The evolution of intermediate castration virulence and ant coexistence in a spatially structured environment

Theory suggests that spatial structuring should select for intermediate levels of virulence in parasites, but empirical tests are rare and have never been conducted with castration (sterilizing) parasites. To test this theory in a natural landscape, we construct a spatially explicit model of the symbiosis between the ant-plant Cordia nodosa and its two, protecting ant symbionts, Allomerus and Azteca . Allomerus is also a castration parasite, preventing fruiting to increase colony fecundity. Limiting the dispersal of Allomerus and host plant selects for intermediate castration virulence. Increasing the frequency of the mutualist, Azteca , selects for higher castration virulence in Allomerus , because seeds from Azteca -inhabited plants are a public good that Allomerus exploits. These results are consistent with field observations and, to our knowledge, provide the first empirical evidence supporting the hypothesis that spatial structure can reduce castration virulence and the first such evidence in a natural landscape for either mortality or castration virulence.     

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point “snapshot” of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes—cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)—as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods.     

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time ±4 cm pan-and-tilt action. Robot-driven ±60° pivots of an integrated ±185° rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[¹⁸F] fluoro-2-deoxy-ᴅ-glucose (¹⁸F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less¹. In this article, we describe new radiation plans for the treatment of moving lung tumors.     

Organization of Enzyme Concentration across the Metabolic Network in Cancer Cells

Rapid advances in mass spectrometry have allowed for estimates of absolute concentrations across entire proteomes, permitting the interrogation of many important biological questions. Here, we focus on a quantitative aspect of human cancer cell metabolism that has been limited by a paucity of available data on the abundance of metabolic enzymes. We integrate data from recent measurements of absolute protein concentration to analyze the statistics of protein abundance across the human metabolic network. At a global level, we find that the enzymes in glycolysis comprise approximately half of the total amount of metabolic proteins and can constitute up to 10% of the entire proteome. We then use this analysis to investigate several outstanding problems in cancer metabolism, including the diversion of glycolytic flux for biosynthesis, the relative contribution of nitrogen assimilating pathways, and the origin of cellular redox potential. We find many consistencies with current models, identify several inconsistencies, and find generalities that extend beyond current understanding. Together our results demonstrate that a relatively simple analysis of the abundance of metabolic enzymes was able to reveal many insights into the organization of the human cancer cell metabolic network.     

A Psychological Exploration of Engagement in Geek Culture

Geek culture is a subculture of enthusiasts that is traditionally associated with obscure media (Japanese animation, science fiction, video games, etc.). However, geek culture is becoming increasingly mainstream; for example, in the past year alone, Dragon*Con, a major Geek convention in Atlanta, Georgia, attracted an attendance of over 57,000 members. The present article uses an individual differences approach to examine three theoretical accounts of geek culture. Seven studies (N = 2354) develop the Geek Culture Engagement Scale (GCES) to quantify geek engagement and assess its relationships to theoretically relevant personality and individual differences variables. These studies present evidence that individuals may engage in geek culture in order to maintain narcissistic self-views (the great fantasy migration hypothesis), to fulfill belongingness needs (the belongingness hypothesis), and to satisfy needs for creative expression (the need for engagement hypothesis). Geek engagement is found to be associated with elevated grandiose narcissism, extraversion, openness to experience, depression, and subjective well-being across multiple samples. These data lay the groundwork for further exploration of geek culture as well as provide a foundation for examining other forms of subculture participation.     

Imaging in five dimensions: time-dependent membrane potentials in individual mitochondria.

Because of its importance in the chemiosmotic theory, mitochondrial membrane potential has been the object of many investigations. Significantly, however, quantitative data on how energy transduction might be regulated or perturbed by the physiological state of the cell has only been gathered via indirect studies on isolated mitochondrial suspensions; quantitative studies on individual mitochondria in situ have not been possible because of their small size, their intrinsic motility, and the absence of appropriate analytical reagents. In this article, we combine techniques for rapid, high resolution, quantitative three-dimensional imaging microscopy and mathematical modeling to determine accurate distributions of a potentiometric fluorescent probe between the cytosol and individual mitochondria inside a living cell. Analysis of this distribution via the Nernst equation permits assignment of potentials to each of the imaged mitochondrial membranes. The mitochondrial membrane potentials are distributed over a narrow range centered at -150 mV within the neurites of differentiated neuroblastoma cells. We find that the membrane potential of a single mitochondrion is generally remarkably stable over times of 40-80 s, but significant fluctuations can occasionally be seen. The motility of individual mitochondria is not directly correlated to membrane potential, but mitochondria do become immobile after prolonged treatment with respiratory inhibitors or uncouplers. Thus, three spatial dimensions, a key physiological parameter, and their changes over time are all quantitated for objects at the resolution limit of light microscopy. The methods described may be readily extended to permit investigations of how mitochondrial function is integrated with other processes in the intact cell.