Digital Commons Network^™

Myh11 Rare Variant Augments Aortic Growth And Induces Cardiac Hypertrophy And Heart Failure With Pressure Overload, Zhen Zhou, Kgosi Hughes, Nisha Saif, Hyoseon Kim, Michael P Massett, Mingjie Zheng, Alana C Cecchi, Dongchuan Guo, David R Murdock, Ping Pan, Jelita S Clinton, Jun Wang, John M Greally, Dianna M Milewicz

Faculty, Staff and Student Publications

Smooth muscle cell-specific myosin heavy chain, encoded by MYH11, is selectively expressed in smooth muscle cells (SMCs). Pathogenic variants in MYH11 predispose to a number of disorders, including heritable thoracic aortic disease associated with patent ductus arteriosus, visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Rare variants of uncertain significance occur throughout the gene, including MYH11 p.Glu1892Asp, and we sought to determine if this variant causes thoracic aortic disease in mice. Genomic editing was used to generate Myh11E1892D/E1892D mice. Wild-type (WT) and mutant mice underwent cardiovascular phenotyping with and without transverse aortic constriction (TAC). Myh11E1892D/E1892D and WT mice displayed …

Diagnostic Guidance For Chronic Complex Regional Pain Syndrome Type I And Type Ii From The American Society Of Interventional Physicians (Asipp), Christopher Gharibo, Miles Day, Steve M Aydin, Alan D Kaye, Salahadin Abdi, Sudhir Diwan, Lisa V Doan, Danielle Feng, Kris Ferguson, Kirolos Georges, Andrew Kaufman, Nebojsa Nick Knezevic, Sean Li, Franzes A Liongson, Devi Nampiaparampil, Annu Navani, Mahendra Sanapati, Michael E Schatman, Amol Soin, Peter S Staats, Giustino Varrassi, Jing Wang, Laxmaiah Manchikanti

Faculty, Staff and Student Publications

Background: Complex Regional Pain Syndrome (CRPS) is a challenging and often disabling condition marked by persistent pain, most commonly in a limb following injury or surgery. It presents with a wide array of symptoms, including intense pain, swelling, alterations in skin color and temperature, motor dysfunction, and trophic changes such as skin and tissue atrophy. While the precise cause of CRPS is not fully understood, it is thought to stem from abnormal nervous system activity, leading to heightened pain sensitivity and inflammatory responses. A thorough understanding of CRPS is essential for accurate diagnosis, effective treatment, and enhancing patients' quality of …

Βiv Spectrin Abundancy, Cellular Distribution And Sensitivity To Akt/Gsk3 Regulation In Schizophrenia, Jessica Di Re, Michela Marini, Syed Ibrar Hussain, Aditya K Singh, Akshaya Venkatesh, Musaad A Alshammari, Tahani K Alshammari, Abdul-Rizaq Ali Hamoud, Ali Sajid Imami, Zahra Haghighijoo, Nickolas Fularcyzk, Laura Stertz, Derek Hawes, Angela Mosebarger, Jordan Jernigan, Claire Chaljub, Ralda Nehme, Consuelo Walss-Bass, Anton Schulmann, Marquis P Vawter, Robert Mccullumsmith, Robert D Damoiseaux, Agenor Limon, Demetrio Labate, Michael F Wells, Fernanda Laezza

Faculty, Staff and Student Publications

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA …

Targeting Cdk2 And Other Novel Cell Cycle Targets For Breast Cancer Therapy, Mei-Kuang Chen, Linjie Luo, Nicole Massoumi, Khandan Keyomarsi

Faculty, Staff and Student Publications

Introduction: The dysregulation of cyclin-dependent kinases (CDKs) is a key driver of cancer progression, making them attractive therapeutic targets. In CDK4/6 inhibitor (CDK4/6i)-resistant breast cancer, targeting CDK2 offers a promising approach. CDK2 is frequently hyperactivated due to cyclin E1 overexpression or retinoblastoma protein loss, acting as a mechanism that sustains proliferation despite CDK4/6 inhibition. CDK2 inhibitors (CDK2i) show strong anti-tumor activity, particularly in combination with CDK4/6i or immune checkpoint inhibitors.

Areas covered: This review explores the biological roles of CDK2 and its regulatory mechanisms. The review highlights the latest advancements in CDK2i, their mechanisms of action, and their potential in …

Institutional Learning Curve And Factors Of Prolonged Operation Time Of Robotic Distal Pancreatectomy: An Analysis Of An Initial 117 Cases, Yuki Hirata, Laura Prakash, Jess Maxwell, Rebecca Snyder, Michael Kim, Hop Tran Cao, Ching-Wei D Tzeng, Jefferey E Lee, Matthew H G Katz, Naruhiko Ikoma

Faculty, Staff and Student Publications

Background: The granular methods by which centers can safely implement and effectively expand robotic distal pancreatectomy (RDP), including those related to appropriate patient selection during the learning curve period, remain unclear. This study aimed to verify that our strategic robotic surgical oncology program effectively implemented RDP as standard practice and to identify factors associated with prolonged operation time.

Materials and methods: We performed a detailed analysis of the intraoperative and short-term outcomes of consecutive patients (October 2018-September 2023) undergoing RDP at our center, beginning with the first patient in our program. Operation time was analyzed using a cumulative sum chart …

Impacts Of Radiation On Metabolism And Vascular Cell Senescence, Junichi Abe, Khanh Chau, Anahita Mojiri, Guangyu Wang, Masayoshi Oikawa, Venkata S K Samanthapudi, Abigail M Osborn, Keila C Ostos-Mendoza, Karla N Mariscal-Reyes, Tammay Mathur, Abhishek Jain, Joerg Herrmann, Syed Wamique Yusuf, Sunil Krishnan, Anita Deswal, Steven H Lin, Sivareddy Kotla, John P Cooke, Nhat-Tu Le

Faculty, Staff and Student Publications

Significance: This review investigates how radiation therapy (RT) increases the risk of delayed cardiovascular disease (CVD) in cancer survivors. Understanding the mechanisms underlying radiation-induced CVD is essential for developing targeted therapies to mitigate these effects and improve long-term outcomes for patients with cancer.

Recent Advances: Recent studies have primarily focused on metabolic alterations induced by irradiation in various cancer cell types. However, there remains a significant knowledge gap regarding the role of chronic metabolic alterations in normal cells, particularly vascular cells, in the progression of CVD after RT.

Critical Issues: This review centers on RT-induced metabolic alterations in vascular cells …

Kap1 Promotes Gastric Adenocarcinoma Progression By Activating Hippo/Yap1 Signaling Via Binding To Hnrnpab, Shumei Song, Yibo Fan, Gengyi Zou, Longfei Huo, Janani Kumar, Yuan Li, Ruiping Wang, Enyu Dai, Jiankang Jin, Ailing W Scott, Shan Shao, Melissa Pool Pizzi, Jody V Vykoukal, Hiroyuki Katayama, Samir Hanash, George A Calin, Xing Zhang, Min Gyu Lee, Zhenning Wang, Yuan-Hung Lo, Qiong Gan, Rebecca E Waters, Feng Yin, Linghua Wang, Xiaodong Cheng, Jaffer A Ajani, Shilpa S Dhar

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter …

1d Thermoembolization Model Using Ct Imaging Data For Porcine Liver, Rohan Amare, Danielle Stolley, Steve Parrish, Megan Jacobsen, Rick R Layman, Chimamanda Santos, Beatrice Riviere, Natalie Fowlkes, David Fuentes, Erik Cressman

Faculty, Staff and Student Publications

Innovative therapies such as thermoembolization are expected to play an important role in improving care for patients with diseases such as hepatocellular carcinoma. Thermoembolization is a minimally invasive strategy that combines thermal ablation and embolization in a single procedure. This approach exploits an exothermic chemical reaction that occurs when an acid chloride is delivered via an endovascular route. However, comprehension of the complexities of the biophysics of thermoembolization is challenging. Mathematical models can aid in understanding such complex processes and assisting clinicians in making informed decisions. In this study, we used a Hagen-Poiseuille 1D blood flow model to predict the …

A Follow-Up Study On The Novel Use Of Contrast-Enhanced Susceptibility-Weighted Imaging For Extremity Desmoid Fibromatosis Response Assessment, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Ken-Pin Hwang, Jingfei Ma, R Jasson Stafford, Ravin Ratan, John E Madewell, Dejka Araujo, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Desmoid tumors are rare mesenchymal neoplasms characterized by a clonal proliferation of fibroblasts and myofibroblasts. Using the novel contrast-enhanced susceptibility-weighted imaging (CE-SWI) for characterizing desmoid tumors can enhance the separation between fibrous T2-hypointense and cellular T1-enhancing components. We aim to evaluate the effectiveness of the CE-SWI signal, volumetric, and radiomics-derived features in assessing desmoid treatment response. This IRB-approved study included 17 single-lesion extremity desmoid fibromatosis patients who underwent standard-of-care MRI, including CE-SWI, from March 2021 to February 2024. Measurements of maximum diameter, volume, and the modified Choi (m-Choi: tumor/muscle T2 ratio) were computed based on CE-SWI and T2-STIR volumetric tumor …

Wnt-Directed Cxcl12-Expressing Apical Papilla Progenitor Cells Drive Tooth Root Formation, Mizuki Nagata, Gaurav T Gadhvi, Taishi Komori, Yuki Arai, Hiroaki Manabe, Angel Ka Yan Chu, Ramandeep Kaur, Meer Ali, Yuntao Yang, Chiaki Tsutsumi-Arai, Yuta Nakai, Yuki Matsushita, Nicha Tokavanich, W Jim Zheng, Joshua D Welch, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

The tooth root is a critical component of the tooth anchored to surrounding alveolar bones. Tooth root formation is driven by cells in the apical papilla (AP) that generate new dentin-forming odontoblasts at the root-forming front. Mesenchymal stem cells have been isolated from AP for regenerative use; however, how AP cells physiologically coordinate tooth root formation remains undefined. We find that CXCL12+ cells emerge in AP under hypoxic environments at the onset of tooth root formation. Using Cxcl12-creER-based cell-lineage analysis, we further find that CXCL12+ AP cells contribute not only to odontoblasts but also to cementum-forming cementoblasts of the elongating …

Seasonal And Landscape-Driven Variations In Forage Resources Of Apis Mellifera Scutellata: Implications For Pollination Sustainability And Colony Health In Taita Taveta County, Kenya, Mary Chege, Mbatha B. Wambua, Wambua J. Kilonzo, Sevgan Subramanian, Beatrice T. Nganso

All Peer-Reviewed Publications

Seasonality and land-use change are key factors influencing forage availability for managed honey bee colonies, yet knowledge of forage identity and how these factors influence forage availability remains limited in Africa. To address these gaps, we used DNA metabarcoding to identify nectar and pollen plant species supporting the nutrition of the African savannah honey bee, Apis mellifera scutellata, across different land-use/land cover types and seasons in Taita Taveta County, Kenya. We identified 224 forage plant species from 65 families, with Asteraceae, Fabaceae, and Myrtaceae being the top contributors. Forage availability was significantly influenced by landscape and season, with honey bees …

Meeting Report On An Integrated Research Agenda For Mosquito-Borne Arboviruses, Angela K. Ulrich, Nicolina M. Moua, Alison Mack, Natsuko Imai-Eaton, J. Erin Staples, Angela J. Mehr, Julia T. Ostrowsky, Tabitha Leighton, Ana Cehovin, Petra C. Fay, Josephine P. Golding, Emma Maynard, Luke Alphey, Diana P. Rojas Alvarez, Lark L. Coffey, Nuno R. Faria, Rafael Maciel-De-Freitas, Kevin Maringer, Kris A. Murray, Henrik Salje, Rosemary Sang, Pedro F.C. Vasconcelos, Yee Sin Leo, Steven P. Sinkins, Jocelyne Neto De Vasconcelos, Samuel K. Dadzie, Eva Harris, Thais H. Dos Santos, Raman Velayudhan

All Peer-Reviewed Publications

The emergence and re-emergence of mosquito-borne arbovirus (MBV) diseases pose a rapidly expanding global health threat fueled by the convergence of multiple ecologic, economic, and social factors, including climate change, land use, poverty, deficiencies of water storage and sanitation, and limitations of vector control programs. On December 6, 2023, the Wellcome Trust and the University of Minnesota's Center for Infectious Disease Research and Policy held a meeting titled "An integrated approach to mosquito-borne arboviruses: a priority research agenda."The meeting comprised presentations, panels, and facilitated discussions aimed at describing the state of the field, highlighting recent accomplishments, identifying novel strategies, and …

Investigating The Role Of Metallothioneins In Fungal Iron Homeostasis, David Eap

Theses and Dissertations

The pathogenic fungi Aspergillus fumigatus requires metals to survive and infect humans, but metal overload can be detrimental. Metallothioneins (MTs) are small, cysteine-rich proteins that alleviate metal toxicity by binding excess metals (typically Zn or Cu) for storage or delivery. A recent report indicates that the Fe-S cluster binding glutaredoxin GrxD and the putative Cu-MT CmtA were interacting under high iron conditions in A. fumigatus. We hypothesize that this MT may have a role in binding iron or Fe-S clusters under iron overload conditions to prevent iron toxicity. We also aim to characterize this new MT by determining its …

Circannual And Kinship Cues Shape Reproduction And Epigenetic Aging In Peromyscus, Kim Tuyen Huynh Dam

Theses and Dissertations

Evolutionary success is defined by the ability of a species to adapt and survive across many generations. This success is not determined by any single attribute but rather includes the entrenched, complex system that could be associated with biological rhythms, reproductive strategies, and regulations of epigenetic and genetic components. By using closed Peromyscus colonies as a model and by coupling mathematical modeling, analyses of breeding records, epigenetic studies, and in vitro and in vivo experiments, this dissertation aims to discover how Peromyscus adjusts to the internal and external pressures to ensure their survival and preserve evolutionary fitness in controlled environments. …

Exploring The Ancestry And Mutational Signatures Of Free-Breeding Dogs From Chernobyl And The Galápagos Islands, Gabriella Jean Spatola

Theses and Dissertations

Two free-breeding dog populations, one in Chernobyl, Ukraine, and the other on the Galápagos Islands, Ecuador, exist on opposite sides of the globe, yet both hold unique scientific potential to further our understanding of free-breeding dog population dynamics and evolutionary processes related to their environments. In the following studies, blood samples from more than 400 individual Chernobyl dogs were collected and their genomes were analyzed alongside over 1500 purebred and 200 global free-breeding dogs, describing genetic relationships and the extent of admixture with purebred migrants. Importantly, the sampled Chernobyl dogs had long-term exposures to ionizing radiation because of the 1986 …

Focus On Wildlife Swifts & Swallows Of Nh, Haley Andreozzi, Pam Hunt

UNH Cooperative Extension

No abstract provided.

Conservation Management Effects On Soil And Agronomic Properties In A Furrow-Irrigated Corn System In East-Central Arkansas, Jeferson P. Pimentel, Christopher G. Henry, Kris R. Brye, Benjamin R. Runkle, Amanda J. Ashworth, Edgar Mersiovsky, Kevin C. Thompson

Biological and Agricultural Engineering Faculty Publications and Presentations

Cover crops can improve soil physical properties and help to sustain agricultural crop yields. A 6-year study conducted from 2017 to 2022 examined the effects of conservation soil management practices in a furrow-irrigated continuous corn (Zea mays L.) system on a silt-loam soil (Typic Albaqualf) in the Lower Mississippi River Delta region of eastern Arkansas. This study compared the effects of conventional tillage (CT), no-tillage (NT), and no-tillage with cover crops (CC) in selected soil physical and chemical properties (i.e., soil bulk density (D b), porosity (& fnof;t), field capacity (Theta FC), Permanent wilting point (Theta PWP), Plant available water …

Cross-Continental Analysis Shows That Disturbance Effects On Reptile Body Condition Do Not Predict Abundance Responses, Kristina J. Macdonald, Don A. Driscoll, Michael D. Craig, Robert A. Davis, Steven J. Hromada, C. M. Gienger, Lee A. Fitzgerald, Daniel J. Leavitt, Danielle K. Walkup, Rickard Abom, Adrian F. Wayne, Gordon R. Friend, Brent Johnson, Danielle Stokeld, Chris R. Dickman, Scott A. Thompson, Graham G. Thompson, Daniel F. Bohórquez Fandiño, Christopher K. Woolley, Annabel L. Smith, Calum Irvine, Tim S. Jessop, Jade E. Keehn, Chris R. Feldman, Xavier Santos, Josabel Belliure

Research outputs 2022 to 2026

Ecological disturbances are discrete events that alter or transform the physical, chemical, or biological characteristics of ecosystems. Disturbance can cause animal populations to decline and, according to the risk-disturbance hypothesis and population collapse framework, these declines can be predicted by declines in animal body condition. However, no research has empirically examined the general relationship between body condition and abundance, nor their relationship in response to disturbance. We used a combined dataset representing 33 studies and > 42,000 observations of 75 species from Australia, New Zealand, Spain and the United States of America to test predictions relating to the relationship between reptile …

Dynamic Microbiome Responses To Structurally Diverse Anthocyanin-Rich Foods In A Western Diet Context, Mohammed F. Almatani, Giovanni Rompato, Eliza C. Stewart, Marcus Hayden, Jeremy Case, Samuel Rice, Korry J. Hintze, Abby D. Benninghoff

Animal, Dairy, and Veterinary Science Student Research

Background/Objectives: Anthocyanin (ACN)-rich foods are known to influence the gut microbiota composition, but the temporal dynamics and structural specificity of these effects remain poorly understood. This study investigated how distinct ACN-rich fruit supplements impact the gut microbiome over time in the context of a Western-style diet. We hypothesized that ACN-induced microbial shifts would occur rapidly, differ by ACN source, and require continued intake to persist. Methods: C57BL/6J mice were fed the total Western diet (TWD) supplemented with freeze-dried powders from bilberry (BB), tart cherry (TC), chokeberry (CB), elderberry (EB), black currant (BC), or black raspberry (BRB) for 0, 1, 3, …

Oatp1b1/1b3 Deficiency Exacerbates Hyperbilirubinemia In Erythropoietic Protoporphyria, Ruizhi Gu, Fu-Ying Qin, Luxuan Wang, Jiaojiao Zhang, Jacob Emerson, Qing Ma, Jie Lu, Karl E Anderson, Junmei Wang, Xiaochao Ma

Faculty, Staff and Student Publications

Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in ferrochelatase (FECH), leading to the accumulation of its substrate, protoporphyrin IX (PPIX). PPIX is primarily produced in the bone marrow and transported to the liver for excretion. Because PPIX is hydrophobic, its elevated levels can cause bile duct blockage, cholestatic liver injury, and even liver failure. However, the specific transporter responsible for PPIX uptake into hepatocytes remains unclear. The OATP1B1/1B3 transporters, which are expressed in hepatocytes, facilitate the uptake of coproporphyrin III, a structural analog of PPIX. Additionally, OATP1B1/1B3 mediates the uptake of bilirubin, a biomarker of liver injury, from plasma …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

Crem Is A Regulatory Checkpoint Of Car And Il-15 Signalling In Nk Cells, Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander Biederstädt, Mecit Kaplan, Xin Ru Jiang, Inci Biederstädt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M Deyter, Natalie Wall Fowlkes, Abhinav K Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM …

Histone Lysine Methyltransferases Mll3 And Mll4 Direct Gene Expression To Produce Platelets Efficiently, Guozhen Gao, Josimar Dornelas Moreira, Prosun Das, Kevin Lin, Kai Ge, Taiping Chen, Yue Lu, Margarida A Santos

Faculty, Staff and Student Publications

Circulating blood platelets are responsible for maintaining hemostasis. They are released into blood vessels from mature megakaryocytes. Although several transcription factors have been reported to orchestrate the transcriptional programs required for platelet production, how chromatin regulators control these processes is still poorly understood. MLL3 and MLL4 are the main lysine methyltransferases responsible for the deposition of H3K4me1 histone marks at enhancers. MLL3 and MLL4 typically form complexes with other co-factors, such as PTIP. Recently, we showed that loss of PTIP leads to decreased platelet numbers in mice. Here, we find that, although MLL3/4 double deficiency does not alter megakaryopoiesis and …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …

Memantine Inhibits Calcium-Permeable Ampa Receptors, Elisa Carrillo, Alejandra Montaño Romero, Cuauhtemoc U Gonzalez, Andreea L Turcu, Santiago Vázquez, Edward C Twomey, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Memantine is an US Food and Drug Administration (FDA) approved drug that is thought to selectively inhibit NMDA-subtype of ionotropic glutamate receptors (NMDARs). NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine …

Basic Rabbit Selection And Breeding Considerations, Joseph Okoh, Jessie Hadfield

All Current Publications

This fact sheet is designed to assist rabbit producers in understanding breed selection for a profitable enterprise. It can also serve as a training tool for new producers, aiding them in breed selection and breeding practices.

Feasibility Of Applying Bacillus Amyloliquefaciens-Derived Solid State Fermentation Products Into The Hatch Cabinet Environment As A Method To Mitigate The Microbial Bloom During The Hatching Phase Authors, Mitchell C. Rowland, Lucas E. Graham, Callie Selby, Aaron J. Forga, Billy M. Hargis, Christine N. Voung, Graham Danielle

Poultry Science Faculty Publications and Presentations

Formaldehyde has been used to control microbial contamination in commercial hatch cabinets. The purpose of the present study was to investigate the effects of spray application of Bacillus amyloliquefaciens solid state fermentation products on the microbial load in the hatch cabinet, pioneer colonization of the gastrointestinal tract (GIT), and early performance compared to formaldehyde fumigation. An environmental challenge model was used to simulate the microbial bloom to compare the application of two B. amyloliquefaciens strains (MCR002, MCR009) to formaldehyde fumigation. Groups included 1) non-challenged control (NC), 2) challenged with pathogen mix (PM) containing Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus …

Evaluation Of The Incremental Effect Of Fasting Length On Ph, Select Cecal Microbial Groups, Cecal Volatile Fatty Acid Concentrations, And Secretory Iga Excretion In Roosters, B.W. Parsons, M.R. Bedford, C.L. Wyatt

Poultry Science Faculty Publications and Presentations

Two experiments were conducted to evaluate the effect of incremental fasting time on the gastrointestinal tract in chickens. Adult White Leghorn roosters with intact ceca were provided a nutrient-adequate corn-soybean meal diet ad libitum for 3 weeks. Prior to initiation of the experimental phase, ad libitum feed intake was recorded for 8 h and immediately after the fasting period commenced. In Experiment 1, roosters were fasted for either 0, 3, 6, 9, 12, 16, or 24 h. At each time point birds were euthanized and pH in the crop, gizzard, and ceca were recorded and cecal contents were collected to …

L-Quebrachitol Modulates The Anti-Convulsant Effects Of Carbamazepine Possibly Through Voltage-Gated Sodium Channel Blocking Mechanism In Chicks: In Vivo And In Silico Studies, Asifa Asrafi, Mohammad Aslam, Ali G. Alkhathami, Md. Sakib Hossain, Imam Hossen Rakib, Md. Sakib Al Hasan, Feroz Khan Nun, Md. Faisal Amin, Muhammad Torequl Islam

School of Integrative Biological & Chemical Sciences Faculty Publications

Introduction: L-Quebrachitol (LQB), a naturally occurring bioactive compound, exhibits anti-inflammatory, anti-oxidant, anti-cancer, and anti-diabetic properties. However, its therapeutic potential in convulsant management remains largely unexplored. The objective of this study was to investigate the anticonvulsant effects of LQB in an In Vivo model and to examine its molecular interactions via In Silico docking simulations.

Methods: In the In Vivo study, pentylenetetrazol (PTZ) was administered intraperitoneally (i.p.) at 80 mg/kg to induce convulsions, and the test animals were treated orally with three doses of LQB (1, 5, and 10 mg/kg), with carbamazepine (CBZ) at 80 mg/kg as a standard drug.

Results: …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …