Digital Commons Network^™

Rediscovery Of The Endangered Carchi Andean Toad, Rhaebo Colomai (Hoogmoed, 1985), In Ecuador, With Comments On Its Conservation Status And Extinction Risk, Carolina Reyes-Puig, Gabriela B. Bittencourt-Silva, María Torres-Sánchez, Mark Wilkinson, Jeffrey W. Streicher, Simon T. Maddock, Ramachandran Kotharambath, Hendrik Müller, Francesca Nicole Angiolani Larrera, Diego Amieda-Reinoso, Santiago R. Ron, Diego Francisco Cisneros-Heredia

Neuroscience Faculty Publications

Since 1984 there have been no records of Rhaebo colomai (Hoogmoed, 1985) within the territory of Ecuador. This species was known from 2 localities in the province of Carchi, northwestern Ecuador, and the department of Nariño, southwestern Colombia, which were reported in 1979 and 2015, respectively. We report the recent sightings of R. colomai at 3 new localities in Ecuador and discuss and evaluate this species’ extinction risk and conservation status.

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.

Secreted Tumor-Associated Cytochrome As A Blood-Based Biomarker For Cancer, Rolf Joseph Craven

Pharmacology and Nutritional Sciences Faculty Patents

Disclosed herein are methods for detecting Pgrmc 1 in bodily fluids, e.g., blood, plasma and serum, wherein detection of Pgrmcl is a biomarker for the presence of cancer, e.g., lung cancer or head or neck cancer. Pgrmc 1 levels in bodily fluids may be used to predict patient prognosis, e.g., survival and response to therapy.

Deletion Of P38Α Mapk In Microglia Blunts Trauma-Induced Inflammatory Responses In Mice, Josh M. Morganti, Danielle S. Goulding, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the USA and other developed countries worldwide. Following the initial mechanical insult, the brain’s primary innate immune effector, microglia, initiate inflammatory signaling cascades and pathophysiological responses that can lead to chronic neuroinflammation and neurodegenerative sequelae. The p38α MAPK signaling pathway in microglia is a key contributor to inflammatory responses to diverse disease-relevant stressors and injury conditions. Therefore, we tested here whether microglia p38α contributes to acute and persistent inflammatory responses induced by a focal TBI. We generated conditional cell-specific knockout of p38α in microglia using a CX3CR1 …

Root Hair Single Cell Type Specific Profiles Of Gene Expression And Alternative Polyadenylation Under Cadmium Stress, Jingyi Cao, Congting Ye, Guijie Hao, Carole Dabney-Smith, Arthur G. Hunt, Qingshun Q. Li

Plant and Soil Sciences Faculty Publications

Transcriptional networks are tightly controlled in plant development and stress responses. Alternative polyadenylation (APA) has been found to regulate gene expression under abiotic stress by increasing the heterogeneity at mRNA 3′-ends. Heavy metals like cadmium pollute water and soil due to mining and industry applications. Understanding how plants cope with heavy metal stress remains an interesting question. The Arabidopsis root hair was chosen as a single cell model to investigate the functional role of APA in cadmium stress response. Primary root growth inhibition and defective root hair morphotypes were observed. Poly(A) tag (PAT) libraries from single cell types, i.e., root …

Water Permeability/Impermeability In Seeds Of 15 Species Of Caragana (Fabaceae), Dali Chen, Rui Zhang, Carol C. Baskin, Xiaowen Hu

Biology Faculty Publications

Majority legumes in the temperate and arctic zones have water-impermeable seeds (physical dormancy, PY). However, various authors have reported that seeds of some Caragana species are water-permeable and thus non-dormant. We (1) tested seeds of 15 species of Caragana matured in the same site in 2014, 2016 and/or 2017 for presence of PY, (2) determined if dry storage decreased or increased the percentage of seeds with PY and (3) located the site on the seed coat of 11 species where water enters the seed. Sixty-three percent and 45% of the seeds of C. roborovskyi had PY in 2016 and 2017, …

What Lies Beneath? Molecular Evolution During The Radiation Of Caecilian Amphibians, María Torres-Sánchez, David J. Gower, David Alvarez-Ponce, Christopher J. Creevey, Mark Wilkinson, Diego San Mauro

Neuroscience Faculty Publications

Background: Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. …

One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang

Saha Cardiovascular Research Center Faculty Publications

Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides in vivo, male low-density lipoprotein receptor (Ldlr) or apolipoprotein E (Apoe) deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in …

Bamorc: A Software Package For Accurate And Robust 13C Reference Correction Of Protein Nmr Spectra, Xi Chen, Andrey Smelter, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

We describe Bayesian Model Optimized Reference Correction (BaMORC), a software package that performs ¹³C chemical shifts reference correction for either assigned or unassigned peak lists derived from protein NMR spectra. BaMORC provides an intuitive command line interface that allows non-nuclear magnetic resonance (NMR) experts to detect and correct ¹³C chemical shift referencing errors of unassigned peak lists at the very beginning of NMR data analysis, further lowering the bar of expertise required for effective protein NMR analysis. Furthermore, BaMORC provides an application programming interface for integration into sophisticated protein NMR data analysis pipelines, both before and after the …

Discovery Of Glycerol Phosphate Modification On Streptococcal Rhamnose Polysaccharides., Rebecca J Edgar, Vincent P Van Hensbergen, Alessandro Ruda, Andrew G Turner, Pan Deng, Yoann Le Breton, Najib M El-Sayed, Ashton T Belew, Kevin S Mciver, Alastair G Mcewan, Andrew J Morris, Gérard Lambeau, Mark J Walker, Jeffrey S. Rush, Konstantin V Korotkov, Göran Widmalm, Nina M Van Sorge, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A

Potential Reduction Of Lung Dose Via Vmat With Jaw Tracking In The Treatment Of Single-Isocenter/Two-Lesion Lung Sbrt, Damodar Pokhrel, Lana Sanford, Matthew Halfman, Janelle A. Molloy

Radiation Medicine Faculty Publications

Purpose/objectives: Due to higher radiosensitivity, non‐target normal tissue dose is a major concern in stereotactic body radiation therapy (SBRT) treatment. The aim of this report was to estimate the dosimetric impact, specifically the reduction of normal lung dose in the treatment of single‐isocenter/two‐lesion lung SBRT via volumetric modulated arc therapy with jaw tracking (JT‐VMAT).

Materials/methods: Twelve patients with two peripherally located early‐stage non‐small‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal non‐coplanar JT‐VMAT SBRT treatment in our institution. The mean isocenter to tumors distance was 5.6 ± 1.9 (range 4.3–9.5) cm. The mean combined planning target volume (PTV) was 38.7 …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

Hdac Regulates Transcription At The Outset Of Axolotl Tail Regeneration, S. Randal Voss, Larissa V. Ponomareva, Varun B. Dwaraka, Kaitlin E. Pardue, Nour W. Al Haj Baddar, A. Katherine Rodgers, M. Ryan Woodcock, Qingchao Qiu, Anne Crowner, Dana Blichmann, Shivam Khatri, Jon S. Thorson

Neuroscience Faculty Publications

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited …

Determination Of Tobacco Alkaloid Enantiomers Using Reversed Phase Uplc/Ms/Ms, Huihua Ji, Ying Wu, Franklin Fannin, Lowell P. Bush

Kentucky Tobacco Research and Development Center Faculty Publications

Nʹ-Nitrosonornicotine (NNN), a carcinogenic tobacco-specific Nʹ-nitrosamine (TSNA), is on the FDA list of harmful and potentially harmful constituents (HPHCs). Nornicotine, a product of the demethylation of nicotine, is the immediate alkaloid precursor for NNN formation. Nicotine, nornicotine and NNN are optically active. The accumulation of the isomers of nicotine, nornicotine, and NNN impacts their biological activity. In this paper, we report the determination of tobacco alkaloid enantiomers (including nicotine, nornicotine, anabasine, and anatabine) in samples of different tobacco lines using a reversed phase ultra-performance liquid chromatography-tandem mass spectrometer (UPLC/MS/MS) method. Current method demonstates excellent detection capability for all alkaloid enantiomers, …

Predicting Habitat Choice After Rapid Environmental Change, Philip H. Crowley, Pete C. Trimmer, Orr Spiegel, Sean M. Ehlman, William S. Cuello, Andrew Sih

Biology Faculty Publications

Decisions made while searching for settlement sites (e.g., nesting, oviposition) often have major fitness implications. Despite numerous case studies, we lack theory to explain why some species are thriving while others are making poor habitat choices after environmental change. We develop a model to predict (1) which kinds of environmental change have larger, negative effects on fitness, (2) how evolutionary history affects susceptibility to environmental change, and (3) how much lost fitness can be recovered via readjustment after environmental change. We model the common scenario where animals search an otherwise inhospitable matrix, encountering habitats of varying quality and settling when …

Arterial Stiffness During Whole-Body Passive Heat Stress In Healthy Older Adults, Zachary J. Schlader, Yoshiyuki Okada, Stuart A. Best, Qi Fu, Craig G. Crandall

Kinesiology and Health Promotion Faculty Publications

We tested the hypothesis that whole‐body passive heat stress reduces arterial stiffness in older adults. At preheat stress (baseline) and when core temperature was elevated by 0.6 ± 0.2°C (mild) and 1.2 ± 0.3°C (moderate), arterial stiffness was measured in eight healthy younger (26 ± 5 years) and eight healthy older (70 ± 4 years) adults in the supine position. Arterial stiffness was estimated from carotid‐to‐femoral pulse wave velocity (cfPWV, applanation tonometry). cfPWV was higher at baseline in older adults (8.8 ± 2.3 m/sec vs. 5.6 ± 0.9 m/sec, P < 0.01) and this difference was maintained throughout passive heat stress (P < 0.01). cfPWV did not change (P ≥ 0.49) with passive heat stress in either …

Macrolide Derivatives Reduce Proinflammatory Macrophage Activation And Macrophage‐Mediated Neurotoxicity, Bei Zhang, Timothy J. Kopper, Xiaodong Liu, Zheng Cui, Steven G. Van Lanen, John C. Gensel

Physiology Faculty Publications

Introduction: Azithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.

Aims: To improve the efficacy and reduce antibiotic resistance risk of AZM‐based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow‐derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF‐gamma) with and without derivative costimulation. Pro‐ and anti‐inflammatory cytokine production, IL‐12 and IL‐10, respectively, was quantified using ELISA. Neuron culture …

Associations Of First Trimester Co-Use Of Tobacco And Cannabis With Prenatal Immune Response And Psychosocial Well-Being, Kristin Ashford, Amanda Fallin-Bennett, Andrea Mccubbin, Amanda T. Wiggins, Sheila Barnhart, Joshua A. Lile

Perinatal Research and Wellness Center Faculty Publications

PURPOSE: This study aims to describe the association of first trimester co-use of tobacco and cannabis with maternal immune response and psychosocial well-being, relative to tobacco use only.

METHODS: A preliminary midpoint analysis included 138 pregnant women with biologically verified tobacco use, 38 of whom (28%) also tested positive for recent cannabis use. Maternal perceived stress (Perceived Stress Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and serum immune markers (IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, CRP, MMP8), were collected, although cytokine data were only available for 122 women.

RESULTS: Participant average age was 29.1 years, approximately half had a high …

Serum Cotinine Versus Parent Reported Measures Of Secondhand Smoke Exposure In Rural Appalachian Children, Samrat Yeramaneni, Kimberly Yolton, Kurunthachalam Kannan, Kim N. Dietrich, Erin N. Haynes

Journal of Appalachian Health

Background: Secondhand smoke (SHS) exposure in Appalachian children and associated adverse effects is understudied and not well documented. This study assessed the prevalence of SHS exposure in Appalachian children by parental self-report and internal biological measure.

Methods: SHS exposure was determined in children residing in rural Appalachian communities during their participation in the Communities Actively Researching Exposure Study between 2009 and 2013. Parents reported the number of smokers in the household and number of cigarettes smoked/day. Children ages 7-9 provided a serum sample for cotinine analysis. Parent reported measures and child serum cotinine measures of SHS exposure were compared with …

The Social Determinants Of Health And The Decline In U.S. Life Expectancy: Implications For Appalachia, Steven H. Woolf, Heidi Schoomaker, Latoya Hill, Christine M. Orndahl

Journal of Appalachian Health

For the past century, life expectancy in industrialized countries has increased, and the U.S. has shared in that progress. However, beginning in the 1980s, advances in U.S. life expectancy began to lose pace with peer countries. By 1998, U.S. life expectancy had fallen below the average for Organisation for Economic Cooperation and Development nations. U.S. life expectancy peaked in 2014 and has been decreasing for three consecutive years, a trend not been seen since the influenza pandemic a century ago. Put simply, U.S. health is in decline.

Integrative Approaches To The Undergraduate Public Health Major Curriculum: Strengths, Challenges, And Examples, Marc T. Kiviniemi, Sarahmona M. Przybyla

Health, Behavior & Society Faculty Publications

Many “first generation” undergraduate public health degree programs were designed based on “siloed” course structures centered around subunits in the discipline (e.g., Introduction to Epidemiology, Introduction to Environmental Health) that may be meaningful primarily to experts in the field. An alternative to the siloed approach is an integrative curricular design, in which courses are designed around meaningful thematic units (e.g., explaining public health problems, asking and answering scientific questions in public health), with an emphasis on drawing connections between knowledge from different but complementary disciplinary areas as a means to improve student learning and retention. The integrative approach shifts the …

Bacterially Expressed Dsrna Causes Gene Silencing In Eab, Lynne Rieske-Kinney

Entomology Research Data

RNA interference (RNAi) is a naturally occurring, biological process in which RNA molecules inhibit gene expression or translation by neutralizing target mRNA molecules. Recent advances in our understanding of the RNAi mechanism have allowed its development as an emerging tool to protect against insect pests. The major challenge for efficient pest management using RNAi as a molecular bio-pesticide in the field is development of convenient and efficient methods for production, and practical delivery of stable dsRNAs to the target insect. Our goal is to assess the potential for deploying bacterially produced RNAi as a bio-pesticide against an invasive forest pest, …

Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Background: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step …

Gamete Nuclear Migration In Animals And Plants, Umma Fatema, Mohammad F. Ali, Zheng Hu, Anthony J. Clark, Tomokazu Kawashima

Plant and Soil Sciences Faculty Publications

The migration of male and female gamete nuclei to each other in the fertilized egg is a prerequisite for the blending of genetic materials and the initiation of the next generation. Interestingly, many differences have been found in the mechanism of gamete nuclear movement among animals and plants. Female to male gamete nuclear movement in animals and brown algae relies on microtubules. By contrast, in flowering plants, the male gamete nucleus is carried to the female gamete nucleus by the filamentous actin cytoskeleton. As techniques have developed from light, electron, fluorescence, immunofluorescence, and confocal microscopy to live-cell time-lapse imaging using …

Semisynthetic Aurones Inhibit Tubulin Polymerization At The Colchicine-Binding Site And Repress Pc-3 Tumor Xenografts In Nude Mice And Myc-Induced T-All In Zebrafish, Yanqi Xie, Liliia M. Kril, Tianxin Yu, Wen Zhang, Mykhaylo S. Frasinyuk, Svitlana P. Bondarenko, Kostyantyn M. Kondratyuk, Elizabeth Hausman, Zachary M. Martin, Przemyslaw P. Wyrebek, Xifu Liu, Agripina G. Deaciuc, Linda P. Dwoskin, Jing Chen, Haining Zhu, Chang-Guo Zhan, Vitaliy M. Sviripa, Jessica S. Blackburn, David S. Watt, Chunming Liu

Molecular and Cellular Biochemistry Faculty Publications

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC₅₀ values below 100 nM. A xenograft study in nude mice using …

The Effects Of A Bacterial Endotoxin On Behavior And Sensory-Cns-Motor Circuits In Drosophila Melanogaster, Oscar Istas, Abigail Greenhalgh, Robin L. Cooper

Biology Faculty Publications

The effect of bacterial sepsis on animal behavior and physiology is complex due to direct and indirect actions. The most common form of bacterial sepsis in humans is from gram-negative bacterial strains. The endotoxin (lipopolysaccharide, LPS) and/or associated peptidoglycans from the bacteria are the key agents to induce an immune response, which then produces a cascade of immunological consequences. However, there are direct actions of LPS and associated peptidoglycans on cells which are commonly overlooked. This study showed behavioral and neural changes in larval Drosophila fed commercially obtained LPS from Serratia marcescens. Locomotor behavior was not altered, but feeding …

Trans-Cinnamic Acid-Induced Leaf Expansion Involves An Auxin-Independent Component, Jasmina Kurepa, Jan A. Smalle

Plant and Soil Sciences Faculty Publications

The phenylpropanoid pathway, the source of a large array of compounds with diverse functions, starts with the synthesis of trans-cinnamic acid (t-CA) that is converted by cinnamate-4-hydroxylase (C4H) into p-coumaric acid. We have recently shown that in Arabidopsis, exogenous t-CA promotes leaf growth by increasing cell expansion and that this response requires auxin signaling. We have also shown that cell expansion is increased in C4H loss-of-function mutants. Here we provide further evidence that leaf growth is enhanced by either t-CA or a t-CA derivative that accumulates upstream of C4H. We also show that …

Transcriptional Regulation Factors Of The Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (Slc25a13): Usf1 As Basal Factor And Foxa2 As Activator In Liver Cells, Paolo Convertini, Simona Todisco, Francesco De Santis, Ilaria Pappalardo, Dominga Iacobazzi, Maria Antonietta Castiglione Morelli, Yvonne N. Fondufe-Mittendorf, Giuseppe Martelli, Ferdinando Palmieri, Vittoria Infantino

Molecular and Cellular Biochemistry Faculty Publications

Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different …

Bovine Milk Extracellular Vesicles (Evs) Modification Elicits Skeletal Muscle Growth In Rats, Hailey A. Parry, Christopher Brooks Mobley, Petey W. Mumford, Matthew A. Romero, Cody T. Haun, Yufeng Zhang, Paul A. Roberson, Janos Zempleni, Arny A. Ferrando, Ivan J. Vechetti Jr., John J. Mccarthy, Kaelin C. Young, Michael D. Roberts, Andreas N. Kavazis

Physiology Faculty Publications

The current study investigated how bovine milk extracellular vesicles (EVs) affected rotarod performance and biomarkers of skeletal muscle physiology in young, growing rats. Twenty-eight-day Fisher 344 rats were provided an AIN-93G-based diet for 4 weeks that either remained unadulterated [EVs and RNA-sufficient (ERS; n = 12)] or was sonicated [EVs and RNA-depleted (ERD; n = 12)]. Prior to (PRE) and on the last day of the intervention (POST), animals were tested for maximal rotarod performance. Following the feeding period, the gastrocnemius muscle was analyzed at the histological, biochemical, and molecular levels and was also used to measure mitochondrial function and …

The Promise Of Anti-Idiotype Revisited, Heinz Köhler, Anastas Pashov, Thomas Kieber-Emmons

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines. This novel strategy can be adapted in Biotech-standard production of therapeutic antibodies.