How mutation accumulation depends on the structure of the cell lineage tree.

All the cells of a multicellular organism are the product of cell divisions that trace out a single binary tree, the so-called cell lineage tree. Because cell divisions are accompanied by replication errors, the shape of the cell lineage tree is a key determinant of how somatic evolution, which can potentially lead to cancer, proceeds. Carcinogenesis requires the accumulation of a certain number of driver mutations. By mapping the accumulation of mutations into a graph theoretical problem, we present an exact numerical method to calculate the probability of collecting a given number of mutations and show that for low mutation rates it can be approximated with a simple analytical formula, which depends only on the distribution of the lineage lengths, and is dominated by the longest lineages. Our results are crucial in understanding how natural selection can shape the cell lineage trees of multicellular organisms and curtail somatic evolution.

Trade-off between reducing mutational accumulation and increasing commitment to differentiation determines tissue organization.

Species-specific differences control cancer risk across orders of magnitude variation in body size and lifespan, e.g., by varying the copy numbers of tumor suppressor genes. It is unclear, however, how different tissues within an organism can control somatic evolution despite being subject to markedly different constraints, but sharing the same genome. Hierarchical differentiation, characteristic of self-renewing tissues, can restrain somatic evolution both by limiting divisional load, thereby reducing mutation accumulation, and by increasing cells' commitment to differentiation, which can "wash out" mutants. Here, we explore the organization of hierarchical tissues that have evolved to limit their lifetime incidence of cancer. Estimating the likelihood of cancer in the presence of mutations that enhance self-proliferation, we demonstrate that a trade-off exists between mutation accumulation and the strength of washing out. Our results explain differences in the organization of widely different hierarchical tissues, such as colon and blood.

Editorial board interlocking across the social sciences: Modelling the geographic, gender, and institutional representation within and between six academic fields.

Editorial boards play a key role in the production, dissemination, and promotion of scientific knowledge. The cross-presence of scholars in different journals, known as editorial board interlocking, maps the connections between such bodies of governance. Former research on this topic is typically restricted to individual disciplines and has failed to consider the relevance of potential interlocking between related, but different academic fields. Further, although existing studies note a significant lack of diversity in editorial board representation, they mainly focus on a single dimension, such as gender or geography. This study addressed these knowledge gaps by offering a complex cross-disciplinary approach to the geographical, gender, and institutional compositions of editorial boards, with a specific emphasis on within- and between-fields editorial board interlocking. We used graph and social network analysis to examine editorial board connections between 281 top journals (13,084 members and 17,092 connections) of six disciplines: communication, psychology, political science, sociology, economics, and management. We found substantial differences in terms of field connections, ranging from sociology with 42% interlocking with other fields, to management with only 11%. Psychology is significantly less connected to the other five disciplines. The results also show a clear overrepresentation of American institutions and native English-speaking countries in all fields, with Harvard, Columbia, Cornell, Stanford, UC Berkeley, and New York University forming a well-connected central cluster. Although female scholars are underrepresented, there are no significant differences in terms of positioning in the network. Female scholars are even employed in more central positions than male scholars in psychology, sociology, and management. Our findings extend the literature on editorial board diversity by evidencing a significant imbalance in their gender, geographical, institutional representation, and interlocking editorship both within and between fields.

Behavioral and molecular markers of death in Drosophila melanogaster.

Fly movement was tracked through 3-dimensional (3D) space as the fly died, using either reflected visible light, reflected infrared (IR) light, or fly GFP fluorescence. Behaviors measured included centrophobism, negative geotaxis, velocity, and total activity. In addition, frequency of directional heading changes (FDHC) was calculated as a measure of erratic movement. Nine middle-aged flies were tracked as they died during normal aging, and fifteen young flies were tracked as they died from dehydration/starvation stress. Episodes of increased FDHC were observed 0-8 h prior to death for the majority of the flies. FDHC was also increased with age in flies with neuronal expression of a human Abeta42 protein fragment associated with Alzheimer's disease. Finally, green autofluorescence appeared in the eye and body immediately prior to and coincident with death, and fluorescence of GFP targeted to the retina increased immediately prior to and coincident with death. The results suggest the potential utility of FDHC, green autofluorescence, and retinal GFP as markers of neuronal malfunction and imminent death.