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Aims: The present study investigated if treatment with the immunotherapeutic, lacto-N-fucopentaose-III (LNFPIII), resulted in amelioration of acute and persisting deficits in synaptic plasticity and transmission as well as trophic factor expression along the hippocampal dorsoventral axis in a mouse model of Gulf War Illness (GWI)., Main Methods: Mice received either coadministered or delayed LNFPIII treatment throughout or following, respectively, exposure to a 15-day GWI induction paradigm. Subsets of animals were subsequently sacrificed 48 h, seven months, or 11 months post GWI-related (GWIR) exposure for hippocampal qPCR or in vitro electrophysiology experiments., Key Findings: Progressively worsened impairments in hippocampal synaptic plasticity, as well as a biphasic effect on hippocampal synaptic transmission, were detected in GWIR-exposed animals. Dorsoventral-specific impairments in hippocampal synaptic responses became more pronounced over time, particularly in the dorsal hippocampus. Notably, delayed LNFPIII treatment ameliorated GWI-related aberrations in hippocampal synaptic plasticity and transmission seven and 11 months post-exposure, an effect that was consistent with enhanced hippocampal trophic factor expression and absence of increased interleukin 6 (IL-6) in animals treated with LNFPIII., Significance: Approximately a third of Gulf War Veterans have GWI; however, GWI therapeutics are presently limited to targeted and symptomatic treatments. As increasing evidence underscores the substantial role of persisting neuroimmune dysfunction in GWI, efficacious neuroactive immunotherapeutics hold substantial promise in yielding GWI remission. The findings in the present report indicate that LNFPIII may be an efficacious candidate for ameliorating persisting neurological abnormalities presented in GWI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

At low oxygen concentrations, respiration of Pseudomonas aeruginosa (Pa) and other bacteria relies on activity of cytochrome cbb 3 oxidases. A diheme cytochrome c 4 (cyt c 4 ) donates electrons to Pa cbb 3 oxidases to enable oxygen reduction and proton pumping by these enzymes. Given the importance of this redox pathway for bacterial pathogenesis, both cyt c 4 and cbb 3 oxidase are potential targets for new antibacterial strategies. The structural information about these two proteins, however, is scarce, and functional insights for Pa and other bacteria have been primarily drawn from analyses of the analogous system from Pseudomonas stutzeri (Ps). Herein, we describe characterization of structural and redox properties of cyt c 4 from Pa. The crystal structure of Pa cyt c 4 has revealed that this protein is organized in two monoheme domains. The interdomain interface is more hydrophobic in Pa cyt c 4 , and the protein surface does not show the dipolar distribution of charges found in Ps cyt c 4 . The reduction potentials of the two hemes are similar in Pa cyt c 4 but differ by about 100 mV in Ps cyt c 4 . Analyses of structural models of these and other cyt c 4 proteins suggest that multiple factors contribute to the potential difference of the two hemes in these proteins, including solvent accessibility of the heme group, the distribution of surface charges, and the nature of the interdomain interface. The distinct properties of cyt c 4 proteins from closely-related Pa and Ps bacteria emphasize the importance of examining the cbb 3 /cyt c 4 redox pathway in multiple species., (Copyright © 2019. Published by Elsevier Inc.)

In this study, the mitochondrial genomes of three Stenogastrinae species, Eustenogaster scitula, Liostenogaster nitidipennis and Parishnogaster mellyi were sequenced and annotated, and a total of 16 vespid mtgenomes are comparatively analyzed. Our results indicate that codon usage bias is mainly dominated by mutational pressure, and affected only slightly by natural selection. Selective pressure analysis of protein-coding genes (PCGs) shows that the highest evolutionary rate is present in NADH complex I, and the lowest in cox1. Compared with the reported mtgenomes of other Vespidae, in Stenogastrinae, trnH is shifted to a new position. Phylogenetic analyses are performed using Bayesian method and Maximum Parsimony. Phylogenetic analysis further confirms that the Stenogastrinae is the sister group of all remaining Vespidae. Divergence time of Stenogastrinae from other Vespidae is estimated at ~ 166 Mya. Our results also support that eusociality evolved twice in the family Vespidae., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study sought to compare the effects of Mitragyna speciosa (Korth.) Havil. extract, alkaloids fraction, and mitragynine, a μ-opioid receptor agonist, to that of morphine and oxycodone in a test of thermal nociception. In Experiment 1, male Sprague-Dawley rats were administered test articles intraperitoneally (IP) 30 min prior to testing to compare the effects of M. speciosa articles to opioid reference compounds on the hotplate assay. Test articles were vehicle, 10 mg/kg morphine, 3 mg/kg oxycodone, 300 mg/kg M. speciosa extract, 75 mg/kg M. speciosa alkaloids fraction, or 30 mg/kg mitragynine. To mirror consumer usage, Experiment 2 sought to determine whether M. speciosa articles retained their biological activity when given orally (PO). Test articles were vehicle, 6 mg/kg oxycodone, 300 mg/kg M. speciosa extract, or 100mg/kg mitragynine with hotplate tests conducted 30 and 60 min after administration. Mitragynine produced antinociceptive effects similar to the reference opioid agonists when administered IP and PO routes. These data suggest that M. speciosa extracts containing significant quantities of mitragynine may warrant consideration for further studies in primate self-administration models to yield insight into the abuse liability of this commercially available product., (Copyright © 2015 Elsevier B.V. All rights reserved.)