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The Effect Of Intensified Illuminance And Artificial Light At Night On Fitness And Susceptibility To Abiotic And Biotic Stressors, Grascen Shidemantle 2020 Binghamton University

The Effect Of Intensified Illuminance And Artificial Light At Night On Fitness And Susceptibility To Abiotic And Biotic Stressors, Grascen Shidemantle

Biological Sciences Student Scholarship

Changing light conditions due to human activities represents an important emerging environmental concern. Although changes to natural light conditions can be independently detrimental, in nature, organisms commonly face multiple stressors. To understand the consequences of altered light conditions, we exposed a model amphibian (wood frog; Lithobates sylvaticus) to a control and two anthropogenic light conditions: intensified daytime illuminance and artificial light at night - ALAN (intensified daytime illuminance + extended photoperiod). We measured (1) metrics of fitness (hatching success as well as survival to, size at, and time to metamorphosis) (2) susceptibility (time to death) to a commonly cooccurring anthropogenic stressor, road ...


Deconstructing Circadian Disruption: Assessing The Contribution Of Reduced Peripheral Oscillator Amplitude On Obesity And Glucose Intolerance In Mice, Vincent van der Vinne, Blanca Martin Burgos, Mary E. Harrington, David R. Weaver 2020 University of Massachusetts Medical School

Deconstructing Circadian Disruption: Assessing The Contribution Of Reduced Peripheral Oscillator Amplitude On Obesity And Glucose Intolerance In Mice, Vincent Van Der Vinne, Blanca Martin Burgos, Mary E. Harrington, David R. Weaver

Neurobiology Publications

Disturbing the circadian regulation of physiology by disruption of the rhythmic environment is associated with adverse health outcomes but the underlying mechanisms are unknown. Here, the response of central and peripheral circadian clocks to an advance or delay of the light-dark cycle was determined in mice. This identified transient damping of peripheral clocks as a consequence of an advanced light-dark cycle. Similar depression of peripheral rhythm amplitude was observed in mice exposed to repeated phase shifts. To assess the metabolic consequences of such peripheral amplitude depression in isolation, temporally chimeric mice lacking a functional central clock (Vgat-Cre(+) Bmal1(fl/fl ...


Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech 2020 University of Massachusetts Medical School

Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech

Open Access Articles

BACKGROUND: The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance.

SCOPE OF REVIEW: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance ...


Mixed-Lineage Kinase-3 (Mlk3) Plays A Negative Modulatory Role In Insulin Secretion From The Pancreatic Β-Cell, Tyler Russeth, Vijayalakshmi Thamilselvan, Anjaneyulu Kowluru 2020 Wayne State University School of Medicine

Mixed-Lineage Kinase-3 (Mlk3) Plays A Negative Modulatory Role In Insulin Secretion From The Pancreatic Β-Cell, Tyler Russeth, Vijayalakshmi Thamilselvan, Anjaneyulu Kowluru

Medical Student Research Symposium

Glucose-stimulated insulin secretion (GSIS) from the pancreatic β-cell in response to elevated levels of glucose is controlled by a variety of signals including intracellular calcium and nucleotides such as cAMP, ATP and GTP. These cellular signals are responsible for activation of specific kinases that mediate phosphorylation of key exocytotic proteins that lead to GSIS. In the context of protein kinases, mixed-lineage kinases (MLKs) have been implicated in an assortment of cellular functions, including cell proliferation and apoptosis. However, very little is known on potential regulatory roles of MLKs in islet β-cell function, including GSIS. The goal of this study is ...


Exogenous Gdf11, But Not Gdf8, Reduces Body Weight And Improves Glucose Homeostasis In Mice, Ryan G. Walker, Hye Lim Noh, Taekyoon Kim, Jason K. Kim, Richard T. Lee 2020 Harvard University

Exogenous Gdf11, But Not Gdf8, Reduces Body Weight And Improves Glucose Homeostasis In Mice, Ryan G. Walker, Hye Lim Noh, Taekyoon Kim, Jason K. Kim, Richard T. Lee

Open Access Articles

Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of ...


Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan McNamara 2020 The University of Akron

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization ...


Recovery Of Viable Endocrine-Specific Cells And Transcriptomes From Human Pancreatic Islet-Engrafted Mice, Sambra D. Redick, Linda Leehy, Ann R. Rittenhouse, David M. Blodgett, Alan G. Derr, Alper Kucukural, Manuel Garber, Leonard D. Shultz, Dale L. Greiner, Jennifer P. Wang, David M. Harlan, Rita Bortell, Agata Jurczyk 2020 University of Massachusetts Medical School

Recovery Of Viable Endocrine-Specific Cells And Transcriptomes From Human Pancreatic Islet-Engrafted Mice, Sambra D. Redick, Linda Leehy, Ann R. Rittenhouse, David M. Blodgett, Alan G. Derr, Alper Kucukural, Manuel Garber, Leonard D. Shultz, Dale L. Greiner, Jennifer P. Wang, David M. Harlan, Rita Bortell, Agata Jurczyk

Program in Molecular Medicine Publications

Human pancreatic islets engrafted into immunodeficient mice serve as an important model for in vivo human diabetes studies. Following engraftment, islet function can be monitored in vivo by measuring circulating glucose and human insulin; however, it will be important to recover viable cells for more complex graft analyses. Moreover, RNA analyses of dissected grafts have not distinguished which hormone-specific cell types contribute to gene expression. We developed a method for recovering live cells suitable for fluorescence-activated cell sorting from human islets engrafted in mice. Although yields of recovered islet cells were relatively low, the ratios of bulk-sorted beta, alpha, and ...


High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White 2019 Massachusetts Institute of Technology

High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White

Open Access Articles

Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected ...


Evaluation Of Kidney Injury Molecule-1 As A Disease Progression Biomarker In Diabetic Nephropathy, Fatima Abid Khan, Syeda Sadia Fatima, Ghulam Mustafa Khan, Sana Shahid 2019 Jinnah Sindh Medical University, Karachi Pakistan

Evaluation Of Kidney Injury Molecule-1 As A Disease Progression Biomarker In Diabetic Nephropathy, Fatima Abid Khan, Syeda Sadia Fatima, Ghulam Mustafa Khan, Sana Shahid

Department of Biological & Biomedical Sciences

Background & Objective: Kidney Injury Molecule-1 (KIM-1) is a peptide whose release into circulation is specific to tubular injury. This study aimed to estimate levels of kidney injury molecule-1 in diabetic patients with and without kidney disease. And evaluate the role of KIM-1 as an early screening marker of progressive kidney injury.
Methods: This follow-up study included n=85 subjects from the diabetic clinic of Jinnah Post Graduate Medical Center (JPMC) in collaboration with Aga Khan University from November 2016 till September 2017. They were divided as: i) Group A1 (n=30) participants with diabetes for <5 years without microalbuminuria ii) Group A2 (n= 30) subjects with diabetes for 6-10 years with microalbuminuria; iii) Group B (n=25) subjects as healthy control group. All study participants were followed for 6 months and their blood glucose, urea, creatinine, electrolytes, albuminuria and serum KIM-1 were assayed.
Results: High KIM-1 at baseline was present in group A2 patients as compared to controls and group A1 (p<0.001). Higher levels were seen after six months in group A1 along with the presence of micro albuminuria (p<0.001) suggesting kidney damage. Moderate positive association were seen for KIM1 with creatinine levels (r=0.530; p<0.001), and HbA1c (r=0.576; p<0.001) in all patients. While a strong positive association was seen for blood urea nitrogen as a marker for kidney function both at baseline (r= 0.728; p=0.000) and follow up (r=0.747; p=0.001). Multiple logistic regression controlling for age showed that KIM1 was independently associated with BUN (r=0.727; p<0.001), creatinine (r=0.510; p<0.001) and HbA1c (r=0.401; p=0.008) in all groups.
Conclusion: Rising KIM-1 levels with progressive kidney damage with or without derangement of kidney function is reported in this study. This finding may pave a way towards identifying KIM1 as a prognostic marker for kidney injury.


Effect Of Sleep Loss On Executive Function And Baseline Corticosterone Levels In An Arctic-Breeding Songbird, The Lapland Longspur (Calcarius Lapponicus), Brett Hodinka 2019 Western Kentucky University

Effect Of Sleep Loss On Executive Function And Baseline Corticosterone Levels In An Arctic-Breeding Songbird, The Lapland Longspur (Calcarius Lapponicus), Brett Hodinka

Masters Theses & Specialist Projects

Sleep is a fundamental and essential component of vertebrate life, although its exact function remains unknown. Animals that are deprived of sleep typically show reduced neurobiological performance, health, and in some cases, survival. However, a number of animals exhibit adaptations that permit them to carry out normal activities even when sleep is restricted or deprived. Lapland longspurs (Calcarius lapponicus), arctic-breeding passerine birds, exhibit around-the-clock activity during their short breeding season, with an inactive period of only 3–4 h/day (71°N). Whether these birds suffer behavioral and physiological costs associated with acute sleep loss (SL) is unknown. To assess ...


Relationship Of Maternal And Infant Cortisol Matrices With Later Infant Behavior And Temperament, Anastasia Perris 2019 University of Massachusetts Amherst

Relationship Of Maternal And Infant Cortisol Matrices With Later Infant Behavior And Temperament, Anastasia Perris

Anastasia Perris

 Prenatal stress has been correlated with adverse developmental outcomes affecting infant cognition and behavior. Previous studies have shown that prenatal stress can lead to increased susceptibility to adult disease but few studies have looked at the physiological stress response system by measuring the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol, the output of the HPA axis can be secreted in many different matrices (saliva, blood, urine, feces and hair). Most studies that do, only look at one measure of hormone production instead of examining multiple matrices. Additionally these studies do not look at the relationship between matrices. Hair provides a ...


The Role Of C-Kit And Insulin Receptor Tyrosine Kinases In Beta Cell Function And Insulin Secretion, Amanda Oakie 2019 The University of Western Ontario

The Role Of C-Kit And Insulin Receptor Tyrosine Kinases In Beta Cell Function And Insulin Secretion, Amanda Oakie

Electronic Thesis and Dissertation Repository

The receptor tyrosine kinases (RTKs) c-Kit and insulin receptor (IR) initiate similar intracellular signalling pathways in pancreatic beta cells to regulate beta cell proliferation, survival, and insulin secretion. Mice with a c-Kit overexpression specifically in beta cells (c-KitβTg) demonstrated improved beta cell proliferation and insulin secretion compared to control mice, and islets from c-KitβTg mice also demonstrated increased IR expression. The potential interplay between c-Kit and IR and their roles during ageing and metabolic stress are not currently known. This work reports the examination of c-Kit and IR signalling using in vitro and in vivo models to determine their effects ...


Cardio-Metabolic Disease Risk Factors Among South Asian Labour Migrants To The Middle East: A Scoping Review And Policy Analysis, Shiva Raj Mishra, Saruna Ghimire, Chandni Joshi, Bishal Gyawali, Archana Shrestha, Dinesh Neupane, Sudesh Raj Sharma, Yashashwi Pokharel, Salim S. Virani 2019 Nepal Development Societ

Cardio-Metabolic Disease Risk Factors Among South Asian Labour Migrants To The Middle East: A Scoping Review And Policy Analysis, Shiva Raj Mishra, Saruna Ghimire, Chandni Joshi, Bishal Gyawali, Archana Shrestha, Dinesh Neupane, Sudesh Raj Sharma, Yashashwi Pokharel, Salim S. Virani

Public Health Faculty Publications

This paper aims to explore the burgeoning burden of cardiovascular and metabolic disease (CMD) risk factors among South Asian labor migrants to the Middle East. We conducted a qualitative synthesis of literature using PubMed/Medline and grey literature searches, supplemented by a policy review of policies from the South Asian countries. We found a high burden of cardio-metabolic risk factors among the migrants as well as among the populations in the home and the host countries. For example, two studies reported the prevalence of diabetes mellitus (DM) ranging between 9 and 17% among South Asian migrants. Overweight and obesity were ...


Seasonal Changes In Susceptibility To Chytridiomycosis In Columbia Spotted Frogs, Delaney Burrows 2019 Carroll College

Seasonal Changes In Susceptibility To Chytridiomycosis In Columbia Spotted Frogs, Delaney Burrows

Carroll College Student Undergraduate Research Festival

Chytridiomycosis is a potentially deadly skin disease found in amphibian populations all over the world. Chytridiomycosis is caused by the fungus Batrachochytrium dendrobatidis (Bd) that grows on the skin of amphibians. The fungus can cause a disruption in the homeostatic functions of the amphibian skin and can lead to death. The relationship between an amphibian’s antimicrobial skin secretions, cutaneous microbial communities and environmental water quality can affect their resistance and susceptibility to Bd infection. Columbia spotted frogs (Lithobates luteiventris) are native to western Montana and have been affected by chytridiomycosis. Three lakes known to be positive for Bd were ...


Rediscovering The Axolotl As A Model For Thyroid Hormone Dependent Development, Anne Crowner, Shivam Khatri, Dana Blichmann, S. Randal Voss 2019 University of Kentucky

Rediscovering The Axolotl As A Model For Thyroid Hormone Dependent Development, Anne Crowner, Shivam Khatri, Dana Blichmann, S. Randal Voss

Neuroscience Faculty Publications

The Mexican axolotl (Ambystoma mexicanum) is an important model organism in biomedical research. Much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. However, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life. Unlike close tiger salamander relatives that undergo a thyroid hormone regulated metamorphosis, the axolotl does not typically undergo a metamorphosis. Instead, the axolotl exhibits a paedomorphic mode of development that enables a completely aquatic life cycle. The evolution of paedomorphosis allowed axolotls ...


Lumen Apposing Metal Stents In Drainage Of Pancreatic Walled-Off Necrosis, Are They Any Better Than Plastic Stents? A Systematic Review And Meta-Analysis Of Studies Published Since The Revised Atlanta Classification Of Pancreatic Fluid Collections, Babu P. Mohan, Mahendran Jayaraj, Ravishankar Asokkumar, Mohammed Shakhatreh, Parul Pahal, Suresh Ponnada, Udayakumar Navaneethan, Douglas G. Adler 2019 University of Arizona

Lumen Apposing Metal Stents In Drainage Of Pancreatic Walled-Off Necrosis, Are They Any Better Than Plastic Stents? A Systematic Review And Meta-Analysis Of Studies Published Since The Revised Atlanta Classification Of Pancreatic Fluid Collections, Babu P. Mohan, Mahendran Jayaraj, Ravishankar Asokkumar, Mohammed Shakhatreh, Parul Pahal, Suresh Ponnada, Udayakumar Navaneethan, Douglas G. Adler

School of Medicine Faculty Publications

Lumen-apposing metal stents (LAMS) are increasingly being used in the drainage of pancreatic walled-off necrosis (WON). Best choice of stent is subject to argument, and studies are varied in the reported outcomes between LAMS and plastic stents (PS) to this end. We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, and Web of Science databases (earliest inception through July 2018) to identify studies that reported on the use of LAMS and PS in WON drainage. Studies published since the release of the revised Atlanta classification for pancreatic fluid collections (2014 to current) were included ...


Multi-Dimensional Transcriptional Remodeling By Physiological Insulin In Vivo, Thiago M. Batista, Ruben Garcia-Martin, Weikang Cai, Masahiro Konishi, Brian T. O'Neill, Masaji Sakaguchi, Jong Hun Kim, Dae Young Jung, Jason K. Kim, C. Ronald Kahn 2019 Harvard Medical School

Multi-Dimensional Transcriptional Remodeling By Physiological Insulin In Vivo, Thiago M. Batista, Ruben Garcia-Martin, Weikang Cai, Masahiro Konishi, Brian T. O'Neill, Masaji Sakaguchi, Jong Hun Kim, Dae Young Jung, Jason K. Kim, C. Ronald Kahn

Open Access Articles

Regulation of gene expression is an important aspect of insulin action but in vivo is intertwined with changing levels of glucose and counter-regulatory hormones. Here we demonstrate that under euglycemic clamp conditions, physiological levels of insulin regulate interrelated networks of more than 1,000 transcripts in muscle and liver. These include expected pathways related to glucose and lipid utilization, mitochondrial function, and autophagy, as well as unexpected pathways, such as chromatin remodeling, mRNA splicing, and Notch signaling. These acutely regulated pathways extend beyond those dysregulated in mice with chronic insulin deficiency or insulin resistance and involve a broad network of ...


Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell 2019 Illinois State University

Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell

Theses and Dissertations

Maternal steroids transferred to eggs can elicit permanent effects on various aspects of offspring phenotype. Although, testosterone was thought to be a key mediator of maternal effects in birds, we now know that vertebrate embryos actively regulate their exposure to maternal testosterone through steroid metabolism, suggesting testosterone metabolites may elicit the observed phenotypic effects. To address the role steroid metabolism plays in mediating yolk testosterone effects, we used European starling (Sturnus vulgaris) eggs to characterize the timing of testosterone metabolism and determine whether etiocholanolone, a prominent testosterone metabolite in avian embryos, is capable of influencing early embryonic development. Tritiated testosterone ...


Important Role Of The Glp-1 Axis For Glucose Homeostasis After Bariatric Surgery, Pierre Larraufie, Geoffrey P. Roberts, Anne K. McGavigan, Richard G. Kay, Joyce H. Li, Andrew B. Leiter, Audrey Melvin, Emma K. Biggs, Peter Ravn, Kathleen Davy, David C. Hornigold, Giles S. Yeo H, Richard H. Hardwick, Frank Reimann, Fiona M. Gribble 2019 Addenbrooke's Hospital

Important Role Of The Glp-1 Axis For Glucose Homeostasis After Bariatric Surgery, Pierre Larraufie, Geoffrey P. Roberts, Anne K. Mcgavigan, Richard G. Kay, Joyce H. Li, Andrew B. Leiter, Audrey Melvin, Emma K. Biggs, Peter Ravn, Kathleen Davy, David C. Hornigold, Giles S. Yeo H, Richard H. Hardwick, Frank Reimann, Fiona M. Gribble

Open Access Articles

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that ...


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 ...


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