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Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells.
O’Sullivan J, Carroll D, Cao Y, Salicru A, Bochner B (2018) Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells. J Allergy Clin Immunol 141:1774-1785.e1777. doi: 10.1016/j.jaci.2017.06.028
Summary: Therapeutic payloads can be targeted selectively to eosinophils and malignant mast cells by exploiting this Siglec-8 endocytic pathway.
Usage: Eosinophil cell death was assessed with 2C4 mAb or isotype control (both at 2.5 μg/mL).
Related Products: Custom Conjugates
Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius.
Fu C, Xue J, Wang R, Chen J, Ma L, Liu Y, Wang X, Guo F, Zhang Y, Zhang X, Wang S (2017) Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius. J Physiol 595:4973-4989.. doi: 10.1113/JP274437
Objective: To investigate whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity.
Summary: Respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO2/H+-sensitive Phox2b-expressing neurons.
Usage: Two protocols were applied for SSP-SAP injections. In immunostaining experiments, to determine how many Phox2b-containing cells were destroyed, a total volume of 100 nl of PBS containing 6 ng of SSP-SAP (3 ng in 50 nl; 2 injections) was injected into one side of the NTS and the contralateral NTS was used as a control (no injection). For in vivo experiments, to determine whether loss of Phox2b cells led to impaired HCVR, bilateral injections with a total volume of 200 nl of PBS containing 6 ng (1.5 ng in 50 nl per injection; 2 injections per side) or 12 ng (3 ng in 50 nl per injection; two injections per side) of toxin into NTS. Breathing was studied in conscious, freely moving mice treated with SSP-SAP and Blank-SAP.
Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)
Induced pluripotent stem cell-derived mesenchymal progenitor cells: Promotion of neuritogenesis and axon elongation through neurotrophin and cytokine production
Brick, R (2017) Induced pluripotent stem cell-derived mesenchymal progenitor cells: Promotion of neuritogenesis and axon elongation through neurotrophin and cytokine production. University of Pittsburgh Thesis.
Objective: To test if mesenchymal progenitor cells (MiMPCs), originally derived from mesenchymal stem cells (MSCs), have the same ability to support neuronal regeneration as the parent MSC.
Summary: Results show that MiMPCs can secrete neurotrophic factors after neuroinductive treatment and can produce factors to improve neurite outgrowth in a chick embryonic dorsal root ganglion (DRG) model. These findings suggest that neurotrophically induced-MiMPCs (NI-MiMPCs) may be considered a suitable substitute cell type to support nerve growth.
Usage: immunofluorescence
Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)
Correction of Hirschsprung-associated mutations in human induced pluripotent stem cells via clustered regularly interspaced short palindromic repeats/cas9, restores neural crest cell function
Lai FP, Lau ST, Wong JK, Gui H, Wang RX, Zhou T, Lai WH, Tse HF, Tam PK, Garcia-Barcelo MM, Ngan ES (2017) Correction of Hirschsprung-associated mutations in human induced pluripotent stem cells via clustered regularly interspaced short palindromic repeats/cas9, restores neural crest cell function. Gastroenterology 153(1):139-153.e8. doi: 10.1053/j.gastro.2017.03.014 PMID: 28342760
Objective: To identify mutations associated with short-segment Hirschsprung disease (S-HSCR), and use the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system to determine how mutations affect enteric neural crest cells (ENCC) function.
Summary: Mutations in vinculin gene (VCL) associated with S-HSCR were identified. Correction of this mutation in iPSC using CRISPR/Cas9 editing, as well as the RET G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored ENCC function. The study demonstrates how human iPSCs can be used to identify disease-associated mutations and determine how they affect cell functions and contribute to pathogenesis.
Usage: Immunofluorescence (1:500)
Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)
G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis.
Casciello F, Al-Ejeh F, Kelly G, Brennan D, Ngiow S, Young A, Stoll T, Windloch K, Hill M, Smyth M, Gannon F, Lee J (2017) G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis. Proc Natl Acad Sci U S A 114:7077-7082. doi: 10.1073/pnas.1618706114 PMID: 28630300
Usage: Western blot
Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)
Current and future issues in the development of spinal agents for the management of pain.
Yaksh T, Fisher C, Hockman T, Wiese A (2017) Current and future issues in the development of spinal agents for the management of pain. Curr Neuropharmacol 15:232-259.. doi: 10.2174/1570159×14666160307145542
Summary: Although conscious pain experience is driven by signals mediated supraspinally, the more high intensity pain generated by strong stimuli, tissue injury, and nerve injury is encoded at the spinal dorsal horn level. The control of pain signals at the spinal dorsal horn level is a tempting target for targeted pain therapy. This review discusses the potential targets for pain therapeutics in the spinal dorsal horn, and some of the spinal agents used to modulate pain transmission through that location. The use of SSP-SAP (Cat. #IT-11) is mentioned as a neurokinin-1 targeted molecule that can block some pain transmission.
Related Products: SSP-SAP (Cat. #IT-11)
Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions
Taxini CL, Moreira TS, Takakura AC, Bicego KC, Gargaglioni LH, Zoccal DB (2017) Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions. Neuroscience 354:146-157.. doi: 10.1016/j.neuroscience.2017.04.033
Summary: The authors utilize Anti-DBH-SAP (Cat. #IT-03) to investigate the involvement of the A5 noradrenergic neurons to the basal and chemoreflex control of the sympathetic and respiratory activities in unanesthetized conditions.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors
Yao P, Ding Y, Han Z, Mu Y, Hong T, Zhu Y, Li H (2017) Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors. Mol Pain 13:744806917708127. doi: 10.1177/1744806917708127 PMID: 28554249
Objective: To determine the functions and targeted suppression of asparaginyl endopeptidase (AEP) in a mouse model of breast cancer-induced bone pain.
Summary: Targeted suppression of AEP with specific small compounds significantly reduced bone pain while purified recombinant AEP proteins increased bone pain. AEP aggravates the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancer-induced bone pain.
Usage: Western blot
Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)
TCR-like antibody drug conjugates mediate killing of tumor cells with low peptide/HLA targets.
Lowe D, Bivens C, Mobley A, Herrera C, McCormick A, Wichner T, Sabnani M, Wood L, Weidanz J (2017) TCR-like antibody drug conjugates mediate killing of tumor cells with low peptide/HLA targets. MAbs 9:603-614. doi: 10.1080/19420862.2017.1302630
Objective: To analyze the killing potential of TCR-like ADCs.
Summary: Data comprise proof-of-principle results that TCR-like ADCs mediate potent tumor cytotoxicity and support their continued development alongside agents that disrupt DNA replication. Additionally, TCR-like antibody ligand binding appears to play an important role in ADC functionality and should be addressed during therapy development to avoid binding patterns that negate ADC killing efficacy.
Usage: TCR-like antibodies were indirectly bound to Saporin using Mab-ZAP. Tumor cells (5×103) were plated in flat-bottom 96-well plates, then Mab-ZAP (100 ng) was added. Various dilutions of isotype control, BB7.2, TCR-like, and 4D5 antibodies were subsequently added to a final volume of 120 mcl and plates were incubated for 3– 5 d at 37 °C with 5% CO2.
Related Products: Mab-ZAP (Cat. #IT-04)
Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion.
Lee S, Cho W, Lee Y, Han J (2018) Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion. Mol Neurobiol 55:3976-3989. doi: 10.1007/s12035-017-0620-5
Objective: Examine the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex.
Summary: The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer’s disease to stress since activation of NF-κB is associated with stress.
Usage: Male Sprague-Dawley rats received injections of 192 IgG-SAP dissolved in sterile 0.01 M PBS) at a concentration of 0.25 μg/μl.
Related Products: 192-IgG-SAP (Cat. #IT-01)