2015 Targeting Trends Review

Akiyama T, Tominaga M, Takamori K, Carstens M, Carstens E (2014) Role of spinal bombesin-responsive neurons in nonhistaminergic itch. J Neurophysiol 112:2283-2289. doi: 10.1152/jn.00409.2014

Summary: Recent papers have demonstrated that pruritogen-evoked scratching behavior is reduced or eliminated by intrathecal injection of Bombesin-SAP (Cat. #IT-40). In this work the authors build on those data by investigating if spinal neurons that are responsive to pruritogens administered intradermally are also responsive to a spinal infusion of bombesin. Through the use of intradermal chloroquine injections, spinal superfusion of bombesin, and noxious pinch, the overlap of neurons processing itch and nociception was examined. The results demonstrate that chloroquine- and bombesin-sensitive neurons are involved in the transmission of itch, and that these are a separate neuronal population from those involved in nociception.

Related Products: Bombesin-SAP (Cat. #IT-40)

Mao C, Li H, Zhang Z, Kiyama T, Panda S, Hattar S, Ribelayga C, Mills S, Wang S (2014) T-box transcription regulator Tbr2 is essential for the formation and maintenance of Opn4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells. J Neurosci 34:13083-13095. doi: 10.1523/JNEUROSCI.1027-14.2014 PMID: 25253855

Summary: Opsin 4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for controlling non-image-forming visual functions in the retina. The findings show that opsin 4 is only expressed in Tbr2-positive ipRGCs, no ipRGCs are found if Tbr2 is deleted before RGC specialization, and most ipRGCs are eliminated when Tbr2 is deleted from established ipRGCs. An antibody against melanopsin (Cat. #AB-N39) was used at a 1:1000 dilution for immunohistochemical analyses.

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

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)

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)

Joly S, Guzik-Kornacka A, Schwab M, Pernet V (2014) New mouse retinal stroke model reveals direction-selective circuit damage linked to permanent optokinetic response loss. Invest Ophthalmol Vis Sci 55:4476-4489. doi: 10.1167/iovs.14-14521 PMID: 24970264

Summary: The authors used a mouse model of ‘retinal stroke’ to better delineate the optokinetic response deficits at the cellular level. Damage was found in the processes of starburst amacrine cells (SACs), and to a lesser extent, the dendrites. Anti-melanopsin (Cat. #AB-N38) at 1:2500 was used for immunohistochemistry.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Akahoshi N, Kamata S, Kubota M, Hishiki T, Nagahata Y, Matsuura T, Yamazaki C, Yoshida Y, Yamada H, Ishizaki Y, Suematsu M, Kasahara T, Ishii I (2014) Neutral aminoaciduria in cystathionine β-synthase-deficient mice; an animal model of homocystinuria. Am J Physiol Renal Physiol 306:F1462-1476. doi: 10.1152/ajprenal.00623.2013 PMID: 24761004

Summary: The authors utilized a mouse model for homocystinuria in order to examine renal amino acid reabsorbtion. Some of the immunohistochemistry experiments used anti-Met (Cat. #AB-T036). It was found that loss of cystathionine β-synthase causes hyperexcretion of both glucogenic and ketogenic neutral amino acids, as well as histidine.

Jokiaho A, Donovan C, Watts A (2014) The rate of fall of blood glucose determines the necessity of forebrain-projecting catecholaminergic neurons for male rat sympathoadrenal responses. Diabetes 63:2854-2865. doi: 10.2337/db13-1753

Summary: Different sets of glucosensors detect insulin-induced hypoglycemia depending on the onset rate. This detection controls the activation of sympathoadrenal counterregulatory responses (CRRs). Slow onset hypoglycemia, common with insulin therapy, is detected by glucosensors in the portal-mesenteric veins. Fast onset is detected by brain elements. The authors lesioned hindbrain catecholaminergic neurons to determine which set of responses-they interact with. Rats received 42 ng bilateral injections of Anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data indicate that these neurons are critical for detection of slow-onset insulin-induced hypoglycemia.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Kiris E, Wang T, Yanpallewar S, Dorsey S, Becker J, Bavari S, Palko M, Coppola V, Tessarollo L (2014) TrkA in vivo function is negatively regulated by ubiquitination. J Neurosci 34:4090-4098. doi: 10.1523/JNEUROSCI.4294-13.2014 PMID: 24623787

Summary: The high affinity nerve growth factor receptor, trkA, plays an intrinsic role in the regulation of various aspects of the mammalian nervous system. The post-translational attachment of ubiquitin to trkA plays a role in the final disposition and function of many proteins; in this work the authors investigate the result of trkA ubiquitination. By removing a 3 amino acid sequence from the receptor the ubiquitination of TrkA was reduced which resulted in an increase in TrkA protein levels and activity. In mice containing this mutation, the rise in TrkA activity was accompanied by enhanced thermal sensitivity and inflammatory pain. Anti-trkA (Cat. #AB-N03) was used at a concentration of 1:500 in immunohistochemistry.

Related Products: trkA Rabbit Polyclonal (Cat. #AB-N03)

Sato M, Akasaka E, Saitoh I, Ohtsuka M, Nakamura S, Sakurai T, Watanabe S (2013) Targeted toxin-based selectable drug-free enrichment of Mammalian cells with high transgene expression. Biology (Basel) 2:341-355. doi: 10.3390/biology2010341

Summary: Cell transfection is a powerful tool for evaluation of function and expression of newly discovered genes as well as for both small and large scale eukaryotic expression of proteins. Most transfection strategies require a selection agent to eliminate cells that do not internalize the plasmid containing the gene of interest. Subsequent maintenance of the tranfected cells requires the presence of the selection agent, and the expression levels of the gene of interest have to be evaluated on a cell by cell basis. In this work the authors designed a system utilizing 50 μg/ml rIB4-SAP (Cat. #IT-10) to eliminate non-transfected cells and select for strong expression of the gene of interest. The data demonstrate that this technique will generate stable transfected cells that express the gene of interest at high levels.

Related Products: IB4-SAP (Cat. #IT-10)