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High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies.
Ha K, Bidlingmaier S, Zhang Y, Su Y, Liu B (2014) High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies. Mol Cell Proteomics 13:3320-3331. doi: 10.1074/mcp.M114.039768
Summary: Macropinocytosis, the internalization of large endocytic vesicles called macropinosomes, is upregulated in Ras-transformed cancers. To date, large-scale antibody generation strategies have not incorporated a selection method for antibodies. In this work the authors demonstrate screening and validation of the antibodies that utilize the macropinosome pathway. One method used was to biotinylate the antibodies and combine them with Streptavidin-ZAP (Cat. #IT-27) at a 1:1 ratio. The conjugate was applied to cells in a concentration curve starting at 200 nM in order to demonstrate internalization and cell killing.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to L-DOPA in the hemi-parkinsonian rat.
Ostock C, Lindenbach D, Goldenberg A, Kampton E, Bishop C (2014) Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to L-DOPA in the hemi-parkinsonian rat. Behav Brain Res 270:75-85. doi: 10.1016/j.bbr.2014.05.009 PMID: 24837745
Objective: To study the effects of L-DOPA treatment on a Parkinson’s model of rats, particularly regarding noradrenergic denervation of the locus coeruleus.
Summary: L-DOPA is the most effective treatment against Parkinson’s disease. There are, however, significant side effects like L-DOPA-induced Dyskinesias (LID) that are overlooked. This study uses 6-OHDA + Anti-DBH-SAP lesioned rats to induce Parkinson’s-like behavior and monitor LID throughout treatment with L-DOPA.
Usage: 10 µg of Anti-DBH-SAP injected into the nigral neurons of the brains of rats.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice.
Criscimanna A, Coudriet G, Gittes G, Piganelli J, Esni F (2014) Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice. Gastroenterology 147:1106-1118.e1111. doi: 10.1053/j.gastro.2014.08.008
Summary: In response to tissue damage or infection, monocytes are recruited to the injured area and differentiate into macrophages. These macrophages can perform different functions depending on the tissue type. The specific differentiation macrophages undergo in response to their environment is called polarization. The authors used a mouse pancreatic lesion model to examine the polarization of macrophages into the two distinct states known, M1 and M2. Mice received 20 μg of Mac-1-SAP mouse (Cat. #IT-06) in a tail vein injection following a pancreatic lesion, and were sacrificed on various days post-injection in order to evaluate macrophage presence at different response stages. The results demonstrate that various aspects of macrophage polarization are required for pancreatic regeneration.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission.
Liu H, Yan W, Lu X, Zhang X, Wei J, Wang X, Wang T, Wu T, Cao J, Shao C, Zhou F, Zhang H, Zhang P, Zang T, Lu X, Cao J, Ding H, Zhang L (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485. doi: 10.1016/j.expneurol.2014.07.018
Summary: The first synapse in the pain pathway is in the spinal dorsal horn, and several sites are involved in the descending control of pain. Previous studies have suggested that cerebrospinal fluid-contacting neurons may facilitate signal transmission and substance transport between the brain parenchyma and the CSF, including processes that modulate pain transmission. The authors administered CTB-SAP (Cat. #IT-14) into the right lateral ventricle of rats. Saporin (Cat. #PR-01) was used as a control. The results indicate that the 5-HT pathway contacting the CSF is an important piece in the descending inhibitory system controlling spinal transmission of pain.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization.
Bostad M, Kausberg M, Weyergang A, Olsen C, Berg K, Høgset A, Selbo P (2014) Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization. Mol Pharm 11:2764-2776. doi: 10.1021/mp500129t
Summary: CD44 is known as a common cancer stem cell (CSC) marker. Given that CSC’s seem to have the ability to resist many therapeutic agents, the authors investigated the use of photochemical internalization (PCI) while targeting CD44-expressing CSC’s. An immunotoxin was constructed by biotinylating a pan CD44 antibody and combining it with Streptavidin-ZAP (Cat. #IT-27) at a 4:1 biotinylated antibody to Streptavidin-ZAP molar ratio. Various cancer cell lines were incubated with the toxin at a concentration of 0.825 nM. The toxin showed specific cytotoxicity to CD44-expressing cell lines, demonstrating the efficacy of PCI in conjunction with targeted toxins to treat some cancers
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD44-SAP (Cat. #IT-72)
Identification of a gene regulatory network associated with prion replication
Marbiah MM, Harvey A, West BT, Louzolo A, Banerjee P, Alden J, Grigoriadis A, Hummerich H, Kan HM, Cai Y, Bloom GS, Jat P, Collinge J, Klöhn PC (2014) Identification of a gene regulatory network associated with prion replication. EMBO J 33(14):1527-1547. doi: 10.15252/embj.201387150 PMID: 24843046
Related Products: Antibody to IQGAP2 (Cat. #AB-V28)
P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat in vitro.
Alvares T, Revill A, Huxtable A, Lorenz C, Funk G (2014) P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat in vitro. J Physiol 592:3089-3111. doi: 10.1113/jphysiol.2013.268136 PMID: 24879869
Summary: P2YR’s are metabotropic purinergic receptors found in some parts of the CNS. A subtype of this receptor excites rhythm generating networks in the preBötzinger complex. In order to better understand the role of these receptors in modulation of motor output the authors used brainstem-spinal cord and medullary slice preparations from neonatal rats to investigate P2Y1R signaling on specific neurons that innervate diaphragm and airway muscles. Anti-NK1r (Cat. #AB-N33AP) at a 1:1000 dilution was used during the immunohistochemistry. The data suggest that loss of purinergic modulation contributes to motoneuron excitability.
Related Products: NK-1 Receptor Rabbit Polyclonal, affinity-purified (Cat. #AB-N33AP)
Featured Article: Corticotropin releasing factor-saporin conjugate selectively lesions nucleus incertus
Lee CL, Rajkumar R, Dawe GS (2014) Featured Article: Corticotropin releasing factor-saporin conjugate selectively lesions nucleus incertus. Targeting Trends 15(2)
Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)
Read the featured article in Targeting Trends.
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Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis.
Jeong D, Lee J, Lee S, Chang W, Kim S, Chang J (2014) Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis. Biomed Res Int 2014:568587. doi: 10.1155/2014/568587
Summary: Deep brain stimulation (DBS) is a technique by which electrical impulses are applied to specific areas of the brain as therapy for various disorders. In this work the authors examined the mechanisms by which DBS can treat dementia. Rats received 5.04 μg intracerebroventricular injections of 192-IgG-SAP (Cat. #IT-01); some rats also received an electrode implanted into the medial septum. Lesioned animals displayed deficits in water maze testing – this deficit was eliminated for the group that received electrical stimulation to the medial septum. The stimulated group also displayed an increase in hippocampal cholinergic activity as well as neurogenesis, indicating that DBS has therapeutic potential.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.
Zheng X, Zhai B, Koivunen P, Shin S, Lu G, Liu J, Geisen C, Chakraborty A, Moslehi J, Smalley D, Wei X, Chen X, Chen Z, Beres J, Zhang J, Tsao J, Brenner M, Zhang Y, Fan C, DePinho R, Paik J, Gygi S, Kaelin W, Zhang Q (2014) Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Genes Dev 28:1429-1444. doi: 10.1101/gad.242131.114 PMID: 24990963
Summary: Members of the FOXO family are thought to act as tumor suppressor genes. In this work the authors investigated the hydroxylation of FOXO3a by EglN2. This hydroxylation pushes FOXO3a toward a protosomal degradation pathway. Loss of FOXO3a in turn allows the accumulation of Cyclin D1, which has been found to be overexpressed in some breast cancers. Some of the data were generated using immunoblots with anti-transhydroxylated proline (Cat. #AB-T044).
Usage: Western blot
Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)
