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Unveiling Bacterial Hitchhikers In The Urobiome, Genevieve Baddoo Jan 2022

Unveiling Bacterial Hitchhikers In The Urobiome, Genevieve Baddoo

Master's Theses

Microbial communities of bacteria, viruses, and fungi form complex interactions in nature. However, our understanding of these communities is limited to those that can be cultured in the lab. Enhanced culture methods have enabled the isolation of numerous fastidious species from urinary tract, definitively proving that the urinary tract of asymptomatic individuals is not sterile. In working with these isolates, our group has observed several instances in which a “purified” isolate actually harbors more than one species. We refer to these additional members as bacterial hitchhikers, a term previously used to describe similar occurrences in soil communities. I hypothesized that …


Psychological Symptoms, Visceral Pain Sensitivity, And Observations Of Parent Pain Behavior Are Related To Somatic Symptoms In Premenarchal Adolescents, Genevieve Roth Jan 2022

Psychological Symptoms, Visceral Pain Sensitivity, And Observations Of Parent Pain Behavior Are Related To Somatic Symptoms In Premenarchal Adolescents, Genevieve Roth

Master's Theses

Somatic symptoms are a risk factor for the development of chronic pelvic pain in women. The present study characterized somatic symptoms and their relations with psychological, pain sensitivity, and parental factors in a community sample of premenarchal adolescents, which marks an initial step in advancing the identification of potential modifiable factors related to menstrual pain and chronic pain development. Pain sensitivity (visceral and bodily factors) and psychological symptoms (anxiety and stress) were predicted to be related to somatic symptoms (e.g, widespread bodily discomfort) in premenarchal adolescents. Additionally, adolescents’ observation of parent pain behavior was expected to be specifically associated with …


Longitudinal Changes Of Cardiorespiratory Fitness Performance In High School: Association With Individual And School-Based Variables, Xihe Zhu, Justin A. Haegele, Jinting Shao, Summer Davis Jan 2022

Longitudinal Changes Of Cardiorespiratory Fitness Performance In High School: Association With Individual And School-Based Variables, Xihe Zhu, Justin A. Haegele, Jinting Shao, Summer Davis

Human Movement Studies & Special Education Faculty Publications

This study aimed to model adolescents’ cardiorespiratory fitness performance change trajectories longitudinally across high school years and its relation to school- and individual/student-level factors. We employed hierarchical linear modeling to examine longitudinal cardiorespiratory fitness performance changes, as measured by the progressive aerobic capacity endurance run (PACER), over the years, between sexes, and in association with the school-level variables. Participants were 76,227 adolescents from 80 high schools in the mid-Atlantic region of the United States. School-level academic performance (SAP), the percent of students eligible for free and reduced-price meals (FARM), and physical education student-faculty ratio were obtained with permission from the …


Graphene Based Electrochemical Biosensors For The Detection Of Blood Biomarkers Of Alzheimer’S Disease, Jagriti Sethi Jan 2022

Graphene Based Electrochemical Biosensors For The Detection Of Blood Biomarkers Of Alzheimer’S Disease, Jagriti Sethi

School of Engineering, Computing and Mathematics Theses

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions of people around the world with no available treatments to cure, reverse or even slow down the disease progression. Detection of AD in the early stages, before the massive neuronal loss, is key to developing disease-modifying treatments and preventive strategies. The current AD diagnosis is largely based on evaluation tests such as Mini-Mental State Examination (MMSE), imaging techniques such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and postmortem autopsies. It is expensive and only available at the later/severe stages when the brain of the patient is already damaged …


Flexible Goal-Directed Manipulation Of Representations: Computational Models Of Healthy And Pathological Human Cognition, Giovanni Granato Jan 2022

Flexible Goal-Directed Manipulation Of Representations: Computational Models Of Healthy And Pathological Human Cognition, Giovanni Granato

School of Engineering, Computing and Mathematics Theses

The brain is able to manipulate itself, adapting its internal world in a changing environment. In particular it continuously manipulates its representations to achieve goals. This competence is supported by many neurocognitive high-order processes that interact during the performance of a goal-directed behaviour (e.g. attention processes, executive functions, motivational systems). Overall, adult humans often face a new problem trough a change of the `perceptual point of view' (i.e. a representational change), rather then an extended research of the correct action to perform. On the other hand, infants and children contemporary develop motor competence and task-directed perceptual representations (e.g. categorical perception). …


Socioeconomic, Clinical, And Molecular Features Of Breast Cancer Influence Overall Survival Of Latin American Women, Liz Maria De Almeida, Sandra Cortés, Marta Vilensky, Olivia Valenzuela, Laura Cortes-Sanabria, Mirian De Souza, Rafael Alonso Barbeito, Eliana Abdelhay, Nora Artagaveytia, Adrian Daneri-Navarro, Andrea S Llera, Bettina Müller, Osvaldo L Podhajcer, Carlos Velazquez, Elsa Alcoba, Isabel Alonso, Alicia I Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raul Delgadillo-Cristerna, Lucia Delgado, Marisa Dreyer Breitenbach, Elmer Fernández, Jorge Fernández, Wanda Fernández, Ramon A Franco-Topete, Fancy Gaete, Jorge Gómez, Leivy P Gonzalez-Ramirez, Marisol Guerrero, Susan A Gutierrez-Rubio, Beatriz Jalfin, Alejandra Lopez-Vazquez, Dora Loria, Silvia Míguez, Andres De J Moran-Mendoza, Gilberto Morgan-Villela, Carina Mussetti, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Rui M Reis, Javier Retamales, Robinson Rodriguez, Cristina Rosales, Efrain Salas-Gonzalez, Laura Segovia, Juan M Sendoya, Aida A Silva-Garcia, Stella Viña, Livia Zagame, Beth Jones, Moysés Szklo, United States-Latin American Cancer Research Network (Us-Lacrn) Jan 2022

Socioeconomic, Clinical, And Molecular Features Of Breast Cancer Influence Overall Survival Of Latin American Women, Liz Maria De Almeida, Sandra Cortés, Marta Vilensky, Olivia Valenzuela, Laura Cortes-Sanabria, Mirian De Souza, Rafael Alonso Barbeito, Eliana Abdelhay, Nora Artagaveytia, Adrian Daneri-Navarro, Andrea S Llera, Bettina Müller, Osvaldo L Podhajcer, Carlos Velazquez, Elsa Alcoba, Isabel Alonso, Alicia I Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raul Delgadillo-Cristerna, Lucia Delgado, Marisa Dreyer Breitenbach, Elmer Fernández, Jorge Fernández, Wanda Fernández, Ramon A Franco-Topete, Fancy Gaete, Jorge Gómez, Leivy P Gonzalez-Ramirez, Marisol Guerrero, Susan A Gutierrez-Rubio, Beatriz Jalfin, Alejandra Lopez-Vazquez, Dora Loria, Silvia Míguez, Andres De J Moran-Mendoza, Gilberto Morgan-Villela, Carina Mussetti, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Rui M Reis, Javier Retamales, Robinson Rodriguez, Cristina Rosales, Efrain Salas-Gonzalez, Laura Segovia, Juan M Sendoya, Aida A Silva-Garcia, Stella Viña, Livia Zagame, Beth Jones, Moysés Szklo, United States-Latin American Cancer Research Network (Us-Lacrn)

Faculty, Staff and Students Publications

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by …


Exercise-Induced Myokines Downregulates The Ace2 Level In Bronchial Epithelial Cells: Implications For Sars-Cov-2 Prevention, Vaishali Bhardwaj, Mart Dela Cruz, Deepika Subramanyam, Rohit Kumar, Sandeep Markan, Beth Parker, Hemant K Roy Jan 2022

Exercise-Induced Myokines Downregulates The Ace2 Level In Bronchial Epithelial Cells: Implications For Sars-Cov-2 Prevention, Vaishali Bhardwaj, Mart Dela Cruz, Deepika Subramanyam, Rohit Kumar, Sandeep Markan, Beth Parker, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: The Covid-19 pandemic has emerged as the leading public health challenge of our time (20th century). While vaccinations have finally blunted the death rate, concern has remained about more virulent forms highlighting the need for alternative approaches. Epidemiological studies indicate that physical activity has been shown to decrease the risk of infection of some respiratory viruses. Part of the salutary effects of exercise is believed to be through the elaboration of cytokines by contracting skeletal muscles (termed myokines). The objective of this study was to investigate whether exercise-induced myokines would mitigate the SARS-CoV-2 infectivity of the bronchial epithelium through …


A Precision Medicine Agenda In Traumatic Brain Injury, Jovany Cruz Navarro, Lucido L Ponce Mejia, Claudia Robertson Jan 2022

A Precision Medicine Agenda In Traumatic Brain Injury, Jovany Cruz Navarro, Lucido L Ponce Mejia, Claudia Robertson

Faculty, Staff and Students Publications

Traumatic brain injury remains a leading cause of death and disability across the globe. Substantial uncertainty in outcome prediction continues to be the rule notwithstanding the existing prediction models. Additionally, despite very promising preclinical data, randomized clinical trials (RCTs) of neuroprotective strategies in moderate and severe TBI have failed to demonstrate significant treatment effects. Better predictive models are needed, as the existing validated ones are more useful in prognosticating poor outcome and do not include biomarkers, genomics, proteonomics, metabolomics, etc. Invasive neuromonitoring long believed to be a "game changer" in the care of TBI patients have shown mixed results, and …


Sensory Descriptors For Three Edible Chilean Seaweeds And Their Relations To Umami Components And Instrumental Texture, Valentina Figueroa, Andrea Bunger, Jaime Ortiz, José Miguel Aguilera Jan 2022

Sensory Descriptors For Three Edible Chilean Seaweeds And Their Relations To Umami Components And Instrumental Texture, Valentina Figueroa, Andrea Bunger, Jaime Ortiz, José Miguel Aguilera

Faculty, Staff and Students Publications

Although seaweeds exhibit many benefits as a food source, few studies have characterized their sensory attributes. An expert nine-member panel developed a vocabulary with 25 descriptors to describe the appearance, aroma, flavor, texture, and aftertaste of raw and cooked seaweeds consumed in Chile: Durvillaea antarctica, Pyropia spp., and Ulva lactuca. Subsequently, the vocabulary was used in a ranking descriptive analysis (RDA) to evaluate the sensory properties and relate them with physicochemical and physical data. Sensory attributes of the three seaweeds were very different from each other but similar between treatments (raw and cooked). Pyropia spp., both cooked and …


Catalytic Asymmetric Synthesis Of Carbocyclic C-Nucleosides, Sourabh Mishra, Florian C T Modicom, Conor L Dean, Stephen P Fletcher Jan 2022

Catalytic Asymmetric Synthesis Of Carbocyclic C-Nucleosides, Sourabh Mishra, Florian C T Modicom, Conor L Dean, Stephen P Fletcher

Faculty, Staff and Student Publications

Access to carbocyclic C-nucleosides (CC-Ns) is currently restricted. The few methods available to make CC-Ns suffer from long syntheses and poor modularity, hindering the examination of potentially important chemical space. Here we report an approach to CC-Ns which uses an asymmetric Suzuki-Miyaura type reaction as the key C-C bond forming step. After coupling the densely functionalized racemic bicyclic allyl chloride and heterocyclic boronic acids, the trisubstituted cyclopentenyl core is elaborated to RNA analogues via a hydroborylation-homologation-oxidation sequence. We demonstrate that the approach can be used to produce a variety of enantiomerically enriched CC-Ns, including a carbocyclic derivative of Showdomycin.


An Analysis Of Anatomy Education Before And During Covid-19: August-December 2020, Stefanie M. Attardi, Derek J. Harmon, Malli Barremkala, Danielle C. Bentley, Kirsten M. Brown, Jennifer F. Dennis, Haviva M. Goldman, Kelly M. Harrell, Barbie A. Klein, Christopher J. Ramnanan, Gary J. Farkas Jan 2022

An Analysis Of Anatomy Education Before And During Covid-19: August-December 2020, Stefanie M. Attardi, Derek J. Harmon, Malli Barremkala, Danielle C. Bentley, Kirsten M. Brown, Jennifer F. Dennis, Haviva M. Goldman, Kelly M. Harrell, Barbie A. Klein, Christopher J. Ramnanan, Gary J. Farkas

Faculty and Staff Publications

Coronavirus disease-2019 (Covid-19) disrupted the in-person teaching format of anatomy. To study changes in gross anatomy education that occurred during August-December, 2020 compared to before the pandemic, an online survey was distributed to anatomy educators. The 191 responses received were analyzed in total and by academic program, geographic region, and institution type. Cadaver use decreased overall (before: 74.1 ± 34.1%, during: 50.3 ± 43.0%, P < 0.0001), as well as across allopathic and osteopathic medicine, therapy, undergraduate, and veterinary programs (P < 0.05), but remained unchanged for other programs (P > 0.05). Cadaver use decreased internationally and in the US (P < 0.0001), at public and private (P < 0.0001) institutions, and among allopathic medical programs in Northeastern, Central, and Southern (P < 0.05), but not Western, US geographical regions. Laboratories during Covid-19 were delivered through synchronous (59%), asynchronous (4%), or mixed (37%) formats (P < 0.0001) and utilized digital resources (47%), dissection (32%), and/or prosection (21%) (P < 0.0001). The practical laboratory examination persisted during Covid-19 (P = 0.419); however, the setting and materials shifted to computer-based (P < 0.0001) and image-based (P < 0.0001), respectively. In-person lecture decreased during Covid-19 (before: 88%, during: 24%, P = 0.003). When anatomy digital resources were categorized, dissection media, interactive software, and open-access content increased (P ≤ 0.008), with specific increases in BlueLink, Acland's Videos, and Complete Anatomy (P < 0.05). This study provided evidence of how gross anatomy educators continued to adapt their courses past the early stages of the pandemic.


A 385-Year Experiment To Erase A People: Intergenerational Acts Of Genocide Against The Narragansett Indian Tribe By The United States Of America And The State Of Rhode Island, Taylor A. Dumpson, Afro-Indigenous; Black, Narragansett, Nanticoke, And Mohawk Ancestry Jan 2022

A 385-Year Experiment To Erase A People: Intergenerational Acts Of Genocide Against The Narragansett Indian Tribe By The United States Of America And The State Of Rhode Island, Taylor A. Dumpson, Afro-Indigenous; Black, Narragansett, Nanticoke, And Mohawk Ancestry

Tribal Law Journal

Since Roger Williams’ arrival in Narragansett Territory in 1636, and his subsequent settlement of the Providence Plantations, the Narragansett Indian Tribe--the Indigenous people to this land--have faced a series of intergenerational atrocities, including attempted genocides. For generations, these heinous wrongs have not been corrected by state or federal courts, which have often compounded the harms against the Narragansett people. Although the American legal system has played a role in perpetuating the intergenerational harms experienced by the Narragansett people, these institutions also have the opportunity to be a part of the solution. The Article examines the existing domestic legal framework for …


Immunotherapy Approaches For The Treatment Of Diffuse Midline Gliomas, Joshua D Bernstock, Samantha E Hoffman, Ari D Kappel, Pablo A Valdes, Walid Ibn Essayed, Neil V Klinger, Kyung-Don Kang, Stacie K Totsch, Hannah E Olsen, Charles W Schlappi, Katharina Filipski, Florian A Gessler, Lissa Baird, Mariella G Filbin, Rintaro Hashizume, Oren J Becher, Gregory K Friedman Jan 2022

Immunotherapy Approaches For The Treatment Of Diffuse Midline Gliomas, Joshua D Bernstock, Samantha E Hoffman, Ari D Kappel, Pablo A Valdes, Walid Ibn Essayed, Neil V Klinger, Kyung-Don Kang, Stacie K Totsch, Hannah E Olsen, Charles W Schlappi, Katharina Filipski, Florian A Gessler, Lissa Baird, Mariella G Filbin, Rintaro Hashizume, Oren J Becher, Gregory K Friedman

Faculty, Staff and Student Publications

Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy …


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 …


Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight Jan 2022

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …


Clinicopathological Correlations In Heart Transplantation Recipients Complicated By Death Or Re-Transplantation, Michelle M Mcdonald, Maks Mihalj, Bihong Zhao, Sriram Nathan, Stanislava Matejin, Giulia Ottaviani, Mateja K Jezovnik, Rajko Radovancevic, Biswajit Kar, Igor D Gregoric, L Maximilian Buja Jan 2022

Clinicopathological Correlations In Heart Transplantation Recipients Complicated By Death Or Re-Transplantation, Michelle M Mcdonald, Maks Mihalj, Bihong Zhao, Sriram Nathan, Stanislava Matejin, Giulia Ottaviani, Mateja K Jezovnik, Rajko Radovancevic, Biswajit Kar, Igor D Gregoric, L Maximilian Buja

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation.

METHODOLOGY AND STUDY DESIGN: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were …


Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Via Mechanotransduction, Max A Skibber, Scott D Olson, Karthik S Prabhakara, Brijesh S Gill, Charles S Cox Jan 2022

Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Via Mechanotransduction, Max A Skibber, Scott D Olson, Karthik S Prabhakara, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of …


Putting The “Comprehensive” In Comprehensive Sexuality Education: A Review Exploring Young Adult Literature As A School-Based Intervention, Margaret M Palmer, Jennifer S Hirsch Jan 2022

Putting The “Comprehensive” In Comprehensive Sexuality Education: A Review Exploring Young Adult Literature As A School-Based Intervention, Margaret M Palmer, Jennifer S Hirsch

Faculty, Staff and Student Publications

INTRODUCTION: In this article, we review research on the impact of young adult literature (YAL) on young people's sexuality-related beliefs. This research points to the potential of YAL as a tool through which schools can offer sex education that is truly "comprehensive" by providing young people an opportunity to grapple with questions about gender, sexuality, and healthy relationships in literature classes, and to complement CSE in health education classes. This broader approach addresses a potential limitation of school-based comprehensive sex education (CSE). CSE certainly promotes young people's health and well-being, but an emphasis on biological dimensions of sexual and reproductive …


Targeting Etosis By Mir-155 Inhibition Mitigates Mixed Granulocytic Asthmatic Lung Inflammation, Ji Young Kim, Patrick Stevens, Manjula Karpurapu, Hyunwook Lee, Joshua A Englert, Pearlly Yan, Tae Jin Lee, Navjot Pabla, Maciej Pietrzak, Gye Young Park, John W Christman, Sangwoon Chung Jan 2022

Targeting Etosis By Mir-155 Inhibition Mitigates Mixed Granulocytic Asthmatic Lung Inflammation, Ji Young Kim, Patrick Stevens, Manjula Karpurapu, Hyunwook Lee, Joshua A Englert, Pearlly Yan, Tae Jin Lee, Navjot Pabla, Maciej Pietrzak, Gye Young Park, John W Christman, Sangwoon Chung

Faculty, Staff and Student Publications

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. …


Emerging Evidence For Intrathecal Management Of Neuropathic Pain Following Spinal Cord Injury, Jay Karri, James Doan, Christian Vangeison, Marissa Catalanotto, Ameet S Nagpal, Sheng Li Jan 2022

Emerging Evidence For Intrathecal Management Of Neuropathic Pain Following Spinal Cord Injury, Jay Karri, James Doan, Christian Vangeison, Marissa Catalanotto, Ameet S Nagpal, Sheng Li

Faculty, Staff and Student Publications

A high prevalence of patients with spinal cord injury (SCI) suffer from chronic neuropathic pain. Unfortunately, the precise pathophysiological mechanisms underlying this phenomenon have yet to be clearly elucidated and targeted treatments are largely lacking. As an unfortunate consequence, neuropathic pain in the population with SCI is refractory to standard of care treatments and represents a significant contributor to morbidity and suffering. In recent years, advances from SCI-specific animal studies and translational models have furthered our understanding of the neuronal excitability, glial dysregulation, and chronic inflammation processes that facilitate neuropathic pain. These developments have served advantageously to facilitate exploration into …


Mri Free Water As A Biomarker For Cognitive Performance: Validation In The Markvcid Consortium, Pauline Maillard, Laura J Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T Gold, Christopher E Bauer, Joel H Kramer, Adam M Staffaroni, Lara Stables, Danny J J Wang, Sudha Seshadri, Claudia L Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H Mosley, Gary A Rosenberg, Baljeet Singh, Herpreet Singh, Kristin Schwab, Karl G Helmer, Steven M Greenberg, Charles Decarli, Arvind Caprihan Jan 2022

Mri Free Water As A Biomarker For Cognitive Performance: Validation In The Markvcid Consortium, Pauline Maillard, Laura J Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T Gold, Christopher E Bauer, Joel H Kramer, Adam M Staffaroni, Lara Stables, Danny J J Wang, Sudha Seshadri, Claudia L Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H Mosley, Gary A Rosenberg, Baljeet Singh, Herpreet Singh, Kristin Schwab, Karl G Helmer, Steven M Greenberg, Charles Decarli, Arvind Caprihan

Faculty, Staff and Student Publications

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.

Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).

Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p …


Emotion Regulation, Parasympathetic Function, And Psychological Well-Being, Ryan L Brown, Michelle A Chen, Jensine Paoletti, Eva E Dicker, E Lydia Wu-Chung, Angie S Leroy, Marzieh Majd, Robert Suchting, Julian F Thayer, Christopher P Fagundes Jan 2022

Emotion Regulation, Parasympathetic Function, And Psychological Well-Being, Ryan L Brown, Michelle A Chen, Jensine Paoletti, Eva E Dicker, E Lydia Wu-Chung, Angie S Leroy, Marzieh Majd, Robert Suchting, Julian F Thayer, Christopher P Fagundes

Faculty, Staff and Student Publications

The negative emotions generated following stressful life events can increase one's risk of depressive symptoms and promote higher levels of perceived stress. The process model of emotion regulation can help distinguish between adaptive and maladaptive emotion regulation strategies to determine who may be at the greatest risk of worse psychological health across the lifespan. Heart rate variability (HRV) may affect these relationships as it indexes aspects of self-regulation, including emotion and behavioral regulation, that enable an individual to dynamically adapt to the changing demands of both internal and external environments. In this study, we expected individual differences in resting vagally …


Saturating Relationship Between Phytoplankton Growth Rate And Nutrient Concentration Explained By Macromolecular Allocation, Jongsun Kim, Gabrielle Armin, Keisuke Inomura Jan 2022

Saturating Relationship Between Phytoplankton Growth Rate And Nutrient Concentration Explained By Macromolecular Allocation, Jongsun Kim, Gabrielle Armin, Keisuke Inomura

School of Earth, Environmental, & Marine Sciences Faculty Publications

Phytoplankton account for about a half of photosynthesis in the world, making them a key player in the ecological and biogeochemical systems. One of the key traits of phytoplankton is their growth rate because it indicates their productivity and affects their competitive capability. The saturating relationship between phytoplankton growth rate and environmental nutrient concentration has been widely observed yet the mechanisms behind the relationship remain elusive. Here we use a mechanistic model and metadata of phytoplankton to show that the saturating relationship between growth rate and nitrate concentration can be interpreted by intracellular macromolecular allocation. At low nitrate levels, the …


A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington Jan 2022

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …


Rev-Erb Is Essential In Cardiac Fibroblasts Homeostasis, Xiaokang Luo, Shiyang Song, Lei Qi, Chih-Liang Tien, Hui Li, Weiyi Xu, Theodore Lemuel Mathuram, Thomas Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang Jan 2022

Rev-Erb Is Essential In Cardiac Fibroblasts Homeostasis, Xiaokang Luo, Shiyang Song, Lei Qi, Chih-Liang Tien, Hui Li, Weiyi Xu, Theodore Lemuel Mathuram, Thomas Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in …


Sr9009 Improves Heart Function After Pressure Overload Independent Of Cardiac Rev-Erb, Hui Li, Shiyang Song, Chih-Liang Tien, Lei Qi, Andrea Graves, Eleni Nasiotis, Thomas P Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang Jan 2022

Sr9009 Improves Heart Function After Pressure Overload Independent Of Cardiac Rev-Erb, Hui Li, Shiyang Song, Chih-Liang Tien, Lei Qi, Andrea Graves, Eleni Nasiotis, Thomas P Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly. To address this question, we generated the REV-ERBα/β cardiac-specific double knockout mice (cDKO). We found that REV-ERB cardiac deficiency leads to profound dilated cardiac myopathy after TAC compared to wild-type (WT) control mice, confirming the critical role of REV-ERB in protecting …


Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov Jan 2022

Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov

Faculty, Staff and Students Publications

Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance. To identify genes with an excess of potentially functional missense or nonsense mutations one needs to compare the observed and expected numbers of mutations in the gene. We estimated the expected numbers of missense and nonsense mutations in individual human genes using (i) the …


Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili Jan 2022

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …


Multi-Antigen-Targeted T-Cell Therapy To Treat Patients With Relapsed/Refractory Breast Cancer, Valentina Hoyos, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Ifigeneia Tzannou, Yovana Velazquez, Matthew French-Kim, Wingchi Leung, Suhasini Lulla, Catherine Robertson, Claudette Foreman, Tao Wang, Shaun Bulsara, Natalia Lapteva, Bambi Grilley, Matthew Ellis, Charles Kent Osborne, Angela Coscio, Julie Nangia, Helen E Heslop, Cliona M Rooney, Juan F Vera, Premal Lulla, Mothaffar Rimawi, Ann M Leen Jan 2022

Multi-Antigen-Targeted T-Cell Therapy To Treat Patients With Relapsed/Refractory Breast Cancer, Valentina Hoyos, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Ifigeneia Tzannou, Yovana Velazquez, Matthew French-Kim, Wingchi Leung, Suhasini Lulla, Catherine Robertson, Claudette Foreman, Tao Wang, Shaun Bulsara, Natalia Lapteva, Bambi Grilley, Matthew Ellis, Charles Kent Osborne, Angela Coscio, Julie Nangia, Helen E Heslop, Cliona M Rooney, Juan F Vera, Premal Lulla, Mothaffar Rimawi, Ann M Leen

Faculty, Staff and Students Publications

PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.

MATERIALS AND METHODS: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 …


Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston Jan 2022

Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston

Faculty, Staff and Students Publications

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER

EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.

RESULTS: Higher baselines …