Digital Commons Network^™

Tractors On The Mall: Unraveling The New Deal, Political Shifts, And The 1980s Farm Crisis, Tracy M. Neblina

UNLV Theses, Dissertations, Professional Papers, and Capstones

In the 1980s, Midwestern farmers faced an economic crisis that rivaled the Great Depression. Agricultural policy in the 1970s and 1980s led to a boom and bust for many of the nation’s farmers, causing the decline in rural communities in the middle of the country. During this period, more efficient agricultural production, shifting federal policy, high inflation, and devalued farmland led farmers in the Midwest to face incredible economic hardships, loss of land, changes in their communities, and challenges to their sense of purpose and identity. The Farm Crisis of the 1980s furnishes an extraordinary opportunity to investigate a confluence …

An Analysis Of The Influence Of Human Disease Pathogens On Core Behaviors Of The Black-Legged Tick, Emily F. Marinko

UNLV Theses, Dissertations, Professional Papers, and Capstones

Ixodes scapularis, the black-legged or deer tick, is a vector for several different disease-causing microbes, including the causative agent of Lyme disease. As such, it is a major health concern for people living within its range in the eastern half of the United States, a habitation area that is increasing due to climate change. Despite its medical relevance as a disease vector, there is still much to learn about the basic behavior of these arachnids in the wild. Thus, the major hypothesis of this thesis is that ticks that are infected with specific human disease-causing microbes behave differently than those …

Analyzing Food Access: An Investigation Of Food Insecurity Amongst Latinos In Rural Nebraska, Natalia Santos

Theses & Dissertations

Background: Food insecurity is a public health issue in the United States, with disproportionately higher rates among Latino/Hispanic households. Rural communities face unique geographical, socioeconomic, and systemic barriers that often exacerbate food access disparities. Despite the growing Latino population in rural areas, particularly in Midwestern states like Nebraska, there remains a critical gap in comprehensive research that integrates both objective and subjective understandings of their food environments. Understanding these multifaceted influences is crucial for developing effective, culturally sensitive interventions.

Problem Statement: This dissertation aims to answer the central question: How does food access and food insecurity manifest amongst Latinos in …

Diverse Cell Types Establish A Pathogenic Immune Environment In Peripheral Neuropathy, Julie Choi

Arts & Sciences Graduate Student Theses and Dissertations

Neuroinflammation plays a complex and context-dependent role in many neurodegenerative diseases. We identified a key pathogenic function of macrophages in a mouse model of a rare human congenital neuropathy in which SARM1, the central executioner of axon degeneration, is activated by hypomorphic mutations in the axon survival factor NMNAT2. Macrophage depletion blocked and reversed neuropathic phenotypes in this sarmopathy model, revealing SARM1-dependent neuroimmune mechanisms as key drivers of disease pathogenesis. In this study, we investigated the impact of chronic subacute SARM1 activation on the peripheral nerve milieu using single cell/nucleus RNA-sequencing (sc/snRNA-seq). Our analyses reveal an expansion of immune cells …

Scientist Perspectives: A Correlation Analysis Of Translational Science Competencies Compared With Principles Of Engagement And Knowledge Integration, Rachel Wenzl

Theses & Dissertations

The competencies identified in the development of the “Fundamental Characteristics of the Translational Scientist” may not consider and fully integrate the concepts of knowledge integration and engagement, key components of the translational science spectrum. This gap may be widening and deepening the “valley of death” and exacerbating ongoing challenges in the field of translational science. This dissertation explored the association of knowledge integration, stakeholder engagement, and community engagement principles compared with translational science competencies.

Utilizing content review and a non-experimental, correlation study design, data were collected through a quantitative survey from adult research subjects all self-identified as a research investigator …

Proteomics-Based Aging Clocks In Midlife Or Late-Life And Their Associated Risk Of Dementia, Sanaz Sedaghat, Saeun Park, Rob F Walker, Shuo Wang, Jialing Liu, Timothy M Hughes, Behnam Sabayan, Weihong Tang, Josef Coresh, James S Pankow, Keenan A Walker, Ramon Casanova, Ruth Dubin, Rajat Deo, Jerome I Rotter, Alexis C Wood, Peter Ganz, Pamela L Lutsey, Weihua Guan, Anna Prizment

Children’s Nutrition Research Center Staff Publications

Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.

Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third …

Multidimensional Analysis Of B7 Homolog 3 Rna Expression In Small Cell Lung Cancer Molecular Subtypes, Carl M Gay, Taofeek K Owonikoko, Lauren A Byers, Noura J Choudhury, Sajid Ahmed, Zachary Cain, Xiaozhong Qian, Matthew Brentnall, Simon Heeke, Ming Poi, Sharon Wu, Charles M Rudin

Faculty, Staff and Student Publications

Purpose: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters.

Experimental design: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor …

An Investigation Of The Association Of Gdf9-C.260g>A Polymorphism With Lamb Live Weight In The Akkaraman Breed, Şeyma Kökkaya, Fadi̇me Daldaban, Davut Bayram, Mehmet Ulaş Çinar, Korhan Arslan, Bi̇lal Akyüz

Turkish Journal of Veterinary & Animal Sciences

In this study, the relationship between the Growth Differentiation Factor-9 (GDF9) gene polymorphism and birth weight, as well as weights on days 30, 60, 90, was investigated in Akkaraman lambs, one of the indigenous sheep breeds of Türkiye. For this purpose, a total of 314 lambs were genotyped by PCR-RFLP method for the single nucleotide polymorphism (SNP) c.260G>A in the GDF9 gene. While GG and GA genotypes were observed in the studied breed, the AA genotype was not observed. The results showed that Akkaraman lambs were in Hardy–Weinberg (H–W) equilibrium for the GDF9-c.260G>A polymorphism (p < 0.05). In this study, a significant association was observed between GDF9-HhaI polymorphism and 30th day weight and 60th day weight in Akkaraman lambs. When the animals were analyzed according to birth type, it was observed that this factor was associated with birth weight, as well as weights on days 30, 60, and 90. It is suggested that the c.260G>A coded SNP …

Growth Curve And Serum Calcium And Magnesium Concentrations In Duck Breeders (Anas Boschas) From Hatching To The Prelaying Period Reared Under Subtropical Conditions, Vanessa Peripolli, Fabiano Dahlke, Ellen Karen Dos Santos, Maila Palmeira, Stelamaris Dezen, Robert Lenock, Elizabeth Schwegler, Juahil Martins De Oliveira Júnior, Ivan Bianchi, Paula Gabriela Da Silva Pires, Betina Raquel Cunha Dos Santos, Andressa Fernanda Campos, Fabiana Moreira

Turkish Journal of Veterinary & Animal Sciences

Optimizing duck production requires understanding growth variability and monitoring serum calcium and magnesium levelsas health indicators. This study aimed to analyze the growth curve, mortality, and serum calcium (Ca) and magnesium (Mg) levels in White Mallard ducks from hatching to the prelaying period in subtropical conditions. A total of 1100 females and 270 males were raised for 146 days. At hatch, day 6 (D6), D13, D23, D34, D50, D64, D80, D94, D111, and D146, ducks were weighed separately to assess body weight (BW). Blood samples were collected at hatch, D50, D94, and D146 to determine serum calcium and magnesium levels. …

A Morphological Study On Acanthocephalan Species From Wild Birds In Northern Türkiye, Mehmet Öztürk, Şi̇nasi̇ Umur

Turkish Journal of Veterinary & Animal Sciences

The phylum Acanthocephala contains approximately 1300 acanthocephalan species. So far, only nine acanthocephalan species of wild birds have been reported in Türkiye. To study the context of acanthocephalan diversity in wild birds in Türkiye, we examined 193 birds from 69 species belonging to 16 orders. Acanthocephalans were found in seven bird species: Centrorhynchus aluconis in Buteo buteo and Buteo rufinus, Centrorhynchus spinosus in Buteo buteo and Strix aluco, Mediorhynchus papillosus in Iduna icterina, Mediorhynchus tenuis in Luscinia svecica, Plagiorhynchus cylindraceus in Erithacus rubecula and Turdus merula, Polymorphus contortus in Anas platyrhynchos, and Sphaerirostris turdi in Turdus merula. Except for Plagiorhynchus …

The Morphologic Structure Of Some Wing Muscles In The Common Pheasant (Phasianus Colchicus), Beste Demi̇rci̇, Murat Erdem Gülti̇ken

Turkish Journal of Veterinary & Animal Sciences

Avians use significant amounts of energy during flight that is supplied by muscles. The Common Pheasant, a member of the Phasianidae family, can fly swiftly over short distances and flies to evade predators. Pheasant species are terrestrial and have a global distribution. This investigation aimed to analyze the anatomical structure of skeletal muscles in pheasants. A cohort of 20 adult pheasants consisting of an equal number of females and males (10 each) was used. Dissections were performed on 5 females and 5 male pheasants for macroscopic evaluation. The remaining samples underwent immunohistochemical staining using an antimyoglobin antibody to measure the …

Expanding Functionalities Of Immune Receptors Through Simultaneous Transfer Of Sensor And Helper Nlrs, Dongjiao Wang, Qibin Wu, Daowen Wang, Youxiong Que, Zheng Qing Fu

Faculty Publications

No abstract provided.

Implementation Of A Forensic Ancestry Inference Indel Panel, Jacqueline Molina

Student Theses

Ancestry-informative markers (AIMs) are genetic variants that exhibit significant frequency differences between populations, making them valuable tools for inferring biogeographical ancestry in forensic investigations. Insertion/deletion polymorphisms (INDELs) offer particular advantages for degraded forensic samples due to their short amplicon sizes and binary allelic nature. As forensic laboratories adopt newer instrumentation, validation of established assays becomes critical to ensure analytical continuity and reliability. This study evaluated the comparative performance of the SeqStudio™ Genetic Analyzer in detecting a 46 AIMs INDEL multiplex panel, previously established with the ABI 3130 Genetic Analyzer. Four commercial blood samples were analyzed using both platforms to assess …

Expanding Functionalities Of Immune Receptors Through Simultaneous Transfer Of Sensor And Helper Nlrs, Dongjiao Wang, Qibin Wu, Daowen Wang, Youxiong Que, Zheng Qing Fu

Faculty Publications

No abstract provided.

An Exciting Future For Microbial Molecular Biology And Physiology, Andrew A Bridges, Leah Guthrie, Mckenzie Lehman, Elizabeth H Kellogg, Samantha Wellington Miranda, Andrew Pountain, Anthony L Shiver, Andrew Varble, Molecular Biology And Physiology Community Of The Council On Microbial Sciences, Heidi B Kaplan, Elizabeth A Shank, Gisela Storz

Faculty, Staff and Student Publications

Continuous advances in technologies ranging from deep sequencing and genetic manipulation to mass spectrometry, single cell imaging, and structural biology have led to previously unimaginable advances in our understanding of microbial physiology and the molecular mechanisms underlying microbial responses in a multitude of environments. Simultaneously, these advances are revealing how much more there is to learn. At the 2024 virtual retreat of the Molecular Biology and Physiology (MBP) Community of the Council on Microbial Sciences (COMS) of the American Society for Microbiology (ASM), eight early-career investigators, along with retreat attendees, discussed some of these astounding advances, as well as the …

Csf-Exosomal Mirnas And Delayed Cerebral Ischemia: Insights Into Pathophysiology But No Definitive Biomarkers, Chathathayil M Shafeeque, Devin W Mcbride, Yuanqing Yan, Hussein A Zeineddine, John P Hagen, H Alex Choi, Jude P Savarraj, Ari Dienel, Spiros L Blackburn, Peeyush Kumar Thankamani

Faculty, Staff and Student Publications

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is notoriously known for its high mortality and morbidity. Approximately one-third of the patients who survive aneurysm rupture are reported to develop delayed cerebral ischemia (DCI), which contributes to a poor clinical outcome. Currently, there are no biomarkers for identifying which aSAH patients are at risk of developing DCI. We aimed to determine the feasibility of cerebrospinal fluid (CSF) exosomal microRNAs (miRNAs) for predicting DCI post-aSAH.

Methods: aSAH patients were prospectively enrolled, and CSF samples were collected at two time points (< 24 h and 72 h post-aSAH) from individuals undergoing external ventricular drainage. Exosomal miRNAs were isolated from the CSF for analysis. In the initial group of patients (discovery cohort), an exploratory analysis was conducted using a CSF panel containing 84 miRNAs, assessed by quantitative real-time PCR (RT-qPCR). Based on this analysis, 27 miRNAs were selected for further evaluation in a second group of patients (validation cohort). Among these, 10 miRNAs had previously been reported in SAH-related CSF studies, supporting their relevance for continued investigation.

Results: In this study, RT-qPCR analysis of 84 miRNAs in CSF samples from …

Ribosome Deficiency Induces Salmonella Filamentation Within Host Cells, Zhihui Lyu, Cierra Wilson, Kalyn Weiss, Spencer Lewis, Kurt Fredrick, William Margolin, Jiqiang Ling

Faculty, Staff and Student Publications

The ribosome is the central hub for protein synthesis and is heavily targeted by antibiotics. Ribosomal mutations, antibiotic treatment, and nutrient starvation can alter translational efficiency and lead to stressed cells. Ribosome deficiency plays a critical role in stress responses and disease progression; yet, how it affects bacteria-host interactions remains poorly understood. In this study, we show that a ribosome-deficient strain exhibits a surprising morphological change from rod shape to filamentous in Salmonella cells growing inside host macrophages. Such filamentation depends on an acidic condition within macrophages and in a defined medium mimicking macrophage conditions. Further genetic analyses revealed that …

Dalbavancin For Treatment Of Staphylococcus Aureus Bacteremia: The Dots Randomized Clinical Trial, Nicholas A Turner, Toshimitsu Hamasaki, Sarah B Doernberg, Thomas P Lodise, Heather A King, Varduhi Ghazaryan, Sara E Cosgrove, Timothy C Jenkins, Catherine Liu, Shrabani Sharma, Smitha Zaharoff, Lana Wahid, Valerie J Renard, Paul Cook, Issam Raad, Ray Hachem, Anne-Marie Chaftari, Matthew Sims, Carmen Demarco, Loren G Miller, Matthew W Mccarthy, Caryn G Morse, Chris Lucasti, Graeme N Forrest, Kartikeya Cherabuddi, Christopher Polk, Tasaduq Fazili, Mark E Rupp, George R Thompson, Kami Kim, Luke Strnad, Amanda E Schnee, James A Mckinnell, Mayur Ramesh, Fernanda P Silveira, Todd P Mccarty, Todd C Lee, Emily G Mcdonald, Kristopher Paolino, Katie Wiegand, Alison Wall, Todd Riccobene, Rinal Patel, Urania Rappo, Scott Evans, Henry F Chambers, Vance G Fowler, Thomas L Holland

Faculty, Staff and Student Publications

Importance: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.

Objective: To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.

Design, setting, and participants: Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus …

Bclaf1 Is A Novel Regulator Of Hematopoietic Stem Cells, Stephanie Crowley

Arts & Sciences Graduate Student Theses and Dissertations

Hematopoietic stem cells (HSC) maintain both a self-renewal capacity to persist throughout life and an ability to differentiate into mature cell lineages. HSC self-renewal programs are often ectopically activated in leukemia cells to sustain developmental arrest and neoplastic proliferation. Recently, the transcriptional regulator Bclaf1 (Bcl2 associated transcription factor 1) was shown to support proliferation and block differentiation of AML blasts. Bclaf1 is ubiquitously expressed in hematopoietic cells but its function in normal hematopoiesis has not been elucidated. Our data demonstrate that BCLAF1 promotes HSC development and function. To study the role of BCLAF1 in normal HSCs, we used murine models …

The Role Of The Poly-N Repeat In The Plasmodium Falciparum Histone Acetyltransferase Protein, Pfgcn5, Kely Johana Rubiano Cardona

Arts & Sciences Graduate Student Theses and Dissertations

P. falciparum possesses the most AT-rich genome sequenced to date, with long AAT repeats coding for asparagines (N) in intragenic regions. As a result, nearly a quarter of its proteome is composed of proteins with poly-N repeats. Since the discovery of its genome, the function of these repeats has remained as one of the biggest mysteries in the biology of this parasite. Furthermore, it has long been known that proteins with N-rich domains aggregate easily, particularly during heat stress (HS). Given that the hallmark of this disease is recurrent febrile episodes, it is not well understood how the parasite survives …

Effects Of Light Wavelength On Broiler Performance, Blood Cell Profiles, Stress Levels, And Tibiotarsi Morphology, Angela Perretti, Victor J. Oyeniran, Jaelen M. Cherry, Rosemarry H. Whittle, Zachary Grider, Alexander H. Nelson, Seong W. Kang, Gisela F. Erf, Shawna L. Wiemer

Poultry Science Faculty Publications and Presentations

Lighting influences broiler production, health, and behavior. The objective of this study was to examine the effects of three light wavelengths (White [350-780 nm], Blue [450 nm], and Green [560 nm]) on broiler production, activity, fear, stress, blood cell profiles, and tibiotarsi (tibia) morphology. Day-of-hatch male broiler chicks (N = 600) were housed in pens (N = 12) with one lighting treatment for 42 days. Body weight and feed consumption were recorded on day (D) 0, 14, 28, and 42, and the feed conversion ratio was calculated. The Tonic Immobility test was used to assess the latency (seconds) to right …

Snake Spirits, Fishermen And Water Birds On Lake Victoria: A Case Study Of Cultural Conservation In The Musambwa Islands, Uganda, And Prospects For Tourism To Improve Local Livelihoods, Joel T. Heinen, Henry Batenda

Journal of Ecological Anthropology

Abstract.

Using a combination of site visits, document reviews, focus group and key informant surveys of fishermen, we explore the cultural beliefs, taboos and norms that protect Musambwa Islands, Uganda. The islands form part of a large protected wetland with nesting habitat for thousands of water birds and a large population of highly-venomous forest cobras that coexist in and around fishermen dwellings. There are strong taboos against cutting trees, allowing women on the island, and harming cobras. We present some of our ideas on how to improve the economic situation of fishermen through the promotion of nature-based and cultural tourism …

Remote Running Gait Analysis Using Smartphone Video And Monocular Pose Estimation: A Feasibility Study, Luke Vankeersbilck

Theses and Dissertations

Introduction: Running is a common form of exercise that comes with many health benefits; however, many people stop exercising because of the high injury risk. Running injury is connected with biomechanical risk factors. Yet, these risk factors often show inconsistent and conflicting results across studies, largely due to small sample sizes limiting statistical power. Low subject numbers may be partly due to the time requirements of traditional motion capture. Monocular pose estimation offers a promising alternative by using machine learning to track body landmarks from a single camera. This study evaluated the feasibility of remotely collecting running biomechanics data using …

Assessing The Muc5b Promoter Variant In A Large Cohort Of Systemic Sclerosis-Associated Interstitial Lung Disease, Carlos Rosa-Baez, Carlos Rangel-Pelaez, Inmaculada Rodriguez-Martin, Martin Kerick, Alfredo Guillen-Del-Castillo, Carmen P Simeon-Aznar, José Luis Callejas, Alexandre E Voskuyl, Alexander Kreuter, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Lorenzo Beretta, Maureen D Mayes, Christopher P Denton, Shervin Assassi, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Objective: The common gain-of-function variant rs35705950, located in the promoter of MUC5B gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.

Methods: Samples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100 Kb were obtained using genomic imputation. Subsequently, we tested their …

Computational And Mathematical Modeling Of Microbial Community And Host Responses To Microbiota-Directed Complementary Foods Administered To Children With Acute Malnutrition., Steven J. Hartman

Arts & Sciences Graduate Student Theses and Dissertations

Globally, millions of children suffer from undernutrition, with stunting affecting 150 million and wasting nearly 50 million under five years old. Current interventions have shown limited effectiveness in mitigating long-term consequences such as stunted growth, cognitive deficits, and immune dysfunction. Through this body of work, I investigated the efficacy of a microbiota- directed complementary food (MDCF-2) as a next generation therapeutic food to combat childhood stunting. Across two randomized controlled trials involving Bangladeshi children with either moderate acute malnutrition or post-severe acute malnutrition, MDCF-2 significantly outperformed standard ready-to-use supplementary foods (RUSF), leading to significantly improved ponderal and sustained linear growth …

Circadian Influences On Glycemic Control In 24-Hr Fasts Initiated At Different Mealtimes, Elizabeth Z. Gipson

Theses and Dissertations

This study investigated whether the timing of a 24-hour fast influences indicators of glycemic control throughout the duration of the fast or upon refeeding. Twenty-four adults who have overweight or obesity (13 female, 11 male) completed this randomized crossover study involving three 24-hour fasts initiated at either 8:00 am, 1:00 pm, or 6:00 pm followed by a 75 g oral glucose tolerance test (OGTT) which lasted 2 hours. Continuous glucose monitors (CGMs) were employed to track interstitial glucose throughout each fast and OGTT. Plasma samples for insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were collected at the …

Growth Of Cylindrical Micelles And Their Use To Prepare Porous Materials With Tailored Dimensions And Alignment, Mengxue Zhang, Xiaomeng Li, Chuanbing Tang, Morgan Stefik

Faculty Publications

Materials with cylindrical pores are optimal for electrochemical devices and filtration due to their straight paths with minimal tortuosity when aligned. Polymer templates have led to many individual cylindrical architectures however the independent tailoring of pore and wall dimensions has remained elusive. Here short cylindrical micelle templates (PEO-b-PS) with glassy cores enabled the fabrication of sample series with constant cylindrical pore diameter (∼63 nm) and tailored wall thickness (TiO₂, ∼45–100 nm). This ShortCyl series (aspect ratio 4.25) had modest alignment that was attributed to the low free-energy cost for misalignment. Though the plasticized micelles (DCM present) …

An Rna Modification Prevents Extended Codon-Anticodon Interactions From Facilitating +1 Frameshifting, Evelyn M. Kimbrough, Ha An Nguyen, Haixing Li, Jacob M. Mattingly, Nevette A. Bailey, Wei Ning, Howard Gamper, Ya-Ming Hou, Ruben L. Gonzalez, Christine M. Dunham

Department of Biochemistry and Molecular Biology Faculty Papers

RNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA (tRNA) modifications outside the anticodon contribute to tRNA stability and accurate protein synthesis. Absence of such modifications causes translation errors, including mRNA frameshifting. By integrating single-molecule fluorescence resonance energy transfer and cryogenic electron microscopy, we demonstrate that the N1-methylguanosine (m1G) modification at position 37 of Escherichia coli tRNAProL is necessary and sufficient for modulating the conformational energy of this tRNA on the ribosome so as to suppress +1 frameshifting otherwise induced …

Hippocampal Avoidance During Prophylactic Cranial Irradiation For Patients With Small Cell Lung Cancer: Randomized Phase Ii/Iii Trial Nrg-Cc003, Vinai Gondi, Stephanie L Pugh, Minesh P Mehta, Jeffrey S Wefel, Wolfgang A Tomé, Alexander Y Sun, John Grecula, Kristin J Redmond, Shannon Fogh, Laurie Gaspar, Andre Konski, Joseph Bovi, Clifford G Robinson, Benjamin Corn, Gregory M Videtic, Benjamin H Lok, Harold A Yoon, John H Heinzerling, Albert S Denittis, Ronald C Mcgarry, Kiran Devisetty, Vijayananda Kundapur, Abraham J Wu, Edward C Mccarron, Isabelle Thibault, Edmund L Simon, Andrew M Baschnagel, Samir Narayan, Jondavid Pollock, Rebecca Paulus, Lisa A Kachnic

Faculty, Staff and Student Publications

Purpose: Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity.

Methods: This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy. The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure (phase III). Secondary end points were failure in any NCF …

Polo-Like Kinase 1 Inactivation Enhances Pi3k Inhibition-Mediated Apoptosis Of Notch1-Mutant Head And Neck Squamous Cell Carcinoma, Pooja A Shah, Tuhina Mazumdar, Soma Ghosh, Lacin Yapindi, Reid T Powell, Yong S Park, Li Shen, Anne M Fernandez, Clifford C Stephan, Jing Wang, Andrew G Sikora, Jawad Kazi, Mitchell J Frederick, Faye M Johnson

Children’s Nutrition Research Center Staff Publications

PI3K inhibition causes apoptosis selectively in NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC), but modest single-agent responses and acquired resistance (AR) limit the clinical efficacy of targeted agents. To address these limitations, we investigated novel combination therapies. We tested the efficacy of 5768 compounds as single agents and 139 in combination with PI3K inhibitors in sensitive and AR NOTCH1-mutant HNSCC cell lines. We generated synergy/efficacy classifications for the combinations using multiple metrics of statistical drug synergy and growth rate indices. The PLK1/PI3K combination's efficacy was validated using orthogonal in vitro methods and in two HNSCC xenograft models. Compound efficacy …