@article{2004, abstract = {We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.}, author = {Lovrics, Anna and Gao, Yu and Juhász, Bianka and Bock, István and Byrne, Helen and Dinnyés, András and Kovács, Krisztián}, journal = {PLoS One}, number = {11}, publisher = {Public Library of Science}, title = {{Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord}}, doi = {10.1371/journal.pone.0111430}, volume = {9}, year = {2014}, } @misc{9722, author = {Lovrics, Anna and Gao, Yu and Juhász, Bianka and Bock, István and Byrne, Helen M. and Dinnyés, András and Kovács, Krisztián}, publisher = {Public Library of Science}, title = {{Transition probability between TF expression states when Dbx2 inhibits Nkx2.2}}, doi = {10.1371/journal.pone.0111430.s006}, year = {2014}, } @article{2039, abstract = {A fundamental question in biology is the following: what is the time scale that is needed for evolutionary innovations? There are many results that characterize single steps in terms of the fixation time of new mutants arising in populations of certain size and structure. But here we ask a different question, which is concerned with the much longer time scale of evolutionary trajectories: how long does it take for a population exploring a fitness landscape to find target sequences that encode new biological functions? Our key variable is the length, (Formula presented.) of the genetic sequence that undergoes adaptation. In computer science there is a crucial distinction between problems that require algorithms which take polynomial or exponential time. The latter are considered to be intractable. Here we develop a theoretical approach that allows us to estimate the time of evolution as function of (Formula presented.) We show that adaptation on many fitness landscapes takes time that is exponential in (Formula presented.) even if there are broad selection gradients and many targets uniformly distributed in sequence space. These negative results lead us to search for specific mechanisms that allow evolution to work on polynomial time scales. We study a regeneration process and show that it enables evolution to work in polynomial time.}, author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Adlam, Ben and Nowak, Martin}, journal = {PLoS Computational Biology}, number = {9}, publisher = {Public Library of Science}, title = {{The time scale of evolutionary innovation}}, doi = {10.1371/journal.pcbi.1003818}, volume = {10}, year = {2014}, } @article{2161, abstract = {Repeated pathogen exposure is a common threat in colonies of social insects, posing selection pressures on colony members to respond with improved disease-defense performance. We here tested whether experience gained by repeated tending of low-level fungus-exposed (Metarhizium robertsii) larvae may alter the performance of sanitary brood care in the clonal ant, Platythyrea punctata. We trained ants individually over nine consecutive trials to either sham-treated or fungus-exposed larvae. We then compared the larval grooming behavior of naive and trained ants and measured how effectively they removed infectious fungal conidiospores from the fungus-exposed larvae. We found that the ants changed the duration of larval grooming in response to both, larval treatment and their level of experience: (1) sham-treated larvae received longer grooming than the fungus-exposed larvae and (2) trained ants performed less self-grooming but longer larval grooming than naive ants, which was true for both, ants trained to fungus-exposed and also to sham-treated larvae. Ants that groomed the fungus-exposed larvae for longer periods removed a higher number of fungal conidiospores from the surface of the fungus-exposed larvae. As experienced ants performed longer larval grooming, they were more effective in fungal removal, thus making them better caretakers under pathogen attack of the colony. By studying this clonal ant, we can thus conclude that even in the absence of genetic variation between colony members, differences in experience levels of brood care may affect performance of sanitary brood care in social insects.}, author = {Westhus, Claudia and Ugelvig, Line V and Tourdot, Edouard and Heinze, Jürgen and Doums, Claudie and Cremer, Sylvia}, issn = {0340-5443}, journal = {Behavioral Ecology and Sociobiology}, number = {10}, pages = {1701 -- 1710}, publisher = {Springer}, title = {{Increased grooming after repeated brood care provides sanitary benefits in a clonal ant}}, doi = {10.1007/s00265-014-1778-8}, volume = {68}, year = {2014}, } @article{2036, abstract = { In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. }, author = {Lagator, Mato and Colegrave, Nick and Neve, Paul}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1794}, publisher = {Royal Society, The}, title = {{Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses}}, doi = {10.1098/rspb.2014.1679}, volume = {281}, year = {2014}, }