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Biology subjects

Takacs, K.

Publications and source records attributed to Takacs, K..

4 recordsLinked to original sources

A Spatiotemporal Reconstruction of the C. elegans Pharyngeal Cuticle Reveals a Structure Rich in Phase-Separating Proteins

Roughly 4.5 million species of ecdysozoan animals repeatedly shed their old cuticle and construct a new one underneath to accommodate growth. How cuticles are constructed is not well understood. Here, we systematically mine gene expression datasets to uncover the spatiotemporal blueprint for how the chitin-based pharyngeal cuticle of the nematode Caenorhabditis elegans is built. We demonstrate that the blueprint correctly predicts expression patterns and functional relevance to cuticle development. We find that as larvae prepare to molt, catabolic enzymes are upregulated and the genes that encode chitin synthase, chitin cross-linkers, and homologs of amyloid regulators subsequently peak in expression. 48% of the gene products secreted during the molt are predicted to be intrinsically disordered proteins (IDPs), many of which belong to four distinct families that are expressed in overlapping waves. These include the IDPAs, IDPBs, and IDPCs that are introduced for the first time here. We find that all four families have sequence properties known to drive phase separation and show in vitro phase separation for one of these proteins. This systematic analysis reveals the massive contribution that IDPs make to the cuticle and highlights how reversibly phase-separating materials may facilitate cuticle disassembly and reassembly during the molt.

systems biology↗

Condition-dependent trade-offs maintain honest signaling: A laboratory experiment

How and why animals and humans signal reliably is a key issue in biology and social sciences. For many years the dominant paradigm in biology was the Handicap Principle. It claims a causal relationship between honesty and signal cost and thus predicts that honest signals have to be costly to produce. However, contrary to the Handicap Principle, game theoretical models predict that honest signaling is maintained by condition dependent signaling trade-offs and honest signals need not be costly at the equilibrium. Due to the difficulties of manipulating signal cost and signal trade-offs there is surprisingly little evidence to test these predictions either from biology or from social sciences. Here we conduct a human laboratory experiment with a two-factorial design to test the role of equilibrium signal cost vs. signalling trade-offs in the maintenance of honest communication. We have found that the trade-off condition has much higher influence on the reliability of communication than the equilibrium cost condition. The highest level of honesty was observed in the condition dependent trade-off condition as predicted by recent models. Negative production cost, i.e. fix benefit-contrary to the prediction of the Handicap Principle-promoted even higher level of honesty than the other type of costs under this condition.

evolutionary biology↗

Scarce and directly beneficial reputations support cooperation

A human solution to the problem of cooperation is the construction and maintenance of informal reputation hierarchies. Reputational information contributes to cooperation by providing guidelines about previous group-beneficial or free-rider behavior of opponents in social dilemma interactions. How reputation information could be credible, however, when outcomes of interactions are not publicly known, remains a puzzle. In this study, we propose that credibility could be ensured if reputation is a scarce resource and it is not believed to be earned for direct benefits. We tested these propositions in a laboratory experiment in which participants played two-person Prisoners Dilemma games without partner selection, could observe some other interactions and could communicate reputational information about possible prospective opponents to each other. We found that scarcity is a necessary condition for reputation scores to be informative. While cooperation has not been sustained at a high level in any of the conditions, reputational information clearly influenced cooperation decisions. The possibility of exchanging third-party information was able to increase the level of cooperation the most if reputation was a scarce resource and contrary to our expectations, when reputational scores have been directly translated into monetary benefits.

evolutionary biology↗

Tracking Subclonal Mutation Frequencies Throughout Lymphomagenesis Identifies Cancer Drivers in Mouse Models of Lymphoma.

Determining whether recurrent but rare cancer mutations are bona fide driver mutations remains a bottleneck in cancer research. Here we present the most comprehensive analysis of retrovirus driven lymphomagenesis produced to date, sequencing 700,000 mutations from >500 malignancies collected at time points throughout tumor development. This enabled identification of positively selected events, and the first demonstration of negative selection of mutations that may be deleterious to tumor development indicating novel avenues for therapy. Customized sequencing and bioinformatics methodologies were developed to quantify subclonal mutations in both premalignant and malignant tissue, greatly expanding the statistical power for identifying driver mutations and yielding a high-resolution, genome wide map of the selective forces surrounding cancer gene loci. Screening two BCL2 transgenic models confirms known drivers of human B-cell non-Hodgkin lymphoma, and implicates novel candidates including modifiers of immunosurveillance such as co-stimulatory molecules and MHC loci. Correlating mutations with genotypic and phenotypic features also gives robust identification of known cancer genes independently of local variance in mutation density. An online resource http://mulv.lms.mrc.ac.uk allows customized queries of the entire dataset.

cancer biology↗