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Species

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Gene

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Platform

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Channel

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HiPlex Channel

  • T1 (85058) Apply T1 filter
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  • T11 (85039) Apply T11 filter
  • T9 (82563) Apply T9 filter
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  • S1 (32) Apply S1 filter
  • 8 (17) Apply 8 filter
  • 1 (1) Apply 1 filter
  • 10 (1) Apply 10 filter
  • 6 (1) Apply 6 filter

Product

  • RNAscope Multiplex Fluorescent Assay (1035) Apply RNAscope Multiplex Fluorescent Assay filter
  • RNAscope (998) Apply RNAscope filter
  • RNAscope Fluorescent Multiplex Assay (732) Apply RNAscope Fluorescent Multiplex Assay filter
  • RNAscope 2.5 HD Red assay (704) Apply RNAscope 2.5 HD Red assay filter
  • RNAscope 2.0 Assay (497) Apply RNAscope 2.0 Assay filter
  • RNAscope 2.5 HD Brown Assay (293) Apply RNAscope 2.5 HD Brown Assay filter
  • TBD (193) Apply TBD filter
  • RNAscope 2.5 LS Assay (191) Apply RNAscope 2.5 LS Assay filter
  • RNAscope 2.5 HD Duplex (160) Apply RNAscope 2.5 HD Duplex filter
  • RNAscope 2.5 HD Reagent Kit - BROWN (108) Apply RNAscope 2.5 HD Reagent Kit - BROWN filter
  • RNAscope Multiplex Fluorescent v2 (97) Apply RNAscope Multiplex Fluorescent v2 filter
  • BASEscope Assay RED (91) Apply BASEscope Assay RED filter
  • RNAscope 2.5 VS Assay (85) Apply RNAscope 2.5 VS Assay filter
  • Basescope (53) Apply Basescope filter
  • RNAscope HiPlex v2 assay (30) Apply RNAscope HiPlex v2 assay filter
  • miRNAscope (26) Apply miRNAscope filter
  • DNAscope HD Duplex Reagent Kit (15) Apply DNAscope HD Duplex Reagent Kit filter
  • RNAscope 2.5 HD duplex reagent kit (13) Apply RNAscope 2.5 HD duplex reagent kit filter
  • BaseScope Duplex Assay (12) Apply BaseScope Duplex Assay filter
  • RNAscope Multiplex fluorescent reagent kit v2 (6) Apply RNAscope Multiplex fluorescent reagent kit v2 filter
  • RNAscope Fluorescent Multiplex Reagent kit (5) Apply RNAscope Fluorescent Multiplex Reagent kit filter
  • RNAscope ISH Probe High Risk HPV (5) Apply RNAscope ISH Probe High Risk HPV filter
  • CTCscope (4) Apply CTCscope filter
  • RNAscope 2.5 HD Reagent Kit (4) Apply RNAscope 2.5 HD Reagent Kit filter
  • RNAscope HiPlex12 Reagents Kit (3) Apply RNAscope HiPlex12 Reagents Kit filter
  • DNAscope Duplex Assay (2) Apply DNAscope Duplex Assay filter
  • RNAscope 2.5 HD Assay (2) Apply RNAscope 2.5 HD Assay filter
  • RNAscope 2.5 LS Assay - RED (2) Apply RNAscope 2.5 LS Assay - RED filter
  • RNAscope Multiplex Fluorescent Assay v2 (2) Apply RNAscope Multiplex Fluorescent Assay v2 filter
  • BOND RNAscope Brown Detection (1) Apply BOND RNAscope Brown Detection filter
  • HybEZ Hybridization System (1) Apply HybEZ Hybridization System filter
  • miRNAscope Assay Red (1) Apply miRNAscope Assay Red filter
  • RNA-Protein CO-Detection Ancillary Kit (1) Apply RNA-Protein CO-Detection Ancillary Kit filter
  • RNAscope 2.0 HD Assay - Chromogenic (1) Apply RNAscope 2.0 HD Assay - Chromogenic filter
  • RNAscope 2.5 HD- Red (1) Apply RNAscope 2.5 HD- Red filter
  • RNAscope 2.5 LS Reagent Kits (1) Apply RNAscope 2.5 LS Reagent Kits filter
  • RNAScope HiPlex assay (1) Apply RNAScope HiPlex assay filter
  • RNAscope HiPlex Image Registration Software (1) Apply RNAscope HiPlex Image Registration Software filter
  • RNAscope LS Multiplex Fluorescent Assay (1) Apply RNAscope LS Multiplex Fluorescent Assay filter
  • RNAscope Multiplex Fluorescent Reagent Kit V3 (1) Apply RNAscope Multiplex Fluorescent Reagent Kit V3 filter
  • RNAscope Multiplex Fluorescent Reagent Kit v4 (1) Apply RNAscope Multiplex Fluorescent Reagent Kit v4 filter
  • RNAscope Multiplex Fluorescent v1 (1) Apply RNAscope Multiplex Fluorescent v1 filter
  • RNAscope Target Retrieval Reagents (1) Apply RNAscope Target Retrieval Reagents filter

Research area

  • Neuroscience (1849) Apply Neuroscience filter
  • Cancer (1385) Apply Cancer filter
  • Development (509) Apply Development filter
  • Inflammation (472) Apply Inflammation filter
  • Infectious Disease (410) Apply Infectious Disease filter
  • Other (406) Apply Other filter
  • Stem Cells (258) Apply Stem Cells filter
  • Covid (237) Apply Covid filter
  • Infectious (220) Apply Infectious filter
  • HPV (187) Apply HPV filter
  • lncRNA (135) Apply lncRNA filter
  • Metabolism (91) Apply Metabolism filter
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  • Immunotherapy (72) Apply Immunotherapy filter
  • Other: Methods (67) Apply Other: Methods filter
  • HIV (64) Apply HIV filter
  • CGT (62) Apply CGT filter
  • Pain (62) Apply Pain filter
  • diabetes (57) Apply diabetes filter
  • LncRNAs (46) Apply LncRNAs filter
  • Aging (43) Apply Aging filter
  • Other: Heart (40) Apply Other: Heart filter
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  • Obesity (29) Apply Obesity filter
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  • Behavior (27) Apply Behavior filter
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  • Other: Kidney (27) Apply Other: Kidney filter
  • Alzheimer's Disease (26) Apply Alzheimer's Disease filter
  • Bone (24) Apply Bone filter
  • Stress (21) Apply Stress filter
  • Other: Zoological Disease (20) Apply Other: Zoological Disease filter
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  • Other: Endocrinology (16) Apply Other: Endocrinology filter
  • Other: Skin (16) Apply Other: Skin filter
  • Injury (15) Apply Injury filter
  • Anxiety (14) Apply Anxiety filter
  • Memory (14) Apply Memory filter
  • Reproductive Biology (14) Apply Reproductive Biology filter

Product sub type

  • Target Probes (256568) Apply Target Probes filter
  • Control Probe - Automated Leica (409) Apply Control Probe - Automated Leica filter
  • Control Probe - Automated Leica Multiplex (284) Apply Control Probe - Automated Leica Multiplex filter
  • Control Probe - Automated Leica Duplex (168) Apply Control Probe - Automated Leica Duplex filter
  • Control Probe- Manual RNAscope Multiplex (148) Apply Control Probe- Manual RNAscope Multiplex filter
  • Control Probe - Automated Ventana (143) Apply Control Probe - Automated Ventana filter
  • Control Probe - Manual RNAscope Singleplex (142) Apply Control Probe - Manual RNAscope Singleplex filter
  • Control Probe - Manual RNAscope Duplex (137) Apply Control Probe - Manual RNAscope Duplex filter
  • Control Probe (73) Apply Control Probe filter
  • Control Probe - Manual BaseScope Singleplex (51) Apply Control Probe - Manual BaseScope Singleplex filter
  • Control Probe - VS BaseScope Singleplex (41) Apply Control Probe - VS BaseScope Singleplex filter
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  • L-HBsAG (15) Apply L-HBsAG filter
  • Cancer (13) Apply Cancer filter
  • Automated Assay 2.5: Leica System (8) Apply Automated Assay 2.5: Leica System filter
  • Control Probe- Manual BaseScope Duplex (8) Apply Control Probe- Manual BaseScope Duplex filter
  • 1765 (8) Apply 1765 filter
  • 1379 (8) Apply 1379 filter
  • 2184 (8) Apply 2184 filter
  • 38322 (8) Apply 38322 filter
  • Manual Assay 2.5: Pretreatment Reagents (5) Apply Manual Assay 2.5: Pretreatment Reagents filter
  • Controls: Manual Probes (5) Apply Controls: Manual Probes filter
  • Control Probe- Manual RNAscope HiPlex (5) Apply Control Probe- Manual RNAscope HiPlex filter
  • Manual Assay RNAscope Brown (4) Apply Manual Assay RNAscope Brown filter
  • Manual Assay RNAscope Duplex (4) Apply Manual Assay RNAscope Duplex filter
  • Manual Assay RNAscope Multiplex (4) Apply Manual Assay RNAscope Multiplex filter
  • Manual Assay BaseScope Red (4) Apply Manual Assay BaseScope Red filter
  • IA: Other (4) Apply IA: Other filter
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  • Manual Assay miRNAscope Red (4) Apply Manual Assay miRNAscope Red filter
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  • Control Probe - Automated Ventana Duplex (3) Apply Control Probe - Automated Ventana Duplex filter
  • Manual Assay BaseScope Duplex (3) Apply Manual Assay BaseScope Duplex filter
  • Manual Assay RNAscope Red (2) Apply Manual Assay RNAscope Red filter
  • Controls: Control Slides (2) Apply Controls: Control Slides filter
  • Control Probe- Manual BaseScope Singleplex (2) Apply Control Probe- Manual BaseScope Singleplex filter
  • Control Probe - Manual BaseScope™Singleplex (2) Apply Control Probe - Manual BaseScope™Singleplex filter
  • Manual Assay: Accessory Reagent (1) Apply Manual Assay: Accessory Reagent filter
  • Accessory Reagent (1) Apply Accessory Reagent filter
  • Controls: Manual RNAscope Multiplex (1) Apply Controls: Manual RNAscope Multiplex filter
  • IA: HybEZ (1) Apply IA: HybEZ filter
  • Automated Assay BaseScope: LS (1) Apply Automated Assay BaseScope: LS filter
  • Automated Assay BaseScope: VS (1) Apply Automated Assay BaseScope: VS filter
  • Software: RNAscope HiPlex Image Registration (1) Apply Software: RNAscope HiPlex Image Registration filter
  • miRNAscope Automated Assay: Leica System (1) Apply miRNAscope Automated Assay: Leica System filter
  • Automated Assay: VS (1) Apply Automated Assay: VS filter
  • Control Probe - VS BaseScope™Singleplex (1) Apply Control Probe - VS BaseScope™Singleplex filter
  • Controls:2.5VS Probes (1) Apply Controls:2.5VS Probes filter
  • Control Probe - Manual RNAscope Multiplex (1) Apply Control Probe - Manual RNAscope Multiplex filter

Sample Compatibility

  • Cell pellets (49) Apply Cell pellets filter
  • FFPE (41) Apply FFPE filter
  • Fixed frozen tissue (31) Apply Fixed frozen tissue filter
  • TMA (31) Apply TMA filter
  • Adherent cells (26) Apply Adherent cells filter
  • Freshfrozen tissue (18) Apply Freshfrozen tissue filter
  • Fresh frozen tissue (13) Apply Fresh frozen tissue filter
  • Cell Cultures (12) Apply Cell Cultures filter
  • TMA(Tissue Microarray) (9) Apply TMA(Tissue Microarray) filter
  • FFPE,Freshfrozen tissue,Fixed frozen tissue,TMA,Cell pellets,Adherent cells (7) Apply FFPE,Freshfrozen tissue,Fixed frozen tissue,TMA,Cell pellets,Adherent cells filter
  • CTC (4) Apply CTC filter
  • PBMC's (4) Apply PBMC's filter
  • Adherent or Cultured Cells (1) Apply Adherent or Cultured Cells filter
  • Fixed frozen (1) Apply Fixed frozen filter
  • FFPE,TMA (1) Apply FFPE,TMA filter
  • Fixed frozen tissues (for chromogenic assays) (1) Apply Fixed frozen tissues (for chromogenic assays) filter

Category

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Application

  • Cancer (139875) Apply Cancer filter
  • Neuroscience (51010) Apply Neuroscience filter
  • Cancer, Neuroscience (32227) Apply Cancer, Neuroscience filter
  • Non-coding RNA (24365) Apply Non-coding RNA filter
  • Cancer, Inflammation (16436) Apply Cancer, Inflammation filter
  • Cancer, Inflammation, Neuroscience (12591) Apply Cancer, Inflammation, Neuroscience filter
  • Inflammation (9879) Apply Inflammation filter
  • Cancer, Stem Cell (7932) Apply Cancer, Stem Cell filter
  • Cancer, Neuroscience, Stem Cell (7028) Apply Cancer, Neuroscience, Stem Cell filter
  • Cancer, Immunotherapy, Inflammation, Neuroscience, Stem Cell (6854) Apply Cancer, Immunotherapy, Inflammation, Neuroscience, Stem Cell filter
  • Cancer, Inflammation, Neuroscience, Stem Cell (5424) Apply Cancer, Inflammation, Neuroscience, Stem Cell filter
  • Immunotherapy (5368) Apply Immunotherapy filter
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  • Cancer, Immunotherapy, Inflammation (2844) Apply Cancer, Immunotherapy, Inflammation filter
  • Cancer, Immunotherapy, Inflammation, Neuroscience (1878) Apply Cancer, Immunotherapy, Inflammation, Neuroscience filter
  • Cancer, Immunotherapy, Neuroscience (1786) Apply Cancer, Immunotherapy, Neuroscience filter
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Neurobiological substrates of persistent working memory deficits and cocaine-seeking in the prelimbic cortex of rats with a history of extended access to cocaine self-administration.

Neurobiol Learn Mem.

2019 Apr 01

Gobin C, Shallcross J, Schwendt M.
PMID: 30946882 | DOI: 10.1016/j.nlm.2019.03.007

Cocaine use disorder (CUD) is associated with prefrontal cortex dysfunction and cognitive deficits that may contribute to persistent relapse susceptibility. As the relationship between cognitive deficits, cortical abnormalities and drug seeking is poorly understood, development of relevant animal models is of high clinical importance. Here, we used an animal model to characterize working memory and reversal learning in rats with a history of extended access cocaine self-administration and prolonged abstinence. We also investigated immediate and long-term functional changes within the prelimbic cortex (PrL) in relation to cognitive performance and drug-seeking. Adult male rats underwent 6 days of short-access (1 h/day) followed by 12 days of long-access (6 h/day) cocaine self-administration, or received passive saline infusions. Next, rats were tested in delayed match-to-sample (DMS) and (non)match-to-sample (NMS) tasks, and finally in a single context + cue relapse test on day 90 of abstinence. We found that a history of chronic cocaine self-administration impaired working memory, though sparing reversal learning, and that the components of these cognitive measures correlated with later drug-seeking. Further, we found that dysregulated metabolic activity and mGlu5 receptor signaling in the PrL of cocaine rats correlated with past working memory performance and/or drug-seeking, as indicated by the analysis of cytochrome oxidase reactivity, mGlu5 and Homer 1b/c protein expression, as well as Arc mRNA expression in mGlu5-positive cells. These findings advocate for a persistent post-cocaine PrL dysfunction, rooted in ineffective compensatory changes and manifested as impaired working memory performance and hyperreactivity to cocaine cues. Considering the possible interplay between the neural correlates underlying post-cocaine cognitive deficits and drug-seeking, cognitive function should be evaluated and considered when developing neurobiologically-based treatments of cocaine relapse.

Anti-Nogo-A antibodies as a potential causal therapy for lower urinary tract dysfunction after spinal cord injury.

J Neurosci.

2019 Mar 22

Schneider MP, Sartori AM, Ineichen BV, Moors S, Engmann AK, Hofer AS, Weinmann O, Kessler TM, Schwab ME.
PMID: 30902870 | DOI: 10.1523/JNEUROSCI.3155-18.2019

Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated if function blocking antibodies against the nerve fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A-antibody treatment led to a significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbo-sacral grey matter in the anti-Nogo-A antibody treated animals, as well as a reduced number of inhibitory interneurons in Lamina X These results suggest that anti-Nogo-A therapy could have positive effects on bladder function also clinically.Significance Statement:Bladder function is after spinal cord injury completely out of control. Detrusor sphincter dyssynergia, a potentially live threatening consequence, is greatly feared. Currently there are only symptomatic treatment options available and first causal treatment options are urgently needed in humans. In this work we show that function blocking antibodies against the nerve fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy enters currently phase II clinical trial in humans and might therefore be soon the first causal treatment option for neurogenic lower urinary tract dysfunction.

WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis.

Nat Commun.

2019 Apr 02

Kaiser K, Gyllborg D, Procházka J, Salašová A, Kompaníková P, Molina FL, Laguna-Goya R, Radaszkiewicz T, Harnoš J, Procházková M, Potěšil D, Barker RA, Casado AG, Zdráhal Z, Sedláček R, Arenas E, Villaescusa JC, Bryja V.
PMID: 30940800 | DOI: 10.1038/s41467-019-09298-4

WNTs are lipid-modified proteins that control multiple functions in development and disease via short- and long-range signaling. However, it is unclear how these hydrophobic molecules spread over long distances in the mammalian brain. Here we show that WNT5A is produced by the choroid plexus (ChP) of the developing hindbrain, but not the telencephalon, in both mouse and human. Since the ChP produces and secretes the cerebrospinal fluid (CSF), we examine the presence of WNT5A in the CSF and find that it is associated with lipoprotein particles rather than exosomes. Moreover, since the CSF flows along the apical surface of hindbrain progenitors not expressing Wnt5a, we examined whether deletion of Wnt5a in the ChP controls their function and find that cerebellar morphogenesis is impaired. Our study thus identifies the CSF as a route and lipoprotein particles as a vehicle for long-range transport of biologically active WNT in the central nervous system.

Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones.

Elife

2019 Feb 20

Giovannone D, Paul S, Schindler S, Arata C, Farmer DT, Patel P, Smeeton J, Crump JG.
PMID: 30785394 | DOI: 10.7554/eLife.42736

Much of the vertebrate skeleton develops from cartilage templates that are progressively remodeled into bone. Lineage tracing studies in mouse suggest that chondrocytes within these templates persist and become osteoblasts, yet the underlying mechanisms of this process and whether chondrocytes can generate other derivatives remain unclear. We find that zebrafish cartilages undergo extensive remodeling and vascularization during juvenile stages to generate fat-filled bones. Growth plate chondrocytes marked by sox10 and col2a1a contribute to osteoblasts, marrow adipocytes, and mesenchymal cells within adult bones. At the edge of the hypertrophic zone, chondrocytes re-enter the cell cycle and express leptin receptor (lepr), suggesting conversion into progenitors. Further, mutation of matrix metalloproteinase 9 (mmp9) results in delayed growth plate remodeling and fewer marrow adipocytes. Our data support Mmp9-dependent growth plate remodeling and conversion of chondrocytes into osteoblasts and marrow adipocytes as conserved features of bony vertebrates.

Immune Activations and Viral Tissue Compartmentalization During Progressive HIV-1 Infection of Humanized Mice.

Front Immunol.

2019 Feb 28

Su H, Cheng Y, Sravanam S, Mathews S, Gorantla S, Poluektova LY, Dash PK, Gendelman HE.
PMID: 30873181 | DOI: 10.3389/fimmu.2019.00340

Human immunodeficiency virus type one (HIV-1) tissue compartments are established soon after viral infection. However, the timing in which virus gains a permanent foothold in tissue and the cellular factors that control early viral-immune events are incompletely understood. These are critical events in studies of HIV-1 pathogenesis and in the development of viral reservoirs after antiretroviral therapy. Moreover, factors affecting the permanence of viral-tissue interactions underlie barriers designed to eliminate HIV-1 infection. To this end we investigated the temporal and spatial viral and host factors during HIV-1 seeding of tissue compartments. Two humanized NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ mouse models were employed. In the first, immune deficient mice were reconstituted with human CD34+ cord blood hematopoietic stem cells (HSC) (hu-HSC) and in the second mice were transplanted with adult mature human peripheral lymphocytes (hu-PBL). Both, in measure, reflect relationships between immune activation and viral infection as seen in an infected human host. Following humanization both mice models were infected with HIV-1ADA at 104 50% tissue culture infective doses. Viral nucleic acids and protein and immune cell profiles were assayed in brain, lung, spleen, liver, kidney, lymph nodes, bone marrow, and gut from 3 to 42 days. Peripheral CD4+ T cell loss began at 3 days together with detection of HIV-1 RNA in both mouse models after initiation of HIV-1 infection. HIV-1 was observed in all tested tissues at days 3 and 14 in hu- PBL and HSC mice, respectively. Immune impairment was most prominent in hu-PBL mice. T cell maturation and inflammation factors were linked directly to viral tissue seeding in both mouse models. We conclude that early viral tissue compartmentalization provides a roadmap for investigations into HIV-1 elimination.

NPY2 receptor activation in the dorsal vagal complex increases food intake and attenuates CCK-induced satiation in male rats.

Am J Physiol Regul Integr Comp Physiol.

2019 Apr 01

Huston NJ, Brenner LA, Taylor ZC, Ritter RC.
PMID: 30726118 | DOI: 10.1152/ajpregu.00011.2019

Neuropeptide Y (NPY), peptide YY (PYY), and their cognate receptors (YR) are expressed by subpopulations of central and peripheral nervous system neurons. Intracerebroventricular injections of NPY or PYY increase food intake, and intrahypothalamic NPY1 or NPY5 receptor agonist injections also increase food intake. In contrast, injection of PYY in the periphery reduces food intake, apparently by activating peripheral Y2R. The dorsal vagal complex (DVC) of the hindbrain is the site where vagal afferents relay gut satiation signals to the brain. While contributions of the DVC are increasingly investigated, a role for DVC YR in control of food intake has not been examined systematically. We used in situ hybridization to confirm expression of Y1R and Y2R, but not Y5R, in the DVC and vagal afferent neurons. We found that nanoinjections of a Y2R agonist, PYY-(3-36), into the DVC significantly increased food intake over a 4-h period in satiated male rats. PYY-(3-36)-evoked food intake was prevented by injection of a selective Y2R antagonist. Injection of a Y1R/Y5R-preferring agonist into the DVC failed to increase food intake at doses reported to increase food intake following hypothalamic injection. Finally, injection of PYY-(3-36) into the DVC prevented reduction of 30-min food intake following intraperitoneal injection of cholecystokinin (CCK). Our results indicate that activation of DVC Y2R, unlike hypothalamic or peripheral Y2R, increases food intake. Furthermore, in the context of available electrophysiological observations, our results are consistent with the hypothesis that DVC Y2R control food intake by dampening vagally mediated satiation signals in the DVC.

A Highly Divergent Picornavirus Infecting the Gut Epithelia of Zebrafish (Danio rerio) in Research Institutions Worldwide.

Zebrafish

2019 Apr 02

Altan E, Kubiski SV, Boros Á, Reuter G, Sadeghi M, Deng X, Creighton EK, Crim MJ, Delwart E.
PMID: 30939077 | DOI: 10.1089/zeb.2018.1710

Zebrafish have been extensively used as a model system for research in vertebrate development and pathogen-host interactions. We describe the complete genome of a novel picornavirus identified during a viral metagenomics analysis of zebrafish gut tissue. The closest relatives of this virus showed identity of <20% in their P1 capsids and <36% in their RdRp qualifying zebrafish picornavirus-1 (ZfPV-1) as member of a novel genus with a proposed name of Cyprivirus. Reverse transcription (RT)-PCR testing of zebrafish from North America, Europe, and Asia showed ZfPV-1 to be globally distributed, being detected in 23 of 41 (56%) institutions tested. In situ hybridization of whole zebrafish showed viral RNA was restricted to a subset of enterocytes and cells in the subjacent lamina propria of the intestine and the intestinal mucosa. This naturally occurring and apparently asymptomatic infection (in wild-type zebrafish lineage AB) provides a natural infection system to study picornavirus-host interactions in an advanced vertebrate model organism. Whether ZfPV-1 infection affects any immunological, developmental, or other biological processes in wild-type or mutant zebrafish lineages remains to be determined.

CD22 blockade restores homeostatic microglial phagocytosis in ageing brains.

Nature

2019 Apr 03

Pluvinage JV, Haney MS, Smith BAH, Sun J, Iram T, Bonanno L, Li L, Lee DP, Morgens DW, Yang AC, Shuken SR, Gate D, Scott M, Khatri P, Luo J, Bertozzi CR, Bassik MC, Wyss-Coray T.
PMID: 30944478 | DOI: 10.1038/s41586-019-1088-4

Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown. We combined CRISPR-Cas9 knockout screens with RNA sequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. These screens identified CD22, a canonical B cell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. CD22 mediates the anti-phagocytic effect of α2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-β oligomers and α-synuclein fibrils in vivo. Long-term central nervous system delivery of an antibody that blocks CD22 function reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice. These findings elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the ageing brain.

Interleukin 1 Up-regulates MicroRNA 135b to Promote Inflammation-Associated Gastric Carcinogenesis in Mice.

Gastroenterology

2019 Feb 14

Han TS, Voon DC, Oshima H, Nakayama M, Echizen K, Sakai E, Yong ZWE, Murakami K, Yu L, Minamoto T, Ock CY, Jenkins BJ, Kim SJ, Yang HK, Oshima M.
PMID: 30508510 | DOI: 10.1053/j.gastro.2018.11.059

Abstract

BACKGROUND & AIMS:

Gastritis is associated with development of stomach cancer, but little is known about changes in microRNA expression patterns during gastric inflammation. Specific changes in gene expression in epithelial cells are difficult to monitor because of the heterogeneity of the tissue. We investigated epithelial cell-specific changes in microRNA expression during gastric inflammation and gastritis-associated carcinogenesis in mice.

METHODS:

We used laser microdissection to enrich epithelial cells from K19-C2mE transgenic mice, which spontaneously develop gastritis-associated hyperplasia, and Gan mice, which express activated prostaglandin E2 and Wnt in the gastric mucosa and develop gastric tumors. We measured expression of epithelial cell-enriched microRNAs and used bioinformatics analyses to integrate data from different systems to identify inflammation-associated microRNAs. We validated our findings in gastric tissues from mice and evaluated protein functions in gastric cell lines (SNU-719, SNU-601, SNU-638, AGS, and GIF-14) and knockout mice. Organoids were cultured from gastric corpus tissues of wild-type and miR-135b-knockout C57BL/6 mice. We measured levels of microRNAs in pairs of gastric tumors and nontumor mucosa from 28 patients in Japan.

RESULTS:

We found microRNA 135b (miR-135B) to be the most overexpressed microRNA in gastric tissues from K19-C2mE and Gan mice: levels increased during the early stages of gastritis-associated carcinogenesis. Levels of miR-135B were also increased in gastric tumor tissues from gp130F/F mice and patients compared with nontumor tissues. In gastric organoids and immortalized cell lines, expression of miR-135B was induced by interleukin 1 signaling. K19-C2mE mice with disruption of Mir-135b developed hyperplastic lesions that were 50% smaller than mice without Mir-135b disruption and had significant reductions in cell proliferation. Expression of miR-135B in gastric cancer cell lines increased their colony formation, migration, and sphere formation. We identified FOXN3 and RECK messenger RNAs (mRNAs) as targets of miR-135B; their knockdown reduced migration of gastric cancer cell lines. Levels of FOXN3 and RECK mRNAs correlated inversely with levels of miR-135B in human gastric tumors and in inflamed mucosa from K19-C2mE mice.

CONCLUSIONS:

We found expression of miR-135B to be up-regulated by interleukin L1 signaling in gastric cancer cells and organoids. miR-135B promotes invasiveness and stem-cell features of gastric cancer cells in culture by reducing FOXN3 and RECK messenger RNAs. Levels of these messenger RNA targets, which encode tumor suppressor, are reduced in human gastric tumors.

NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies.

Nat Commun.

2019 Apr 01

Fledrich R, Akkermann D, Schütza V, Abdelaal TA, Hermes D, Schäffner E, Soto-Bernardini MC, Götze T, Klink A, Kusch K, Krueger M, Kungl T, Frydrychowicz C, Möbius W, Brück W, Mueller WC, Bechmann I, Sereda MW, Schwab MH, Nave KA, Stassart RM.
PMID: 30931926 | DOI: 10.1038/s41467-019-09385-6

In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental.

Estrogen Receptor-α Quantification in Breast Cancer: Concordance Between Immunohistochemical Assays and mRNA-In Situ Hybridization for ESR1 Gene.

Appl Immunohistochem Mol Morphol.

2019 Mar 27

Thomsen C, Nielsen S, Nielsen BS, Pedersen SH, Vyberg M.
PMID: 30920963 | DOI: 10.1097/PAI.0000000000000760

Immunohistochemical (IHC) quantification of estrogen receptor-α (ER) is used for assessment of treatment regimen in breast cancer. Different ER IHC assays may produce diverging results, because of different antibody clones, protocols, and stainer platforms. Objective tissue-based techniques to assess sensitivity and specificity of IHC assays are therefore needed. We tested the usability of ER mRNA-in situ hybridization (mRNA-ISH) in comparison with assays based on clones SP1 and 6F11. We selected 56 archival specimens according to their reported ER IHC positivity, representing a wide spectrum from negative to strongly positive cases. The specimens were used to prepare 4 TMAs with 112 cores. Serial sections of each TMA were stained for ER and pan-cytokeratin (PCK) by IHC and ESR1 (ER gene) by mRNA-ISH. Digital image analysis (DIA) was used to determine ER IHC H-score. ESR1 mRNA-ISH was scored both manually and by DIA. DIA showed a nonlinear correlation between IHC and ESR1 mRNA-ISH with R-values of 0.80 and 0.78 for the ER antibody clones SP1 and 6F11, respectively. Comparison of manual mRNA-ISH scoring categories and SP1 and 6F11 IHC H-scores showed a highly significant relationship (P<0.001). In conclusion, the study showed good correlation between mRNA-ISH and IHC, suggesting that mRNA-ISH can be a valuable tool in the assessment of the sensitivity and specificity of ER IHC assays.

The dyslexia susceptibility KIAA0319 gene shows a specific expression pattern during zebrafish development supporting a role beyond neuronal migration.

J Comp Neurol.

2019 Apr 04

Gostic M, Martinelli A, Tucker C, Yang Z, Gasparoli F, Ewart JY, Dholakia K, Sillar KT, Tello JA, Paracchini S.
PMID: 30950042 | DOI: 10.1002/cne.24696

Dyslexia is a common neurodevelopmental disorder caused by a significant genetic component. The KIAA0319 gene is one of the most robust dyslexia susceptibility factors but its function remains poorly understood. Initial RNA-interference studies in rats suggested a role in neuronal migration whereas subsequent work with double knock-out mouse models for both Kiaa0319 and its paralogue Kiaa0319-like reported effects in the auditory system but not in neuronal migration. To further understand the role of KIAA0319 during neurodevelopment, we carried out an expression study of its zebrafish orthologue at different embryonic stages. We used different approaches including RNAscope in situ hybridization combined with light-sheet microscopy. The results show particularly high expression during the first few hours of development. Later, expression becomes localised in well-defined structures. In addition to high expression in the brain, we report for the first time expression in the eyes and the notochord. Surprisingly, kiaa0319-like, which generally shows a similar expression pattern to kiaa0319, was not expressed in the notochord suggesting a distinct role for kiaa0319 in this structure. This observation was supported by the identification of notochord enhancers enriched upstream of the KIAA0319 transcription start site, in both zebrafish and humans. This study supports a developmental role for KIAA0319 in the brain as well as in other developing structures, particularly in the notochord which, is key for establishing body patterning in vertebrates.

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Description
sense
Example: Hs-LAG3-sense
Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron#
Example: Mm-Htt-intron2
Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan
Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)
A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp
Example: Hs-PDGFB-No-XMm
Does not cross detect with the species (Sp)
XSp
Example: Rn-Pde9a-XMm
designed to cross detect with the species (Sp)
O#
Example: Mm-Islr-O1
Alternative design targeting different regions of the same transcript or isoforms
CDS
Example: Hs-SLC31A-CDS
Probe targets the protein-coding sequence only
EnEmProbe targets exons n and m
En-EmProbe targets region from exon n to exon m
Retired Nomenclature
tvn
Example: Hs-LEPR-tv1
Designed to target transcript variant n
ORF
Example: Hs-ACVRL1-ORF
Probe targets open reading frame
UTR
Example: Hs-HTT-UTR-C3
Probe targets the untranslated region (non-protein-coding region) only
5UTR
Example: Hs-GNRHR-5UTR
Probe targets the 5' untranslated region only
3UTR
Example: Rn-Npy1r-3UTR
Probe targets the 3' untranslated region only
Pan
Example: Pool
A mixture of multiple probe sets targeting multiple genes or transcripts

Enabling research, drug development (CDx) and diagnostics

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