Perturbations highlight importance of social history in parakeet rank dynamics

Dominance hierarchies can provide many benefits to individuals, such as access to resources or mates, depending on their ranks. In some species, rank can emerge as a product of a group’s history of social interactions. However, it can be difficult to determine whether social history is critical to rank in observation-based studies. Here, we investigated rank dynamics in three captive groups of monk parakeets (Myiopsitta monachus). We used experimental social perturbations to test whether social history shapes rank emergence in these groups. Using targeted removals and reintroductions, we tested whether differently ranked individuals could re-take their ranks in hierarchies after reintroduction following their removal period from the group. We performed perturbations that consisted of an 8-day removal and an 8-day reintroduction period of 15 differently ranked focal birds. We found that no focal birds could regain their previous rank immediately following reintroduction and that the top-ranked birds showed greater relative rank loss than middle/low-ranked birds. We also found that morphology, specifically bodyweight, was unassociated with rank. Combined with previous results, this experiment supports the hypothesis that rank in monk parakeet dominance hierarchies is more likely to be an emergent outcome of past interactions and memory rather than based on individual characteristics. Gaining a better understanding of how individuals achieve and maintain rank can give insight into the role of cognition on rank acquisition, as rank position can have significant biological effects on individuals in hierarchically structured groups

Energy Metabolism, Metabolite, and Inflammatory Profiles in Human Ex Vivo Adipose Tissue Are Influenced by Obesity Status, Metabolic Dysfunction, and Treatment Regimes in Patients with Oesophageal Adenocarcinoma

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients (n = 32). Compared to visceral fat from non-obese patients (n = 16), visceral fat explants from obese OAC patients (n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy (n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-β and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes

Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on “toxin sponge” proteins

Many poisonous organisms carry small-molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui poison birds and Phyllobates poison frogs stands out because of its lethality and unusual effects on NaV function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NaV DIVS6 pore-forming helix N-to-T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog NaVs, incurs a strong cost compromising channel function, and fails to produce BTX-resistant channels in poison frog NaVs. We also show that captivity-raised poison frogs are resistant to two NaV-directed toxins, BTX and saxitoxin (STX), even though they bear NaVs sensitive to both. Moreover, we demonstrate that the amphibian STX “toxin sponge” protein saxiphilin is able to protect and rescue NaVs from block by STX. Taken together, our data contradict the hypothesis that BTX autoresistance is rooted in the DIVS6 N→T mutation, challenge the idea that ion channel mutations are a primary driver of toxin resistance, and suggest the possibility that toxin sequestration mechanisms may be key for protecting poisonous species from the action of small-molecule toxins

COVID-19 Patient Vaccine Program Design and Implementation: An Academic Children\u27s Hospital\u27s Model, Approach, and Outcomes

To slow the spread of the 2019 novel coronavirus disease (COVID-19) and reduce the associated morbidity and mortality, the Children\u27s National Hospital developed a multidisciplinary, collaborative vaccine program aimed at equitably and expeditiously vaccinating the pediatric population of the surrounding community. Interdepartmental collaboration, professional expertise, and community partnerships allowed for a dynamic and successful program design that began as large volume-centralized vaccine clinics and expanded to smaller volume ambulatory clinics. This strategy proved successful at meeting local vaccine demand; however, strategies to improve vaccine uptake in communities with high rates of hesitancy are still needed to maximize vaccine equity