Medical Specialties Commons^™

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Transdisciplinarity At The Boundaries: Exploring A Sylvan Metaphor For Health, Peter J. Whitehouse

Faculty Scholarship

Transdisciplinarity is an action oriented intellectual and ethical endeavor to address complex ecological, economic, and political challenges that humans face. Language is viewed as a powerful tool for necessary cultural change. Blending art and science looking for the difficult to define but critically important hidden spaces between apparently rigid conceptual structures is a core of transdisciplinarity. Metaphor is a particular powerful tool for examining boundaries and developing creative blends of structures and processes. Forests are biologically and culturally critical to life on the planet. In this paper we explore, a performance character named Sylvanus, the Tree Doctor, named after the …

Quantitative Clinical And Autoimmune Assessments In Stiff Person Syndrome: Evidence For A Progressive Disorder., Goran Rakocevic, Harry Alexopoulos, Marinos C. Dalakas

Department of Neurology Faculty Papers

BACKGROUND: Stiff Person Syndrome (SPS) is an under-diagnosed disorder that affects mobility and the quality of life of affected patients. The aim of the study is to describe the natural history of SPS, the extent of accumulated disability and the associated clinical and immunological features in patients followed for up to 8 years in a single center.

METHODS: Our collective cohort included 57 SPS patients. Additionally, 32 of these patients were examined every 6 months for a two-year period in a longitudinal study protocol, to assess disease progression using quantitative measures of stiffness and heightened sensitivity.

RESULTS: The most frequent …

Potential Applications Of Capsaicinoids In Small Cell Lung Cancer Therapy, Jamie Rae Friedman

Theses, Dissertations and Capstones

Lung cancer continues to be the leading cause of cancer related mortality worldwide. Lung cancer is not a single disease but an umbrella that encompasses two major classifications, nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). SCLC represents about 15- 20% of all lung cancer cases and is almost exclusively diagnosed in smokers. Typically, patients will respond very well to first line treatment, but face inevitable relapse. The fact that SCLC still carries a grim 5-year survival rate of less than 5% highlights the lack of advancement in treatment options to effectively improve patient response and survival. …

Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a …

Progressive Hypoxia-On-A-Chip: An In Vitro Oxygen Gradient Model For Capturing The Effects Of Hypoxia On Primary Hepatocytes In Health And Disease, Young Bok Abraham Kang, Jinsu Eo, Beyza Bulutoglu, Martin L. Yarmush, O. Berk Usta

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Oxygen is vital to the function of all tissues including the liver and lack of oxygen, that is, hypoxia can result in both acute and chronic injuries to the liver in vivo and ex vivo. Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiology of liver diseases. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concentrations on a single continuous microtissue, ranging from normoxia to severe hypoxia. This range approximately captures both the physiologically relevant oxygen gradient …

Identification Of Extracellular Dna-Binding Proteins In The Biofilm Matrix., Jeffrey S. Kavanaugh, Caralyn E. Flack, Jessica Lister, Erica B. Ricker, Carolyn B. Ibberson, Christian Jenul, Derek E. Moormeier, Elizabeth A. Delmain, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

We developed a new approach that couples Southwestern blotting and mass spectrometry to discover proteins that bind extracellular DNA (eDNA) in bacterial biofilms. Using Staphylococcus aureus as a model pathogen, we identified proteins with known DNA-binding activity and uncovered a series of lipoproteins with previously unrecognized DNA-binding activity. We demonstrated that expression of these lipoproteins results in an eDNA-dependent biofilm enhancement. Additionally, we found that while deletion of lipoproteins had a minimal impact on biofilm accumulation, these lipoprotein mutations increased biofilm porosity, suggesting that lipoproteins and their associated interactions contribute to biofilm structure. For one of the lipoproteins, SaeP, we …

Neurogenesis In Neurodegenerative Diseases: Role Of Mfg-E8, Cletus Cheyuo, Monowar Aziz, Ping Wang

Faculty & Staff Scholarship

Neurodegenerative diseases are devastating medical conditions with no effective treatments. Restoration of impaired neurogenesis represents a promising therapeutic strategy for neurodegenerative diseases. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein that plays a wide range of cellular functions including phagocytosis of apoptotic cells, anti-inflammation, tissue regeneration, and homeostasis. The beneficial role of MFG-E8 has been shown in cerebral ischemia (stroke), neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, and traumatic brain injury. In stroke, MFG-E8 promotes neural stem cell proliferation and their migration toward the ischemic brain tissues. These novel functions of MFG-E8 are primarily mediated …

An Exploratory Study Examining The Associations Between Sunlight Exposure, Sleep Behaviours And Sleep Outcomes During An Arctic Summer, Margaret M. Lubas, Ralitsa S. Maduro, Mariana Szklo-Coxe

Community & Environmental Health Faculty Publications

Few evidence-based recommendations exist for maintaining healthy sleep during Arctic summers. Our study aimed to examine associations between sleep hygiene, sunlight exposure and sleep outcomes in workers living in and/or near the Arctic Circle during a 24-h light period. A survey was administered July 2017 to 19 workers at 3 Arctic base camps in Northeastern Alaska. Participants with poorer sleep hygiene reported increased sleepiness (r=.62, p=0.01); this correlation remained moderately strong, albeit not statistically significant (NS), after controlling for shift work (r=.46, p=0.06). No other statistically significant correlations between sleep hygiene and sleep outcomes were found. Weekly daytime (8pm) sunlight …

Dna Damage And Cytokine Production In Non-Target Irradiated Lymphocytes, Jane Bryant, Laura Shields, Christopher Hynes, Orla L. Howe, Brendan Mcclean, Fiona Lyng

Articles

In advanced radiotherapy, treatment of the tumor with high-intensity modulated fields is balanced with normal tissue sparing. However, the non-target dose delivered to surrounding healthy tissue within the irradiated volume is a potential cause for concern. Whether the effects observed are caused after exposure to out-of-field radiation or bystander effects through neighboring irradiated cells is not fully understood. The goal of this study was to determine the effect of exposure to out-of-field radiation in lymphocyte cell lines and primary blood cells. The role of cellular radiosensitivity in altering bystander responses in out-of-field exposed cells was also investigated. Target cells were …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Obesity: Modern Medicine Vs. Lifestyle, Jenny Christianson

Physician Assistant Scholarly Project Posters

• Obesity is a rising epidemic, and is one of the most common, costly and preventable health problems the world is experiencing today (Center for Disease Control and Prevention, [CDC], 2017).

• From this, it is important to establish an effective treatment plan that can be implemented across the nation for maximum patient benefit.

• Lifestyle changes such as diet and exercise are important to any health care plan and are equally necessary to reduce health risks. However, in certain patients, lifestyle changes are not enough due to the maladaptive biologic process in their brain. Thus, additional treatment options need …

The Role Of Activin A Signaling In Gastric Reflux-Related Diseases And The Progression To Esophageal Adenocarcinoma, Cedric J. Roudebush

Honors Undergraduate Theses

Gastroesophageal reflux disease (GERD), or acid reflux, affects 6-9 million people in the United States. It is characterized by a reflux of gastric acid and bile salts from the stomach into the esophagus, causing injuries to the esophagus known as Barrett's esophagus (BE). BE is the main risk factor for the development of esophageal adenocarcinoma (EAC), a devastating cancer in the esophagus whose molecular roots remain poorly understood. In recent years, evidence points to the esophageal epithelium itself as responsible for causing and promoting inflammation upon injury by gastric reflux, namely via an increase in inflammatory cytokine secretion. This project …

Reanalysis Of The Nccn Pd-L1 Companion Diagnostic Assay Study For Lung Cancer In The Context Of Pd-L1 Expression Findings In Triple-Negative Breast Cancer, David L. Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, Anja C. Roden, Fred R. Hirsch, Ignacio I. Wistuba, Lajos Pusztai

Journal Articles: Pathology and Microbiology

The companion diagnostic test for checkpoint inhibitor immune therapy is an immunohistochemical test for PD-L1. The test has been shown to be reproducible for expression in tumor cells, but not in immune cells. Immune cells were used in the IMpassion130 trial which showed PD-L1 expression was associated with a better outcome. Two large studies have been done assessing immune cell PD-L1 expression in lung cancer. Here, we reanalyze one of those studies, to show that, even with an easier scoring method, there is still only poor agreement between assays and pathologist for immune cell PD-L1 expression.

Observations Of Shear Stress Effects On Staphylococcus Aureus Biofilm Formation, Erica Sherman, Kenneth W. Bayles, Derek E. Moormeier, Jennifer L. Endres, Timothy Wei

Journal Articles: Pathology and Microbiology

Staphylococcus aureus bacteria form biofilms and distinctive microcolony or "tower" structures that facilitate their ability to tolerate antibiotic treatment and to spread within the human body. The formation of microcolonies, which break off, get carried downstream, and serve to initiate biofilms in other parts of the body, is of particular interest here. It is known that flow conditions play a role in the development, dispersion, and propagation of biofilms in general. The influence of flow on microcolony formation and, ultimately, what factors lead to microcolony development are, however, not well understood. The hypothesis being examined is that microcolony structures form …

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

The Risk Of New-Onset Epilepsy And Refractory Epilepsy In Older Adult Stroke Survivors, Jorge G. Burneo, Tresah C. Antaya, Britney N. Allen, Andrea Belisle, Salimah Z. Shariff, Gustavo Saposnik

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• Stroke is a common cause of epilepsy in older adults, but little is known about stroke-related epilepsy or its outcomes in this population.
• 1.1% of older adult stroke survivors developed epilepsy in this study, of whom 12.9% developed refractory epilepsy, indicating that this population is particularly responsive to treatment.
• Over 85% of deaths in this population are not due to stroke or epilepsy.

Long-Term Outcomes Of Neonatal Herpes Simplex Virus Infection And Treatment, Genesis M. Brador

Honors Undergraduate Theses

The prevalence of herpes simplex virus (HSV) infection globally is high, and although there is no cure for it, the antiviral drug acyclovir is used to alleviate symptoms. There are two types of HSV: HSV-1, which typically infects the oral area, and HSV-2, which is associated with genital infections. A mother who carries the infection may transmit it to a neonate in different ways, most commonly via vaginal delivery in the presence of active lesions. There are three types of HSV disease that affect newborns: skin, eyes or mouth (SEM) disease, central nervous system (CNS) disease, or disseminated disease. The …

Reverting Immune Suppression To Enhance Cancer Immunotherapy., Bella S Guerrouahen, Cristina Maccalli, Chiara Cugno, Sergio Rutella, Emmanuel T Akporiaye

Articles, Abstracts, and Reports

Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …

Initiation Of Action Potential In Murine Ventricular Myocytes By Bursts Of Nanosecond Pulses, Iurii Semenov

Bioelectrics Publications

[First slide] Current situation

I. Among 300,000 persons die from sudden cardiac arrest every year over 40% are victims of fibrillation

II. Defibrillation by an electric shock is the effective therapy against sudden cardiac death

III. Current approach to stop fibrillation may involve disruption of plasma membrane (PM) by an electroporation

IV. Electroporation is damaging, it can: I. Induce post shock arrhythmias II. Complicate patient's recovery III. Lead to death after initially successful resuscitation

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

A Systems Thinking Approach For Eliciting Mental Models From Visual Boundary Objects In Hydropolitical Contexts: A Case Study From The Pilcomayo River Basin, Riveraine S. Walters, Erin S. Kenzie, Alexander E. Metzger, William Jesse Baltutis, Kakali B. Chakrabarti, Shana Lee Hirsch, Bethany Laursen

Complex Systems Faculty Publications and Presentations

Transboundary collaborations related to international freshwater are critical for ensuring equitable, efficient, and sustainable shared access to our planet’s most fundamental resources. Visual artifacts, such as knowledge maps, functioning as boundary objects, are used in hydropolitical contexts to convey understandings and facilitate discussion across scales about challenges and opportunities from multiple perspectives. Such focal points for discussion are valuable in creating shared, socially negotiated priorities and integrating diverse and often disparate cultural perspectives that naturally exist in the context of international transboundary water resources. Visual boundary objects can also represent the collective mental models of the actor countries and transboundary …

Therapeutic Targeting Of Relaxin Signaling In Ischemic Heart Disease, Siva Teja Vk Devarakonda

Theses and Dissertations

Ischemic heart disease is characterized by reduced perfusion of oxygenated blood to the myocardium, potentially resulting in infarction upon occlusion of coronary arteries. While prompt reperfusion and advances in in-hospital care have led to a decline in short term mortality, sustained damage to the ventricle, along with reperfusion injury, can lead to progressive deterioration in cardiac function. Limiting the extent of this initial ischemia-reperfusion injury and combating the course of adverse remodeling remains the scope of several preclinical studies geared towards improving cardiac health after MI. To this, relaxin-2 – the peptide hormone that regulates maternal hemodynamic function during pregnancy …

การเปรียบเทียบการเกิดภาวะเอียงของกระดูกเชิงกรานขณะวิ่งที่ระดับความหนักปานกลางในกลุ่มนักวิ่งมือใหม่และนักวิ่งสันทนาการเพศหญิง, หทัยภัทร ทิพยุทธ

Chulalongkorn University Theses and Dissertations (Chula ETD)

การวิจัยครั้งนี้มีวัตถุประสงค์เพื่อศึกษาผลของการวิ่งที่ระดับความหนักปานกลางต่อระยะเวลาการเกิดภาวะเอียงของกระดูกเชิงกราน (pelvic drop) ในนักวิ่งมือใหม่ และนักวิ่งสันทนาการเพศหญิง และศึกษาความสัมพันธ์ระหว่างแนวการเอียงของกระดูกเชิงกราน (pelvic alignment)กับอัตราการเต้นของหัวใจ (heart rate; HR), การใช้ออกซิเจน (VO2 uptake), ค่าความรู้สึกเหนื่อย (Rating of Perceived Exertion; RPE), ค่าความรู้สึกล้าของขา (Rating of Perceived Exertion for legs; RPElegs) และความล้าของกล้ามเนื้อ Gluteus medius และ Gluteus maximus กลุ่มตัวอย่างในงานวิจัยครั้งนี้อายุระหว่าง 18 - 35 ปี เป็นนักวิ่งมือใหม่ (ประสบการณ์น้อยกว่า 1 ปี) 27 คน และนักวิ่งสันทนาการ (ประสบการณ์ 2 - 4 ปี) 27 คน ซึ่งทั้งสองกลุ่มได้รับการทดสอบประสิทธิภาพการใช้ออกซิเจนสูงสุด (VO2max) และวิ่งบนลู่วิ่ง 30 นาที ที่ระดับความหนักปานกลางที่อัตราเร็วที่เลือกเอง (นักวิ่งมือใหม่; 5.87 ± 0.62 กม./ชม. vs. นักวิ่งสันทนาการเพศหญิง; 6.44 ± 0.58 กม./ชม.) โดยอยู่ในช่วงอัตราการเต้นหัวใจที่ 40 - 59% ของอัตราการเต้นหัวใจสำรองสูงสุด (heart rate reserve; HRR) ขณะทดสอบบนลู่วิ่ง 30 นาที นักวิ่งทั้งสองกลุ่มจะถูกบันทึกค่าอัตราการเต้นของหัวใจ, การใช้ออกซิเจน, ค่าความรู้สึกเหนื่อย, ค่าความรู้สึกล้าของขา และวัดการทำงานของกล้ามเนื้อ (muscle activity) จากสัญญาณไฟฟ้า (electromyography; EMG) ที่กล้ามเนื้อ Gluteus medius และ Gluteus maximus ทุก ๆ …

การศึกษาฤทธิ์ของ Fluoxetine ในการยับยั้งการเจริญเติบโตและเหนี่ยวนำการตายแบบ Apoptosis ผ่านวิถี Pi3k/Akt และ Sigma-1 Receptor ใน Leukemic Cell Lines, ชนิชนม์ ชมเชย

Chulalongkorn University Theses and Dissertations (Chula ETD)

Fluoxetine เป็นยากลุ่ม SSRI (selective serotonin reuptake inhibitor) ที่ใช้ในการรักษาโรคซึมเศร้า ยาหลายตัวในกลุ่ม SSRI สามารถจับแบบจำเพาะ sigma-1 receptor แต่ในกรณี fluoxetine จะมีกลไกออกฤทธิ์จำเพาะต่อ serotonin transporter (Ki = 0.81 nM) มากกว่า sigma-1 receptor (Ki = 214–240 nM) หลายงานวิจัยรายงานว่า sigma-1 receptor แสดงออกบนเซลล์มะเร็งหลายชนิด และมีรายงานว่า antagonist สามารถลดการเพิ่มจำนวนและเหนี่ยวนำให้เกิด apoptosis แต่การทำงานร่วมกันระหว่าง fluoxetine กับ sigma-1 receptor ต่อเซลล์มะเร็ง ยังไม่ทราบกลไกการออกฤทธิ์ที่ชัดเจน งานวิจัยนี้มีวัตถุประสงค์เพื่อศึกษาฤทธิ์ของ fluoxetine ในการยับยั้งการแบ่งตัวและเหนี่ยวนำให้เกิด apoptosis ผ่าน sigma-1 receptor ในเซลล์มะเร็งเม็ดเลือดขาว ผลการทดสอบพบว่า fluoxetine สามารถลดเปอร์เซ็นต์การรอดชีวิตของเซลล์ Jurkat และ U937 ได้ โดยมีค่า IC50 เท่ากับ 28 ± 1.4 และ 36 ± 1.6 uM ตามลำดับ เมื่อเซลล์ Jurkat ถูกทดสอบด้วย fluoxetine ตามระดับความเข้มข้นและระยะเวลาที่เพิ่มขึ้น พบว่าfluoxetine สามารถยับยั้งการแบ่งตัวของเซลล์ Jurkat ได้อย่างมีนัยสำคัญทางสถิติ โดยมีกลไกหยุดยั้งวัฎจักรเซลล์ที่ระยะ G2/M และลดการหลั่งไซโตไคน์ IL-2 รวมทั้งเหนี่ยวนำให้เกิด apoptosis โดยการลดการแสดงออกของโปรตีน pro caspase 9 ผ่านการยับยั้งการเกิด phosphorylation ของ AKT ในวิถี PI3K/Akt และ การถูกกระตุ้นของ sigma-1 receptor …

Differences In The M1 And M2 Macrophage Subtypes Between The Sexes Determine Susceptibility To Francisella Tularensis Infection, Michelle Arlene Sanchez

Open Access Theses & Dissertations

Francisella tularensis is the causative agent of the human disease tularemia. It is highly infectious with as few as 10 microorganisms via inhalation causing a lethal infection. F. tularensis infects a variety of cell types, including macrophages and neutrophils, since it needs to enter, survive and proliferate in order to cause pathogenicity. Disease is the result of over activating the host's own inflammatory response initiated by the macrophage's response to infection.

Known differences exist in the intensity of the inflammatory response between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more …

Improving Access To Clean Water In Rural Ecuador: The Connection Between Willingness To Pay And Population Health, Micalea Leaska

Capstone Collection

Climate change is affecting social and environmental determinants of health through access to safe drinking water, safely managed sanitation systems, and access to health care services and the ability for individuals to break free from unsuitable circumstances. Ecological disturbances such as those caused by climate change can cause a shift in host vectors or a change in habitat that results in a greater likelihood of the pathogen coming in contact with humans. Water, sanitation, and hygiene (WASH) services and their accessibility to populations can directly impact a community’s vulnerability to diseases and limiting factors to increase economic growth. If rural …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …