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Search

Probes for INS

ACD can configure probes for the various manual and automated assays for INS for RNAscope Assay, or for Basescope Assay compatible for your species of interest.

Your search for "INS" returned results. Search for our Top genes LGR5, vglut2, gad67, brca1

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    The role of EBV in hematolymphoid proliferations: Emerging concepts relevant to diagnosis and treatment

    Histopathology

    2021 Apr 07

    Ababneh, E;Saad, AM;Crane, GM;
    PMID: 33829526 | DOI: 10.1111/his.14379

    Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus with >90% of the adult population worldwide harboring latent infection. A small subset of those infected develop EBV-associated neoplasms including a range of lymphoproliferative disorders (LPD). The diagnostic distinction of these entities appears increasingly relevant as our understanding of EBV-host interactions and mechanisms of EBV-driven lymphomagenesis improves. EBV may lower the mutational threshold for malignant transformation, create potential vulnerabilities related to viral alteration of cell metabolism and allow for improved immune targeting. However, these tumors may escape immune surveillance by affecting their immune microenvironment, limiting viral gene expression or potential loss of the viral episome. Methods to manipulate the latency state of the virus to enhance immunogenicity are emerging as well as the potential to detect so-called "hit and run" cases where EBV has been lost. Finally, measurement of EBV DNA remains an important biomarker for screening and monitoring of LPD. Methods to distinguish EBV DNA derived from virions during lytic activation from latent, methylated EBV DNA present in EBV-associated neoplasms may broaden the utility of this testing, particularly in patients with compromised immune function. We will highlight some of these emerging areas relevant to the diagnosis and treatment of EBV-associated LPD with potential applicability to other EBV-associated neoplasms. This article is protected by
    Top-Down Control of Sweet and Bitter Taste in the Mammalian Brain

    Cell

    2021 Jan 07

    Jin, H;Fishman, ZH;Ye, M;Wang, L;Zuker, CS;
    PMID: 33417862 | DOI: 10.1016/j.cell.2020.12.014

    Hardwired circuits encoding innate responses have emerged as an essential feature of the mammalian brain. Sweet and bitter evoke opposing predetermined behaviors. Sweet drives appetitive responses and consumption of energy-rich food sources, whereas bitter prevents ingestion of toxic chemicals. Here we identified and characterized the neurons in the brainstem that transmit sweet and bitter signals from the tongue to the cortex. Next we examined how the brain modulates this hardwired circuit to control taste behaviors. We dissect the basis for bitter-evoked suppression of sweet taste and show that the taste cortex and amygdala exert strong positive and negative feedback onto incoming bitter and sweet signals in the brainstem. Finally we demonstrate that blocking the feedback markedly alters responses to ethologically relevant taste stimuli. These results illustrate how hardwired circuits can be finely regulated by top-down control and reveal the neural basis of an indispensable behavioral response for all animals.
    Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

    Cell.

    2018 Aug 09

    Saunders A, Macosko EZ, Wysoker A, Goldman M, Krienen FM, de Rivera H, Bien E, Baum M, Bortolin L, Wang S, Goeva A, Nemesh J, Kamitaki N, Brumbaugh S, Kulp D, McCarroll SA.
    PMID: 30096299 | DOI: 10.1016/j.cell.2018.07.028

    The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in the co-deployment of voltage-gated ion channels, functional distinctions among the cells of the vasculature and specialization of glutamatergic neurons across cortical regions. Systematic neuronal classifications for two complex basal ganglia nuclei and the striatum revealed a rare population of spiny projection neurons. This adult mouse brain cell atlas, accessible through interactive online software (DropViz), serves as a reference for development, disease, and evolution.

    Quantitative Analysis of Inflammatory Uterine Lesions of Pregnant Gilts with Digital Image Analysis Following Experimental PRRSV-1 Infection

    Animals : an open access journal from MDPI

    2023 Feb 24

    Horváth, DG;Abonyi-Tóth, Z;Papp, M;Szász, AM;Rümenapf, T;Knecht, C;Kreutzmann, H;Ladinig, A;Balka, G;
    PMID: 36899686 | DOI: 10.3390/ani13050830

    Reproductive disorders caused by porcine reproductive and respiratory syndrome virus-1 are not yet fully characterized. We report QuPath-based digital image analysis to count inflammatory cells in 141 routinely, and 35 CD163 immunohistochemically stained endometrial slides of vaccinated or unvaccinated pregnant gilts inoculated with a high or low virulent PRRSV-1 strain. To illustrate the superior statistical feasibility of the numerical data determined by digital cell counting, we defined the association between the number of these cells and endometrial, placental, and fetal features. There was strong concordance between the two manual scorers. Distributions of total cell counts and endometrial and placental qPCR results differed significantly between examiner1's endometritis grades. Total counts' distribution differed significantly between groups, except for the two unvaccinated. Higher vasculitis scores were associated with higher endometritis scores, and higher total cell counts were expected with high vasculitis/endometritis scores. Cell number thresholds of endometritis grades were determined. A significant correlation between fetal weights and total counts was shown in unvaccinated groups, and a significant positive correlation was found between these counts and endometrial qPCR results. We revealed significant negative correlations between CD163+ counts and qPCR results of the unvaccinated group infected with the highly virulent strain. Digital image analysis was efficiently applied to assess endometrial inflammation objectively.
    Evaluation of the Antiseizure Activity of Endemic Plant Halfordia kendack Guillaumin and Its Main Constituent, Halfordin, on a Zebrafish Pentylenetetrazole (PTZ)-Induced Seizure Model

    International journal of molecular sciences

    2023 Jan 30

    Skiba, A;Kozioł, E;Luca, SV;Budzyńska, B;Podlasz, P;Van Der Ent, W;Shojaeinia, E;Esguerra, CV;Nour, M;Marcourt, L;Wolfender, JL;Skalicka-Woźniak, K;
    PMID: 36768918 | DOI: 10.3390/ijms24032598

    Epilepsy is a neurological disease that burdens over 50 million people worldwide. Despite the considerable number of available antiseizure medications, it is estimated that around 30% of patients still do not respond to available treatment. Herbal medicines represent a promising source of new antiseizure drugs. This study aimed to identify new drug lead candidates with antiseizure activity from endemic plants of New Caledonia. The crude methanolic leaf extract of Halfordia kendack Guillaumin (Rutaceae) significantly decreased (75 μg/mL and 100 μg/mL) seizure-like behaviour compared to sodium valproate in a zebrafish pentylenetetrazole (PTZ)-induced acute seizure model. The main coumarin compound, halfordin, was subsequently isolated by liquid-liquid chromatography and subjected to locomotor, local field potential (LFP), and gene expression assays. Halfordin (20 μM) significantly decreased convulsive-like behaviour in the locomotor and LFP analysis (by 41.4% and 60%, respectively) and significantly modulated galn, and penka gene expression.
    Nucleic Acid Pharmaceutical Agents

    Haschek and Rousseaux's Handbook of Toxicologic Pathology, Volume 2 : Safety Assessment Environmental Toxicologic Pathology

    2023 Feb 27

    Kohnken, R;Harbison, C;Klein, S;Engelhardt, J;
    | DOI: 10.1016/B978-0-12-821047-5.00017-8

    Nucleic acid pharmaceutical (NAP) agents are a relatively recent class of therapeutics that are uniquely capable of inhibiting protein translation through direct interaction with RNA. These classes of pharmaceuticals have demonstrated clinical benefit for diseases previously considered untreatable by small molecules and biologics by their theoretical ability to target any cellular RNA associated with disease. This chapter provides an overview of the major types of NAPs and the types of indications for which they are being developed, with examples of therapeutics on the market and in clinical development. The reader is also provided with a review of the most common delivery systems and chemical modifications that enable the biodistribution and efficacy of these drugs. A brief discussion of the nonclinical safety package is provided, and finally the most common toxicities that have been observed in preclinical species are discussed.
    Reagents for Mass Cytometry

    Chemical reviews

    2023 Jan 25

    Arnett, LP;Rana, R;Chung, WW;Li, X;Abtahi, M;Majonis, D;Bassan, J;Nitz, M;Winnik, MA;
    PMID: 36696538 | DOI: 10.1021/acs.chemrev.2c00350

    Mass cytometry (cytometry by time-of-flight detection [CyTOF]) is a bioanalytical technique that enables the identification and quantification of diverse features of cellular systems with single-cell resolution. In suspension mass cytometry, cells are stained with stable heavy-atom isotope-tagged reagents, and then the cells are nebulized into an inductively coupled plasma time-of-flight mass spectrometry (ICP-TOF-MS) instrument. In imaging mass cytometry, a pulsed laser is used to ablate ca. 1 μm2 spots of a tissue section. The plume is then transferred to the CyTOF, generating an image of biomarker expression. Similar measurements are possible with multiplexed ion bean imaging (MIBI). The unit mass resolution of the ICP-TOF-MS detector allows for multiparametric analysis of (in principle) up to 130 different parameters. Currently available reagents, however, allow simultaneous measurement of up to 50 biomarkers. As new reagents are developed, the scope of information that can be obtained by mass cytometry continues to increase, particularly due to the development of new small molecule reagents which enable monitoring of active biochemistry at the cellular level. This review summarizes the history and current state of mass cytometry reagent development and elaborates on areas where there is a need for new reagents. Additionally, this review provides guidelines on how new reagents should be tested and how the data should be presented to make them most meaningful to the mass cytometry user community.
    Immunity to the microbiota promotes sensory neuron regeneration

    Cell

    2023 Jan 06

    Enamorado, M;Kulalert, W;Han, SJ;Rao, I;Delaleu, J;Link, VM;Yong, D;Smelkinson, M;Gil, L;Nakajima, S;Linehan, JL;Bouladoux, N;Wlaschin, J;Kabat, J;Kamenyeva, O;Deng, L;Gribonika, I;Chesler, AT;Chiu, IM;Le Pichon, CE;Belkaid, Y;
    PMID: 36640762 | DOI: 10.1016/j.cell.2022.12.037

    Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with neuronal interaction and repair, and promote axon growth and local nerve regeneration following injury. Mechanistically, our data reveal that the cytokine interleukin-17A (IL-17A) released by commensal-specific Th17 cells upon injury directly signals to sensory neurons via IL-17 receptor A, the transcription of which is specifically upregulated in injured neurons. Collectively, our work reveals that in the context of tissue damage, preemptive immunity to the microbiota can rapidly bridge biological systems by directly promoting neuronal repair, while also identifying IL-17A as a major determinant of this fundamental process.
    Targeting Peripheral μ-opioid Receptors or μ-opioid Receptor-Expressing Neurons Does not Prevent Morphine-induced Mechanical Allodynia and Anti-allodynic Tolerance

    Neuroscience bulletin

    2023 Jan 09

    Du, F;Yin, G;Han, L;Liu, X;Dong, D;Duan, K;Huo, J;Sun, Y;Cheng, L;
    PMID: 36622575 | DOI: 10.1007/s12264-022-01009-2

    The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
    Incorporating Molecular Classification When Stratifying the Survival Risk of Patients with High-Grade Endometrial Carcinomas

    Journal of clinical medicine

    2023 Jan 09

    Zong, L;Mo, S;Sun, Z;Lu, Z;Chen, J;Yu, S;Xiang, Y;
    PMID: 36675462 | DOI: 10.3390/jcm12020530

    Assessing survival risk in patients with high-grade endometrial carcinomas has remained challenging. We aimed to investigate the distribution of molecular subtypes and assess their prognostic role in a large cohort of 355 patients with high-grade endometrial carcinoma. Molecular classification was determined using DNA polymerase epsilon (POLE) sequencing as well as immunohistochemical staining for p53 and mismatch repair (MMR) proteins. Endometrial carcinomas were stratified into four subtypes: POLE ultramutated, MMR-deficient, non-specific molecular profile (NSMP), and p53-mutant. This study included 177 and 178 patients with endometrioid and non-endometrioid carcinomas, respectively. Forty-two patients (11.8%) were categorized as POLE ultramutated, 106 (29.9%) as MMR-deficient, 128 (36.1%) as p53-mutant, and 79 (22.2%) as NSMP. Patients of different molecular subtypes had distinct survival times; molecular classification, but not histotype, was significantly associated with survival outcomes. When incorporating molecular classification into the stratification model, 52 patients (15.5%) switched risk groups, with 40 (11.9%) shifting to a lower risk for having a POLE mutation and 12 (3.6%) shifting to a higher risk owing to p53-mutant status. Molecular classification may provide more accurate prognostic information among patients with high-grade endometrial carcinomas and improve their stratification for purposes of clinical management.
    Leveraging circuits to understand addiction

    Neurocircuitry of Addiction

    2023 Jan 19

    Salling, M;
    | DOI: 10.1016/B978-0-12-823453-2.00002-3

    Advancements in neuroscientific methods often drive new waves of insight into our understanding of addiction. While addiction research questions persist, technical improvements can augment our observational sensitivity, allowing us to update and extend existing addiction models through method development, creative application, and scientific discovery. As a result of this iterative process, we have reached the point where neuroscientists can now readily identify, monitor, and control specific neural circuits during behavior, thereby opening new windows of inquiry into the neurobiology of addiction. The objective of this chapter is to familiarize the reader with standard and emerging techniques used to observe and interrogate neural circuitry that are prevalent in contemporary clinical and preclinical addiction neuroscience labs and that are presented throughout the book. This chapter will further discuss the historical context, benefits, and limitations of these techniques with a look forward into how they can be applied to questions of addiction neurocircuitry.
    Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness

    Cancer cell

    2022 Dec 20

    Li, Y;Lih, TM;Dhanasekaran, SM;Mannan, R;Chen, L;Cieslik, M;Wu, Y;Lu, RJ;Clark, DJ;Kołodziejczak, I;Hong, R;Chen, S;Zhao, Y;Chugh, S;Caravan, W;Naser Al Deen, N;Hosseini, N;Newton, CJ;Krug, K;Xu, Y;Cho, KC;Hu, Y;Zhang, Y;Kumar-Sinha, C;Ma, W;Calinawan, A;Wyczalkowski, MA;Wendl, MC;Wang, Y;Guo, S;Zhang, C;Le, A;Dagar, A;Hopkins, A;Cho, H;Leprevost, FDV;Jing, X;Teo, GC;Liu, W;Reimers, MA;Pachynski, R;Lazar, AJ;Chinnaiyan, AM;Van Tine, BA;Zhang, B;Rodland, KD;Getz, G;Mani, DR;Wang, P;Chen, F;Hostetter, G;Thiagarajan, M;Linehan, WM;Fenyö, D;Jewell, SD;Omenn, GS;Mehra, R;Wiznerowicz, M;Robles, AI;Mesri, M;Hiltke, T;An, E;Rodriguez, H;Chan, DW;Ricketts, CJ;Nesvizhskii, AI;Zhang, H;Ding, L;Clinical Proteomic Tumor Analysis Consortium, ;
    PMID: 36563681 | DOI: 10.1016/j.ccell.2022.12.001

    Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.

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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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