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Untangling Appetite Circuits with Optogenetics and Chemogenetics
Published in Ruth B.S. Harris, Appetite and Food Intake, 2017
The importance of the PBN in modulating satiety led to the discovery of a neural population marked by calcitonin gene-related peptide (CGRP) that suppresses appetite (Carter et al. 2013). Fos expression in the PBN following the ablation of ARCAgRP neurons, intraperitoneal injection of lithium chloride (LiCl), injection of lipopolysaccharide (LPS), or the administration of the satiety hormones amylin or cholecystokinin (CCK) highly colocalized with immunohistochemical detection of CGRP, suggesting a key node for dampening appetite following a meal or during illness or exposure to toxins. Employing a toolbox of genetically encoded actuators, it was demonstrated that the activation of PBNCGRP neurons severely reduced food intake, while inhibition increased food intake during adverse conditions that normally subdue appetite (Figure 5.3) (Carter et al. 2013). Furthermore, these neurons mediated conditioned taste aversion, implying the encoding of a negative valence state (Carter, Han, and Palmiter 2015). Optogenetic photoactivation of PBNCGRP neurons projecting to the CeA (CeAlc), but not to the bed nucleus of the stria terminalus (BNST), recapitulated the loss of feeding observed after stimulation of PBNCGRP soma, while an innovative “collision” strategy combining the retrograde properties of a canine adenovirus (CAV2) carrying Cre recombinase with Cre-dependent inhibitory DREADD receptors, established the necessity of this projection to elevate feeding in circumstances that curb appetite (Carter et al. 2013).
Immunogenicity and protection efficacy of enhanced fitness recombinant Salmonella Typhi monovalent and bivalent vaccine strains against acute toxoplasmosis
Published in Pathogens and Global Health, 2021
Fei-Kean Loh, Sheila Nathan, Sek-Chuen Chow, Chee-Mun Fang
In order to improve the overall protective efficacy, different antigen combinations shall be selected. Rhoptry proteins (ROPs) have emerged as one of the most highly explored and immunogenic T. gondii antigen. As reviewed, ROP16 delivered by canine adenovirus type 2 (CAV2) has conferred the highest protection among the T. gondii DNA vaccine candidates in previous five years and is characterized by high levels of proinflammatory cytokines IFN-ɣ and IL-2 [22,50]. Apart from that, the S. Typhi bivalent strains can be potentially developed as a combination toxoplasmosis and typhoid fever vaccine to improve its commercial value. For instance, the two most established licensure combination vaccines – diphtheria, tetanus, and pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine have formulated multiple antigens as a single product to facilitate fewer immunizations with broader disease coverage [61]. Hence, the selection of T. gondii antigens that are conserved with phylogenetically closely related parasites such as Neospora, may lead to vaccines developed for both parasitic diseases. Preliminary study reported that mice immunized with plasmid-expressed T. gondii MIC3 showed lower parasite burden following T. gondii and N. caninum challenge [62]. The future construction of multivalent S. Typhi strains can also include antigens from closely related intracellular pathogens which require the induction of similar immune responses.
Targeting central nervous system pathologies with nanomedicines
Published in Journal of Drug Targeting, 2019
Shoshy Mizrahy, Anna Gutkin, Paolo Decuzzi, Dan Peer
As described in Figure 2, pathogens do not only utilise CNS receptors for cell entry but also exploit several cellular mechanisms for CNS penetration. For example, several pathogens utilise intracellular transport, a mechanism essential for the distribution of neuronal organelles and proteins. The retrograde transport facilitated by the cytoplasmic dynein motor enables the transfer of cargo from the nerve terminus to the cell body. The use of motor based axonal transport is a key mechanism for viral spread across the CNS, especially when taking into account axon length, which makes relying on passive diffusion irrelevant [123]. The use of motor-based axonal transport following entry at peripheral nerve endings has been documented for several neurotropic viruses, bacteria and toxins including the Rabies, Poliovirus, Canine adenovirus type 2 and Tetanus toxin [123]. Therefore, it is possible that NPs conjugated with viral proteins will also be able to exploit the motor-based axonal transport for CNS spreading.
An oral bait vaccination approach for the Tasmanian devil facial tumor diseases
Published in Expert Review of Vaccines, 2020
Andrew S. Flies, Emily J. Flies, Samantha Fox, Amy Gilbert, Shylo R. Johnson, Guei-Sheung Liu, A. Bruce Lyons, Amanda L. Patchett, David Pemberton, Ruth J. Pye
The most straightforward DFT bait-vaccine approach would build on the successes and failures of oral rabies vaccine development. Many viral vectors were tested for oral rabies vaccines, including baculovirus [91], canine adenovirus type 2 [92–95], and raccoonpox virus [96]. More recently, an adenovirus platform was more effective in inducing seroconversion of baited raccoons in comparison to the areas baited with the vaccinia platform [97]. Vaccinia and adenoviruses have both been reported to infect marsupials [98–100], and we have confirmed that adenoviruses infect DFT cells (Flies et al., unpublished).