Digital Commons Network^™

Isolation Of Marker Compounds From Copaiba Essential Oil And Mimosa Pigra For Quality Evaluation Of Dietary Supplements, Mohammed Hawwal

Electronic Theses and Dissertations

Natural products have been used as a primary means of treating illness since ancient times, and they remain an important pool of U.S. FDA approved drugs. Approximately 33% of all current pharmaceutical medications discovered between 1981 and 2014 are either natural products or derived from natural products (Newman and Cragg 2016). The process of isolating specialized metabolites from medicinal plants has led to the development of particularly important medicines worldwide (Rakotomalala, Agard et al. 2013) such as Taxol® from Taxus brevifolia Nutt. (Taxaceae) and salicylic acid from the bark of Salix spp. This research is composed of five chapters; the …

Crispr Systems For Covid-19 Diagnosis, Hossein Rahimi, Marziyeh Salehiabar, Murat Barsbay, Mohammadreza Ghaffarlou, Taras Kavetskyy, Ali Sharafi, Soodabeh Davaran, Subhash C. Chauhan, Hossein Danafar, Murali M. Yallapu

School of Medicine Publications

The emergence of the new coronavirus 2019 (COVID-19) was first seen in December 2019, which has spread rapidly and become a global pandemic. The number of cases of COVID-19 and its associated mortality have raised serious concerns worldwide. Early diagnosis of viral infection undoubtedly allows rapid intervention, disease management, and substantial control of the rapid spread of the disease. Currently, the standard approach for COVID-19 diagnosis globally is the RTqPCR test; however, the limited access to kits and associated reagents, the need for specialized lab equipment, and the need for highly skilled personnel has led to a detection slowdown. Recently, …

Biocompatible And Multifunctional Trityl Spin Probes For Electron Paramagnetic Resonance Spectroscopy, Teresa D. Gluth

Graduate Theses, Dissertations, and Problem Reports (ETD)

The primary objective of my thesis was to develop and utilize a biocompatible multifunctional trityl spin probe for concurrent measurement of pO₂, pH_e, and [P_i] in vivo by electron paramagnetic resonance (EPR) spectroscopy (Chapter 2). My first goal was to synthesize the proposed probe we are terming HOPE71. Secondly, HOPE71 was characterized by X-band and L-band EPR spectroscopy. Next, the biocompatibility of HOPE71 was assessed through an albumin binding test, cytotoxicity assays, and in vivo intravenous tolerance. Then, the use of HOPE71 to measure the target parameters was demonstrated in a breast cancer …

Evaluation Of Somatic Mutations In Solid Metastatic Pan-Cancer Patients, Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Joseph Chao, Chen Chen, Mohd W. Nasser, Ramakanth C. Venkata, Maneesh Jain, Lynette M. Smith, Susan E. Yost, Karen L. Reckamp, Raju Pillai, Leonidas Arvanitis, Michelle Afkhami, Edward W. Wang, Vincent Chung, Mihaela Cristea, Marwan Fakih, Marianna Koczywas, Erminia Massarelli, Joanne Mortimer, Yuan Yuan, Surinder K. Batra, Sumanta Pal, Ravi Salgia

Journal Articles: Biochemistry & Molecular Biology

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations …

Harnessing Acoustic Streaming For Bioanalysis In Microfluidics, Xiaojun Li

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the past few decades, microfluidic technology has been developed rapidly in both fabrication methods and multifunctionality integrations, making it a powerful tool for a wider variety of biological applications. The device fabrication method has expanded from conventional polymer-based micro devices to 3D-printed micro devices, and allows multiple functions such as electric, optic, magnetic and acoustic to be integrated on a single platform. This dissertation focuses on method development of acoustic streaming-based microfluidics in bioanalysis such as immunoassay, enzyme kinetics and DNA fragmentation analysis. In this dissertation, a micromixer was developed based on acoustic streaming generated from sharp-edge structure vibration …

Co-Distribution Of Ambient Light At Night And Incidence Of Human Cancers And Covid-19, Yidan Meng

Public Health Theses

Introduction and BackgroundThere are increasing concerns about the effects of artificial lights on human health, including hormone-related disease and immune functions. In January 2020, the outbreak of COVID-19 disrupted everyone’s life, and people who infected have various severity. Thus, we want to analyze whether people exposed to different ambient light at night (LAN) levels make them more susceptible to COVID-19 for our summer research. Besides the effects of LAN on immune functions, we also discussed the association of LAN and multiple cancers in seven states of Northeastern U.S. We used similar statistical and geographic analysis methods and separate them into …

Antioxidant Activity Of Thunbergia Laurifolia Lindl. Ethanolic Extract In Keratinocytes, Buakotchaphan Jirabanjerdsiri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Fine particulate matter (PM2.5) can cause skin damage through the induction of oxidative stress in epidermis. Antioxidants help counteract with cellular oxidant species and maintain cell homeostasis. This study aims to examine the protective effect of Thunbergia laurifolia lindl. ethanolic extract on PM2.5-mediated oxidative stress in epidermal keratinocytes. High-performance liquid chromatography with diode array detection was conducted for quantitative analysis of rosmarinic acid content in the extract. Cell viability was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay. Intracellular ROS was monitored using 2’,7’-Dichlorodihydrofluorescein diacetate. Proteins related to p62-Keap1-Nrf2 signaling pathway were examined by western blot analysis. Expressions of Nrf2 and p62 …

Α-Glucosidase Inhibitors From Dendrobium Delacourii, Dendrobium Gibsonii And Aerides Multiflora, May Thazin Thant

Chulalongkorn University Theses and Dissertations (Chula ETD)

In this study, three plants from the Orchidaceae family, i.e., Dendrobium delacourii, Dendrobium gibsonii, and Aerides multiflora, were investigated for their chemical constituents and α-glucosidase inhibitory activities. A total of thirty compounds were isolated and structurally characterized. Eleven known compounds were identified from Dendrobium delacourii, including hircinol, ephemeranthoquinone, densiflorol B, moscatin, 4,9-dimethoxy-2,5-phenanthrenediol, gigantol, batatasin III, lusianthridin, 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene, phoyunnanin E, and phoyunnanin C. Two new compounds, i.e., dihydrodengibsinin and dendrogibsol, were isolated from Dendrobium gibsonii, along with seven known compounds including ephemeranthol A, dengibsinin, nobilone, aloifol I, lusianthridin, denchrysan A, and 4-methoxy-9H-fluorene-2,5,9-triol. Four new compounds, i.e., aerimultins A-C and dihydrosinapyl dihydroferulate, …

Lipase Inhibitors From Dendrobium Senile, Myat Pann Phyu

Chulalongkorn University Theses and Dissertations (Chula ETD)

Obesity is characterized as an abnormal lipid metabolism due the imbalance between the energy intake and output. Pancreatic lipase is secreted by the pancreas and plays an important role in the digestion and absorption of lipids in the small intestine. Inhibition of pancreatic lipase enzyme can reduce dietary fat absorption which will lead to loss of weight and finally result in hypocholesterolemia and hypoglycemia. From the whole plant of Dendrobium senile, a new phenanthrene derivative was isolated, together with seven known compounds, including 2,5,7-trihydroxy-4-methoxyphenanthrene (1), moscatin (2), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3), moscatilin (4), aloifol I (5), 4,4ʹ,8,8ʹ-tetramethoxy[1,1ʹ-biphenanthrene]-2,2ʹ,7,7ʹ-tetrol (6), 2,2ʹ,7,7ʹ-tetrahydroxy-4,4ʹ-dimethoxy-1,1ʹ-biphenanthrene (7) and bleformin …

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

Investigation Into The Structure And Function Of Streptococcal Antigen I/Ii Family Of Proteins, Joshua L. Mieher

All ETDs from UAB

Streptococci are involved in the infections of the oral cavity as well as at various sites throughout the body. Their initial contact with tissues/surfaces is enabled by adhesins present on the microbial surface. Among these the Antigen I/II- family (AgI/II) of adhesins are known be important factors in these infections as they enable adherence to multiple host proteins thus allowing the bacteria to gain a foot hold. In this thesis, we have structurally and functionally characterized yet another adhesin on S. mutans, the glucan binding protein C, which resembles the V-region of AgI/II. In addition, we have also resolved the …

Rapid Induction Of The Unfolded Protein Response And Apoptosis By Estrogen Mimic Ttc-352 For The Treatment Of Endocrine-Resistant Breast Cancer, Balkees Abderrahman, Philipp Y Maximov, Ramona F Curpan, Sean W Fanning, Jay S Hanspal, Ping Fan, Charles E Foulds, Yue Chen, Anna Malovannaya, Antrix Jain, Rui Xiong, Geoffrey L Greene, Debra A Tonetti, Gregory R J Thatcher, V Craig Jordan

Faculty, Staff and Students Publications

Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen’s anti-tumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecological and non-gynecological adverse events thus the development of safer estrogenic agents remains a clinical priority. Here, we study synthetic selective estrogen mimics (SEMs) BMI-135 and TTC-352, and the naturally-occurring estrogen estetrol (E4), which are proposed as safer estrogenic agents compared to 17β-estradiol (E2), for the treatment of endocrine-resistant BC. TTC-352 and E4 are being evaluated in BC clinical trials. …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Sansevieria: An Evaluation Of Potential Cytotoxic Activity In Reference To Metabolomic And Molecular Docking Studies, Amgad Albohy

Pharmacy

Sansevieria trifasciata Prain. and Sansevieria suffruticosa N.E.Br. were selected to evaluate their cytotoxic activity against colon (CACO2), lung (A-549) and liver (HepG-2) carcinoma cell lines. Results indicated that S. suffruticosa N.E.Br. showed a significant cytotoxic effect on CACO2 with IC50= 30.9 ± 0.72 μg/ml. Evaluating the phenolic and flavonoid contents, S. suffruticosa N.E.Br. has higher total phenolic and flavonoid contents than S. trifasciata Prain. The phenolic content was estimated using HPLC detecting the presence of apigenin-7-glucoside and cinnamic acid only in S. suffruticosa N.E.Br. with p-hydroxybenzoic acid and p-coumaric acid being the major compounds. While, catechin and kaempferol are the …

Assessing The Comfort Level Of Speech-Language Pathologists In Assessing And Treating Deaf And Hard Of Hearing Children, Kaitlyn Burkamper

Honors Program Theses

When a child is diagnosed with a hearing loss, there are many different facets of their diagnosis to consider, and all of these facets are affected by the configuration, type, and severity of the hearing loss. Because of the patient's age, all decisions are at least impacted, if not made, by their parents or guardians. Depending on these factors, there are options for assistive devices, such as hearing aids, and one of the main concerns is access to language. While signed language is a completely valid path for a child with hearing loss, some parents make the decision that their …

Searching For A Technology-Driven Acute Rheumatic Fever Test: The Start Study Protocol, Anna P. Ralph, Rachel Webb, Nicole J. Moreland, Reuben Mcgregor, Anthony Bosco, David Broadhurst, Timo Lassmann, Timothy C. Barnett, Rym Benothman, Jennifer Yan, Bo Remenyi, Julie Bennett, Nigel Wilson, Mark Mayo, Glenn Pearson, Tobias Kollmann, Jonathan R. Carapetis

Research outputs 2014 to 2021

Introduction:

The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus. It is the precursor to rheumatic heart disease (RHD), a leading cause of health inequity and premature mortality for Indigenous peoples of Australia, New Zealand and internationally.

Methods and analysis:

Searching for a Technology-Driven Acute Rheumatic Fever Test' (START) is a biomarker discovery study that aims to detect and test a biomarker signature that distinguishes ARF cases from non-ARF, and use systems biology and serology to …

Small-Molecule Inhibitor Of Af9/Enl-Dot1l/Af4/Aff4 Interactions Suppresses Malignant Gene Expression And Tumor Grow, Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song

Faculty, Staff and Students Publications

Chromosome translocations involving mixed lineage leukemia (MLL) gene cause acute leukemia with a poor prognosis. MLL is frequently fused with transcription cofactors AF4 (~35%), AF9 (25%) or its paralog ENL (10%). The AHD domain of AF9/ENL binds to AF4, its paralog AFF4, or histone-H3 lysine-79 (H3K79) methyltransferase DOT1L. Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and the catalytic activity of DOT1L are essential for MLL-rearranged leukemia. Protein-protein interactions (PPI) between AF9/ENL and DOT1L/AF4/AFF4 are therefore a potential drug target.

Methods: Compound screening followed by medicinal chemistry was used to find inhibitors of such PPIs, which were examined for their biological …

Novel Heat Index Models For Subtropical Region Based On Daily Milk Production Incrossbred Holstein Cows, Neeraj Kashyap, Atish Kumar Chakravarty, Bharti Deshmukh

Turkish Journal of Veterinary & Animal Sciences

The quantification of the effect of heat stress imposed due to higher rate of heat gain on animal production is a prerequisite while estimating effects of heat stress. Temperature humidity index (THI) models developed empirically using meteorological parameters have been utilized as an indicator of heat stress. This study attempted to develop a heat index model with respect to productivity of the crossbred Holstein cows. More than 1.23 million daily milk yield records of 1860 crossbred cattle spread over a duration of 30 years were utilized. Statistically significant (p < 0.0001) partial regression coefficients were estimated as 0.0748 ± 0.0009 for dry bulb temperature (T$_{db}$) and -0.2228 ± 0.0011 for wet bulb temperature in model 1, -0.0182 ± 0.0005 T$_{db}$ and -0.1205 ± 0.0006 for vapour pressure in model 2, -0.0150 ± 0.0006 for Tdb and -0.1151 ± 0.0006 for dew point temperature in model 3 while as -0.1283 ± 0.0004 for T$_{db}$ and -0.0394 ± 0.0002 for relative humidity in model 4. The ratio of the partial regression coefficients of meteorological parameters (ß2/ß1) was -2.9791 in model 1, 6.8739 in model 2, 7.6731 in model 3 and 0.3073 in model 4. The developed THI models are based on the effect of meteorological parameters on daily productivity of the dairy animals, so the weightages to meteorological parameters were contrastingly different than the reported THI models. These models may successfully be used to evaluate the impact of heat stress on crossbred Holstein cows with respect to milk productivity and many other traits.

Some Histological Reveals On Reproduction Of One Of The Lessepsian Species, Nemipterus Randalli In Antalya (Turkey), Mehmet Rüştü Özen

Turkish Journal of Veterinary & Animal Sciences

In this study, the reproduction of Nemipterus randalli, one of the lessepsian fish catch from the Gulf of Antalya, Turkey was interpreted histologically. Regarding the fish used in this study (N = 1715), it is noteworthy to mention that male individuals are larger than females. The first sexual maturity in males was determined 17 cm TL and 60 g in BW, whereas 13 cm TL and 25 g BW in females. Females reached sexual maturity at age I+ and males at the age of II+. Seven different stages (O1-O7) were identified in oocyte maturation in the ovaries. The spawning time …

Mouse Mutant Phenotyping At Scale Reveals Novel Genes Controlling Bone Mineral Density., Anna L Swan, Christine Schütt, Jan Rozman, Maria Del Mar Muñiz Moreno, Stefan Brandmaier, Michelle Simon, Stefanie Leuchtenberger, Mark Griffiths, Robert Brommage, Piia Keskivali-Bond, Harald Grallert, Thomas Werner, Raffaele Teperino, Lore Becker, Gregor Miller, Ala Moshiri, John R Seavitt, Derek D Cissell, Terrence F Meehan, Elif F Acar, Christopher J Lelliott, Ann M Flenniken, Marie-France Champy, Tania Sorg, Abdel Ayadi, Robert E Braun, Heather Cater, Mary E Dickinson, Paul Flicek, Juan Gallegos, Elena J Ghirardello, Jason D Heaney, Sylvie Jacquot, Connor Lally, John G Logan, Lydia Teboul, Jeremy Mason, Nadine Spielmann, Colin Mckerlie, Stephen A Murray, Lauryl M J Nutter, Kristian F Odfalk, Helen Parkinson, Jan Prochazka, Corey L Reynolds, Mohammed Selloum, Frantisek Spoutil, Karen L. Svenson, Taylor S Vales, Sara E Wells, Jacqueline K White, Radislav Sedlacek, Wolfgang Wurst, Kent K C Lloyd, Peter I Croucher, Helmut Fuchs, Graham R Williams, Duncan Bassett, Valerie Gailus-Durner, Yann Herault, Ann-Marie Mallon, Steve D M Brown, Philipp Mayer-Kuckuk, Martin Hrabe De Angelis, Impc Consortium

Faculty Research 2020

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored …

Imaging The Tumor Microenvironment Using 1,2-Dioxetane Chemiluminescence Agents, Lucas Ryan

Chemistry Theses and Dissertations

As complex organisms, animals and humans rely on a delicate interplay between many connected systems to maintain proper cellular and whole-body function. Oxygen regulation and homeostasis are vital for proper function in healthy cells, as are core components of aerobic metabolism and efficient ATP generation to supply our energy needs. Maintaining pH homeostasis is also of primary importance; cells maintain pH homeostasis through a host of active and passive transporters to maintain pH balance both inside and outside of the cell.

Events of uncontrolled cellular proliferation, also known as cancer, survive and thrive under conditions that perturb the delicate balance …

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff

DNP Qualifying Manuscripts

Background: According to the National Institute for Occupational Safety and Health (2016), oral anticancer agents (OAC) are hazardous drugs (HD) and require the same safe handling interventions in the home setting as in controlled health care environments. The use of a safe handling checklist for OAC administration is a way nurses can provide safe handling education to patients and caregivers and assess for understanding and competency for critical tasks. Effective home management strategies outlining caregiver protections, proper storage, administration of OACs, spill clean-up, and waste disposal could reduce exposure risks to toxic agents.

Objective: To present a safe-handling checklist …

Usp <800> Compliance: A Hazardous Drug Safe Handling Ppe Toolkit For Infusion Nurses, Cynthia Huff

Doctor of Nursing Practice (DNP) Projects

Problem: Safety concerns have existed for more than 40 years about how hazardous drug (HD) exposure contributes to long- and short-term adverse health outcomes for healthcare workers (HCWs). Careless handling may cause toxic residues to infiltrate hospital environments and patient care areas, and can even be traced to patients’ homes. New government regulations will require healthcare organizations to minimize exposure risks to HCWs by fully implementing the U.S. Pharmacopeia (USP) Convention Chapter 800: Hazardous Drugs: Handling in Healthcare Settings (USP, 2016) on December 1, 2019. According to Polovich and Olsen (2017), “The implementation of the USP <800> Standards will represent …

Usp<800> Compliance: A Hazardous Drug Safe-Handling Quality Improvement Project For Ambulatory Care Infusion Nurses, Cynthia Huff

Doctor of Nursing Practice (DNP) Projects

Problem: The U.S. Pharmacopeia (USP, 2016) Convention Chapter 800: Hazardous Drugs: Handling in Healthcare Settings took effect on December 1, 2019. According to Polovich and Olsen (2017), " The implementation of the USP <800> Standards. will represent an important step forward to protect nurses and other potentially exposed healthcare workers (HCWs): (p.1).

Context: The Doctor of Nursing Practice (DNP) project implemented a hazardous drug (HD) safe-handling personal protective equipment (PPE) toolkit in accordance to USP <800>standards and hospital policies at an ambulatory cancer infusion center to improve nurses' adherence with PPE use.

Interventions: The project consisted of (a) a safe-handling PPE …

What Is The Efficacy Of Biologics For Chronic Plaque-Type Psoriasis Among Pediatric Patients?, Uduakobong Akpainyang

Health Informatics Student Papers and Projects

Chronic plaque psoriasis is an inflammatory skin disease characterized by red thick, raised, silvery scaly patches. It is the most common type of psoriasis, often appearing on the knees, postauricular area, elbows, scalp, and lower back. Chronic plaque psoriasis was the most prevalent (73.7%) among children with psoriasis and was found to increase with age in a study at Olmsted County, Minnesota (Tollefson et al., 2010). Chronic plaque psoriasis is a life-changing condition that significantly impacts the overall health and well-being (emotional, physical, social, and psychological) as well as quality of life in pediatric patients. As a result of data …

Development Of Computational To Ols To Target Microrna, Luo Song

Dissertations and Theses (Open Access)

MicroRNAs (a.k.a, miRNAs) play an important role in disease development. However, few of their structures have been determined and structure-based computational methods remain challenging in accurately predicting their interactions with small molecules. To address this issue, my thesis is to develop integrated approaches to screening for novel inhibitors by targeting specific structure motifs in miRNAs. The project starts with implementing a tool to find potential miRNA targets with desired motifs. I combined both sequence information of miRNAs and known RNA structure data from Protein Data Bank (PDB) to predict the miRNA structure and identify the motif to target, then I …

Morphologic Remission Status Is Limited Compared To Δn Flow Cytometry: A Children's Oncology Group Aaml0531 Report., Lisa Eidenschink Brodersen, Robert B. Gerbing, M Laura Pardo, Todd A. Alonzo, Dana Paine, Wayne Fritschle, Fan-Chi Hsu, Jessica A. Pollard, Richard Aplenc, Samir B. Kahwash, Betsy Hirsch, Susana Ramondi, Denise Wells, E Anders Kolb, Alan S. Gamis, Soheil Meshinchi, Michael R. Loken

Manuscripts, Articles, Book Chapters and Other Papers

Risk stratification for acute myeloid leukemia (AML) uses molecular and cytogenetic abnormalities identified at diagnosis. Response to therapy informs risk, and morphology continues to be used more frequently than flow cytometry. Herein, the largest cohort of pediatric patients prospectively assessed for measurable residual disease (MRD) by flow cytometry (N = 784) is reported. The "difference from normal" (ΔN) technique was applied: 31% of all patients tested positive (AML range, 0.02% to 91%) after the first course of treatment on Children's Oncology Group study AAML0531. Detection of MRD following initial chemotherapy proved the strongest predicator of overall survival (OS) in univariable …

Ampk Regulation Of Raptor And Tsc2 Mediate Metformin Effects On Transcriptional Control Of Anabolism And Inflammation, Jeanine L Van Nostrand, Kristina Hellberg, En-Ching Luo, Eric L Van Nostrand, Alina Dayn, Jingting Yu, Maxim N Shokhirev, Yelena Dayn, Gene W Yeo, Reuben J Shaw

Faculty, Staff and Students Publications

Despite being the frontline therapy for type 2 diabetes, the mechanisms of action of the biguanide drug metformin are still being discovered. In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of metformin are still ill defined. Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1. Here we investigated the role of direct AMPK-mediated serine phosphorylation of RAPTOR in a new

Age And Apoe Genotype Affect The Relationship Between Objectively Measured Physical Activity And Power In The Alpha Band, A Marker Of Brain Disease, Jaisalmer De Frutos-Lucas, Pablo Cuesta, Federico Ramírez-Toraño, Alberto Nebreda, Esther Cuadrado-Soto, África Peral-Suárez, David Lopez-Sanz, Ricardo Bruña, Silvia Marcos-De Pedro, María Luisa Delgado-Losada, Ana María López-Sobaler, Inmaculada Concepción Rodríguez-Rojo, Ana Barabash, Juan Manuel Serrano Rodriguez, Simon M. Laws, Alberto Marcos Dolado, Ramón López-Higes, Belinda M. Brown, Fernando Maestú

Research outputs 2014 to 2021

BACKGROUND: Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer's disease (AD) continuum. Physical activity (PA) is a protective factor that has proved to reduce AD risk and pathological brain burden. Previous research has confirmed that exercise increases power in the alpha range. However, little is known regarding whether other non-modifiable risk factors for AD, such as increased age or APOE ε4 carriage, alter the association between PA and power in the alpha band. METHODS: The relationship between PA and alpha band power was examined in a sample of 113 healthy adults using …