Biology subjects

Dunbar, R.

Publications and source records attributed to Dunbar, R..

6 recordsLinked to original sources

bioRxiv2024

A novel approach to digital characterisation of Tertiary Lymphoid Structures in colorectal cancer

Tertiary Lymphoid Structures (TLS) in cancer tissue are potential sites for the organisation of immune responses to cancer, and correlate positively with improved clinical outcomes for patients including in colorectal cancer (CRC). However it has proven challenging to standardise assessment of TLS due to the highly variable appearances of circumscribed domains of TLS within tissue sections. A recent three-dimensional reconstruction of TLS in CRC tissue showed that TLS are often large, multi-lobular structures, suggesting that assessing TLS across whole sections may be necessary to provide an accurate view of TLS activity in a patients tumour. In a pilot study we therefore used whole slide scans of multiplexed immunofluorescence images to characterise TLS from 22 subjects with CRC. Multiplexed staining for CD20, CD3, CD8, FoxP3 and Ki-67 enabled us to identify B-cells, CD8+ T cells, FoxP3- CD4 T-cells, and Foxp3+ CD4 T cells in all sections, and quantify both the presence of these cell subsets in lymphocytic clusters and their degree of proliferation within those clusters. In total we identified 524 lymphocytic clusters with morphology consistent with TLS. The count of TLS domains varied substantially between samples (from 4 to 100, mean 24) as did the proportion of total section area occupied by TLS (0.2%-7.8%) as well as size, morphology and cellular constituents; reflecting the intersection of the section plane with complex 3-dimensional structures. We quantified proliferation of B-cells and T-cell subsets within TLS domains across entire sections and compared to the canonical approach of counting and phenotyping individual TLS domains. The whole-slide approach proved far simpler than the canonical approach, generating digital summaries across our sample set clearly identifying patients with strikingly different levels of immune activity within their TLS. It also allowed us to demonstrate strong correlations between the proliferation of B-cells within CRC TLS and that of T-cell subsets. In summary we find that whole-section digital quantification of immune cell activity within TLS has major advantages over canonical approaches. Such whole-section approaches should accelerate research into correlations between TLS status and clinical outcomes, and ultimately enable standardised clinical tests based on automated analysis of multiplexed images.

cancer biology↗

bioRxiv2023

Optimal Social Group Size in Spotted Hyaenas (Crocuta crocuta): Insights into a Multilevel Society

The spotted hyaena lives in unusually large social groups for a carnivore. Since the infertility trap normally limits the size of social groups in mammals, it seems likely that this species has evolved some way of mitigating the stresses involved. In primates, this usually takes the form of female-female alliances, often embedded in multilevel social systems. I show (1) that the distribution of hyaena clan sizes is multimodal, with a fractal scaling close to 3 and a base unit of 12-15 individuals (3-5 reproductive females) and (2) that fertility is a trade off between the benefits of having more males in the group and the costs incurred by having more females, with 4-5 as the limit on the number of females that can live together without their reproductive rates falling below the demographic replacement rate. I present evidence that females buffer themselves against the infertility trap by forming matrilineal alliances that in turn create a multilevel structure. In this respect, hyaena resemble cercopithecine primates in using social strategies to enable animals to live in larger groups than they would otherwise be able to do.

ecology↗

bioRxiv2023

Fractal Structure of Human and Primate Social Networks Optimizes Information Flow

Primate and human social groups exhibit a fractal structure that has a very limited range of preferred layer sizes, with groups of 5, 15, 50 and (in humans) 150 and 500 predominating. This same fractal distribution is also observed in the distribution of species mean group sizes in primates. Here we demonstrate that this preferential numbering arises because of the critical nature of dynamic self-organization within complex social networks. We calculate the size dependence of the scaling properties of complex social network models and argue that this aggregate behaviour exhibits a form of collective intelligence. Direct calculation establishes that the complexity of social networks as measured by their scaling behaviour is non-monotonic, peaking globally around 150 with a secondary peak at 500 and tertiary peaks centred on 15 and 50, thereby providing a theory-based rationale for the fractal layering of primate and human social groups.

animal behavior and cognition↗

bioRxiv2022

Structural and Cognitive Solutions to Prevent Group Fragmentation in Group-Living Species

Group-living is one of the six major evolutionary transitions. However, group-living creates stresses that naturally cause group fragmentation, and hence loss of the benefits that group-living provides. How species that live in large groups counteract these forces is not well understood. I analyse comparative data on grooming networks from a large sample of primate species and show that two different social grades can be differentiated in terms of network size and structure. I show that living in large, stable groups involves a combination of increased investment in bonding behaviours (made possible by a dietary adjustment) and the evolution of neuronally expensive cognitive skills of the kind known to underpin social relationships in humans. The first allows the stresses created by these relationships to be defused; the second allows large numbers of weak relationships to be managed, creating a form of multilevel sociality based on strong versus weak ties similar to that found in human social networks.

animal behavior and cognition↗

bioRxiv2019

High-resolution 3D imaging and topological mapping of the lymph node conduit system

The conduit network is a hallmark of lymph node microanatomy, but lack of suitable imaging technology has prevented comprehensive investigation of its topology. We employed an extended-volume imaging system to capture the conduit network of an entire murine lymph node ({approx}280,000 segments). The extensive 3D images provide a comprehensive overview of the regions supplied by conduits including perivascular sleeves, and distinctive \"follicular reservoirs\" within B cell follicles, surrounding follicular dendritic cells. A 3D topology map of conduits within the T cell zone showed homogeneous branching, but conduit density was significantly higher in the superficial T cell zone compared to the deep zone, where distances between segments are sufficient for T cells to lose contact with fibroblastic reticular cells. This topological mapping of the conduit anatomy can now aid modeling of its roles in lymph node function, as we demonstrate by simulating T cell motility in the different T cell zones.

immunology↗

bioRxiv2018

Network Structure and Social Complexity in Primates

Primates use social grooming to create and maintain coalitions. Because of this, individuals focus their time on a small number of individuals, and this means that in many cases group networks are not fully connected. I use data on primate grooming networks to show that three different social grades can be differentiated in terms of network structuring. These grades seem to arise from a glass ceiling imposed on group size by limits on the time available for social grooming. It seems that certain genera have managed to circumvent this constraint by a phase shift in the behavioural and cognitive mechanisms that underpin social relationships in a way that allows a form of multilevel sociality based on weak and strong ties not unlike those found in human social networks.

animal behavior and cognition↗