption will result in reduced circulating myonectin and irisin levels. Mice were fed an ethanol-containing or control diet for 10 days or 6 weeks. Tissues ...


Cystic Fibrosis-Related Diabetes Is Caused By Islet Loss And Inflammation, Nathaniel J. Hart, Jenny Aurielle B. Babon, Megan E. DeNicola, Sally C. Kent, Alvin C. Powers 2018 Vanderbilt University Medical Center

Cystic Fibrosis-Related Diabetes Is Caused By Islet Loss And Inflammation, Nathaniel J. Hart, Jenny Aurielle B. Babon, Megan E. Denicola, Sally C. Kent, Alvin C. Powers

Open Access Articles

Cystic fibrosis-related (CF-related) diabetes (CFRD) is an increasingly common and devastating comorbidity of CF, affecting approximately 35% of adults with CF. However, the underlying causes of CFRD are unclear. Here, we examined cystic fibrosis transmembrane conductance regulator (CFTR) islet expression and whether the CFTR participates in islet endocrine cell function using murine models of beta cell CFTR deletion and normal and CF human pancreas and islets. Specific deletion of CFTR from murine beta cells did not affect beta cell function. In human islets, CFTR mRNA was minimally expressed, and CFTR protein and electrical activity were not detected. Isolated CF/CFRD ...


Markers Of Cardiometabolic Risk And Thyroid Dysfunction In U.S. Adolescents: Nhanes Iii, Jonathan Austin 2018 Illinois State University

Markers Of Cardiometabolic Risk And Thyroid Dysfunction In U.S. Adolescents: Nhanes Iii, Jonathan Austin

Theses and Dissertations

The global prevalence of metabolic syndrome (MetS) and its associated components (high fasting glucose, waist circumference, blood pressure, triglycerides, and low HDL) have increased over the past few decades. In addition, abnormal thyroid hormone levels have been found to manifest in a cascade of metabolic dysfunction, which may be linked to MetS in youth. PURPOSE: The purpose of the study is to investigate the association between MetS, its components, and markers of thyroid function in a nationally-representative sample of adolescents. METHODS: The National Health and Nutrition Examination Survey III (1988-1994) collected data on the components of metabolic syndrome and thyroid ...


Aldosterone Regulation Of Protein Kinase D And Sodium Reabsorption In The Renal Cortical Collecting Duct, Sinéad Quinn 2018 Royal College of Surgeons in Ireland

Aldosterone Regulation Of Protein Kinase D And Sodium Reabsorption In The Renal Cortical Collecting Duct, Sinéad Quinn

PhD theses

Aldosterone is the key regulating hormone of whole body fluid and electrolyte balance. Perturbations in aldosterone synthesis and activation of its receptor, the mineralocorticoid receptor (MR), can lead to hypertension. Consequences of impaired sodium handling, for example hypertension, are a key risk factor in both renal and cardiovascular disease and indicative of impaired electrolyte homeostasis in the body. Renal sodium homeostasis can be modulated in several ways for example, by increasing aldosterone synthesis and activation of MR. Hypertension can also occur due to a dysregulation of aldosterone signalling which can often result in chronic pathologies of the kidney such as ...


Alpha Cell Function And Gene Expression Are Compromised In Type 1 Diabetes, Marcela Brissova, David Blodgett, Dale L. Greiner, David M. Harlan, Alvin C. Powers 2018 Vanderbilt University Medical Center

Alpha Cell Function And Gene Expression Are Compromised In Type 1 Diabetes, Marcela Brissova, David Blodgett, Dale L. Greiner, David M. Harlan, Alvin C. Powers

Open Access Articles

Many patients with type 1 diabetes (T1D) have residual beta cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual beta cells and alpha cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant beta cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D alpha cells was markedly reduced, and these cells had alterations in transcription factors constituting alpha and ...


Diabetes Impairs Wound Healing By Dnmt1-Dependent Dysregulation Of Hematopoietic Stem Cells Differentiation Towards Macrophages, Jinglian Yan, Guodong Tie, Shoying Wang, Amanda A. Tutto, Natale DeMarco, Lyne Khair, Thomas G. Fazzio, Louis M. Messina 2018 University of Massachusetts Medical School

Diabetes Impairs Wound Healing By Dnmt1-Dependent Dysregulation Of Hematopoietic Stem Cells Differentiation Towards Macrophages, Jinglian Yan, Guodong Tie, Shoying Wang, Amanda A. Tutto, Natale Demarco, Lyne Khair, Thomas G. Fazzio, Louis M. Messina

Open Access Articles

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU.1, and Klf4 ...


Oral Glucose Insulin Secretion Test For Identifying Patients With Insulin Resistance, David Kershner 2018 Walden University

Oral Glucose Insulin Secretion Test For Identifying Patients With Insulin Resistance, David Kershner

Walden Dissertations and Doctoral Studies

Insulin resistance is an increasing public health issue with the current literature, suggesting reduced sensitivity of insulin leads to adult onset diabetes and associated downstream pathologies that reduce life expectancy. The main objectives of this study were to evaluate the ability of the Oral Glucose Insulin Secretion Test (OGIST) to identify insulin resistance and examine differences in the insulin sensitivity based on gender, age, and ethnicity. This study was supported by the insulin resistance theory which focuses on the reduced ability of insulin to bind to the cellular insulin receptor, reducing the sensitivity of insulin. The OGIST lab results of ...


The Impact Of Insulin Dysregulation On Protein Metabolism In Horses, Caroline Margot Marcelle Loos 2018 University of Kentucky

The Impact Of Insulin Dysregulation On Protein Metabolism In Horses, Caroline Margot Marcelle Loos

Theses and Dissertations--Animal and Food Sciences

Insulin plays a vital role in whole-body metabolism and provides a major anabolic stimulus for cellular signaling pathways, including those involved in the metabolism of glucose and protein. Consequently, insulin dysregulation (ID) is known to alter molecular signal transduction in insulin-sensitive tissues such as skeletal muscle, thereby disrupting glucose metabolism and compromising protein synthetic capacity. Our first objective was to induce ID in healthy horses by administering dexamethasone (DEX), a potent glucocorticoid, for 21 days. We evaluated the effects on insulin-stimulated muscle protein signaling components involved in the mammalian target of rapamycin (mTOR) pathway. DEX-induced ID reduced insulin-stimulated activation of ...


Consequences Of Porcine Zona Pellucida Immunocontraception To Feral Horses, Cassandra M.V. Nuñez 2018 Iowa State University

Consequences Of Porcine Zona Pellucida Immunocontraception To Feral Horses, Cassandra M.V. Nuñez

Human–Wildlife Interactions

Porcine zona pellucida (PZP) immunocontraception was developed to provide a more humane, effective, and inexpensive method of population regulation for wildlife species. It has been used to regulate populations of several species including white tailed deer (Odocoileus virginianus), elk (Cervus elaphus ), black bear (Ursus americanus ), and the feral horse (Equus ferus caballus) with varying levels of success. Early studies on Assateague Island National Seashore, Maryland, USA, suggested PZP was as an ideal form of fertility control because it reduced the likelihood of conception to


Effects Of Income And Education Levels On Diurnal Cortisol In Black And White American Youth Transitioning Into Adulthood, Shannin Nicole Moody 2018 Iowa State University

Effects Of Income And Education Levels On Diurnal Cortisol In Black And White American Youth Transitioning Into Adulthood, Shannin Nicole Moody

Graduate Theses and Dissertations

Cortisol patterns differ across both socioeconomic status and racial minority groups. Yet, whether the underlying constructs that are used to measure socioeconomic status impacts the output of cortisol differentially across racial groups is unclear. Using a secondary data analysis from the Parents Who Care longitudinal study, which integrated the biomarker cortisol as youth entered emerging adulthood, the goal of this thesis is to parse apart the common conflation of income and education into a single catchall variable.

The following data was collected in 2 waves from a group of youth who were (M=20.24; R=18.51-22.89) years ...


Incidence Of Second Malignancy In Patients With Papillary Thyroid Cancer From Surveillance, Epidemiology, And End Results 13 Dataset, Mayumi Endo, Jessica Liu, Marcelle Dougan, Jennifer Lee 2018 Ohio State University - Main Campus

Incidence Of Second Malignancy In Patients With Papillary Thyroid Cancer From Surveillance, Epidemiology, And End Results 13 Dataset, Mayumi Endo, Jessica Liu, Marcelle Dougan, Jennifer Lee

Faculty Publications

Increased risk of second primary malignancy (SPM) in papillary thyroid cancer (PTC) has been reported. Here, we present the most updated incidence rates of second primary malignancy from original diagnosis of PTC by using the data from the Surveillance, Epidemiology, and End Results. In this cohort, 3,200 patients developed SPM, a substantially higher number than in the reference population of 2,749 with observed to expected ratio (O/E) of 1.16 (95% CI; 1.12–1.21). Bone and joint cancer had the highest O/E ratio of 4.26 (95% confidence interval [CI] 2.33–7.15 ...


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