A selective C5a-derived peptidomimetic enhances IgG response following inactivated SARS-CoV-2 immunization and confers rapid disease resolution following murine coronavirus infection

The host complement system is a critical component of innate immunity and serves as a principal mechanism of pathogen defense in mammals. EP67 is an engineered decapeptide derived from the C terminus of human complement protein C5a, which displays selective immunostimulatory activity. EP67 preferentially activates phagocyte mononuclear cells but shows minimal activity towards inflammatory granulocytes, including neutrophils. Previous studies of viral infection showed that EP67 possessed antiviral efficacy when used following infection and enhanced antibody responses to antigen challenges when used as an adjuvant. Here, we show in a rodent model that immunization with inactivated γ-irradiated SARS-CoV-2 in combination with EP67 can produce elevated nucleocapsid-specific IgG antibodies compared to viral lysate alone, supporting an enhanced adaptive immune response. Additionally, intranasal administration of EP67 following infection with live MHV-A59 coronavirus resulted in a rapid health improvement in symptomatic infections compared to PBS vehicle controls. Taken together, these results suggest EP67 shows efficacy towards betacoronaviruses when used as an adjuvant during immunization or as a therapeutic during active infections. Moreover, these findings continue to support the capability of EP67 as an antiviral agent and a useful immunostimulatory peptide

Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibioticadministered marmosets, which might be a coping mechanism in response to gut dysbiosisinduced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior

The relation of food quantity to rumination behavior.

Preliminary work suggested that the quantity of food ingested by retarded individuals who usually ruminated following meals was related to the frequency and duration of ruminating responses. This possible relation was experimentally examined by systematically varying food quantity from regular portions to satiation levels for three retarded individuals who exhibited high levels of ruminating. A clear functional relation of food quantity to ruminating emerged, with satiation procedures producing rapid and large decreases in the relatively high frequencies and durations of ruminating characteristic of baseline food quantity conditions

Measuring embeddedness: Hierarchical scale-dependent information exchange efficiency of the human brain connectome

This article presents a novel approach for understanding information exchange efficiency and its decay across hierarchies of modularity, from local to global, of the structural human brain connectome. Magnetic resonance imaging techniques have allowed us to study the human brain connectivity as a graph, which can then be analyzed using a graph-theoretical approach. Collectively termed brain connectomics, these sophisticated mathematical techniques have revealed that the brain connectome, like many networks, is highly modular and brain regions can thus be organized into communities or modules. Here, using tractography-informed structural connectomes from 46 normal healthy human subjects, we constructed the hierarchical modularity of the structural connectome using bifurcating dendrograms. Moving from fine to coarse (i.e., local to global) up the connectome's hierarchy, we computed the rate of decay of a new metric that hierarchically preferentially weighs the information exchange between two nodes in the same module. By computing "embeddedness"-the ratio between nodal efficiency and this decay rate, one could thus probe the relative scale-invariant information exchange efficiency of the human brain. Results suggest that regions that exhibit high embeddedness are those that comprise the limbic system, the default mode network, and the subcortical nuclei. This supports the presence of near-decomposability overall yet relative embeddedness in select areas of the brain. The areas we identified as highly embedded are varied in function but are arguably linked in the evolutionary role they play in memory, emotion and behavior