Medical Sciences Commons^™

Development Of An Hipsc-Cortical Neuron Long-Term Potentiation Model And Its Application To Alzheimer's Disease Modeling And Drug Evaluation, Kaveena Autar

Electronic Theses and Dissertations, 2020-

Alzheimer's disease (AD) is commonly characterized by a loss of cognitive function due to the deterioration of neuronal synapses from the presence of senile amyloid beta-42 (Aß42) plaques. Evaluating cognitive deficits caused by Aß42 using human cortical neurons poses a challenge due to sourcing difficulties, and the use of animal models to assess drug efficacy creates biological hurdles from lack of species translatability. Recent advances in induced-pluripotent stem cell technology have enabled the development of mature, human-based cortical neuron models. The development of an hiPSC-cortical neuron differentiation protocol facilitates the exploration of disease onset and functional analysis from a patient-derived …

Treatment Of Hypothyroidism: Desiccated Thyroid Extract, Aimee Fong

Capstone Showcase

The treatment of hypothyroidism with Levothyroxine (T4) has been well studied and FDA approved. However, many patients continue to have signs and symptoms of hypothyroidism while on Levothyroxine treatment despite reaching appropriate thyroid levels. An additional thyroid treatment known as desiccated thyroid extract (DTE) is made from dried pig thyroid glands and is advertised as a “natural” alternative to Levothyroxine. Despite lack of FDA approval and studies surrounding DTE, clinicians have prescribed DTE to patients, many of whom reported relief of their symptoms. The following poster highlights the approach to the treatment of hypothyroidism with Levothyroxine and DTE and outlines …

ผลกระทบของการปลูกถ่ายจุลินทรีย์ในลำไส้ของผู้ป่วยโรคนิ่วไตต่อการเกิดโรคนิ่วแคลเซียมออกซาเลตในทางเดินปัสสาวะของหนู, สิทธิพงษ์ หุ่นไทย

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคนิ่วไตพบมากในคนไทยโดยเฉพาะผู้ที่อาศัยในเขตภาคตะวันออกเฉียงเหนือและภาคเหนือ มีปัจจัยเสี่ยงคือ ภาวะซิเตรทในปัสสาวะต่ำ แคลเซียมและออกซาเลตในปัสสาวะสูง โดยพบมากในผู้ที่มีอายุ 40 ปีขึ้นไป จากการศึกษาก่อนหน้าพบความแตกต่างของประชากรจุลินทรีย์ในลำไส้ของผู้ป่วยโรคนิ่วไตจากคนสุขภาพดี จึงเชื่อว่าความแตกต่างของจุลินทรีย์ลำไส้ส่งผลให้เกิดความเสี่ยงของการเกิดโรคนิ่วไต เพื่อศึกษาความผิดปกตินี้ ผู้วิจัยจึงศึกษาความแตกต่างของจุลินทรีย์ในลำไส้เปรียบเทียบระหว่างอาสาสมัครคนปกติและผู้ป่วยโรคนิ่วไต พบว่าจุลินทรีย์ phylum Bacteroidata ในอุจจาระของผู้ป่วยโรคนิ่วไตสูงกว่าคนสุขภาพดี และพบ genus Bifidobacterium ต่ำกว่าคนสุขภาพดี จากนั้นนำจุลินทรีย์จากอุจจาระของอาสาสมัครทั้งสองกลุ่ม ปลูกถ่ายลงในหนู Wistar เป็นเวลา 4 สัปดาห์ พบว่า หนูกลุ่มที่ได้รับจุลินทรีย์จากกลุ่มผู้ป่วยโรคนิ่วไตมีปริมาณออกซาเลตในปัสสาวะมีแนวโน้มสูงขึ้น ปริมาณแมกนีเซียมในปัสสาวะลดลง รวมทั้ง pH ในปัสสาวะเป็นด่างมากขึ้น และพบดัชนีความเสี่ยงต่อการเกิดนิ่ว (Tiselius’s supersaturation index) เพิ่มสูงขึ้น นอกจากนี้ ยังพบ จุลินทรีย์ genus Muribaculaceae สูงขึ้นในหนูที่ได้รับการปลูกถ่ายเชื้อจุลินทรีย์จากผู้ป่วยโรคนิ่วไต และ genus Roseburia มีจำนวนลดลง รวมถึงการแสดงออกของ tight junction (Zonula occluden-1 หรือ ZO-1) ที่ลดลง และพบการแสดงออกของ oxalate transporter มีแนวโน้มสูงขึ้น สรุปได้ว่าหนูที่ได้รับเชื้อจุลินทรีย์ในอุจจาระจากผู้ป่วยโรคนิ่วไตมีความเสี่ยงต่อการเกิดโรคนิ่วสูงขึ้น โดยมีกลไกจากการแสดงออกของโปรตีน ZO-1 ลดลง และเพิ่ม oxalate transporter ที่ลำไส้ ทำให้ร่างกายได้รับออกซาเลตจากอาหารในลำไส้เพิ่มขึ้น และขับออกทางปัสสาวะเพิ่มขึ้น เป็นหลักฐานยืนยันว่าความผิดปกติของสมดุลเชื้อจุลินทรีย์ในลำไส้เพิ่มความเสี่ยงต่อการเกิดโรคนิ่วไต

Effects Of Chitosan Oligosaccharide And Probiotics On Chronic Kidney Disease Rats, Weerapat Anegkamol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chronic kidney disease (CKD) patients suffer from the accumulation of toxic substances in their blood due to the loss of kidney function, which results in hyperphosphatemia. This condition contributes to hyperparathyroidism, leading to the development of chronic kidney disease-related mineral bone disorder (CKD-MBD). Additionally, CKD patients experience changes in their gut microbiota, disrupting epithelial tight junctions and allowing excessive absorption of dietary phosphate. In this study, we aimed to investigate the effects of various oligosaccharides and probiotics on the gut microbiota, intestinal barrier, hyperphosphatemia, and hyperparathyroidism in CKD rats. We isolated Lactobacillus and Bifidobacterium strains from healthy participants and tested …

Exploring Roles Of Mir-885-5p In Hepatocellular Carcinoma, Archittapon Nokkeaw

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, exerts a significant burden on Southeast Asian countries and stands as the third leading cause of cancer-related mortality worldwide. Despite this alarming impact, effective treatments for HCC are lacking, resulting in low survival rates and high recurrence rates. Therefore, a comprehensive understanding of the disease's underlying mechanisms is crucial for the development of novel and potent therapies. Recently, it has been recognized that microRNAs (miRNAs) play a vital role in tumorigenesis, including HCC. Our bioinformatic analysis has highlighted hsa-miR-885-5p as a potential candidate miRNA due to its downregulation in HCC …

Characterization Of A New Whim Syndrome Mutant Reveals Mechanistic Differences In Regulation Of The Chemokine Receptor Cxcr4, Jiansong Luo, Francesco De Pascali, G Wendell Richmond, Amer M Khojah, Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild-type CXCR4 and a previously identified WHIM syndrome mutant, R334X. The S339fs5 and R334X mutants exhibited significantly increased signaling compared …

Time-Resolved Cryo-Em Visualizes Ribosomal Translocation With Ef-G And Gtp, Christine E Carbone, Anna B Loveland, Howard Gamper, Ya-Ming Hou, Gabriel Demo, Andrei A Korostelev

Department of Biochemistry and Molecular Biology Faculty Papers

During translation, a conserved GTPase elongation factor-EF-G in bacteria or eEF2 in eukaryotes-translocates tRNA and mRNA through the ribosome. EF-G has been proposed to act as a flexible motor that propels tRNA and mRNA movement, as a rigid pawl that biases unidirectional translocation resulting from ribosome rearrangements, or by various combinations of motor- and pawl-like mechanisms. Using time-resolved cryo-EM, we visualized GTP-catalyzed translocation without inhibitors, capturing elusive structures of ribosome•EF-G intermediates at near-atomic resolution. Prior to translocation, EF-G binds near peptidyl-tRNA, while the rotated 30S subunit stabilizes the EF-G GTPase center. Reverse 30S rotation releases Pi and translocates peptidyl-tRNA and …

Targeting Oncogenic Gαq/11 In Uveal Melanoma, Dominic Lapadula, Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Uveal melanoma is the most common intraocular cancer in adults and arises from the transformation of melanocytes in the uveal tract. While treatment of the primary tumor is often effective, 36–50% of patients develop metastatic disease primarily to the liver. While various strategies have been used to treat the metastatic disease, there remain no effective treatments that improve survival. Significant insight has been gained into the pathways that are altered in uveal melanoma, with mutually exclusive activating mutations in the GNAQ and GNA11 genes being found in over 90% of patients. These genes encode the alpha subunits of the hetetrotrimeric …

The Physiological Benefits Of A Plant-Based Diet On Cardiovascular Health, Jenevieve Petray

Nursing | Senior Theses

Cardiovascular disease (CVD) is increasingly more prevalent in today’s society and is attributed to an alarming percentage of American hospitalizations and deaths. Americans are unhealthier than ever before, and the main contributor is the Western diet. Diet is a double-edged sword that can offer benefits or detriments to one’s health. CVD encompasses numerous diagnoses originating from various underlying physiological alterations. These alterations are downstream effects of increased body weight and BMI, increased cholesterol levels, decreased insulin sensitivity and increased arterial plaque buildup. Research shows that a plant-based diet has the potential to manage and reverse all fundamental physiological alterations that …

Association Of Serum Magnesium With Blood Pressure In Patients With Hypertensive Crises: A Retrospective Cross-Sectional Study, Ifeanyichukwu O. Onor, Lashira M. Hill, Modupe M. Famodimu, Mallory R. Coleman, Carolkim H. Huynh, Robbie A. Beyl, Casey J. Payne, Emily K. Johnston, John I. Okogbaa, Christopher J. Gillard, Daniel F. Sarpong, Amne Borghol, Samuel C. Okpechi, Ifeyinwa Norbert, Shane E. Sanne, Shane G. Guillory

School of Graduate Studies Faculty Publications

The role of magnesium in blood pressure has been studied among hypertensive patients; however, there is a dearth of studies exploring the role of magnesium in hypertensive crises. The primary objective of this study was to evaluate the relationship between serum magnesium and blood pressure in patients with hypertensive crises. This was a singlecenter, retrospective, chart review, cross-sectional study of patients with hypertensive crises. Patients were included if they were eighteen years of age or older, with an international classification disease ninth revision (ICD-9) code of 401.9 (hypertensive crises: emergency or urgency) and a documented magnesium level on their electronic …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

Characterizing And Overcoming Resistance To Aminomethylspectinomycins In Gram-Negative Bacteria, Nisha Das

Theses and Dissertations (ETD)

Spectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3")(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to …

Understanding Blue Light Retinal Damages And The Methods Of Prevention, Amelia Lee

Senior Honors Theses

Light emitting diode (LED) lights that comprise television screens, phone displays, laptops, and tablets have been studied by scientists in order to understand the implications of blue light radiation and the effects that it has on the human body—especially the retina of the eye. The retina is comprised of highly metabolic cells, and when those cells are placed under oxidative stress, death occurs causing ocular disease. Additionally, excess blue light exposure causes shifts in biological rhythms that govern patterns of alertness and sleep. Recently scientists began studying the methods of blue light prevention. Some studies show that blue light radiation …

A Characterization Of Rgnef Biophysical Properties And Interactome, Brooke E. Wile

Electronic Thesis and Dissertation Repository

ALS is a progressive and fatal neurodegenerative disorder whose pathologic hallmark is the presence of neuronal cytoplasmic inclusions (NCIs). In approximately 97% of ALS cases, NCIs are found to be TDP-43+. Rho-guanine nucleotide exchange factor (RGNEF) has recently been implicated in ALS pathophysiology through its co-localization and coimmunoprecipitation with TDP-43+. RGNEF has also been shown to harbour cytoprotective effects in the N-terminal region and is responsible for the regulation of low molecular weight-neurofilament (NFL), intimately involved neural structure, through its predicted RNA-binding domain (RBD). This study looked to purify constructs of RGNEF through nickel immobilized metal affinity chromatography (Ni-IMAC) and …

Tera-Seq: True End-To-End Sequencing Of Native Rna Molecules For Transcriptome Characterization, Fadia Ibrahim, Jan Oppelt, Manolis Maragkakis, Zissimos Mourelatos

Department of Biochemistry and Molecular Biology Faculty Papers

Direct sequencing of single, native RNA molecules through nanopores has a strong potential to transform research in all aspects of RNA biology and clinical diagnostics. The existing platform from Oxford Nanopore Technologies is unable to sequence the very 5′ ends of RNAs and is limited to polyadenylated molecules. Here, we develop True End-to-end RNA Sequencing (TERA-Seq), a platform that addresses these limitations, permitting more thorough transcriptome characterization. TERA-Seq describes both poly-and non-polyadenylated RNA molecules and accurately identifies their native 5′ and 3′ ends by ligating uniquely designed adapters that are sequenced along with the transcript. We find that capped, full-length …

Expression And Purification Of Phage T7 Ejection Proteins For Cryo-Em Analysis, Nicholas A. Swanson, Ravi K Lokareddy, Fenglin Li, Chun-Feng Hou, Mikhail Pavlenok, Michael Niederweis, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Bacteriophages of the Podoviridae family densely package their genomes into precursor capsids alongside internal virion proteins called ejection proteins. In phage T7 these proteins (gp14, gp15, and gp16) are ejected into the host envelope forming a DNA-ejectosome for genome delivery. Here, we describe the purification and characterization of recombinant gp14, gp15, and gp16. This protocol was used for high-resolution cryo-EM structure analysis of the T7 periplasmic tunnel and can be adapted to study ejection proteins from other phages. For complete details on the use and execution of this protocol, please refer to Swanson et al.

Inability To Switch From Arid1a-Baf To Arid1b-Baf Impairs Exit From Pluripotency And Commitment Towards Neural Crest Formation In Arid1b-Related Neurodevelopmental Disorders, Luca Pagliaroli, Patrizia Porazzi, Alyxandra T Curtis, Chiara Scopa, Harald M M Mikkers, Christian Freund, Lucia Daxinger, Sandra Deliard, Sarah A Welsh, Sarah Offley, Connor A Ott, Bruno Calabretta, Samantha A Brugmann, Gijs W E Santen, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Subunit switches in the BAF chromatin remodeler are essential during development. ARID1B and its paralog ARID1A encode for mutually exclusive BAF subunits. De novo ARID1B haploinsufficient mutations cause neurodevelopmental disorders, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we leveraged ARID1B+/- Coffin-Siris patient-derived iPSCs and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF). ARID1B-BAF regulates exit from pluripotency and lineage commitment by attenuating thousands of enhancers and genes of …

Creating Tools To Study The Signaling And Function Of The Adhesion Family Of Gpcrs, Victor M. Mirka

Electronic Thesis and Dissertation Repository

Adhesion GPCRs (aGPCRs) are difficult to study because they are activated by mechanical force. aGPCRs are autoproteolytically cleaved into N-terminal and C-terminal fragments. Mechanical force removes the N-terminal fragment revealing a tethered ligand activating the receptor. Proteinase Activated Receptors (PARs) are N-terminally cleaved by proteinases revealing a tethered ligand activating the receptor. We hypothesized the tethered ligand of aGPCRs could be revealed by replacing the N-terminal fragment with a PAR N-terminus. We fused the PAR2 N-terminus to the C-terminal fragments of four aGPCRs: CD97, EMR2, GPR56, and BAI1. PAR2-aGPCR chimeric receptors dose dependently recruited G-proteins and β-arrestins, supporting our hypothesis. …

Multifunctionality Of Prostatic Acid Phosphatase In Prostate Cancer Pathogenesis, Evgenia Alpert, Armin Akhavan, Arie Gruzman, William J. Hansen, Joshua Lehrer-Graiwer, Steven C. Hall, Eric Johansen, Sean Mcallister, Mittul Gulati, Ming-Fong Lin, Vishwanath R Lingappa

Journal Articles: Biochemistry & Molecular Biology

The role of human prostatic acid phosphatase (PAcP, P15309|PPAP_HUMAN) in prostate cancer was investigated using a new proteomics tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum (ER), magnifying normally difficult to detect subsets of the protein of interest. For PAcP, this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP …

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα_s so it was long assumed that all ACs are activated by Gα_s-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …

Regulatory Function Of The Anticoagulant Protein S In Patients With Chuvashpolycythemia, Devin M. Melancon, Verima Pereira, Rinku Majumder

Medical Student Research Poster Symposium

Background: Chuvash polycythemia is a hematological disorder that is present worldwide but endemic to the Chuvash population, a Turkish ethnic group, in Russia. The disorder is caused by a homozygous germline mutation (R200W) in the von Hippel Lindau gene. This mutation impairs binding of pVHL to hypoxia-inducible factor 1-alpha (HIF-1α); lack of this interaction prevents degradation of HIF-1α. The resultant upregulation of HIF-1α, even in a normal oxygen state, increases the activity of erythropoietin, thereby causing polycythemia. Affected individuals experience increased rates of arterial and venous thrombosis unrelated to the increased concentration of hemoglobin. Aims: To determine whether upregulation of …

Novel Biomarkers For Early And Accurate Detection Of A Fatal Gut Inflammatory Diseasein Preemie Babies, Lana Thaljeh, Rebecca Buckley, Anne Tufton, Maya Heath, Brian Barkemeyer, Zhide Fang, Lee Mcdaniel, Andrew Chapple, Kelly Laborde, Beverly Ogden, Misty Good, Duna Penn, Steven Spedale, Sunyoung Kim

Medical Student Research Poster Symposium

Necrotizing enterocolitis (NEC) is an inflammatory disease that primarily affects the intestinal tract of premature and low birthweight infants. It is one of the most common complications that occur with prematurity, which also results in high morbidity and mortality due to unchecked pathogenic bacterial growth. The median time between death and x-ray diagnosis is 1 day and, currently, there are no reliable molecular methods to predict the onset of NEC in infants. Association of intestinal alkaline phosphatase (iAP) with moderate and severe forms of the disease suggested that iAP can be a diagnostic tool that is accurate and specific for …

Cellular Origins Of Egfr-Driven Lung Cancer Cells Determine Sensitivity To Therapy, Fan Chen, Jinpeng Liu, Robert M. Flight, Kassandra J. Naughton, Alexsandr Lukyanchuk, Abigail R Edgin, Xiulong Song, Haikuo Zhang, Kwok-Kin Wong, Hunter N. B. Moseley, Chi Wang, Christine F. Brainson

Toxicology and Cancer Biology Faculty Publications

Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first- and second-generation TKIs, third-generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR-driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells …

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

The Effects Of Estrogen In The Glucoregulatory Response To Exercise In Type 1 Diabetes, Mitchell James Sammut

Undergraduate Student Research Internships Conference

Regular exercise has shown to benefit the health of individuals with type 1 diabetes mellitus (T1DM). However, a barrier to regular exercise for this population is the fear of low blood glucose (BG) levels, also known as hypoglycemia. Hypoglycemia can result in short and long-term side-effects, such as recurring loss of consciousness or in severe cases death.

In non-diabetics, sex-related differences in fuel selection during exercise are well established. Women shift towards using fats as fuel whereas men rely mostly on sugars (i.e., carbohydrates) for energy production. Exercise during the luteal phase of the female menstrual cycle, where estrogen levels …

The Penn State Protein Ladder System For Inexpensive Protein Molecular Weight Markers, Ryan T Santilli, John E Williamson, Yoshitaka Shibata, Rosalie P Sowers, Andrew N. Fleischman, Song Tan

Department of Anesthesiology Faculty Papers

We have created the Penn State Protein Ladder system to produce protein molecular weight markers easily and inexpensively (less than a penny a lane). The system includes plasmids which express 10, 15, 20, 30, 40, 50, 60, 80 and 100 kD proteins in E. coli. Each protein migrates appropriately on SDS-PAGE gels, is expressed at very high levels (10–50 mg per liter of culture), is easy to purify via histidine tags and can be detected directly on Western blots via engineered immunoglobulin binding domains. We have also constructed plasmids to express 150 and 250 kD proteins. For more efficient production, …

Thermal Properties Of 18f-Fdg Uptake And Imaging In Positron Emission Tomography Scans Of Cancerous Cells, Carleigh R. Eagle

PANDION: The Osprey Journal of Research and Ideas

Positron Emission Tomography (PET) scans can utilize a radioactive tracer, in this case 2-deoxy2-[fluorine-18] fluoro-D-glucose (¹⁸F-FDG), to visualize malignant tumors in cancer patients. The uptake was compared to glucose to understand the difference in thermal properties, which contribute to the ability to image the cancerous cells. The uptake of ¹⁸F-FDG by cancer cells and the imaging process of positron emission tomography were reviewed from a thermodynamic perspective. Gastrointestinal and neurological imaging techniques were reviewed to understand the role of PET imaging in different areas of the human body.

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

MSU Graduate Theses

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …