Target genes of neuron-restrictive silencer factor are abnormally up-regulated in human myotilinopathy.
AuthorsBarrachina M, Moreno J, Juves S, Moreno D, Olive M, Ferrer I
JournalAm J Pathol
PubMed ID17823282
Myotilinopathy is a subgroup of myofibrillar myopathies caused by mutations in the myotilin gene in which there is aggregation of abnormal cytoskeletal proteins and ubiquitin. We report here on the accumulation of neuron-related proteins such as ubiquitin carboxy-terminal hydrolase L1 (UCHL1), synaptosomal-associated protein 25, synaptophysin, and alpha-internexin in aberrant protein ... More
Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours.
'Background For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as ... 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
Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells.
AuthorsSieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M, Martens JW, Gratama JW, Sleijfer S, Foekens JA
JournalJ Natl Cancer Inst
PubMed ID19116383
'Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five ... More
Altered GABAA receptor-mediated synaptic transmission disrupts the firing of gonadotropin-releasing hormone neurons in male mice under conditions that mimic steroid abuse.
AuthorsPenatti CA, Davis MC, Porter DM, Henderson LP
JournalJ Neurosci
PubMed ID20463213
'Gonadotropin-releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion. Self-administration of excessive doses of anabolic androgenic steroids (AAS) disrupts reproductive function and may have critical repercussions for pubertal onset in adolescent users. Here, we demonstrate that ... More
Studying copy number variations using a nanofluidic platform.
AuthorsQin J, Jones RC, Ramakrishnan R
JournalNucleic Acids Res
PubMed ID18710881
'Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). All these approaches are limited in resolution and can at best ... More
Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin
'Skin hair follicles (HF) contain bulge stem cells (SC) that regenerate HFs during hair cycles, and repair skin epithelia following injury. As natural aging is associated with decreased skin repair capacity in humans, we have investigated the impact of age on human scalp HF bulge cell number and function. Here, ... More
Molecular and functional characteristics of dendritic cells generated from highly purified CD14+ peripheral blood monocytes.
AuthorsPickl WF, Majdic O, Kohl P, Stöckl J, Riedl E, Scheinecker C, Bello-Fernandez C, Knapp W
JournalJ Immunol
PubMed ID8892615
'Dendritic cells (DC) are the most potent APCs within the immune system. We show here that highly purified CD14(bright) peripheral blood monocytes supplemented with granulocyte-monocyte (GM)-CSF plus IL-4 develop with high efficacy (>95% of input cells) into DC. They neo-expressed CD1a, CD1b, CD1c, CD80, and CD5; they massively up-regulated CD40 ... More
Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
AuthorsRalston A, Cox BJ, Nishioka N, Sasaki H, Chea E, Rugg-Gunn P, Guo G, Robson P, Draper JS, Rossant J
JournalDevelopment
PubMed ID20081188
'The mouse blastocyst and stem cells derived from its tissue lineages provide a unique genetic system for examining the establishment and loss of pluripotency. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4, and promoting extraembryonic trophoblast fate at the blastocyst stage. However, genetic ... More
Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages.
AuthorsLondon A, Itskovich E, Benhar I, Kalchenko V, Mack M, Jung S, Schwartz M
JournalJ Exp Med
PubMed ID21220455
'The death of retinal ganglion cells (RGCs) is a hallmark of many retinal neuropathies. Neuroprotection, axonal regeneration, and cell renewal are vital for the integrity of the visual system after insult but are scarce in the adult mammalian retina. We hypothesized that monocyte-derived macrophages, known to promote healing in peripheral ... More
Gene expression patterns in the human breast after pregnancy.
AuthorsAsztalos S, Gann PH, Hayes MK, Nonn L, Beam CA, Dai Y, Wiley EL, Tonetti DA
JournalCancer Prev Res (Phila Pa)
PubMed ID20179293
'Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal ... More
Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells.
AuthorsYuan P, Han J, Guo G, Orlov YL, Huss M, Loh YH, Yaw LP, Robson P, Lim B, Ng HH
JournalGenes Dev
PubMed ID19884257
'The histone H3 Lys 9 (H3K9) methyltransferase Eset is an epigenetic regulator critical for the development of the inner cell mass (ICM). Although ICM-derived embryonic stem (ES) cells are normally unable to contribute to the trophectoderm (TE) in blastocysts, we find that depletion of Eset by shRNAs leads to ... More
Detection and quantification of mRNA in single human polar bodies: a minimally invasive test of gene expression during oogenesis.
AuthorsKlatsky PC, Wessel GM, Carson SA
JournalMol Hum Reprod
PubMed ID20837506
'Proteins and mRNA produced in oogenesis support embryonic development until the zygotic transition, 3 days after fertilization. Since polar bodies can be biopsied with little if any harm to the oocyte, we tested the hypothesis that mRNA originating from expression in the meiotic oocyte is present and detectable in a ... More
High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA.
AuthorsMestdagh P, Feys T, Bernard N, Guenther S, Chen C, Speleman F, Vandesompele J
JournalNucleic Acids Res
PubMed ID18940866
'MicroRNAs (miRNAs) are an emerging class of small non-coding RNAs implicated in a wide variety of cellular processes. Research in this field is accelerating, and the growing number of miRNAs emphasizes the need for high-throughput and sensitive detection methods. Here we present the successful evaluation of the Megaplex reverse transcription ... More
TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3(neg)CD127+ immune cells in spleen and mucosa.
'In adaptive immunity, Th17 lymphocytes produce the IL-17 and IL-22 cytokines that stimulate mucosal antimicrobial defenses and tissue repair. In this study, we observed that the TLR5 agonist flagellin induced swift and transient transcription of genes encoding IL-17 and IL-22 in lymphoid, gut, and lung tissues. This innate response also ... More
Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection.
AuthorsPark NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, Wong DT
JournalClin Cancer Res
PubMed ID19706812
'PURPOSE: We have previously shown that a transcriptome is found in saliva and subpanels of these mRNAs can be used as oral cancer biomarkers. In this study, we measured the presence of microRNAs (miRNA) in saliva and determined their potential as an additional set of oral cancer biomarkers. EXPERIMENTAL DESIGN: ... More
Ligation of notch receptors in human conventional and plasmacytoid dendritic cells differentially regulates cytokine and chemokine secretion and modulates th cell polarization.
AuthorsPerez-Cabezas B, Naranjo-Gomez M, Bastos-Amador P, Requena-Fernandez G, Pujol-Borrell R, Borras FE
JournalJ Immunol
PubMed ID21593384
'Notch signaling is involved in multiple cellular processes. Recent data also support the prominent role of Notch signaling in the regulation of the immune response. In this study, we analyzed the expression and function of Notch receptors and ligands on both human blood conventional dendritic cells (cDCs) and plasmacytoid DCs ... More
AFLP markers for the R-gene in the flea beetle, Phyllotreta nemorum, conferring resistance to defenses in Barbarea vulgaris.
AuthorsBreuker CJ, Victoir K, De Jong PW, van der Meijden E, Brakefield PM, Vrieling K
JournalJ Insect Sci
PubMed ID17119620
'A so-called R-gene renders the yellow-striped flea beetle Phyllotreta nemorum L. (Coleoptera: Chrysomelidae: Alticinae) resistant to the defenses of the yellow rocket Barbarea vulgaris R.Br. (Brassicacea) and enables it to use it as a host plant in Denmark. In this study, genetic markers for an autosomal R-gene, inherited as ... More
Methylation status and transcriptional expression of the MHC class I loci in human trophoblast cells from term placenta.
AuthorsGuillaudeux T, Rodriguez AM, Girr M, Mallet V, Ellis SA, Sargent IL, Fauchet R, Alsat E, Le Bouteiller P
JournalJ Immunol
PubMed ID7897212
'Of the various molecular regulatory mechanisms that may be used by human trophoblast cells to down-regulate expression of HLA class I genes, we chose to investigate the methylation of DNA, generally associated with inhibition of transcription. We analyzed the methylation status of different HLA class I loci in villous and ... More
An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II.
AuthorsLee VH, Lee LT, Chu JY, Lam IP, Siu FK, Vaudry H, Chow BK
JournalFaseb J
PubMed ID20739612
'Fluid balance is critical to life and hence is tightly controlled in the body. Angiotensin II (ANGII), one of the most important components of this regulatory system, is recognized as a dipsogenic hormone that stimulates vasopressin (VP) expression and release. However, detailed mechanisms regarding how ANGII brings about these changes ... More
Identification of rabbit reticulocyte E217K as a UBC7 homologue and functional characterization of its core domain loop.
AuthorsLin H, Wing SS
JournalJ Biol Chem
PubMed ID10329663
'The structural basis by which ubiquitin (Ub)-conjugating enzymes (E2s) determine substrate specificity remains unclear. We cloned rabbit reticulocyte E217K because unlike the similarly sized class I E2s, E214K and UBC4, it is unable to support ubiquitin-protein ligase (E3)-dependent conjugation to endogenous proteins. RNA analysis revealed that this E2 was ... More
miR-126 is downregulated in cystic fibrosis airway epithelial cells and regulates TOM1 expression.
'Cystic fibrosis (CF) is one of the most common lethal genetic diseases in which the role of microRNAs has yet to be explored. Predicted to be regulated by miR-126, TOM1 (target of Myb1) has been shown to interact with Toll-interacting protein, forming a complex to regulate endosomal trafficking of ubiquitinated ... More
A new device for rapid isolation by size and characterization of rare circulating tumor cells.
AuthorsDesitter I, Guerrouahen BS, Benali-Furet N, Wechsler J, Janne PA, Kuang Y, Yanagita M, Wang L, Berkowitz JA, Distel RJ, Cayre YE
JournalAnticancer Res
PubMed ID21378321
'BACKGROUND: Circulating tumor cells (CTCs) likely derive from clones in the primary tumor, suggesting that they can be used for all biological tests applying to the primary cells. MATERIALS AND METHODS: The ScreenCell(R) devices are single-use and low-cost innovative devices that use a filter to isolate and sort tumor cells ... More
High throughput gene expression measurement with real time PCR in a microfluidic dynamic array.
AuthorsSpurgeon SL, Jones RC, Ramakrishnan R
JournalPlos One
PubMed ID18301740
We describe a high throughput gene expression platform based on microfluidic dynamic arrays. This system allows 2,304 simultaneous real time PCR gene expression measurements in a single chip, while requiring less pipetting than is required to set up a 96 well plate. We show that one can measure the ... More
Induction of triggering receptors of myeloid cell (TREM-1) expression in fetal membranes and higher concentration of soluble TREM-1 in amniotic fluid with spontaneous preterm birth.
AuthorsMenon R, Fortunato SJ
JournalReprod Sci
PubMed ID19017817
OBJECTIVE: To document triggering receptors of myeloid cells (TREM-1) expression in fetal membranes and to estimate soluble TREM-1 (sTREM-1) concentrations in the amniotic fluid (AF) from spontaneous preterm birth (PTB). METHODS: Fetal membranes at term not in labor placed in an organ explant system were stimulated with lipopolysaccharide ... 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
Bioinformatics construction of the human cell surfaceome.
Authorsda Cunha JP, Galante PA, de Souza JE, de Souza RF, Carvalho PM, Ohara DT, Moura RP, Oba-Shinja SM, Marie SK, Silva WA Jr, Perez RO, Stransky B, Pieprzyk M, Moore J, Caballero O, Gama-Rodrigues J, Habr-Gama A, Kuo WP, Simpson AJ, Camargo AA, Old LJ, de Sou
JournalProc Natl Acad Sci U S A
PubMed ID19805368
Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of ... More
Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells
The histone H3 Lys 9 (H3K9) methyltransferase Eset is an epigenetic regulator critical for the development of the inner cell mass (ICM). Although ICM-derived embryonic stem (ES) cells are normally unable to contribute to the trophectoderm (TE) in blastocysts, we find that depletion of Eset by shRNAs leads to differentiation ... More
Global gene expression profiling of hyperkeratotic skin lesions from inner Mongolians chronically exposed to arsenic.
AuthorsBailey K, Xia Y, Ward WO, Knapp G, Mo J, Mumford JL, Owen RD, Thai SF
JournalToxicol Pathol
PubMed ID19841129
The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately ... More
Improved RNA quality and TaqMan Pre-amplification method (PreAmp) to enhance expression analysis from formalin fixed paraffin embedded (FFPE) materials.
AuthorsLi J, Smyth P, Cahill S, Denning K, Flavin R, Aherne S, Pirotta M, Guenther SM, O'Leary JJ, Sheils O
JournalBmc Biotechnol
PubMed ID18254955
BACKGROUND: Archival formalin-fixed paraffin-embedded (FFPE) tissues represent an abundant source of clinical specimens; however their use is limited in applications involving analysis of gene expression due to RNA degradation and modification during fixation and processing. This study improved the quality of RNA extracted from FFPE by introducing a heating step ... More
Activation of bone marrow-derived microglia promotes photoreceptor survival in inherited retinal degeneration.
AuthorsSasahara M, Otani A, Oishi A, Kojima H, Yodoi Y, Kameda T, Nakamura H, Yoshimura N
JournalAm J Pathol
PubMed ID18483210
The role of microglia in neurodegeneration is controversial, although microglial activation in the retina has been shown to provide an early response against infection, injury, ischemia, and degeneration. Here we show that endogenous bone marrow (BM)-derived microglia play a protective role in vascular and neural degeneration in the ... More
RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts.
AuthorsTsuei DJ, Hsu HC, Lee PH, Jeng YM, Pu YS, Chen CN, Lee YC, Chou WC, Chang CJ, Ni YH, Chang MH
JournalOncogene
PubMed ID15184870
The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein. The RBMY transcripts, ... More
Increased expression and secretion of resistin in epicardial adipose tissue of patients with acute coronary syndrome.
AuthorsLangheim S, Dreas L, Veschini L, Maisano F, Foglieni C, Ferrarello S, Sinagra G, Zingone B, Alfieri O, Ferrero E, Maseri A, Ruotolo G
JournalAm J Physiol Heart Circ Physiol
PubMed ID20061546
The purpose of this study was to test the hypothesis that specific epicardial adipose tissue (EAT) proinflammatory adipokines might be implicated in acute coronary syndrome (ACS). We compared expression and protein secretion of several EAT adipokines of male ACS with those of matched stable coronary artery disease (CAD) patients ... More
MicroRNA regulation of DNA repair gene expression in hypoxic stress.
AuthorsCrosby ME, Kulshreshtha R, Ivan M, Glazer PM
JournalCancer Res
PubMed ID19141645
Genetic instability is a hallmark of cancer; the hypoxic tumor microenvironment has been implicated as a cause of this phenomenon. MicroRNAs (miR) are small nonprotein coding RNAs that can regulate various cellular pathways. We report here that two miRs, miR-210 and miR-373, are up-regulated in a hypoxia-inducible factor-1alpha-dependent manner ... More
Characterization of extracellular circulating microRNA.
AuthorsTurchinovich A, Weiz L, Langheinz A, Burwinkel B
JournalNucleic Acids Res
PubMed ID21609964
MicroRNAs (miRNAs), a class of post-transcriptional gene expression regulators, have recently been detected in human body fluids, including peripheral blood plasma as extracellular nuclease resistant entities. However, the origin and function of extracellular circulating miRNA remain essentially unknown. Here, we confirmed that circulating mature miRNA in contrast to mRNA or ... More
Regulatory effects of TLR2 on megakaryocytic cell function.
AuthorsBeaulieu LM, Lin E, Morin KM, Tanriverdi K, Freedman JE
JournalBlood
PubMed ID21454454
TLR2, a functional, inflammatory-related receptor, is known to be expressed on megakaryocytes and platelets and to lead to infection and immune-mediated activation of platelets; however, the role of this receptor in megakaryocytes is not understood. Using Meg-01 cells and mouse megakaryocytes, we found that NFkappaB, ERK-MAPK, and PI3K/Akt pathways, known ... More
Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR
AuthorsSieuwerts, AM; Kraan, J; Bolt-de Vries, J; van der Spoel, P; Mostert, B; Martens, JWM; Gratama, JW; Sleijfer, S; Foekens, JA
Journal
PubMed ID
Detection of circulating tumor cells (CTCs) in whole blood from metastatic cancer patients by the Cell-Search™ CTC Test (Veridex LLC, Warren, NJ, USA) has been shown to have clinical relevance. In addition to enumeration, there is great interest in molecular characterization of these CTCs. We aimed to establish a robust ... More
ABCB8 mediates doxorubicin resistance in melanoma cells by protecting the mitochondrial genome.
AuthorsElliott AM, Al-Hajj MA
JournalMol Cancer Res
PubMed ID19147539
Despite their initial effectiveness in the treatment of melanoma, chemotherapeutic agents are ultimately futile against this most aggressive form of skin cancer, and patients inevitably succumb to the disease. One of the mechanisms by which residual melanoma cells become chemoresistant is via the decreased efficiency of chemotherapeutics through the action ... 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
Type I Interferon: Potential Therapeutic Target for Psoriasis?
Background: Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors. ... More
A pro-inflammatory signature mediates FGF2-induced angiogenesis
AuthorsAndres, G; Leali, D; Mitola, S; Coltrini, D; Camozzi, M; Corsini, M; Belleri, M; Hirsch, E; Schwendener, RA; Christofori, G; Alcami, A; Presta, M
Journal
PubMed ID
Fibroblast growth factor-2 (FGF2) is a potent angiogenic growth factor. Here, gene expression profiling of FGF2-stimulated microvascular endothelial cells revealed, together with a prominent pro-angiogenic profile, a pro-inflammatory signature characterized by the up-regulation of pro-inflammatory cytokine/chemokines and their receptors, endothelial cell adhesion molecules and members of the eicosanoid pathway. Real-time ... More
The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development.
AuthorsHarries LW, Locke JM, Shields B, Hanley NA, Hanley KP, Steele A, Njolstad PR, Ellard S, Hattersley AT
JournalDiabetes
PubMed ID18356407
OBJECTIVE: Mutations in the alternatively spliced HNF4A gene cause maturity-onset diabetes of the young (MODY). We characterized the spatial and developmental expression patterns of HNF4A transcripts in human tissues and investigated their role as potential moderators of the MODY phenotype. RESEARCH DESIGN AND METHODS: We measured the expression ... More
A TaqMan low-density array to predict outcome in advanced Hodgkin's lymphoma using paraffin-embedded samples.
AuthorsSanchez-Espiridion B, Sanchez-Aguilera A, Montalban C, Martin C, Martinez R, Gonzalez-Carrero J, Poderos C, Bellas C, Fresno MF, Morante C, Mestre MJ, Mendez M, Mazorra F, Conde E, Castano A, Sanchez-Godoy P, Tomas JF, Morente MM, Piris MA, Garcia JF
JournalClin Cancer Res
PubMed ID19228737
PURPOSE: Despite major advances in the treatment of classic Hodgkin's lymphoma (cHL), approximately 30% of patients in advanced stages may eventually die as result of the disease, and current methods to predict prognosis are rather unreliable. Thus, the application of robust techniques for the identification of biomarkers associated with ... More
Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
AuthorsWang Y, Barbacioru CC, Shiffman D, Balasubramanian S, Iakoubova O, Tranquilli M, Albornoz G, Blake J, Mehmet NN, Ngadimo D, Poulter K, Chan F, Samaha RR, Elefteriades JA
JournalPlos One
PubMed ID17940614
BACKGROUND: Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to ... More
High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays
AuthorsWang, J; Lin, M; Crenshaw, A; Hutchinson, A; Hicks, B; Yeager, M; Berndt, S; Huang, WY; Hayes, RB; Chanock, SJ; Jones, RC; Ramakrishnan, R
Journal
PubMed ID
Background: Single nucleotide polymorphisms (SNPs) have emerged as the genetic marker of choice for mapping disease loci and candidate gene association studies, because of their high density and relatively even distribution in the human genomes. There is a need for systems allowing medium multiplexing (ten to hundreds of SNPs) with ... More
Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathology.
AuthorsSimunovic F, Yi M, Wang Y, Macey L, Brown LT, Krichevsky AM, Andersen SL, Stephens RM, Benes FM, Sonntag KC
JournalBrain
PubMed ID19052140
Parkinson's disease is caused by a progressive loss of the midbrain dopamine (DA) neurons in the substantia nigra pars compacta. Although the main cause of Parkinson's disease remains unknown, there is increasing evidence that it is a complex disorder caused by a combination of genetic and environmental factors, which affect ... More
Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression.
Single-minded 1 (SIM1) mutations are one of the few known causes of nonsyndromic monogenic obesity in both humans and mice. Although the role of Sim1 in the formation of the hypothalamus has been described, its postdevelopmental, physiological functions have not been well established. Here we demonstrate that postnatal ... More
Sequence variation in the primate dopamine transporter gene and its relationship to social dominance.
AuthorsMiller-Butterworth CM, Kaplan JR, Shaffer J, Devlin B, Manuck SB, Ferrell RE
JournalMol Biol Evol
PubMed ID17934207
Dopaminergic activity differs between socially dominant and subordinate monkeys, and in humans, it correlates significantly with extraversion, a trait analogous to social dominance in monkeys. Furthermore, concentrations of monoamine metabolites within the cerebrospinal fluid are highly heritable. Dopaminergic activity is modulated by the dopamine transporter (DAT), and the gene ... More
Embryo mitochondrial DNA depletion is reversed during early embryogenesis in cattle.
The extensive replication of mitochondria during oogenesis and the wide variability in mitochondrial DNA (mtDNA) copy numbers present in fully grown oocytes indicate that mtDNA amount may play an important role during early embryogenesis. Using bovine oocytes derived from follicles of different sizes to study the influence of mtDNA ... More
Embryo Mitochondrial DNA Depletion Is Reversed During Early Embryogenesis in Cattle
The extensive replication of mitochondria during oogenesis and the wide variability in mitochondrial DNA ( mtDNA) copy numbers present in fully grown oocytes indicate that mtDNA amount may play an important role during early embryogenesis. Using bovine oocytes derived from follicles of different sizes to study the influence of mtDNA ... More
Absence of functional inducible NO synthase enhances the efficacy of tolerance induced by high dose antigen feeding.
AuthorsKahn DA, Archer DC, Kelly CJ
JournalJ Immunol
PubMed ID11086044
Recent studies have suggested that IL-12 and IFN-gamma may impair the ability of fed Ag to induce systemic tolerance. Because both of these cytokines can function to directly or indirectly induce inducible NO synthase (iNOS) expression, we have investigated whether the functional expression of iNOS regulates oral tolerance. ... More
Role of the transcription factor sox4 in insulin secretion and impaired glucose tolerance.
AuthorsGoldsworthy M, Hugill A, Freeman H, Horner E, Shimomura K, Bogani D, Pieles G, Mijat V, Arkell R, Bhattacharya S, Ashcroft FM, Cox RD
JournalDiabetes
PubMed ID18477811
OBJECTIVES: To identify, map, clone, and functionally validate a novel mouse model for impaired glucose tolerance and insulin secretion. RESEARCH DESIGN AND METHODS: Haploinsufficiency of the insulin receptor and associated mild insulin resistance has been used to sensitize an N-ethyl-N-nitrosourea (ENU) screen to identify novel mutations resulting in impaired glucose ... More