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Validation Of A Novel Trpm8 Knockout Mouse Model, Bilan Mohamed 2021 University of Southern Maine

Validation Of A Novel Trpm8 Knockout Mouse Model, Bilan Mohamed

Thinking Matters Symposium

Recent studies suggest that the use of thermoregulatory treatments that affect brown fat may help curb obesity. However it is unknown how these treatments may affect bone homeostasis. Our work has focused on the transient receptor potential melastatin (TRPM8) protein, which is responsible for detecting colder temperatures in sensory neurons. Previous work within the Motyl laboratory has found that Trpm8 plays a role in bone acquisition. Mice with a global deletion of the Trpm8 gene have reduced trabecular bone volume fraction due to reduced bone formation by osteoblasts. However, it is unclear whether sensory neuron or osteoblast-mediated expression of Trpm8 ...


Predictors Of Irritability Symptoms In Mildly Depressed Perimenopausal Women, Anouk E. de Wit, Erik J. Giltay, Marrit K. de Boer, Margo Nathan, Aleta Wiley, Sybil L. Crawford, Hadine Joffe 2021 Harvard Medical School

Predictors Of Irritability Symptoms In Mildly Depressed Perimenopausal Women, Anouk E. De Wit, Erik J. Giltay, Marrit K. De Boer, Margo Nathan, Aleta Wiley, Sybil L. Crawford, Hadine Joffe

Graduate School of Nursing Publications

OBJECTIVE: Irritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with depressive symptoms during perimenopause, more insight is needed into reproductive hormone dynamics and other factors that predispose perimenopausal women to irritable mood.

METHODS: Among 50 mildly depressed perimenopausal women (mean (SD) age 48.4 (3.9) years), severity of irritability symptoms (on Symptom Questionnaire Hostility subscale, range 0-23) was assessed weekly for eight weeks, concurrent with potential predictors. Associations between these were examined using generalized estimating equating models.

RESULTS: Most women (82.0%) reported having moderate ...


Morph- And Sex-Specific Differences In Corticosterone Of The Arizona Tiger Salamander (Ambystoma Mavortium Nebulosum), Megan Zerger 2021 Murray State University

Morph- And Sex-Specific Differences In Corticosterone Of The Arizona Tiger Salamander (Ambystoma Mavortium Nebulosum), Megan Zerger

Scholars Week

Life history morph, sex, and body condition are traits that may influence stress within salamander populations because of differences in physiology and environmental conditions. Given widespread declines and the effects chronic stress can have on amphibian health, it is important to understand within-population drivers of stress and how population level variation may influence population viability. Thus, the objective of our study was to assess how corticosterone varies within the Arizona tiger salamander (Ambystoma mavortium nebulosum) population at the Mexican Cut Nature Preserve. We used a non-invasive skin swabbing method to collect baseline and elevated corticosterone from paedomorph (aquatic morph; N ...


A Feed-Forward Regulatory Loop In Adipose Tissue Promotes Signaling By The Hepatokine Fgf21, Myoung Souk Han, Rachel J. Perry, Joao-Paulo Camporez, Philipp E. Scherer, Gerald I. Shulman, Guangping Gao, Roger J. Davis 2021 University of Massachusetts Medical School

A Feed-Forward Regulatory Loop In Adipose Tissue Promotes Signaling By The Hepatokine Fgf21, Myoung Souk Han, Rachel J. Perry, Joao-Paulo Camporez, Philipp E. Scherer, Gerald I. Shulman, Guangping Gao, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is activated by metabolic stress and promotes the development of metabolic syndrome, including hyperglycemia, hyperlipidemia, and insulin resistance. This integrated physiological response involves cross-talk between different organs. Here we demonstrate that JNK signaling in adipocytes causes an increased circulating concentration of the hepatokine fibroblast growth factor 21 (FGF21) that regulates systemic metabolism. The mechanism of organ crosstalk is mediated by a feed-forward regulatory loop caused by JNK-regulated FGF21 autocrine signaling in adipocytes that promotes increased expression of the adipokine adiponectin and subsequent hepatic expression of the hormone FGF21. The mechanism of organ cross-talk ...


Effect Of Acute Sleep Fragmentation Upon Inflammatory Response Of Brown And White Adipose Tissue In Male Mice, Zach Wriedt 2021 Western Kentucky University

Effect Of Acute Sleep Fragmentation Upon Inflammatory Response Of Brown And White Adipose Tissue In Male Mice, Zach Wriedt

Mahurin Honors College Capstone Experience/Thesis Projects

Sleep is an important process required for vertebrates, including humans, to function. When sleep is disrupted, it leads to deleterious effects such as inflammatory responses throughout the body. Past studies have shown that acute (24 h) sleep fragmentation (SF) leads to an inflammatory response in white adipose tissue. However, whether brown adipose tissue responds in a similar fashion is unknown. Male adult (>8 weeks of age) C57BL/6j mice were subjected to SF for 24 h using a cage outfitted with a bar that moves horizontally across the cage every 2 min to periodically awaken mice (N =10). Controls were ...


Circadian Regulation Of The Timing Of Pre-Ovulatory Luteinizing Hormone Surge In Mice And Hamsters, Ajay Kumar 2020 University of Massachusetts Amherst

Circadian Regulation Of The Timing Of Pre-Ovulatory Luteinizing Hormone Surge In Mice And Hamsters, Ajay Kumar

Doctoral Dissertations

Endogenous daily (circadian) oscillators ensure the proper timing of physiological and behavioral processes that are essential to health. A set of core clock genes and their protein products function in transcriptional/translational feedback loops (TTFLs) that time and coordinate vital homeostatic, cognitive, and hormonal processes. A master pacemaker in the suprachiasmatic nucleus (SCN) coordinates circadian function throughout the organism. Investigating the causal role of genetically defined cell types in the suprachiasmatic nucleus for circadian rhythms is essential to understand how an animal’s physiology is temporally organized. This thesis explores the role of molecular clocks within particular cell types in ...


Insulin Resistance And Oxidative Stress: In Relation To Cognitive Function And Psychopathology In Drug-Naive, First-Episode Drug-Free Schizophrenia, Qi Tao, Yu Miao, Huihui Li, Xiuxia Yuan, Xufeng Huang, Yunpeng Wang, Ole A. Andreassen, Xiaoduo Fan, Yongfeng Yang, Xueqin Song 2020 Zhengzhou University

Insulin Resistance And Oxidative Stress: In Relation To Cognitive Function And Psychopathology In Drug-Naive, First-Episode Drug-Free Schizophrenia, Qi Tao, Yu Miao, Huihui Li, Xiuxia Yuan, Xufeng Huang, Yunpeng Wang, Ole A. Andreassen, Xiaoduo Fan, Yongfeng Yang, Xueqin Song

Open Access Publications by UMMS Authors

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients.

Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also ...


Characterization Of Viral Insulins Reveals White Adipose Tissue-Specific Effects In Mice, Martina Chrudinova, Francois Moreau, Hye Lim Noh, Terezie Panikova, Lenka Zakova, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis 2020 Boston College

Characterization Of Viral Insulins Reveals White Adipose Tissue-Specific Effects In Mice, Martina Chrudinova, Francois Moreau, Hye Lim Noh, Terezie Panikova, Lenka Zakova, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis

Open Access Publications by UMMS Authors

OBJECTIVE: Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e., more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis ...


Sexually Dimorphic Oxytocin Receptor-Expressing Neurons In The Anteroventral Periventricular Nucleus Regulates Maternal Behavior, Kaustubh Sharma 2020 Louisiana State University and Agricultural and Mechanical College

Sexually Dimorphic Oxytocin Receptor-Expressing Neurons In The Anteroventral Periventricular Nucleus Regulates Maternal Behavior, Kaustubh Sharma

LSU Doctoral Dissertations

The neurohypophysial hormone oxytocin is involved in the regulation of social behaviors, including social recognition, pair bonding, and sex-specific parental behaviors in a variety of species. Oxytocin triggers these social behaviors by binding to oxytocin receptors (OXTR) in various parts of the brain. Oxytocin-induced sex-typical behavior, therefore, suggests a sexual dimorphic distribution of OXTR in the brain. In recent years, the oxytocin system in the brain received tremendous attention as a potential pharmacological target for treatment of many psychiatric disorders, such as anxiety, autism spectrum disorders, and even sex-specific psychiatric disorder like postpartum depression (PPD). An important problem and a ...


Stochastic Modeling Of Ovarian Follicle Growth In Adult Female Rats, Zhaozhi Li 2020 Illinois State University

Stochastic Modeling Of Ovarian Follicle Growth In Adult Female Rats, Zhaozhi Li

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Roles Of Adipokines In Digestive Diseases: Markers Of Inflammation, Metabolic Alteration And Disease Progression, Ming-Ling Chang, Zinger Yang, Sien-Sing Yang 2020 Chang Gung University

Roles Of Adipokines In Digestive Diseases: Markers Of Inflammation, Metabolic Alteration And Disease Progression, Ming-Ling Chang, Zinger Yang, Sien-Sing Yang

Open Access Publications by UMMS Authors

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related ...


Coxsackievirus B Type 4 Infection In Beta Cells Downregulates The Chaperone Prefoldin Uri To Induce A Mody4-Like Diabetes Via Pdx1 Silencing, Hugo Bernard, Ana Teijeiro, Almudena Chaves-Perez, Cristian Perna, Basanthi Satish, Anna Novials, Jennifer P. Wang, Nabil Djouder 2020 National Cancer Research Center

Coxsackievirus B Type 4 Infection In Beta Cells Downregulates The Chaperone Prefoldin Uri To Induce A Mody4-Like Diabetes Via Pdx1 Silencing, Hugo Bernard, Ana Teijeiro, Almudena Chaves-Perez, Cristian Perna, Basanthi Satish, Anna Novials, Jennifer P. Wang, Nabil Djouder

University of Massachusetts Medical School Faculty Publications

Enteroviruses are suspected to contribute to insulin-producing beta cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice and in rat insulinoma cells displays loss of unconventional prefoldin RPB5 interactor (URI) and PDX1, affecting beta cell function and identity. Genetic URI ablation in the mouse pancreas causes PDX1 depletion in beta cells. Importantly, diabetic PDX1 heterozygous mice overexpressing URI in beta cells are more glucose tolerant. Mechanistically, URI loss triggers estrogen receptor nuclear translocation leading to DNA methyltransferase 1 (DNMT1) expression, which induces Pdx1 promoter ...


Beta-Cell Specific Insulin Resistance Promotes Glucose-Stimulated Insulin Hypersecretion [Preprint], Søs Skovsø, Hye Lim Noh, Sujin Suk, Brian Gablaski, Jason K. Kim, James D. Johnson 2020 University of British Columbia

Beta-Cell Specific Insulin Resistance Promotes Glucose-Stimulated Insulin Hypersecretion [Preprint], Søs Skovsø, Hye Lim Noh, Sujin Suk, Brian Gablaski, Jason K. Kim, James D. Johnson

University of Massachusetts Medical School Faculty Publications

Insulin receptor (Insr) protein can be found at higher levels in pancreatic β-cells than in most other cell types, but the consequences of β-cell insulin resistance remain enigmatic. Ins1cre allele was used to delete Insr specifically in β-cells of both female and male mice which were compared to Ins1cre-containing littermate controls at multiple ages and on multiple diets. RNA-seq of recombined β-cells revealed significant differences in multiple pathways previously implicated in insulin secretion and cellular fate, including rewired Ras and NFκB signaling. Male, but not female, βInsrKO mice had reduced oxygen consumption rate, while action ...


Crispr-Enhanced Human Adipocyte 'Browning' As Cell Therapy For Metabolic Disease [Preprint], Emmanouela Tsagkaraki, Sarah M. Nicoloro, Tiffany DeSouza, Javier Solivan-Rivera, Anand Desai, Yuefei Shen, Mark Kelly, Adilson L. Guilherme, Felipe Henriques, Raed Ibraheim, Nadia Amrani, Kevin Luk, Stacy Maitland, Randall H. Friedline, Lauren Tauer, Xiaodi Hu, Jason K. Kim, Scot A. Wolfe, Erik J. Sontheimer, Silvia Corvera, Michael P. Czech 2020 University of Massachusetts Medical School

Crispr-Enhanced Human Adipocyte 'Browning' As Cell Therapy For Metabolic Disease [Preprint], Emmanouela Tsagkaraki, Sarah M. Nicoloro, Tiffany Desouza, Javier Solivan-Rivera, Anand Desai, Yuefei Shen, Mark Kelly, Adilson L. Guilherme, Felipe Henriques, Raed Ibraheim, Nadia Amrani, Kevin Luk, Stacy Maitland, Randall H. Friedline, Lauren Tauer, Xiaodi Hu, Jason K. Kim, Scot A. Wolfe, Erik J. Sontheimer, Silvia Corvera, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

Obesity and type 2 diabetes (T2D) are associated with poor tissue responses to insulin [1,2], disturbances in glucose and lipid fluxes [3-5] and comorbidities including steatohepatitis [6] and cardiovascular disease [7,8]. Despite extensive efforts at prevention and treatment [9,10], diabetes afflicts over 400 million people worldwide [11]. Whole body metabolism is regulated by adipose tissue depots [12-14], which include both lipid-storing white adipocytes and less abundant 'brown' and 'brite/beige' adipocytes that express thermogenic uncoupling protein UCP1 and secrete factors favorable to metabolic health [15-18]. Application of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing [19 ...


The Lipid Handling Capacity Of Subcutaneous Fat Is Programmed By Mtorc2 During Development, Wen-Yu Hsiao, Su Myung Jung, Yuefeng Tang, John A. Haley, Rui Li, Huawei Li, Camila Martinez Calejman, Joan Sanchez-Gurmaches, Chien-Min Hung, Amelia K. Luciano, Victoria DeMambro, Kathryn E. Wellen, Clifford J. Rosen, Lihua Julie Zhu, David A. Guertin 2020 University of Massachusetts Medical School

The Lipid Handling Capacity Of Subcutaneous Fat Is Programmed By Mtorc2 During Development, Wen-Yu Hsiao, Su Myung Jung, Yuefeng Tang, John A. Haley, Rui Li, Huawei Li, Camila Martinez Calejman, Joan Sanchez-Gurmaches, Chien-Min Hung, Amelia K. Luciano, Victoria Demambro, Kathryn E. Wellen, Clifford J. Rosen, Lihua Julie Zhu, David A. Guertin

Open Access Publications by UMMS Authors

Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness ...


Melatonin Patterns And Levels During The Human Menstrual Cycle And After Menopause, Gail A. Greendale, Paula Witt-Enderby, Arun S. Karlamangla, Fahima Munmun, Sybil L. Crawford, MeiHua Huang, Nanette Santoro 2020 University of California, Los Angeles

Melatonin Patterns And Levels During The Human Menstrual Cycle And After Menopause, Gail A. Greendale, Paula Witt-Enderby, Arun S. Karlamangla, Fahima Munmun, Sybil L. Crawford, Meihua Huang, Nanette Santoro

Graduate School of Nursing Publications

Context: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging.

Objective: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging.

Methods: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and ...


Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice [Preprint], Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis 2020 Boston College

Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice [Preprint], Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis

University of Massachusetts Medical School Faculty Publications

Members of the insulin/IGF superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single chain (sc), i.e. IGF-1-like, forms of the viral insulin/IGF-1 like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e. more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 ...


Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Toward Goblet Cell Lineage In The Mouse Intestine, Joyce H. Li, Subir Ray, Alper Kucukural, Gerard Gradwohl, Andrew B. Leiter 2020 University of Massachusetts Medical School

Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Toward Goblet Cell Lineage In The Mouse Intestine, Joyce H. Li, Subir Ray, Alper Kucukural, Gerard Gradwohl, Andrew B. Leiter

University of Massachusetts Medical School Faculty Publications

BACKGROUND and AIMS: Transient expression of Neurog3 commits intestinal secretory progenitors to become enteroendocrine-biased progenitors and hence drive enteroendocrine differentiation. Loss of Neurog3 in mouse resulted in the depletion of intestinal enteroendocrine cells (EECs) and an increase in goblet cells. Earlier studies in developing mouse pancreas showed Neurog3 gene dosage in endocrine and exocrine cell fate allocation. We aimed to determine whether Neurog3 gene dosage controls fate choice of enteroendocrine progenitors.

METHODS: We acquired mutant Neurog3 reporter mice carrying 2, 1, or null Neurog3 alleles to study Neurog3 gene dosage effect by lineage tracing. Cell types arising from Neurog3+ progenitors ...


Physiology Of A Basal Vertebrate, The Sea Lamprey (Petromyzon Marinus): Osmoregulation And Corticosteroid Action, Ciaran A. S. Shaughnessy 2020 University of Massachusetts Amherst

Physiology Of A Basal Vertebrate, The Sea Lamprey (Petromyzon Marinus): Osmoregulation And Corticosteroid Action, Ciaran A. S. Shaughnessy

Doctoral Dissertations

Lamprey represent the most basal living example of a vertebrate animal which regulates its internal fluid and ion homeostasis. This phylogenetic position among vertebrates makes lamprey an important model organism for understanding the basal state, and thus the evolution, of physiological systems such as the mechanisms of osmo- and ionoregulation and the endocrine factors controlling them. Sea lamprey (Petromyzon marinus) are an anadromous fish, migrating from freshwater (FW) to seawater (SW) as juveniles, then returning back upstream as mature adults to spawn. Surviving this transition from a solute-poor FW environment to a solute-concentrated SW environment requires many changes to osmo- ...


How Do Adult Songbirds Learn New Sounds? Using Neuromodulators To Probe The Function Of The Auditory Association Cortex, Matheus Macedo-Lima 2020 University of Massachusetts Amherst

How Do Adult Songbirds Learn New Sounds? Using Neuromodulators To Probe The Function Of The Auditory Association Cortex, Matheus Macedo-Lima

Doctoral Dissertations

The ability to associate sounds and outcomes is vital in the life history of many species. Animals constantly assess the soundscape for cues associated with threats, competitors, allies, mates or prey, and experience is crucial for those associations. For vocal learning species such as humans and songbirds, learning sounds (i.e. perception and association learning) is also the first step in the process of vocal learning. Auditory learning is thought to depend on high-order cortical brain structures, where sounds and meaning are bound. In songbirds, the caudomedial nidopallium (NCM) is part of the auditory association cortex and is known to ...


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