Quantitative analyses of T cell motion in tissue reveals factors driving T cell search in tissues.

T cells are required to clear infection, and T cell motion plays a role in how quickly a T cell finds its target, from initial naive T cell activation by a dendritic cell to interaction with target cells in infected tissue. To better understand how different tissue environments affect T cell motility, we compared multiple features of T cell motion including speed, persistence, turning angle, directionality, and confinement of T cells moving in multiple murine tissues using microscopy. We quantitatively analyzed naive T cell motility within the lymph node and compared motility parameters with activated CD8 T cells moving within the villi of small intestine and lung under different activation conditions.

Agent-based modeling predicts RAC1 is critical for ovarian cancer metastasis.

Experimental and computational studies pinpoint rate-limiting step(s) in metastasis governed by Rac1. Using ovarian cancer cell and animal models, Rac1 expression was manipulated, and quantitative measurements of cell-cell and cell-substrate adhesion, cell invasion, mesothelial clearance, and peritoneal tumor growth discriminated the tumor behaviors most highly influenced by Rac1. The experimental data were used to parameterize an agent-based computational model simulating peritoneal niche colonization, intravasation, and hematogenous metastasis to distant organs.

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection.

A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads.

Distributed Adaptive Search in T Cells: Lessons From Ants.

There are striking similarities between the strategies ant colonies use to forage for food and immune systems use to search for pathogens. Searchers (ants and cells) use the appropriate combination of random and directed motion, direct and indirect agent-agent interactions, and traversal of physical structures to solve search problems in a variety of environments. An effective immune response requires immune cells to search efficiently and effectively for diverse types of pathogens in different tissues and organs, just as different species of ants have evolved diverse search strategies to forage effectively for a variety of resources in a variety of habitats.

How does mobility help distributed systems compute?

Brains are composed of connected neurons that compute by transmitting signals. The neurons are generally fixed in space, but the communication patterns that enable information processing change rapidly. By contrast, other biological systems, such as ant colonies, bacterial colonies, slime moulds and immune systems, process information using agents that communicate locally while moving through physical space.

Quantitative Measurement of Naïve T Cell Association With Dendritic Cells, FRCs, and Blood Vessels in Lymph Nodes.

T cells play a vital role in eliminating pathogenic infections. To activate, naïve T cells search lymph nodes (LNs) for dendritic cells (DCs). Positioning and movement of T cells in LNs is influenced by chemokines including CCL21 as well as multiple cell types and structures in the LNs.

ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs.

Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood. Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue.

Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search.

Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated.

Spatial Modeling of Drug Delivery Routes for Treatment of Disseminated Ovarian Cancer.

In ovarian cancer, metastasis is typically confined to the peritoneum. Surgical removal of the primary tumor and macroscopic secondary tumors is a common practice, but more effective strategies are needed to target microscopic spheroids persisting in the peritoneal fluid after debulking surgery. To treat this residual disease, therapeutic agents can be administered by either intravenous or intraperitoneal infusion.

Bringing statistics up to speed with data in analysis of lymphocyte motility.

Two-photon (2P) microscopy provides immunologists with 3D video of the movement of lymphocytes in vivo. Motility parameters extracted from these videos allow detailed analysis of lymphocyte motility in lymph nodes and peripheral tissues. However, standard parametric statistical analyses such as the Student's t-test are often used incorrectly, and fail to take into account confounds introduced by the experimental methods, potentially leading to erroneous conclusions about T cell motility.

PKCθ regulates T cell motility via ezrin-radixin-moesin localization to the uropod.

Cell motility is a fundamental process crucial for function in many cell types, including T cells. T cell motility is critical for T cell-mediated immune responses, including initiation, activation, and effector function. While many extracellular receptors and cytoskeletal regulators have been shown to control T cell migration, relatively few signaling mediators have been identified that can modulate T cell motility.

Fast and flexible: argentine ants recruit from nearby trails.

Argentine ants (Linepithema humile) live in groups of nests connected by trails to each other and to stable food sources. In a field study, we investigated whether some ants recruit directly from established, persistent trails to food sources, thus accelerating food collection. Our results indicate that Argentine ants recruit nestmates to food directly from persistent trails, and that the exponential increase in the arrival rate of ants at baits is faster than would be possible if recruited ants traveled from distant nests.

Quantifying the effect of colony size and food distribution on harvester ant foraging.

Desert seed-harvester ants, genus Pogonomyrmex, are central place foragers that search for resources collectively. We quantify how seed harvesters exploit the spatial distribution of seeds to improve their rate of seed collection. We find that foraging rates are significantly influenced by the clumpiness of experimental seed baits.

A general model for effects of temperature on ectotherm ontogenetic growth and development.

The temperature size rule (TSR) is the tendency for ectotherms to develop faster but mature at smaller body sizes at higher temperatures. It can be explained by a simple model in which the rate of growth or biomass accumulation and the rate of development have different temperature dependence. The model accounts for both TSR and the less frequently observed reverse-TSR, predicts the fraction of energy allocated to maintenance and synthesis over the course of development, and also predicts that less total energy is expended when developing at warmer temperatures for TSR and vice versa for reverse-TSR.

A general basis for quarter-power scaling in animals.

It has been known for decades that the metabolic rate of animals scales with body mass with an exponent that is almost always <1, >2/3, and often very close to 3/4. The 3/4 exponent emerges naturally from two models of resource distribution networks, radial explosion and hierarchically branched, which incorporate a minimum of specific details. Both models show that the exponent is 2/3 if velocity of flow remains constant, but can attain a maximum value of 3/4 if velocity scales with its maximum exponent, 1/12.

Shifts in metabolic scaling, production, and efficiency across major evolutionary transitions of life.

The diversification of life involved enormous increases in size and complexity. The evolutionary transitions from prokaryotes to unicellular eukaryotes to metazoans were accompanied by major innovations in metabolic design. Here we show that the scalings of metabolic rate, population growth rate, and production efficiency with body size have changed across the evolutionary transitions.

Population stability, cooperation, and the invasibility of the human species.

The biogeographic expansion of modern humans out of Africa began approximately 50,000 years ago. This expansion resulted in the colonization of most of the land area and habitats throughout the globe and in the replacement of preexisting hominid species. However, such rapid population growth and geographic spread is somewhat unexpected for a large primate with a slow, density-dependent life history.

Energy uptake and allocation during ontogeny.

All organisms face the problem of how to fuel ontogenetic growth. We present a model, empirically grounded in data from birds and mammals, that correctly predicts how growing animals allocate food energy between synthesis of new biomass and maintenance of existing biomass. Previous energy budget models have typically had their bases in rates of either food consumption or metabolic energy expenditure.

Scaling theory for information networks.

Networks distribute energy, materials and information to the components of a variety of natural and human-engineered systems, including organisms, brains, the Internet and microprocessors. Distribution networks enable the integrated and coordinated functioning of these systems, and they also constrain their design. The similar hierarchical branching networks observed in organisms and microprocessors are striking, given that the structure of organisms has evolved via natural selection, while microprocessors are designed by engineers.

Revisiting a model of ontogenetic growth: estimating model parameters from theory and data.

The ontogenetic growth model (OGM) of West et al. provides a general description of how metabolic energy is allocated between production of new biomass and maintenance of existing biomass during ontogeny. Here, we reexamine the OGM, make some minor modifications and corrections, and further evaluate its ability to account for empirical variation on rates of metabolism and biomass in vertebrates both during ontogeny and across species of varying adult body size.

The allometry of host-pathogen interactions.

Background: Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.

Global patterns of city size distributions and their fundamental drivers.

Urban areas and their voracious appetites are increasingly dominating the flows of energy and materials around the globe. Understanding the size distribution and dynamics of urban areas is vital if we are to manage their growth and mitigate their negative impacts on global ecosystems. For over 50 years, city size distributions have been assumed to universally follow a power function, and many theories have been put forth to explain what has become known as Zipf's law (the instance where the exponent of the power function equals unity).

Comment on "The illusion of invariant quantities in life histories".

Nee et al. (Reports, 19 August 2005, p. 1236) used a null model to argue that life history invariants are illusions.