@article{11758, author = {Aceto, Luca and Henzinger, Monika H and Sgall, Jiří}, issn = {0890-5401}, journal = {Information and Computation}, number = {1}, pages = {1}, publisher = {Elsevier}, title = {{38th International Colloquium on Automata, Languages and Programming}}, doi = {10.1016/j.ic.2012.11.002}, volume = {222}, year = {2013}, } @article{11759, abstract = {Matching markets play a prominent role in economic theory. A prime example of such a market is the sponsored search market. Here, as in other markets of that kind, market equilibria correspond to feasible, envy free, and bidder optimal outcomes. For settings without budgets such an outcome always exists and can be computed in polynomial-time by the so-called Hungarian Method. Moreover, every mechanism that computes such an outcome is incentive compatible. We show that the Hungarian Method can be modified so that it finds a feasible, envy free, and bidder optimal outcome for settings with budgets. We also show that in settings with budgets no mechanism that computes such an outcome can be incentive compatible for all inputs. For inputs in general position, however, the presented mechanism—as any other mechanism that computes such an outcome for settings with budgets—is incentive compatible.}, author = {Dütting, Paul and Henzinger, Monika H and Weber, Ingmar}, issn = {0020-0190}, journal = {Information Processing Letters}, number = {3}, pages = {67--73}, publisher = {Elsevier}, title = {{Sponsored search, market equilibria, and the Hungarian Method}}, doi = {10.1016/j.ipl.2012.11.006}, volume = {113}, year = {2013}, } @inproceedings{11791, abstract = {The focus of classic mechanism design has been on truthful direct-revelation mechanisms. In the context of combinatorial auctions the truthful direct-revelation mechanism that maximizes social welfare is the VCG mechanism. For many valuation spaces computing the allocation and payments of the VCG mechanism, however, is a computationally hard problem. We thus study the performance of the VCG mechanism when bidders are forced to choose bids from a subspace of the valuation space for which the VCG outcome can be computed efficiently. We prove improved upper bounds on the welfare loss for restrictions to additive bids and upper and lower bounds for restrictions to non-additive bids. These bounds show that the welfare loss increases in expressiveness. All our bounds apply to equilibrium concepts that can be computed in polynomial time as well as to learning outcomes.}, author = {Dütting, Paul and Henzinger, Monika H and Starnberger, Martin}, booktitle = {9th International Conference on Web and Internet Economics}, isbn = {9783642450457}, issn = {1611-3349}, location = {Cambridge, MA, USA}, pages = {146–159}, publisher = {Springer Nature}, title = {{Valuation compressions in VCG-based combinatorial auctions}}, doi = {10.1007/978-3-642-45046-4_13}, volume = {8289}, year = {2013}, } @inproceedings{11792, abstract = {We study the problem of maximizing a monotone submodular function with viability constraints. This problem originates from computational biology, where we are given a phylogenetic tree over a set of species and a directed graph, the so-called food web, encoding viability constraints between these species. These food webs usually have constant depth. The goal is to select a subset of k species that satisfies the viability constraints and has maximal phylogenetic diversity. As this problem is known to be NP-hard, we investigate approximation algorithm. We present the first constant factor approximation algorithm if the depth is constant. Its approximation ratio is (1−1𝑒√). This algorithm not only applies to phylogenetic trees with viability constraints but for arbitrary monotone submodular set functions with viability constraints. Second, we show that there is no (1 − 1/e + ε)-approximation algorithm for our problem setting (even for additive functions) and that there is no approximation algorithm for a slight extension of this setting.}, author = {Dvořák, Wolfgang and Henzinger, Monika H and Williamson, David P.}, booktitle = {21st Annual European Symposium on Algorithms}, isbn = {9783642404498}, issn = {1611-3349}, location = {Sophia Antipolis, France}, pages = {409 -- 420}, publisher = {Springer Nature}, title = {{Maximizing a submodular function with viability constraints}}, doi = {10.1007/978-3-642-40450-4_35}, volume = {8125}, year = {2013}, } @inproceedings{11793, abstract = {We study the problem of maintaining a breadth-first spanning tree (BFS tree) in partially dynamic distributed networks modeling a sequence of either failures or additions of communication links (but not both). We show (1 + ε)-approximation algorithms whose amortized time (over some number of link changes) is sublinear in D, the maximum diameter of the network. This breaks the Θ(D) time bound of recomputing “from scratch”. Our technique also leads to a (1 + ε)-approximate incremental algorithm for single-source shortest paths (SSSP) in the sequential (usual RAM) model. Prior to our work, the state of the art was the classic exact algorithm of [9] that is optimal under some assumptions [27]. Our result is the first to show that, in the incremental setting, this bound can be beaten in certain cases if a small approximation is allowed.}, author = {Henzinger, Monika H and Krinninger, Sebastian and Nanongkai, Danupon}, booktitle = {40th International Colloquium on Automata, Languages, and Programming}, isbn = {9783642392115}, issn = {1611-3349}, location = {Riga, Latvia}, pages = {607–619}, publisher = {Springer Nature}, title = {{Sublinear-time maintenance of breadth-first spanning tree in partially dynamic networks}}, doi = {10.1007/978-3-642-39212-2_53}, volume = {7966}, year = {2013}, } @article{7774, abstract = {In 2005, Wyart et al. [Europhys. Lett., 2005, 72, 486] showed that the low frequency vibrational properties of jammed amorphous sphere packings can be understood in terms of a length scale, called l*, that diverges as the system becomes marginally unstable. Despite the tremendous success of this theory, it has been difficult to connect the counting argument that defines l* to other length scales that diverge near the jamming transition. We present an alternate derivation of l* based on the onset of rigidity. This phenomenological approach reveals the physical mechanism underlying the length scale and is relevant to a range of systems for which the original argument breaks down. It also allows us to present the first direct numerical measurement of l*.}, author = {Goodrich, Carl Peter and Ellenbroek, Wouter G. and Liu, Andrea J.}, issn = {1744-683X}, journal = {Soft Matter}, number = {46}, publisher = {Royal Society of Chemistry}, title = {{Stability of jammed packings I: The rigidity length scale}}, doi = {10.1039/c3sm51095f}, volume = {9}, year = {2013}, } @article{7775, abstract = {As a function of packing fraction at zero temperature and applied stress, an amorphous packing of spheres exhibits a jamming transition where the system is sensitive to boundary conditions even in the thermodynamic limit. Upon further compression, the system should become insensitive to boundary conditions provided it is sufficiently large. Here we explore the linear response to a large class of boundary perturbations in 2 and 3 dimensions. We consider each finite packing with periodic-boundary conditions as the basis of an infinite square or cubic lattice and study properties of vibrational modes at arbitrary wave vector. We find that the stability of such modes can be understood in terms of a competition between plane waves and the anomalous vibrational modes associated with the jamming transition; infinitesimal boundary perturbations become irrelevant for systems that are larger than a length scale that characterizes the transverse excitations. This previously identified length diverges at the jamming transition.}, author = {Schoenholz, Samuel S. and Goodrich, Carl Peter and Kogan, Oleg and Liu, Andrea J. and Nagel, Sidney R.}, issn = {1744-683X}, journal = {Soft Matter}, number = {46}, publisher = {Royal Society of Chemistry}, title = {{Stability of jammed packings II: The transverse length scale}}, doi = {10.1039/c3sm51096d}, volume = {9}, year = {2013}, } @article{7785, abstract = {Neural circuit assembly requires selection of specific cell fates, axonal trajectories, and synaptic targets. By analyzing the function of a secreted semaphorin, Sema-2b, in Drosophila olfactory receptor neuron (ORN) development, we identified multiple molecular and cellular mechanisms that link these events. Notch signaling limits Sema-2b expression to ventromedial ORN classes, within which Sema-2b cell-autonomously sensitizes ORN axons to external semaphorins. Central-brain-derived Sema-2a and Sema-2b attract Sema-2b-expressing axons to the ventromedial trajectory. In addition, Sema-2b/PlexB-mediated axon-axon interactions consolidate this trajectory choice and promote ventromedial axon-bundle formation. Selecting the correct developmental trajectory is ultimately essential for proper target choice. These findings demonstrate that Sema-2b couples ORN axon guidance to postsynaptic target neuron dendrite patterning well before the final target selection phase, and exemplify how a single guidance molecule can drive consecutive stages of neural circuit assembly with the help of sophisticated spatial and temporal regulation.}, author = {Joo, William J. and Sweeney, Lora Beatrice Jaeger and Liang, Liang and Luo, Liqun}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {673--686}, publisher = {Elsevier}, title = {{Linking cell fate, trajectory choice, and target selection: Genetic analysis of sema-2b in olfactory axon targeting}}, doi = {10.1016/j.neuron.2013.03.022}, volume = {78}, year = {2013}, } @article{8030, abstract = {While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.}, author = {Vogels, Tim P and Froemke, R. C. and Doyon, N. and Gilson, M. and Haas, J. S. and Liu, R. and Maffei, A. and Miller, P. and Wierenga, C. J. and Woodin, M. A. and Zenke, F. and Sprekeler, H.}, issn = {1662-5110}, journal = {Frontiers in Neural Circuits}, publisher = {Frontiers Media}, title = {{Inhibitory synaptic plasticity: Spike timing-dependence and putative network function}}, doi = {10.3389/fncir.2013.00119}, volume = {7}, year = {2013}, } @article{810, abstract = {Cryo-electron tomography combined with image processing by sub-tomogram averaging is unique in its power to resolve the structures of proteins and macromolecular complexes in situ. Limitations of the method, including the low signal to noise ratio within individual images from cryo-tomographic datasets and difficulties in determining the defocus at which the data was collected, mean that to date the very best structures obtained by sub-tomogram averaging are limited to a resolution of approximately 15. Å. Here, by optimizing data collection and defocus determination steps, we have determined the structure of assembled Mason-Pfizer monkey virus Gag protein using sub-tomogram averaging to a resolution of 8.5. Å. At this resolution alpha-helices can be directly and clearly visualized. These data demonstrate for the first time that high-resolution structural information can be obtained from cryo-electron tomograms using sub-tomogram averaging. Sub-tomogram averaging has the potential to allow detailed studies of unsolved and biologically relevant structures under biologically relevant conditions.}, author = {Florian Schur and Hagen, Wim J and De Marco, Alex and Briggs, John A}, journal = {Journal of Structural Biology}, number = {3}, pages = {394 -- 400}, publisher = {Academic Press}, title = {{Determination of protein structure at 8.5Å resolution using cryo-electron tomography and sub-tomogram averaging}}, doi = {10.1016/j.jsb.2013.10.015}, volume = {184}, year = {2013}, } @article{811, abstract = {Cell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In two-dimensional migration, protrusion of these thin sheets of cytoplasm is considered relevant to both exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodium formation can be potently stimulated by Rho GTPases of the Rac subfamily, but alsoby RhoG or Cdc42. Here we describe viable fibroblast cell lines geneticallydeficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac-deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac - although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signaling is essential for lamellipodium protrusion and for efficient cell migration, but not for spreading or filopodium formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.}, author = {Steffen, Anika and Ladwein, Markus and Georgi Dimchev and Hein, Anke and Schwenkmezger, Lisa and Arens, Stefan and Ladwein, Kathrin I and Holleboom, J. Margit and Florian Schur and Small, John V and Schwarz, Janett and Gerhard, Ralf and Faix, Jan and Stradal, Theresia E and Brakebusch, Cord H and Rottner, Klemens}, journal = {Journal of Cell Science}, number = {20}, pages = {4572 -- 4588}, publisher = {Company of Biologists}, title = {{Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation}}, doi = {10.1242/jcs.118232}, volume = {126}, year = {2013}, } @article{812, abstract = {Lamellipodia are sheet-like protrusions formed during migration or phagocytosis and comprise a network of actin filaments. Filament formation in this network is initiated by nucleation/branching through the actin-related protein 2/3 (Arp2/3) complex downstream of its activator, suppressor of cAMP receptor/WASP-family verprolin homologous (Scar/WAVE), but the relative relevance of Arp2/3-mediated branching versus actin filament elongation is unknown. Here we use instantaneous interference with Arp2/3 complex function in live fibroblasts with established lamellipodia. This allows direct examination of both the fate of elongating filaments upon instantaneous suppression of Arp2/3 complex activity and the consequences of this treatment on the dynamics of other lamellipodial regulators. We show that Arp2/3 complex is an essential organizer of treadmilling actin filament arrays but has little effect on the net rate of actin filament turnover at the cell periphery. In addition, Arp2/3 complex serves as key upstream factor for the recruitment of modulators of lamellipodia formation such as capping protein or cofilin. Arp2/3 complex is thus decisive for filament organization and geometry within the network not only by generating branches and novel filament ends, but also by directing capping or severing activities to the lamellipodium. Arp2/3 complex is also crucial to lamellipodia-based migration of keratocytes.}, author = {Koestler, Stefan A and Steffen, Anika and Maria Nemethova and Winterhoff, Moritz and Luo, Ningning and Holleboom, J. Margit and Krupp, Jessica and Jacob, Sonja and Vinzenz, Marlene and Florian Schur and Schlüter, Kai and Gunning, Peter W and Winkler, Christoph and Schmeiser, Christian and Faix, Jan and Stradal, Theresia E and Small, John V and Rottner, Klemens}, journal = {Molecular Biology of the Cell}, number = {18}, pages = {2861 -- 2875}, publisher = {American Society for Biology}, title = {{Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin}}, doi = {10.1091/mbc.E12-12-0857}, volume = {24}, year = {2013}, } @article{8245, abstract = {Background: Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena. Methods: We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS). Results: ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells. Conclusion: The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This finding supports the application of trastuzumab at any stage of the disease.}, author = {Petricevic, Branka and Laengle, Johannes and Singer, Josef and Sachet, Monika and Fazekas, Judit and Steger, Guenther and Bartsch, Rupert and Jensen-Jarolim, Erika and Bergmann, Michael}, issn = {1479-5876}, journal = {Journal of Translational Medicine}, publisher = {Springer Nature}, title = {{Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients}}, doi = {10.1186/1479-5876-11-307}, volume = {11}, year = {2013}, } @article{827, abstract = {As sessile organisms, plants have to be able to adapt to a continuously changing environment. Plants that perceive some of these changes as stress signals activate signaling pathways to modulate their development and to enable them to survive. The complex responses to environmental cues are to a large extent mediated by plant hormones that together orchestrate the final plant response. The phytohormone cytokinin is involved in many plant developmental processes. Recently, it has been established that cytokinin plays an important role in stress responses, but does not act alone. Indeed, the hormonal control of plant development and stress adaptation is the outcome of a complex network of multiple synergistic and antagonistic interactions between various hormones. Here, we review the recent findings on the cytokinin function as part of this hormonal network. We focus on the importance of the crosstalk between cytokinin and other hormones, such as abscisic acid, jasmonate, salicylic acid, ethylene, and auxin in the modulation of plant development and stress adaptation. Finally, the impact of the current research in the biotechnological industry will be discussed.}, author = {O'Brien, José and Benková, Eva}, journal = {Frontiers in Plant Science}, publisher = {Frontiers Research Foundation}, title = {{Cytokinin cross talking during biotic and abiotic stress responses}}, doi = {10.3389/fpls.2013.00451}, volume = {4}, year = {2013}, } @article{828, abstract = {The plant root system is essential for providing anchorage to the soil, supplying minerals and water, and synthesizing metabolites. It is a dynamic organ modulated by external cues such as environmental signals, water and nutrients availability, salinity and others. Lateral roots (LRs) are initiated from the primary root post-embryonically, after which they progress through discrete developmental stages which can be independently controlled, providing a high level of plasticity during root system formation. Within this review, main contributions are presented, from the classical forward genetic screens to the more recent high-throughput approaches, combined with computer model predictions, dissecting how LRs and thereby root system architecture is established and developed.}, author = {Cuesta, Candela and Wabnik, Krzysztof T and Benková, Eva}, journal = {Frontiers in Plant Science}, publisher = {Frontiers Research Foundation}, title = {{Systems approaches to study root architecture dynamics}}, doi = {10.3389/fpls.2013.00537}, volume = {4}, year = {2013}, } @article{830, abstract = {Upon hormonal signaling, ovules develop as lateral organs from the placenta. Ovule numbers ultimately determine the number of seeds that develop, and thereby contribute to the final seed yield in crop plants. We demonstrate here that CUP-SHAPED COTYLEDON 1 (CUC1), CUC2 and AINTEGUMENTA (ANT) have additive effects on ovule primordia formation. We show that expression of the CUC1 and CUC2 genes is required to redundantly regulate expression of PINFORMED1 (PIN1), which in turn is required for ovule primordia formation. Furthermore, our results suggest that the auxin response factor MONOPTEROS (MP/ARF5) may directly bind ANT, CUC1 and CUC2 and promote their transcription. Based on our findings, we propose an integrative model to describe the molecular mechanisms of the early stages of ovule development.}, author = {Galbiati, Francesca and Sinha Roy, Dola and Simonini, Sara and Cucinotta, Mara and Ceccato, Luca and Cuesta, Candela and Šimášková, Mária and Benková, Eva and Kamiuchi, Yuri and Aida, Mitsuhiro and Weijers, Dolf and Simon, Rüdiger and Masiero, Simona and Colombo, Lucia}, journal = {The Plant journal for cell and molecular biology}, number = {3}, pages = {446 -- 455}, publisher = {Wiley-Blackwell}, title = {{An integrative model of the control of ovule primordia formation}}, doi = {10.1111/tpj.12309}, volume = {76}, year = {2013}, } @article{831, abstract = {In Arabidopsis, lateral roots originate from pericycle cells deep within the primary root. New lateral root primordia (LRP) have to emerge through several overlaying tissues. Here, we report that auxin produced in new LRP is transported towards the outer tissues where it triggers cell separation by inducing both the auxin influx carrier LAX3 and cell-wall enzymes. LAX3 is expressed in just two cell files overlaying new LRP. To understand how this striking pattern of LAX3 expression is regulated, we developed a mathematical model that captures the network regulating its expression and auxin transport within realistic three-dimensional cell and tissue geometries. Our model revealed that, for the LAX3 spatial expression to be robust to natural variations in root tissue geometry, an efflux carrier is required--later identified to be PIN3. To prevent LAX3 from being transiently expressed in multiple cell files, PIN3 and LAX3 must be induced consecutively, which we later demonstrated to be the case. Our study exemplifies how mathematical models can be used to direct experiments to elucidate complex developmental processes.}, author = {Péret, Benjamin and Middleton, Alistair M and French, Andrew P and Larrieu, Antoine and Bishopp, Anthony and Njo, Maria and Wells, Darren M and Porco, Silvana and Mellor, Nathan and Band, Leah R and Casimiro, Ilda and Kleine-Vehn, Jürgen and Vanneste, Steffen and Sairanen, Ilkka and Mallet, Romain and Sandberg, Göran and Ljung, Karin and Beeckman, Tom and Eva Benková and Jirí Friml and Kramer, Eric and King, John R and De Smet, Ive and Pridmore, Tony and Owen, Markus and Bennett, Malcolm J}, journal = {Molecular Systems Biology}, publisher = {Nature Publishing Group}, title = {{Sequential induction of auxin efflux and influx carriers regulates lateral root emergence}}, doi = {10.1038/msb.2013.43}, volume = {9}, year = {2013}, } @article{8461, abstract = {Solid-state NMR provides insight into protein motion over time scales ranging from picoseconds to seconds. While in solution state the methodology to measure protein dynamics is well established, there is currently no such consensus protocol for measuring dynamics in solids. In this article, we perform a detailed investigation of measurement protocols for fast motions, i.e. motions ranging from picoseconds to a few microseconds, which is the range covered by dipolar coupling and relaxation experiments. We perform a detailed theoretical investigation how dipolar couplings and relaxation data can provide information about amplitudes and time scales of local motion. We show that the measurement of dipolar couplings is crucial for obtaining accurate motional parameters, while systematic errors are found when only relaxation data are used. Based on this realization, we investigate how the REDOR experiment can provide such data in a very accurate manner. We identify that with accurate rf calibration, and explicit consideration of rf field inhomogeneities, one can obtain highly accurate absolute order parameters. We then perform joint model-free analyses of 6 relaxation data sets and dipolar couplings, based on previously existing, as well as new data sets on microcrystalline ubiquitin. We show that nanosecond motion can be detected primarily in loop regions, and compare solid-state data to solution-state relaxation and RDC analyses. The protocols investigated here will serve as a useful basis towards the establishment of a routine protocol for the characterization of ps–μs motions in proteins by solid-state NMR.}, author = {Haller, Jens D. and Schanda, Paul}, issn = {0925-2738}, journal = {Journal of Biomolecular NMR}, keywords = {Spectroscopy, Biochemistry}, number = {3}, pages = {263--280}, publisher = {Springer Nature}, title = {{Amplitudes and time scales of picosecond-to-microsecond motion in proteins studied by solid-state NMR: a critical evaluation of experimental approaches and application to crystalline ubiquitin}}, doi = {10.1007/s10858-013-9787-x}, volume = {57}, year = {2013}, } @article{8462, abstract = {The transition of proteins from their soluble functional state to amyloid fibrils and aggregates is associated with the onset of several human diseases. Protein aggregation often requires some structural reshaping and the subsequent formation of intermolecular contacts. Therefore, the study of the conformation of excited protein states and their ability to form oligomers is of primary importance for understanding the molecular basis of amyloid fibril formation. Here, we investigated the oligomerization processes that occur along the folding of the amyloidogenic human protein β2-microglobulin. The combination of real-time two-dimensional NMR data with real-time small-angle X-ray scattering measurements allowed us to derive thermodynamic and kinetic information on protein oligomerization of different conformational states populated along the folding pathways. In particular, we could demonstrate that a long-lived folding intermediate (I-state) has a higher propensity to oligomerize compared to the native state. Our data agree well with a simple five-state kinetic model that involves only monomeric and dimeric species. The dimers have an elongated shape with the dimerization interface located at the apical side of β2-microglobulin close to Pro32, the residue that has a trans conformation in the I-state and a cis conformation in the native (N) state. Our experimental data suggest that partial unfolding in the apical half of the protein close to Pro32 leads to an excited state conformation with enhanced propensity for oligomerization. This excited state becomes more populated in the transient I-state due to the destabilization of the native conformation by the trans-Pro32 configuration.}, author = {Rennella, E. and Cutuil, T. and Schanda, Paul and Ayala, I. and Gabel, F. and Forge, V. and Corazza, A. and Esposito, G. and Brutscher, B.}, issn = {0022-2836}, journal = {Journal of Molecular Biology}, keywords = {Molecular Biology}, number = {15}, pages = {2722--2736}, publisher = {Elsevier}, title = {{Oligomeric states along the folding pathways of β2-microglobulin: Kinetics, thermodynamics, and structure}}, doi = {10.1016/j.jmb.2013.04.028}, volume = {425}, year = {2013}, } @article{894, abstract = {Background: Genetic variation at the melanocortin-1 receptor (MC1R) gene is correlated with melanin color variation in many birds. Feral pigeons (Columba livia) show two major melanin-based colorations: a red coloration due to pheomelanic pigment and a black coloration due to eumelanic pigment. Furthermore, within each color type, feral pigeons display continuous variation in the amount of melanin pigment present in the feathers, with individuals varying from pure white to a full dark melanic color. Coloration is highly heritable and it has been suggested that it is under natural or sexual selection, or both. Our objective was to investigate whether MC1R allelic variants are associated with plumage color in feral pigeons. Findings. We sequenced 888 bp of the coding sequence of MC1R among pigeons varying both in the type, eumelanin or pheomelanin, and the amount of melanin in their feathers. We detected 10 non-synonymous substitutions and 2 synonymous substitution but none of them were associated with a plumage type. It remains possible that non-synonymous substitutions that influence coloration are present in the short MC1R fragment that we did not sequence but this seems unlikely because we analyzed the entire functionally important region of the gene. Conclusions: Our results show that color differences among feral pigeons are probably not attributable to amino acid variation at the MC1R locus. Therefore, variation in regulatory regions of MC1R or variation in other genes may be responsible for the color polymorphism of feral pigeons.}, author = {Derelle, Romain and Kondrashov, Fyodor and Arkhipov, Vladimir and Corbel, Hélène and Frantz, Adrien and Gasparini, Julien and Jacquin, Lisa and Jacob, Gwenaël and Thibault, Sophie and Baudry, Emmanuelle}, journal = {BMC Research Notes}, number = {1}, publisher = {BioMed Central}, title = {{Color differences among feral pigeons (Columba livia) are not attributable to sequence variation in the coding region of the melanocortin-1 receptor gene MC1R}}, doi = {10.1186/1756-0500-6-310}, volume = {6}, year = {2013}, }