Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons™

Open Access. Powered by Scholars. Published by Universities.®

Discipline
Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 26131 - 26160 of 255943

Full-Text Articles in Life Sciences

The Palestinian Feature Film "200 Meters" Addresses The Issue Of The Apartheid Wall, Samar Abd Al Karim Farahat May 2024

The Palestinian Feature Film "200 Meters" Addresses The Issue Of The Apartheid Wall, Samar Abd Al Karim Farahat


This study aimed to explain the methods of processing the Palestinian feature film" 200 meters " to the issue of the apartheid wall, using sub-objectives highlighting political, social and psychological issues and topics in addition to the characters and cinematic elements, to identify the form of processing carried out by the film in an integrated manner. Given the nature of this study, which aimed to find out how the 200-meter film dealt with the issue of the apartheid wall, the researcher adopted the most appropriate approach to studying this type of phenomena, which is the analytical approach. The results of …


Antibiotic-Induced Changes In Efflux Transporter Expression: A Key Factor In Pseudomonas Aeruginosa Biofilm Resistance, Zara Imtiaz, Avinash Chatoo, Will Wang, Weiqi Li, Paramita Basu May 2024

Antibiotic-Induced Changes In Efflux Transporter Expression: A Key Factor In Pseudomonas Aeruginosa Biofilm Resistance, Zara Imtiaz, Avinash Chatoo, Will Wang, Weiqi Li, Paramita Basu

Touro College of Pharmacy (New York) Publications and Research

Listed by WHO as an antibiotic-resistant priority pathogen, Pseudomonas aeruginosa(P.A.) is a serious threat in nosocomial infections. Its high antibiotic resistance is attributed to major mechanisms that can be categorized into intrinsic, acquired, and adaptive resistance. This study tests the ability of three commonly used antibiotics to inhibit new biofilm formation and eradicate mature biofilm growth, as well as investigate changes in the expression levels of selected genes coding for multidrug efflux pumps in P.A. planktonic cells and biofilms before and after treatment with antibiotics to provide a conceptual estimate of the activity of the efflux transporters that work to …


Comparing Executive Control: Bilingualism's Cognitive Advantage, Malcolm Jasmin, Tonya Buchanan Ph.D. May 2024

Comparing Executive Control: Bilingualism's Cognitive Advantage, Malcolm Jasmin, Tonya Buchanan Ph.D.

Symposium Of University Research and Creative Expression (SOURCE)

The Stroop Task is a widely used method for studying executive control. It helps to understand cognitive processes like inhibition and attentional regulation to examine how reading text and naming colors can interfere with each other. The study intends to use the Stroop Task to explore the executive control abilities of both bilingual and monolingual individuals. Previous research has shown that bilingual individuals perform better in the Stroop test compared to those who only speak one language (Bialystok et al., 2010). The impact of this advantage is believed to be due to the need to switch between languages and prevent …


Novel Tetrazolium-Based Colorimetric Assay For Helicase Nsp13 In Sars-Cov-2, Triet M. Pham, Morgan G. Howard, Shane M. Carey, Lindsey R. Baker, Edward L. D'Antonio May 2024

Novel Tetrazolium-Based Colorimetric Assay For Helicase Nsp13 In Sars-Cov-2, Triet M. Pham, Morgan G. Howard, Shane M. Carey, Lindsey R. Baker, Edward L. D'Antonio

Natural Sciences Faculty Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a human pathogenic virus that encodes for a helicase (SC2Hel) that is essential for viral replication. SC2Hel has the ability to unravel dsRNA or dsDNA in an NTP-dependent manner from the 5′ to 3′ directionality. The standard helicase assay from studies involving SARS-CoV and SARS-CoV-2 have relied on the concept of fluorescence resonance energy transfer. Adding to the collection of helicase assays, herein, we have developed a novel tetrazolium-based colorimetric assay system for the detection of ADP that is produced via SC2Hel activity. This SC2Hel assay combines three enzyme-coupled steps involving the …


Temporal And Spatial Influences On Fawn Summer Survival In Pronghorn Populations: Management Implications From Noninvasive Monitoring, Cole A. Bleke, Eric M. Gese, Juan J. Villalba, Shane B. Roberts, Susannah S. French May 2024

Temporal And Spatial Influences On Fawn Summer Survival In Pronghorn Populations: Management Implications From Noninvasive Monitoring, Cole A. Bleke, Eric M. Gese, Juan J. Villalba, Shane B. Roberts, Susannah S. French

Wildland Resources Student Research

Monitoring vital rates allows managers to estimate trends in growth rates of ungulate populations. However, connecting the influence of nutrition on ungulate demography is challenging. Noninvasive sampling offers a low-cost, low-effort alternative for measuring nutritional indices, allowing for an increased understanding of the mechanistic relationships between environmental factors, nutrition, and specific population vital rates. We examined the temporal influence of intrinsic and extrinsic factors on pronghorn (Antilocapra americana) fawn recruitment. We collected fresh fecal samples from adult female pronghorn in five subpopulations spanning three sampling periods associated with critical maternal life-history stages (late gestation, early lactation, breeding season) …


Design And Implementation Of A Machine Learning Predictive Model For Crop Yield In Indoor Vertical Hydroponics Farming, Emna Bouzid May 2024

Design And Implementation Of A Machine Learning Predictive Model For Crop Yield In Indoor Vertical Hydroponics Farming, Emna Bouzid

Theses and Dissertations

To optimize agricultural practices and address water scarcity, this work introduces Vertical Hydroponics and Machine Learning (ML) to smart agriculture, using data from Internet of Things (IoT) sensors to enhance crop production in low and medium-income countries, particularly Tunisia's, hydroponic farms. This research is an innovative approach to enhancing crop production within indoor vertical hydroponic systems by utilizing different ML predictive models and assessing their performance. This part was done at UALR while the data collection was done at MedTech, with 21 basil plants. This study compares Linear Regression, Long Short-Term Memory (LSTM), and Deep Neural Networks (DNN) for precision …


The North Central Extension Risk Management Education Center, Part Ii: Activities And Success Stories, Sheila Aikanathan Johnson, Christine Lockert, Bradley D. Lubben May 2024

The North Central Extension Risk Management Education Center, Part Ii: Activities And Success Stories, Sheila Aikanathan Johnson, Christine Lockert, Bradley D. Lubben

Cornhusker Economics

The North Central Extension Risk Management Education Center is committed to educating American farmers and ranchers on effectively managing the distinct risks associated with producing food for global consumption. So far, we've funded 523 projects totaling over $18.7 million, benefiting more than 168,000 participants.

Part I provided an overview of the North Central Extension Risk Management Education Center, including its operations, priorities, service areas, and how the grant program functions. Part II details the center's activities and highlight some of the numerous projects that have been supported over 23 years since the awarding process started. In the forthcoming segment, Part …


An Exploration Of Learning And Teaching Methods In Agricultural Extension, Jeremy Levinson, Dave Lamie, Michael Vassalos, Chris Eck, Juang Chong, Francis P. F. Reay-Jones May 2024

An Exploration Of Learning And Teaching Methods In Agricultural Extension, Jeremy Levinson, Dave Lamie, Michael Vassalos, Chris Eck, Juang Chong, Francis P. F. Reay-Jones

Journal of Extension

Abstract

The Train-the-Trainer approach is widely used in Cooperative Extension education to efficiently disseminate research-based information to many clientele groups, including farmers. This paper compares the traditional Train-the-Trainer model to a comprehensive Collaborative Train-the-Trainer model and discusses weaknesses of the traditional model that are addressed in the Collaborative model. Sources of information used by farmers (growers) and overall effectiveness were measured through a survey instrument created and distributed to farmers in South and North Carolina. The Collaborative Train-the-Trainer model, which emphasizes peer-to-peer interaction and feedback loops, represents an enhanced approach for conceptualizing and implementing Extension educational programs.


Hay Inventory And Purchasing Calculator For Horse Owners, Robyn L. Stewart, Brooklyne M. Wassel May 2024

Hay Inventory And Purchasing Calculator For Horse Owners, Robyn L. Stewart, Brooklyne M. Wassel

Journal of Extension

The Hay Inventory and Purchasing Calculator for Horse Owners is an Excel-based tool for estimating hay needs and expenses for horse owners. Challenges with hay quality and availability can result in higher than expected costs for horse owners as they attempt to purchase enough horse-quality hay to meet their needs. Estimating intake requirements and creating a budget for hay purchasing is key for the effective management and profitability of equine operations. This tool can be used regardless of geographic location and will benefit a diverse audience including Extension educators, equine business owners, and horse owners.


Expanded Food And Nutrition Education Program Generates Economic Value Through Body Mass Index Improvement: A Cost-Benefit Analysis, Andrea Leschewski, M. Catalina Aragon, Dave Weatherspoon, Karen Barale, Garry Auld, Richard Acquah-Sarpong, Susan S. Baker May 2024

Expanded Food And Nutrition Education Program Generates Economic Value Through Body Mass Index Improvement: A Cost-Benefit Analysis, Andrea Leschewski, M. Catalina Aragon, Dave Weatherspoon, Karen Barale, Garry Auld, Richard Acquah-Sarpong, Susan S. Baker

Journal of Extension

Prior economic evaluations of the Expanded Food and Nutrition Education Program (EFNEP) perform cost-benefit analyses (CBA) reliant on self-reported behavioral data and unvalidated criteria for disease prevention. This study aims to conduct a CBA of Colorado and Washington EFNEP using an objective biomarker, Body Mass Index, to monetize program benefits. A longitudinal study of a convenience sample of EFNEP participants was conducted utilizing a single-group pretest-posttest design. Results indicate Colorado and Washington EFNEP generates $9.23 of benefits per $1.00 of costs and demonstrate the feasibility and value of using biomarkers in economic evaluations of nutrition education interventions delivered through Extension.


Perceived Benefits And Barriers To Livestock Mortality Composting, Rachel Wieme, Lynne Carpenter-Boggs May 2024

Perceived Benefits And Barriers To Livestock Mortality Composting, Rachel Wieme, Lynne Carpenter-Boggs

Journal of Extension

We conducted webinars in 2020 about livestock mortality composting (LMC). Forty-five attendees completed a survey to evaluate the webinar and help define future educational needs. Major barriers to LMC were lack of experience, public and neighbor perceptions, and environmental management. Most respondents indicated convenience, cost, biosafety, use of product, and environmental management as benefits. An unexpected emotional theme indicated that LMC also supports the “circle of life” and “respect for the animal.” We propose that this theme may be a uniting message to improve public and producer perception of LMC, increase use of LMC, and improve public-producer relationships overall.


Age-Related Brain Atrophy And The Positive Effects Of Behavioral Enrichment In Middle-Aged Beagles., Jessica A Noche, Hamsanandini Radhakrishnan, Margo F. Ubele, Kathy Boaz, Jennifer L Mefford, Erin D Jones, Hollie Y Van Rooyen, Jessica A Perpich, Katie Mccarty, Beverly Meacham, Jeffrey R. Smiley, Stasia A Bembenek Bailey, László G Puskás, David K. Powell, Lorena Sordo, Michael J Phelan, Christopher M. Norris, Elizabeth Head, Craig E L Stark May 2024

Age-Related Brain Atrophy And The Positive Effects Of Behavioral Enrichment In Middle-Aged Beagles., Jessica A Noche, Hamsanandini Radhakrishnan, Margo F. Ubele, Kathy Boaz, Jennifer L Mefford, Erin D Jones, Hollie Y Van Rooyen, Jessica A Perpich, Katie Mccarty, Beverly Meacham, Jeffrey R. Smiley, Stasia A Bembenek Bailey, László G Puskás, David K. Powell, Lorena Sordo, Michael J Phelan, Christopher M. Norris, Elizabeth Head, Craig E L Stark

Neuroscience Faculty Publications

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that …


Adopting Yield-Improving Practices To Meet Maize Demand In Sub-Saharan Africa Without Cropland Expansion, Fernando Aramburu-Merlos, Fatima A. M. Tenorio, Nester Mashingaidze, Alex Sananka, Stephen Aston, Jonathan J. Ojeda, Patricio Grassini May 2024

Adopting Yield-Improving Practices To Meet Maize Demand In Sub-Saharan Africa Without Cropland Expansion, Fernando Aramburu-Merlos, Fatima A. M. Tenorio, Nester Mashingaidze, Alex Sananka, Stephen Aston, Jonathan J. Ojeda, Patricio Grassini

Department of Agronomy and Horticulture: Faculty Publications

Maize demand in Sub-Saharan Africa is expected to increase 2.3 times during the next 30 years driven by demographic and dietary changes. Over the past two decades, the area croppedwithmaize has expanded by 17million hectares in the region, with limited yield increase. Following this trend could potentially result in further maize cropland expansion and the need for imports to satisfy domestic demand. Here, we use data collected from 14,773 smallholder fields in the region to identify agronomic practices that can improve farm yield gains. We find that agronomic practices related to cultivar selection, and nutrient, pest, and crop management can …


Cereal Rye Cover Crop Termination At Or Before Soybean Planting Has Minimal Effect On Soybean Yield Across The Midwestern Us, Tatiane Severo Silva, Spyridon Mourtzinis, Anthony Justin Mcmechan, Gabriela Inveninato Carmona, Bruce D. Potter, Kelley J. Tilmon, Louis S. Hesler, Nicholas J. Seiter, Robert Wright, Shannon L. Osborne, Thomas E. Hunt, Shawn P. Conley May 2024

Cereal Rye Cover Crop Termination At Or Before Soybean Planting Has Minimal Effect On Soybean Yield Across The Midwestern Us, Tatiane Severo Silva, Spyridon Mourtzinis, Anthony Justin Mcmechan, Gabriela Inveninato Carmona, Bruce D. Potter, Kelley J. Tilmon, Louis S. Hesler, Nicholas J. Seiter, Robert Wright, Shannon L. Osborne, Thomas E. Hunt, Shawn P. Conley

Department of Entomology: Faculty Publications

Context: Interest is growing among farmers in the Midwestern US region in the potential benefits of establishing cereal rye (Secale cereale L.) as a cover crop. However, they are concerned about the implications and potential trade-offs due to this practice. Objective: We aimed to evaluate the effects of cereal rye cover crop termination at or before soybean planting on soybean (Glycine max [L.] Merr.) seed yield. Methods: Field experiments were conducted from 2019 to 2021 across 28 location-years in the Midwestern US. Treatments consisted of no cereal rye, cereal rye termination before soybean planting, and termination at planting. …


Delivering Crispr To The Hiv-1 Reservoirs, Theodore Gurrola, Samuel Effah, Ilker Sariyer, Will Dampier, Michael Nonnemacher, Brian Wigdahl May 2024

Delivering Crispr To The Hiv-1 Reservoirs, Theodore Gurrola, Samuel Effah, Ilker Sariyer, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) infection is well known as one of the most complex and difficult viral infections to cure. The difficulty in developing curative strategies arises in large part from the development of latent viral reservoirs (LVRs) within anatomical and cellular compartments of a host. The clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9 (CRISPR/Cas9) system shows remarkable potential for the inactivation and/or elimination of integrated proviral DNA within host cells, however, delivery of the CRISPR/Cas9 system to infected cells is still a challenge. In this review, the main factors impacting delivery, the challenges for delivery …


Maturation Of An Off-Channel Habitat Concept To Conserve Native Fishes In The Lower Colorado River, Paul C. Marsh, Thomas E. Dowling, Thomas F. Turner, Megan J. Osborne, Brian R. Kesner May 2024

Maturation Of An Off-Channel Habitat Concept To Conserve Native Fishes In The Lower Colorado River, Paul C. Marsh, Thomas E. Dowling, Thomas F. Turner, Megan J. Osborne, Brian R. Kesner

Monographs of the Western North American Naturalist

Two endemic, “large river” fishes of the Colorado River basin of western North America, bonytail Gila elegans and razorback sucker Xyrauchen texanus, are among several critically endangered species in the system. Wild populations of bonytail are gone, and there are no self-sustaining populations of razorback sucker anywhere; reproduction occurs but recruitment does not. Both species have been under intensive management in the Lower Colorado River since the 1980s. Today, with the single exception of Lake Mead, remaining populations are composed entirely of repatriated individuals that depend on stocking for their continued existence. In 2003, a conceptual off-channel habitat (OCH) …


On-Farm Hog Processing Demonstration For Teenage Exhibitors: Blending Academic, Laboratory, And Farm-Based Learning, Katherine A. Wells, Chris L. Bruynis, Lyda G. Garcia May 2024

On-Farm Hog Processing Demonstration For Teenage Exhibitors: Blending Academic, Laboratory, And Farm-Based Learning, Katherine A. Wells, Chris L. Bruynis, Lyda G. Garcia

Journal of Extension

COVID-19 challenges induced a U.S. meatpacking industry bottleneck. [University] Extension identified the need and responded by creating a three-step hands-on training for teenage junior fair exhibitors. [University] Extension Meat Scientist and graduate students assisted in demonstrating an on-farm hog harvest and processing event in collaboration with a local Extension office for 4-H and FFA teenagers. To add a practical perspective, a local hog-producing and harvesting family was asked to assist with the event. An online post-survey reflected 90-100% gains in five educational areas and 100% said they would a similar event in the future and recommend it to a friend.


An Evaluation Of A Cooperative Extension Internship Program, Lisa Ellis Mccormick, Karen A. Vines, Subrato Kumar Kuri May 2024

An Evaluation Of A Cooperative Extension Internship Program, Lisa Ellis Mccormick, Karen A. Vines, Subrato Kumar Kuri

Journal of Extension

The purpose of this project was to evaluate the Virginia Cooperative Extension internship program from the perspective of student participants and their supervisors. Three focus groups were conducted with internship supervisors from the summer of 2019. Student survey data was used to identify concerns from the student perspective to inform the supervisor focus group questions. In addition to the questions, a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was also used to collect qualitative data within the supervisor focus groups. Findings suggest areas of strength that can be used in marketing as well as opportunities for program improvement.


Teens Teach Nutrition Virtually To Youth During Covid-19: Improved Leadership Skills And Health Behaviors, Wendy S. Wolfe, Jacqueline Davis-Manigaulte, Dana M. Wheeler, Emma R. Dhimitri, Josie G. Ford, Kieu A. Phan, Dylan G. Ratnarajah May 2024

Teens Teach Nutrition Virtually To Youth During Covid-19: Improved Leadership Skills And Health Behaviors, Wendy S. Wolfe, Jacqueline Davis-Manigaulte, Dana M. Wheeler, Emma R. Dhimitri, Josie G. Ford, Kieu A. Phan, Dylan G. Ratnarajah

Journal of Extension

The Choose Health Action Teens (CHAT) program of Cornell Cooperative Extension engages teens to teach a nutrition curriculum to younger youth, with the goal of enhancing the leadership skills and health behaviors of the teen teachers. Due to COVID-19, an in-person CHAT program in New York City was converted to virtual and implemented online during Summer 2020. Twelve teens, mentored by eight college interns, taught youth virtually in their homes. Quantitative and qualitative assessments demonstrated improvement in teen leadership and facilitation skills and health behaviors, and suggest that converting this type of programming to a virtual environment can be successful.


Designing Future Agriculture: Design For Complex Systems And Cross-Cultural Interactions, Karina Madzari May 2024

Designing Future Agriculture: Design For Complex Systems And Cross-Cultural Interactions, Karina Madzari

Dartmouth College Master’s Theses

Climate change is now recognized by businesses as a major challenge, prompting the agribusiness sector to transform to meet sustainability goals. However, there are many ways to achieve sustainability. Precision agriculture and agroecology are two concepts that evolved from conventional and regenerative approaches respectively, and offer distinct perspectives on sustainability attainment. Precision agriculture relies on technological solutions like artificial intelligence (AI), robotics, gene editing, and carbon dioxide removal technologies (CDR) and aims to revolutionize industry operations through automatization. Agroecology, on the other hand, creates a symbiotic relationship between farming practices and ecosystem services. It aims to replace non-renewable resources with …


College Students’ Domestic Kitchen Food Safety Perceptions And Knowledge, Kailing Chen, Zhihong Lin, Isabelle Do Prado, Zahra Mohammad, Karla M. Acosta, Sujata A. Sirsat May 2024

College Students’ Domestic Kitchen Food Safety Perceptions And Knowledge, Kailing Chen, Zhihong Lin, Isabelle Do Prado, Zahra Mohammad, Karla M. Acosta, Sujata A. Sirsat

Journal of Extension

This study investigates college students’ current food safety knowledge and food-handling perceptions and utilized an online survey which designed based on previous studies as method. The questionnaire measured respondents’ food safety knowledge and perception, and were divided into knowledge, attitudes and perception categories. The results show that college students significantly lacked in basic food safety knowledge as well as food handling skills and implies a high need to develop enhanced food safety resources for college students, especially on topics related to cross-contamination prevention, correct food preparation procedures, time and temperature control, and awareness of pathogens that cause foodborne illness.


Differences Between Acute Embolic And Atherosclerotic Middle Cerebral Artery Occlusion In Multiphase Arterial Spin-Labeling Imaging, Yasuhiro Ito, Taku Sugiyama, Shunsuke Terasaka, Hitoshi Matsuzawa, Kuniaki Harada, Masaki Ito, Miki Fujimura May 2024

Differences Between Acute Embolic And Atherosclerotic Middle Cerebral Artery Occlusion In Multiphase Arterial Spin-Labeling Imaging, Yasuhiro Ito, Taku Sugiyama, Shunsuke Terasaka, Hitoshi Matsuzawa, Kuniaki Harada, Masaki Ito, Miki Fujimura

Faculty, Staff and Student Publications

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) …


Heterogeneous Profile Of Ror1 Protein Expression Across Tumor Types, Maria Gabriela Raso, Elizve Barrientos Toro, Kurt Evans, Yasmeen Rizvi, Rossana Lazcano, Patrizia Sini, Eva Johanna Madlener, Lorenz Waldmeier, Alexander Lazar, Funda Meric-Bernstam May 2024

Heterogeneous Profile Of Ror1 Protein Expression Across Tumor Types, Maria Gabriela Raso, Elizve Barrientos Toro, Kurt Evans, Yasmeen Rizvi, Rossana Lazcano, Patrizia Sini, Eva Johanna Madlener, Lorenz Waldmeier, Alexander Lazar, Funda Meric-Bernstam

Faculty, Staff and Student Publications

The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 …


Ataxia-Telangiectasia Mutated Loss-Of-Function Displays Variant And Tissue-Specific Differences Across Tumor Types, Patrick G Pilié, Virginia Giuliani, Wei-Lien Wang, Daniel J Mcgrail, Christopher A Bristow, Keith Kyewalabye, Hung Le, Erick Campbell, Nora S Sanchez, Dong Yang, Jinesh S Gheeya, Rohit Vivek Goswamy, Vijaykumar Holla, Kenna Rael Shaw, Funda Meric-Bernstam, Chiu-Yi Liu, Xiaoyan Ma, Ningping Feng, Annette A Machado, Jennifer P Bardenhagen, Christopher P Vellano, Joseph R Marszalek, Eeson Rajendra, Desiree Piscitello, Timothy I Johnson, Maria Likhatcheva, Elias Elinati, Jayesh Majithiya, Joana Neves, Vera Grinkevich, Marco Ranzani, Marina Roy Luzarraga, Marie Boursier, Lucy Armstrong, Lerin Geo, Giorgia Lillo, Wai Yiu Tse, Alexander J Lazar, Scott E Kopetz, Mary K Geck Do, Sarah Lively, Michael G Johnson, Helen M R Robinson, Graeme C M Smith, Christopher L Carroll, M Emilia Di Francesco, Philip Jones, Timothy P Heffernan, Timothy A Yap May 2024

Ataxia-Telangiectasia Mutated Loss-Of-Function Displays Variant And Tissue-Specific Differences Across Tumor Types, Patrick G Pilié, Virginia Giuliani, Wei-Lien Wang, Daniel J Mcgrail, Christopher A Bristow, Keith Kyewalabye, Hung Le, Erick Campbell, Nora S Sanchez, Dong Yang, Jinesh S Gheeya, Rohit Vivek Goswamy, Vijaykumar Holla, Kenna Rael Shaw, Funda Meric-Bernstam, Chiu-Yi Liu, Xiaoyan Ma, Ningping Feng, Annette A Machado, Jennifer P Bardenhagen, Christopher P Vellano, Joseph R Marszalek, Eeson Rajendra, Desiree Piscitello, Timothy I Johnson, Maria Likhatcheva, Elias Elinati, Jayesh Majithiya, Joana Neves, Vera Grinkevich, Marco Ranzani, Marina Roy Luzarraga, Marie Boursier, Lucy Armstrong, Lerin Geo, Giorgia Lillo, Wai Yiu Tse, Alexander J Lazar, Scott E Kopetz, Mary K Geck Do, Sarah Lively, Michael G Johnson, Helen M R Robinson, Graeme C M Smith, Christopher L Carroll, M Emilia Di Francesco, Philip Jones, Timothy P Heffernan, Timothy A Yap

Faculty, Staff and Student Publications

PURPOSE: Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.

EXPERIMENTAL DESIGN: We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF …


A Gold Standard-Derived Modular Barcoding Approach To Cancer Transcriptomics, Yan Zhu, Mohamad Karim I Koleilat, Jason Roszik, Man Kam Kwong, Zhonglin Wang, Scott Kopetz May 2024

A Gold Standard-Derived Modular Barcoding Approach To Cancer Transcriptomics, Yan Zhu, Mohamad Karim I Koleilat, Jason Roszik, Man Kam Kwong, Zhonglin Wang, Scott Kopetz

Faculty, Staff and Student Publications

A challenge with studying cancer transcriptomes is in distilling the wealth of information down into manageable portions of information. In this resource, we develop an approach that creates and assembles cancer type-specific gene expression modules into flexible barcodes, allowing for adaptation to a wide variety of uses. Specifically, we propose that modules derived organically from high-quality gold standards such as The Cancer Genome Atlas (TCGA) can accurately capture and describe functionally related genes that are relevant to specific cancer types. We show that such modules can: (1) uncover novel gene relationships and nominate new functional memberships, (2) improve and speed …


Ire1Α Determines Ferroptosis Sensitivity Through Regulation Of Glutathione Synthesis, Dadi Jiang, Youming Guo, Tianyu Wang, Liang Wang, Yuelong Yan, Rakesh Bam, Hyemin Lee, Takao Iwawaki, Boyi Gan, Albert C Koong May 2024

Ire1Α Determines Ferroptosis Sensitivity Through Regulation Of Glutathione Synthesis, Dadi Jiang, Youming Guo, Tianyu Wang, Liang Wang, Yuelong Yan, Rakesh Bam, Hyemin Lee, Takao Iwawaki, Boyi Gan, Albert C Koong

Faculty, Staff and Student Publications

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is …


Accelerated Somatic Mutation Calling For Whole-Genome And Whole-Exome Sequencing Data From Heterogenous Tumor Samples, Shuangxi Ji, Tong Zhu, Ankit Sethia, Wenyi Wang May 2024

Accelerated Somatic Mutation Calling For Whole-Genome And Whole-Exome Sequencing Data From Heterogenous Tumor Samples, Shuangxi Ji, Tong Zhu, Ankit Sethia, Wenyi Wang

Faculty, Staff and Student Publications

Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenges were overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE 2, powered by multistep parallelization and efficient memory allocation, to resolve the computing time bottleneck. MuSE 2 speeds up 50 times more than MuSE 1 and eight to 80 times more than other popular callers. Our benchmark study suggests combining MuSE 2 and the recently accelerated Strelka2 achieves high efficiency and accuracy in analyzing …


Transcriptomic Profiling Of Plasma Extracellular Vesicles Enables Reliable Annotation Of The Cancer-Specific Transcriptome And Molecular Subtype, Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Jason T Henry, Bret M Stephens, Sarah Dhebat, Mark W Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A Guerrero May 2024

Transcriptomic Profiling Of Plasma Extracellular Vesicles Enables Reliable Annotation Of The Cancer-Specific Transcriptome And Molecular Subtype, Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Jason T Henry, Bret M Stephens, Sarah Dhebat, Mark W Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A Guerrero

Faculty, Staff and Student Publications

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach …


The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Jon Wisler, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman May 2024

The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Jon Wisler, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman

Faculty, Staff and Student Publications

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse …


Targeting Ccl2/Ccr2 Signaling Overcomes Mek Inhibitor Resistance In Acute Myeloid Leukemia, Rucha V Modak, Katia G De Oliveira Rebola, John Mcclatchy, Mona Mohammadhosseini, Alisa Damnernsawad, Christopher A Eide, Ted Laderas, Tamilla Nechiporuk, Marina A Gritsenko, Joshua R Hansen, Chelsea Hutchinson, Sara J C Gosline, Paul Piehowski, Daniel Bottomly, Nicholas Short, Karin Rodland, Shannon K Mcweeney, Jeffrey W Tyner, Anupriya Agarwal May 2024

Targeting Ccl2/Ccr2 Signaling Overcomes Mek Inhibitor Resistance In Acute Myeloid Leukemia, Rucha V Modak, Katia G De Oliveira Rebola, John Mcclatchy, Mona Mohammadhosseini, Alisa Damnernsawad, Christopher A Eide, Ted Laderas, Tamilla Nechiporuk, Marina A Gritsenko, Joshua R Hansen, Chelsea Hutchinson, Sara J C Gosline, Paul Piehowski, Daniel Bottomly, Nicholas Short, Karin Rodland, Shannon K Mcweeney, Jeffrey W Tyner, Anupriya Agarwal

Faculty, Staff and Student Publications

Purpose: Emerging evidence underscores the critical role of extrinsic factors within the microenvironment in protecting leukemia cells from therapeutic interventions, driving disease progression, and promoting drug resistance in acute myeloid leukemia (AML). This finding emphasizes the need for the identification of targeted therapies that inhibit intrinsic and extrinsic signaling to overcome drug resistance in AML.

Experimental design: We performed a comprehensive analysis utilizing a cohort of ∼300 AML patient samples. This analysis encompassed the evaluation of secreted cytokines/growth factors, gene expression, and ex vivo drug sensitivity to small molecules. Our investigation pinpointed a notable association between elevated levels of CCL2 …