A requirement for Lim domain binding protein 1 in erythropoiesis.
AuthorsLi L, Lee JY, Gross J, Song SH, Dean A, Love PE
JournalJ Exp Med
PubMed ID21041453
During erythrocyte development, the nuclear cofactor Lim domain binding protein 1 (Ldb1) functions as a core subunit of multiprotein DNA binding complexes that include the transcription factors Scl and Gata-1 and the Lim-only adapter Lmo2. Scl, Gata-1, and Lmo2 are each required for erythropoiesis, suggesting that Ldb1-nucleated transcription complexes regulate ... More
The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice.
To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared ... More
Dynamic changes in the expression of DEP-1 and other PDGF receptor-antagonizing PTPs during onset and termination of neointima formation.
AuthorsKappert K, Paulsson J, Sparwel J, Leppanen O, Hellberg C, Ostman A, Micke P
JournalFaseb J
PubMed ID17158785
'Growth factor-dependent tissue remodeling, such as restenosis, is believed to be predominantly regulated by changes in expression of receptor-tyrosine-kinases (RTKs) and their ligands. As endogenous antagonists of RTKs, protein-tyrosine-phosphatases (PTPs) are additional candidate regulators of these processes. Using laser-capture-microdissection and quantitative RT-polymerase chain reaction (qRT-PCR), we investigated the layer-specific ... More
Molecular mechanisms of induction of antigen-specific allograft tolerance by intranasal peptide administration.
'We have previously shown that intranasal (i.n.) administration of a single MHC class II-restricted HY peptide to female mice induces tolerance to up to five additional epitopes expressed on test male grafts, a phenomenon known as linked suppression. In this study, we investigated the molecular mechanisms involved both in the ... More
Highly specific alternative splicing of transcripts encoding BK channels in the chicken's cochlea is a minor determinant of the tonotopic gradient.
AuthorsMiranda-Rottmann S, Kozlov AS, Hudspeth AJ
JournalMol Cell Biol
PubMed ID20479127
'The frequency sensitivity of auditory hair cells in the inner ear varies with their longitudinal position in the sensory epithelium. Among the factors that determine the differential cellular response to sound is the resonance of a hair cell''s transmembrane electrical potential, whose frequency correlates with the kinetic properties of ... More
Ultraviolet A within sunlight induces mutations in the epidermal basal layer of engineered human skin.
AuthorsHuang XX, Bernerd F, Halliday GM
JournalAm J Pathol
PubMed ID19264911
'The ultraviolet B (UVB) waveband within sunlight is an important carcinogen; however, UVA is also likely to be involved. By ascribing mutations to being either UVB or UVA induced, we have previously shown that human skin cancers contain similar numbers of UVB- and UVA-induced mutations, and, importantly, the UVA ... More
Transcriptional signature of flavopiridol-induced tumor cell death.
'Flavopiridol has been shown to inhibit the proliferation of a variety of human tumor cells and is currently undergoing clinical evaluation in cancer treatment. Although the antiproliferative effect of flavopiridol has been attributed to the inhibition of cyclin-dependent kinases 2 and 4, recent reports indicate that the ... More
Protein disulphide isomerase protects against protein aggregation and is S-nitrosylated in amyotrophic lateral sclerosis.
'Amyotrophic lateral sclerosis is a rapidly progressing fatal neurodegenerative disease characterized by the presence of protein inclusions within affected motor neurons. Endoplasmic reticulum stress leading to apoptosis was recently recognized to be an important process in the pathogenesis of sporadic human amyotrophic lateral sclerosis as well as in transgenic models ... More
Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF.
AuthorsBharti K, Liu W, Csermely T, Bertuzzi S, Arnheiter H
JournalDevelopment
PubMed ID18272592
'During vertebrate eye development, the transcription factor MITF plays central roles in neuroepithelial domain specification and differentiation of the retinal pigment epithelium. MITF is not a single protein but represents a family of isoforms generated from a common gene by alternative promoter/exon use. To address the question of the ... More
Hedgehog signaling regulates sensory cell formation and auditory function in mice and humans.
AuthorsDriver EC, Pryor SP, Hill P, Turner J, Ruther U, Biesecker LG, Griffith AJ, Kelley MW
JournalJ Neurosci
PubMed ID18632939
'Auditory perception is mediated through a finite number of mechanosensory hair cells located in a specialized sensory epithelium within the inner ear. The formation of the appropriate number of hair cells and the location of those cells is crucial for normal auditory function. However, the factors that regulate the formation ... More
KCl cotransporter-3 down-regulates E-cadherin/beta-catenin complex to promote epithelial-mesenchymal transition.
'The potassium chloride cotransporter (KCC) is a major determinant of osmotic homeostasis and plays an emerging role in tumor biology. Here, we investigate if KCC is involved in the regulation of epithelial-mesenchymal transition (EMT), a critical cellular event of malignancy. E-cadherin and beta-catenin colocalize in the cell-cell junctions, ... More
Addressing fluorogenic real-time qPCR inhibition using the novel custom Excel file system 'FocusField2-6GallupqPCRSet-upTool-001' to attain consistently high fidelity qPCR reactions.
AuthorsGallup JM, Ackermann MR
JournalBiol Proced Online
PubMed ID17033699
'The purpose of this manuscript is to discuss fluorogenic real-time quantitative polymerase chain reaction (qPCR) inhibition and to introduce/define a novel Microsoft Excel-based file system which provides a way to detect and avoid inhibition, and enables investigators to consistently design dynamically-sound, truly LOG-linear qPCR reactions very quickly. The qPCR problems ... More
Feedback regulation of p38 activity via ATF2 is essential for survival of embryonic liver cells.
AuthorsBreitwieser W, Lyons S, Flenniken AM, Ashton G, Bruder G, Willington M, Lacaud G, Kouskoff V, Jones N
JournalGenes Dev
PubMed ID17699753
'The ATF2 transcription factor is phosphorylated by the stress-activated mitogen-activated protein kinases (MAPKs) JNK and p38. We show that this phosphorylation is essential for ATF2 function in vivo, since a mouse carrying mutations in the critical phosphorylation sites has a strong phenotype identical to that seen upon deletion of ... More
Cyclic AMP-mediated endocytosis of intestinal epithelial NHE3 requires binding to synaptotagmin 1.
AuthorsMusch MW, Arvans DL, Wang Y, Nakagawa Y, Solomaha E, Chang EB
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID19926819
'The apical membrane Na(+)-H(+) exchanger (NHE)3 is regulated by cAMP-dependent phosphorylation, which inhibits its activity through membrane endocytosis. The clathrin complex adaptor protein synaptotagmin 1 (Syt 1) appears to be essential to this process, but little is known about its expression in intestinal epithelial cells or interaction with NHE3. The ... More
Conversion of CD4+ CD25- cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus.
AuthorsLiang S, Alard P, Zhao Y, Parnell S, Clark SL, Kosiewicz MM
JournalJ Exp Med
PubMed ID15630140
'The CD4+ CD25+ regulatory T cells play a critical role in controlling autoimmunity, but little is known about their development and maintenance. In this study, we investigated whether CD4+ CD25- cells can convert to CD4+ CD25+ regulatory T cells in vivo under natural conditions. CD4+ CD25- cells from CD45.1+ mice ... More
Gene expression profiling of human oocytes following in vivo or in vitro maturation.
AuthorsJones GM, Cram DS, Song B, Magli MC, Gianaroli L, Lacham-Kaplan O, Findlay JK, Jenkin G, Trounson AO
JournalHum Reprod
PubMed ID18346995
'BACKGROUND: Immature human oocytes matured in vitro, particularly those from gonadotrophin stimulated ovaries, are developmentally incompetent when compared with oocytes matured in vivo. This developmental incompetence has been explained as poor oocyte cytoplasmic maturation without any determination of the likely molecular basis of this observation. METHODS: Replicate whole human ... More
AuthorsIwasaki K, Bajenova E, Somogyi-Ganss E, Miller M, Nguyen V, Nourkeyhani H, Gao Y, Wendel M, Ganss B
JournalJ Dent Res
PubMed ID16304441
'We aimed to analyze the differential gene expression in various murine dental tissues, expecting to find novel factors that are involved in tooth formation. We here describe the identification of a novel ameloblast-specific gene, amelotin (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of microdissected ameloblasts, odontoblasts, dental pulp, and ... More
Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer.
AuthorsCasadei S, Norquist BM, Walsh T, Stray S, Mandell JB, Lee MK, Stamatoyannopoulos JA, King MC
JournalCancer Res
PubMed ID21285249
'Inherited mutations in the BRCA2-interacting protein PALB2 are known to be associated with increased risks of developing breast cancer. To evaluate the contribution of PALB2 to familial breast cancer in the United States, we sequenced the coding sequences and flanking regulatory regions of the gene from constitutional genomic DNA of ... More
Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers.
AuthorsGray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, Bai W, Frantz G, Zhang Z, Koeppen H, de Sauvage FJ, Davis DP
JournalCancer Res
PubMed ID16266996
'To identify genes that could serve as targets for novel cancer therapeutics, we used a bioinformatic analysis of microarray data comparing gene expression between normal and tumor-derived primary human tissues. From this approach, we have found that maternal embryonic leucine zipper kinase (Melk), a member of the AMP serine/threonine ... More
Defective chromatin structure in somatic cell cloned mouse embryos.
AuthorsZhang M, Wang F, Kou Z, Zhang Y, Gao S
JournalJ Biol Chem
PubMed ID19602512
'Epigenetic reprogramming plays a central role in the development of cloned embryos generated by somatic cell nuclear transfer, and it is believed that aberrant reprogramming leads to the abnormal development of most cloned embryos. Recent studies show that trimethylation of H3K27 (H3K27me3) contributes to the maintenance of embryonic stem ... More
Heme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels.
AuthorsJaggar JH, Li A, Parfenova H, Liu J, Umstot ES, Dopico AM, Leffler CW
JournalCirc Res
PubMed ID16166559
'Carbon monoxide (CO) is an endogenous paracrine and autocrine gaseous messenger that regulates physiological functions in a wide variety of tissues. CO induces vasodilation by activating arterial smooth muscle large-conductance Ca2+-activated potassium (BK(Ca)) channels. However, the mechanism by which CO activates BK(Ca) channels remains unclear. Here, we tested the hypothesis ... More
Increased mitochondrial DNA damage and down-regulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid.
AuthorsWang AL, Lukas TJ, Yuan M, Neufeld AH
JournalMol Vis
PubMed ID18392142
'PURPOSE: In the central nervous system (CNS), increased mitochondrial DNA (mtDNA) damage is associated with aging and may underlie, contribute to, or increase the susceptibility to neurodegenerative diseases. Because of the focus on the retinal pigment epithelium (RPE) and choroid as tissue relevant to age-related macular degeneration (AMD), we ... More
Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity.
AuthorsUnger TJ, Calderon GA, Bradley LC, Sena-Esteves M, Rios M
JournalJ Neurosci
PubMed ID18160634
'Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are expressed in several hypothalamic and hindbrain nuclei involved in regulating energy homeostasis, developmentally and in the adult animal. Their depletion during the fetal or early postnatal periods when developmental processes are still ongoing elicits hyperphagic behavior and obesity in mice. ... More
Orthotopic growth of human glioma cells quantitatively and qualitatively influences radiation-induced changes in gene expression.
AuthorsCamphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ
JournalCancer Res
PubMed ID16288029
'The effect of radiation on gene expression has been most frequently studied using tissue culture models. To determine the influence of experimental growth condition on radiation-induced changes in gene expression, microarray analysis was done on two human glioma cell lines (U87 and U251) grown in tissue culture and as s.c. ... More
CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth.
AuthorsAugsten M, Hagglof C, Olsson E, Stolz C, Tsagozis P, Levchenko T, Frederick MJ, Borg A, Micke P, Egevad L, Ostman A
JournalProc Natl Acad Sci U S A
PubMed ID19218429
'This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. ... More
Changes in Gene Expression during Pituitary Morphogenesis and Organogenesis in the Chick Embryo.
AuthorsProszkowiec-Weglarz M, Higgins SE, Porter TE
JournalEndocrinology
PubMed ID21239434
'The anterior pituitary gland plays an important role in the regulation of many physiological processes. Formation of Rathke''s pouch (RP), the precursor of the anterior pituitary, involves evagination of the oral ectoderm in a multi-step process regulated by cell interactions, signaling pathways, and transcription factors. Chickens are an excellent model ... More
Approaches to DNA/RNA Extraction and whole genome amplification.
AuthorsSantella RM
JournalCancer Epidemiol Biomarkers Prev
PubMed ID16985017
'Analysis of DNA and/or RNA is an important component of most epidemiologic studies. The methods used for their preparation vary depending on the number of samples in the study as well as the amount of tissue or cells available, the specific downstream assay, and the resources available. They range from ... More
NANOS3 function in human germ cell development.
AuthorsJulaton VT, Reijo Pera RA
JournalHum Mol Genet
PubMed ID21421998
'Human infertility is common and frequently linked to poor germ cell development. Yet, human germ cell development is poorly understood, at least in part due to the inaccessibility of germ cells to study especially during fetal development. Here, we explored the function of a highly conserved family of genes, the ... More
Laser capture microdissection of cells from plant tissues.
AuthorsKerk NM, Ceserani T, Tausta SL, Sussex IM, Nelson TM
JournalPlant Physiol
PubMed ID12746508
Laser capture microdissection (LCM) is a technique by which individual cells can be harvested from tissue sections while they are viewed under the microscope, by tacking selected cells to an adhesive film with a laser beam. Harvested cells can provide DNA, RNA, and protein for the profiling of ... More
Mullerian inhibiting substance acts as a motor neuron survival factor in vitro.
AuthorsWang PY, Koishi K, McGeachie AB, Kimber M, Maclaughlin DT, Donahoe PK, McLennan IS
JournalProc Natl Acad Sci U S A
PubMed ID16260730
The survival of motor neurons is controlled by multiple factors that regulate different aspects of their physiology. The identification of these factors is important because of their relationship to motor neuron disease. We investigate here whether Mullerian Inhibiting Substance (MIS) is a motor neuron survival factor. We find that motor ... More
New quick method for isolating RNA from laser captured cells stained by immunofluorescent immunohistochemistry; RNA suitable for direct use in fluorogenic TaqMan one-step real-time RT-PCR.
We describe a new approach for reliably isolating one-step real-time quantitative RT-PCR-quality RNA from laser captured cells retrieved from frozen sections previously subjected to immunofluorescent immunohistochemistry (IF-IHC) and subsequently subjected to fluorogenic one-step real-time RT-PCR analysis without the need for costly, time-consuming linear amplification. One cell's worth of RNA can ... More
Human saliva proteome and transcriptome.
AuthorsHu S, Li Y, Wang J, Xie Y, Tjon K, Wolinsky L, Loo RR, Loo JA, Wong DT
JournalJ Dent Res
PubMed ID17122167
This paper tests the hypothesis that salivary proteins and their counterpart mRNAs co-exist in human whole saliva. Global profiling of human saliva proteomes and transcriptomes by mass spectrometry (MS) and expression microarray technologies, respectively, revealed many similarities between saliva proteins and mRNAs. Of the function-known proteins identified in saliva, ... More
Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties.
AuthorsBowie MB, Kent DG, Dykstra B, McKnight KD, McCaffrey L, Hoodless PA, Eaves CJ
JournalProc Natl Acad Sci U S A
PubMed ID17379664
Hematopoietic stem cells (HSCs) execute self-renewal divisions throughout fetal and adult life, although some of their properties do alter. Here we analyzed the magnitude and timing of changes in the self-renewal properties and differentiated cell outputs of transplanted HSCs obtained from different sources during development. We also assessed the ... More
Loss of transforming growth factor-beta type II receptor promotes metastatic head-and-neck squamous cell carcinoma.
AuthorsLu SL, Herrington H, Reh D, Weber S, Bornstein S, Wang D, Li AG, Tang CF, Siddiqui Y, Nord J, Andersen P, Corless CL, Wang XJ
JournalGenes Dev
PubMed ID16702406
The prognosis of head-and-neck squamous cell carcinoma (HNSCC) has not been improved in the past 20 years. Validation of HNSCC biomarkers for targeted therapy has been hindered by a lack of animal models mimicking human HNSCC at both the pathological and molecular levels. Here we report that overexpression of K-ras ... More
V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway.
AuthorsHurtado-Lorenzo A, Skinner M, El Annan J, Futai M, Sun-Wada GH, Bourgoin S, Casanova J, Wildeman A, Bechoua S, Ausiello DA, Brown D, Marshansky V
JournalNat Cell Biol
PubMed ID16415858
The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. ... More
Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells.
AuthorsChan G, Cheung LS, Yang W, Milyavsky M, Sanders AD, Gu S, Hong WX, Liu AX, Wang X, Barbara M, Sharma T, Gavin J, Kutok JL, Iscove NN, Shannon KM, Dick JE, Neel BG, Braun BS
JournalBlood
PubMed ID21398220
Src homology 2 domain-containing phosphatase 2 (Shp2), encoded by Ptpn11, is a member of the nonreceptor protein-tyrosine phosphatase family, and functions in cell survival, proliferation, migration, and differentiation in many tissues. Here we report that loss of Ptpn11 in murine hematopoietic cells leads to bone marrow aplasia and lethality. Mutant ... More
Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis.
AuthorsTian H, Callahan CA, DuPree KJ, Darbonne WC, Ahn CP, Scales SJ, de Sauvage FJ
JournalProc Natl Acad Sci U S A
PubMed ID19246386
The Hedgehog (Hh) pathway has been implicated in pancreatic cancer but its role remains controversial. To delineate the cell populations able to respond to Hh ligand stimulation, we expressed an oncogenic allele of Smoothened (SmoM2) to cell autonomously activate Hh signaling in the mouse pancreas. Surprisingly, we found that expression ... More
AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies.
AuthorsMoldenhauer G, Popov SW, Wotschke B, Bruderlein S, Riedl P, Fissolo N, Schirmbeck R, Ritz O, Moller P, Leithauser F
JournalBlood
PubMed ID16269615
Neoplastic transformation of mature B cells can be triggered by class-switch recombination of the immunoglobulin gene, which aberrantly targets a protooncogene and promotes translocation. Class-switch recombination is initiated by the B-cell-specific protein activation-induced cytidine deaminase (AID). Using immunohistochemistry with a newly generated monoclonal antibody and quantitative reverse-transcription-polymerase chain reaction ... More
Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube.
AuthorsRibes V, Balaskas N, Sasai N, Cruz C, Dessaud E, Cayuso J, Tozer S, Yang LL, Novitch B, Marti E, Briscoe J
JournalGenes Dev
PubMed ID20516201
The secreted ligand Sonic Hedgehog (Shh) organizes the pattern of cellular differentiation in the ventral neural tube. For the five neuronal subtypes, increasing levels and durations of Shh signaling direct progenitors to progressively more ventral identities. Here we demonstrate that this mode of action is not applicable to the generation ... More
DARPP-32 involvement in the photic pathway of the circadian system.
AuthorsYan L, Bobula JM, Svenningsson P, Greengard P, Silver R
JournalJ Neurosci
PubMed ID16971527
The multifunctional regulator of protein kinases and phosphatases dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is an important molecular target of the dopamine signaling pathway. In the present study, we investigated the possible involvement of DARPP-32 regulation in the circadian system using DARPP-32 knock-out (KO) mice. These mice showed ... More
Radiation-induced changes in gene expression involve recruitment of existing messenger RNAs to and away from polysomes.
AuthorsLu X, de la Pena L, Barker C, Camphausen K, Tofilon PJ
JournalCancer Res
PubMed ID16424041
Although ionizing radiation has been shown to influence gene transcription, little is known about the effects of radiation on gene translational efficiency. To obtain a genome-wide perspective of the effects of radiation on gene translation, microarray analysis was done on polysome-bound RNA isolated from irradiated human brain tumor cells; ... More
Options available for profiling small samples: a review of sample amplification technology when combined with microarray profiling.
AuthorsNygaard V, Hovig E
JournalNucleic Acids Res
PubMed ID16473852
The possibility of performing microarray analysis on limited material has been demonstrated in a number of publications. In this review we approach the technical aspects of mRNA amplification and several important implicit consequences, for both linear and exponential procedures. Amplification efficiencies clearly allow profiling of extremely small samples. The conservation ... More
Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids.
AuthorsMuller P, Warr E, Stevenson BJ, Pignatelli PM, Morgan JC, Steven A, Yawson AE, Mitchell SN, Ranson H, Hemingway J, Paine MJ, Donnelly MJ
JournalPlos Genet
PubMed ID19043575
Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive. Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Saharan Africa. An understanding of the molecular mechanisms ... More
Deficiency in NOD antigen-presenting cell function may be responsible for suboptimal CD4+CD25+ T-cell-mediated regulation and type 1 diabetes development in NOD mice.
AuthorsAlard P, Manirarora JN, Parnell SA, Hudkins JL, Clark SL, Kosiewicz MM
JournalDiabetes
PubMed ID16804081
Various defects in antigen-presenting cells (APCs) and T-cells, including regulatory cells, have been associated with type 1 diabetes development in NOD mice. CD4(+)CD25(+) regulatory cells play a crucial role in controlling various autoimmune diseases, and a deficiency in their number or function could be involved in disease development. The current ... More
Multiple gene expression analyses in paraffin-embedded tissues by TaqMan low-density array: Application to hedgehog and Wnt pathway analysis in ovarian endometrioid adenocarcinoma.
AuthorsSteg A, Wang W, Blanquicett C, Grunda JM, Eltoum IA, Wang K, Buchsbaum DJ, Vickers SM, Russo S, Diasio RB, Frost AR, LoBuglio AF, Grizzle WE, Johnson MR
JournalJ Mol Diagn
PubMed ID16436637
Recent studies have shown the hedgehog and Wnt families of signaling proteins to be associated with tumor initiation, growth, and survival. However, these pathways remain unexplored in ovarian endometrioid adenocarcinoma (OEA). Here, we describe a novel TaqMan low-density array to examine the expression of 26 and 20 genes ... More
Utility of linearly amplified RNA for RT-PCR detection of chromosomal translocations: validation using the t(2;5)(p23;q35) NPM-ALK chromosomal translocation.
AuthorsSchumacher JA, Jenson SD, Elenitoba-Johnson KS, Lim MS
JournalJ Mol Diagn
PubMed ID14736822
The requirement for sufficient quantities of starting RNA has limited the ability to evaluate multiple transcripts using reverse transcriptase-polymerase chain reaction (RT-PCR). In this study, we demonstrate the utility of linear RNA amplification for RT-PCR analysis of multiple gene transcripts including a chromosomal translocation, using the t(2;5)(p23;q35) as a model. ... More
Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer.
AuthorsDe Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Di Carlo V, Doglioni C, Protti MP
JournalJ Exp Med
PubMed ID21339327
Pancreatic cancer is a very aggressive disease characterized by a marked desmoplasia with a predominant Th2 (GATA-3+) over Th1 (T-bet+) lymphoid infiltrate. We found that the ratio of GATA-3+/T-bet+ tumor-infiltrating lymphoid cells is an independent predictive marker of patient survival. Patients surgically treated for stage IB/III disease with a ratio ... More
Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors.
BACKGROUND: Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in ... More
Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo.
AuthorsJedrusik A, Parfitt DE, Guo G, Skamagki M, Grabarek JB, Johnson MH, Robson P, Zernicka-Goetz M
JournalGenes Dev
PubMed ID18832072
Genesis of the trophectoderm and inner cell mass (ICM) lineages occurs in two stages. It is initiated via asymmetric divisions of eight- and 16-cell blastomeres that allocate cells to inner and outer positions, each with different developmental fates. Outside cells become committed to the trophectoderm at the blastocyst stage through ... More
Transcriptional profiling of laser capture microdissected rat arterial elements: fenoldopam-induced vascular toxicity as a model system.
AuthorsDalmas DA, Scicchitano MS, Chen Y, Kane J, Mirabile R, Schwartz LW, Thomas HC, Boyce RW
JournalToxicol Pathol
PubMed ID18467687
Transcriptional profiling of specific elements of vasculature from animal models of vascular toxicity is an approach to gain insight into molecular mechanisms of vascular injury. Feasibility of using laser capture microdissection (LCM) to evaluate differential gene expression in selected elements of mesenteric arteries (MA) from untreated rats and ... More
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis.
AuthorsTober J, Koniski A, McGrath KE, Vemishetti R, Emerson R, de Mesy-Bentley KK, Waugh R, Palis J
JournalBlood
PubMed ID17062726
In the adult, platelets are derived from unipotential megakaryocyte colony-forming cells (Meg-CFCs) that arise from bipotential megakaryocyte/erythroid progenitors (MEPs). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes, and circulating platelets, were examined in the murine embryo. We found that a ... More
Reproducibility, fidelity, and discriminant validity of mRNA amplification for microarray analysis from primary hematopoietic cells.
AuthorsLi L, Roden J, Shapiro BE, Wold BJ, Bhatia S, Forman SJ, Bhatia R
JournalJ Mol Diagn
PubMed ID15681474
Analysis of gene expression in clinical samples poses special challenges, including limited RNA availability and poor RNA quality. Quantitative information regarding reliability of RNA amplification methodologies applied to primary cells and representativeness of resulting gene expression profiles is limited. We evaluated four protocols for RNA amplification from peripheral blood mononuclear ... More
Distinctive expression of chemokines and transforming growth factor-beta signaling in human arterial endothelium during atherosclerosis.
AuthorsVolger OL, Fledderus JO, Kisters N, Fontijn RD, Moerland PD, Kuiper J, van Berkel TJ, Bijnens AP, Daemen MJ, Pannekoek H, Horrevoets AJ
JournalAm J Pathol
PubMed ID17591977
Knowledge about the in vivo role of endothelium in chronic human atherosclerosis has mostly been derived by insights from mouse models. Therefore, we set out to establish by microarray analyses the gene expression profiles of endothelium from human large arteries, as isolated by laser microbeam microdissection, having focal atherosclerosis ... More
Relative reduction of endothelial nitric-oxide synthase expression and transcription in atherosclerosis-prone regions of the mouse aorta and in an in vitro model of disturbed flow.
AuthorsWon D, Zhu SN, Chen M, Teichert AM, Fish JE, Matouk CC, Bonert M, Ojha M, Marsden PA, Cybulsky MI
JournalAm J Pathol
PubMed ID17982133
Atherosclerosis develops in distinct regions of the arterial tree. Defining patterns and mechanisms of endothelial cell gene expression in different regions of normal arteries is key to understanding the initial molecular events in atherogenesis. In this study, we demonstrated that the expression of endothelial nitric-oxide synthase (eNOS), an ... More
Influence of in vivo growth on human glioma cell line gene expression: convergent profiles under orthotopic conditions.
AuthorsCamphausen K, Purow B, Sproull M, Scott T, Ozawa T, Deen DF, Tofilon PJ
JournalProc Natl Acad Sci U S A
PubMed ID15928080
Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype ... More
Genomic analysis of post-mating changes in the honey bee queen (Apis mellifera).
AuthorsKocher SD, Richard FJ, Tarpy DR, Grozinger CM
JournalBmc Genomics
PubMed ID18489784
BACKGROUND: The molecular mechanisms underlying the post-mating behavioral and physiological transitions undergone by females have not been explored in great detail. Honey bees represent an excellent model system in which to address these questions because they exhibit a range of "mating states,"" with two extremes (virgins and egg-laying, mated ... More
Salt-sensitive splice variant of nNOS expressed in the macula densa cells.
AuthorsLu D, Fu Y, Lopez-Ruiz A, Zhang R, Juncos R, Liu H, Manning RD Jr, Juncos LA, Liu R
JournalAm J Physiol Renal Physiol
PubMed ID20335319
Neuronal nitric oxide synthase (nNOS), which is abundantly expressed in the macula densa cells, attenuates tubuloglomerular feedback (TGF). We hypothesize that splice variants of nNOS are expressed in the macula densa, and nNOS-beta is a salt-sensitive isoform that modulates TGF. Sprague-Dawley rats received a low-, normal-, or high-salt diet for ... More
Gene expression in rat lacrimal gland duct cells collected using laser capture microdissection: evidence for K+ secretion by duct cells.
PURPOSE: To compare gene expression profiles of lacrimal gland duct and acinar cells after laser capture microdissection (LCM) and identify molecular networks related to K+ secretion, testing the hypothesis that duct cells are responsible for high K+ levels in tears. METHODS: Frozen sections of lacrimal glands from five rats were ... More
Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm.
AuthorsKan NG, Stemmler MP, Junghans D, Kanzler B, de Vries WN, Dominis M, Kemler R
JournalDevelopment
PubMed ID17138661
During mammalian embryogenesis the trophectoderm represents the first epithelial structure formed. The cell adhesion molecule E-cadherin is ultimately necessary for the transition from compacted morula to the formation of the blastocyst to ensure correct establishment of adhesion junctions in the trophectoderm. Here, we analyzed to what extent E-cadherin confers ... More
APC activation restores functional CD4(+)CD25(+) regulatory T cells in NOD mice that can prevent diabetes development.
AuthorsManirarora JN, Kosiewicz MM, Parnell SA, Alard P
JournalPlos One
PubMed ID19011680
BACKGROUND: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4(+)CD25(+) regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4(+)CD25(+) regulatory cells in vivo could ... More
Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial.
AuthorsLe Deley MC, Delattre O, Schaefer KL, Burchill SA, Koehler G, Hogendoorn PC, Lion T, Poremba C, Marandet J, Ballet S, Pierron G, Brownhill SC, Nesslbock M, Ranft A, Dirksen U, Oberlin O, Lewis IJ, Craft AW, Jurgens H, Kovar H
JournalJ Clin Oncol
PubMed ID20308673
PURPOSE EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA ... More
Low dietary folate initiates intestinal tumors in mice, with altered expression of G2-M checkpoint regulators polo-like kinase 1 and cell division cycle 25c.
AuthorsKnock E, Deng L, Wu Q, Leclerc D, Wang XL, Rozen R
JournalCancer Res
PubMed ID17079455
Clinical reports have suggested that low dietary folate increases risk for colorectal cancer. Animal studies for investigation of folate and tumorigenesis have used carcinogen induction or mice with germ-line mutations. We have developed a new spontaneous tumor model in which mice, with or without a null allele in a key ... More
The unique transcriptome through day 3 of human preimplantation development.
AuthorsDobson AT, Raja R, Abeyta MJ, Taylor T, Shen S, Haqq C, Pera RA
JournalHum Mol Genet
PubMed ID15150160
Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in culture or following transfer to the ... More
Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled.
AuthorsReigstad CS, Hultgren SJ, Gordon JI
JournalJ Biol Chem
PubMed ID17504765
Uropathogenic Escherichia coli (UPEC), the principal cause of urinary tract infection in women, colonizes the gut as well as the genitourinary tract. Studies of mice inoculated with UTI89, a sequenced isolate, have revealed a complex life cycle that includes formation of intracellular bacterial communities (IBCs) in bladder urothelial cells. ... More
Retinal cell responses to elevated intraocular pressure: a gene array comparison between the whole retina and retinal ganglion cell layer.
AuthorsGuo Y, Cepurna WO, Dyck JA, Doser TA, Johnson EC, Morrison JC
JournalInvest Ophthalmol Vis Sci
PubMed ID20071680
PURPOSE: To determine and compare gene expression patterns in the whole retina and retinal ganglion cell layer (RGCL) in a rodent glaucoma model. METHODS: IOP was unilaterally elevated in Brown Norway rats (N = 26) by injection of hypertonic saline and monitored for 5 weeks. A cDNA microarray was used ... More
Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men.
AuthorsRiserus U, Sprecher D, Johnson T, Olson E, Hirschberg S, Liu A, Fang Z, Hegde P, Richards D, Sarov-Blat L, Strum JC, Basu S, Cheeseman J, Fielding BA, Humphreys SM, Danoff T, Moore NR, Murgatroyd P, O'Rahilly S, Sutton P, Willson T, Hassall D, Frayn KN, Karpe F
JournalDiabetes
PubMed ID18024853
OBJECTIVE: Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPARdelta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS: The PPARdelta agonist (10 mg o.d. GW501516), ... More
Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: implications for host-microbial interactions in the gut.
AuthorsMelmed G, Thomas LS, Lee N, Tesfay SY, Lukasek K, Michelsen KS, Zhou Y, Hu B, Arditi M, Abreu MT
JournalJ Immunol
PubMed ID12538701
Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to ... More
Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy.
AuthorsGhadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, Fuzesi L, Langer C, Becker H, Liersch T, Ried T
JournalJ Clin Oncol
PubMed ID15774776
PURPOSE: There is a wide spectrum of tumor responsiveness of rectal adenocarcinomas to preoperative chemoradiotherapy ranging from complete response to complete resistance. This study aimed to investigate whether parallel gene expression profiling of the primary tumor can contribute to stratification of patients into groups of responders or nonresponders. PATIENTS ... More
Endothelium-derived hyperpolarizing factor in human internal mammary artery is 11,12-epoxyeicosatrienoic acid and causes relaxation by activating smooth muscle BK(Ca) channels.
AuthorsArcher SL, Gragasin FS, Wu X, Wang S, McMurtry S, Kim DH, Platonov M, Koshal A, Hashimoto K, Campbell WB, Falck JR, Michelakis ED
JournalCirculation
PubMed ID12578883
BACKGROUND: Left internal mammary arteries (LIMAs) synthesize endothelium-derived hyperpolarizing factor (EDHF), a short-lived K(+) channel activator that persists after inhibition of nitric oxide (NO) and prostaglandin synthesis. EDHF hyperpolarizes and relaxes smooth muscle cells (SMCs). The identity of EDHF in humans is unknown. We hypothesized that EDHF (1) is 11,12-epoxyeicosatrienoic ... More