Life Sciences Commons^™

Alternative Splicing Mediates The Compensatory Upregulation Of Mbnl2 Upon Mbnl1 Loss-Of-Function, Larissa Nitschke, Rong-Chi Hu, Andrew N Miller, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

Loss of gene function can be compensated by paralogs with redundant functions. An example of such compensation are the paralogs of the Muscleblind-Like (MBNL) family of RNA-binding proteins that are sequestered and lose their function in Myotonic Dystrophy Type 1 (DM1). Loss of MBNL1 increases the levels of its paralog MBNL2 in tissues where Mbnl2 expression is low, allowing MBNL2 to functionally compensate for MBNL1 loss. Here, we show that loss of MBNL1 increases the inclusion of Mbnl2 exon 6 and exon 9. We find that inclusion of Mbnl2 exon 6 increases the translocation of MBNL2 to the nucleus, while …

Editorial: Special Issue “Protein Modeling And Simulation: Selected Articles From The Computational Structural Bioinformatics Workshop 2021”, Negin Forouzesh, Kamal Ai Nasr

Computer Science Faculty Research

No abstract provided.

A Scanning-To-Incision Switch In Tfiih-Xpg Induced By Dna Damage Licenses Nucleotide Excision Repair, Amer Bralić, Muhammad Tehseen, Mohamed A Sobhy, Chi-Lin Tsai, Lubna Alhudhali, Gang Yi, Jina Yu, Chunli Yan, Ivaylo Ivanov, Susan E Tsutakawa, John A Tainer, Samir M Hamdan

Faculty, Staff and Student Publications

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding …

Evofosfamide For The Treatment Of Human Papillomavirus-Negative Head And Neck Squamous Cell Carcinoma, Stephen Mf Jamieson, Peter Tsai, Maria K Kondratyev, Pratha Budhani, Arthur Liu, Neil N Senzer, E Gabriela Chiorean, Shadia I Jalal, John J Nemunaitis, Dennis Kee, Avik Shome, Way W Wong, Dan Li, Nooriyah Poonawala-Lohani, Purvi M Kakadia, Nicholas S Knowlton, Courtney Rh Lynch, Cho R Hong, Tet Woo Lee, Reidar A Grénman, Laura Caporiccio, Trevor D Mckee, Mark Zaidi, Sehrish Butt, Andrew Mj Macann, Nicholas P Mcivor, John M Chaplin, Kevin O Hicks, Stefan K Bohlander, Bradly G Wouters, Charles P Hart, Cristin G Print, William R Wilson, Michael A Curran, Francis W Hunter

Faculty, Staff and Student Publications

Evofosfamide (TH-302) is a clinical-stage hypoxia-activated prodrug of a DNA-crosslinking nitrogen mustard that has potential utility for human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC), in which tumor hypoxia limits treatment outcome. We report the preclinical efficacy, target engagement, preliminary predictive biomarkers and initial clinical activity of evofosfamide for HPV-negative HNSCC. Evofosfamide was assessed in 22 genomically characterized cell lines and 7 cell line–derived xenograft (CDX), patient-derived xenograft (PDX), orthotopic, and syngeneic tumor models. Biomarker analysis used RNA sequencing, whole-exome sequencing, and whole-genome CRISPR knockout screens. Five advanced/metastatic HNSCC patients received evofosfamide monotherapy (480 mg/m2 qw × …

Hyperprogression Of Cutaneous T Cell Lymphoma After Anti-Pd-1 Treatment, Yumei Gao, Simeng Hu, Ruoyan Li, Shanzhao Jin, Fengjie Liu, Xiangjun Liu, Yingyi Li, Yicen Yan, Weiping Liu, Jifang Gong, Shuxia Yang, Ping Tu, Lin Shen, Fan Bai, Yang Wang

Faculty, Staff and Student Publications

BACKGROUND

Immune checkpoint blockade is an emerging treatment for T cell non-Hodgkin’s lymphoma (T-NHL), but some patients with T-NHL have experienced hyperprogression with undetermined mechanisms upon anti–PD-1 therapy.

METHODS

Single-cell RNA-Seq, whole-genome sequencing, whole-exome sequencing, and functional assays were performed on primary malignant T cells from a patient with advanced cutaneous T cell lymphoma who experienced hyperprogression upon anti–PD-1 treatment.

RESULTS

The patient was enrolled in a clinical trial of anti–PD-1 therapy and experienced disease hyperprogression. Single-cell RNA-Seq revealed that PD-1 blockade elicited a remarkable activation and proliferation of the CD4+ malignant T cells, which showed functional PD-1 expression and …

The Trade Impact Of Economic Integration Agreements, Byungyul Park, John C. Beghin

Cornhusker Economics

A year ago, Cornhusker Economics reported on the substantial trade integration that has been taking place globally in recent decades (see Beghin, 2022). With this proliferation of Economic Integration Agreements (EIAs) through regional and bilateral trade agreements and customs unions since the 1990s, many economists have investigated the effect of these agreements on merchandise trade. Early investigations struggled to find robust findings. They reached two opposite conclusions, with an eventual rejoinder on their limitations. Some investigations found statistically insignificant or negligible effects of EIAs on trade flows. Other investigations found significant effects, sometimes negative, of EIAs on trade. See Park …

Update On Options For Managing Thin Alfalfa Stands, Jimmy C. Henning

Kentucky Alfalfa and Stored Forage Conference

Alfalfa is the highest yielding, highest quality hay crop grown in Kentucky. Well cured alfalfa and alfalfa‐grass hay is in high demand for dairy and in particular, horse owners. Alfalfa stands in Kentucky remain productive from four to as long as 8 years or more depending on several factors. Long stand life is favored by:

1. Using an improved variety with high resistance to the major diseases of Kentucky and that is proven to be high yielding in relevant trials such as conducted at the University of Kentucky.

2. Deep, well drained soils,

3. Soils that have been limed to …

Investigating Respiratory Simplification Caused By Prenatal Rage Upregulation, Paul Reynolds

Annual Research Symposium

No abstract provided.

Potential Role For Rage In The Development Of Secondhand Smoke-Induced Chronic Sinusitis, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Inhibition Reduces Timp And Decreases Cell Invasion In Cigarette Smoke Extract (Cse) Treated Oral Squamous Carcinoma Cells, Paul Reynolds

Annual Research Symposium

No abstract provided.

Inflammatory Cytokine Elaboration Following Secondhand Smoke Exposure Is Mediated In Part By Rage Signaling, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Availability Lessens The Degree Of Dysfunctional Mitochondrial Bioenergetics Following Chronic Secondhand Smoke Exposure, Paul Reynolds

Annual Research Symposium

No abstract provided.

Gestational Dependent Responses To Second Hand Smoke (Shs) In Mouse Pregnancies, Paul Reynolds

Annual Research Symposium

No abstract provided.

Attacking The Yield Plateau: Assessing The Nutrient Status Of Kentucky Alfalfa Stands, W. R. Fleming, C. D. Teutsch, E. L. Ritchey, J. H. Grove

Kentucky Alfalfa and Stored Forage Conference

Soil and tissue analyses indicated that alfalfa yields may be limited in some cases by soil fertility. Soil pH was below the optimal range in more than 40% of the fields sampled. This may result in decreased nitrogen fixation and nutrient availability. Potassium was reported low in approximately one‐quarter of the sampled stands according to tissue analysis. This was not unexpected since hay production removes large quantities of potash. Sulfur and magnesium were reported low in 13 and 23 percent of stands, respectively. More work is needed to better understand if these two 2023 Kentucky Alfalfa and Stored Forage Conference …

Hay Mechanization And New Equipment, Noah Pendry

Kentucky Alfalfa and Stored Forage Conference

Review of the latest developments in hay mechanization equipment.

Options For Hay Mechanization: Collecting And Storing Small Square Bales, Dennis Wright

Kentucky Alfalfa and Stored Forage Conference

A producer's evaluation of the various available methods for collecting hay, including traditional flat wagon, stack wagon, accumulators, and bale banders.

Hay Production In The Deep South: Bermudagrass And Alfalfa A Perfect Combination, Jennifer J. Tucker

Kentucky Alfalfa and Stored Forage Conference

No abstract provided.

National Producer And Consumer Survey: Increasing Alfalfa Hay Sales To Horse Owners, Krista Lea, Bob Coleman, Laurie Lawrence, Jen Zimmerman, Ray Smith

Kentucky Alfalfa and Stored Forage Conference

Horse owners were surveyed regarding their hay feeding choices. Unique factors of this market are discussed.

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin

Reversible Emerging Neuropsychological Pattern In Chronic Intractable Migraine, Tanner Williford, Pooja Chemiti, Mason Allen, Brandon Burrell, Stephanie Chavez, Jude Emego, Bridger Gunter, Matthew Huertas, Matthew Jennings, Roshni Jogin, Paulo Kelly, Laura Minor, Steven Salazar, Jameson Williams, David W. Sant, John A. Kriak, Kyle B. Bills

Annual Research Symposium

No abstract provided.

Potential Yield Of Cocksfoot (Dactylis Glomerata) Monocultures In Response To Irrigation And Nitrogen, A. Mills, D. J. Moot, R. L. Lucas, P. D. Jamieson, B. A. Mckenzie

IGC Proceedings (1977-2023)

Cocksfoot is a widely sown grass in temperate pastures. However, while potential yield of cocksfoot can exceed 28 t DM/ha per year, it is often restricted by water, temperature and nitrogen (N). Of these, Peri et al. (2002) showed that N was severely limiting in all seasons. The aim of this study was to confirm the potential yield of cocksfoot and quantify the extent of yield reductions due to environmental constraints.

Diverse Forage Mixtures Effect On Herbage Yield, Sward Composition, And Dairy Cattle Performance, M. A. Sanderson, K. Soder, N. Brzezinski, S. Goslee, H. Skinner, M. Wachendorf, F. Taube, L. Muller

IGC Proceedings (1977-2023)

Managing complex mixtures of plants to take advantage of spatial and temporal variability in land and climate may be one ecological approach to increase productivity of pastures. We tested the hypothesis that complex mixtures of forage species would yield more herbage and reduce weed competition compared with a simple grass-legume mixture in grazed pastures.

Hygienic Value And Mycotoxins Level Of Grass Silage In Bales For Horses, A. Potkański, J. Grajewski, K. Raczkowska-Werwińska, B. Miklaszewska, A. Gubała, M. Selwet, M. Szumacher-Strabel

IGC Proceedings (1977-2023)

Mycotoxins are secondary metabolites of moulds which have adverse effects on humans, animals, and crops and result in illnesses and economic losses. The toxins may occur in storage under conditions favourable for the growth of the toxin-producing fungus or fungi. The highest forage concentration of toxins was found in horizontal storage methods such as bunker silos and feed piles, which were left open to oxygen. In any fermentation storage system, temperature and the presence of moisture is sufficient for toxin production. In a plastic covered storage system, oxygen penetration is slowed but not eliminated. The longer silage is stored, the …

Participatory Approach To Common Use Grazing Management In Dry Area Developing Countries, J. Tiedeman, A. Larbi, F. Ghassali, N. Battikha

IGC Proceedings (1977-2023)

Key points

1. Range restoration technology is available but useless when not followed by management.

2. Institutional mechanisms for grazing management are needed for communal range.

3. Community participatory approaches help pastoralists better manage rangeland grazing.

Biochar Influences Phytochemical Concentrations Of Viola Cornuta Flowers, Abishkar Regmi, Shital Poudyal, Sukhbir Singh, Cade Coldren, Naima Moustaid-Moussa, Catherine Simpson

Plants, Soils, and Climate Faculty Publications

Edible flowers are a rich source of phytochemicals with potential health benefits. Yet, changes in production practices can influence the phytochemical composition of edible flowers. Practices such as the addition of biochar have been used to affect growing media properties as well as to conserve peat resources. However, there is little known about how biochar affects the phytochemical composition of edible flowers. To determine if biochar affects phytochemicals in Viola cornuta, four cultivars were subjected to different rates of biochar, with and without fertilizer. At the rate of 10% biochar and without fertilizer application, flower polyphenol and flavonoid concentrations …

Find Gene Expression Data Quickly, Grace Salmons, Aaron Joyce Fabelico, James Wengler, Stephen R. Piccolo

Library/Life Sciences Undergraduate Poster Competition 2023

Public repositories are:

• vital for validating studies

• incredible for addressing novel hypothesis.

However, it can be difficult to find data related to discrete topics due to:

• large quantity of data

• heterogeneity in how researchers describe their data and study designs.

Manual annotation of data cannot keep pace with the rapid pace of science. We turned to Natural Language Processing (NLP) for a solution!

Promoting Health Equity: Identifying Parent And Child Reactions To A Culturally-Grounded Obesity Prevention Program Specifically Designed For Black Girls Using Community-Engaged Research, Haley Allen, Chishinga Callender, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

The Butterfly Girls (BFG) Study is a culturally and developmentally appropriate online obesity prevention program for 8-10-year-old Black girls designed with key stakeholders in the Black community. This multi-methods investigation, conducted with parent-child dyads who participated in an outcome evaluation of the intervention, aimed to understand parent and child reactions to the program. We were particularly interested in understanding perceptions regarding its cultural and developmental appropriateness, relevance and acceptability. Program participation and survey data (demographics, parent and child write-in comments on process evaluation surveys) were analyzed. Participation data demonstrated high adherence in treatment and comparison groups. Descriptive statistics were calculated …

Editorial: Community Series In Tools, Techniques, And Strategies For Teaching In A Real-World Context With Microbiology, Volume Ii, Davida S. Smyth, Nicole A. Broderick, Carlos C. Goller

All Faculty Scholarship (Archived)

This Research Topic is the second volume in the Community Series Tools, Techniques, and Strategies for Teaching in a Real-World Context with Microbiology. Making microbiology relevant to our students increases student engagement with science, which could not be more important as we emerge from the COVID-19 pandemic. We have learned much during this period as we adapted and modified our learning environments and strategies, all while demonstrating the many ways microbes impact our world beyond disease. Placing microbes at center stage leads to engaging and exciting curricula and assignments. Microbes also are wonderful tools as they are easy to manipulate …

Fixitfelix: Improving Genomic Analysis By Fixing Reference Errors, Sairam Behera, Jonathon Lefaive, Peter Orchard, Medhat Mahmoud, Luis F Paulin, Jesse Farek, Daniela C Soto, Stephen C J Parker, Albert V Smith, Megan Y Dennis, Justin M Zook, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an efficient remapping approach, together with a modified version of the GRCh38 reference genome that improves the subsequent analysis across these genes within minutes for an existing alignment file while maintaining the same coordinates. We showcase these improvements over multi-ethnic control samples, demonstrating improvements for population variant calling as well as eQTL studies.

Predicting Patient-Specific Tumor Dynamics: How Many Measurements Are Necessary?, Isha Harshe, Heiko Enderling, Renee Brady-Nicholls

Faculty, Staff and Student Publications

Acquiring sufficient data is imperative to accurately predict tumor growth dynamics and effectively treat patients. The aim of this study was to investigate the number of volume measurements necessary to predict breast tumor growth dynamics using the logistic growth model. The model was calibrated to tumor volume data from 18 untreated breast cancer patients using a varying number of measurements interpolated at clinically relevant timepoints with different levels of noise (0-20%). Error-to-model parameters and the data were compared to determine the sufficient number of measurements needed to accurately determine growth dynamics. We found that without noise, three tumor volume measurements …