RNAscope Multiplex Fluorescent Assay

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes

Bone morphogenetic protein (BMP)-9, a member of the TGFβ-family of cytokines, is believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21. However, whether BMP-9 also regulates the expression of the related FGF19 is not clear.

Characterisation of NPFF-expressing neurons in the superficial dorsal horn of the mouse spinal cord

Excitatory interneurons in the superficial dorsal horn (SDH) are heterogeneous, and include a class known as vertical cells, which convey information to lamina I projection neurons. We recently used pro-NPFF antibody to reveal a discrete population of excitatory interneurons that express neuropeptide FF (NPFF). Here, we generated a new mouse line (NPFFCre) in which Cre is knocked into the Npff locus, and used Cre-dependent viruses and reporter mice to characterise NPFF cell properties.

A proof-of-concept assay for quantitative and optical assessment of drug-induced toxicity in renal organoids

Kidneys are complex organs, and reproducing their function and physiology in a laboratory setting remains difficult. During drug development, potential compounds may exhibit unexpected nephrotoxic effects, which imposes a significant financial burden on pharmaceutical companies. As a result, there is an ongoing need for more accurate model systems. The use of renal organoids to simulate responses to nephrotoxic insults has the potential to bridge the gap between preclinical drug efficacy studies in cell cultures and animal models, and the stages of clinical trials in humans.

The extracellular matrix of lymph node reticular fibres modulates follicle border interactions and germinal centre formation

Germinal centre (GC) formation and antibody production in lymph node follicles require coordinated interactions between B-cells, T-cells and dendritic cells (DCs), orchestrated by the extracellular matrix-rich reticular fibre (RF) network. We describe a unique laminin 523-containing RF network around and between follicles that associates with PDGFrec highCCL19lowgp38low fibroblastic reticular cells (FRC).

Cell culture systems for isolation of SARS-CoV-2 clinical isolates and generation of recombinant virus

A simple and robust cell culture system is essential for generating authentic SARS-CoV-2 stocks for evaluation of viral pathogenicity, screening of antiviral compounds, and preparation of inactivated vaccines. Evidence suggests that Vero E6, a cell line commonly used in the field to grow SARS-CoV-2, does not support efficient propagation of new viral variants and triggers rapid cell culture adaptation of the virus. We generated a panel of 17 human cell lines overexpressing SARS-CoV-2 entry factors and tested their ability to support viral infection.

Synaptic Targets of Glycinergic Neurons in Laminae I-III of the Spinal Dorsal Horn

A great deal of evidence supports the inevitable importance of spinal glycinergic inhibition in the development of chronic pain conditions. However, it remains unclear how glycinergic neurons contribute to the formation of spinal neural circuits underlying pain-related information processing. Thus, we intended to explore the synaptic targets of spinal glycinergic neurons in the pain processing region (laminae I-III) of the spinal dorsal horn by combining transgenic technology with immunocytochemistry and in situ hybridization accompanied by light and electron microscopy.

Decreased expression of synaptic genes in the vestibular ganglion of rodents following subchronic ototoxic stress

The vestibular ganglion contains primary sensory neurons that are postsynaptic to the transducing hair cells (HC) and project to the central nervous system. Understanding the response of these neurons to HC stress or loss is of great interest as their survival and functional competence will determine the functional outcome of any intervention aiming at repair or regeneration of the HCs. We have shown that subchronic exposure to the ototoxicant 3,3'-iminodipropionitrile (IDPN) in rats and mice causes a reversible detachment and synaptic uncoupling between the HCs and the ganglion neurons.

IRX5 promotes DNA damage repair and activation of hair follicle stem cells

The molecular mechanisms allowing hair follicles to periodically activate their stem cells (HFSCs) are incompletely characterized. Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice have delayed anagen onset, with increased DNA damage and diminished HFSC proliferation. Open chromatin regions form near cell cycle progression and DNA damage repair genes in Irx5-/- HFSCs. DNA damage repair factor BRCA1 is an IRX5 downstream target.

Btg1 and Btg2 regulate neonatal cardiomyocyte cell cycle arrest

Rodent cardiomyocytes undergo mitotic arrest in the first postnatal week. Here, we investigate the role of transcriptional co-regulator Btg2 (B-cell translocation gene 2) and functionally-similar homolog Btg1 in postnatal cardiomyocyte cell cycling and maturation. Btg1 and Btg2 (Btg1/2) are expressed in neonatal C57BL/6 mouse left ventricles coincident with cardiomyocyte cell cycle arrest. Btg1/2 constitutive double knockout (DKO) mouse hearts exhibit increased pHH3+ mitotic cardiomyocytes compared to Wildtype at postnatal day (P)7, but not at P30.

Upregulation of carbonic anhydrase 1 beneficial for depressive disorder

Carbonic Anhydrase 1 (CAR1) is a zinc-metalloenzyme that catalyzes the hydration of carbon dioxide, and the alteration of CAR1 has been implicated in neuropsychiatric disorders. However, the mechanism underlying the role of CAR1 in major depressive disorder (MDD) remains largely unknown. In this study, we report the decreased level of CAR1 in MDD patients and depression-like model rodents. We found that CAR1 is expressed in hippocampal astrocytes and CAR1 regulates extracellular bicarbonate concentration and pH value in the partial hilus.

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