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The Role Of The British Grassland Society In Technology Transfer, J. M. Crichton Aug 2023

The Role Of The British Grassland Society In Technology Transfer, J. M. Crichton

IGC Proceedings (1977-2023)

Since its formation in 1945, the British Grassland Society (BGS) has been active in disseminating information to the grassland and associated sectors of agriculture and has adapted to a change from production-based agriculture to its current output mix of private and public goods. The BGS has as its remit: (a) improved production and utilisation of grass and forage crops for the promotion of agriculture and the public benefit, and (b) the advancement of education and research in grass and forage crop production and utilisation, and the publication of results.


Moving Lab-Based In-Person Training To Online Delivery: The Case Of A Continuing Engineering Education Program, Catherine Maware, David M. Parsley Ii, Kun Huang, Gerry M. Swan, Nelson Akafuah Aug 2023

Moving Lab-Based In-Person Training To Online Delivery: The Case Of A Continuing Engineering Education Program, Catherine Maware, David M. Parsley Ii, Kun Huang, Gerry M. Swan, Nelson Akafuah

Institute of Research for Technology Development Faculty Publications

Background: Online learning has recently surged due to the COVID-19 global pandemic. Because of the pandemic, many universities were forced to move to online learning, and various online teaching and learning environments emerged, both asynchronous and synchronous.

Objective: This study explores how a large university in the Southeastern United States of America converted an in-person Lean Manufacturing professional course into synchronous online learning for industry participants.

Method: The study analysed the performance of 212 in-person and 43 online industry participants and examined the views of online participants about the training. Paired t-tests, one-way multivariate analysis of covariance (MANCOVA), and univariate …


Activation Of The Renin–Angiotensin–Aldosterone System Is Attenuated In Hypertensive Compared With Normotensive Pregnancy, Robin C. Shoemaker, Marko Poglitsch, Hong Huang, Katherine Vignes, Aarthi Srinivasan, Cynthia Cockerham-Morris, Aric Schadler, John Anthony Bauer, John O'Brien Aug 2023

Activation Of The Renin–Angiotensin–Aldosterone System Is Attenuated In Hypertensive Compared With Normotensive Pregnancy, Robin C. Shoemaker, Marko Poglitsch, Hong Huang, Katherine Vignes, Aarthi Srinivasan, Cynthia Cockerham-Morris, Aric Schadler, John Anthony Bauer, John O'Brien

UK CARES Faculty Publications

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin–angiotensin–aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development …


Assessment Of Land And Renewable Energy Resource Potential For Regional Power System Integration With Ml Spatio-Temporal Clustering, Rosemary E. Alden, Claire Halloran, Donovin D. Lewis, Dan M. Ionel Aug 2023

Assessment Of Land And Renewable Energy Resource Potential For Regional Power System Integration With Ml Spatio-Temporal Clustering, Rosemary E. Alden, Claire Halloran, Donovin D. Lewis, Dan M. Ionel

Electrical and Computer Engineering Graduate Research

Toward the planning and development of future electric power systems with extremely large penetration of renewable resources (DERs), detailed assessment of power and energy potential is needed considering both spatial and temporal data per region. Within this paper, a methodology for spatio-temporal DER capacity potential considering land cover types and weather variation are presented using spatio-temporal data. Additionally, an application of empirical orthogonal functions (EOFs) and max-p unsupervised learning techniques is proposed for DER generation to identify zones of similar output power in space and time. A detailed case study for the example region of Kentucky, USA is completed with …


Exposure To A Phthalate Mixture Disrupts Ovulatory Progesterone Receptor Signaling In Human Granulosa Cells In Vitro, Patrick R. Hannon, James W. Akin, Thomas E. Curry Jr Aug 2023

Exposure To A Phthalate Mixture Disrupts Ovulatory Progesterone Receptor Signaling In Human Granulosa Cells In Vitro, Patrick R. Hannon, James W. Akin, Thomas E. Curry Jr

UK CARES Faculty Publications

Exposure to phthalates disrupts ovarian function. However, limited studies have investigated the effects of phthalate mixtures on ovulation, especially in women. Human granulosa cells were used to test the hypothesis that exposure to a phthalate mixture (PHTmix) disrupts progesterone (P4)/progesterone receptor (PGR) signaling, which is a crucial pathway for ovulation. In addition, progestin and cyclic adenosine 3′, 5′-monophosphate (cAMP) supplementation were tested as methods to circumvent phthalate toxicity. Granulosa cells from women undergoing in vitro fertilization were acclimated in culture to regain responsiveness to human chorionic gonadotropin (hCG; clinical luteinizing hormone analogue). Granulosa cells were treated with or without hCG, …


Fear Of Sin And Fear Of God: Scrupulosity Predicts Women's Daily Experiences Of Mental Contamination Following Sexual Trauma, Alyssa C. Jones, Jordyn M. Tipsword, C. Alex Brake, Emily E. Fenlon, Thomas G. Adams Jr., Jesse P. Mccann, Christal L. Badour Aug 2023

Fear Of Sin And Fear Of God: Scrupulosity Predicts Women's Daily Experiences Of Mental Contamination Following Sexual Trauma, Alyssa C. Jones, Jordyn M. Tipsword, C. Alex Brake, Emily E. Fenlon, Thomas G. Adams Jr., Jesse P. Mccann, Christal L. Badour

UK CARES Faculty Publications

Mental contamination refers to feelings of dirtiness in response to thoughts, images, or memories. Mental contamination is frequently reported after sexual trauma and is associated with symptoms of posttraumatic stress disorder (PTSD). Differences in individuals’ views about morality and purity may influence the severity of mental contamination, though this has been studied primarily outside of samples assessed for trauma and/or PTSD. The present study addressed this gap by investigating scrupulosity as a prospective predictor of daily sexual trauma–related mental contamination and PTSD symptoms. Participants included 40 adult women with a history of sexual trauma and current sexual trauma–related mental contamination …


Histamine Excretion In Common Indoor And Hematophagous Arthropods, Simona Principato, Alvaro Romero, Chow-Yang Lee, Kathleen Campbell, Dong-Hwan Choe, Coby Schal, Zachary C. Devries Aug 2023

Histamine Excretion In Common Indoor And Hematophagous Arthropods, Simona Principato, Alvaro Romero, Chow-Yang Lee, Kathleen Campbell, Dong-Hwan Choe, Coby Schal, Zachary C. Devries

UK CARES Faculty Publications

Histamine is a biogenic amine that regulates multiple physiological functions in diverse organisms, specifically playing a central role in the mammalian immune response. The common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), excretes histamine in large amounts in its feces as a component of its aggregation pheromone, which contaminates homes. The potential health risks associated with the presence of indoor histamine are unclear, but to predict future exposure risks, it is critical that we understand if other arthropods excrete histamine in any discernible phylogenetic pattern. In the present study, we evaluated histamine excretion by various arthropods; specifically those commonly found …


Association Of Sustained Low Or High Income And Income Changes With Risk Of Incident Type 2 Diabetes Among Individuals Aged 30 To 64 Years, Jimin Clara Park, Ga Eun Nam, Jinna Yu, Ketrell L. Mcwhorter, Junxiu Liu, Hong Seok Lee, Seong-Su Lee, Kyungdo Han Aug 2023

Association Of Sustained Low Or High Income And Income Changes With Risk Of Incident Type 2 Diabetes Among Individuals Aged 30 To 64 Years, Jimin Clara Park, Ga Eun Nam, Jinna Yu, Ketrell L. Mcwhorter, Junxiu Liu, Hong Seok Lee, Seong-Su Lee, Kyungdo Han

UK CARES Faculty Publications

IMPORTANCE Evidence of the association between income fluctuation and risk of type 2 diabetes (T2D) is scarce.

OBJECTIVE To investigate whether sustained low or high income and income changes are associated with incidence of T2D.

DESIGN, SETTING, AND PARTICIPANTS In this population-based cohort study, more than 7.8 million adults without T2D aged 30 to 64 years from a nationally representative sample from the Korean Health Insurance Service database were enrolled in 2012 and followed up to 2019 (median follow-up, 6.3 years [IQR, 6.1-6.6 years]).

EXPOSURES Twenty quantiles of monthly health insurance premiums determined income levels. Income quartiles were annually analyzed …


Friction And Texture Equipment Correlation Study, David Hacker, Kean H. Ashurst Jr., Clark Graves Aug 2023

Friction And Texture Equipment Correlation Study, David Hacker, Kean H. Ashurst Jr., Clark Graves

Kentucky Transportation Center Research Report

The Kentucky Transportation Cabinet’s (KYTC) foremost goal is building and maintaining a safe road network. To accomplish this goal, KYTC needs reliable pavement friction and macrotexture data, both of which influence road performance and safety. KYTC currently measures fiction using a lock-wheel skid tester (AASHTO T 242), however, the agency has not been able to collect data at the network level due to equipment and personnel limitations. In 2020 the Cabinet commissioned a study to collect friction and macrotexture data. Investigators used a sideway-force coefficient routine investigation machine (SCRIM) (AASHTO TP 143) to measure friction. To understand the performance of …


Combined Behavioral And Engineering Approach To Preventing Highway Fatalities, Benjamin Blandford, Reginald Souleyrette, Caitlin N. Pope, Tony Fields, Erin Lammers-Staats Aug 2023

Combined Behavioral And Engineering Approach To Preventing Highway Fatalities, Benjamin Blandford, Reginald Souleyrette, Caitlin N. Pope, Tony Fields, Erin Lammers-Staats

Kentucky Transportation Center Research Report

Traditional, single-discipline highway safety approaches can be augmented through multidisciplinary approaches that consider both engineering and behavioral interventions (e.g., education, enforcement, public outreach campaigns). Leveraging a systems-based conceptual framework of roadway safety, multiple forms of statistical and geospatial analysis, and SPF modeling and network screening, this report proposes and demonstrates methods for unpacking the influence of behavioral-related factors on crash occurrences and outcomes. The primary focus is on behaviors targeted in the Strategic Highway Safety Plan — aggressive driving, distracted driving, impaired driving, and driving without proper restraint (i.e., seatbelts). Based on application of these methods, the report highlights areas …


Evaluating The Use Of A Near-Miss Reporting Program To Enhance Employee Safety Performance, Gabriel Dadi, Farshid Taherpour, Seth Atkins, Ashtarout Ammar, Jon Wilcoxson Aug 2023

Evaluating The Use Of A Near-Miss Reporting Program To Enhance Employee Safety Performance, Gabriel Dadi, Farshid Taherpour, Seth Atkins, Ashtarout Ammar, Jon Wilcoxson

Kentucky Transportation Center Research Report

Using safety incidents and crashes to improve safety performance is an outdated and reactive practice in safety and health programs. One component of a modern approach to safety is a near-miss reporting program. This type of program tracks close calls or near misses that do not result in an incident or crash, but which often can be an early indicator that one may happen. While most construction companies have implemented some methods for reporting near-miss events, many agencies, such as the Kentucky Transportation Cabinet (KYTC), struggle getting employees to report near misses. To fill this gap, potential factors that result …


Innovative Methods To Strengthen Internal Kytc Communications, P. Gayle Marks, Jeff Jasper Aug 2023

Innovative Methods To Strengthen Internal Kytc Communications, P. Gayle Marks, Jeff Jasper

Kentucky Transportation Center Research Report

Communication is the linchpin of every organization. Poor communication leads to inefficiencies, frustration among staff, and employee disaffection and disengagement. Although some state transportation agencies have adopted comprehensive strategic plans for internal communications, many have taken a more piecemeal approach, with some Offices and units (e.g., incident management) developing their own plans that apply only to their operations. The latter approach is less than ideal because establishing a comprehensive communications plan provides an organizing framework for all communications within an organization and is critical for uniting staff around a shared sense of purpose and equipping them with the tools they …


Facilitated Identification Of Kytc Performance Measures, Candice Wallace, Jon Wilcoxson Aug 2023

Facilitated Identification Of Kytc Performance Measures, Candice Wallace, Jon Wilcoxson

Kentucky Transportation Center Research Report

Federal and state government agencies are embracing performance management as a means to (1) justify the use of tax dollars and (2) monitor and report program accomplishments. The Kentucky Transportation Cabinet’s (KYTC) efforts to fold Transportation Performance Management (TPM) into its business processes and workplace culture required training that would educate personnel about TPM’s benefits, objectives, and activities. After reviewing training resources on performance management from FHWA, NHI, AASHTO, and state DOTs, Cabinet leadership concluded that their emphasis on federal requirements was not exactly what KYTC was looking for in a training program. Instead, KYTC wanted a training program that …


Exploring Food-Based Cultural Practices To Address Food Insecurity In Rural Appalachia, Lauren Cassidy Batey, Emily M. Dewitt, Dawn Brewer, Kathryn M. Cardarelli, Heather Norman-Burgdolf Aug 2023

Exploring Food-Based Cultural Practices To Address Food Insecurity In Rural Appalachia, Lauren Cassidy Batey, Emily M. Dewitt, Dawn Brewer, Kathryn M. Cardarelli, Heather Norman-Burgdolf

UK CARES Faculty Publications

Background. Health behaviors, like diet, are influenced by a person’s culture and the society where they reside, contributing to the presence of health disparities within a unique region. Such disparities are evident in Central Appalachia where a unique cultural identity exists. Culture-based initiatives focused on improving food security and other nutritional challenges have had success in other diverse groups, yet similar interventions considering geographically tied culture, like Appalachia, are limited. Aim. This study aims to identify specific aspects of Appalachian culture that address food insecurity to inform future initiatives that may improve adult dietary habits and food security status. Methods. …


Fault Tolerant Electric Machine Concept For Aircraft Propulsion With Pm Rotor And Dc Current Stator Dual-Stage Excitation, Donovin D. Lewis, Oluwaseun A. Badewa, Ali Mohammadi, Matin Vatani, Dan M. Ionel Aug 2023

Fault Tolerant Electric Machine Concept For Aircraft Propulsion With Pm Rotor And Dc Current Stator Dual-Stage Excitation, Donovin D. Lewis, Oluwaseun A. Badewa, Ali Mohammadi, Matin Vatani, Dan M. Ionel

Electrical and Computer Engineering Graduate Research

The development of electrically propelled aircraft requires electric machines that are fault-tolerant, compact, and efficient at multiple operating points. This paper proposes a novel machine topology combining a coreless Halbach PM array axial flux unit and a PM-less synchronous hybrid excited radial flux unit. Both units are coupled on the same shaft to take advantage of the opportunities available in the unique usage profile for aviation. The machines can be used simultaneously for the take off and altitude climbing stage or used individually during the cruising stage. The coreless axial flux PM (CAFPM) motor unit consists of two Halbach array …


Coreless Axial Flux Halbach Array Permanent Magnet Generator Concept For Direct-Drive Wind Turbine, Matin Vatani, Ali Mohammadi, Donovin Lewis, John F. Eastham, Dan M. Ionel Aug 2023

Coreless Axial Flux Halbach Array Permanent Magnet Generator Concept For Direct-Drive Wind Turbine, Matin Vatani, Ali Mohammadi, Donovin Lewis, John F. Eastham, Dan M. Ionel

Electrical and Computer Engineering Graduate Research

This paper proposes a concept for a coreless axial flux permanent magnet (CAFPM) generator with a double sided Halbach array rotor for direct-drive offshore wind turbine applications. The application of printed circuit board (PCB) technology is explored as applied to a concentrated winding stator due to its high reliability, repeatability, and fast mass production. A double-sided Halbach array rotor is employed to intensify the airgap flux density and to enable the elimination of the rotor back iron, decreasing the generator’s total active mass. The effect of the Halbach array rotor pole number and magnet-to-magnet (M2M) gap on the airgap flux …


Functional Exploration Of Conserved Sequences In The Distal Face Of Angiotensinogen - Brief Report, Naofumi Amioka, Chia-Hua Wu, Hisashi Sawada, Sohei Ito, Alex C. Pettey, Congqing Wu, Jessica J. Moorleghen, Deborah A. Howatt, Gregory A. Graf, Craig W. Vander Kooi, Alan Daugherty, Hong S. Lu Aug 2023

Functional Exploration Of Conserved Sequences In The Distal Face Of Angiotensinogen - Brief Report, Naofumi Amioka, Chia-Hua Wu, Hisashi Sawada, Sohei Ito, Alex C. Pettey, Congqing Wu, Jessica J. Moorleghen, Deborah A. Howatt, Gregory A. Graf, Craig W. Vander Kooi, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Angiotensinogen (AGT) is an essential component in the renin-angiotensin system. AGT has highly conserved sequences in the loop and β-sheet regions among species; however, their functions have not been studied.

METHODS: Adeno-associated viral vector (AAV) serotype 2/8 encoding mouse AGT with mutations of conserved sequences in the loop (AAV.loop-Mut), β-sheet (AAV.βsheet-Mut), or both regions (AAV.loop/βsheet-Mut) was injected into male hepatocyte-specific AGT-deficient (hepAGT−/− ) mice in an LDL (low-density lipoprotein) receptor–deficient background. AAV containing mouse wild-type AGT (AAV.mAGT) or a null vector (AAV.null) were used as controls. Two weeks after AAV administration, all mice were fed a western diet for …


Fructose Induced Khk-C Can Increase Er Stress Independent Of Its Effect On Lipogenesis To Drive Liver Disease In Diet-Induced And Genetic Models Of Nafld, Se-Hyung Park, Robert N. Helsley, Taghreed Fadhul, Jennifer L. S. Willoughby, Leila Noetzli, Ho-Chou Tu, Marie H. Solheim, Shiho Fujisaka, Hui Pan, Jonathan M. Dreyfuss, Joanna Bons, Jacob Rose, Christina D. King, Birgit Schilling, Aldons J. Lusis, Calvin Pan, Manoj Gupta, Rohit N. Kulkarni, Kevin Fitzgerald, Philip A. Kern, Senad Divanovic, C. Ronald Kahn, Samir Softic Aug 2023

Fructose Induced Khk-C Can Increase Er Stress Independent Of Its Effect On Lipogenesis To Drive Liver Disease In Diet-Induced And Genetic Models Of Nafld, Se-Hyung Park, Robert N. Helsley, Taghreed Fadhul, Jennifer L. S. Willoughby, Leila Noetzli, Ho-Chou Tu, Marie H. Solheim, Shiho Fujisaka, Hui Pan, Jonathan M. Dreyfuss, Joanna Bons, Jacob Rose, Christina D. King, Birgit Schilling, Aldons J. Lusis, Calvin Pan, Manoj Gupta, Rohit N. Kulkarni, Kevin Fitzgerald, Philip A. Kern, Senad Divanovic, C. Ronald Kahn, Samir Softic

Saha Cardiovascular Research Center Faculty Publications

Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform leads to unresolved endoplasmic reticulum (ER) stress when coupled with a HFD intake. Conversely, a liver-specific knockdown of KHK in mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and …


Assessing Hip Joint–Related Structure And Patient-Reported Outcomes In People With Marfan Syndrome, Ziyu Zhang, Wen Dai, Wen Zhu, Maya Rodriguez, Hayley Lund, Yuhe Xia, Yiliang Chen, Mary Rau, Ellen Anje Schneider, Mary Beth Graham, Shawn Jobe, Demin Wang, Weiguo Cui, Renren Wen, Sidney W. Whiteheart, Jeremy P. Wood, Roy Silverstein, Jeffery S. Berger, Lisa Baumann Kreuziger, Tessa J. Barrett, Ze Zheng Aug 2023

Assessing Hip Joint–Related Structure And Patient-Reported Outcomes In People With Marfan Syndrome, Ziyu Zhang, Wen Dai, Wen Zhu, Maya Rodriguez, Hayley Lund, Yuhe Xia, Yiliang Chen, Mary Rau, Ellen Anje Schneider, Mary Beth Graham, Shawn Jobe, Demin Wang, Weiguo Cui, Renren Wen, Sidney W. Whiteheart, Jeremy P. Wood, Roy Silverstein, Jeffery S. Berger, Lisa Baumann Kreuziger, Tessa J. Barrett, Ze Zheng

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown.

Objectives: To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how …


Asparagine Restriction Enhances Cd8+ T Cell Metabolic Fitness And Antitumoral Functionality Through An Nrf2-Dependent Stress Response, J. N. Rashida Gnanaprakasam, Bhavana Kushwaha, Lingling Liu, Xuyong Chen, Siwen Kang, Tingting Wang, Teresa A. Cassel, Christopher M. Adams, Richard M. Higashi, David A. Scott, Gang Xin, Zihai Li, Jun Yang, Andrew N. Lane, Teresa Whei-Mei Fan, Ji Zhang, Ruoning Wang Aug 2023

Asparagine Restriction Enhances Cd8+ T Cell Metabolic Fitness And Antitumoral Functionality Through An Nrf2-Dependent Stress Response, J. N. Rashida Gnanaprakasam, Bhavana Kushwaha, Lingling Liu, Xuyong Chen, Siwen Kang, Tingting Wang, Teresa A. Cassel, Christopher M. Adams, Richard M. Higashi, David A. Scott, Gang Xin, Zihai Li, Jun Yang, Andrew N. Lane, Teresa Whei-Mei Fan, Ji Zhang, Ruoning Wang

Markey Cancer Center Faculty Publications

Robust and effective T cell immune surveillance and cancer immunotherapy require proper allocation of metabolic resources to sustain energetically costly processes, including growth and cytokine production. Here, we show that asparagine (Asn) restriction on CD8+ T cells exerted opposing effects during activation (early phase) and differentiation (late phase) following T cell activation. Asn restriction suppressed activation and cell cycle entry in the early phase while rapidly engaging the nuclear factor erythroid 2-related factor 2 (NRF2)-dependent stress response, conferring robust proliferation and effector function on CD8+ T cells during differentiation. Mechanistically, NRF2 activation in CD8+ T cells conferred by Asn restriction …


Chemokine Receptor Cxcr7 Activates Aurora Kinase A And Promotes Neuroendocrine Prostate Cancer Growth, Galina Gritsina, Ka-Wing Fong, Xiaodong Lu, Zhuoyuan Lin, Wanqing Xie, Shivani Agarwal, Dong Lin, Gary E. Schiltz, Himisha Beltran, Eva Corey, Colm Morrissey, Yuzhuo Wang, Jonathan C. Zhao, Maha Hussain, Jindan Yu Aug 2023

Chemokine Receptor Cxcr7 Activates Aurora Kinase A And Promotes Neuroendocrine Prostate Cancer Growth, Galina Gritsina, Ka-Wing Fong, Xiaodong Lu, Zhuoyuan Lin, Wanqing Xie, Shivani Agarwal, Dong Lin, Gary E. Schiltz, Himisha Beltran, Eva Corey, Colm Morrissey, Yuzhuo Wang, Jonathan C. Zhao, Maha Hussain, Jindan Yu

Markey Cancer Center Faculty Publications

CXCR7 is an atypical chemokine receptor that recruits β-arrestin (ARRB2) and internalizes into clathrin-coated intracellular vesicles where the complex acts as a scaffold for cytoplasmic kinase assembly and signal transduction. Here, we report that CXCR7 was elevated in the majority of prostate cancer (PCa) cases with neuroendocrine features (NEPC). CXCR7 markedly induced mitotic spindle and cell cycle gene expression. Mechanistically, we identified Aurora Kinase A (AURKA), a key regulator of mitosis, as a novel target that was bound and activated by the CXCR7-ARRB2 complex. CXCR7 interacted with proteins associated with microtubules and golgi, and, as such, the CXCR7-ARRB2-containing vesicles trafficked …


Chronic Nsmase Inhibition Suppresses Neuronal Exosome Spreading And Sex-Specifically Attenuates Amyloid Pathology In App Knock-In Alzheimer's Disease Mice, Francesca E. Mowry, Francisco Espejo-Porras, Shijie Jin, Zainuddin Quadri, Limin Wu, Marcela Bertolio, Rachel Jarvis, Caroline Reynolds, Rashed Alananzeh, Erhard Bieberich, Yongjie Yang Aug 2023

Chronic Nsmase Inhibition Suppresses Neuronal Exosome Spreading And Sex-Specifically Attenuates Amyloid Pathology In App Knock-In Alzheimer's Disease Mice, Francesca E. Mowry, Francisco Espejo-Porras, Shijie Jin, Zainuddin Quadri, Limin Wu, Marcela Bertolio, Rachel Jarvis, Caroline Reynolds, Rashed Alananzeh, Erhard Bieberich, Yongjie Yang

Markey Cancer Center Faculty Publications

Female biased pathology and cognitive decline in Alzheimer’s disease (AD) have been consistently observed with unclear underlying mechanisms. Although brain sphingolipid ceramide is elevated in AD patients, whether and how ceramide may contribute to sex-specific differences in amyloid pathology is unknown. Here we investigated the sex-specific impact of chronic pharmacological inhibition of neutral sphingomyelinase (nSMase), a key enzyme responsible for ceramide metabolism, on in vivo neuron-derived exosome dynamics, Aβ plaque load, and cognitive function in the APPNL-F/NL-F knock-in (APP NL-F) AD mouse model. Our results found sex-specific increase of cortical C20:0 ceramide and brain exosome levels only in APP NL-F …


Co-Targeting Nucleus Accumbens Associate 1 And Nf-Κb Signaling Synergistically Inhibits Melanoma Growth, Lixiang Gu, Xingcong Ren, Chrispus Ngule, Xiaofang Xiong, Jianxun Song, Zhiguo Li, Jin-Ming Yang Aug 2023

Co-Targeting Nucleus Accumbens Associate 1 And Nf-Κb Signaling Synergistically Inhibits Melanoma Growth, Lixiang Gu, Xingcong Ren, Chrispus Ngule, Xiaofang Xiong, Jianxun Song, Zhiguo Li, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Nucleus-accumbens-associated protein-1 (NAC1) is a cancer-related transcriptional factor encoded by the NACC1 gene, which is amplified and overexpressed in various human cancers and has been appreciated as one of the top potential cancer driver genes. NAC1 has therefore been explored as a potential therapeutic target for managing malignant tumors. Here, we show that NAC1 is a negative regulator of NF-κB signaling, and NAC1 depletion enhances the level of the nuclear NF-κB in human melanoma. Furthermore, the inhibition of NF-κB signaling significantly potentiates the antineoplastic activity of the NAC1 inhibition in both the cultured melanoma cells and xenograft tumors. This study …


Identification Of Immunodominant T Cell Epitopes Induced By Natural Zika Virus Infection, Christopher S. Eickhoff, Krystal A. Meza, Frances E. Terry, Chase G. Colbert, Azra Blazevic, Andres H. Gutiérrez, E. Taylor Stone, James D. Brien, Amelia K. Pinto, Hana M. El Sahly, Mark J. Mulligan, Nadine Rouphael, Maria L. Alcaide, Kay M. Tomashek, Chris Focht, William D. Martin, Leonard Moise, Anne S. De Groot, Daniel F. Hoft Aug 2023

Identification Of Immunodominant T Cell Epitopes Induced By Natural Zika Virus Infection, Christopher S. Eickhoff, Krystal A. Meza, Frances E. Terry, Chase G. Colbert, Azra Blazevic, Andres H. Gutiérrez, E. Taylor Stone, James D. Brien, Amelia K. Pinto, Hana M. El Sahly, Mark J. Mulligan, Nadine Rouphael, Maria L. Alcaide, Kay M. Tomashek, Chris Focht, William D. Martin, Leonard Moise, Anne S. De Groot, Daniel F. Hoft

Markey Cancer Center Faculty Publications

Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which …


Identification Of Monotonically Expressed Long Non-Coding Rna Signatures For Breast Cancer Using Variational Autoencoders, Dongjiao Wang, Ling Gao, Xinliang Gao, Chi Wang, Suyan Tian Aug 2023

Identification Of Monotonically Expressed Long Non-Coding Rna Signatures For Breast Cancer Using Variational Autoencoders, Dongjiao Wang, Ling Gao, Xinliang Gao, Chi Wang, Suyan Tian

Markey Cancer Center Faculty Publications

As breast cancer is a multistage progression disease resulting from a genetic sequence of mutations, understanding the genes whose expression values increase or decrease monotonically across pathologic stages can provide insightful clues about how breast cancer initiates and advances. Utilizing variational autoencoder (VAE) networks in conjunction with traditional statistical testing, we successfully ascertain long non-coding RNAs (lncRNAs) that exhibit monotonically differential expression values in breast cancer. Subsequently, we validate that the identified lncRNAs really present monotonically changed patterns. The proposed procedure identified 248 monotonically decreasing expressed and 115 increasing expressed lncRNAs. They correspond to a total of 65 and 33 …


Impact Of A Cancer Education Curriculum On Appalachian Kentucky Middle And High School Students, Lauren Hudson‑Rose, L. Todd Weiss, Nathan L. Vanderford Aug 2023

Impact Of A Cancer Education Curriculum On Appalachian Kentucky Middle And High School Students, Lauren Hudson‑Rose, L. Todd Weiss, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Appalachian Kentucky is disproportionately affected by elevated cancer incidence and mortality rates. This disparity is driven by inequities in health behaviors and social determinants of health including decreased education attainment levels that cause lower health literacy. To increase cancer literacy in the region, a three-part cancer education curriculum was designed for Appalachian Kentucky middle and high school students. This study was designed to evaluate the effect the curriculum had on students’ cancer literacy. The curriculum lessons were disseminated to Appalachian Kentucky middle and high school teachers who engaged 223 students with the material. For each lesson, students filled out a …


Inhibition Of Acid Sphingomyelinase Reduces Reactive Astrocyte Secretion Of Mitotoxic Extracellular Vesicles And Improves Alzheimer’S Disease Pathology In The 5xfad Mouse, Simone M. Crivelli, Zainuddin Quadri, Hemendra J. Vekaria, Zhihui Zhu, Priyanka Tripathi, Ahmed Elsherbini, Liping Zhang, Patrick G. Sullivan, Erhard Bieberich Aug 2023

Inhibition Of Acid Sphingomyelinase Reduces Reactive Astrocyte Secretion Of Mitotoxic Extracellular Vesicles And Improves Alzheimer’S Disease Pathology In The 5xfad Mouse, Simone M. Crivelli, Zainuddin Quadri, Hemendra J. Vekaria, Zhihui Zhu, Priyanka Tripathi, Ahmed Elsherbini, Liping Zhang, Patrick G. Sullivan, Erhard Bieberich

Markey Cancer Center Faculty Publications

In Alzheimer’s disease (AD), reactive astrocytes produce extracellular vesicles (EVs) that affect mitochondria in neurons. Here, we show that Aβ-induced generation of the sphingolipid ceramide by acid sphingomyelinase (A-SMase) triggered proinflammatory cytokine (C1q, TNF-α, IL-1α) release by microglia, which induced the reactive astrocytes phenotype and secretion of EVs enriched with ceramide. These EVs impeded the capacity of neurons to respond to energy demand. Inhibition of A-SMase with Arc39 and Imipramine reduced the secretion of cytokines from microglia, prompting us to test the effect of Imipramine on EV secretion and AD pathology in the 5xFAD mouse model. Brain derived-EVs from 5xFAD …


Liver Transplantation For Biliary Cysts: Perioperative And Long-Term Outcomes, Gabriel Orozco, Malay B. Shah, Meera Gupta, Francesc Marti, Xiaonan Mei, Alexandre Ancheta, Siddharth Desai, Michael Cavnar, B. Mark Evers, Joseph B. Zwischenberger, Roberto Gedaly Aug 2023

Liver Transplantation For Biliary Cysts: Perioperative And Long-Term Outcomes, Gabriel Orozco, Malay B. Shah, Meera Gupta, Francesc Marti, Xiaonan Mei, Alexandre Ancheta, Siddharth Desai, Michael Cavnar, B. Mark Evers, Joseph B. Zwischenberger, Roberto Gedaly

Markey Cancer Center Faculty Publications

Background: Biliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT).

Methods: We queried the UNOS dataset to identify patients who underwent OLT for Caroli’s disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival.

Results: 261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and …


Metabolic Disruption Induced By Mtor Signaling Pathway Inhibition In Regulatory T-Cell Expansion For Clinical Application, Roberto Gedaly, Gabriel Orozco, Alexandre P. Ancheta, Mackenzie Donoho, Siddharth Desai, Fanny Chapelin, Aman Khurana, Lillie J. Lewis, Cuiping Zhang, Francesc Marti Aug 2023

Metabolic Disruption Induced By Mtor Signaling Pathway Inhibition In Regulatory T-Cell Expansion For Clinical Application, Roberto Gedaly, Gabriel Orozco, Alexandre P. Ancheta, Mackenzie Donoho, Siddharth Desai, Fanny Chapelin, Aman Khurana, Lillie J. Lewis, Cuiping Zhang, Francesc Marti

Markey Cancer Center Faculty Publications

Background: Regulatory T cell (Treg) therapy is considered an alternative approach to induce tolerance in transplantation. If successful, this therapy may have implications on immunosuppression minimization/withdrawal to reduce drug-induced toxicity in patients. The aim of this study was to assess the efficacy of the mTORC1/C2 inhibitor, AZD8055, in the manufacturing of clinically competent Treg cells and compare the effects with those induced by rapamycin (RAPA), another mTOR inhibitor commonly used in Treg expansion protocols.

Methods: Primary human Treg cells were isolated from leukapheresis product. Cell viability, expansion rates, suppressive function, autophagy, mitochondrial unfolded protein response (mitoUPR), and cell metabolic profile …


Pcb126 Exposure During Pregnancy Alters Maternal And Fetal Gene Expression, Cetewayo S. Rashid, Joshua D. Preston, Sara Y. Ngo Tenlep, Marissa K. Cook, Eric M. Blalock, Changcheng Zhou, Hollie I. Swanson, Kevin J. Pearson Aug 2023

Pcb126 Exposure During Pregnancy Alters Maternal And Fetal Gene Expression, Cetewayo S. Rashid, Joshua D. Preston, Sara Y. Ngo Tenlep, Marissa K. Cook, Eric M. Blalock, Changcheng Zhou, Hollie I. Swanson, Kevin J. Pearson

Markey Cancer Center Faculty Publications

Polychlorinated biphenyls (PCBs) are organic pollutants that can have lasting impacts on offspring health. Here, we sought to examine maternal and fetal gene expression differences of aryl hydrocarbon receptor (AHR)- regulated genes in a mouse model of prenatal PCB126 exposure. Female mice were bred and gavaged with 1 μmole/kg bodyweight PCB126 or vehicle control on embryonic days 0 and 14, and maternal and fetal tissues were collected on embryonic day 18.5. Total RNAs were isolated, and gene expression levels were analyzed in both maternal and fetal tissues using the NanoString nCounter system. Interestingly, we found that the expression levels of …