Digital Commons Network^™

Uchl1 Is A Potential Molecular Indicator And Therapeutic Target For Neuroendocrine Carcinomas, Shiqin Liu, Timothy Chai, Fernando Garcia-Marques, Qingqing Yin, En-Chi Hsu, Michelle Shen, Angus Martin Shaw Toland, Abel Bermudez, Alifiani B Hartono, Christopher F Massey, Chung S Lee, Liwei Zheng, Maya Baron, Caden J Denning, Merve Aslan, Holly M Nguyen, Rosalie Nolley, Amina Zoubeidi, Millie Das, Christian A Kunder, Brooke E Howitt, H Tom Soh, Irving L Weissman, Michael A Liss, Arnold I Chin, James D Brooks, Eva Corey, Sharon J Pitteri, Jiaoti Huang, Tanya Stoyanova

Faculty, Staff and Student Publications

Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of …

An Extended Bayesian Semi-Mechanistic Dose-Finding Design For Phase I Oncology Trials Using Pharmacokinetic And Pharmacodynamic Information, Chao Yang, Yisheng Li

Faculty, Staff and Student Publications

We propose a model-based, semi-mechanistic dose-finding (SDF) design for phase I oncology trials that incorporates pharmacokinetic/pharmacodynamic (PK/PD) information when modeling the dose-toxicity relationship. This design is motivated by a phase Ib/II clinical trial of anti-CD20/CD3 T cell therapy in non-Hodgkin lymphoma patients; it extends a recently proposed SDF model framework by incorporating measurements of a PD biomarker relevant to the primary dose-limiting toxicity (DLT). We propose joint Bayesian modeling of the PK, PD, and DLT outcomes. Our extensive simulation studies show that on average the proposed design outperforms some common phase I trial designs, including modified toxicity probability interval (mTPI) …

Molecular, Metabolic, And Subcellular Mapping Of The Tumor Immune Microenvironment Via 3d Targeted And Non-Targeted Multiplex Multi-Omics Analyses, Sammy Ferri-Borgogno, Jared K Burks, Erin H Seeley, Trevor D Mckee, Danielle L Stolley, Akshay V Basi, Javier A Gomez, Basant T Gamal, Shamini Ayyadhury, Barrett C Lawson, Melinda S Yates, Michael J Birrer, Karen H Lu, Samuel C Mok

Faculty, Staff and Student Publications

Most platforms used for the molecular reconstruction of the tumor-immune microenvironment (TIME) of a solid tumor fail to explore the spatial context of the three-dimensional (3D) space of the tumor at a single-cell resolution, and thus lack information about cell-cell or cell-extracellular matrix (ECM) interactions. To address this issue, a pipeline which integrated multiplex spatially resolved multi-omics platforms was developed to identify crosstalk signaling networks among various cell types and the ECM in the 3D TIME of two FFPE (formalin-fixed paraffin embedded) gynecologic tumor samples. These platforms include non-targeted mass spectrometry imaging (glycans, metabolites, and peptides) and Stereo-seq (spatial transcriptomics) …

Circulating Microrna Biomarkers Of Thiazide Response In Hypertension, Lakshmi Manasa S Chekka, Marwa Tantawy, Taimour Langaee, Danxin Wang, Rolf Renne, Arlene B Chapman, John G Gums, Eric Boerwinkle, Rhonda M Cooper-Dehoff, Julie A Johnson

Faculty, Staff and Student Publications

Background: Thiazide diuretics are the second most frequently prescribed class of antihypertensives, but up to 50% of patients with hypertension have minimal antihypertensive response to thiazides. We explored circulating microRNAs (miRNAs) in search of predictive biomarkers of thiazide response.

Methods and results: We profiled 754 miRNAs in baseline plasma samples of 36 hypertensive European American adults treated with hydrochlorothiazide, categorized into responders (n=18) and nonresponders (n=18) on the basis of diastolic blood pressure response to hydrochlorothiazide. miRNAs with ≥2.5-fold differential expression between responders and nonresponders were considered for validation in 3 cohorts (n=50 each): hydrochlorothiazide-treated European Americans, chlorthalidone-treated European Americans, …

Current Strategies For Increasing Knock-In Efficiency In Crispr/Cas9-Based Approaches, Andrés Felipe Leal, Angelica María Herreno-Pachón, Eliana Benincore-Flórez, Amali Karunathilaka, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Since its discovery in 2012, the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has supposed a promising panorama for developing novel and highly precise genome editing-based gene therapy (GT) alternatives, leading to overcoming the challenges associated with classical GT. Classical GT aims to deliver transgenes to the cells via their random integration in the genome or episomal persistence into the nucleus through lentivirus (LV) or adeno-associated virus (AAV), respectively. Although high transgene expression efficiency is achieved by using either LV or AAV, their nature can result in severe side effects in humans. For instance, …

Commercially Available Products In Increase Soil Water-Holding Capacity, Shital Poudyal, Jake Powell, Rowe Zwahlen, Grant Cardon

All Current Publications

Although adding organic matter is traditionally the most effective way to enhance soil water-holding capacity, several commercial products in the market also have the potential to increase soil water-holding capacity. In this fact sheet, we discuss the properties and characteristics of those commercially available products and recommended application rates. We also explore some limitations of using these products.

Imputation Of Plasma Lipid Species To Facilitate Integration Of Lipidomic Datasets, Aleksandar Dakic, Jingqin Wu, Tingting Wang, Kevin Huynh, Natalie Mellett, Thy Duong, Habtamu B. Beyene, Dianna J. Magliano, Joanne E. Curran, John Blangero

School of Medicine Publications

Recent advancements in plasma lipidomic profiling methodology have significantly increased specificity and accuracy of lipid measurements. This evolution, driven by improved chromatographic and mass spectrometric resolution of newer platforms, has made it challenging to align datasets created at different times, or on different platforms. Here we present a framework for harmonising such plasma lipidomic datasets with different levels of granularity in their lipid measurements. Our method utilises elastic-net prediction models, constructed from high-resolution lipidomics reference datasets, to predict unmeasured lipid species in lower-resolution studies. The approach involves (1) constructing composite lipid measures in the reference dataset that map to less …

Multimodal Neuro-Nanotechnology: Challenging The Existing Paradigm In Glioblastoma Therapy, Sergej Kudruk, Connor M Forsyth, Michelle Z Dion, Jenny K Hedlund Orbeck, Jingqin Luo, Robyn S Klein, Albert H Kim, Amy B Heimberger, Chad A Mirkin, Alexander H Stegh, Natalie Artzi

2020-Current year OA Pubs

Integrating multimodal neuro- and nanotechnology-enabled precision immunotherapies with extant systemic immunotherapies may finally provide a significant breakthrough for combatting glioblastoma (GBM). The potency of this approach lies in its ability to train the immune system to efficiently identify and eradicate cancer cells, thereby creating anti-tumor immune memory while minimizing multi-mechanistic immune suppression. A critical aspect of these therapies is the controlled, spatiotemporal delivery of structurally defined nanotherapeutics into the GBM tumor microenvironment (TME). Architectures such as spherical nucleic acids or poly(beta-amino ester)/dendrimer-based nanoparticles have shown promising results in preclinical models due to their multivalency and abilities to activate antigen-presenting cells …

Inhibition Of Csf1r And Kit With Pexidartinib Reduces Inflammatory Signaling And Cell Viability In Endometriosis, Timothy N Dunn, Dominique I Cope, Suni Tang, Tirupataiah Sirupangi, Sydney E Parks, Zian Liao, Fei Yuan, Chad J Creighton, Ramya P Masand, Linda Alpuing Radilla, Xiaoming Guan, Laura Detti, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis is a common and debilitating disease, affecting ∼170 million women worldwide. Affected patients have limited therapeutic options such as hormonal suppression or surgical excision of the lesions, though therapies are often not completely curative. Targeting receptor tyrosine kinases (RTKs) could provide a nonhormonal treatment option for endometriosis. We determined that 2 RTKs, macrophage-colony stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor KIT (KIT), are overexpressed in endometriotic lesions and could be novel nonhormonal therapeutic targets for endometriosis. The kinase activity of CSF1R and KIT is suppressed by pexidartinib, a small molecule inhibitor that was recently approved …

Possible Role Of The One-Half Heuristic In Overconfidence Research, Vojtěch Zíka

ESI Working Papers

Overconfidence research often involves estimating performance within a fixed range. Recent studies suggest that overprecision is affected by central tendency bias, the tendency to estimate near the center of a perceived distribution. This paper examines whether a similar pattern influences the other two overconfidence types, overestimation and overplacement. In a laboratory experiment (N = 120), participants estimated their own and the average performance over five rounds of ten Rock–Paper–Scissors games. Each round earned for up to 40 points, but average performance varied across three treatments, with means of 16.6, 20, and 23.3 points. The main question was whether this manipulation …

I-Prf : A Smart Cell Scaffold, Dr.Lochini Suriya

Annual Research Symposium

In regenerative dentistry, platelet rich plasma (PRP) has been used as a supra-physiological concentration of autologous growth factors capable of encouraging tissue regeneration. Despite this, there have been concerns raised about the use of anticoagulants, which are known to impair wound healing. In this work, a liquid formulation of platelet rich fibrin (PRF) called injectable-PRF (I-PRF) was studied without the need of anti-coagulants .

Development Of A Protocol For Obtaining Biological Samples For Genetic Testing From Remote Individuals, Noah R. Schultz, Brandon J. Burger, Jacob Warner, Alfred Amendolara, Jameson Williams, Molly Henley, Layla Risdon, Alessandra Maisie Rivera, Amanda Page, Millicent Jiang, Denisse Castaneda, Garret Phillips, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Pharmacogenomic sequencing allows individuals to learn more about how they will respond to certain medications but requires shipping of a biological sample. One complication of sending biological samples to remote laboratories is stability. Blood generally yields sufficient quantities of high-quality DNA but requires a clinic visit. Saliva and buccal swabs are routinely used for DNA extractions, but the DNA quality is notoriously low due to the presence of bacteria in the mouth. Additionally, elderly individuals have difficulty producing enough saliva for testing, and the tubes contain several milliliters of liquid and shipping requires special considerations. Dried blood spot cards, which …

Surface Modifications Of Orthodontic Bone Screws - A Novel Approach, Sai Kalyan Menta Dr, Ravi M. S

Annual Research Symposium

Anchorage control plays a key role in the correction of malocclusion. With the advent of orthodontic bone screws, attaining absolute anchorage control has become hassle free. They have the advantages of low cost, simple surgical placement, and ease of removal; therefore, they are convenient in the treatment of various malocclusions. Although the clinical stability of bone screws is exceptionally high, stability of the bone screws is compromised by factors such as microbial contamination and morphological defects. To overcome this, surface modifications are introduced to enhance the stability of the bone screws.

The Transformative Potential Of Ligaplants In Replicating Natural Tooth Connections, Mohan Prasad, Mohan Muthu Kumar

Annual Research Symposium

Over the past decade, dental implants have become the gold standard in tooth replacement, with osseointegrated implants reigning supreme. However, these implants present certain limitations, notably the absence of the periodontal ligament (PDL). In response to this challenge, innovative periodontal ligament implants, known as ligaplants, have emerged. By combining tissue engineering principles with cutting-edge implant materials, ligaplants offer a promising alternative to traditional implants, showcasing superior biological performance and potentially extending prosthetic life.Dental implantology has witnessed a transformative shift over the last ten years, with osseointegrated implants dominating the landscape of tooth replacement. Despite their widespread adoption, these implants face …

Automated Micronuclei Detection In Exfoliated Oral Epithelial Cells Of Smokers Using Image Analysing Softwares, Mukul Saini, Sowmya Sv, Dominic Augustine, Sanjana Shetty, Saiprasad Alva

Annual Research Symposium

Micronuclei assay yields an excellent path to monitor individuals or populations exposed to mutagenic, genotoxic or teratogenic events. Micronuclei are small nucleic structures formed due to the deposition of nuclear envelopes around lagging chromosomes that persist in the interphase. Mutagenic and carcinogenic compounds, such as polycyclic aromatic hydrocarbons and N-nitrosamines are believed to be responsible for the formation of micronuclei. Hence, micronuclei detection in exfoliated oral epithelial cells of smokers is a significant biomarker for genotoxicity and to identify cellular changes of biological importance to carcinogenesis. While studies have been conducted for the detection of micronuclei in smokers, they may …

Investigating The Role Of Chaos In Minimizing Tumor Growth, Maxwell Geiger

Annual Research Symposium

Chaos is a type of motion found in mathematical systems that is highly sensitive to initial conditions. While many biological systems described in literature have been analyzed for the presence of chaotic dynamics, there are still many that are yet to be discovered. The goal of this project is to reassess Itik and Banks’ discovery of chaotic behavior in their population dynamics model of cancer growth. Once chaotic behavior is confirmed, we want to investigate how chaos could possibly be controlled to minimize tumor growth and discover novel treatments for cancer patients.

Herbaceous Tropical Legume Integration Into Small-Holder Crop-Livestock Systems In Eastern Indonesia: Results Of 10-Years Of Multi-Disciplinary Systems Research, L. W. Bell, D. Mayberry, K. Cox, S. Traill, J. Nulik, E. J. Hosang, D. Kana Hau

IGC Proceedings (1977-2023)

Integration a forage legume into crop-livestock systems of Eastern Indonesia was tested to establish the capacity to improve nitrogen supply and yields of staple cereal crops (maize and rice) and allow for intensification of beef production to ultimately increase farm income and alleviate rural poverty in the region. Species evaluation sites across a diversity of environments showed Clitoria ternatea (butterfly pea) to be the most resilient and adaptable forage legume for use in association with cropping systems. Crop rotation experiments demonstrated that legumes grown in rotation with maize or rice can increase grain yields by 50% where legume was cut …

Drone And Digital Camera Imagery Estimate C3 And C4 Grass Ratios In Pastures, J. A. Bush, C. D. Teutsch, S. R. Smith, J. C. Henning

IGC Proceedings (1977-2023)

The following study investigates the accuracy and practicality of exploiting the color dichotomy present between C3 and C4 grass species to estimate their respective proportions from drone or camera captured imagery. Understanding the proportions of C3 and C4 grasses in pastures is vital to sound decision making for livestock production. The ability to monitor these proportions remotely will also allow for large scale monitoring as well as detection of changes in botanical composition over time and in response to weather events, management, or climate change. A free green canopy cover (GCC) analyzing software, Canopeo, was used to quantify green plants …

Ecosystem Services And Life Cycle Assessment Of Perennial And Annual Cropping Systems, M. Berti, A. Cecchin

IGC Proceedings (1977-2023)

Corn cultivation has negative impacts to the environment, such as nitrate leaching, soil erosion, and nitrous oxide emissions. Perennial crops such as alfalfa (Medicago sativa L.) reduce annual disturbance of soil, which affects many biogeochemical cycles that are key to provide resilience and stability to cropping systems. Four three-year crop sequences were evaluated. 1) Corn-soybean-corn (CSC); 2) alfalfa-alfalfa-alfalfa (AAA); 3) Corn-spring planted alfalfa-alfalfa (CAA); and 4) Corn-intercropped/alfalfa-alfalfa-alfalfa (CAIAA). Modeling of C and N cycles were conducted with the Denitrification-Decomposition (DNDC) model and global warming potential (GWP) was estimated using life cycle assessment (LCA) methodology. The soil organic carbon (SOC) balance …

Choosing The Best Online Platform, L. L. Baxter, A. Best

IGC Proceedings (1977-2023)

Social media is a powerful tool that enables forage-livestock researchers and Extension specialists to connect with a wide audience of producers, Extension personnel, colleagues, and industry partners. This presentation in the thematic session on “Understanding the role of social media and digital resources in forage education and promotion” will provide an overview of popular social media platforms (Facebook, Twitter, Instagram, TikTok, and YouTube) and discuss how to transform impactful research and Extension programming into effective social content before leading into the panel discussion.

Role Of Social Media And Digital Resources In Forage Education, L. L. Baxter

IGC Proceedings (1977-2023)

Social media and digital resources are powerful tools that enable forage-livestock researchers and Extension specialists to connect with a wide audience of producers, Extension personnel, colleagues, and industry partners. This presentation in the thematic session on “Understanding the role of social media and digital resources in forage education and promotion” will focus on the role digital resources play in forage education.

The Nutritional Dynamic Is Key For Use Optimal Forage And Increase Of Meat Production, Bernal-Flores Alvaro, E. A. Pizarro, Quero Carillo Raymundo, Pérez Rodríguez Paulino

IGC Proceedings (1977-2023)

The nutritional content grass could be considered a key tool to determine the optimal forage use, based on the requirements of the cattle to maximize production and achieve a highly productive and profitable livestock. The degradation protein complex associated with autophagy plant determines to a great extent the protein content of the grass over time, being priority found the value nutritional required for the livestock for intensification the animal production. The crude protein requirements (CP, 13.5%) to cover nutritional needs in cattle, was established between 28±1 y 30±1 for the dry period and wet period respectively in Camello® hybrid grass. …

Regenera+.Uy: Designing A Co-Innovation Process To Apply The Principles Of Regenerative Livestock Production, Oscar Blumetto, M. Bustamante, A. Castagna, D. Caresani, G. Ciappesoni, R. Baptista, I. De Barbieri

IGC Proceedings (1977-2023)

Consumers around the world are beginning to demand products whose production systems have environmental guarantees. Among them, those derived from regenerative agriculture have a growing demand in many markets. A comprehensive environmental assessment was carried out in 9 case studies of mixed livestock production farms (cattle and sheep) in Uruguay as a basis for the development of a system redesign process following the principles of regenerative agriculture. The results show that emission intensity was 16.0, 10.5, and 49.2 kg CO2 eq kg-1 of beef, sheep meat, and greasy wool, respectively. Also, a simulation exercise shows a significative reduction of emission …

Estimating Forage Biomass Using Unmanned Ground And Aerial Vehicles, B. A. Koc, J. Singh, M. J. Aguerre,

IGC Proceedings (1977-2023)

The assessment of the amount of biomass in the field is one of the critical factors that helps to manage and optimize numerous operations associated with forage management in the livestock industry. Pasture management decisions about stocking rate, grazing duration, and fertilizer application rate depend on accurate forage availability measurements. The objective of this study was to develop different nondestructive methods of forage biomass estimation using unmanned vehicles based on the relationship between crop height (CH) and the measured above-ground biomass. The unmanned vehicle-based methods were developed and tested on Alfalfa (Medicago Sativa) and Tall Fescue (Schedonorus …

Genetic Modification – Applications For Forage And Grassland Production Systems, J. R. Caradus

IGC Proceedings (1977-2023)

Genetic modification has been extensively used in crops for 25 years but has rarely been a technology used to advance trait expression in forage and grassland species. The exceptions are the use of herbicide tolerance and low lignin traits in alfalfa which are currently commercially available. In crop species genetic modification has been a valuable option for delivering improved economic and environmental outcomes through providing solutions for many of the challenges facing mankind. There are a many beneficial characteristics that genetic modification has the potential to provide in forage and grassland species. Managing these in the environment and understanding consumer …

A Framework For Promoting Diverse Perennial Circular Forage Systems For More Resilient Agricultural Landscapes: Developing Extension And Educational Tools For Resilience And Sustainability, Cassida K. A., W. Lamp, S. Gruss

IGC Proceedings (1977-2023)

The Resilience CAP Team seeks to use diverse, perennial, circular forage systems (DPCFS) to enhance biodiversity, improve soil and plant health, support ecosystem service, all towards achieving greater resilience to global change and improving the farm economy and quality of life. Our project will design a transdisciplinary framework that combines agronomic, ecological, economic, and sociological factors to achieve greater resilience and stability in agricultural systems through use of DPCFS. In this paper, we describe two of the project’s six objectives. Objective 5 is our extension/outreach arm where we will develop extension media, activities, and actionable decision tools to communicate concepts …

Convalescing Soil Functionality Of Degraded Lands: An Experience From Semi-Arid India, A. Chandra, H. Baradwal, A. Ghosh, A. K. Singh, S. S. Manjangouda

IGC Proceedings (1977-2023)

Land loss is not only whittling away India’s gross domestic product by 2.5% every year and affecting its crop yield but also exacerbating climate change events in the country. To test applicability of alternate land use systems for improving soil functionality in restored ecologies, soils were sampled from the 0-15, 15-30 and 30-45 cm layers of Leucaena leucocephala (LL), Hardwickia binata (HB), Emblica officinalis (EO), Azadiracta indica (AI) based silviculture systems, Acacia nilotica-based silvipasture systems (AN), and natural grassland (NG) and compared with a fallow land (F). They were evaluated for carbon management index (CMI), nutrient supply capacity (NSC), …

Stoloniferous Forage Legumes For Sustainable Mixed Pastures In The Tropics, R. M. Boddey, C De P Rezende, J. Marques Pereira, C. A. Dos Santos, Animal Husbandry Station Of The Extreme South Of Bahia, Brazil, I. O. Ramalho, R. M. Macedo, B. C. G. Homem, D. R. Casagrande, S. Urquiaga, B. J. R. Alves

IGC Proceedings (1977-2023)

Brazil has over 80 million ha of tropical pastures formed with species of Brachiaria (syn. Urochloa), mostly grazed by beef cattle and with low fertilizer inputs, especially nitrogen. Recent investigations by our team show that stoloniferous legumes such as forage peanut (Arachis pintoi) and Desmodium ovalifolium are able to persist in mixed swards with Brachiaria brizantha (cv. Marandu) if grazing height is regulated (maximum 30 cm) so that radiation can reach the soil surface allowing stolons to take root. These legumes can persist in mixed pastures and produce milk or animal weight gains similar to the application …

Ecosystem Benefits Of Invasive Annual Grass Removal, S. L. Clark

IGC Proceedings (1977-2023)

Invasive winter annual grasses (IAGs) are altering rangeland ecosystems across millions of hectares in the western US. These winter annuals outcompete native plants for soil moisture and nutrients, leading to devastating impacts on ecosystem functions. The IAG seedbank is short-lived and often does not persist beyond 3 years. Past tools for IAG control have only provided short-term control or caused injury to the native plant community, making it difficult for researchers to assess the ecosystem benefits of IAG removal. A newer herbicide option, indaziflam, provides IAG control for three or more years. Indaziflam’s extended soil residual control and tolerance of …

Exploring Profitable, Sustainable Livestock Businesses In An Increasingly Variable Climate, B. R. Cullen, M. T. Harrison, D. Mayberry, D. Cobon, N. Reichelt, A. Sinnet, Km Christie, F. Bilotto, D-A An-Vo, C. Stokes, L. Perry, T. Davison

IGC Proceedings (1977-2023)

Livestock production systems will need to change in many regions of the world to meet the dual challenges of adaptation to a changing climate and reducing net greenhouse gas (GHG) emissions. The ‘Nexus project’ is exploring these options using seven case studies in eastern Australia spanning a range of production systems from semi-arid beef production in northern Australia to mixed beef and sheep production in cool temperate climates of southern Australia. Regional reference groups, made up of 4-6 local farmers and advisers, identified a series of farm systems changes that could be made to meet these challenges. Options were categorised …