@article{3399, abstract = {Context-dependent adjustment of mating tactics can drastically increase the mating success of behaviourally flexible animals. We used the ant Cardiocondyla obscurior as a model system to study adaptive adjustment of male mating tactics. This species shows a male diphenism of wingless fighter males and peaceful winged males. Whereas the wingless males stay and exclusively mate in the maternal colony, the mating behaviour of winged males is plastic. They copulate with female sexuals in their natal nests early in life but later disperse in search for sexuals outside. In this study, we observed the nest-leaving behaviour of winged males under different conditions and found that they adaptively adjust the timing of their dispersal to the availability of mating partners, as well as the presence, and even the type of competitors in their natal nests. In colonies with virgin female queens winged males stayed longest when they were the only male in the nest. They left earlier when mating partners were not available or when other males were present. In the presence of wingless, locally mating fighter males, winged males dispersed earlier than in the presence of docile, winged competitors. This suggests that C. obscurior males are capable of estimating their local breeding chances and adaptively adjust their dispersal behaviour in both an opportunistic and a risk-sensitive way, thus showing hitherto unknown behavioural plasticity in social insect males.}, author = {Cremer, Sylvia and Schrempf, Alexandra and Heinze, Jürgen}, journal = {PLoS One}, number = {3}, publisher = {Public Library of Science}, title = {{Competition and opportunity shape the reproductive tactics of males in the ant Cardiocondyla obscurior}}, doi = {10.1371/journal.pone.0017323}, volume = {6}, year = {2011}, } @article{3401, abstract = {The Bicoid morphogen gradient directs the patterning of cell fates along the anterior-posterior axis of the syncytial Drosophila embryo and serves as a paradigm of morphogen-mediated patterning. The simplest models of gradient formation rely on constant protein synthesis and diffusion from anteriorly localized source mRNA, coupled with uniform protein degradation. However, currently such models cannot account for all known gradient characteristics. Recent work has proposed that bicoid mRNA spatial distribution is sufficient to produce the observed protein gradient, minimizing the role of protein transport. Here, we adapt a novel method of fluorescent in situ hybridization to quantify the global spatio-temporal dynamics of bicoid mRNA particles. We determine that >90% of all bicoid mRNA is continuously present within the anterior 20% of the embryo. bicoid mRNA distribution along the body axis remains nearly unchanged despite dynamic mRNA translocation from the embryo core to the cortex. To evaluate the impact of mRNA distribution on protein gradient dynamics, we provide detailed quantitative measurements of nuclear Bicoid levels during the formation of the protein gradient. We find that gradient establishment begins 45 minutes after fertilization and that the gradient requires about 50 minutes to reach peak levels. In numerical simulations of gradient formation, we find that incorporating the actual bicoid mRNA distribution yields a closer prediction of the observed protein dynamics compared to modeling protein production from a point source at the anterior pole. We conclude that the spatial distribution of bicoid mRNA contributes to, but cannot account for, protein gradient formation, and therefore that protein movement, either active or passive, is required for gradient formation.}, author = {Little, Shawn and Tkacik, Gasper and Kneeland, Thomas and Wieschaus, Eric and Gregor, Thomas}, journal = {PLoS Biology}, number = {3}, publisher = {Public Library of Science}, title = {{The formation of the Bicoid morphogen gradient requires protein movement from anteriorly localized source}}, doi = {10.1371/journal.pbio.1000596}, volume = {9}, year = {2011}, } @article{3405, abstract = {Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K+ channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.}, author = {Janovjak, Harald L and Sandoz, Guillaume and Isacoff, Ehud}, journal = {Nature Communications}, number = {232}, pages = {1 -- 6}, publisher = {Nature Publishing Group}, title = {{Modern ionotropic glutamate receptor with a K+ selectivity signature sequence}}, doi = {10.1038/ncomms1231}, volume = {2}, year = {2011}, } @article{341, abstract = {An oriented attachment and growth mechanism allows an accurate control of the size and morphology of Cu2-xS nanocrystals, from spheres and disks to tetradecahedrons and dodecahedrons. The synthesis conditions and the growth mechanism are detailed here.}, author = {Li, Wenhua and Shavel, Alexey and Guzman, Roger and Rubio Garcia, Javier and Flox, Cristina and Fan, Jiandong and Cadavid, Doris and Ibáñez, Maria and Arbiol, Jordi and Morante, Joan and Cabot, Andreu}, journal = {Chemical Communications}, number = {37}, pages = {10332 -- 10334}, publisher = {Royal Society of Chemistry (RSC) }, title = {{Morphology evolution of Cu2−xS nanoparticles: from spheres to dodecahedrons}}, doi = {10.1039/c1cc13803k}, volume = {47}, year = {2011}, } @article{3429, abstract = {Transcription factors are central to sustaining pluripotency, yet little is known about transcription factor dynamics in defining pluripotency in the early mammalian embryo. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the kinetic behaviour of Oct4, a key transcription factor controlling pre-implantation development in the mouse embryo. FDAP measurements reveal that each cell in a developing embryo shows one of two distinct Oct4 kinetics, before there are any morphologically distinguishable differences or outward signs of lineage patterning. The differences revealed by FDAP are due to differences in the accessibility of Oct4 to its DNA binding sites in the nucleus. Lineage tracing of the cells in the two distinct sub-populations demonstrates that the Oct4 kinetics predict lineages of the early embryo. Cells with slower Oct4 kinetics are more likely to give rise to the pluripotent cell lineage that contributes to the inner cell mass. Those with faster Oct4 kinetics contribute mostly to the extra-embryonic lineage. Our findings identify Oct4 kinetics, rather than differences in total transcription factor expression levels, as a predictive measure of developmental cell lineage patterning in the early mouse embryo.}, author = {Plachta, Nicolas and Bollenbach, Mark Tobias and Pease, Shirley and Fraser, Scott and Pantazis, Periklis}, journal = {Nature Cell Biology}, number = {2}, pages = {117 -- 123}, publisher = {Nature Publishing Group}, title = {{Oct4 kinetics predict cell lineage patterning in the early mammalian embryo}}, doi = {10.1038/ncb2154}, volume = {13}, year = {2011}, } @article{3505, abstract = {Cell migration on two-dimensional (2D) substrates follows entirely different rules than cell migration in three-dimensional (3D) environments. This is especially relevant for leukocytes that are able to migrate in the absence of adhesion receptors within the confined geometry of artificial 3D extracellular matrix scaffolds and within the interstitial space in vivo. Here, we describe in detail a simple and economical protocol to visualize dendritic cell migration in 3D collagen scaffolds along chemotactic gradients. This method can be adapted to other cell types and may serve as a physiologically relevant paradigm for the directed locomotion of most amoeboid cells.}, author = {Sixt, Michael K and Lämmermann, Tim}, journal = {Cell Migration}, pages = {149 -- 165}, publisher = {Springer}, title = {{In vitro analysis of chemotactic leukocyte migration in 3D environments}}, doi = {10.1007/978-1-61779-207-6_11}, volume = {769}, year = {2011}, } @inbook{3724, abstract = {Small photochromic molecules are widespread in nature and serve as switches for a plethora of light-controlled processes. In a typical photoreceptor, the different geometries and polarities of the photochrome isomers are tightly coupled to functionally relevant conformational changes in the proteins. The past decade has seen extensive efforts to mimic nature and create proteins controlled by synthetic photochromes in the laboratory. Here, we discuss the role of molecular modeling to gain a structural understanding of photochromes and to design light-controlled peptides and proteins. We address several fundamental questions: What are the molecular structures of photochromes, particularly for metastable isomers that cannot be addressed experimentally? How are the structures of bistable photoisomers coupled to the conformational states of peptides and proteins? Can we design light-controlled proteins rapidly and reliably? After an introduction to the principles of molecular modeling, we answer these questions by examining systems that range from the size of isolated photochromes, to that of peptides and large cell surface receptors, each from its unique computational perspective.}, author = {Harald Janovjak and Isacoff, Ehud Y}, booktitle = {Photosensitive Molecules for the Control of Biological Function}, pages = {233 -- 266}, publisher = {Springer}, title = {{Structure-based design of light-controlled proteins}}, doi = {10.1007/978-1-61779-031-7_13}, volume = {55}, year = {2011}, } @article{3770, abstract = {The pink dolphin (Inia geoffrensis) is widely distributed along the Amazon and Orinoco basins, covering an area of approximately 7 million km2. Previous morphological and genetic studies have proposed the existence of at least two evolutionary significant units: one distributed across the Orinoco and Amazon basins and another confined to the Bolivian Amazon. The presence of barriers in the riverine environment has been suggested to play a significant role in shaping present-day patterns of ecological and genetic structure for this species. In the present study, we examined the phylogeographic structure, lineage divergence time and historical demography using mitochondrial (mt)DNA sequences in different pink dolphin populations distributed in large and small spatial scales, including two neighbouring Brazilian Amazon populations. mtDNA control region (CR) analysis revealed that the Brazilian haplotypes occupy an intermediate position compared to three previously studied geographic locations: the Colombian Amazon, the Colombian Orinoco, and the Bolivian Amazon. On a local scale, we have identified a pattern of maternal isolation between two neighbouring populations from Brazil. Six mtDNA CR haplotypes were identified in Brazil with no sharing between the two populations, as well as specific cytochrome b (cyt b) haplotypes identified in each locality. In addition, we analyzed autosomal microsatellites to investigate male-mediated gene flow and demographic changes within the study area in Brazil. Data analysis of 14 microsatellite loci failed to detect significant population subdivision, suggesting that male-mediated gene flow may maintain homogeneity between these two locations. Moreover, both mtDNA and microsatellite data indicate a major demographic collapse within Brazil in the late Pleistocene. Bayesian skyline plots (BSP) of mtDNA data revealed a stable population for Colombian and Brazilian Amazon lineages through time, whereas a population decline was demonstrated in the Colombian Orinoco lineage. Moreover, BSP and Tajima's D and Fu's Fs tests revealed a recent population expansion exclusively in the Bolivian sample. Finally, we estimated that the diversification of the Inia sp. lineage began in the Late Pliocene (approximately 3.1 Mya) and continued throughout the Pleistocene.}, author = {Hollatz, Claudia and Vilaça, Sibelle and Fernandes Redondo, Rodrigo A and Marmontel, Míriam and Baker, Cyndi and Santos, Fabrício}, journal = {Biological Journal of the Linnean Society}, number = {4}, pages = {812 -- 827}, publisher = {Wiley}, title = {{The Amazon River system as an ecological barrier driving genetic differentiation of the pink dolphin (Inia geoffrensis)}}, doi = {10.1111/j.1095-8312.2011.01616.x}, volume = {102}, year = {2011}, } @article{3771, abstract = {The small-sized frugivorous bat Carollia perspicillata is an understory specialist and occurs in a wide range of lowland habitats, tending to be more common in tropical dry or moist forests of South and Central America. Its sister species, Carollia brevicauda, occurs almost exclusively in the Amazon rainforest. A recent phylogeographic study proposed a hypothesis of origin and subsequent diversification for C. perspicillata along the Atlantic coastal forest of Brazil. Additionally, it also found two allopatric clades for C. brevicauda separated by the Amazon Basin. We used cytochrome b gene sequences and a more extensive sampling to test hypotheses related to the origin and diversification of C. perspicillata plus C. brevicauda clade in South America. The results obtained indicate that there are two sympatric evolutionary lineages within each species. In C. perspicillata, one lineage is limited to the Southern Atlantic Forest, whereas the other is widely distributed. Coalescent analysis points to a simultaneous origin for C. perspicillata and C. brevicauda, although no place for the diversification of each species can be firmly suggested. The phylogeographic pattern shown by C. perspicillata is also congruent with the Pleistocene refugia hypothesis as a likely vicariant phenomenon shaping the present distribution of its intraspecific lineages.}, author = {Pavan, Ana and Martins, Felipe and Santos, Fabrício and Ditchfield, Albert and Fernandes Redondo, Rodrigo A}, journal = {Biological Journal of the Linnean Society}, number = {3}, pages = {527 -- 539}, publisher = {Wiley-Blackwell}, title = {{Patterns of diversification in two species of short-tailed bats (Carollia Gray, 1838): the effects of historical fragmentation of Brazilian rainforests.}}, doi = {10.1111/j.1095-8312.2010.01601.x}, volume = {102}, year = {2011}, } @article{3778, author = {Barton, Nicholas H}, journal = {Heredity}, number = {2}, pages = {205 -- 206}, publisher = {Nature Publishing Group}, title = {{Estimating linkage disequilibria}}, doi = {10.1038/hdy.2010.67}, volume = {106}, year = {2011}, } @article{3781, abstract = {We bound the difference in length of two curves in terms of their total curvatures and the Fréchet distance. The bound is independent of the dimension of the ambient Euclidean space, it improves upon a bound by Cohen-Steiner and Edelsbrunner, and it generalizes a result by Fáry and Chakerian.}, author = {Fasy, Brittany Terese}, journal = {Acta Sci. Math. (Szeged)}, number = {1-2}, pages = {359 -- 367}, publisher = {Szegedi Tudományegyetem}, title = {{The difference in length of curves in R^n}}, volume = {77}, year = {2011}, } @article{3784, abstract = {Advanced stages of Scyllarus phyllosoma larvae were collected by demersal trawling during fishery research surveys in the western Mediterranean Sea in 2003–2005. Nucleotide sequence analysis of the mitochondrial 16S rDNA gene allowed the final-stage phyllosoma of Scyllarus arctus to be identified among these larvae. Its morphology is described and illustrated. This constitutes the second complete description of a Scyllaridae phyllosoma with its specific identity being validated by molecular techniques (the first was S. pygmaeus). These results also solved a long lasting taxonomic anomaly of several species assigned to the ancient genus Phyllosoma Leach, 1814. Detailed examination indicated that the final-stage phyllosoma of S. arctus shows closer affinities with the American scyllarid Scyllarus depressus or with the Australian Scyllarus sp. b (sensu Phillips et al., 1981) than to its sympatric species S. pygmaeus.}, author = {Palero, Ferran and Guerao, Guillermo and Clark, Paul and Abello, Pere}, journal = {Journal of the Marine Biological Association of the United Kingdom}, number = {2}, pages = {485 -- 492}, publisher = {Cambridge University Press}, title = {{Scyllarus arctus (Crustacea: Decapoda: Scyllaridae) final stage phyllosoma identified by DNA analysis, with morphological description}}, doi = {10.1017/S0025315410000287}, volume = {91}, year = {2011}, } @inbook{3791, abstract = {During the development of multicellular organisms, cell fate specification is followed by the sorting of different cell types into distinct domains from where the different tissues and organs are formed. Cell sorting involves both the segregation of a mixed population of cells with different fates and properties into distinct domains, and the active maintenance of their segregated state. Because of its biological importance and apparent resemblance to fluid segregation in physics, cell sorting was extensively studied by both biologists and physicists over the last decades. Different theories were developed that try to explain cell sorting on the basis of the physical properties of the constituent cells. However, only recently the molecular and cellular mechanisms that control the physical properties driving cell sorting, have begun to be unraveled. In this review, we will provide an overview of different cell-sorting processes in development and discuss how these processes can be explained by the different sorting theories, and how these theories in turn can be connected to the molecular and cellular mechanisms driving these processes.}, author = {Krens, Gabriel and Heisenberg, Carl-Philipp J}, booktitle = {Forces and Tension in Development}, editor = {Labouesse, Michel}, pages = {189 -- 213}, publisher = {Elsevier}, title = {{Cell sorting in development}}, doi = {10.1016/B978-0-12-385065-2.00006-2}, volume = {95}, year = {2011}, } @inbook{3796, abstract = {We address the problem of covering ℝ n with congruent balls, while minimizing the number of balls that contain an average point. Considering the 1-parameter family of lattices defined by stretching or compressing the integer grid in diagonal direction, we give a closed formula for the covering density that depends on the distortion parameter. We observe that our family contains the thinnest lattice coverings in dimensions 2 to 5. We also consider the problem of packing congruent balls in ℝ n , for which we give a closed formula for the packing density as well. Again we observe that our family contains optimal configurations, this time densest packings in dimensions 2 and 3.}, author = {Edelsbrunner, Herbert and Kerber, Michael}, booktitle = {Rainbow of Computer Science}, editor = {Calude, Cristian and Rozenberg, Grzegorz and Salomaa, Arto}, pages = {20 -- 35}, publisher = {Springer}, title = {{Covering and packing with spheres by diagonal distortion in R^n}}, doi = {10.1007/978-3-642-19391-0_2}, volume = {6570}, year = {2011}, } @article{386, abstract = {We present a detailed study of the local density of states (LDOS) associated with the surface-state band near a step edge of the strong topological insulator Bi2Te3 and reveal a one-dimensional bound state that runs parallel to the step edge and is bound to it at some characteristic distance. This bound state is clearly observed in the bulk gap region, while it becomes entangled with the oscillations of the warped surface band at high energy, and with the valence-band states near the Dirac point. We obtain excellent fits to theoretical predictions [Alpichshev, 2011] that properly incorporate the three-dimensional nature of the problem to the surface state. Fitting the data at different energies, we can recalculate the LDOS originating from the Dirac band without the contribution of the bulk bands or incoherent tunneling effects. }, author = {Alpichshev, Zhanybek and Analytis, J G and Chu, J H and Fisher, I R and Kapitulnik, A}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {4}, publisher = {American Physical Society}, title = {{STM imaging of a bound state along a step on the surface of the topological insulator Bi2Te3}}, doi = {10.1103/PhysRevB.84.041104}, volume = {84}, year = {2011}, } @article{3965, abstract = {The elevation function on a smoothly embedded 2-manifold in R-3 reflects the multiscale topography of cavities and protrusions as local maxima. The function has been useful in identifying coarse docking configurations for protein pairs. Transporting the concept from the smooth to the piecewise linear category, this paper describes an algorithm for finding all local maxima. While its worst-case running time is the same as of the algorithm used in prior work, its performance in practice is orders of magnitudes superior. We cast light on this improvement by relating the running time to the total absolute Gaussian curvature of the 2-manifold.}, author = {Wang, Bei and Edelsbrunner, Herbert and Morozov, Dmitriy}, journal = {Journal of Experimental Algorithmics}, number = {2.2}, pages = {1 -- 13}, publisher = {ACM}, title = {{Computing elevation maxima by searching the Gauss sphere}}, doi = {10.1145/1963190.1970375}, volume = {16}, year = {2011}, } @article{469, abstract = {Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release. }, author = {Vyleta, Nicholas and Smith, Stephen}, journal = {European Journal of Neuroscience}, number = {12}, pages = {4593 -- 4606}, publisher = {Wiley-Blackwell}, title = {{Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor}}, doi = {10.1523/JNEUROSCI.6398-10.2011}, volume = {31}, year = {2011}, } @article{490, abstract = {BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals. }, author = {Schlögl, Alois and Vidaurre, Carmen and Sander, Tilmann}, journal = {Computational Intelligence and Neuroscience}, publisher = {Hindawi Publishing Corporation}, title = {{BioSig: The free and open source software library for biomedical signal processing}}, doi = {10.1155/2011/935364}, volume = {2011}, year = {2011}, } @article{491, abstract = {In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static.}, author = {Eichner, Alexander and Sixt, Michael K}, journal = {Science Signaling}, number = {198}, publisher = {American Association for the Advancement of Science}, title = {{Setting the clock for recirculating lymphocytes}}, doi = {10.1126/scisignal.2002617}, volume = {4}, year = {2011}, } @article{518, abstract = {Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.}, author = {Schraivogel, Daniel and Weinmann, Lasse and Beier, Dagmar and Tabatabai, Ghazaleh and Eichner, Alexander and Zhu, Jia and Anton, Martina and Sixt, Michael K and Weller, Michael and Beier, Christoph and Meister, Gunter}, journal = {EMBO Journal}, number = {20}, pages = {4309 -- 4322}, publisher = {Wiley-Blackwell}, title = {{CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells}}, doi = {10.1038/emboj.2011.301}, volume = {30}, year = {2011}, }