Biology subjects

Birch, G.

Publications and source records attributed to Birch, G..

3 recordsLinked to original sources

bioRxiv2024

Strategic use of male alternative reproductive tactics in cooperatively breeding banded mongoose groups

Alternative reproductive tactics (ARTs) allow smaller or less competitive individuals to reproduce by avoiding direct fights through sneaky strategies. Within cooperatively breeding groups ARTs are rarely reported, potentially due to difficulties observing male reproductive behaviour in the wild, or reproductive suppression by fellow group members. In societies where all mating opportunities cannot be monopolised by one male, young males could use sneaky tactics as a stepping-stone to gain limited reproductive success while they grow in resource holding potential (RHP). Using 20 years of pedigree, weight, group demography, and behavioural data, we investigated the use of sneaky pesterer ARTs in wild banded mongooses. Instead of a stepping stone, pestering tactics were typically a rare back-up used by males displaced from mate guarding tactics by higher RHP rivals. Additionally, pesterers have lower siring success compared to mate guards, despite similar weight loss costs, which may explain why most males settle for reproductive inactivity rather than use pestering tactics. However, pestering allows younger males to gain access to older, higher fecundity females in the group and may even facilitate inbreeding avoidance. Overall, ARTs provide a viable option for reproductive fitness for some males that lose out on reproductive positions in highly male-skewed groups.

animal behavior and cognition↗

bioRxiv2024

Reproductive restraint to avoid the costs of reproductive conflict in a cooperatively breeding mammal

The costs of reproductive conflict can be an important factor shaping the evolution of life histories in animal societies. These costs may change as individuals age and grow, and with within-group competition. Social costs of reproductive conflict have been invoked to explain why females might gain from delaying maturity or ceasing reproduction midway through life, but not in males. Here we analyze more than 20 years of data to understand how individual male banded mongooses adjust their reproductive activity in response to the costs of reproductive conflict. In banded mongooses groups multiple female breeders enter oestrus synchronously and males compete to mate guard the females. The oldest and heaviest males in the group gained the greatest share of paternity, while younger and lighter males obtained little or no paternity. Those lighter males that are reproductively active paid disproportionate survival costs. Our results suggest that by delaying or suppressing reproduction early in life, males may reduce their mortality. Males may also avoid inflicting costs on their male kin by queuing. These results from an egalitarian cooperative breeding mammal may provide a rare example of voluntary reproductive restraint, although we cannot discount reproductive suppression by rival males.

animal behavior and cognition↗

bioRxiv2023

Preventing NK cell activation in the damaged liver induced by cabozantinib/PD-1 blockade increases survival in hepatocellular carcinoma models

Combining multikinase inhibitors with immune checkpoint blockade improves tumor control in hepatocellular carcinoma (HCC), but survival benefits remain inconsistent. To define this discordance, we integrated COSMIC-312 with orthotopic and autochthonous murine HCC models with or without liver fibrosis. In patients treated with cabozantinib plus atezolizumab, baseline liver function stratified overall survival but not progression-free survival, indicating uncoupling of tumor control from survival. In contrast, sorafenib outcomes tracked with both endpoints, supporting a treatment-specific effect rather than a purely prognostic effect of liver status. In murine HCC models, cabozantinib plus PD-1 blockade induced comparable tumor regression regardless of liver condition, but improved survival only in mice with preserved liver function, whereas fibrotic hosts developed hepatotoxicity. Immune profiling revealed compartment-specific remodeling, with enhanced cytotoxic T-cell programs in tumors but expansion of NK-lineage innate lymphocytes with ILC1-like features in fibrotic liver. Depletion of NK1.1-positive cells reduced liver injury and restored survival without compromising antitumor efficacy, whereas CD4-positive or CD8-positive T-cell depletion did not protect from hepatotoxicity. Transcriptomic, single-cell, adoptive-transfer, and human in vitro studies supported a model in which the fibrotic liver niche promotes NK-to-ILC1-like reprogramming, hepatocyte stress signaling, and TNF/TRAIL-associated epithelial injury. Consistently, cabozantinib and nivolumab showed liver-predominant remodeling of CD56-positive innate lymphocyte-enriched populations in human HCC samples, and ex vivo TGF-beta induced ILC1-like phenotypic changes in human NK cells. These findings identify liver fibrosis as a host determinant that can limit the survival benefit of multikinase inhibitor immunotherapy by promoting innate immune-mediated hepatotoxicity despite preserved tumor control in HCC. One Sentence SummaryLiver fibrosis limits the survival benefit of multikinase inhibitor immunotherapy in hepatocellular carcinoma by promoting innate immune-mediated hepatotoxicity despite preserved tumor control.

cancer biology↗