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Atf4/Txnip/Redd1/Mtor Signaling Mediates The Antitumor Activities Of Liver X Receptor In Pancreatic Cancers, Zhikang Chen, Xiaobo Lai, Hui Ding, Aijun Zhang, Yufei Sun, Jianhua Ling, Paul J Chiao, Zihua Chen, Xuefeng Xia Jun 2022

Atf4/Txnip/Redd1/Mtor Signaling Mediates The Antitumor Activities Of Liver X Receptor In Pancreatic Cancers, Zhikang Chen, Xiaobo Lai, Hui Ding, Aijun Zhang, Yufei Sun, Jianhua Ling, Paul J Chiao, Zihua Chen, Xuefeng Xia

Faculty, Staff and Student Publications

Background: Limited by difficulties in early detection and availabilities of effective treatments, pancreatic cancer is a highly malignant disease with poor prognosis. Nuclear receptors are a family of ligand-dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development, including cancer. In this study, we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor (LXR) agonist GW3965 in pancreatic cancer.

Methods: Soft-agar colony formation assay, xenograft tumors, Oligonucleotide microarray, Reverse transcription real-time polymerase chain reaction, Western immunoblotting and Immunohistochemistry were used in this study.

Results: We demonstrated pleotropic …


Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib May 2022

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …


Oxygen Deprivation Masks For Training, Brittany M. Hanlon Apr 2022

Oxygen Deprivation Masks For Training, Brittany M. Hanlon

Student Publications

Oxygen deprivation masks are being advertised towards athletes as a piece of fitness equipment that can simulate the effects of high altitude, as well as a respiratory muscle training device. Studies that investigated the claims as to whether ODMs increased VO2max and improved endurance were looked into. Experimental data did not find that the use of these masks increased VO2max, nor was there any supporting data to prove that it improved endurance. The function of ODMs as a training tool to increase respiratory muscle strength was also examined. There were contradicting results between the three different studies examined. One study …


Incidence Of Injuries In The Opinion Of Young Volleyball Players And Ways To Prevent Them, Monika Opanowska, Barbara Wilk, Malgorzata Kusmierczyk, Karol Opanowski Mar 2022

Incidence Of Injuries In The Opinion Of Young Volleyball Players And Ways To Prevent Them, Monika Opanowska, Barbara Wilk, Malgorzata Kusmierczyk, Karol Opanowski

Baltic Journal of Health and Physical Activity

Background: The aim of the research was to establish the types and incidence of motor organ injuries in young volleyball players and to indicate methods of preventing them. Material/Methods: The research was carried out in a population of 70 volleyball players aged 16-19, students of the Sports Championships Schools No. 2 and 3 in Gdansk, players of the Lotos Trefl Gdansk sports club. The employed method was a diagnostic survey based on an original questionnaire entitled "The Characteristics of Motor Organ Injuries in Young People Aged 16-19 Who Train Volleyball." Results: 85.7% adolescent players experienced different motor organ injuries, the …


An Analysis Of The Correlation Between Kinesthetic Differentiation Capacity And The Maximum Force Level In Lower Limbs, Dariusz Harmacinski, Tadeusz Stefaniak, Anna Burdukiewicz, Jadwiga Pietraszewska, Aleksandra Stachon, Justyna Andrzejewska, Krystyna Chromik, Kazimierz Witkowski, Jarosław Maslinski Mar 2022

An Analysis Of The Correlation Between Kinesthetic Differentiation Capacity And The Maximum Force Level In Lower Limbs, Dariusz Harmacinski, Tadeusz Stefaniak, Anna Burdukiewicz, Jadwiga Pietraszewska, Aleksandra Stachon, Justyna Andrzejewska, Krystyna Chromik, Kazimierz Witkowski, Jarosław Maslinski

Baltic Journal of Health and Physical Activity

Background: Among specific coordination abilities, kinesthetic differentiation capacity of movement belongs to the most crucial factors fostering rational human behavior in the surrounding environment. The capacity is universal – indispensable in nearly all sports disciplines. One of the most important constituent elements of kinesthetic differentiation is the so-called “force sense,” defined as differentiation of movement with respect to administering appropriate force. The authors of the study analyzed the correlation between the maximum force level in lower limbs and the accuracy of applying a targeted force value. Material/Methods: The study was conducted on 54 participants, students from the University School of …


Lactate Threshold Changes In Soccer Players During The Preparation Period, Zbigniew Jastrzebski, Robert Dargiewicz, Wojciech Ignatiuk, Lukasz Radziminski, Pawel Rompa, Anna Konieczna Mar 2022

Lactate Threshold Changes In Soccer Players During The Preparation Period, Zbigniew Jastrzebski, Robert Dargiewicz, Wojciech Ignatiuk, Lukasz Radziminski, Pawel Rompa, Anna Konieczna

Baltic Journal of Health and Physical Activity

Background: The aim of the study was to assess the anaerobic threshold (lactate threshold LT) changes during winter and summer preparation period in soccer premier league and first division players. It was assumed that the index value varies depending on the stage of a one-year training cycle. Material/Methods: Tests were conducted on the premier league and first division soccer players. Physical capacity tests were carried out at the beginning and at the end of the winter and summer preparation period. The tests covered 3 years: 2008 – 2010. Subjects performed an incremental running test according to Jastrzębski’s method. The most …


Analysis Of Interrelations Of Psychophysiological And Hysiological Indicators Of Martial Arts Athletes, Vyacheslav Romanenko, Sergii Iermakov, Leonid Podrigalo, Olga Rovnaya, Zhanna Sotnikova-Meleshkina, Valeriy Goloha, Larysa Ruban Mar 2022

Analysis Of Interrelations Of Psychophysiological And Hysiological Indicators Of Martial Arts Athletes, Vyacheslav Romanenko, Sergii Iermakov, Leonid Podrigalo, Olga Rovnaya, Zhanna Sotnikova-Meleshkina, Valeriy Goloha, Larysa Ruban

Baltic Journal of Health and Physical Activity

Background: The article presents a comparative analysis of interrelations of psychophysiological and physiological indicators of martial art athletes while performing functional tests. Material and methods: 63 martial art athletes were divided into groups: the 1st group – 34 athletes of "striking" martial arts (taekwondo ITF, WTF, karate, hand-to-hand fight), age (17.58±0.08) years; the 2nd group – 18 Greco-Roman and freestyle wrestlers, age (18.94±0.33) years; the 3rd group – 11 judo and sambo athletes, age (18.73±0.23) years. Participants performed a test to define the choice reaction time with parallel control of the heart rate for 3 minutes. Results: Indicators of the …


The Level Of Somatic Health, Sports Specialization And Alification Of An Athlete As Indicators Of Intermediate Selection In The Mixed Martial Arts, Alexander Alexandrovich Gorelov, Vladimir Mikhailovich Voronov, Andrei Ivanovich Krylov, Viktor Leonidovich Kondakov Mar 2022

The Level Of Somatic Health, Sports Specialization And Alification Of An Athlete As Indicators Of Intermediate Selection In The Mixed Martial Arts, Alexander Alexandrovich Gorelov, Vladimir Mikhailovich Voronov, Andrei Ivanovich Krylov, Viktor Leonidovich Kondakov

Baltic Journal of Health and Physical Activity

Background: This article presents the results of experimental research to identify high-priority types of martial arts whose representatives successfully implement their skills in mixed martial arts, as well as the results of the study of somatic health. Objective: To explore the mechanisms of the intermediate selection in sport of the highest achievements and to explore the possibility of using them in mixed martial arts. Materials and methods: We have attracted twelve fully qualified athletes of mixed martial arts for a study to identify criteria of talent prediction and intermediate selection in terms of somatic health. We have engaged eighteen leading …


Participation Trends And Performance Analysis Of Turkey’S Long-Distance Runs Between 2007-2017, Melda Pelin Yargic, Naila Babayeva, Mehmet Sinan İyi̇Soy, Galip Bilen Kurklu, Gürhan Dönmez Mar 2022

Participation Trends And Performance Analysis Of Turkey’S Long-Distance Runs Between 2007-2017, Melda Pelin Yargic, Naila Babayeva, Mehmet Sinan İyi̇Soy, Galip Bilen Kurklu, Gürhan Dönmez

Baltic Journal of Health and Physical Activity

Background: Long-distance running events have gained more popularity worldwide over years. However, the number of participants to such events, age and sex distribution of participants may vary by country. Material and methods: We have investigated participation trends and performances of the finishers of three different courses (15km, half-marathon, marathon) in two of the biggest running events in Turkey (The Antalya and Istanbul marathons) between 2007-2017. Results: Our results have shown that runners who completed the 15km course were the highest and marathon finishers were the lowest in number each year. Among native runners, male participation in each distance and event …


Effects Of Interval Training Of Maximal Effort Intensity, Henryk Norkowski, Anna Kuder, Tadeusz Hucinski, Stanislaw Przybylski Mar 2022

Effects Of Interval Training Of Maximal Effort Intensity, Henryk Norkowski, Anna Kuder, Tadeusz Hucinski, Stanislaw Przybylski

Baltic Journal of Health and Physical Activity

Background: The purpose of this study was to determine changes in anaerobic capacity at 100% physical effort intensity in the examined people. Material/Methods: 12 male students from the University of Physical Education in Warsaw were subject to these examinations. The average age was 23.6 years, mean body height 178.7 cm, and body mass 80.6 kg. The experiment was carried out from 7th January to 8th March 2008. The experiment (one group) was carried out in two stages. The first stage had 25 training units on a cycloergometer within 5 weeks. The second stage was connected with controlling the obtained results …


Recommendations For Daytime, Evening, And Nighttime Indoor Light Exposure To Best Support Physiology, Sleep, And Wakefulness In Healthy Adults, Timothy M Brown, George Brainard, Christian Cajochen, Charles A Czeisler, John P Hanifin, Steven W Lockley, Robert J Lucas, Mirjam Münch, John B O'Hagan, Stuart N Peirson, Luke L A Price, Till Roenneberg, Luc J M Schlangen, Debra J Skene, Manuel Spitschan, Céline Vetter, Phyllis C Zee, Kenneth P Wright Mar 2022

Recommendations For Daytime, Evening, And Nighttime Indoor Light Exposure To Best Support Physiology, Sleep, And Wakefulness In Healthy Adults, Timothy M Brown, George Brainard, Christian Cajochen, Charles A Czeisler, John P Hanifin, Steven W Lockley, Robert J Lucas, Mirjam Münch, John B O'Hagan, Stuart N Peirson, Luke L A Price, Till Roenneberg, Luc J M Schlangen, Debra J Skene, Manuel Spitschan, Céline Vetter, Phyllis C Zee, Kenneth P Wright

Department of Neurology Faculty Papers

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, …


Utilization Of The Calm Apparatus To Adult Men And Women With Atrial Fibrillation To Decrease Emergency Department Visits For Atrial Fibrillation, Ami Klein Feb 2022

Utilization Of The Calm Apparatus To Adult Men And Women With Atrial Fibrillation To Decrease Emergency Department Visits For Atrial Fibrillation, Ami Klein

Doctor of Nursing Practice Scholarly Projects

The purpose of this project is two-fold. The first is to determine if the CALM APP use by adult men and women with atrial fibrillation (AF) will decrease anxiety. The second is to determine if decreased anxiety utilizing the CALM APP will deter admissions to the emergency department (ED) for AF in the first month post-catheter ablation of AF. The Zung SAS was used to determine the pre- and post-anxiety scores. The Seven Days of Calm (free app) was used to teach deep breathing and meditation. This study showed a moderate decrease in ED visits with use of the Calm …


Ces2 Sustains Hnf4Α Expression To Promote Pancreatic Adenocarcinoma Progression Through An Epoxide Hydrolase-Dependent Regulatory Loop, Yihui Chen, Michela Capello, Mayrim V Rios Perez, Jody V Vykoukal, David Roife, Ya'an Kang, Laura R Prakash, Hiroyuki Katayama, Ehsan Irajizad, Alia Fleury, Sammy Ferri-Borgogno, Dodge L Baluya, Jennifer B Dennison, Kim-Anh Do, Oliver Fiehn, Anirban Maitra, Huamin Wang, Paul J Chiao, Matthew H G Katz, Jason B Fleming, Samir M Hanash, Johannes F Fahrmann Feb 2022

Ces2 Sustains Hnf4Α Expression To Promote Pancreatic Adenocarcinoma Progression Through An Epoxide Hydrolase-Dependent Regulatory Loop, Yihui Chen, Michela Capello, Mayrim V Rios Perez, Jody V Vykoukal, David Roife, Ya'an Kang, Laura R Prakash, Hiroyuki Katayama, Ehsan Irajizad, Alia Fleury, Sammy Ferri-Borgogno, Dodge L Baluya, Jennifer B Dennison, Kim-Anh Do, Oliver Fiehn, Anirban Maitra, Huamin Wang, Paul J Chiao, Matthew H G Katz, Jason B Fleming, Samir M Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Objective: Intra-tumoral expression of the serine hydrolase carboxylesterase 2 (CES2) contributes to the activation of the pro-drug irinotecan in pancreatic ductal adenocarcinoma (PDAC). Given other potential roles of CES2, we assessed its regulation, downstream effects, and contribution to tumor development in PDAC.

Methods: Association between the mRNA expression of CES2 in pancreatic tumors and overall survival was assessed using The Cancer Genome Atlas. Cell viability, clonogenic, and anchorage-independent growth assays as well as an orthotopic mouse model of PDAC were used to evaluate the biological relevance of CES2 in pancreatic cancer. CES2-driven metabolic changes were determined by untargeted and targeted …


Effects Of Placebo Administration On Immune Mechanisms And Relationships With Central Endogenous Opioid Neurotransmission, Alan Prossin, Alisa Koch, Phillip Campbell, Geoffroy Laumet, Christian S Stohler, Robert Dantzer, Jon-Kar Zubieta Feb 2022

Effects Of Placebo Administration On Immune Mechanisms And Relationships With Central Endogenous Opioid Neurotransmission, Alan Prossin, Alisa Koch, Phillip Campbell, Geoffroy Laumet, Christian S Stohler, Robert Dantzer, Jon-Kar Zubieta

Faculty, Staff and Student Publications

Behavioral conditioning and expectation can have profound impact on animal and human physiology. Placebo, administered under positive expectation in clinical trials, can have potent effects on disease pathology, obscuring active medications. Emerging evidence suggests placebo-responsive neurotransmitter systems (e.g., endogenous opioid) regulate immune function by manipulating inflammatory proteins including IL-18, a potent pro-inflammatory, nociceptive cytokine implicated in pathophysiology of various diseases. Validation that neuroimmune interactions involving brain μ-opioid receptor (MOR) activity and plasma IL-18 underlie placebo analgesic expectation could have widespread clinical applications. Unfortunately, current lack of mechanistic clarity obfuscates clinical translation. To elucidate neuroimmune interactions underlying placebo analgesia, we exposed …


Stroboscopic Augmented Reality As An Approach To Mitigate Gravitational Transition Effects During Interplanetary Spaceflight, Ethan Waisberg, Joshua Ong, Nasif Zaman, Sharif Amit Kamran, Andrew G. Lee, Alireza Tavakkoli Jan 2022

Stroboscopic Augmented Reality As An Approach To Mitigate Gravitational Transition Effects During Interplanetary Spaceflight, Ethan Waisberg, Joshua Ong, Nasif Zaman, Sharif Amit Kamran, Andrew G. Lee, Alireza Tavakkoli

International Journal of Aviation, Aeronautics, and Aerospace

During interplanetary spaceflight, periods of extreme gravitational transitions will occur such as transitions between hypergravity, hypogravity, and microgravity. Following gravitational transitions, rapid sensorimotor adaptation or maladaptation may occur which can affect gaze control and weaken dynamic visual acuity in astronauts. A reduction in dynamic visual acuity during spaceflight could possibly impact or impair mission critical activities (e.g., control of extraterrestrial machinery/vehicles and other important tasks). Stroboscopic visual training is an emerging visual tool that has been terrestrially observed to enhance visual performance and perception by performing tasks under conditions of intermittent vision. This technique has also been seen to increase …


Head-Mounted Digital Metamorphopsia Suppression As A Countermeasure For Macular-Related Visual Distortions For Prolonged Spaceflight Missions And Terrestrial Health, Joshua Ong, Nasif Zaman, Ethan Waisberg, Sharif Amit Kamran, Andrew G Lee, Alireza Tavakkoli Jan 2022

Head-Mounted Digital Metamorphopsia Suppression As A Countermeasure For Macular-Related Visual Distortions For Prolonged Spaceflight Missions And Terrestrial Health, Joshua Ong, Nasif Zaman, Ethan Waisberg, Sharif Amit Kamran, Andrew G Lee, Alireza Tavakkoli

Faculty, Staff and Student Publications

During long-duration spaceflight, astronauts are exposed to various risks including spaceflight-associated neuro-ocular syndrome, which serves as a risk to astronaut vision and a potential physiological barrier to future spaceflight. When considering exploration missions that may expose astronauts to longer periods of microgravity, radiation exposure, and natural aging processes during spaceflight, more severe changes to functional vision may occur. The macula plays a critical role in central vision and disruptions to this key area in the eye may compromise functional vision and mission performance. In this article, we describe the development of a countermeasure technique to digitally suppress monocular central visual …


Identification Of Circulating Plasma Ceramides As A Potential Sexually Dimorphic Biomarker Of Pancreatic Cancer-Induced Cachexia., Jeffery M Chakedis, Mary E Dillhoff, Carl R Schmidt, Priyani V Rajasekera, David C Evans, Terence M Williams, Denis C Guttridge, Erin E Talbert Jan 2022

Identification Of Circulating Plasma Ceramides As A Potential Sexually Dimorphic Biomarker Of Pancreatic Cancer-Induced Cachexia., Jeffery M Chakedis, Mary E Dillhoff, Carl R Schmidt, Priyani V Rajasekera, David C Evans, Terence M Williams, Denis C Guttridge, Erin E Talbert

Oncology Articles

BACKGROUND: Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.

METHODS: Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia …


Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee Jan 2022

Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee

Faculty, Staff and Student Publications

PURPOSE: In vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems.

METHODS: Quiescent bovine chondrocytes were entrained for 3 days by …


Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell Jan 2022

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …


Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley Jan 2022

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …


Use Of Human Tissue Stem Cell-Derived Organoid Cultures To Model Enterohepatic Circulation, Sarah E Blutt, Sue E Crawford, Carolyn Bomidi, Xi-Lei Zeng, James R Broughman, Matthew Robertson, Cristian Coarfa, Mary Elizabeth M Tessier, Tor Savidge, F Blaine Hollinger, Steven A Curley, Mark Donowitz, Mary K Estes Sep 2021

Use Of Human Tissue Stem Cell-Derived Organoid Cultures To Model Enterohepatic Circulation, Sarah E Blutt, Sue E Crawford, Carolyn Bomidi, Xi-Lei Zeng, James R Broughman, Matthew Robertson, Cristian Coarfa, Mary Elizabeth M Tessier, Tor Savidge, F Blaine Hollinger, Steven A Curley, Mark Donowitz, Mary K Estes

Faculty, Staff and Students Publications

The use of human tissue stem cell-derived organoids has advanced our knowledge of human physiological and pathophysiological processes that are unable to be studied using other model systems. Increased understanding of human epithelial tissues including intestine, stomach, liver, pancreas, lung, and brain have been achieved using organoids. However, it is not yet clear whether these cultures recapitulate in vivo organ-to-organ signaling or communication. In this work, we demonstrate that mature stem cell-derived intestinal and liver organoid cultures each express functional molecules that modulate bile acid uptake and recycling. These organoid cultures can be physically coupled in a Transwell system and …


Crosstalk Between Beta-Adrenergic And Insulin Signaling Mediates Mechanistic Target Of Rapamycin Hyperactivation In Liver Of High-Fat Diet-Fed Male Mice, Sadia Ashraf, Nadia Ashraf, Gizem Yilmaz, Romain Harmancey Jul 2021

Crosstalk Between Beta-Adrenergic And Insulin Signaling Mediates Mechanistic Target Of Rapamycin Hyperactivation In Liver Of High-Fat Diet-Fed Male Mice, Sadia Ashraf, Nadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. While increased nutrient intake and sympathetic activity have been associated with the disease, the pathogenesis of NAFLD remains incompletely understood. We investigated the impact of the interaction of high dietary fat and sugar intake with increased beta-adrenergic receptor (β-AR) signaling on the activity of nutrient-sensing pathways and fuel storage in the liver. C57BL/6J mice were fed a standard rodent diet (STD), a high-fat diet (HFD), a high-fat/high-sugar Western diet (WD), a high-sugar diet with mixed carbohydrates (HCD), or a high-sucrose diet (HSD). After 6 week on …


Crosstalk Between Beta-Adrenergic And Insulin Signaling Mediates Mechanistic Target Of Rapamycin Hyperactivation In Liver Of High-Fat Diet-Fed Male Mice, Sadia Ashraf, Nadia Ashraf, Gizem Yilmaz, Romain Harmancey Jul 2021

Crosstalk Between Beta-Adrenergic And Insulin Signaling Mediates Mechanistic Target Of Rapamycin Hyperactivation In Liver Of High-Fat Diet-Fed Male Mice, Sadia Ashraf, Nadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. While increased nutrient intake and sympathetic activity have been associated with the disease, the pathogenesis of NAFLD remains incompletely understood. We investigated the impact of the interaction of high dietary fat and sugar intake with increased beta-adrenergic receptor (β-AR) signaling on the activity of nutrient-sensing pathways and fuel storage in the liver. C57BL/6J mice were fed a standard rodent diet (STD), a high-fat diet (HFD), a high-fat/high-sugar Western diet (WD), a high-sugar diet with mixed carbohydrates (HCD), or a high-sucrose diet (HSD). After 6 week on …


Defining The Relative Role Of Insulin Clearance In Early Dysglycemia In Relation To Insulin Sensitivity And Insulin Secretion: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Gautam Ramesh, Stephen S Rich, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi Jun 2021

Defining The Relative Role Of Insulin Clearance In Early Dysglycemia In Relation To Insulin Sensitivity And Insulin Secretion: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Gautam Ramesh, Stephen S Rich, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions …


Development Of The Infant Gut Microbiome Predicts Temperament Across The First Year Of Life, Molly Fox, S. Melanie Lee, Kyle S. Wiley, Venu Lagishetty, Curt A. Sandman, Jonathan P. Jacobs, Laura M. Glynn Jun 2021

Development Of The Infant Gut Microbiome Predicts Temperament Across The First Year Of Life, Molly Fox, S. Melanie Lee, Kyle S. Wiley, Venu Lagishetty, Curt A. Sandman, Jonathan P. Jacobs, Laura M. Glynn

Psychology Faculty Articles and Research

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta …


Flash Radiotherapy: Skin Pigmentation As A Non-Invasive Indicator For Radiation-Induced Damage, Brady Mccallister Jun 2021

Flash Radiotherapy: Skin Pigmentation As A Non-Invasive Indicator For Radiation-Induced Damage, Brady Mccallister

ENGS 88 Honors Thesis (AB Students)

FLASH ultra-high dose rate radiotherapy (RT) is one of the most rapidly growing subfields of radiation oncology today due to its potential to increase the limits of the therapeutic ratio. The FLASH effect, which includes heightened normal tissue sparing paired with iso-effective tumor cell killing, has been literature documented, in a limited manner, in rodent models, a few large animals, and one clinical patients.

A porcine-based experiment was conducted to test the effects of FLASH RT on normal tissue compared to conventional (CONV) RT. A clinical linear accelerator (LINAC) was reversibly converted to be capable of FLASH RT. A female …


A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen Apr 2021

A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen

Faculty, Staff and Students Publications

To generate physiologically-relevant experimental models, the study of enteric diarrheal diseases is turning increasingly to advanced in vitro models that combine ex vivo, stem cell-derived "organoid" cell lines with bioengineered culture environments that expose them to mechanical stimuli, such as fluid flow. However, such approaches require considerable technical expertise with both microfabrication and organoid culture, and are, therefore, inaccessible to many researchers. For this reason, we have developed a perfusion system that is simple to fabricate, operate, and maintain. Its dimensions approximate the volume and cell culture area of traditional 96-well plates and allow the incorporation of fastidious primary, stem …


Wearable Activity Tracking Device Use In An Adolescent Weight Management Clinic: A Randomized Controlled Pilot Trial, Kanika Bowen-Jallow, Omar Nunez-Lopez, Alex Wright, Erika Fuchs, Mollie Ahn, Elizabeth Lyons, Daniel Jupiter, Lindsey Berry, Oscar Suman, Ravi S Radhakrishnan, Andrea M Glaser, Deborah I Thompson Jan 2021

Wearable Activity Tracking Device Use In An Adolescent Weight Management Clinic: A Randomized Controlled Pilot Trial, Kanika Bowen-Jallow, Omar Nunez-Lopez, Alex Wright, Erika Fuchs, Mollie Ahn, Elizabeth Lyons, Daniel Jupiter, Lindsey Berry, Oscar Suman, Ravi S Radhakrishnan, Andrea M Glaser, Deborah I Thompson

Children’s Nutrition Research Center Staff Publications

Background: The use of physical activity tracker devices has increased within the general population. However, there is limited medical literature studying the efficacy of such devices in adolescents with obesity. In this study, we explored the feasibility of using wearable activity tracking devices as an adjunct intervention on adolescents with obesity.

Methods: Randomized controlled pilot trial evaluated the feasibility (attrition ≤50%) of an activity tracking intervention (ATI) and its effects on weight loss in adolescents with obesity enrolled in an adolescent weight management clinic (AWMC). Outcomes included feasibility (attrition rate) and absolute change in BMI. Differences between groups at 6, …


Opportunities, Barriers, And Recommendations In Down Syndrome Research., James A. Hendrix, Angelika Amon, Leonard Abbeduto, Stamatis Agiovlasitis, Tarek Alsaied, Heather A. Anderson, Lisa J. Bain, Nicole Baumer, Anita Bhattacharyya, Dusan Bogunovic, Kelly N. Botteron, George Capone, Priya Chandan, Isabelle Chase, Brian Chicoine, Cécile Cieuta-Walti, Lara R. Deruisseau, Sophie Durand, Anna Esbensen, Juan Fortea, Sandra Giménez, Ann-Charlotte Granholm, Laura J. Hahn, Elizabeth Head, Hampus Hillerstrom, Lisa M. Jacola, Matthew P. Janicki, Joan M. Jasien, Angela R. Kamer, Raymond D. Kent, Bernard Khor, Jeanne B. Lawrence, Catherine Lemonnier, Amy Feldman Lewanda, William Mobley, Paul E. Moore, Linda Pollak Nelson, Nicolas M. Oreskovic, Ricardo S. Osorio, David Patterson, Sonja A. Rasmussen, Roger H. Reeves, Nancy Roizen, Stephanie Santoro, Stephanie L. Sherman, Nasreen Talib, Ignacio E. Tapia, Kyle M. Walsh, Steven F. Warren, A Nicole White, Guang William Wong, John S. Yi Jan 2021

Opportunities, Barriers, And Recommendations In Down Syndrome Research., James A. Hendrix, Angelika Amon, Leonard Abbeduto, Stamatis Agiovlasitis, Tarek Alsaied, Heather A. Anderson, Lisa J. Bain, Nicole Baumer, Anita Bhattacharyya, Dusan Bogunovic, Kelly N. Botteron, George Capone, Priya Chandan, Isabelle Chase, Brian Chicoine, Cécile Cieuta-Walti, Lara R. Deruisseau, Sophie Durand, Anna Esbensen, Juan Fortea, Sandra Giménez, Ann-Charlotte Granholm, Laura J. Hahn, Elizabeth Head, Hampus Hillerstrom, Lisa M. Jacola, Matthew P. Janicki, Joan M. Jasien, Angela R. Kamer, Raymond D. Kent, Bernard Khor, Jeanne B. Lawrence, Catherine Lemonnier, Amy Feldman Lewanda, William Mobley, Paul E. Moore, Linda Pollak Nelson, Nicolas M. Oreskovic, Ricardo S. Osorio, David Patterson, Sonja A. Rasmussen, Roger H. Reeves, Nancy Roizen, Stephanie Santoro, Stephanie L. Sherman, Nasreen Talib, Ignacio E. Tapia, Kyle M. Walsh, Steven F. Warren, A Nicole White, Guang William Wong, John S. Yi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community.

OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan.

METHODS: NDSS and LuMind IDSC assembled over 50 experts across …


Role For Carbohydrate Response Element-Binding Protein (Chrebp) In High Glucose-Mediated Repression Of Long Noncoding Rna Tug1, Jianyin Long, Daniel L Galvan, Koki Mise, Yashpal S Kanwar, Li Li, Naravat Poungavrin, Paul A Overbeek, Benny H Chang, Farhad R Danesh Nov 2020

Role For Carbohydrate Response Element-Binding Protein (Chrebp) In High Glucose-Mediated Repression Of Long Noncoding Rna Tug1, Jianyin Long, Daniel L Galvan, Koki Mise, Yashpal S Kanwar, Li Li, Naravat Poungavrin, Paul A Overbeek, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

Long noncoding RNAs (lncRNAs) have been shown to play key roles in a variety of biological activities of the cell. However, less is known about how lncRNAs respond to environmental cues and what transcriptional mechanisms regulate their expression. Studies from our laboratory have shown that the lncRNA Tug1 (taurine upregulated gene 1) is crucial for the progression of diabetic kidney disease, a major microvascular complication of diabetes. Using a combination of proximity labeling with the engineered soybean ascorbate peroxidase (APEX2), ChIP-qPCR, biotin-labeled oligonucleotide pulldown, and classical promoter luciferase assays in kidney podocytes, we extend our initial observations in the current …