Digital Commons Network^™

Compensatory Fetal Membrane Mechanisms Between Biglycan And Decorin In Inflammation., Luciana Batalha De Miranda De Araujo, Casie E Horgan, Abraham Aron, Renato V. Iozzo, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, …

Effects Of Chronic Manganese Exposure On Attention And Working Memory In Non-Human Primates., Jay S. Schneider, Charles Williams, Mark Ault, Tomás R. Guilarte

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Manganese (Mn) is essential for a variety of physiological processes, but at elevated levels, can be neurotoxic. While cognitive dysfunction has been recently appreciated to occur as a result of chronic Mn exposures, it is still unclear as to which cognitive domains are most susceptible to disruption by Mn exposure. We previously described early appearing Mn-induced changes in performance on a paired associate learning task in monkeys chronically exposed to Mn and suggested that performance of this task might be a sensitive tool for detecting cognitive dysfunction resulting from Mn exposure. As chronic Mn exposure has been suggested to be …

Powerful Anti-Tumor And Anti-Angiogenic Activity Of A New Anti-Vascular Endothelial Growth Factor Receptor 1 Peptide In Colorectal Cancer Models, Valeria Cicatiello, Ivana Apicella, Laura Tudisco, Valeria Tarallo, Luigi Formisano, Annamaria Sandomenico, Younghee Kim, Ana Bastos-Carvalho, Augusto Orlandi, Jayakrishna Ambati, Menotti Ruvo, Roberto Bianco, Sandro De Falco

Ophthalmology and Visual Science Faculty Publications

To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit …

Multi-Level Effects Of Low Dose Rate Ionizing Radiation On Southern Toad, Anaxyrus [Bufo] Terrestris, Karolina Stark, David E. Scott, Olga Tsyusko, Daniel P. Coughlin, Thomas G. Hinton

Plant and Soil Sciences Faculty Publications

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d^-1, resulting in total doses up to 15.8 …

Loregic: A Method To Characterize The Cooperative Logic Of Regulatory Factors, Daifeng Wang, Koon-Kiu Yan, Cristina Sisu, Chao Cheng, Joel Rozowsky, William Meyerson, Mark B. Gerstein

Dartmouth Scholarship

The topology of the gene-regulatory network has been extensively analyzed. Now, given the large amount of available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements. To this end, we present Loregic, a computational method integrating gene expression and regulatory network data, to characterize the cooperativity of regulatory factors. Loregic uses all 16 possible two-input-one-output logic gates (e.g. AND or XOR) to describe triplets of two factors regulating a common target. We attempt to find the gate that best matches each triplet’s observed gene expression pattern across many conditions. …

The Comparative Osmoregulatory Ability Of Two Water Beetle Genera Whose Species Span The Fresh-Hypersaline Gradient In Inland Waters (Coleoptera: Dytiscidae, Hydrophilidae)., Susana Pallarés, Paula Arribas, David T. Bilton, Andrés Millán, Josefa Velasco

School of Biological and Marine Sciences

A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their …

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Mapk Signaling Pathway Alters Expression Of Midgut Alp And Abcc Genes And Causes Resistance To Bacillus Thuringiensis Cry1ac Toxin In Diamondback Moth, Zhaojiang Guo, Shi Kang, Defeng Chen, Qingjun Wu, Shaoli Wang, Wen Xie, Xun Zhu, Simon W. Baxter, Xuguo Zhou, Juan Luis Jurat-Fuentes, Youjun Zhang

Entomology Faculty Publications

Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP …

Transcriptional Activity Of The Islet Β Cell Factor Pdx1 Is Augmented By Lysine Methylation Catalyzed By The Methyltransferase Set7/9, Aarthi V. Maganti, Bernhard Maier, Sarah A. Tersey, Megan L. Sampley, Amber L. Mosley, Sabire Özcan, Boobalan Pachaiyappan, Patrick M. Woster, Chad S. Hunter, Roland Stein, Raghavendra G. Mirmira

Molecular and Cellular Biochemistry Faculty Publications

The transcription factor Pdx1 is crucial to islet β cell function and regulates target genes in part through interaction with coregulatory factors. Set7/9 is a Lys methyltransferase that interacts with Pdx1. Here we tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Using mass spectrometry and mutational analysis of purified proteins, we found that Set7/9 methylates the N-terminal residues Lys-123 and Lys-131 of Pdx1. Methylation of these residues occurred only in the context of intact, full-length Pdx1, suggesting a specific requirement of secondary and/or tertiary structural elements for catalysis by Set7/9. Immunoprecipitation assays and mass …

One-Step Generation Of Multiple Transgenic Mouse Lines Using An Improved Pronuclear Injection-Based Targeted Transgenesis (I-Pitt)., Masato Ohtsuka, Hiromi Miura, Keiji Mochida, Michiko Hirose, Ayumi Hasegawa, Atsuo Ogura, Ryuta Mizutani, Minoru Kimura, Ayako Isotani, Masahito Ikawa, Masahiro Sato, Channabasavaiah B. Gurumurthy

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The pronuclear injection (PI) is the simplest and widely used method to generate transgenic (Tg) mice. Unfortunately, PI-based Tg mice show uncertain transgene expression due to random transgene insertion in the genome, usually with multiple copies. Thus, typically at least three or more Tg lines are produced by injecting over 200 zygotes and the best line/s among them are selected through laborious screening steps. Recently, we developed technologies using Cre-loxP system that allow targeted insertion of single-copy transgene into a predetermined locus through PI. We termed the method as PI-based Targeted Transgenesis (PITT). A similar method using PhiC31-attP/B system …

Seasonal Change In The Avian Hippocampus., David F Sherry, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

The hippocampus plays an important role in cognitive processes, including memory and spatial orientation, in birds. The hippocampus undergoes seasonal change in food-storing birds and brood parasites, there are changes in the hippocampus during breeding, and further changes occur in some species in association with migration. In food-storing birds, seasonal change in the hippocampus occurs in fall and winter when the cognitively demanding behaviour of caching and retrieving food occurs. The timing of annual change in the hippocampus of food-storing birds is quite variable, however, and appears not to be under photoperiod control. A variety of factors, including cognitive performance, …

Antibody-Mediated Targeting Of Iron Oxide Nanoparticles To The Folate Receptor Alpha Increases Tumor Cell Association In Vitro And In Vivo, Christian Ndong, Seiko Toraya-Brown, Katsiaryna Kekalo, Ian Baker, Tillman U. Gerngross, Steven N. Fiering, Karl E. Griswold

Dartmouth Scholarship

Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLRα) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLRα-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLRα-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm …

Pathways Involved In Interleukin-1Β-Mediated Murine Cardiomyocyte Apoptosis, Yi Shen, Jie Qin, Peili Bu

The Texas Heart Institute Journal

Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an essential role in the pathogenesis of heart failure by inducing cardiomyocyte apoptosis, but the mechanisms of this process are poorly defined. We further explored these molecular pathways.

We isolated cardiomyocytes from neonatal mice and then cultured and stimulated them with murine IL-1β in vitro. Cell apoptotic ratios were measured by means of flow cytometry. Expression of effector molecules was analyzed by means of enzyme-linked immunosorbent assay, Western blotting, and real-time quantitative polymerase chain reaction. The results showed that IL-1β induced murine cardiomyocyte apoptosis through a release of cytochrome c into cytoplasm …

Stably Expressed Housekeeping Genes Across Developmental Stages In The Two-Spotted Spider Mite, Tetranychus Urticae, Chunxiao Yang, Huipeng Pan, Yong Liu, Xuguo Zhou

Entomology Faculty Publications

Quantitative real-time PCR (qRT-PCR) is a reliable and reproducible technique for measuring mRNA expression. To facilitate gene expression studies and obtain more accurate qRT-PCR analysis, normalization relative to stable housekeeping genes is mandatory. In this study, ten housekeeping genes, including beta-actin (Actin), elongation factor 1 α (EF1A), glyceralde hyde-3-phosphate dehydrogenase (GAPDH), ribosomal protein L13 (RPL13), ribosomal protein 49 (RP49), α-tubulin (Tubulin), vacuolar-type H+-ATPase (v-ATPase), succinate dehydrogenase subunit A (SDHA) , 28S ribosomal RNA (28S), and 18S ribosomal RNA (18S) from …

Lactobacillus Rhamnosus Lowers Zebrafish Lipid Content By Changing Gut Microbiota And Host Transcription Of Genes Involved In Lipid Metabolism., Silvia Falcinelli, Simona Picchietti, Ana Rodiles, Lina Cossignani, Daniel L. Merrifield, Anna Rita Taddei, Francesca Maradonna, Ike Olivotto, Giorgia Gioacchini, Oliana Carnevali

School of Biological and Marine Sciences

The microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed that Lactobacillus rhamnosus was able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in …

Hco3(-)-Independent Ph Regulation In Astrocytes In Situ Is Dominated By V-Atpase., Daniel Bloch Hansen, Nestor Garrido-Comas, Mike Salter, Robert Fern

More Faculty of Health Research

The mechanisms of HCO3(-)-independent intracellular pH (pHi) regulation were examined in fibrous astrocytes within isolated neonatal rat optic nerve (RON) and in cultured cortical astrocytes. In agreement with previous studies, resting pHi in cultured astrocytes was 6.82 ± 0.06 and inhibition of the V-ATPase H(+) pump by Cl(-) removal or via the selective inhibitor bafilomycin had only a small effect upon resting pHi and recovery following an acid load. In contrast, resting pHi in RON astrocytes was 7.10 ± 0.04, significantly less acidic than that in cultured cells (p < 0.001), and responded to inhibition of V-ATPase with profound acidification to the 6.3-6.5 range. Fluorescent immuno-staining and immuno-gold labeling confirmed the presence V-ATPase in the cell membrane of RON astrocyte processes and somata. Using ammonia pulse recovery, pHi recovery in RON astrocyte was achieved largely via V-ATPase with sodium-proton exchange (NHE) playing a minor role. The findings indicate that astrocytes in a whole-mount preparation such as the optic nerve rely to a greater degree upon V-ATPase for HCO3(-)-independent pHi regulation than do cultured astrocytes, with important functional consequences for the regulation of pH in the CNS.

Review Of Nanomaterials In Dentistry: Interactions With The Oral Microenvironment, Clinical Applications, Hazards, And Benefits., Alexandros Besinis, Peralta T De, Christopher J. Tredwin, Richard D. Handy

School of Engineering, Computing and Mathematics

Interest in the use of engineered nanomaterials (ENMs) as either nanomedicines or dental materials/devices in clinical dentistry is growing. This review aims to detail the ultrafine structure, chemical composition, and reactivity of dental tissues in the context of interactions with ENMs, including the saliva, pellicle layer, and oral biofilm; then describes the applications of ENMs in dentistry in context with beneficial clinical outcomes versus potential risks. The flow rate and quality of saliva are likely to influence the behavior of ENMs in the oral cavity, but how the protein corona formed on the ENMs will alter bioavailability, or interact with …

Individual Quality And Personality: Bolder Males Are Less Fecund In The Hermit Crab Pagurus Bernhardus., Danielle Bridger, Simon J. Bonner, Mark Briffa

School of Biological and Marine Sciences

One explanation for animal personality is that different behavioural types derive from different life-history strategies. Highly productive individuals, with high growth rates and high fecundity, are assumed to live life at a fast pace showing high levels of boldness and risk taking, compared with less productive individuals. Here, we investigate among-individual differences in mean boldness (the inverse of the latency to recover from a startling stimulus) and in the consistency of boldness, in male hermit crabs in relation to two aspects of life-history investment. We assessed aerobic scope by measuring the concentration of the respiratory pigment haemocyanin, and we assessed …

Predicted Protein-Protein Interactions In The Moss Physcomitrella Patens: A New Bioinformatic Resource., Scott Schuette, Brian Piatkowski, Aaron Corley, Daniel Lang, Matt Geisler

Publications

BACKGROUND: Physcomitrella patens, a haploid dominant plant, is fast becoming a useful molecular genetics and bioinformatics tool due to its key phylogenetic position as a bryophyte in the post-genomic era. Genome sequences from select reference species were compared bioinformatically to Physcomitrella patens using reciprocal blasts with the InParanoid software package. A reference protein interaction database assembled using MySQL by compiling BioGrid, BIND, DIP, and Intact databases was queried for moss orthologs existing for both interacting partners. This method has been used to successfully predict interactions for a number of angiosperm plants.

RESULTS: The first predicted protein-protein interactome for a bryophyte …

Methyl Farnesoate Plays A Dual Role In Regulating Drosophila Metamorphosis, Di Wen, Crisalejandra Rivera-Perez, Mohamed Abdou, Qiangqiang Jia, Qianyu He, Xi Liu, Ola Zyaan, Jingjing Xu, William G. Bendena, Stephen S. Tobe, Fernando G. Noriega, Subba R. Palli, Jian Wang, Sheng Li

Entomology Faculty Publications

Corpus allatum (CA) ablation results in juvenile hormone (JH) deficiency and pupal lethality in Drosophila. The fly CA produces and releases three sesquiterpenoid hormones: JH III bisepoxide (JHB3), JH III, and methyl farnesoate (MF). In the whole body extracts, MF is the most abundant sesquiterpenoid, followed by JHB3 and JH III. Knockout of JH acid methyl transferase (jhamt) did not result in lethality; it decreased biosynthesis of JHB3, but MF biosynthesis was not affected. RNAi-mediated reduction of 3-hydroxy-3-methylglutaryl CoA reductase (hmgcr) expression in the CA decreased biosynthesis and titers of the three sesquiterpenoids, resulting in …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

Cd47 Deficiency Protects Mice From Diet-Induced Obesity And Improves Whole Body Glucose Tolerance And Insulin Sensitivity, Hasiyeti Maimaitiyiming, Heather Norman, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were …

Metabolic Reprogramming Of Cancer-Associated Fibroblasts By Idh3Α Downregulation, Daoxiang Zhang, Yongbin Wang, Zhimin Shi, Jingyi Liu, Pan Sun, Xiaodan Hou, Jian Zhang, Shimin Zhao, Binhua P. Zhou, Jun Mi

Markey Cancer Center Faculty Publications

Cancer-associated fibroblasts (CAFs) provide critical metabolites for tumor growth and undergo metabolic reprogramming to support glycolysis. However, the molecular mechanisms responsible for this change remain unclear. Here, we report that TGF-β1- or PDGF-induced CAFs switch from oxidative phosphorylation to aerobic glycolysis. We identify downregulation of isocitrate dehydrogenase 3α (IDH3α) as a marker for this switch. Furthermore, miR-424 downregulates IDH3α during CAF formation. Downregulation of IDH3α decreases the effective level of α-ketoglutarate (α-KG) by reducing the ratio of α-KG to fumarate and succinate, resulting in PHD2 inhibition and HIF-1α protein stabilization. The accumulation of HIF-1α, in turn, promotes glycolysis by increasing …

Identification Of A Family Of Fatty Acid-Speciated Sonic Hedgehog Proteins, Whose Members Display Differential Biological Properties, Jun Long, Robert Tokhunts, William M. Old, Stephane Houel, Jezabel Rodgriguez-Blanco, Samer Singh, Neal Schilling, Anthony J. Capobianco, Natalie G. Ahn, David J. Robbins

Dartmouth Scholarship

Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH …

Overexpression Of Mir‑145 In U87 Cells Reduces Glioma Cell Malignant Phenotype And Promotes Survival After In Vivo Implantation, Yong Lu, Michael Chopp, Xuguang Zheng, Mark Katakowski, Ding Wang, Elise Fraser, Monique Nguyen, Feng Jiang

Neurology Articles

In the present study, we sought to elucidate the effect of miR‑145 on glioma cell progression and its mechanisms of action. We examined the effects of miR‑145 on proliferation and invasion of U87 glioma cells and on capillary tube formation. Our data show that restoration of miR‑145 in U87 glioma cells significantly reduced their in vitro proliferation, invasion and angiogenesis. However, decreased miR‑145 expression promoted U87 glioma cell proliferation, invasion and angiogenesis, and reduced-expression of miR‑145 increased ADAM17 and EGFR expression in U87 cells. Overexpression of miR‑145 reduced ADAM17 and EGFR expression. VEGF secretion and VEGF expression were decreased by …

Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the …

Cosmetics For The Matrix: An Attractive New Style For Matrix Biology., Renato V. Iozzo, Thomas Neill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation In Calyx-Bearing Vestibular Afferents, J. Chris Holt, Kevin Kewin, Paivi M. Jordan, Peter Cameron, Marcin Klapczynski, J. Michael Mcintosh, Peter A. Crooks, Linda P. Dwoskin, Anna Lysakowski

Pharmaceutical Sciences Faculty Publications

Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton …

Analysis Of Cathepsin And Furin Proteolytic Enzymes Involved In Viral Fusion Protein Activation In Cells Of The Bat Reservoir Host, Farah El Najjar, Levi Lampe, Michelle L. Baker, Lin-Fa Wang, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Bats of different species play a major role in the emergence and transmission of highly pathogenic viruses including Ebola virus, SARS-like coronavirus and the henipaviruses. These viruses require proteolytic activation of surface envelope glycoproteins needed for entry, and cellular cathepsins have been shown to be involved in proteolysis of glycoproteins from these distinct virus families. Very little is currently known about the available proteases in bats. To determine whether the utilization of cathepsins by bat-borne viruses is related to the nature of proteases in their natural hosts, we examined proteolytic processing of several viral fusion proteins in cells derived from …