Cancer exosomes trigger fibroblast to myofibroblast differentiation.
AuthorsWebber J, Steadman R, Mason MD, Tabi Z, Clayton A
JournalCancer Res
PubMed ID21098712
There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated ... More
Chimeric transcript discovery by paired-end transcriptome sequencing.
AuthorsMaher CA, Palanisamy N, Brenner JC, Cao X, Kalyana-Sundaram S, Luo S, Khrebtukova I, Barrette TR, Grasso C, Yu J, Lonigro RJ, Schroth G, Kumar-Sinha C, Chinnaiyan AM
JournalProc Natl Acad Sci U S A
PubMed ID19592507
'Recurrent gene fusions are a prevalent class of mutations arising from the juxtaposition of 2 distinct regions, which can generate novel functional transcripts that could serve as valuable therapeutic targets in cancer. Therefore, we aim to establish a sensitive, high-throughput methodology to comprehensively catalog functional gene fusions in cancer by ... More
Deep RNA sequencing at single base-pair resolution reveals high complexity of the rice transcriptome.
AuthorsZhang G, Guo G, Hu X, Zhang Y, Li Q, Li R, Zhuang R, Lu Z, He Z, Fang X, Chen L, Tian W, Tao Y, Kristiansen K, Zhang X, Li S, Yang H, Wang J, Wang J
JournalGenome Res
PubMed ID20305017
'Understanding the dynamics of eukaryotic transcriptome is essential for studying the complexity of transcriptional regulation and its impact on phenotype. However, comprehensive studies of transcriptomes at single base resolution are rare, even for modern organisms, and lacking for rice. Here, we present the first transcriptome atlas for eight organs of ... More
Biotic and abiotic stimulation of root epidermal cells reveals common and specific responses to arbuscular mycorrhizal fungi.
AuthorsGenre A, Ortu G, Bertoldo C, Martino E, Bonfante P
JournalPlant Physiol
PubMed ID19151131
'During arbuscular mycorrhizal (AM) colonization, a focal accumulation of organelles occurs in root epidermal cells, prior to fungal penetration, beneath adhering hyphopodia. This is followed by the appearance of the prepenetration apparatus (PPA), a transcellular column of cytoplasm connected to the nucleus and rich in cytoskeleton and secretory endomembranes. This ... More
Deletion of CD14 attenuates Alzheimer's disease pathology by influencing the brain's inflammatory milieu.
AuthorsReed-Geaghan EG, Reed QW, Cramer PE, Landreth GE
JournalJ Neurosci
PubMed ID21084593
'Alzheimer''s disease (AD) is characterized by the deposition of beta-amyloid (Abeta)-containing plaques within the brain that is accompanied by a robust microglial-mediated inflammatory response. This inflammatory response is reliant upon engagement of innate immune signaling pathways involving the toll-like receptors (TLRs). Studies assessing the roles of TLRs in AD pathogenesis ... More
Transmission of Tomato chlorotic dwarf viroid by bumblebees (Bombus ignitus) in tomato plants
AuthorsMatsuura, S; Matsushita, Y; Kozuka, R; Shimizu, S; Tsuda, S
Journal
PubMed ID
'Quantitative PCR revealed that Tomato chlorotic dwarf viroid (TCDVd) was present in substantial amounts in viroid-infected tomato flowers. Healthy tomato plants were arranged in two different glasshouses, and plants were mechanically inoculated with TCDVd. Bumblebees (Bombus ignitus) were then introduced into the glasshouses to reveal whether the viroid was transmitted ... More
Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo
'Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted ... More
Wnt signaling promotes oral but suppresses aboral structures in Hydractinia metamorphosis and regeneration.
AuthorsDuffy DJ, Plickert G, Kuenzel T, Tilmann W, Frank U
JournalDevelopment
PubMed ID20685735
'We studied the role of Wnt signaling in axis formation during metamorphosis and regeneration in the cnidarian Hydractinia. Activation of Wnt downstream events during metamorphosis resulted in a complete oralization of the animals and repression of aboral structures (i.e. stolons). The expression of Wnt3, Tcf and Brachyury was upregulated and ... More
Hormone depletion-insensitivity of prostate cancer cells is supported by the AR without binding to classical response elements.
AuthorsGonit M, Zhang J, Salazar M, Cui H, Shatnawi A, Trumbly R, Ratnam M
JournalMol Endocrinol
PubMed ID21330406
'A need for androgen response elements (AREs) for androgen receptor (AR)-dependent growth of hormone depletion-insensitive prostate cancer is generally presumed. In such cells, androgen-independent activation by AR of certain genes has been attributed to selective increases in basal associations of AR with putative enhancers. We examined the importance of AR ... More
A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target.
AuthorsHe C, Nora GP, Schneider EL, Kerr ID, Hansell E, Hirata K, Gonzalez D, Sajid M, Boyd SE, Hruz P, Cobo ER, Le C, Liu WT, Eckmann L, Dorrestein PC, Houpt ER, Brinen LS, Craik CS, Roush WR, McKerrow J, Reed SL
JournalJ Biol Chem
PubMed ID20378535
'Entamoeba histolytica cysteine proteinases (EhCPs) play a key role in disrupting the colonic epithelial barrier and the innate host immune response during invasion of E. histolytica, the protozoan cause of human amebiasis. EhCPs are encoded by 50 genes, of which ehcp4 (ehcp-a4) is the most up-regulated during invasion and ... More
Calpain 1 and Calpastatin expression is developmentally regulated in rat brain
AuthorsLi, YZ; Bondada, V; Joshi, A; Geddes, JW
Journal
PubMed ID
'Calpains and caspases are cysteine endopeptidases which share many similar substrates. Caspases are essential for caspase-dependent apoptotic death where calpains may play an augmentive role, while calpains are strongly implicated in necrotic cell death morphologies. Previous studies have demonstrated a down-regulation in the expression of many components of the caspase-dependent ... More
Direct interaction of nuclear liver X receptor-beta with ABCA1 modulates cholesterol efflux.
AuthorsHozoji M, Munehira Y, Ikeda Y, Makishima M, Matsuo M, Kioka N, Ueda K
JournalJ Biol Chem
PubMed ID18782758
'Cholesterol is an essential component of eukaryotic cells; at the same time, however, hyperaccumulation of cholesterol is harmful. Therefore, the ABCA1 gene, the product of which mediates secretion of cholesterol, is highly regulated at both the transcriptional and post-transcriptional levels. The transcription of ABCA1 is regulated by intracellular oxysterol ... More
MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4.
AuthorsYao G, Yin M, Lian J, Tian H, Liu L, Li X, Sun F
JournalMol Endocrinol
PubMed ID20118412
'Many members of the TGF-beta superfamily are indicated to play important roles in ovarian follicular development, such as affecting granulosa cell function and oocyte maturation. Abnormalities associated with TGF-beta1 signaling transduction could result in female infertility. MicroRNAs (miRNAs), as small noncoding RNAs, were recently found to regulate gene expression ... More
Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling.
AuthorsRocha PP, Scholze M, Bleiss W, Schrewe H
JournalDevelopment
PubMed ID20630950
'The Mediator complex is commonly seen as a molecular bridge that connects DNA-bound transcription factors to the RNA polymerase II (Pol II) machinery. It is a large complex of 30 subunits that is present in all eukaryotes. The Med12 subunit has been implicated not only in the regulation of Pol ... More
4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice.
'Our objective was to contrast the effect of apolipoprotein (apo) A-I mimetic peptides, such as 4F and 4F-Pro-4F (Pro), on nascent and mature atherosclerotic lesions and on levels of antibodies against oxidation-specific epitopes. Chow-fed apoE(-/-) mice were injected intraperitoneally with either the 4F peptide or a tandem helix apoA-I mimetic ... More
SCF/{beta}-TrCP Promotes Glycogen Synthase Kinase 3-Dependent Degradation of the Nrf2 Transcription Factor in a Keap1-Independent Manner.
AuthorsRada P, Rojo AI, Chowdhry S, McMahon M, Hayes JD, Cuadrado A
JournalMol Cell Biol
PubMed ID21245377
'Regulation of transcription factor Nrf2 (NF-E2-related factor 2) involves redox-sensitive proteasomal degradation via the E3 ubiquitin ligase Keap1/Cul3. However, Nrf2 is controlled by other mechanisms that have not yet been elucidated. We now show that glycogen synthase kinase 3 (GSK-3) phosphorylates a group of Ser residues in the Neh6 domain ... More
Expression of I-CreI endonuclease generates deletions within the rDNA of Drosophila.
AuthorsParedes S, Maggert KA
JournalGenetics
PubMed ID19171942
'The rDNA arrays in Drosophila contain the cis-acting nucleolus organizer regions responsible for forming the nucleolus and the genes for the 28S, 18S, and 5.8S/2S RNA components of the ribosomes and so serve a central role in protein synthesis. Mutations or alterations that affect the nucleolus organizer region have ... More
Phosphorylation of the RNA polymerase II C-terminal domain by TFIIH kinase is not essential for transcription of Saccharomyces cerevisiae genome.
AuthorsHong SW, Hong SM, Yoo JW, Lee YC, Kim S, Lis JT, Lee DK
JournalProc Natl Acad Sci U S A
PubMed ID19666497
'Ser-5 phosphorylation of the RNA polymerase II (Pol II) C-terminal domain by TFIIH kinase has been implicated in critical steps in mRNA synthesis, such as Pol II promoter escape and mRNA 5''-capping. However, the general requirement and precise role of TFIIH kinase in Pol II transcription still remain elusive. Here ... More
A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis.
'A G to C polymorphism (rs2910164) is located within the sequence of miR-146a precursor, which leads to a change from a G:U pair to a C:U mismatch in its stem region. The predicted miR-146a target genes include BRCA1 and BRCA2, which are key breast and ovarian cancer genes. To ... More
Unique SNP in CD44 intron 1 and its role in breast cancer development.
AuthorsZhou J, Nagarkatti PS, Zhong Y, Creek K, Zhang J, Nagarkatti M
JournalAnticancer Res
PubMed ID20530438
'In the current study, we investigated if CD44 polymorphisms are associated with increased susceptibility to breast cancer. Direct nucleotide sequencing analysis identified a novel and unique single nucleotide polymorphism (SNP, designated as CD44 Ex2+14 A>G) in the CD44 intron 1 region in 84% of breast cancer patients, which was significantly ... More
Tyrosine and serine phosphorylation of α-synuclein have opposing effects on neurotoxicity and soluble oligomer formation
'Mutations in the neuronal protein α-synuclein cause familial Parkinson disease. Phosphorylation of α-synuclein at serine 129 is prominent in Parkinson disease and influences α-synuclein neurotoxicity. Here we report that α-synuclein is also phosphorylated at tyrosine 125 in transgenic Drosophila expressing wildtype human α-synuclein and that this tyrosine phosphorylation protects from ... More
Lymphangiogenesis and angiogenesis: concurrence and/or dependence? Studies in inbred mouse strains.
AuthorsNakao S, Maruyama K, Zandi S, Melhorn MI, Taher M, Noda K, Nusayr E, Doetschman T, Hafezi-Moghadam A
JournalFaseb J
PubMed ID19858096
'Genetic background significantly affects angiogenesis in mice. However, lymphangiogenic response to growth factors (GFs) in different strains has not been studied. We report constitutive expression of corneal lymphatics that extends beyond the limits of normal limbal vessels. In untreated corneas, the total number (P=0.006), the number above blood vessels (P=10(-8)), ... More
H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice.
AuthorsIchise T, Yoshida N, Ichise H
JournalDevelopment
PubMed ID20179099
'Mammalian Ras, which is encoded by three independent genes, has been thought to be a versatile component of intracellular signalling. However, when, where and how Ras signalling plays essential roles in development and whether the three Ras genes have overlapping functions in particular cells remain unclear. Here, we show that ... More
Plasticity of stem cells derived from adult periodontal ligament
'Background: The neural crest contains pluripotent cells that can give rise to neurons and glial cells of the peripheral nervous system, endocrine cells, connective tissue cells, muscle cells and pigment cells during embryonic development. Stem cells derived from the neural crest may still reside in neural crest derivatives including the ... More
The Suppression of MAD1 by AKT-Mediated Phosphorylation Activates MAD1 Target Genes Transcription
'MAX dimerization protein 1 (MAD1) is a transcription suppressor that antagonizes MYC-mediated transcription activation, and the inhibition mechanism occurs mainly through the competition of target genes'' promoter MYC binding sites by MAD1. The promoter binding proteins switch between MYC and MAD1 affects cell proliferation and differentiation. However, little is known ... More
Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis.
AuthorsHashimoto Y, Akiyama Y, Otsubo T, Shimada S, Yuasa Y,
JournalCarcinogenesis
PubMed ID20080834
'Aberrant expression of microRNA (miRNA) has been reported in various cancers. To clarify the role of miRNA in gastric carcinogenesis, we performed miRNA microarray analysis and investigated expression changes of miRNAs in a 5-aza-2''-deoxycytidine (5-aza-CdR)-treated gastric cancer cell line, KATO-III. On microarray analysis, five miRNAs were found to be upregulated ... More
Murine gammaherpesvirus 68 open reading frame 75c tegument protein induces the degradation of PML and is essential for production of infectious virus.
AuthorsLing PD, Tan J, Sewatanon J, Peng R
JournalJ Virol
PubMed ID18508901
'Promyelocytic Leukemia nuclear body (PML NB) proteins mediate an intrinsic cellular host defense response against virus infections. Herpesviruses express proteins that modulate PML or PML-associated proteins by a variety of strategies, including degradation of PML or relocalization of PML NB proteins. The consequences of PML-herpesvirus interactions during infection in vivo ... More
Quercetin administration ameliorates pulmonary complications of cirrhosis in rats.
'In the hepatopulmonary syndrome (HPS), a common complication of liver cirrhosis, pulmonary endothelial endothelin B (ETB) receptor overexpression, enhanced endothelial nitric oxide (NO) synthase (eNOS)-derived NO production, and increases in pulmonary inducible NO synthase (iNOS) and heme oxygenase (HO-1) are important factors in the development of vasodilatation. These changes ... More
Differential modulation of human β-defensins expression in human gingival epithelia by Porphyromonas gingivalis lipopolysaccharide with tetra- and penta-acylated lipid A structures
'Porphyromonas gingivalis lipopolysaccharide (LPS) is a crucial virulence factor strongly involved in the development of chronic periodontitis. It displays a significant amount of lipid A structural heterogeneity, containing both tetra-(LPS(1435/1449)) and penta-acylated (LPS(1690)) lipid A structures with opposing effects on E-selectin expression in human endothelial cells. Little is known about ... More
Kinase activity of the dgk gene product is involved in the virulence of Streptococcus mutans.
AuthorsShibata Y, van der Ploeg JR, Kozuki T, Shirai Y, Saito N, Kawada-Matsuo M, Takeshita T, Yamashita Y
JournalMicrobiology
PubMed ID19202104
'C-terminal deletion of the diacylglycerol kinase (Dgk) homologue of the cariogenic oral bacterium Streptococcus mutans resulted in loss of aciduricity. To confirm the role of the C terminus of the Dgk homologue in aciduricity, various mutants of S. mutans UA159 with a C-terminally truncated Dgk homologue were constructed. The deletion ... More
Retinoblastoma cells are inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase.
AuthorsTheodoropoulou S, Kolovou PE, Morizane Y, Kayama M, Nicolaou F, Miller JW, Gragoudas E, Ksander BR, Vavvas DG
JournalFaseb J
PubMed ID20371623
'5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an analog of AMP, is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. We studied the effects of AICAR on the growth of retinoblastoma cell lines (Y79, WERI, and RB143). AICAR inhibited Rb cell growth, induced ... More
Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes.
AuthorsKoller E, Vincent TM, Chappell A, De S, Manoharan M, Bennett CF
JournalNucleic Acids Res
PubMed ID21345934
'Single-stranded antisense oligonucleotides (SSOs) are used to modulate the expression of genes in animal models and are being investigated as potential therapeutics. To better understand why synthetic SSOs accumulate in the same intracellular location as the target RNA, we have isolated a novel mouse hepatocellular SV40 large T-antigen carcinoma cell ... More
Toll-like receptor 2 mediates the activation of human monocytes and endothelial cells by antiphospholipid antibodies.
AuthorsSatta N, Kruithof EK, Fickentscher C, Dunoyer-Geindre S, Boehlen F, Reber G, Burger D, de Moerloose P
JournalBlood
PubMed ID21330474
'The presence of antiphospholipid antibodies (aPLAs) is associated with arterial or venous thrombosis and/or recurrent fetal loss. The proposed pathogenic mechanisms for aPLA effects include the inflammatory activation of monocytes and endothelial cells. Toll-like receptors (TLRs) are candidate signaling intermediates. The aim of this study was to investigate the relative ... More
Neuronal insulin receptor substrate 2 (IRS2) expression is regulated by ZBP89 and SP1 binding to the IRS2 promoter.
AuthorsUdelhoven M, Pasieka M, Leeser U, Krone W, Schubert M
JournalJ Endocrinol
PubMed ID19875459
'Since neuronal insulin receptor substrate 2 (IRS2)-mediated signals coordinate key processes in rodent physiology such as food intake, fertility, longevity, and aging-related behavior, we analyzed the mechanisms of neuronal IRS2 expression in neuroblastoma (SHSY5Y) and hypothalamic (GT1-7) cell lines. Using dual luciferase reporter assays and IRS2 promoter deletion constructs, we ... More
An inducible RNA interference system for the functional dissection of mouse embryogenesis.
AuthorsVidigal JA, Morkel M, Wittler L, Brouwer-Lehmitz A, Grote P, Macura K, Herrmann BG
JournalNucleic Acids Res
PubMed ID20350929
'Functional analysis of multiple genes is key to understanding gene regulatory networks controlling embryonic development. We have developed an integrated vector system for inducible gene silencing by shRNAmir-mediated RNA interference in mouse embryos, as a fast method for dissecting mammalian gene function. For validation of the vector system, we ... More
Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury.
AuthorsLeedom AJ, Sullivan AB, Dong B, Lau D, Gronert K
JournalAm J Pathol
PubMed ID20008149
'Inflammation and angiogenesis are intimately linked, and their dysregulation leads to pathological angiogenesis in human diseases. 15-lipoxygenase (15-LOX) and lipoxin A(4) receptors (ALX) constitute a LXA(4) circuit that is a key feature of inflammatory resolution. LXA(4) analogs have been shown to regulate vascular endothelial growth factor (VEGF)-A-induced angiogenic response in ... More
Effects of feed supplementation with specific hen egg yolk antibody (immunoglobin Y) on Salmonella species cecal colonization and growth performances of challenged broiler chickens
AuthorsChalghoumi, R; Marcq, C; Thewis, A; Portetelle, D; Beckers, Y
Journal
PubMed ID
'Anti-Salmonella spp. egg yolk antibodies (IgY) simultaneously directed against Salmonella Enteritidis and Salmonella Typhimurium were tested to determine if their inclusion in feed decreased Salmonella spp. cecal colonization in experimentally infected broiler chickens. Egg yolk powder (EYP) was obtained by freeze-drying egg yolks containing anti-Salmonella spp. Immunoglobin Y was included ... More
MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions.
Authorsdu Rieu MC, Torrisani J, Selves J, Al Saati T, Souque A, Dufresne M, Tsongalis GJ, Suriawinata AA, Carrere N, Buscail L, Cordelier P
JournalClin Chem
PubMed ID20093556
'BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the poorest overall prognosis among gastrointestinal cancers; however, curative resection in early-stage PDAC greatly improves survival rates, indicating the importance of early detection. Because abnormal microRNA production is commonly detected in cancer, we investigated noninvasive precursor pancreatic intraepithelial neoplasia (PanIN) lesions for microRNA production ... More
Tumor necrosis factor-α augments lipopolysaccharide-induced suppressor of cytokine signalling 3 (SOCS-3) protein expression by preventing the degradation
'The regulatory role of tumour necrosis factor-α (TNF-α) on the expression of suppressor of cytokine signalling 3 (SOCS-3) in response to lipopolysaccharide (LPS) was examined using peritoneal macrophages from TNF-α-deficient mice. The LPS-induced SOCS-3 expression was markedly augmented in macrophages from wild-type mice whereas such augmentation was not seen in ... More
Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P(2)
AuthorsFerguson, CJ; Lenk, GM; Meisler, MH
Journal
PubMed ID
'Mutations affecting the conversion of PI3P to the signaling lipid PI(3,5)P(2) result in spongiform degeneration of mouse brain and are associated with the human disorders Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis (ALS). We now report accumulation of the proteins LC3-II, p62 and LAMP-2 in neurons and astrocytes of mice with ... More
Presenilin 1 affects focal adhesion site formation and cell force generation via c-Src transcriptional and posttranslational regulation.
AuthorsWaschbusch D, Born S, Niediek V, Kirchgessner N, Tamboli IY, Walter J, Merkel R, Hoffmann B
JournalJ Biol Chem
PubMed ID19176482
'Presenilin 1 and 2 (PS) are critical components of the gamma-secretase complex that cleaves type I transmembrane proteins within their transmembrane domains. This process leads to release of proteolytically processed products from cellular membranes and plays an essential role in signal transduction or vital functions as cell adhesion. Here we ... More
Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients.
AuthorsPauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK
JournalArthritis Res Ther
PubMed ID18759964
'INTRODUCTION: MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this ... More
p65/RelA modulates BECN1 transcription and autophagy.
AuthorsCopetti T, Bertoli C, Dalla E, Demarchi F, Schneider C
JournalMol Cell Biol
PubMed ID19289499
'Recently, autophagy has emerged as a critical process in the control of T-cell homeostasis. Given the pivotal role of NF-kappaB in the signaling events of T cells, we have analyzed and unveiled a conserved NF-kappaB binding site in the promoter of the murine and human BECN1 autophagic gene (Atg6). Accordingly, ... More
Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice
AuthorsFushimi, S; Ogino, T; Hara, J; Takahata, T; Wakabayashi, H; Watanabe, H; Arashima, Y; Kubo, M; Matsukawa, A
Journal
PubMed ID
'T cells play central rotes in liver diseases, but the regulatory mechanism by cytokine signaling is not well understood. In the present study, we explored the role of SOCS3 in T cells in concanavalin A (ConA)-induced hepatitis. Mice with T-cell-specific overexpression of SOCS3 (SOCS3-cTg) showed reduced hepatic damage and improved ... More
Reduced levels of reactive oxygen species correlate with inhibition of apoptosis, rise in thioredoxin expression and increased bovine leukemia virus proviral loads
AuthorsBouzar, AB; Boxus, M; Florins, A; Francois, C; Reichert, M; Willems, L
Journal
PubMed ID
'Background: Bovine Leukemia virus (BLV) is a deltaretrovirus that induces lymphoproliferation and leukemia in ruminants. In ex vivo cultures of B lymphocytes isolated from BLV-infected sheep show that spontaneous apoptosis is reduced. Here, we investigated the involvement of reactive oxygen species (ROS) in this process. Results: We demonstrate that ... More
PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype.
AuthorsFonsato V, Buttiglieri S, Deregibus MC, Bussolati B, Caselli E, Di Luca D, Camussi G
JournalBlood
PubMed ID18056486
'In the present study, we evaluated whether infection of microvascular endothelial cells (HMECs) with HHV-8 can trigger the expression of PAX2 oncogene and whether PAX2 protein is involved in HHV-8-induced transformation of HMECs. We found that HHV-8 infection induced the expression of both the PAX2 gene and PAX2 ... More
TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation
AuthorsBaeumer, D; Parkinson, N; Talbot, K
Journal
PubMed ID
Background: Mutations in the gene encoding TDP-43 have been identified in both familial and sporadic amyotrophic lateral sclerosis (ALS). Methods: A mutation screen and copy number analysis in a motor neuron disease clinic cohort was conducted to characterise the genetic contribution of TARDBP. Results: A novel missense mutation in a ... More
Urotensin II receptor expression in human right atrium and aorta: effects of ischaemic heart disease.
AuthorsLeonard AD, Thompson JP, Hutchinson EL, Young SP, McDonald J, Swanevelder J, Lambert DG
JournalBr J Anaesth
PubMed ID19258379
""BACKGROUND: Urotensin II (UII) and its receptor UT are involved in control of the cardiovascular system and are implicated in heart failure. We measured UT expression by quantitative PCR (Q-PCR) in atrial and aortic tissue, and plasma UII while simultaneously assessing cardiac function in 40 patients undergoing coronary artery bypass ... More
Efficient Delivery of Antisense Oligodeoxyribonucleotide G3139 by Human Serum Albumin-Coated Liposomes
Human serum albumin (HSA)-coated liposomal formulations were synthesized and evaluated for the delivery of antisense oligodeoxyribonucleotide (ODN) 63139 in KB human oral carcinoma cells. Liposomes composed of dimethyldioctadecylammonium bromide/egg phosphatidylcholine/α-tocopheryl polyethylene glycol 1000 succinate (58:40:2 molar ratio) complexed with G3139 and coated with HSA were investigated for Bcl-2 downregulating activity. ... More
Interaction of FLASH with arsenite resistance protein 2 is involved in cell cycle progression at S phase.
AuthorsKiriyama M, Kobayashi Y, Saito M, Ishikawa F, Yonehara S
JournalMol Cell Biol
PubMed ID19546234
FLASH has been shown to be required for S phase progression and to interact with a nuclear protein, ataxia-telangiectasia locus (NPAT), a component of Cajal bodies in the nucleus and an activator of histone transcription. We investigated the role of human FLASH by using an inducible FLASH knockdown ... More
RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion.
AuthorsBoeing S, Rigault C, Heidemann M, Eick D, Meisterernst M
JournalJ Biol Chem
PubMed ID19901026
The largest subunit of RNA polymerase II (RNAPII) C-terminal heptarepeat domain (CTD) is subject to phosphorylation during initiation and elongation of transcription by RNA polymerase II. Here we study the molecular mechanisms leading to phosphorylation of Ser-7 in the human enzyme. Ser-7 becomes phosphorylated before initiation of transcription at promoter ... More
Ameloblastin regulates osteogenic differentiation by inhibiting Src kinase via cross talk between integrin beta1 and CD63.
AuthorsIizuka S, Kudo Y, Yoshida M, Tsunematsu T, Yoshiko Y, Uchida T, Ogawa I, Miyauchi M, Takata T
JournalMol Cell Biol
PubMed ID21149578
Ameloblastin, the most abundant nonamelogenin enamel matrix protein, plays a role in ameloblast differentiation. Here, we found that ameloblastin was expressed in osteosarcoma cells; to explore the potential functions of ameloblastin in osteoblasts, we investigated whether this protein is involved in osteogenic differentiation and bone formation on the premise that ... More
PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence.
AuthorsGonzalo-Asensio J, Mostowy S, Harders-Westerveen J, Huygen K, Hernandez-Pando R, Thole J, Behr M, Gicquel B, Martin C
JournalPlos One
PubMed ID18946503
Inactivation of the transcriptional regulator PhoP results in Mycobacterium tuberculosis attenuation. Preclinical testing has shown that attenuated M. tuberculosis phoP mutants hold promise as safe and effective live vaccine candidates. We focused this study to decipher the virulence networks regulated by PhoP. A combined transcriptomic and proteomic analysis revealed that ... More
Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects.
AuthorsTakashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara T
JournalBiol Reprod
PubMed ID19228594
Although spermatogonial stem cells (SSCs) are committed to spermatogenesis, they may also convert to an embryonic stem cell-like pluripotent state at a low frequency. Because changes in DNA methylation patterns are associated with this conversion, we examined the effect of manipulating DNA methyltransferase (Dnmt) expression on the fate of ... More
Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation.
AuthorsWatanabe A, Tatematsu M, Saeki K, Shibata S, Shime H, Yoshimura A, Obuse C, Seya T, Matsumoto M
JournalJ Biol Chem
PubMed ID21266579
The double-stranded RNA analog, poly(I:C), extracellularly activates both the endosomal Toll-like receptor (TLR) 3 and the cytoplasmic RNA helicase, melanoma differentiation-associated gene 5, leading to the production of type I interferons (IFNs) and inflammatory cytokines. The mechanism by which extracellular poly(I:C) is delivered to TLR3-positive organelles and the cytoplasm remains ... More
Effect of point mutations in translation initiation context on the expression of recombinant human α(1)-proteinase inhibitor in transgenic tomato plants
AuthorsAgarwal, S; Jha, S; Sanyal, I; Amla, DV
Journal
PubMed ID
The functional and biological significance of translation initiation context sequence in determining high-level expression of modified synthetic human α(1)-proteinase inhibitor (α(1)-PI) gene was documented in stable transgenic tomato plants. Context sequence of initiator ATG codon derived from statistical analysis of databases was identified as taaA(A/C) aATGGCt in highly expressed dicot ... More
Primary Root Growth Regulation: The Role of Auxin and Ethylene Antagonists
AuthorsZhao, YC; Hasenstein, KH
Journal
PubMed ID
We investigated the growth and development of flax roots in the presence of auxin antagonists 4,4,4-trifluoro-3-(indole-3-)-butyric acid (TFIBA), p-chlorophenoxyisobutyric acid (PCIB), and the ethylene inhibitor silver thiosulfate. Of these compounds, silver thiosulfate was most effective in promoting root elongation. All compounds reduced root diameter and root hair development. The effects ... More
MicroRNAs (miRNAs) play vital roles in down-regulating gene expression at the post-transcriptional level.. A set of 24 UV-B stress-responsive miRNAs (13 up-regulated and 11 down-regulated) was identified in Populus tremula plantlet by expression profiling with our in-house miRNA filter array. Six of the UV-B-responsive miRNA and their corresponding target genes ... More
The tumor suppressor protein HBP1 is a novel c-myc-binding protein that negatively regulates c-myc transcriptional activity.
AuthorsEscamilla-Powers JR, Daniel CJ, Farrell A, Taylor K, Zhang X, Byers S, Sears R
JournalJ Biol Chem
PubMed ID20008325
c-Myc is an important transcription factor that regulates cellular proliferation, cell growth, and differentiation. A number of transcriptional co-factors for c-Myc have been described that have binding sites within highly conserved regions of the c-Myc transactivational domain (TAD). Given the importance of the c-Myc TAD, we set out to identify ... More
Degradation behaviors of nerve guidance conduits made up of silk fibroin in vitro and in vivo
We have developed anew design of nerve guidance conduits (NGCs) made up of silk fibroin (SF), referred to as SF-NGCs, by a well-established method. The present study aimed to comprehensively investigate the degradation behaviors of SF-NGCs versus SF fibers. After they were allowed to incubate in the protease XIV solution ... More
Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs.
AuthorsChen TS, Lai RC, Lee MM, Choo AB, Lee CN, Lim SK
JournalNucleic Acids Res
PubMed ID19850715
Intercellular exchange of protein and RNA-containing microparticles is an increasingly important mode of cell-cell communication. Here we investigate if mesenchymal stem cells (MSCs) known for secreting therapeutic paracrine factors also secrete RNA-containing microparticles. We observed that human embryonic stem cell (hESC)-derived MSC conditioned medium contained small RNAs (less than 300 ... More
Microbial Populations Responsive to Denitrification-Inducing Conditions in Rice Paddy Soil, as Revealed by Comparative 16S rRNA Gene Analysis
AuthorsIshii, S; Yamamoto, M; Kikuchi, M; Oshima, K; Hattori, M; Otsuka, S; Senoo, K
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Rice paddy soil has been shown to have strong denitrifying activity. However, the microbial populations responsible for nitrate respiration and denitrification have not been well characterized. In this study, we performed a clone library analysis of >1,000 clones of the nearly full-length 16S rRNA gene to characterize bacterial community structure ... More
High-resolution profiling and discovery of planarian small RNAs.
AuthorsFriedlander MR, Adamidi C, Han T, Lebedeva S, Isenbarger TA, Hirst M, Marra M, Nusbaum C, Lee WL, Jenkin JC, Sanchez Alvarado A, Kim JK, Rajewsky N
JournalProc Natl Acad Sci U S A
PubMed ID19564616
Freshwater planarian flatworms possess uncanny regenerative capacities mediated by abundant and collectively totipotent adult stem cells. Key functions of these cells during regeneration and tissue homeostasis have been shown to depend on PIWI, a molecule required for Piwi-interacting RNA (piRNA) expression in planarians. Nevertheless, the full complement of piRNAs ... More
Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma.
AuthorsCheung AK, Lung HL, Hung SC, Law EW, Cheng Y, Yau WL, Bangarusamy DK, Miller LD, Liu ET, Shao JY, Kou CW, Chua D, Zabarovsky ER, Tsao SW, Stanbridge EJ, Lung ML
JournalCancer Res
PubMed ID18829573
Functional studies to identify the potential role of a chromosome 3p14-21 gene, protein tyrosine phosphatase receptor type G (PTPRG), were performed. PTPRG was identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) by differential gene profiling of tumorigenic and nontumorigenic NPC chromosome 3 microcell hybrids (MCH). Down-regulation ... More
Electrophilic fatty acids regulate matrix metalloproteinase activity and expression.
Nitro-fatty acids (NO(2)-FA) are electrophilic signaling mediators formed by reactions of nitric oxide and nitrite. NO(2)-FA exert anti-inflammatory signaling actions through post-translational protein modifications. We report that nitro-oleic acid (OA-NO(2)) stimulates proMMP-7 and proMMP-9 proteolytic activity via adduction of the conserved cysteine switch domain thiolate. Biotin-labeled OA-NO(2) showed this adduction ... More
Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress.
AuthorsHayashi T, Yamashita C, Matsumoto C, Kwak CJ, Fujii K, Hirata T, Miyamura M, Mori T, Ukimura A, Okada Y, Matsumura Y, Kitaura Y
JournalAm J Physiol Heart Circ Physiol
PubMed ID18326795
Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp91(phox)-containing NADPH oxidase in the development of left ventricular (LV) remodeling ... More
The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: A novel immunological cascade with potential relevance in psoriasis
AuthorsWolk, K; Witte, E; Warszawska, K; Schulze-Tanzil, G; Witte, K; Philipp, S; Kunz, S; Doecke, WD; Asadullah, K; Volk, HD; Sterry, W; Sabat, R
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Psoriasis is a common chronic skin disease. Recent studies demonstrated that IL-20 and IL-22, cytokines produced by keratinocytes and T cells, respectively, both inhibit keratinocyte terminal differentiation and induce psoriasis-like epidermis alterations. Here, we investigated the relationship between these mediators. Although IL-20 was not able to regulate IL-22 production, IL-22 ... More
Immunomodulatory effect of 5-azacytidine (5-azaC): potential role in the transplantation setting.
AuthorsSanchez-Abarca LI, Gutierrez-Cosio S, Santamaria C, Caballero-Velazquez T, Blanco B, Herrero-Sanchez C, Garcia JL, Carrancio S, Hernandez-Campo P, Gonzalez FJ, Flores T, Ciudad L, Ballestar E, Del Canizo C, San Miguel JF, Perez-Simon JA
JournalBlood
PubMed ID19887673
Cytokine genes are targets of multiple epigenetic mechanisms in T lymphocytes. 5-azacytidine (5-azaC) is a nucleoside-based DNA methyltransferase inhibitor that induces demethylation and gene reactivation. In the current study, we analyzed the effect of 5-azaC in T-cell function and observed that 5-azaC inhibits T-cell proliferation and activation, blocking cell ... More
Anovel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis
Tumors depend upon angiogenesis for growth and metastasis. It is therefore critical to understand the inhibitory signaling mechanisms in endothelial cells that control angiogenesis. Epac is a cyclic adenosine 5'-monophosphate-activated guanine nucleotide exchange factor for Rap1. In this study, we show that activation of Epac or Rap1 leads to potent ... More
The Single RBP-J{kappa} Site within the LANA Promoter Is Crucial for Establishing Kaposi's Sarcoma-Associated Herpesvirus Latency during Primary Infection.
AuthorsLu J, Verma SC, Cai Q, Robertson ES
JournalJ Virol
PubMed ID21507979
Kaposi's sarcoma-associated herpesvirus (KSHV; or human herpesvirus 8 [HHV8]) is implicated in the pathogenesis of many human malignancies including Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). KSHV infection displays two alternative life cycles, referred to as the latent and lytic or productive cycle. Previously, we ... More
Prolonged duration local anesthesia with minimal toxicity.
AuthorsEpstein-Barash H, Shichor I, Kwon AH, Hall S, Lawlor MW, Langer R, Kohane DS
JournalProc Natl Acad Sci U S A
PubMed ID19365067
Injectable local anesthetics that would last for many days could have a marked impact on periprocedural care and pain management. Formulations have often been limited in duration of action, or by systemic toxicity, local tissue toxicity from local anesthetics, and inflammation. To address those issues, we developed liposomal formulations of ... More
Differentially regulated splice variants and systems biology analysis of Kaposi's sarcoma-associated herpesvirus-infected lymphatic endothelial cells.
AuthorsChang TY, Wu YH, Cheng CC, Wang HW
JournalNucleic Acids Res
PubMed ID21646333
Alternative RNA splicing greatly increases proteome diversity, and the possibility of studying genome-wide alternative splicing (AS) events becomes available with the advent of high-throughput genomics tools devoted to this issue. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiological agent of KS, a tumor of lymphatic endothelial cell (LEC) lineage, but ... More
Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2gamma-deficient mice.
AuthorsYoda E, Hachisu K, Taketomi Y, Yoshida K, Nakamura M, Ikeda K, Taguchi R, Nakatani Y, Kuwata H, Murakami M, Kudo I, Hara S
JournalJ Lipid Res
PubMed ID20625036
Group VIB Ca(2+)-independent phospholipase A(2)gamma (iPLA(2)gamma) is a membrane-bound iPLA(2) enzyme with unique features, such as the utilization of distinct translation initiation sites and the presence of mitochondrial and peroxisomal localization signals. Here we investigated the physiological functions of iPLA(2)gamma by disrupting its gene in mice. iPLA(2)gamma-knockout (KO) mice were ... More
The polycomb group protein Bmi1 binds to the herpes simplex virus 1 latent genome and maintains repressive histone marks during latency.
AuthorsKwiatkowski DL, Thompson HW, Bloom DC
JournalJ Virol
PubMed ID19515780
The mechanism by which herpes simplex virus 1 (HSV-1) establishes latency in sensory neurons is largely unknown. Recent studies indicate that epigenetic modifications of the chromatin associated with the latent genome may play a key role in the transcriptional control of lytic genes during latency. In this study, we found ... More
Amplification of the urokinase-type plasminogen activator receptor (uPAR) gene in ductal pancreatic carcinomas identifies a clinically high-risk group.
AuthorsHildenbrand R, Niedergethmann M, Marx A, Belharazem D, Allgayer H, Schleger C, Strobel P
JournalAm J Pathol
PubMed ID19435784
The serine protease urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are known to be involved in the invasion and metastasis of many solid tumors. In this study, we analyzed the role of the uPAR/uPA system in both the development and progression of pancreatic cancer in invasive ductal adenocarcinomas of ... More
Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis.
AuthorsGelber SE, Aguilar JL, Lewis KL, Ratner AJ
JournalJ Bacteriol
PubMed ID18390664
Pore-forming toxins are essential to the virulence of a wide variety of pathogenic bacteria. Gardnerella vaginalis is a bacterial species associated with bacterial vaginosis (BV) and its significant adverse sequelae, including preterm birth and acquisition of human immunodeficiency virus. G. vaginalis makes a protein toxin that generates host immune ... More
Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity.
AuthorsQiao L, Hamamichi S, Caldwell KA, Caldwell GA, Yacoubian TA, Wilson S, Xie ZL, Speake LD, Parks R, Crabtree D, Liang Q, Crimmins S, Schneider L, Uchiyama Y, Iwatsubo T, Zhou Y, Peng L, Lu Y, Standaert DG, Walls KC, Shacka JJ, Roth KA, Zhang J
JournalMol Brain
PubMed ID19021916
ABSTRACT: alpha-synuclein (alpha-syn) is a main component of Lewy bodies (LB) that occur in many neurodegenerative diseases, including Parkinson's disease (PD), dementia with LB (DLB) and multi-system atrophy. alpha-syn mutations or amplifications are responsible for a subset of autosomal dominant familial PD cases, and overexpression causes neurodegeneration and motor disturbances ... More
Tonicity-responsive microRNAs contribute to the maximal induction of osmoregulatory transcription factor OREBP in response to high-NaCl hypertonicity.
AuthorsHuang W, Liu H, Wang T, Zhang T, Kuang J, Luo Y, Chung SS, Yuan L, Yang JY
JournalNucleic Acids Res
PubMed ID20852262
Osmotic response element binding protein (OREBP) is a Rel-like transcription factor critical for cellular osmoresponses. Previous studies suggest that hypertonicity-induced accumulation of OREBP protein might be mediated by transcription activation as well as posttranscriptional mRNA stabilization or increased translation. However, the underlying mechanisms remain incompletely elucidated. Here, we report that ... More
IL-17 promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation.
AuthorsRoussel L, Houle F, Chan C, Yao Y, Berube J, Olivenstein R, Martin JG, Huot J, Hamid Q, Ferri L, Rousseau S
JournalJ Immunol
PubMed ID20228195
Neutrophilic inflammation plays an important role in lung tissue destruction occurring in many chronic pulmonary diseases. Neutrophils can be recruited to sites of inflammation via the action of the cytokine IL-17. In this study, we report that IL-17RA and IL-17RC mRNA expression is significantly increased in asthmatic bronchoscopic biopsies and ... More
Sensitive Detection of KRAS Mutations in Archived Formalin-Fixed Paraffin-Embedded Tissue Using Mutant-Enriched PCR and Reverse-Hybridization
AuthorsAusch, C; Buxhofer-Ausch, V; Oberkanins, C; Holzer, B; Minai-Pour, M; Jahn, S; Dandachi, N; Zeillinger, R; Kriegshaeuser, G
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Recently, evidence has emerged indicating that assessment of KRAS mutations before anti-epidermal growth factor receptor therapy improves outcome in patients with metastatic colorectal cancer (CRC). We report here a novel reverse-hybridization (RH) assay to screen for KRAS mutations in formalin-fixed paraffin-embedded colorectal tissue samples. We combined mutant-enriched PCR based on ... More
ERp29 Regulates {Delta}F508 and Wild-type Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Trafficking to the Plasma Membrane in Cystic Fibrosis (CF) and Non-CF Epithelial Cells.
AuthorsSuaud L, Miller K, Alvey L, Yan W, Robay A, Kebler C, Kreindler JL, Guttentag S, Hubbard MJ, Rubenstein RC
JournalJ Biol Chem
PubMed ID21525008
Sodium 4-phenylbutyrate (4PBA) improves the intracellular trafficking of DeltaF508-CFTR in cystic fibrosis (CF) epithelial cells. The underlying mechanism is uncertain, but 4PBA modulates the expression of some cytosolic molecular chaperones. To identify other 4PBA-regulated proteins that might regulate DeltaF508-CFTR trafficking, we performed a differential display RT-PCR screen on IB3-1 CF ... More
Structure-function correlation of G6, a novel small molecule inhibitor of Jak2: indispensability of the stilbenoid core.
AuthorsMajumder A, Govindasamy L, Magis A, Kiss R, Polgar T, Baskin R, Allan RW, Agbandje-McKenna M, Reuther GW, Keseru GM, Bisht KS, Sayeski PP
JournalJ Biol Chem
PubMed ID20667821
Somatic mutations in the Jak2 protein, such as V617F, cause aberrant Jak/STAT signaling and can lead to the development of myeloproliferative neoplasms. This discovery has led to the search for small molecule inhibitors that target Jak2. Using structure-based virtual screening, our group recently identified a novel small molecule inhibitor of ... More
Cytoplasmic accumulation of the RNA-binding protein HuR stabilizes the ornithine decarboxylase transcript in a murine nonmelanoma skin cancer model.
AuthorsNowotarski SL, Shantz LM
JournalJ Biol Chem
PubMed ID20685649
Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. Under normal physiological conditions, polyamine content and ODC enzyme activity are highly regulated. However, the induction of ODC activity is an early step in neoplastic transformation. The studies described here use normal mouse keratinocytes (C5N ... More
Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection.
AuthorsAlgood HM, Allen SS, Washington MK, Peek RM Jr, Miller GG, Cover TL
JournalJ Immunol
PubMed ID19812196
Th17-driven immune responses contribute to the pathogenesis of many chronic inflammatory diseases. In this study, we investigated the role of IL-17 signaling in chronic gastric inflammation induced by Helicobacter pylori, a Gram-negative bacterium that persistently colonizes the human stomach. Wild-type C57BL/6 mice and mice lacking IL-17RA (IL-17RA(-/-)) were orogastrically infected ... More
Activation of Nuclear Factor kappa B in Mammary Epithelium Promotes Milk Loss During Mammary Development and Infection
We investigated whether nuclear factor kappa B (NF-κB), which exhibits a regulated pattern of activity during murine mammary gland development, plays an important role during lactation and involution, when milk production ceases and the gland undergoes apoptosis and re-modeling. We generated a doxycycline inducible transgenic mouse model to activate NF-κB ... More
Increased adiposity in the retinol saturase-knockout mouse.
AuthorsMoise AR, Lobo GP, Erokwu B, Wilson DL, Peck D, Alvarez S, Dominguez M, Alvarez R, Flask CA, de Lera AR, von Lintig J, Palczewski K
JournalFaseb J
PubMed ID19940255
The enzyme retinol saturase (RetSat) catalyzes the saturation of all-trans-retinol to produce (R)-all-trans-13,14-dihydroretinol. As a peroxisome proliferator-activated receptor (PPAR) gamma target, RetSat was shown to be required for adipocyte differentiation in the 3T3-L1 cell culture model. To understand the mechanism involved in this putative proadipogenic effect of RetSat, we ... More
Combined Costimulation Blockade Inhibits Accelerated Rejection Mediated by Alloantigen-primed Memory T Cells in Mice
Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median ... More
Evolutional Conservation of Molecular Structure and Antiviral Function of a Viral RNA Receptor, LGP2, in Japanese Flounder, Paralichthys olivaceus.
AuthorsOhtani M, Hikima J, Kondo H, Hirono I, Jung TS, Aoki T
JournalJ Immunol
PubMed ID21098234
LGP2 is an important intracellular receptor that recognizes viral RNAs in innate immunity. To understand the mechanism of viral RNA recognition, we cloned an LGP2 cDNA and gene in Japanese flounder (Paralichthys olivaceus). Viral hemorrhagic septicemia virus-induced expressions of LGP2 mRNA were evaluated in vivo and in vitro by quantitative ... More
Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells
The mutant JAK2V617F tyrosine kinase (TK) is present in the majority of patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). JAK2V617F activates downstream signaling through the signal transducers and activators of transcription (STAT), RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3 (PI3)/AKT pathways, conferring proliferative and survival advantages in the MPN hematopoietic progenitor ... More
Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor.
AuthorsAdinolfi E, Cirillo M, Woltersdorf R, Falzoni S, Chiozzi P, Pellegatti P, Callegari MG, Sandona D, Markwardt F, Schmalzing G, Di Virgilio F
JournalFaseb J
PubMed ID20453110
P2X7 is the largest member of the P2X subfamily of purinergic receptors. A typical feature is the carboxyl tail, which allows formation of a large pore. Recently a naturally occurring truncated P2X7 splice variant, isoform B (P2X7B), has been identified. Here we show that P2X7B expression in HEK293 cells, ... More
Expression of the autoimmune susceptibility gene FcRL3 on human regulatory T cells is associated with dysfunction and high levels of programmed cell death-1.
AuthorsSwainson LA, Mold JE, Bajpai UD, McCune JM
JournalJ Immunol
PubMed ID20190142
CD4(+)FoxP3(+) regulatory T cells (T(reg)) play a critical role in maintaining self-tolerance and inhibiting autoimmune disease. Despite being a major focus of modern immunological investigation, many aspects of T(reg) biology remain unknown. In a screen for novel candidate genes involved in human T(reg) function, we detected the expression of ... More
Paired box gene 8-peroxisome proliferator-activated receptor-gamma fusion protein and loss of phosphatase and tensin homolog synergistically cause thyroid hyperplasia in transgenic mice.
AuthorsDiallo-Krou E, Yu J, Colby LA, Inoki K, Wilkinson JE, Thomas DG, Giordano TJ, Koenig RJ
JournalEndocrinology
PubMed ID19797117
Approximately 35% of follicular thyroid carcinomas and a small fraction of follicular adenomas are associated with a t(2;3)(q13;p25) chromosomal translocation that fuses paired box gene 8 (PAX8) with the peroxisome proliferator-activated receptor-gamma gene (PPARG), resulting in expression of a PAX8-PPARgamma fusion protein, PPFP. The mechanism by which PPFP contributes ... More
Molecular Characterization of the Schistosoma mansoni Zinc Finger Protein SmZF1 as a Transcription Factor
Background: During its development, the parasite Schistosoma mansoni is exposed to different environments and undergoes many morphological and physiological transformations as a result of profound changes in gene expression. Characterization of proteins involved in the regulation of these processes is of importance for the understanding of schistosome biology. Proteins containing ... More
Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability.
AuthorsCani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM
JournalGut
PubMed ID19240062
BACKGROUND AND AIMS: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that ... More
Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation.
AuthorsBrown MR, Kronengold J, Gazula VR, Spilianakis CG, Flavell RA, von Hehn CA, Bhattacharjee A, Kaczmarek LK
JournalJ Physiol
PubMed ID18787033
The rates of activation and unitary properties of Na+-activated K+ (K(Na)) currents have been found to vary substantially in different types of neurones. One class of K(Na) channels is encoded by the Slack gene. We have now determined that alternative RNA splicing gives rise to at least five different ... More
Evaluation of putative reference genes for gene expression normalization in soybean by quantitative real-time RT-PCR
AuthorsHu, RB; Fan, CM; Li, HY; Zhang, QZ; Fu, YF
Journal
PubMed ID
Background: Real-time quantitative reverse transcription PCR (RT-qPCR) data needs to be normalized for its proper interpretation. Housekeeping genes are routinely employed for this purpose, but their expression level cannot be assumed to remain constant under all possible experimental conditions. Thus, a systematic validation of reference genes is required to ensure ... More
Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice
Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because ... More
E Unibus Plurum: Genomic Analysis of an Experimentally Evolved Polymorphism in Escherichia coli
AuthorsKinnersley, MA; Holben, WE; Rosenzweig, F
Journal
PubMed ID
Microbial populations founded by a single clone and propagated under resource limitation can become polymorphic. We sought to elucidate genetic mechanisms whereby a polymorphism evolved in Escherichia coli under glucose limitation and persisted because of cross-feeding among multiple adaptive clones. Apart from a 29 kb deletion in the dominant clone, ... More
Expression profiling of rainbow trout testis development identifies evolutionary conserved genes involved in spermatogenesis
Background: Spermatogenesis is a late developmental process that involves a coordinated expression program in germ cells and a permanent communication between the testicular somatic cells and the germ-line. Current knowledge regarding molecular factors driving male germ cell proliferation and differentiation in vertebrates is still limited and mainly based on existing ... More
Self-inactivating alpharetroviral vectors with a split-packaging design.
AuthorsSuerth JD, Maetzig T, Galla M, Baum C, Schambach A
JournalJ Virol
PubMed ID20410274
Accidental insertional activation of proto-oncogenes and potential vector mobilization pose serious challenges for human gene therapy using retroviral vectors. Comparative analyses of integration sites of different retroviral vectors have elucidated distinct target site preferences, highlighting vectors based on the alpharetrovirus Rous sarcoma virus (RSV) as those with the most neutral ... More