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- ItemGenome-wide identification of regulatory elements and reconstruction of gene regulatory networks of the green alga Chlamydomonas reinhardtii under carbon deprivation(San Francisco, CA : Public Library of Science (PLoS), 2013) Winck, F.V.; Arvidsson, S.; Riaño-Pachón, D.M.; Hempe, S.; Koseska, A.; Nikoloski, Z.; Gomez, D.A.U.; Rupprecht, J.; Mueller-Roeber, B.The unicellular green alga Chlamydomonas reinhardtii is a long-established model organism for studies on photosynthesis and carbon metabolism-related physiology. Under conditions of air-level carbon dioxide concentration [CO 2], a carbon concentrating mechanism (CCM) is induced to facilitate cellular carbon uptake. CCM increases the availability of carbon dioxide at the site of cellular carbon fixation. To improve our understanding of the transcriptional control of the CCM, we employed FAIRE-seq (formaldehyde-assisted Isolation of Regulatory Elements, followed by deep sequencing) to determine nucleosome-depleted chromatin regions of algal cells subjected to carbon deprivation. Our FAIRE data recapitulated the positions of known regulatory elements in the promoter of the periplasmic carbonic anhydrase (Cah1) gene, which is upregulated during CCM induction, and revealed new candidate regulatory elements at a genome-wide scale. In addition, time series expression patterns of 130 transcription factor (TF) and transcription regulator (TR) genes were obtained for cells cultured under photoautotrophic condition and subjected to a shift from high to low [CO2]. Groups of co-expressed genes were identified and a putative directed gene-regulatory network underlying the CCM was reconstructed from the gene expression data using the recently developed IOTA (inner composition alignment) method. Among the candidate regulatory genes, two members of the MYB-related TF family, Lcr1 (Low-CO2 response regulator 1) and Lcr2 (Low-CO2 response regulator 2 ), may play an important role in down-regulating the expression of a particular set of TF and TR genes in response to low [CO2]. The results obtained provide new insights into the transcriptional control of the CCM and revealed more than 60 new candidate regulatory genes. Deep sequencing of nucleosome-depleted genomic regions indicated the presence of new, previously unknown regulatory elements in the C. reinhardtii genome. Our work can serve as a basis for future functional studies of transcriptional regulator genes and genomic regulatory elements in Chlamydomonas.
- ItemCardio-respiratory coordination increases during sleep apnea(San Francisco, CA : Public Library of Science (PLoS), 2014) Riedl, M.; Müller, A.; Kraemer, J.F.; Penzel, T.; Kurths, J.; Wessel, N.Cardiovascular diseases are the main source of morbidity and mortality in the United States with costs of more than $170 billion. Repetitive respiratory disorders during sleep are assumed to be a major cause of these diseases. Therefore, the understanding of the cardio-respiratory regulation during these events is of high public interest. One of the governing mechanisms is the mutual influence of the cardiac and respiratory oscillations on their respective onsets, the cardiorespiratory coordination (CRC). We analyze this mechanism based on nocturnal measurements of 27 males suffering from obstructive sleep apnea syndrome. Here we find, by using an advanced analysis technique, the coordigram, not only that the occurrence of CRC is significantly more frequent during respiratory sleep disturbances than in normal respiration (p-value<10-51) but also more frequent after these events (p-value<10-15). Especially, the latter finding contradicts the common assumption that spontaneous CRC can only be observed in epochs of relaxed conditions, while our newly discovered epochs of CRC after disturbances are characterized by high autonomic stress. Our findings on the connection between CRC and the appearance of sleep-disordered events require a substantial extension of the current understanding of obstructive sleep apneas and hypopneas.
- ItemNoise-Aided Logic in an Electronic Analog of Synthetic Genetic Networks(San Francisco, CA : Public Library of Science (PLoS), 2013) Hellen, E.H.; Dana, S.K.; Kurths, J.; Kehler, E.; Sinha, S.We report the experimental verification of noise-enhanced logic behaviour in an electronic analog of a synthetic genetic network, composed of two repressors and two constitutive promoters. We observe good agreement between circuit measurements and numerical prediction, with the circuit allowing for robust logic operations in an optimal window of noise. Namely, the input-output characteristics of a logic gate is reproduced faithfully under moderate noise, which is a manifestation of the phenomenon known as Logical Stochastic Resonance. The two dynamical variables in the system yield complementary logic behaviour simultaneously. The system is easily morphed from AND/NAND to OR/NOR logic.
- ItemIdentifying controlling nodes in neuronal networks in different scales(San Francisco, CA : Public Library of Science (PLoS), 2012) Tang, Y.; Gao, H.; Zou, W.; Kurths, J.Recent studies have detected hubs in neuronal networks using degree, betweenness centrality, motif and synchronization and revealed the importance of hubs in their structural and functional roles. In addition, the analysis of complex networks in different scales are widely used in physics community. This can provide detailed insights into the intrinsic properties of networks. In this study, we focus on the identification of controlling regions in cortical networks of cats' brain in microscopic, mesoscopic and macroscopic scales, based on single-objective evolutionary computation methods. The problem is investigated by considering two measures of controllability separately. The impact of the number of driver nodes on controllability is revealed and the properties of controlling nodes are shown in a statistical way. Our results show that the statistical properties of the controlling nodes display a concave or convex shape with an increase of the allowed number of controlling nodes, revealing a transition in choosing driver nodes from the areas with a large degree to the areas with a low degree. Interestingly, the community Auditory in cats' brain, which has sparse connections with other communities, plays an important role in controlling the neuronal networks.
- ItemAnalysing dynamical behavior of cellular networks via stochastic bifurcations(San Francisco, CA : Public Library of Science (PLoS), 2011) Zakharova, A.; Kurths, J.; Vadivasova, T.; Koseska, A.The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types.
- ItemAn electronic analog of synthetic genetic networks(San Francisco, CA : Public Library of Science (PLoS), 2011) Hellen, E.H.; Volkov, E.; Kurths, J.; Dana, S.K.An electronic analog of a synthetic genetic network known as the repressilator is proposed. The repressilator is a synthetic biological clock consisting of a cyclic inhibitory network of three negative regulatory genes which produces oscillations in the expressed protein concentrations. Compared to previous circuit analogs of the repressilator, the circuit here takes into account more accurately the kinetics of gene expression, inhibition, and protein degradation. A good agreement between circuit measurements and numerical prediction is observed. The circuit allows for easy control of the kinetic parameters thereby aiding investigations of large varieties of potential dynamics.
- ItemA human development framework for CO 2 reductions(San Francisco, CA : Public Library of Science (PLoS), 2011) Costa, L.; Rybski, D.; Kropp, J.P.Although developing countries are called to participate in CO 2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO 2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO 2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300 Gt of cumulative CO 2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20 % to 30 % of previously calculated CO 2 budgets limiting global warming to 2°C. These constraints and results are incorporated into a CO 2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2°C target after a particular development threshold is reached. For example, in each time step of five years, countries with an HDI of 0.85 would need to reduce their per capita emissions by approx. 17% and countries with an HDI of 0.9 by 33 %. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100 Gt of CO 2. These values are within the uncertainty range of emissions to limit global temperatures to 2°C.
- ItemTiming cellular decision making under noise via cell-cell communication(San Francisco, CA : Public Library of Science (PLoS), 2009) Koseska, A.; Zaikin, A.; Kurths, J.; GarcÃa-Ojalvo, J.Many cellular processes require decision making mechanisms, which must act reliably even in the unavoidable presence of substantial amounts of noise. However, the multistable genetic switches that underlie most decision-making processes are dominated by fluctuations that can induce random jumps between alternative cellular states. Here we show, via theoretical modeling of a population of noise-driven bistable genetic switches, that reliable timing of decision-making processes can be accomplished for large enough population sizes, as long as cells are globally coupled by chemical means. In the light of these results, we conjecture that cell proliferation, in the presence of cell-cell communication, could provide a mechanism for reliable decision making in the presence of noise, by triggering cellular transitions only when the whole cell population reaches a certain size. In other words, the summation performed by the cell population would average out the noise and reduce its detrimental impact.
- ItemEmbodied Greenhouse Gas Emissions in Diets(San Francisco, CA : Public Library of Science (PLoS), 2013) Pradhan, P.; Reusser, D.E.; Kropp, J.P.Changing food consumption patterns and associated greenhouse gas (GHG) emissions have been a matter of scientific debate for decades. The agricultural sector is one of the major GHG emitters and thus holds a large potential for climate change mitigation through optimal management and dietary changes. We assess this potential, project emissions, and investigate dietary patterns and their changes globally on a per country basis between 1961 and 2007. Sixteen representative and spatially differentiated patterns with a per capita calorie intake ranging from 1,870 to <3,400 kcal/day were derived. Detailed analyses show that low calorie diets are decreasing worldwide, while in parallel diet composition is changing as well: a discernable shift towards more balanced diets in developing countries can be observed and steps towards more meat rich diets as a typical characteristics in developed countries. Low calorie diets which are mainly observable in developing countries show a similar emission burden than moderate and high calorie diets. This can be explained by a less efficient calorie production per unit of GHG emissions in developing countries. Very high calorie diets are common in the developed world and exhibit high total per capita emissions of 3.7-6.1 kg CO2eq./day due to high carbon intensity and high intake of animal products. In case of an unbridled demographic growth and changing dietary patterns the projected emissions from agriculture will approach 20 Gt CO2eq./yr by 2050.
- ItemDigital IIR filters design using differential evolution algorithm with a controllable probabilistic population size(San Francisco, CA : Public Library of Science (PLoS), 2012) Zhu, W.; Fang, J.-A.; Tang, Y.; Zhang, W.; Du, W.Design of a digital infinite-impulse-response (IIR) filter is the process of synthesizing and implementing a recursive filter network so that a set of prescribed excitations results a set of desired responses. However, the error surface of IIR filters is usually non-linear and multi-modal. In order to find the global minimum indeed, an improved differential evolution (DE) is proposed for digital IIR filter design in this paper. The suggested algorithm is a kind of DE variants with a controllable probabilistic (CPDE) population size. It considers the convergence speed and the computational cost simultaneously by nonperiodic partial increasing or declining individuals according to fitness diversities. In addition, we discuss as well some important aspects for IIR filter design, such as the cost function value, the influence of (noise) perturbations, the convergence rate and successful percentage, the parameter measurement, etc. As to the simulation result, it shows that the presented algorithm is viable and comparable. Compared with six existing State-of-the-Art algorithms-based digital IIR filter design methods obtained by numerical experiments, CPDE is relatively more promising and competitive.