References

Grady FS, Boes AD, Geerling JC (2022) A century searching for the neurons necessary for wakefulness. Front Neurosci 16:930514. doi: 10.3389/fnins.2022.930514

Objective: This review article attempts to summarize research that has investigated the neurons necessary for wakefulness.

Summary: The authors summarize animal experiments and research performed in different brain regions to further understand wakefulness. Several saporin conjugates are discussed.

Usage: Lesions of the basal forebrain were done by injecting a 0.1% solution of either 192-IgG-SAP or Orexin-SAP at four different sites (Fuller et al. and Geraschenko et al.); Intraventricular injection of Anti-DBH-SAP (Gompf et al.); Bilateral injections of 192-IgG-SAP (Kaur et al.).

Related Products: Orexin-B-SAP (Cat. #IT-20)

See Also:

• Fuller P et al. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956, 2011.
• Gerashchenko D et al. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36, 2006.
• Gompf HS et al. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551, 2010.
• Kaur S et al. Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504, 2008.

Ryan Y, Harrison A, Trivett H, Hartley C, David J, Clark GC, Hiscox JA (2022) RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing. Toxins (Basel) 14(7):470. doi: 10.3390/toxins14070470 PMID: 35878208

Objective: The Depurination event could be detected using Oxford Nanopore Technologies (ONT) direct RNA sequencing, detecting a change in charge in the ricin loop.

Summary: Collectively, this work highlights the potential for ONT and direct RNA sequencing to detect and quantify depurination events caused by ribosome-inactivating proteins such as ricin.

Usage: Saporin was added as described by Rust et al., at 100 nM [22] for 24 h.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Rust A et al. Two complementary approaches for intracellular delivery of exogenous enzymes. Sci Rep 5:12444, 2015.

Van Hentenryck M, Li Z, Murphy PM, Czechowicz A (2022) Antibody-based preparative regimens for cell, tissue and organ transplantation. (eds. 162). OBM Transplantation 6(3):162. doi: 10.21926/obm.transplant.2203162

Objective: Provide a review of progress in the use of antibodies to support cell and tissue transplantation with a particular focus on induction of donor-specific tolerance for solid organ transplantation.

Summary: Antibody-based conditioning to prepare the recipient is a promising approach towards achieving transplant tolerance in both hematopoietic and solid organ transplant settings.

Usage: To enhance HSC depletion while avoiding bystander toxicity (neutropenia, lymphopenia, and thrombocytopenia) caused by CD45-radioimmunotherapy, Palchaudhuri et al. developed a saporin-based CD45 (CD45-SAP) immunotoxin using a biotinylated antibody and Streptavidin-ZAP.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

See Also:

• Palchaudhuri R Featured Article: Targeted depletion of hematopoietic stem cells promises safer transplantation. Targeting Trends 17(3), 2016.
• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.

Takahashi JI, Nakamura S, Onuma I, Zhou Y, Yokoyama S, Sakurai H (2022) Synchronous intracellular delivery of EGFR-targeted antibody-drug conjugates by p38-mediated non-canonical endocytosis. Sci Rep 12(1):11561. doi: 10.1038/s41598-022-15838-8 PMID: 35798841

Objective: The binding of cetuximab to EGFR suppresses ligand-induced signaling events. The authors demonstrate that synchronous non-canonical EGFR endocytosis can increase the efficacy of EGFR-targeting ADCs.

Summary: Epidermal growth factor (EGFR) has been a popular target in the treatment of cancer via monoclonal antibodies, specifically cetuximab and panitumumab. They have been applied to antibody-drug conjugates (ADCs) and their clinical efficacy had been demonstrated, but this efficacy has also been limited by acquired resistance via secondary mutations or the activation of bypass pathways. To overcome these limiting factors, the authors investigated if non-canonical clathrin-mediated endocytosis (CME) of EGFR induced the internalization of membrane-bound EGFR-targeted mAbs. Their results show that tumor necrosis factor-alpha strongly induces endocytosis of the cetuximab-EGFR complex via the p38 phosphorylation of EGFR and that Hum-ZAP, a secondary antibody conjugated to saporin, will also undergo internalization with the complex and enhance anti-proliferative activity.

Related Products: Hum-ZAP (Cat. #IT-22)

Alhassan M (2022) Sensory and motor visual functions in Parkinson’s Disease with respect to freezing of gait symptoms. J Ophthalmol & Vis Sci 7(2):1069.

Objective: This review article summarizes the results from previous studies focusing on visual functions in Parkinson’s Disease patients.

Summary: Freezing of gait (FOG) is considered to be a motor disorder symptom that affects some Parkinson Disease (PD) patients; however, it is hypothesized that sensory systems may also be involved in FOG. Visual functions include high contrast visual acuity, low contrast visual acuity, contrast sensitivity, Vernier acuity, mesopic vision, stereopsis, motion perception, and vergence eye movements and are all affected in PD patients with FOG patients having more deficits in some of these functions. FOG patients also had impairments in non-dopaminergic mediated functions which suggests greater impairment in two functions that involve cholinergic neurotransmitters. 192-IgG-SAP (Cat. IT-01) was used to create a PD rat animal model to study the contribution of the cholinergic system to motor functions. It was found that the fall rates were more frequent in rats, that were injected with dual 192 IgG-saporin /6-hydroxydopamine (6-OHDA) than rats with either isolated cholinergic or isolated dopaminergic lesions.

Related Products: 192-IgG-SAP (Cat. #IT-01)

See Also:

• Kucinski A et al. Modeling fall propensity in Parkinson’s disease: deficits in the attentional control of complex movements in rats with cortical-cholinergic and striatal-dopaminergic deafferentation. J Neurosci 33(42):16522-16539, 2013.

Gao X, Zhang S, Gou J, Wen Y, Fan L, Zhou J, Zhou G, Xu G, Zhang Z (2022) Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection. J Infect 85(4):418-427. doi: 10.1016/j.jinf.2022.06.030 PMID: 35793758

Objective: To determine the role of angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19.

Summary: The downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.

Usage: Western blot

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Levine AS, Jewett DC, Kotz CM, Olszewski PK (2022) Behavioral plasticity: Role of neuropeptides in shaping feeding responses. Appetite 174:106031. doi: 10.1016/j.appet.2022.106031 PMID: 35395362

Objective: Review studies on feeding behavior involving neuropeptides that influence behavioral plasticity – primarily opioids, orexin, neuropeptide Y, and oxytocin.

Summary: Eating behavior is influenced by a number of external factors, including time of day, type of food available, energy balance state, and stressors. The reviewed work underscores that environmental factors play a critical role in feeding behavior and energy balance, but changes in eating behavior also result from a multitude of non-environmental factors, such that there can be no single mechanism or variable that can explain ingestive behavior.

Usage: References a previous publication using Oxytocin-SAP (IT-46).

Related Products: Oxytocin-SAP (Cat. #IT-46)

See Also:

• Baskin DG et al. A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain. Endocrinology 151(9):4207-4213, 2010.

Maki Y, Kawata K, Liu Y, Goo KY, Okamoto R, Kajihara Y, Satoh A (2022) Design and synthesis of glycosylated cholera toxin b subunit as a tracer of glycoprotein trafficking in organelles of living cells. Chemistry 28(37):e202201253. doi: 10.1002/chem.202201253 PMID: 35604098

Related Products: Cholera Toxin B, Recombinant (Cat. #PR-14)

Murphy ER, Thompson R, Osman KL, Haxton C, Brothers M, Lee L, Warncke K, Smith CL, Keilholz AN, Hamad A, Golzy M, Bunyak F, Ma L, Nichols NL, Lever TE (2022) A strength endurance exercise paradigm mitigates deficits in hypoglossal-tongue axis function, strength, and structure in a rodent model of hypoglossal motor neuron degeneration. Front Neurosci 16:869592. doi: 10.3389/fnins.2022.869592 PMID: 35844238

Objective: To investigate the effect of high-repetition/low-resistance tongue exercise on tongue function, strength, and structure.

Summary: The tongue plays a crucial role in swallowing and impairment can lead to dysphagia, particularly in motor neuron diseases such as amyotrophic lateral sclerosis. This study utilized the authors previously established inducible rodent model of dysphagia due to targeted degeneration of the hypoglossal-tongue axis by injecting cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue base for retrograde transport to the hypoglossal (XII) nucleus via the hypoglossal nerve, which provides the sole motor control of the tongue. Results showed that sham-exercised CTB-SAP rats had significant deficits in lick rate, swallow timing, and lick force. In exercised CTB-SAP rats, lick rate and lick force were preserved; however, swallow timing deficits persisted.

Usage: Rats received either a single “control” injection of unconjugated CTB + SAP (20μg CTB+25μg SAP) or CTB-SAP (Cat. #IT-14) injection (25μg of CTB conjugated to SAP) into the midline genioglossus muscle in the tongue base.

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)

Li S, Li W, Yuan J, Bullova P, Wu J, Zhang X, Liu Y, Plescher M, Rodriguez J, Bedoya-Reina OC, Jannig PR, Valente-Silva P, Yu M, Henriksson MA, Zubarev RA, Smed-Sörensen A, Suzuki CK, Ruas JL, Holmberg J, Larsson C, Christofer Juhlin C, von Kriegsheim A, Cao Y, Schlisio S (2022) Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel-Lindau syndrome. Nat Metab 4(6):739-758. doi: 10.1038/s42255-022-00593-x PMID: 35760869

Objective: To investigate how mitochondria sense oxygen levels.

Summary: The authors report an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel–Lindau syndrome. The data obtained from this study offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria.

Usage: Immunoprecipitation (IP), Immunoblot (IB); 1:1000

Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)