@article{9917, abstract = {Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasizes that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.}, author = {Westram, Anja M and Rafajlović, Marina and Chaube, Pragya and Faria, Rui and Larsson, Tomas and Panova, Marina and Ravinet, Mark and Blomberg, Anders and Mehlig, Bernhard and Johannesson, Kerstin and Butlin, Roger}, issn = {2056-3744}, journal = {Evolution Letters}, number = {4}, pages = {297--309}, publisher = {Wiley}, title = {{Clines on the seashore: The genomic architecture underlying rapid divergence in the face of gene flow}}, doi = {10.1002/evl3.74}, volume = {2}, year = {2018}, } @misc{9929, abstract = {The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favour reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence.}, author = {Hollander, Johan and Montaño-Rendón, Mauricio and Bianco, Giuseppe and Yang, Xi and Westram, Anja M and Duvaux, Ludovic and Reid, David G. and Butlin, Roger K.}, publisher = {Dryad}, title = {{Data from: Are assortative mating and genital divergence driven by reinforcement?}}, doi = {10.5061/dryad.51sd2p5}, year = {2018}, } @misc{9930, abstract = {Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g. outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e. focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally-suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasises that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.}, author = {Westram, Anja M and Rafajlović, Marina and Chaube, Pragya and Faria, Rui and Larsson, Tomas and Panova, Marina and Ravinet, Mark and Blomberg, Anders and Mehlig, Bernhard and Johannesson, Kerstin and Butlin, Roger}, publisher = {Dryad}, title = {{Data from: Clines on the seashore: the genomic architecture underlying rapid divergence in the face of gene flow}}, doi = {10.5061/dryad.bp25b65}, year = {2018}, } @inproceedings{34, abstract = {Partially observable Markov decision processes (POMDPs) are widely used in probabilistic planning problems in which an agent interacts with an environment using noisy and imprecise sensors. We study a setting in which the sensors are only partially defined and the goal is to synthesize “weakest” additional sensors, such that in the resulting POMDP, there is a small-memory policy for the agent that almost-surely (with probability 1) satisfies a reachability objective. We show that the problem is NP-complete, and present a symbolic algorithm by encoding the problem into SAT instances. We illustrate trade-offs between the amount of memory of the policy and the number of additional sensors on a simple example. We have implemented our approach and consider three classical POMDP examples from the literature, and show that in all the examples the number of sensors can be significantly decreased (as compared to the existing solutions in the literature) without increasing the complexity of the policies.}, author = {Chatterjee, Krishnendu and Chemlík, Martin and Topcu, Ufuk}, location = {Delft, Netherlands}, pages = {47 -- 55}, publisher = {AAAI Press}, title = {{Sensor synthesis for POMDPs with reachability objectives}}, volume = {2018}, year = {2018}, } @inproceedings{35, abstract = {We consider planning problems for graphs, Markov decision processes (MDPs), and games on graphs. While graphs represent the most basic planning model, MDPs represent interaction with nature and games on graphs represent interaction with an adversarial environment. We consider two planning problems where there are k different target sets, and the problems are as follows: (a) the coverage problem asks whether there is a plan for each individual target set; and (b) the sequential target reachability problem asks whether the targets can be reached in sequence. For the coverage problem, we present a linear-time algorithm for graphs, and quadratic conditional lower bound for MDPs and games on graphs. For the sequential target problem, we present a linear-time algorithm for graphs, a sub-quadratic algorithm for MDPs, and a quadratic conditional lower bound for games on graphs. Our results with conditional lower bounds establish (i) model-separation results showing that for the coverage problem MDPs and games on graphs are harder than graphs and for the sequential reachability problem games on graphs are harder than MDPs and graphs; and (ii) objective-separation results showing that for MDPs the coverage problem is harder than the sequential target problem.}, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Svozil, Alexander}, booktitle = {28th International Conference on Automated Planning and Scheduling }, location = {Delft, Netherlands}, publisher = {AAAI Press}, title = {{Algorithms and conditional lower bounds for planning problems}}, year = {2018}, } @article{36, abstract = {Wheat (Triticum ssp.) is one of the most important human food sources. However, this crop is very sensitive to temperature changes. Specifically, processes during wheat leaf, flower, and seed development and photosynthesis, which all contribute to the yield of this crop, are affected by high temperature. While this has to some extent been investigated on physiological, developmental, and molecular levels, very little is known about early signalling events associated with an increase in temperature. Phosphorylation-mediated signalling mechanisms, which are quick and dynamic, are associated with plant growth and development, also under abiotic stress conditions. Therefore, we probed the impact of a short-term and mild increase in temperature on the wheat leaf and spikelet phosphoproteome. In total, 3822 (containing 5178 phosphosites) and 5581 phosphopeptides (containing 7023 phosphosites) were identified in leaf and spikelet samples, respectively. Following statistical analysis, the resulting data set provides the scientific community with a first large-scale plant phosphoproteome under the control of higher ambient temperature. This community resource on the high temperature-mediated wheat phosphoproteome will be valuable for future studies. Our analyses also revealed a core set of common proteins between leaf and spikelet, suggesting some level of conserved regulatory mechanisms. Furthermore, we observed temperature-regulated interconversion of phosphoforms, which probably impacts protein activity.}, author = {Vu, Lam and Zhu, Tingting and Verstraeten, Inge and Van De Cotte, Brigitte and Gevaert, Kris and De Smet, Ive}, journal = {Journal of Experimental Botany}, number = {19}, pages = {4609 -- 4624}, publisher = {Oxford University Press}, title = {{Temperature-induced changes in the wheat phosphoproteome reveal temperature-regulated interconversion of phosphoforms}}, doi = {10.1093/jxb/ery204}, volume = {69}, year = {2018}, } @inbook{37, abstract = {Developmental processes are inherently dynamic and understanding them requires quantitative measurements of gene and protein expression levels in space and time. While live imaging is a powerful approach for obtaining such data, it is still a challenge to apply it over long periods of time to large tissues, such as the embryonic spinal cord in mouse and chick. Nevertheless, dynamics of gene expression and signaling activity patterns in this organ can be studied by collecting tissue sections at different developmental stages. In combination with immunohistochemistry, this allows for measuring the levels of multiple developmental regulators in a quantitative manner with high spatiotemporal resolution. The mean protein expression levels over time, as well as embryo-to-embryo variability can be analyzed. A key aspect of the approach is the ability to compare protein levels across different samples. This requires a number of considerations in sample preparation, imaging and data analysis. Here we present a protocol for obtaining time course data of dorsoventral expression patterns from mouse and chick neural tube in the first 3 days of neural tube development. The described workflow starts from embryo dissection and ends with a processed dataset. Software scripts for data analysis are included. The protocol is adaptable and instructions that allow the user to modify different steps are provided. Thus, the procedure can be altered for analysis of time-lapse images and applied to systems other than the neural tube.}, author = {Zagórski, Marcin P and Kicheva, Anna}, booktitle = {Morphogen Gradients }, isbn = {978-1-4939-8771-9}, issn = {1064-3745}, pages = {47 -- 63}, publisher = {Springer Nature}, title = {{Measuring dorsoventral pattern and morphogen signaling profiles in the growing neural tube}}, doi = {10.1007/978-1-4939-8772-6_4}, volume = {1863}, year = {2018}, } @article{38, abstract = {Genomes of closely-related species or populations often display localized regions of enhanced relative sequence divergence, termed genomic islands. It has been proposed that these islands arise through selective sweeps and/or barriers to gene flow. Here, we genetically dissect a genomic island that controls flower color pattern differences between two subspecies of Antirrhinum majus, A.m.striatum and A.m.pseudomajus, and relate it to clinal variation across a natural hybrid zone. We show that selective sweeps likely raised relative divergence at two tightly-linked MYB-like transcription factors, leading to distinct flower patterns in the two subspecies. The two patterns provide alternate floral guides and create a strong barrier to gene flow where populations come into contact. This barrier affects the selected flower color genes and tightlylinked loci, but does not extend outside of this domain, allowing gene flow to lower relative divergence for the rest of the chromosome. Thus, both selective sweeps and barriers to gene flow play a role in shaping genomic islands: sweeps cause elevation in relative divergence, while heterogeneous gene flow flattens the surrounding "sea," making the island of divergence stand out. By showing how selective sweeps establish alternative adaptive phenotypes that lead to barriers to gene flow, our study sheds light on possible mechanisms leading to reproductive isolation and speciation.}, author = {Tavares, Hugo and Whitley, Annabel and Field, David and Bradley, Desmond and Couchman, Matthew and Copsey, Lucy and Elleouet, Joane and Burrus, Monique and Andalo, Christophe and Li, Miaomiao and Li, Qun and Xue, Yongbiao and Rebocho, Alexandra B and Barton, Nicholas H and Coen, Enrico}, issn = {00278424}, journal = {PNAS}, number = {43}, pages = {11006 -- 11011}, publisher = {National Academy of Sciences}, title = {{Selection and gene flow shape genomic islands that control floral guides}}, doi = {10.1073/pnas.1801832115}, volume = {115}, year = {2018}, } @article{384, abstract = {Can orthologous proteins differ in terms of their ability to be secreted? To answer this question, we investigated the distribution of signal peptides within the orthologous groups of Enterobacterales. Parsimony analysis and sequence comparisons revealed a large number of signal peptide gain and loss events, in which signal peptides emerge or disappear in the course of evolution. Signal peptide losses prevail over gains, an effect which is especially pronounced in the transition from the free-living or commensal to the endosymbiotic lifestyle. The disproportionate decline in the number of signal peptide-containing proteins in endosymbionts cannot be explained by the overall reduction of their genomes. Signal peptides can be gained and lost either by acquisition/elimination of the corresponding N-terminal regions or by gradual accumulation of mutations. The evolutionary dynamics of signal peptides in bacterial proteins represents a powerful mechanism of functional diversification.}, author = {Hönigschmid, Peter and Bykova, Nadya and Schneider, René and Ivankov, Dmitry and Frishman, Dmitrij}, journal = {Genome Biology and Evolution}, number = {3}, pages = {928 -- 938}, publisher = {Oxford University Press}, title = {{Evolutionary interplay between symbiotic relationships and patterns of signal peptide gain and loss}}, doi = {10.1093/gbe/evy049}, volume = {10}, year = {2018}, } @article{39, abstract = {We study how a block of genome with a large number of weakly selected loci introgresses under directional selection into a genetically homogeneous population. We derive exact expressions for the expected rate of growth of any fragment of the introduced block during the initial phase of introgression, and show that the growth rate of a single-locus variant is largely insensitive to its own additive effect, but depends instead on the combined effect of all loci within a characteristic linkage scale. The expected growth rate of a fragment is highly correlated with its long-term introgression probability in populations of moderate size, and can hence identify variants that are likely to introgress across replicate populations. We clarify how the introgression probability of an individual variant is determined by the interplay between hitchhiking with relatively large fragments during the early phase of introgression and selection on fine-scale variation within these, which at longer times results in differential introgression probabilities for beneficial and deleterious loci within successful fragments. By simulating individuals, we also investigate how introgression probabilities at individual loci depend on the variance of fitness effects, the net fitness of the introduced block, and the size of the recipient population, and how this shapes the net advance under selection. Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation.}, author = {Sachdeva, Himani and Barton, Nicholas H}, issn = {00166731}, journal = {Genetics}, number = {4}, pages = {1411--1427}, publisher = {Genetics Society of America}, title = {{Replicability of introgression under linked, polygenic selection}}, doi = {10.1534/genetics.118.301429}, volume = {210}, year = {2018}, } @article{394, abstract = {The valley pseudospin in monolayer transition metal dichalcogenides (TMDs) has been proposed as a new way to manipulate information in various optoelectronic devices. This relies on a large valley polarization that remains stable over long time scales (hundreds of nanoseconds). However, time-resolved measurements report valley lifetimes of only a few picoseconds. This has been attributed to mechanisms such as phonon-mediated intervalley scattering and a precession of the valley pseudospin through electron-hole exchange. Here we use transient spin grating to directly measure the valley depolarization lifetime in monolayer MoSe2. We find a fast valley decay rate that scales linearly with the excitation density at different temperatures. This establishes the presence of strong exciton-exciton Coulomb exchange interactions enhancing the valley depolarization. Our work highlights the microscopic processes inhibiting the efficient use of the exciton valley pseudospin in monolayer TMDs. }, author = {Mahmood, Fahad and Alpichshev, Zhanybek and Lee, Yi and Kong, Jing and Gedik, Nuh}, journal = {Nano Letters}, number = {1}, pages = {223 -- 228}, publisher = {American Chemical Society}, title = {{Observation of exciton-exciton interaction mediated valley Depolarization in Monolayer MoSe2}}, doi = {10.1021/acs.nanolett.7b03953}, volume = {18}, year = {2018}, } @phdthesis{395, abstract = {Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. }, author = {Tarlungeanu, Dora-Clara}, issn = {2663-337X}, pages = {88}, publisher = {Institute of Science and Technology Austria}, title = {{The branched chain amino acids in autism spectrum disorders }}, doi = {10.15479/AT:ISTA:th_992}, year = {2018}, } @inproceedings{397, abstract = {Concurrent sets with range query operations are highly desirable in applications such as in-memory databases. However, few set implementations offer range queries. Known techniques for augmenting data structures with range queries (or operations that can be used to build range queries) have numerous problems that limit their usefulness. For example, they impose high overhead or rely heavily on garbage collection. In this work, we show how to augment data structures with highly efficient range queries, without relying on garbage collection. We identify a property of epoch-based memory reclamation algorithms that makes them ideal for implementing range queries, and produce three algorithms, which use locks, transactional memory and lock-free techniques, respectively. Our algorithms are applicable to more data structures than previous work, and are shown to be highly efficient on a large scale Intel system. }, author = {Arbel Raviv, Maya and Brown, Trevor A}, isbn = {978-1-4503-4982-6}, location = {Vienna, Austria}, number = {1}, pages = {14 -- 27}, publisher = {ACM}, title = {{Harnessing epoch-based reclamation for efficient range queries}}, doi = {10.1145/3178487.3178489}, volume = {53}, year = {2018}, } @article{398, abstract = {Objective: To report long-term results after Pipeline Embolization Device (PED) implantation, characterize complex and standard aneurysms comprehensively, and introduce a modified flow disruption scale. Methods: We retrospectively reviewed a consecutive series of 40 patients harboring 59 aneurysms treated with 54 PEDs. Aneurysm complexity was assessed using our proposed classification. Immediate angiographic results were analyzed using previously published grading scales and our novel flow disruption scale. Results: According to our new definition, 46 (78%) aneurysms were classified as complex. Most PED interventions were performed in the paraophthalmic and cavernous internal carotid artery segments. Excellent neurologic outcome (modified Rankin Scale 0 and 1) was observed in 94% of patients. Our data showed low permanent procedure-related mortality (0%) and morbidity (3%) rates. Long-term angiographic follow-up showed complete occlusion in 81% and near-total obliteration in a further 14%. Complete obliteration after deployment of a single PED was achieved in all standard aneurysms with 1-year follow-up. Our new scale was an independent predictor of aneurysm occlusion in a multivariable analysis. All aneurysms with a high flow disruption grade showed complete occlusion at follow-up regardless of PED number or aneurysm complexity. Conclusions: Treatment with the PED should be recognized as a primary management strategy for a highly selected cohort with predominantly complex intracranial aneurysms. We further show that a priori assessment of aneurysm complexity and our new postinterventional angiographic flow disruption scale predict occlusion probability and may help to determine the adequate number of per-aneurysm devices.}, author = {Dodier, Philippe and Frischer, Josa and Wang, Wei and Auzinger, Thomas and Mallouhi, Ammar and Serles, Wolfgang and Gruber, Andreas and Knosp, Engelbert and Bavinzski, Gerhard}, journal = {World Neurosurgery}, pages = {e568--e578}, publisher = {Elsevier}, title = {{Immediate flow disruption as a prognostic factor after flow diverter treatment long term experience with the pipeline embolization device}}, doi = {10.1016/j.wneu.2018.02.096}, volume = {13}, year = {2018}, } @article{399, abstract = {Following an earlier calculation in 3D, we calculate the 2D critical temperature of a dilute, translation-invariant Bose gas using a variational formulation of the Bogoliubov approximation introduced by Critchley and Solomon in 1976. This provides the first analytical calculation of the Kosterlitz-Thouless transition temperature that includes the constant in the logarithm.}, author = {Napiórkowski, Marcin M and Reuvers, Robin and Solovej, Jan}, journal = {EPL}, number = {1}, publisher = {IOP Publishing Ltd.}, title = {{Calculation of the critical temperature of a dilute Bose gas in the Bogoliubov approximation}}, doi = {10.1209/0295-5075/121/10007}, volume = {121}, year = {2018}, } @article{4, abstract = {We present a data-driven technique to instantly predict how fluid flows around various three-dimensional objects. Such simulation is useful for computational fabrication and engineering, but is usually computationally expensive since it requires solving the Navier-Stokes equation for many time steps. To accelerate the process, we propose a machine learning framework which predicts aerodynamic forces and velocity and pressure fields given a threedimensional shape input. Handling detailed free-form three-dimensional shapes in a data-driven framework is challenging because machine learning approaches usually require a consistent parametrization of input and output. We present a novel PolyCube maps-based parametrization that can be computed for three-dimensional shapes at interactive rates. This allows us to efficiently learn the nonlinear response of the flow using a Gaussian process regression. We demonstrate the effectiveness of our approach for the interactive design and optimization of a car body.}, author = {Umetani, Nobuyuki and Bickel, Bernd}, journal = {ACM Trans. Graph.}, number = {4}, publisher = {ACM}, title = {{Learning three-dimensional flow for interactive aerodynamic design}}, doi = {10.1145/3197517.3201325}, volume = {37}, year = {2018}, } @article{40, abstract = {Hanemaaijer et al. (Molecular Ecology, 27, 2018) describe the genetic consequences of the introgression of an insecticide resistance allele into a mosquito population. Linked alleles initially increased, but many of these later declined. It is hard to determine whether this decline was due to counter‐selection, rather than simply to chance.}, author = {Barton, Nicholas H}, issn = {1365294X}, journal = {Molecular Ecology}, number = {24}, pages = {4973--4975}, publisher = {Wiley}, title = {{The consequences of an introgression event}}, doi = {10.1111/mec.14950}, volume = {27}, year = {2018}, } @article{400, abstract = {We consider the two-dimensional BCS functional with a radial pair interaction. We show that the translational symmetry is not broken in a certain temperature interval below the critical temperature. In the case of vanishing angular momentum, our results carry over to the three-dimensional case.}, author = {Deuchert, Andreas and Geisinge, Alissa and Hainzl, Christian and Loss, Michael}, journal = {Annales Henri Poincare}, number = {5}, pages = {1507 -- 1527}, publisher = {Springer}, title = {{Persistence of translational symmetry in the BCS model with radial pair interaction}}, doi = {10.1007/s00023-018-0665-7}, volume = {19}, year = {2018}, } @article{401, abstract = {The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontaneously in a wide variety of systems. Although much of the signal cascade regulating myosin activity has been characterized, the origin of such oscillatory behavior is still unclear. Here, we show that basal myosin II oscillation in Drosophila ovarian epithelium is not controlled by actomyosin cortical tension, but instead relies on a biochemical oscillator involving ROCK and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self-activation loop reliant on ROCK kinase activity. In response to the resulting myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and optogenetics, we uncover an intrinsic biochemical oscillator at the core of myosin II regulatory network, shedding light on the spatio-temporal dynamics of force generation.}, author = {Qin, Xiang and Hannezo, Edouard B and Mangeat, Thomas and Liu, Chang and Majumder, Pralay and Liu, Jjiaying and Choesmel Cadamuro, Valerie and Mcdonald, Jocelyn and Liu, Yinyao and Yi, Bin and Wang, Xiaobo}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{A biochemical network controlling basal myosin oscillation}}, doi = {10.1038/s41467-018-03574-5}, volume = {9}, year = {2018}, } @article{402, abstract = {During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.}, author = {Brown, Markus and Assen, Frank P and Leithner, Alexander F and Abe, Jun and Schachner, Helga and Asfour, Gabriele and Bagó Horváth, Zsuzsanna and Stein, Jens and Uhrin, Pavel and Sixt, Michael K and Kerjaschki, Dontscho}, journal = {Science}, number = {6382}, pages = {1408 -- 1411}, publisher = {American Association for the Advancement of Science}, title = {{Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice}}, doi = {10.1126/science.aal3662}, volume = {359}, year = {2018}, }