Induction of pluripotent stem cells from human third molar mesenchymal stromal cells.
AuthorsOda Y, Yoshimura Y, Ohnishi H, Tadokoro M, Katsube Y, Sasao M, Kubo Y, Hattori K, Saito S, Horimoto K, Yuba S, Ohgushi H
JournalJ Biol Chem
PubMed ID20595386
The expression of four transcription factors (OCT3/4, SOX2, KLF4, and MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. We generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 ... 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
Human serum amyloid p functions as a negative regulator of the innate and adaptive immune responses to DNA vaccines.
AuthorsWang Y, Guo Y, Wang X, Huang J, Shang J, Sun S
JournalJ Immunol
PubMed ID21278351
'The utility of DNA vaccines has been limited by their failure to elicit sufficiently potent immune responses in many human applications, whereas DNA vaccinations in mice have been very successful. However, the underlying mechanisms remain unknown. We hypothesize that serum amyloid P component (SAP), which has a species-specific, DNA-binding ability, ... More
Costimulation of dendritic epidermal gammadelta T cells by a new NKG2D ligand expressed specifically in the skin.
AuthorsWhang MI, Guerra N, Raulet DH
JournalJ Immunol
PubMed ID19342629
'Dendritic epidermal T cells (DETCs) are a highly specialized population of gammadelta T cells that resides in the murine skin and participates in wound healing and tumor surveillance. Despite the expression of other stimulatory receptors on these cells, mechanisms involving activation have focused primarily on the invariant Vgamma3-Vdelta1 TCR ... More
GCN2 protein kinase is required to activate amino acid deprivation responses in mice treated with the anti-cancer agent L-asparaginase.
AuthorsBunpo P, Dudley A, Cundiff JK, Cavener DR, Wek RC, Anthony TG
JournalJ Biol Chem
PubMed ID19783659
'Asparaginase depletes circulating asparagine and glutamine, activating amino acid deprivation responses (AADR) such as phosphorylation of eukaryotic initiation factor 2 (p-eIF2) leading to increased mRNA levels of asparagine synthetase and CCAAT/enhancer-binding protein beta homologous protein (CHOP) and decreased mammalian target of rapamycin complex 1 (mTORC1) signaling. The objectives of this ... More
Aldosterone Postnatally, but not at Birth, Is Required for Optimal Induction of Renal Mineralocorticoid Receptor Expression and Sodium Reabsorption.
AuthorsMartinerie L, Viengchareun S, Meduri G, Kim HS, Luther JM, Lombes M
JournalEndocrinology
PubMed ID21467193
'Sodium wasting during the neonatal period is the consequence of a physiological aldosterone resistance, related to a low renal mineralocorticoid receptor (MR) expression at birth, both in humans and mice. To investigate whether aldosterone is involved in the neonatal regulation of MR expression, we compared aldosterone and corticosterone levels and ... More
Cochlear pericyte responses to acoustic trauma and the involvement of hypoxia-inducible factor-1alpha and vascular endothelial growth factor.
AuthorsShi X
JournalAm J Pathol
PubMed ID19349367
'This study explored the effect of acoustic trauma on cochlear pericytes. Transmission electron microscopy revealed that pericytes on capillaries of the stria vascularis were closely associated with the endothelium in both control guinea pigs and mice. Pericyte foot processes were tightly positioned adjacent to endothelial cells. Exposure to wide-band noise ... 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
Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis.
AuthorsNakao S, Zandi S, Hata Y, Kawahara S, Arita R, Schering A, Sun D, Melhorn MI, Ito Y, Lara-Castillo N, Ishibashi T, Hafezi-Moghadam A
JournalBlood
PubMed ID20705758
'Angio- and lymphangiogenesis are inherently related processes. However, how blood and lymphatic vessels regulate each other is unknown. This work introduces a novel mechanism explaining the temporal and spatial relation of blood and lymphatic vessels. Vascular endothelial growth factor-A (VEGF-A) surprisingly reduced VEGF-C in the supernatant of blood vessel endothelial ... 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
Multiple Biochemical and Morphological Factors Underlie the Production of Methylketones in Tomato Trichomes
AuthorsBen-Israel, I; Yu, G; Austin, MB; Bhuiyan, N; Auldridge, M; Nguyen, T; Schauvinhold, I; Noel, JP; Pichersky, E; Fridman, E
Journal
PubMed ID
'Genetic analysis of interspecific populations derived from crosses between the wild tomato species Solanum habrochaites f. sp. glabratum, which synthesizes and accumulates insecticidal methylketones (MK), mostly 2-undecanone and 2-tridecanone, in glandular trichomes, and cultivated tomato (Solanum lycopersicum), which does not, demonstrated that several genetic loci contribute to MK metabolism in ... 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
Type XIV Collagen Regulates Fibrillogenesis: PREMATURE COLLAGEN FIBRIL GROWTH AND TISSUE DYSFUNCTION IN NULL MICE.
AuthorsAnsorge HL, Meng X, Zhang G, Veit G, Sun M, Klement JF, Beason DP, Soslowsky LJ, Koch M, Birk DE
JournalJ Biol Chem
PubMed ID19136672
'Type XIV collagen is a fibril-associated collagen with an interrupted triple helix. This collagen interacts with the fibril surface and has been implicated as a regulator of fibrillogenesis; however, a specific role has not been elucidated. Functional roles for type XIV collagen were defined utilizing a new type XIV collagen-deficient ... More
Quantitative detection of Schistosoma japonicum cercariae in water by real-time PCR.
AuthorsHung YW, Remais J
JournalPlos Negl Trop Dis
PubMed ID19015722
'In China alone, an estimated 30 million people are at risk of schistosomiasis, caused by the Schistosoma japonicum parasite. Disease has re-emerged in several regions that had previously attained transmission control, reinforcing the need for active surveillance. The environmental stage of the parasite is known to exhibit high spatial and ... More
TIMP-3: A novel target for glucocorticoid signaling at the blood-brain barrier
'Glucocorticoids (GCs) are used in the treatment of neuroinflammatory diseases such as multiple sclerosis. Several studies have demonstrated the beneficial effect of GCs on the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors, the TIMPs (tissue inhibitors of metalloproteinases). We could demonstrate that all four known TIMPs are present ... 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
TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.
AuthorsLim DM, Narasimhan S, Michaylira CZ, Wang ML
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID19779021
'Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. ... More
Numb Promotes an Increase in Skeletal Muscle Progenitor Cells in the Embryonic Somite
AuthorsJory, A; Le Roux, I; Gayraud-Morel, B; Rocheteau, P; Cohen-Tannoudji, M; Cumano, A; Tajbakhsh, S
Journal
PubMed ID
'Multiple cell types arise from cells in the dermomyotome of the somite that express Pax3 and Pax7, and myogenesis is regulated by Notch signaling. The asymmetric cell fate determinant Numb is thought to promote differentiation of skeletal muscle and other lineages by negatively regulating Notch signaling. We used transgenesis to ... More
Effects of sampling location and time, and host animal on assessment of bacterial diversity and fermentation parameters in the bovine rumen
AuthorsLi, M; Penner, GB; Hernandez-Sanabria, E; Oba, M; Guan, LL
Journal
PubMed ID
'Aims: To investigate, using culture-independent methods, whether the ruminal bacterial structure, population and fermentation parameters differed between sampling locations and time. Methods and Results: The detectable bacteria and fermentation parameters in the digesta from five locations in the rumen of three cows at three time points were analysed. ... More
Activation of IFN-{beta} expression by a viral mRNA through RNase L and MDA5.
AuthorsLuthra P, Sun D, Silverman RH, He B
JournalProc Natl Acad Sci U S A
PubMed ID21245317
'IFNs play a critical role in innate immunity against viral infections. Melanoma differentiation-associated protein 5 (MDA5), an RNA helicase, is a key component in activating the expression of type I IFNs in response to certain types of viral infection. MDA5 senses noncellular RNA and triggers the signaling cascade that leads ... 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
Quantification of Cyprinid Herpesvirus 3 in Environmental Water by Using an External Standard Virus
'Cyprinid herpesvirus 3 (CyHV-3), a lethal DNA virus that spreads in natural lakes and rivers, infects common carp and koi. We established a quantification method for CyHV-3 that includes a viral concentration method and quantitative PCR combined with an external standard virus. Viral concentration methods were compared using the cation-coated ... More
Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms
'Background: Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers. Methods: Fifty-one population-based MSS colon cancers were assessed for ACVR1, ACVR2 and pSMAD2 protein. ... More
Serum response factor utilizes distinct promoter- and enhancer-based mechanisms to regulate cytoskeletal gene expression in macrophages.
'Cells of the monocyte/macrophage lineage play essential roles in tissue homeostasis and immune responses, but mechanisms underlying the coordinated expression of cytoskeletal genes required for specialized functions of these cells, such as directed migration and phagocytosis, remain unknown. Here, using genetic and genomic approaches, we provide evidence that serum response ... More
Paracoccidioides brasiliensis enolase is a surface protein that binds plasminogen and mediates interaction of yeast forms with host cells.
AuthorsNogueira SV, Fonseca FL, Rodrigues ML, Mundodi V, Abi-Chacra EA, Winters MS, Alderete JF, de Almeida Soares CM
JournalInfect Immun
PubMed ID20605975
'Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis, is a disseminated, systemic disorder that involves the lungs and other organs. The ability of the pathogen to interact with host components, including extracellular matrix (ECM) proteins, is essential to further colonization, invasion, and growth. Previously, enolase (EC 4.2.1.11) was characterized ... 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
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
Tumor cell kill by c-MYC depletion: role of MYC-regulated genes that control DNA double-strand break repair.
'MYC regulates a myriad of genes controlling cell proliferation, metabolism, differentiation, and apoptosis. MYC also controls the expression of DNA double-strand break (DSB) repair genes and therefore may be a potential target for anticancer therapy to sensitize cancer cells to DNA damage or prevent genetic instability. In this report, we ... 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
CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice.
AuthorsNoda M, Omatsu Y, Sugiyama T, Oishi S, Fujii N, Nagasawa T
JournalBlood
PubMed ID20944068
'Natural killer (NK) cells are granular lymphocytes that are generated from hematopoietic stem cells and play vital roles in the innate immune response against tumors and viral infection. Generation of NK cells is known to require several cytokines, including interleukin-15 (IL-15) and Fms-like tyrosine kinase 3 ligand, but not IL-2 ... More
Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal
'Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interacting factors that converge on a critical threshold. To elucidate the transcriptional network ... 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
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
Glycerol kinase activity and glycerol kinase-3 gene are up-regulated by acclimation to 5 °C in diapause eggs of the silkworm, Bombyx mori
AuthorsKihara, F; Itoh, K; Iwasaka, M; Niimi, T; Yamashita, O; Yaginuma, T
Journal
PubMed ID
With initiation of diapause, glycogen is converted into sorbitol and glycerol in eggs of the silkworm Bombyx mori. At diapause termination promoted by incubation at 5 °C, sorbitol and glycerol are utilized. Although sorbitol utilization is triggered by NAD-sorbitol dehydrogenase induced by acclimation to 5 °C, the initial enzyme utilizing ... More
Genome wide DNA-profiling of HIV-related B-cell lymphomas
AuthorsCapello, D; Scandurra, M; Poretti, G; Rancoita, PMV; Mian, M; Gloghini, A; Deambrogi, C; Martini, M; Rossi, D; Greiner, TC; Chan, WC; Ponzoni, M; Moreno, SM; Piris, MA; Canzonieri, V; Spina, M; Tirelli, U; Inghirami, G; Rinaldi, A; Zucca, E; Favera, RD; C
Journal
PubMed ID
Non-Hodgkin lymphomas (NHL) represent a frequent complication of human immunodeficiency virus (HIV) infection. To elucidate HIV-NHL pathogenesis, we performed a genome-wide DNA profiling based on a single nucleotide polymorphism-based microarray comparative genomic hybridization in 57 HIV-lymphomas and, for comparison, in 105 immunocompetent diffuse large B-cell lymphomas (IC-DLBCL). Genomic complexity varied ... More
miR-Q: a novel quantitative RT-PCR approach for the expression profiling of small RNA molecules such as miRNAs in a complex sample.
AuthorsSharbati-Tehrani S, Kutz-Lohroff B, Bergbauer R, Scholven J, Einspanier R
JournalBmc Mol Biol
PubMed ID18400113
BACKGROUND: MicroRNAs (miRNAs) are small endogenous non-coding interfering RNA molecules regarded as major regulators in eukaryotic gene expression. Different methods are employed for miRNA expression profiling. For a better understanding of their role in essential biological processes, convenient methods for differential miRNA expression analysis are required. RESULTS: Here, we present ... More
Studying human telomerase gene transcription by a chromatinized reporter generated by recombinase-mediated targeting of a bacterial artificial chromosome
AuthorsWang, SW; Zhao, YJ; Leiby, MA; Zhu, JY
Journal
PubMed ID
The endogenous human telomerase reverse transcriptase (hTERT) gene is repressed in somatic cells. To study the mechanisms of its repression, we developed a strategy of retrovirus-directed Cre recombinase-mediated BAC targeting, or RMBT, to generate single-copy integrations of BAC at pre-engineered chromosomal sites. This technique involved retroviral transduction of acceptor loci, ... 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
A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP.
AuthorsMcWhirter SM, Barbalat R, Monroe KM, Fontana MF, Hyodo M, Joncker NT, Ishii KJ, Akira S, Colonna M, Chen ZJ, Fitzgerald KA, Hayakawa Y, Vance RE
JournalJ Exp Med
PubMed ID19652017
The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di-guanosine ... More
Forkhead box M1 transcriptional factor is required for smooth muscle cells during embryonic development of blood vessels and esophagus
The forkhead box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) is expressed in a variety of tissues during embryogenesis. including vascular, airway, and intestinal smooth muscle cells (SMCs). Although global deletion of Foxm1 in Foxm1(-/-) mice is lethal in the embryonic period due to ... More
Developmental role and auxin responsiveness of Class III homeodomain leucine zipper gene family members in rice.
AuthorsItoh J, Hibara K, Sato Y, Nagato Y
JournalPlant Physiol
PubMed ID18567825
Members of the Class III homeodomain leucine zipper (Class III HD-Zip) gene family are central regulators of crucial aspects of plant development. To better understand the roles of five Class III HD-Zip genes in rice (Oryza sativa) development, we investigated their expression patterns, ectopic expression phenotypes, and auxin responsiveness. Four ... More
Common fragile sites are characterized by histone hypoacetylation
AuthorsJiang, YW; Lucas, I; Young, DJ; Davis, EM; Karrison, T; Rest, JS; Le Beau, MM
Journal
PubMed ID
Common fragile sites (CFSs) represent large, highly unstable regions of the human genome. CFS sequences are sensitive to perturbation of replication; however, the molecular basis for the instability at CFSs is poorly understood. We hypothesized that a unique epigenetic pattern may underlie the unusual sensitivity of CFSs to replication interference. ... 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
Reduced NR4A gene dosage leads to mixed myelodysplastic/myeloproliferative neoplasms in mice.
AuthorsRamirez-Herrick AM, Mullican SE, Sheehan AM, Conneely OM
JournalBlood
PubMed ID21205929
The NR4A subfamily of nuclear receptors (NR4A1, NR4A2, and NR4A3) function as transcription factors that transduce diverse extracellular signals into altered gene transcription to coordinate apoptosis, proliferation, cell cycle arrest, and DNA repair. We previously discovered that 2 of these receptors, NR4A1 and NR4A3, are potent tumor suppressors of acute ... 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
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
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
Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal.
AuthorsMunger SC, Aylor DL, Syed HA, Magwene PM, Threadgill DW, Capel B
JournalGenes Dev
PubMed ID19884258
Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interacting factors that converge on a critical threshold. To elucidate the transcriptional ... More
Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase.
AuthorsElshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Smith AD, Drevon CA, Refsum H, Perrone CE
JournalJ Lipid Res
PubMed ID20871132
Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in fatty acid and energy metabolism, but little is known about its nutritional regulation. Dietary methionine restriction in rats decreases hepatic Scd1 mRNA and protein, increases energy expenditure, and decreases fat-pad mass/body-weight% (FM/BW%). In humans, plasma concentrations of the methionine product, cysteine, are ... 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
Three new O-methyltransferases are sufficient for all O-methylation reactions of ipecac alkaloid biosynthesis in root culture of Psychotria ipecacuanha.
AuthorsNomura T, Kutchan TM
JournalJ Biol Chem
PubMed ID20061395
The medicinal plant Psychotria ipecacuanha produces ipecac alkaloids, a series of monoterpenoid-isoquinoline alkaloids such as emetine and cephaeline, whose biosynthesis derives from condensation of dopamine and secologanin. Here, we identified three cDNAs, IpeOMT1-IpeOMT3, encoding ipecac alkaloid O-methyltransferases (OMTs) from P. ipecacuanha. They were coordinately transcribed with the recently identified ipecac ... 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
miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia.
AuthorsKlusmann JH, Li Z, Bohmer K, Maroz A, Koch ML, Emmrich S, Godinho FJ, Orkin SH, Reinhardt D
JournalGenes Dev
PubMed ID20194440
Children with trisomy 21/Down syndrome (DS) are at high risk to develop acute megakaryoblastic leukemia (DS-AMKL) and the related transient leukemia (DS-TL). The factors on human chromosome 21 (Hsa21) that confer this predisposing effect, especially in synergy with consistently mutated transcription factor GATA1 (GATA1s), remain poorly understood. Here, we ... More
Significance of thymidylate synthase for resistance to pemetrexed in lung cancer
AuthorsOzasa, H; Oguri, T; Uemura, T; Miyazaki, M; Maeno, K; Sato, S; Ueda, R
Journal
PubMed ID
Pemetrexed (MTA) is a multitargeted antifolate with promising clinical activity in lung cancer. We exposed the small cell lung cancer cell line PC6 to stepwise-increasing pemetrexed concentrations of 0.4, 1.6, and 4.0 μm, and established three pemetrexed-resistant lung cancer cell lines: PC6/MTA-0.4, PC6/MTA-1.6, and PC6/MTA-4.0 cells. To investigate the mechanisms ... More
Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4(+) T cell activation via Toll-like receptors 1 and 2.
AuthorsLancioni CL, Li Q, Thomas JJ, Ding X, Thiel B, Drage MG, Pecora ND, Ziady AG, Shank S, Harding CV, Boom WH, Rojas RE
JournalInfect Immun
PubMed ID21078852
The success of Mycobacterium tuberculosis as a pathogen relies on its ability to regulate the host immune response. M. tuberculosis can manipulate adaptive T cell responses indirectly by modulating antigen-presenting cell (APC) function or by directly interacting with T cells. Little is known about the role of M. tuberculosis molecules ... More
A rapid and inexpensive labeling method for microarray gene expression analysis
AuthorsOuellet, M; Adams, PD; Keasling, JD; Mukhopadhyay, A
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PubMed ID
Background: Global gene expression profiling by DNA microarrays is an invaluable tool in biological research. However, existing labeling methods are time consuming and costly and therefore often limit the scale of microarray experiments and sample throughput. Here we introduce a new, fast, inexpensive method for direct random-primed fluorescent labeling 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
Thyroid hormone controls cone opsin expression in the retina of adult rodents.
AuthorsGlaschke A, Weiland J, Del Turco D, Steiner M, Peichl L, Glosmann M
JournalJ Neurosci
PubMed ID21451022
Mammalian retinas display an astonishing diversity in the spatial arrangement of their spectral cone photoreceptors, probably in adaptation to different visual environments. Opsin expression patterns like the dorsoventral gradients of short-wave-sensitive (S) and middle- to long-wave-sensitive (M) cone opsin found in many species are established early in development and thought ... 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
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
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
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
GCN2 Protein Kinase Is Required to Activate Amino Acid Deprivation Responses in Mice Treated with the Anti-cancer Agent L-Asparaginase
Asparaginase depletes circulating asparagine and glutamine, activating amino acid deprivation responses (AADR) such as phosphorylation of eukaryotic initiation factor 2 (p-eIF2) leading to increased mRNA levels of asparagine synthetase and CCAAT/enhancer-binding protein β homologous protein (CHOP) and decreased mammalian target of rapamycin complex 1 (mTORC1) signaling. The objectives of this ... More
Characterization of Resistance to the Protease Inhibitor Boceprevir in Hepatitis C Virus-Infected Patients
Boceprevir is a hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor that is currently being evaluated in combination with peginterferon alfa-2b and ribavirin in phase 3 studies. The clinical resistance profile of boceprevir is not characterized in detail so far. The NS3 protease domain of viral RNA was ... More
Persistence of nucleic acid markers of health-relevant organisms in seawater microcosms: Implications for their use in assessing risk in recreational waters
AuthorsWalters, SP; Yamahara, KM; Boehm, AB
Journal
PubMed ID
In the last decade, the use of culture-independent methods for detecting indicator organisms and pathogens in recreational waters has increased and has led to heightened interest in their use for routine water quality monitoring. However, a thorough understanding of the persistence of genetic markers in environmental waters is lacking. In ... 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
Light Directs Zebrafish period2 Expression via Conserved D and E Boxes
For most species, light represents the principal environmental signal for entraining the endogenous circadian clock. The zebrafish is a fascinating vertebrate model for studying this process since unlike mammals, direct exposure of most of its tissues to light leads to local clock entrainment. Importantly, light induces the expression of a ... More
TLR3-mediated NF-κB signaling in human esophageal epithelial cells
AuthorsLim, DM; Narasimhan, S; Michaylira, CZ; Wang, ML
Journal
PubMed ID
Lim DM, Narasimhan S, Michaylira CZ, Wang ML. TLR3-mediated NF-κB signaling in human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol 297: G1172-G1180, 2009. First published September 24, 2009; doi: 10.1152/ajpgi.00065.2009.-Despite its position at the front line against ingested pathogens, very little is presently known about the role of ... More
Nme protein family evolutionary history, a vertebrate perspective
Background: The Nme family, previously known as Nm23 or NDPK, is involved in various molecular processes including tumor metastasis and some members of the family, but not all, exhibit a Nucleoside Diphosphate Kinase (NDPK) activity. Ten genes are known in humans, in which some members have been extensively studied. In ... More
Dopamine Induces IL-6-Dependent IL-17 Production via D1-Like Receptor on CD4 Naive T Cells and D1-Like Receptor Antagonist SCH-23390 Inhibits Cartilage Destruction in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model.
AuthorsNakano K, Yamaoka K, Hanami K, Saito K, Sasaguri Y, Yanagihara N, Tanaka S, Katsuki I, Matsushita S, Tanaka Y
JournalJ Immunol
PubMed ID21307293
A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1-D5. Several studies have shown that dopamine not only mediates interactions into the nervous system, but can contribute to the modulation of immunity via receptors expressed on immune cells. We have previously shown an autocrine/paracrine release ... 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
Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma.
AuthorsCheung AK, Lung HL, Ko JM, Cheng Y, Stanbridge EJ, Zabarovsky ER, Nicholls JM, Chua D, Tsao SW, Guan XY, Lung ML
JournalProc Natl Acad Sci U S A
PubMed ID19667180
Chromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously transferred chromosome 14 were tumor suppressive in ... More
A single anti-microRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interference.
AuthorsLu Y, Xiao J, Lin H, Bai Y, Luo X, Wang Z, Yang B
JournalNucleic Acids Res
PubMed ID19136465
Anti-miRNA antisense inhibitors (AMOs) have demonstrated their utility in miRNA research and potential in miRNA therapy. Here we report a modified AMO approach in which multiple antisense units are engineered into a single unit that is able to simultaneously silence multiple-target miRNAs, the multiple-target AMO or MTg-AMO. We validated ... More
Elongation and gene expression in bovine cloned embryos transferred to temporary recipients
Elongated embryos provide a unique source of information about trophoblastic differentiation, gene expression and maternal-embryonic interactions; however they are difficult and costly to obtain, especially elongated cloned embryos. One alternative is their production in heterologous temporary recipients such as sheep and goats. We aimed to produce elongated bovine cloned embryos ... More
Antipermeability function of PEDF involves blockade of the MAP kinase/GSK/beta-catenin signaling pathway and uPAR expression.
AuthorsYang J, Duh EJ, Caldwell RB, Behzadian MA
JournalInvest Ophthalmol Vis Sci
PubMed ID20089873
PURPOSE: Pigment epithelium-derived factor (PEDF) is a potent inhibitor of vascular endothelial growth factor (VEGF)-induced endothelial permeability. The goal of this study was to understand the mechanism by which PEDF blocks VEGF-induced increases in vascular permeability. METHODS: The paracellular permeability of bovine retinal endothelial (BRE) cells was measured by assaying ... More
Regulation of hematopoietic cell clusters in the placental niche through SCF/Kit signaling in embryonic mouse.
AuthorsSasaki T, Mizuochi C, Horio Y, Nakao K, Akashi K, Sugiyama D
JournalDevelopment
PubMed ID20980401
Hematopoietic stem cells (HSCs) emerge from and expand in the mouse placenta at mid-gestation. To determine their compartment of origin and define extrinsic signals governing their commitment to this lineage, we identified hematopoietic cell (HC) clusters in mouse placenta, defined as cells expressing the embryonic HSC markers CD31, CD34 and ... More
Influence of fatty acid diets on gene expression in rat mammary epithelial cells.
AuthorsMedvedovic M, Gear R, Freudenberg JM, Schneider J, Bornschein R, Yan M, Mistry MJ, Hendrix H, Karyala S, Halbleib D, Heffelfinger S, Clegg DJ, Anderson MW
JournalPhysiol Genomics
PubMed ID19351911
BACKGROUND: This study examines the impact of dietary fatty acids on regulation of gene expression in mammary epithelial cells before and during puberty. METHODS: Diets primarily consisted of n-9 monounsaturated fatty acids (olive oil), n-6 polyunsaturated fatty acids (safflower), saturated acids (butter), and the reference AIN-93G diet (soy oil). The ... More
Cardiac L-type calcium channel (Cav1.2) associates with {gamma} subunits.
AuthorsYang L, Katchman A, Morrow JP, Doshi D, Marx SO
JournalFaseb J
PubMed ID21127204
The cardiac voltage-gated Ca(2+) channel, Ca(v)1.2, mediates excitation-contraction coupling in the heart. The molecular composition of the channel includes the pore-forming alpha1 subunit and auxiliary alpha2/delta-1 and beta subunits. Ca(2+) channel gamma subunits, of which there are 8 isoforms, consist of 4 transmembrane domains with intracellular N- and C-terminal ends. ... More
Reciprocal regulation of activating and inhibitory Fc{gamma} receptors by TLR7/8 activation: implications for tumor immunotherapy.
AuthorsButchar JP, Mehta P, Justiniano SE, Guenterberg KD, Kondadasula SV, Mo X, Chemudupati M, Kanneganti TD, Amer A, Muthusamy N, Jarjoura D, Marsh CB, Carson WE 3rd, Byrd JC, Tridandapani S
JournalClin Cancer Res
PubMed ID20332325
PURPOSE: Activation of Toll-like receptors (TLR) 7 and 8 by engineered agonists has been shown to aid in combating viruses and tumors. Here, we wished to test the effect of TLR7/8 activation on monocyte Fcgamma receptor (FcgammaR) function, as they are critical mediators of antibody therapy. EXPERIMENTAL DESIGN: The effect ... More
Role of defensins in corneal epithelial barrier function against Pseudomonas aeruginosa traversal.
AuthorsAugustin DK, Heimer SR, Tam C, Li WY, Le Due JM, Evans DJ, Fleiszig SM
JournalInfect Immun
PubMed ID21115716
Studies have shown that epithelium-expressed antimicrobial peptides (AMPs), e.g., beta-defensins, play a role in clearing bacteria from mouse corneas already infected with Pseudomonas aeruginosa. Less is known about the role of AMPs in allowing the cornea to resist infection when healthy. We previously reported that contact lens exposure, a major ... More
The human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune ... More
Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer.
AuthorsEdwards RA, Witherspoon M, Wang K, Afrasiabi K, Pham T, Birnbaumer L, Lipkin SM
JournalCancer Res
PubMed ID19638594
Sporadic human mismatch repair (MMR)-deficient colorectal cancers account for approximately 12.5% of all cases of colorectal cancer. MMR-deficient colorectal cancers are classically characterized by right-sided location, multifocality, mucinous histology, and lymphocytic infiltration. However, tumors in germ-line MMR-deficient mouse models lack these histopathologic features. Mice lacking the heterotrimeric G protein ... More
Liver-restricted expression of the canine factor VIII gene facilitates prevention of inhibitor formation in factor VIII-deficient mice
Background Gene therapy for hemophilia A with adeno-associated virus (AAV) vectors involves difficulties in the efficient expression of factor VIII (FVIII) and in antibody formation against transgene-derived FVIII. Methods AAV8 vectors carrying the canine B domain deleted FVIII (cFVIII) gene under the control of the ubiquitous β-actin promoter, the ... More
The rice transcription factor IDEF1 is essential for the early response to iron deficiency, and induces vegetative expression of late embryogenesis abundant genes
AuthorsKobayashi, T; Itai, RN; Ogo, Y; Kakei, Y; Nakanishi, H; Takahashi, M; Nishizawa, NK
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PubMed ID
Higher plants maintain iron homeostasis by regulating the expression of iron (Fe)-related genes in accordance with Fe availability. The transcription factor IDEF1 regulates the response to Fe deficiency in Oryza sativa (rice) by recognizing CATGC sequences within the Fe deficiency-responsive cis-acting element IDE1. To investigate the function of IDEF1 in ... More
Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism.
AuthorsSemmler A, Hermann S, Mormann F, Weberpals M, Paxian SA, Okulla T, Schafers M, Kummer MP, Klockgether T, Heneka MT
JournalJ Neuroinflammation
PubMed ID18793399
BACKGROUND: Septic encephalopathy is a severe brain dysfunction caused by systemic inflammation in the absence of direct brain infection. Changes in cerebral blood flow, release of inflammatory molecules and metabolic alterations contribute to neuronal dysfunction and cell death. METHODS: To investigate the relation of electrophysiological, metabolic and morphological changes ... More
Insulin up-regulates heme oxygenase-1 expression in 3T3-L1 adipocytes via PI3-kinase- and PKC-dependent pathways and heme oxygenase-1-associated microRNA downregulation.
AuthorsChang CL, Au LC, Huang SW, Fai Kwok C, Ho LT, Juan CC
JournalEndocrinology
PubMed ID21147878
Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has antioxidant, antiinflammatory, and antiapoptotic effects in many physiological systems. HO-1 activity in obese mice is lower than in controls, and a sustained increase in HO-1 protein levels ameliorates insulin resistance and compensatory hyperinsulinemia. In the present study, we explored the ... More
Delineating biological pathways unique to embryonic stem cell-derived insulin-producing cell lines from their noninsulin-producing progenitor cell lines.
AuthorsChen TS, Tan SS, Yeo RW, Teh BJ, Luo R, Li G, Lim SK
JournalEndocrinology
PubMed ID20501672
To identify unique biochemical pathways in embryonic stem cell-derived insulin-producing cells as potential therapeutic targets to prevent or delay beta-cell dysfunction or death in diabetic patients, comparative genome-wide gene expression studies of recently derived mouse insulin-producing cell lines and their progenitor cell lines were performed using microarray technology. Differentially expressed ... More
ACE inhibition promotes upregulation of endothelial progenitor cells and neoangiogenesis in cardiac pressure overload.
AuthorsMuller P, Kazakov A, Jagoda P, Semenov A, Bohm M, Laufs U
JournalCardiovasc Res
PubMed ID19380417
AIMS: Inhibition of the angiotensin-converting enzyme (ACE) prevents maladaptive cardiac remodelling. Endothelial progenitor cells (EPC) from the bone marrow contribute to endothelial repair and neovascularization, effects that are potentially important during cardiac remodelling. We hypothesized that ACE inhibitors may exert beneficial effects during pressure-induced myocardial hypertrophy by regulating progenitor ... More
DNA cytosine methylation in the bovine leukemia virus promoter is associated with latency in a lymphoma-derived B-cell line: potential involvement of direct inhibition of cAMP-responsive element (CRE)-binding protein/CRE modulator/activation transcription factor binding.
AuthorsPierard V, Guiguen A, Colin L, Wijmeersch G, Vanhulle C, Van Driessche B, Dekoninck A, Blazkova J, Cardona C, Merimi M, Vierendeel V, Calomme C, Nguyen TL, Nuttinck M, Twizere JC, Kettmann R, Portetelle D, Burny A, Hirsch I, Rohr O, Van Lint C
JournalJ Biol Chem
PubMed ID20413592
Bovine leukemia virus (BLV) proviral latency represents a viral strategy to escape the host immune system and allow tumor development. Besides the previously demonstrated role of histone deacetylation in the epigenetic repression of BLV expression, we showed here that BLV promoter activity was induced by several DNA methylation inhibitors ... More
Protective and damaging effects of platelets in acute cholestatic liver injury revealed by depletion and inhibition strategies.
AuthorsSullivan BP, Wang R, Tawfik O, Luyendyk JP
JournalToxicol Sci
PubMed ID20133375
Alpha-naphthylisothiocyanate (ANIT) causes cholestatic hepatitis characterized by intrahepatic bile duct epithelial cell injury and periportal hepatocellular necrosis. The progression of ANIT-induced hepatocyte injury is reported to involve extrahepatic cells including platelets. We showed recently that the procoagulant protein tissue factor (TF) is essential for ANIT-induced coagulation and contributes to ANIT-induced ... More