Medicine and Health Sciences Commons^™

Bovine Mammary Gland Biopsy Techniques, Veridiana L. Daley, Charles Dye, Sophie H. Bogers, R. Michael Akers, Francisco C. Rodriguez, John P. Cant, John Doelman, Peter Yoder, Karan Kumar, Dane Webster, Mark D. Hanigan

Animal and Food Sciences Faculty Publications

Bovine mammary gland biopsies allow researchers to collect tissue samples to study cell biology including gene expression, histological analysis, signaling pathways, and protein translation. This article describes two techniques for biopsy of the bovine mammary gland (MG). Three healthy Holstein dairy cows were the subjects. Before biopsies, cows were milked and subsequently restrained in a cattle chute. An analgesic (flunixin meglumine, 1.1 to 2.2 mg/kg of body weight) was administered via jugular intravenous [IV] injection 15-20 min prior to biopsy. For standing sedation, xylazine hydrochloride (0.01-0.05 mg/kg of body weight) was injected via the coccygeal vessels 5-10 min before the …

Kinetics Of The Chromosome 14 Microrna Cluster Ortholog And Its Potential Role During Placental Development In The Pregnant Mare, Pouya Dini, Peter Daels, Shavahn C. Loux, Alejandro Esteller-Vico, Mariano Carossino, Kirsten E. Scoggin, Barry A. Ball

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: The human chromosome 14 microRNA cluster (C14MC) is a conserved microRNA (miRNA) cluster across eutherian mammals, reported to play an important role in placental development. However, the expression kinetics and function of this cluster in the mammalian placenta are poorly understood. Here, we evaluated the expression kinetics of the equine C24MC, ortholog to the human C14MC, in the chorioallantoic membrane during the course of gestation.

Results: We demonstrated that C24MC-associated miRNAs presented a higher expression level during early stages of pregnancy, followed by a decline later in gestation. Evaluation of one member of C24MC (miR-409-3p) by in situ hybridization …

Dichotomous Scoring Of Tdp-43 Proteinopathy From Specific Brain Regions In 27 Academic Research Centers: Associations With Alzheimer's Disease And Cerebrovascular Disease Pathologies, Yuriko Katsumata, David W. Fardo, Walter A. Kukull, Peter T. Nelson

Biostatistics Faculty Publications

TAR-DNA binding protein 43 (TDP-43) proteinopathy is a common brain pathology in elderly persons, but much remains to be learned about this high-morbidity condition. Published stage-based systems for operationalizing disease severity rely on the involvement (presence/absence) of pathology in specific anatomic regions. To examine the comorbidities associated with TDP-43 pathology in aged individuals, we studied data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set. Data were analyzed from 929 included subjects with available TDP-43 pathology information, sourced from 27 different American Alzheimer’s Disease Centers (ADCs). Cases with relatively unusual diseases including autopsy-proven frontotemporal lobar degeneration (FTLD-TDP or FTLD-tau) …

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Association Between Spatial Access To Food Outlets, Frequency Of Grocery Shopping, And Objectively-Assessed And Self-Reported Fruit And Vegetable Consumption, Jared T. Mcguirt, Stephanie B. Jilcott Pitts, Alison Gustafson

Dietetics and Human Nutrition Faculty Publications

Because supermarkets are a critical part of the community food environment, the purpose of this paper is to examine the association between accessibility to the supermarket where participants were surveyed, frequency of shopping at the supermarket, and self-reported and objectively-assessed fruit and vegetable consumption. Accessibility was assessed using Geographic Information Systems (GIS) measured distance and multiple versions of the modified Retail Food Environment Index (mRFEI), including a localized road network buffer version. Frequency of shopping was assessed using self-report. The National Cancer Institute Fruit and Vegetable screener was used to calculate daily servings of fruits and vegetables. Skin carotenoids were …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Adaptation Mechanism And Tolerance Of Rhodopseudomonas Palustris Psb-S Under Pyrazosulfuron-Ethyl Stress, Xiang-Wen Luo, De-Yang Zhang, Teng-Hui Zhu, Xuguo Zhou, Jing Peng, Song-Bai Zhang, Yong Liu

Entomology Faculty Publications

Background: Pyrazosulfuron-ethyl is a long lasting herbicide in the agro-ecosystem and its residue is toxic to crops and other non-target organisms. A better understanding of molecular basis in pyrazosulfuron-ethyl tolerant organisms will shed light on the adaptive mechanisms to this herbicide.

Results: Pyrazosulfuron-ethyl inhibited biomass production in Rhodopseudomonas palustris PSB-S, altered cell morphology, suppressed flagella formation, and reduced pigment biosynthesis through significant suppression of carotenoids biosynthesis. A total of 1127 protein spots were detected in the two-dimensional gel electrophoresis. Among them, 72 spots representing 56 different proteins were found to be differently expressed using MALDI-TOF/TOF-MS, including 26 up- and 30 …

Canvass: A Crowd-Sourced, Natural-Product Screening Library For Exploring Biological Space, Sara E. Kearney, Gergely ZahoráNszky-KőHalmi, Kyle R. Brimacombe, Mark J. Henderson, Caitlin Lynch, Tongan Zhao, Kanny K. Wan, Zina Itkin, Christopher Dillon, Min Shen, Dorian M. Cheff, Tobie D. Lee, Danielle Bougie, Ken Cheng, Nathan P. Coussens, Dorjbal Dorjsuren, Richard T. Eastman, Ruili Huang, Michael J. Iannotti, Surendra Karavadhi, Carleen Klumpp-Thomas, Jacob S. Roth, Srilatha Sakamuru, Wei Sun, Steven A. Titus, Adam Yasgar, Ya-Qin Zhang, Jinghua Zhao, Rodrigo B. Andrade, M. Kevin Brown, Robert B. Grossman

Chemistry Faculty Publications

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The …

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …

Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM …

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO₂) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO₂ exposure (i.e., the effects of nTiO₂-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO₂ (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Macrophage-Derived Netrin-1 Promotes Abdominal Aortic Aneurysm Formation By Activating Mmp3 In Vascular Smooth Muscle Cells, Tarik Hadi, Ludovic Boytard, Michele Silvestro, Dornazsadat Alebrahim, Samson Jacob, Jordyn Feinstein, Krista Barone, Wes Spiro, Susan Hutchison, Russell Simon, Debra L. Rateri, Florence Pinet, David Fenyo, Mark Adelman, Kathryn J. Moore, Holger K. Eltzschig, Alan Daugherty, Bhama Ramkhelawon

Physiology Faculty Publications

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms by which these events are coupled thereby fueling focal vascular damage are undefined. Here we report through single-cell RNA-sequencing of diseased aorta that the neuronal guidance cue netrin-1 can act at the interface of macrophage-driven injury and ECM degradation. Netrin-1 expression peaks in human and murine aneurysmal macrophages. Targeted deletion of netrin-1 in macrophages protects mice from developing AAA. Through its receptor neogenin-1, netrin-1 induces a robust intracellular calcium flux necessary for the transcriptional regulation and persistent catalytic activation of matrix metalloproteinase-3 (MMP3) …

Comparison Between Kinetic And Kinetic-Kinematic Driven Knee Joint Finite Element Models, Paul O. Bolcos, Mika E. Mononen, Ali Mohammadi, Mohammadhossein Ebrahimi, Matthew S. Tanaka, Michael A. Samaan, Richard B. Souza, Xiaojuan Li, Juha-Sampo Suomalainen, Jukka S. Jurvelin, Juha Töyräs, Rami K. Korhonen

Kinesiology and Health Promotion Faculty Publications

Use of knee joint finite element models for diagnostic purposes is challenging due to their complexity. Therefore, simpler models are needed for studies where a high number of patients need to be analyzed, without compromising the results of the model. In this study, more complex, kinetic (forces and moments) and simpler, kinetic-kinematic (forces and angles) driven finite element models were compared during the stance phase of gait. Patella and tendons were included in the most complex model, while they were absent in the simplest model. The greatest difference between the most complex and simplest models was observed in the internal-external …

Mitochondrial Metabolism In Major Neurological Diseases, Zhengqiu Zhou, Grant L. Austin, Lyndsay E. A. Young, Lance A. Johnson, Ramon Sun

Molecular and Cellular Biochemistry Faculty Publications

Mitochondria are bilayer sub-cellular organelles that are an integral part of normal cellular physiology. They are responsible for producing the majority of a cell’s ATP, thus supplying energy for a variety of key cellular processes, especially in the brain. Although energy production is a key aspect of mitochondrial metabolism, its role extends far beyond energy production to cell signaling and epigenetic regulation–functions that contribute to cellular proliferation, differentiation, apoptosis, migration, and autophagy. Recent research on neurological disorders suggest a major metabolic component in disease pathophysiology, and mitochondria have been shown to be in the center of metabolic dysregulation and possibly …

Quantitative Gadolinium-Free Cardiac Fibrosis Imaging In End Stage Renal Disease Patients Reveals A Longitudinal Correlation With Structural And Functional Decline, Tori A. Stromp, Tyler J. Spear, Rebecca M. Holtkamp, Kristin N. Andres, Joshua C. Kaine, Wissam H. Alghuraibawi, Steve W. Leung, Brandon K. Fornwalt, Moriel H. Vandsburger

Physiology Faculty Publications

Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function. Quantification of changes in MT revealed significantly greater fibrotic burden in patients with ESRD compared to …

H3k9 Methyltransferases And Demethylases Control Lung Tumor-Propagating Cells And Lung Cancer Progression, S. P. Rowbotham, F Li, A. F. M. Dost, S. M. Louie, B. P. Marsh, P. Pessina, C. R. Anbarasu, Christine Fillmore Brainson, S. J. Tuminello, A. Lieberman, S. Ryeom, T. M. Schlaeger, B. J. Aronow, H. Watanabe, K. K. Wong, C. F. Kim

Toxicology and Cancer Biology Faculty Publications

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition …

The Effect Of Coronal Prosthetic Alignment Changes On Socket Reaction Moments, Spatiotemporal Parameters, And Perception Of Alignment During Gait In Individuals With Transtibial Amputation, Hiroshi Hashimoto, Toshiki Kobayashi, Fan Gao, Masataka Kataoka, Kuniharu Okuda

Kinesiology and Health Promotion Faculty Publications

Introduction: The alignment of a prosthesis is clinically determined based on observations by clinicians and the subjective perception of amputees during gait. However, this process has been reported to be unreliable. Socket reaction moment has been reported to be significantly impacted by alignment changes, but the impact of these alignment changes on other gait parameters is unclear. The aim of this study was to investigate the effects of coronal alignment changes of a transtibial prosthesis on socket reaction moment, spatiotemporal parameters, and perceptions of alignment during gait in amputees.

Methods: Nine individuals with transtibial amputation participated in this study. Socket …

Improved Reference Genome For The Domestic Horse Increases Assembly Contiguity And Composition, Theodore S. Kalbfleisch, Edward S. Rice, Michael S. Depriest Jr., Brian P. Walenz, Matthew S. Hestand, Joris R. Vermeesch, Brendan L. O'Connell, Ian T. Fiddes, Alisa O. Vershinina, Nedda F. Saremi, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone, Molly E Mccue, Samantha A. Brooks, Ernest Bailey, Ludovic Orlando, Richard E. Green, Donald C. Miller, Douglas F. Antczak, James N. Macleod

Maxwell H. Gluck Equine Research Center Faculty Publications

Recent advances in genomic sequencing technology and computational assembly methods have allowed scientists to improve reference genome assemblies in terms of contiguity and composition. EquCab2, a reference genome for the domestic horse, was released in 2007. Although of equal or better quality compared to other first-generation Sanger assemblies, it had many of the shortcomings common to them. In 2014, the equine genomics research community began a project to improve the reference sequence for the horse, building upon the solid foundation of EquCab2 and incorporating new short-read data, long-read data, and proximity ligation data. Here, we present EquCab3. The count of …

Waardenburg Syndrome And Left Persistent Superior Vena Cava, Driss Raissi, Alexander Christie, Kimberly Applegate

Radiology Faculty Publications

Waardenburg syndrome (WS) is a rare genetic disorder secondary to neural crest cell developmental abnormalities. It is predominantly described as an auditory-pigmentary syndrome with diverse patient presentation, typically involving congenital sensorineural hearing loss and pigmentation abnormalities of the skin, hair, and iris. Other developmental abnormalities that may be associated with this syndrome are Hirschsprung's disease and a myriad of cardiovascular congenital defects. We present a case of a young girl with WS who found to have a persistent left superior vena cava (PLSVC) draining into the coronary sinus. The prevalence of PLSVC is increased in patients with chromosomal and genetic …

Myeloablative Vs Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation For Chronic Myeloid Leukemia, Saurabh Chhabra, Kwang Woo Ahn, Zhen-Huan Hu, Sandeep Jain, Amer Assal, Jan Cerny, Edward A. Copelan, Andrew Daly, Zachariah Defilipp, Shahinaz M Gadalla, Robert Peter Gale, Siddhartha Ganguly, Betty K. Hamilton, Gerhard C. Hildebrandt, Jack W. Hsu, Yoshihiro Inamoto, Abraham S. Kanate, H. Jean Khoury, Hillard M. Lazarus, Mark R. Litzow, Sunita Nathan, Richard F. Olsson, Attaphol Pawarode, Olle Ringden, Jacob M. Rowe, Ayman Saad, Bipin N. Savani, Harry C. Schouten, Sachiko Seo, Nirav N. Shah

Markey Cancer Center Faculty Publications

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients …

Modulation Of Auxin And Cytokinin Responses By Early Steps Of The Phenylpropanoid Pathway, Jasmina Kurepa, Timothy E. Shull, Sumudu S. Karunadasa, Jan A. Smalle

Plant and Soil Sciences Faculty Publications

Background: The phenylpropanoid pathway is responsible for the synthesis of numerous compounds important for plant growth and responses to the environment. In the first committed step of phenylpropanoid biosynthesis, the enzyme phenylalanine ammonia-lyase (PAL) deaminates L-phenylalanine into trans-cinnamic acid that is then converted into p-coumaric acid by cinnamate-4-hydroxylase (C4H). Recent studies showed that the Kelch repeat F-box (KFB) protein family of ubiquitin ligases control phenylpropanoid biosynthesis by promoting the proteolysis of PAL. However, this ubiquitin ligase family, alternatively named Kiss Me Deadly (KMD), was also implicated in cytokinin signaling as it was shown to promote the degradation of …

Development Of A Diagnostic Marker For Phlebotomus Papatasi To Initiate A Potential Vector Surveillance Program In North America, Austin Merchant, Tian Yu, Jizhe Shi, Xuguo Zhou

Entomology Faculty Publications

Phlebotomus papatasi, an Old World sand fly species, is primarily responsible for the transmission of leishmaniasis, a highly infectious and potentially lethal disease. International travel, especially military rotations, between domestic locations and P. papatasi-prevalent regions in the Middle East poses an imminent threat to the public health of US citizens. Because of its small size and cryptic morphology, identification of P. papatasi is challenging and labor-intensive. Here, we developed a ribosomal DNA-polymerase chain reaction (PCR)-based diagnostic assay that is capable of detecting P. papatasi genomic DNA from mixed samples containing multiple sand flies native to the Americas. Serial …

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …

Isobavachalcone Sensitizes Cells To E2-Induced Paclitaxel Resistance By Down-Regulating Cd44 Expression In Er+ Breast Cancer Cells, Junfeng Shi, Yi Chen, Wenxing Chen, Cuiju Tang, Honghong Zhang, Yuetong Chen, Xiuwei H. Yang, Zhi Xu, Jingsun Wei, Jinfei Chen

Pharmacology and Nutritional Sciences Faculty Publications

Oestrogen receptor (ER) is expressed in approximately 60%‐70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER‐positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER‐negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β‐estradiol (E₂)‐induced paclitaxel resistance and that E₂ could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E₂ could …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Rationale, Design And Methods Of "Set The Rules": A Tailored Peer-To-Peer Health Information Intervention, Jennifer R. Warren, Brandi M. White

Health and Clinical Sciences Faculty Publications

Ensuring equitable access to health information is one strategy to promote health equity for underserved communities, especially for low-income African Americans (AAs). Childcare centers are one viable site to deliver health information to address this disparity. This paper describes the methods used in a community-based participatory research project with a childcare facility that aimed to reduce environmental tobacco smoke (ETS) exposure among low-income AA children. Through collaboration and multiple data collection methods, partners identified communication strategies to overcome informational barriers. These initial findings indicated a peer-to-peer health information intervention, entitled “Set the Rules”, as the best strategy to increase awareness. …

A Novel Tetracycline-Responsive Transgenic Mouse Strain For Skeletal Muscle-Specific Gene Expression, Masahiro Iwata, Davis A. Englund, Yuan Wen, Cory M. Dungan, Kevin A. Murach, Ivan J. Vechetti Jr., Christopher B. Mobley, Charlotte A. Peterson, John J. Mccarthy

Center for Muscle Biology Faculty Publications

Background: The tetracycline-responsive system (Tet-ON/OFF) has proven to be a valuable tool for manipulating gene expression in an inducible, temporal, and tissue-specific manner. The purpose of this study was to create and characterize a new transgenic mouse strain utilizing the human skeletal muscle α-actin (HSA) promoter to drive skeletal muscle-specific expression of the reverse tetracycline transactivator (rtTA) gene which we have designated as the HSA-rtTA mouse.

Methods: To confirm the HSA-rtTA mouse was capable of driving skeletal muscle-specific expression, we crossed the HSA-rtTA mouse with the tetracycline-responsive histone H2B-green fluorescent protein (H2B-GFP) transgenic mouse in order to label myonuclei.

Results: …