'Inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (IP(7)), are water-soluble inositol phosphates that contain high energy diphosphate moieties on the inositol ring. Inositol hexakisphosphate kinase 1 (IP6K1) participates in inositol pyrophosphate synthesis, converting inositol hexakisphosphate (IP(6)) to IP(7). In the present study, we show that mouse embryonic fibroblasts (MEFs) lacking IP6K1 ... More
IDO1 metabolites activate ß-catenin signaling to promote cancer cell proliferation and colon tumorigenesis in mice.
AuthorsThaker AI, Rao MS, Bishnupuri KS, Kerr TA, Foster L, Marinshaw JM, Newberry RD, Stenson WF, Ciorba MA
Journal
PubMed ID23669411
Indoleamine 2,3 dioxygenase-1 (IDO1) catabolizes tryptophan along the kynurenine pathway. Although IDO1 is expressed in inflamed and neoplastic epithelial cells of the colon, its role in colon tumorigenesis is not well understood. We used genetic and pharmacologic approaches to manipulate IDO1 activity in mice with colitis-associated cancer and human colon ... More
Lung myofibroblasts are characterized by down-regulated cyclooxygenase-2 and its main metabolite, prostaglandin E2.
AuthorsGabasa M, Royo D, Molina-Molina M, Roca-Ferrer J, Pujols L, Picado C, Xaubet A, Pereda J
Journal
PubMed ID23755232
Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing a-smooth muscle actin (a-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human ... More
An organotypic coculture model supporting proliferation and differentiation of medullary thymic epithelial cells and promiscuous gene expression.
Understanding intrathymic T cell differentiation has been greatly aided by the development of various reductionist in vitro models that mimic certain steps/microenvironments of this complex process. Most models focused on the faithful in vitro restoration of T cell differentiation and selection. In contrast, suitable in vitro models emulating the developmental ... More
PARG dysfunction enhances DNA double strand break formation in S-phase after alkylation DNA damage and augments different cell death pathways.
AuthorsShirai H, Poetsch AR, Gunji A, Maeda D, Fujimori H, Fujihara H, Yoshida T, Ogino H, Masutani M,
Journal
PubMed ID23744356
Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for the degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; however, the details of this effect have not been fully elucidated. Here, we investigated the mechanism by which PARG deficiency leads to cell death in different ... More
Evaluation of proliferation of neural stem cells in vitro and in vivo.
AuthorsMorte MI, Carreira BP, Machado V, Carmo A, Nunes-Correia I, Carvalho CM, Araújo IM,
JournalCurr Protoc Stem Cell Biol
PubMed ID23404673
This unit describes two basic protocols for the detection of the proliferation of neural stem cells (NSC). The first one addresses cell proliferation in cultures, starting with primary cell cultures isolated from the mouse subventricular zone (SVZ), in which SVZ-derived NSC are kept in culture as neurospheres. By using this ... More
Camptothecin (CPT), a topoisomerase (Top) I-targeting drug that stabilizes Top1-DNA covalent adducts, can induce S-phase-specific cytotoxicity due to the arrest of progressing replication forks. However, CPT-induced non-S-phase cytotoxicity is less well characterized. In this study, we have identified topoisomerase IIß (Top2ß) as a specific determinant for CPT sensitivity, but not ... More
Ubiquitylation of p53 by the APC/C inhibitor Trim39.
AuthorsZhang L, Huang NJ, Chen C, Tang W, Kornbluth S
JournalProc Natl Acad Sci U S A
PubMed ID23213260
Tripartite motif 39 (Trim39) is a RING domain-containing E3 ubiquitin ligase able to inhibit the anaphase-promoting complex (APC/C) directly. Through analysis of Trim39 function in p53-positive and p53-negative cells, we have found, surprisingly, that p53-positive cells lacking Trim39 could not traverse the G1/S transition. This effect did not result from ... More
A method for evaluating the host range of bacteriophages using phages fluorescently labeled with 5-ethynyl-2'-deoxyuridine (EdU).
AuthorsOhno S, Okano H, Tanji Y, Ohashi A, Watanabe K, Takai K, Imachi H
JournalAppl Microbiol Biotechnol
PubMed ID22660768
The evaluation of bacteriophage (phage) host range is a significant issue in understanding phage and prokaryotic community interactions. However, in conventional methods, such as plaque assay, target host strains must be isolated, although almost all environmental prokaryotes are recalcitrant to cultivation. Here, we introduce a novel phage host range evaluation ... More
Prenatally acquired vitamin A deficiency alters innate immune responses to human rotavirus in a gnotobiotic pig model.
AuthorsVlasova AN, Chattha KS, Kandasamy S, Siegismund CS, Saif LJ
JournalJ Immunol
PubMed ID23536630
We examined how prenatally acquired vitamin A deficiency (VAD) modulates innate immune responses and human rotavirus (HRV) vaccine efficacy in a gnotobiotic (Gn) piglet model of HRV diarrhea. The VAD and vitamin A-sufficient (VAS) Gn pigs were vaccinated with attenuated HRV (AttHRV) with or without concurrent oral vitamin A supplementation ... More