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Neutralizing Interleukin-6 In Tumor-Bearing Mice Does Not Abrogate Behavioral Fatigue Induced By Lewis Lung Carcinoma, Kiersten Scott, Thien Trong Phan, A Phillip West, Cullen M Taniguchi, Robert Dantzer

Faculty, Staff and Student Publications

Tumor growth is associated with metabolic reprogramming of various organs including the liver. This metabolic reprogramming is responsible for the development of behavioral fatigue represented by decreased voluntary wheel running in a murine model of lung cancer. To determine whether interleukin (IL-)6 induced by the tumor is responsible for the metabolic reprogramming, mice injected with Lewis lung carcinoma cells in the flank were treated with an anti-mouse IL-6 monoclonal neutralizing antibody using a 2 × 2 factorial design (+/- tumor and +/- anti-IL-6 antibody). Endpoints were represented by behavioral, metabolic and immune phenotypes. Despite its ability to abrogate the increase …

Neuronal Population Activity Dynamics Reveal A Low-Dimensional Signature Of Operant Learning In Aplysia, Renan M Costa, Douglas A Baxter, John H Byrne

Faculty, Staff and Student Publications

Learning engages a high-dimensional neuronal population space spanning multiple brain regions. However, it remains unknown whether it is possible to identify a low-dimensional signature associated with operant conditioning, a ubiquitous form of learning in which animals learn from the consequences of behavior. Using single-neuron resolution voltage imaging, here we identify two low-dimensional motor modules in the neuronal population underlying Aplysia feeding. Our findings point to a temporal shift in module recruitment as the primary signature of operant learning. Our findings can help guide characterization of learning signatures in systems in which only a smaller fraction of the relevant neuronal population …

Common Genetic Variants Contribute To Risk Of Transposition Of The Great Arteries, Doris Škorić-Milosavljević, Rafik Tadros, Fernanda M Bosada, Federico Tessadori, Jan Hendrik Van Weerd, Odilia I Woudstra, Fleur V Y Tjong, Najim Lahrouchi, Fanny Bajolle, Heather J Cordell, A J Agopian, Gillian M Blue, Daniela Q C M Barge-Schaapveld, Marc Gewillig, Christoph Preuss, Elisabeth M Lodder, Phil Barnett, Aho Ilgun, Leander Beekman, Karel Van Duijvenboden, Regina Bokenkamp, Martina Müller-Nurasyid, Hubert W Vliegen, Thelma C Konings, Joost P Van Melle, Arie P J Van Dijk, Roland R J Van Kimmenade, Jolien W Roos-Hesselink, Gertjan T Sieswerda, Folkert Meijboom, Hashim Abdul-Khaliq, Felix Berger, Sven Dittrich, Marc-Phillip Hitz, Julia Moosmann, Frank-Thomas Riede, Stephan Schubert, Pilar Galan, Mark Lathrop, Hans M Munter, Ammar Al-Chalabi, Christopher E Shaw, Pamela J Shaw, Karen E Morrison, Jan H Veldink, Leonard H Van Den Berg, Sylvia Evans, Marcelo A Nobrega, Ivy Aneas, Milena Radivojkov-Blagojević, Thomas Meitinger, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John F Smythe, Luis Altamirano-Diaz, Jane Lougheed, Berto J Bouma, Marie-A Chaix, Jennie Kline, Anne S Bassett, Gregor Andelfinger, Roel L F Van Der Palen, Patrice Bouvagnet, Sally-Ann B Clur, Jeroen Breckpot, Wilhelmina S Kerstjens-Frederikse, David S Winlaw, Ulrike M M Bauer, Seema Mital, Elizabeth Goldmuntz, Bernard Keavney, Damien Bonnet, Barbara J Mulder, Michael W T Tanck, Jeroen Bakkers, Vincent M Christoffels, Cornelis J Boogerd, Alex V Postma, Connie R Bezzina

Faculty, Staff and Student Publications

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.

OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA.

METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients …

B Cell Receptor Isotypes Differentially Associate With Cell Signaling, Kinetics, And Outcome In Chronic Lymphocytic Leukemia, Andrea N Mazzarello, Eva Gentner-Göbel, Marcus Dühren-Von Minden, Tatyana N Tarasenko, Antonella Nicolò, Gerardo Ferrer, Stefano Vergani, Yun Liu, Davide Bagnara, Kanti R Rai, Jan A Burger, Peter J Mcguire, Palash C Maity, Hassan Jumaa, Nicholas Chiorazzi

Faculty, Staff and Student Publications

In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We showed that IgM, not IgD, level …

Cxcl10 Chemokine Regulates Heterogeneity Of The Cd8+ T Cell Response And Viral Set Point During Chronic Infection, Aleksandra J Ozga, Melvyn T Chow, Mateus E Lopes, Rachel L Servis, Mauro Di Pilato, Philippe Dehio, Jeffrey Lian, Thorsten R Mempel, Andrew D Luster

Faculty, Staff and Student Publications

CD8+ T cells responding to chronic infection adapt an altered differentiation program that provides some restrain on pathogen replication yet limits immunopathology. This adaptation is imprinted in stem-like cells and propagated to their progeny. Understanding the molecular control of CD8+ T cell differentiation in chronic infection has important therapeutic implications. Here, we found that the chemokine receptor CXCR3 was highly expressed on viral-specific stem-like CD8+ T cells and that one of its ligands, CXCL10, regulated the persistence and heterogeneity of responding CD8+ T cells in spleens of mice chronically infected with lymphocytic choriomeningitis virus. CXCL10 was produced by inflammatory monocytes …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Faculty, Staff and Student Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Faculty, Staff and Student Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

Emergence Of Clinical Clostridioides Difficile Isolates With Decreased Susceptibility To Vancomycin, Charles Darkoh, Kadiatou Keita, Chioma Odo, Micah Oyaro, Eric L Brown, Cesar A Arias, Blake M Hanson, Herbert L Dupont

Faculty, Staff and Student Publications

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of hospital-associated antibiotic-related diarrhea and deaths worldwide. Vancomycin is one of the few antibiotics recommended for both nonsevere and severe CDI cases. We sought to determine whether vancomycin nonsusceptible C. difficile strains are circulating in the patient population.

METHODS: Stool samples from patients with CDI were collected from 438 and 98 patients at a large university hospital in Houston, Texas, and Nairobi, Kenya, respectively. The stools were examined for the presence of vancomycin and metronidazole nonsusceptible C. difficile using broth dilution culture, Etest (BioMérieux, France), polymerase chain reaction (PCR), whole-genome sequencing, …

Transcranial Stimulation Of Alpha Oscillations Up-Regulates The Default Mode Network, Kevin J Clancy, Jeremy A Andrzejewski, Yuqi You, Jens T Rosenberg, Mingzhou Ding, Wen Li

Faculty, Staff and Student Publications

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, …

Differential Cd4+ T-Cell Cytokine And Cytotoxic Responses Between Reactivation And Latent Phases Of Herpes Zoster Infection, Wenjie Jin, Mike Fang, Ismail Sayin, Carson Smith, Jeffrey L Hunter, Brian Richardson, Jackelyn B Golden, Christopher Haley, Kenneth E Schmader, Michael R Betts, Stephen K Tyring, Cheryl M Cameron, Mark J Cameron, David H Canaday

Faculty, Staff and Student Publications

BACKGROUND: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined.

METHODS: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing.

RESULTS: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ. VZV-specific CD4+ memory …

Characterization Of The Blood Oxygen Level Dependent Hemodynamic Response Function In Human Subcortical Regions With High Spatiotemporal Resolution, Jung Hwan Kim, Amanda J Taylor, Marc Himmelbach, Gisela E Hagberg, Klaus Scheffler, David Ress

Faculty, Staff and Student Publications

Subcortical brain regions are absolutely essential for normal human function. These phylogenetically early brain regions play critical roles in human behaviors such as the orientation of attention, arousal, and the modulation of sensory signals to cerebral cortex. Despite the critical health importance of subcortical brain regions, there has been a dearth of research on their neurovascular responses. Blood oxygen level dependent (BOLD) functional MRI (fMRI) experiments can help fill this gap in our understanding. The BOLD hemodynamic response function (HRF) evoked by brief (<4 >s) neural activation is crucial for the interpretation of fMRI results because linear analysis between neural …

Differential Gene Expression In Cord Blood Of Infants Diagnosed With Cerebral Palsy: A Pilot Analysis Of The Beam Cohort, Maria L V Dizon, Raye-Ann O Deregnier, Steven J Weiner, Michael W Varner, Dwight J Rouse, Maged M Costantine, Ronald J Wapner, John M Thorp, Sean C Blackwell, Nina K Ayala, Antonio F Saad, Steve N Caritis, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network

Faculty, Staff and Student Publications

The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated …

Methodologies To Unlock The Molecular Expression And Cellular Structure Of Ocular Lens Epithelial Cells, Justin Parreno, Grace Emin, Michael P Vu, Jackson T Clark, Sandeep Aryal, Shaili D Patel, Catherine Cheng

Faculty, Staff and Student Publications

The transparent ocular lens in the anterior chamber of the eye is responsible for fine focusing of light onto the retina. The lens is entirely cellular with bulk of the tissue composed of fiber cells, and the anterior hemisphere of the lens is covered by a monolayer of epithelial cells. Lens epithelial cells are important for maintaining fiber cell homeostasis and for continual growth of the lens tissue throughout life. Cataracts, defined as any opacity in the lens, remain the leading cause of blindness in the world. Following cataract surgery, lens epithelial cells can undergo a process of epithelial-to-mesenchymal transition …

Ahcc® Supplementation To Support Immune Function To Clear Persistent Human Papillomavirus Infections, Judith A Smith, Anjali A Gaikwad, Lata Mathew, Barbara Rech, Jonathan P Faro, Joseph A Lucci, Yu Bai, Randall J Olsen, Teresa T Byrd

Faculty, Staff and Student Publications

OBJECTIVE: To determine the efficacy, safety, and durability of the use of AHCC supplementation for 6 months to support the host immune system to clear high-risk human papillomavirus (HPV) infections. The AHCC supplement is a proprietary, standardized extract of cultured lentinula edodes mycelia (AHCC

STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study (CTN: NCT02405533) in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 …

Brain Antigens Stimulate Proliferation Of T Lymphocytes With A Pathogenic Phenotype In Multiple Sclerosis Patients, Assaf Gottlieb, Hoai Phuong T Pham, John William Lindsey

Faculty, Staff and Student Publications

A method to stimulate T lymphocytes with a broad range of brain antigens would facilitate identification of the autoantigens for multiple sclerosis and enable definition of the pathogenic mechanisms important for multiple sclerosis. In a previous work, we found that the obvious approach of culturing leukocytes with homogenized brain tissue does not work because the brain homogenate suppresses antigen-specific lymphocyte proliferation. We now report a method that substantially reduces the suppressive activity. We used this non-suppressive brain homogenate to stimulate leukocytes from multiple sclerosis patients and controls. We also stimulated with common viruses for comparison. We measured proliferation, selected the …

Ret Signaling Pathway And Ret Inhibitors In Human Cancer, Angelina T Regua, Mariana Najjar, Hui-Wen Lo

Faculty, Staff and Student Publications

Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer types and are most prevalent in thyroid carcinomas and non-small cell lung cancer (NSCLC). In other tumor types such as breast cancer and salivary gland carcinomas, RET alterations can be found at lower frequencies. Aberrant RET activity is associated with poor prognosis of thyroid and lung carcinoma patients, and is strongly correlated with increased risk of distant metastases. RET aberrations encompass a variety of genomic or …

Cross-Talk Between Histone Methyltransferases And Demethylases Regulate Rest Transcription During Neurogenesis, Jyothishmathi Swaminathan, Shinji Maegawa, Shavali Shaik, Ajay Sharma, Javiera Bravo-Alegria, Lei Guo, Lin Xu, Arif Harmanci, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The RE1 Silencing Transcription Factor (REST) is a major regulator of neurogenesis and brain development. Medulloblastoma (MB) is a pediatric brain cancer characterized by a blockade of neuronal specification. REST gene expression is aberrantly elevated in a subset of MBs that are driven by constitutive activation of sonic hedgehog (SHH) signaling in cerebellar granular progenitor cells (CGNPs), the cells of origin of this subgroup of tumors. To understand its transcriptional deregulation in MBs, we first studied control of Rest gene expression during neuronal differentiation of normal mouse CGNPs. Higher Rest expression was observed in proliferating CGNPs compared to differentiating neurons. …

Risk Of Alzheimer's Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching, Avram S Bukhbinder, Yaobin Ling, Omar Hasan, Xiaoqian Jiang, Yejin Kim, Kamal N Phelps, Rosemarie E Schmandt, Albert Amran, Ryan Coburn, Srivathsan Ramesh, Qian Xiao, Paul E Schulz

Faculty, Staff and Student Publications

BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized.

OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years …

Caries Risk Documentation And Prevention: Emeasures For Dental Electronic Health Records, Suhasini Bangar, Ana Neumann, Joel M White, Alfa Yansane, Todd R Johnson, Gregory W Olson, Shwetha V Kumar, Krishna K Kookal, Aram Kim, Enihomo Obadan-Udoh, Elizabeth Mertz, Kristen Simmons, Joanna Mullins, Ryan Brandon, Muhammad F Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

BACKGROUND: Longitudinal patient level data available in the electronic health record (EHR) allows for the development, implementation, and validations of dental quality measures (eMeasures).

OBJECTIVE: We report the feasibility and validity of implementing two eMeasures. The eMeasures determined the proportion of patients receiving a caries risk assessment (eCRA) and corresponding appropriate risk-based preventative treatments for patients at elevated risk of caries (appropriateness of care [eAoC]) in two academic institutions and one accountable care organization, in the 2019 reporting year.

METHODS: Both eMeasures define the numerator and denominator beginning at the patient level, populations' specifications, and validated the automated queries. For …

Predicting Clinical Response To Everolimus In Er+ Breast Cancers Using Machine-Learning, Aritro Nath, Patrick A Cosgrove, Jeffrey T Chang, Andrea H Bild

Faculty, Staff and Student Publications

Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced ER+ breast cancers ultimately develop resistance to endocrine. This acquired resistance to endocrine therapy is often driven by the activation of the PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits the mTOR complex has been shown to improve clinical outcomes in metastatic ER+ breast cancers. However, there are no biomarkers currently available to guide the use of everolimus in the clinic for progressive patients, where multiple therapeutic options are available. Here, we utilized gene expression signatures from 9 ER+ breast cancer cell lines and …

A Structural, Cognitive, And Behavioral Model For Error Analysis Of Group B Streptococcus Prophylaxis In Pregnancy, Robert E Murphy, Jane C Ibekwe, Stella I Ibekwe, Jerrie S Refuerzo

Faculty, Staff and Student Publications

The objective of this study was to develop a structural-cognitive-behavioral model for error analysis of group B streptococcus (GBS) prophylaxis failure, classify delivery cases into this model, and examine compliance with treatment guidelines. A retrospective, cohort study was conducted of women with liveborn pregnancies greater than 24 weeks in April 2018 at a single hospital. We created a structural-cognitive-behavioral model of five assessments for adherence to GBS prophylaxis guidelines and then classified these into four distinct error stages. A descriptive analysis was performed to determine if the pregnancy had a perfect process, a GBS prophylaxis failure, or a fortuitous outcome. …

The Impact Of Merkel Cell Polyomavirus Positivity On Prognosis Of Merkel Cell Carcinoma: A Systematic Review And Meta-Analysis, Aimin Yang, Wilson Adrian Wijaya, Lei Yang, Yinhai He, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

INTRODUCTION: There are numerous findings over the past decade have indicated that Merkel cell carcinoma (MCC) may have two pathways of pathogenesis: one related to ultraviolet irradiation and the other to the Merkel cell polyomavirus (MCPyV). However, the predictive and clinicopathological value of MCPyV positivity in MCC patients is still debatable. This article aims to examine the most recent data regarding this issue.

METHODS: The thorough literature searches were conducted in the Medline Ovid, PubMed, Web of Science, the Cochrane CENTRAL Databases, and Embase Databases until December 31, 2021. The associations between overall survival (OS), Merkel cell carcinoma-specific survival (MSS), …

Metabolic Imaging Using Hyperpolarization For Assessment Of Premalignancy, Shivanand Pudakalakatti, Priyank Raj, Travis C Salzillo, José S Enriquez, Dontrey Bourgeois, Prasanta Dutta, Mark Titus, Shayan Shams, Priya Bhosale, Michael Kim, Florencia Mcallister, Pratip K Bhattacharya

Faculty, Staff and Student Publications

There is an unmet need for noninvasive surrogate markers that can help identify premalignant lesions across different tumor types. Here we describe the methodology and technical details of protocols employed for in vivo

Advances In Non-Invasive Biosensing Measures To Monitor Wound Healing Progression, Walker D Short, Oluyinka O Olutoye, Benjamin W Padon, Umang M Parikh, Daniel Colchado, Hima Vangapandu, Shayan Shams, Taiyun Chi, Jangwook P Jung, Swathi Balaji

Faculty, Staff and Student Publications

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and …

The Potential Of Biology-Guided Radiation Therapy In Thoracic Cancer: A Preliminary Treatment Planning Study, Steven N Seyedin, Rostem Bassalow, Osama R Mawlawi, Lehendrick M Turner, Roshal R Patel, Samuel R Mazin, Oluwaseyi M Oderinde, Yevgen Voronenko, Cody A Wages, Peter D Olcott, Joe Y Chang, Peter A Balter, James W Welsh

Faculty, Staff and Student Publications

PURPOSE: We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.

METHODS: Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).

RESULTS: For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT …

A Transgenic Bacterial Artificial Chromosome Approach To Identify Regulatory Regions That Direct Amhr2 And Osterix Expression In Müllerian Duct Mesenchyme, Malcolm M Moses, Rachel D Mullen, Daniel I Idowu, Peter Maye, Soazik P Jamin, Richard R Behringer

Faculty, Staff and Student Publications

A transgenic mouse approach using bacterial artificial chromosomes (BAC) was used to identify regulatory regions that direct Müllerian duct expression for Amhr2 and Osterix (Osx, also known as Sp7). Amhr2 encodes the receptor that mediates anti-Müllerian hormone (AMH) signaling for Müllerian duct regression in male embryos. Amhr2 is expressed in the Müllerian duct mesenchyme of both male and female embryos. A ∼147-kb BAC clone containing the Amhr2 locus was used to generate transgenic mice. The transgene was able to rescue the block in Müllerian duct regression of Amhr2-null males, suggesting that the BAC clone contains regulatory …

Magi1 Inhibits Interferon Signaling To Promote Influenza A Infection, Yin Wang, Jun-Ichi Abe, Khanh M Chau, Yongxing Wang, Hang Thi Vu, Loka Reddy Velatooru, Fahad Gulraiz, Masaki Imanishi, Venkata S K Samanthapudi, Minh T H Nguyen, Kyung Ae Ko, Ling-Ling Lee, Tamlyn N Thomas, Elizabeth A Olmsted-Davis, Sivareddy Kotla, Keigi Fujiwara, John P Cooke, Di Zhao, Scott E Evans, Nhat-Tu Le

Faculty, Staff and Student Publications

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may …

Morphological Description Of Laevicaulisstuhlmanni (Simroth, 1895) (Pulmonata, Veronicellidae) From Egypt, Reham Fathey Ali, David G Robinson, Fabio Liberto

Faculty, Staff and Student Publications

BACKGROUND: Terrestrial slugs and snails are increasingly becoming serious pests of agricultural, horticultural and ornamental plants in Egypt, resulting in major economic losses.

NEW INFORMATION: This paper provides a detailed morphological and anatomical description of the veronicellid slug Laevicaulisstuhlmanni (Simroth, 1895) that has been recently recorded from Egypt. This population from Egypt is compared with Laevicaulis populations recently reported and described from Libya as L.striatus (Simroth, 1896) and with available data in literature. Some notes and a distribution map of the veronicellids introduced in north-eastern Africa are provided.

Cancer Treatment-Induced Nad+ Depletion In Premature Senescence And Late Cardiovascular Complications, Priyanka Banerjee, Elizabeth A Olmsted-Davis, Anita Deswal, Minh Th Nguyen, Efstratios Koutroumpakis, Nicholas L Palaskas, Steven H Lin, Sivareddy Kotla, Cielito Reyes-Gibby, Sai-Ching J Yeung, Syed Wamique Yusuf, Momoko Yoshimoto, Michihiro Kobayashi, Bing Yu, Keri Schadler, Joerg Herrmann, John P Cooke, Abhishek Jain, Eduardo Chini, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family …

Review Of Evidence For Environmental Causes Of Uveal Coloboma, Evan B Selzer, Delphine Blain, Robert B Hufnagel, Philip J Lupo, Laura E Mitchell, Brian P Brooks

Faculty, Staff and Student Publications

Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative …