@article{63, abstract = {African cichlids display a remarkable assortment of jaw morphologies, pigmentation patterns, and mating behaviors. In addition to this previously documented diversity, recent studies have documented a rich diversity of sex chromosomes within these fishes. Here we review the known sex-determination network within vertebrates, and the extraordinary number of sex chromosomes systems segregating in African cichlids. We also propose a model for understanding the unusual number of sex chromosome systems within this clade.}, author = {Gammerdinger, William J and Kocher, Thomas}, journal = {Genes}, number = {10}, publisher = {MDPI}, title = {{Unusual diversity of sex chromosomes in African cichlid fishes}}, doi = {10.3390/genes9100480}, volume = {9}, year = {2018}, } @article{6339, abstract = {We introduce a diagrammatic Monte Carlo approach to angular momentum properties of quantum many-particle systems possessing a macroscopic number of degrees of freedom. The treatment is based on a diagrammatic expansion that merges the usual Feynman diagrams with the angular momentum diagrams known from atomic and nuclear structure theory, thereby incorporating the non-Abelian algebra inherent to quantum rotations. Our approach is applicable at arbitrary coupling, is free of systematic errors and of finite-size effects, and naturally provides access to the impurity Green function. We exemplify the technique by obtaining an all-coupling solution of the angulon model; however, the method is quite general and can be applied to a broad variety of systems in which particles exchange quantum angular momentum with their many-body environment.}, author = {Bighin, Giacomo and Tscherbul, Timur and Lemeshko, Mikhail}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Diagrammatic Monte Carlo approach to angular momentum in quantum many-particle systems}}, doi = {10.1103/physrevlett.121.165301}, volume = {121}, year = {2018}, } @article{6354, abstract = {Blood platelets are critical for hemostasis and thrombosis, but also play diverse roles during immune responses. We have recently reported that platelets migrate at sites of infection in vitro and in vivo. Importantly, platelets use their ability to migrate to collect and bundle fibrin (ogen)-bound bacteria accomplishing efficient intravascular bacterial trapping. Here, we describe a method that allows analyzing platelet migration in vitro, focusing on their ability to collect bacteria and trap bacteria under flow.}, author = {Fan, Shuxia and Lorenz, Michael and Massberg, Steffen and Gärtner, Florian R}, issn = {2331-8325}, journal = {Bio-Protocol}, keywords = {Platelets, Cell migration, Bacteria, Shear flow, Fibrinogen, E. coli}, number = {18}, publisher = {Bio-Protocol}, title = {{Platelet migration and bacterial trapping assay under flow}}, doi = {10.21769/bioprotoc.3018}, volume = {8}, year = {2018}, } @article{6355, abstract = {We prove that any cyclic quadrilateral can be inscribed in any closed convex C1-curve. The smoothness condition is not required if the quadrilateral is a rectangle.}, author = {Akopyan, Arseniy and Avvakumov, Sergey}, issn = {2050-5094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Any cyclic quadrilateral can be inscribed in any closed convex smooth curve}}, doi = {10.1017/fms.2018.7}, volume = {6}, year = {2018}, } @article{6368, abstract = {An optical network of superconducting quantum bits (qubits) is an appealing platform for quantum communication and distributed quantum computing, but developing a quantum-compatible link between the microwave and optical domains remains an outstanding challenge. Operating at T < 100 mK temperatures, as required for quantum electrical circuits, we demonstrate a mechanically mediated microwave–optical converter with 47% conversion efficiency, and use a classical feed-forward protocol to reduce added noise to 38 photons. The feed-forward protocol harnesses our discovery that noise emitted from the two converter output ports is strongly correlated because both outputs record thermal motion of the same mechanical mode. We also discuss a quantum feed-forward protocol that, given high system efficiencies, would allow quantum information to be transferred even when thermal phonons enter the mechanical element faster than the electro-optic conversion rate.}, author = {Higginbotham, Andrew P and Burns, P. S. and Urmey, M. D. and Peterson, R. W. and Kampel, N. S. and Brubaker, B. M. and Smith, G. and Lehnert, K. W. and Regal, C. A.}, issn = {1745-2473}, journal = {Nature Physics}, number = {10}, pages = {1038--1042}, publisher = {Springer Nature}, title = {{Harnessing electro-optic correlations in an efficient mechanical converter}}, doi = {10.1038/s41567-018-0210-0}, volume = {14}, year = {2018}, } @article{6369, abstract = {We construct a metamaterial from radio-frequency harmonic oscillators, and find two topologically distinct phases resulting from dissipation engineered into the system. These phases are distinguished by a quantized value of bulk energy transport. The impulse response of our circuit is measured and used to reconstruct the band structure and winding number of circuit eigenfunctions around a dark mode. Our results demonstrate that dissipative topological transport can occur in a wider class of physical systems than considered before.}, author = {Rosenthal, Eric I. and Ehrlich, Nicole K. and Rudner, Mark S. and Higginbotham, Andrew P and Lehnert, K. W.}, issn = {2469-9950}, journal = {Physical Review B}, number = {22}, publisher = {American Physical Society (APS)}, title = {{Topological phase transition measured in a dissipative metamaterial}}, doi = {10.1103/physrevb.97.220301}, volume = {97}, year = {2018}, } @article{64, abstract = {Tropical geometry, an established field in pure mathematics, is a place where string theory, mirror symmetry, computational algebra, auction theory, and so forth meet and influence one another. In this paper, we report on our discovery of a tropical model with self-organized criticality (SOC) behavior. Our model is continuous, in contrast to all known models of SOC, and is a certain scaling limit of the sandpile model, the first and archetypical model of SOC. We describe how our model is related to pattern formation and proportional growth phenomena and discuss the dichotomy between continuous and discrete models in several contexts. Our aim in this context is to present an idealized tropical toy model (cf. Turing reaction-diffusion model), requiring further investigation.}, author = {Kalinin, Nikita and Guzmán Sáenz, Aldo and Prieto, Y and Shkolnikov, Mikhail and Kalinina, V and Lupercio, Ernesto}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {35}, pages = {E8135 -- E8142}, publisher = {National Academy of Sciences}, title = {{Self-organized criticality and pattern emergence through the lens of tropical geometry}}, doi = {10.1073/pnas.1805847115}, volume = {115}, year = {2018}, } @article{19806, abstract = {Transition-metal dichalcogenides (TMDs) are renowned for their rich and varied bulk properties, while their single-layer variants have become one of the most prominent examples of two-dimensional materials beyond graphene. Their disparate ground states largely depend on transition metal d-electron-derived electronic states, on which the vast majority of attention has been concentrated to date. Here, we focus on the chalcogen-derived states. From density-functional theory calculations together with spin- and angle-resolved photoemission, we find that these generically host a co-existence of type-I and type-II three-dimensional bulk Dirac fermions as well as ladders of topological surface states and surface resonances. We demonstrate how these naturally arise within a single p-orbital manifold as a general consequence of a trigonal crystal field, and as such can be expected across a large number of compounds. Already, we demonstrate their existence in six separate TMDs, opening routes to tune, and ultimately exploit, their topological physics.}, author = {Bahramy, M. S. and Clark, O. J. and Yang, B.-J. and Feng, J. and Bawden, L. and Riley, J. M. and Marković, I. and Mazzola, F. and Sunko, Veronika and Biswas, D. and Cooil, S. P. and Jorge, M. and Wells, J. W. and Leandersson, M. and Balasubramanian, T. and Fujii, J. and Vobornik, I. and Rault, J. E. and Kim, T. K. and Hoesch, M. and Okawa, K. and Asakawa, M. and Sasagawa, T. and Eknapakul, T. and Meevasana, W. and King, P. D. C.}, issn = {1476-4660}, journal = {Nature Materials}, pages = {21--28}, publisher = {Springer Nature}, title = {{Ubiquitous formation of bulk Dirac cones and topological surface states from a single orbital manifold in transition-metal dichalcogenides}}, doi = {10.1038/nmat5031}, volume = {17}, year = {2018}, } @article{19808, abstract = {The single-band, quasi-two dimensional metals PdCoO2 and PtCoO2 have recently come to prominence because of their extremely long mean free paths, which establish them as some of the most electronically pure materials known, and as potential hosts of previously unobservable regimes of electronic transport. To fully establish their magnetotransport properties, we have studied the magnetoresistance and Hall effect in bulk single crystals to which electrical contacts have been made with high precision using focused ion beam machining. We observe a strong temperature dependence of the Hall resistivity in small applied fields, linked to a large violation of Kohler’s rule in the magnetoresistance. We discuss the extent to which these observations can be accounted for by standard transport theory.}, author = {Nandi, Nabhanila and Scaffidi, Thomas and Kushwaha, Pallavi and Khim, Seunghyun and Barber, Mark E. and Sunko, Veronika and Mazzola, Federico and King, Philip D. C. and Rosner, Helge and Moll, Philip J. W. and König, Markus and Moore, Joel E. and Hartnoll, Sean and Mackenzie, Andrew P.}, issn = {2397-4648}, journal = {npj Quantum Materials}, publisher = {Springer Nature}, title = {{Unconventional magneto-transport in ultrapure PdCoO2 and PtCoO2}}, doi = {10.1038/s41535-018-0138-8}, volume = {3}, year = {2018}, } @article{19813, abstract = {We study the low-energy surface electronic structure of the transition-metal dichalcogenide superconductor PdTe2 by spin- and angle-resolved photoemission, scanning tunneling microscopy, and density-functional theory-based supercell calculations. Comparing PdTe2 with its sister compound PtSe2, we demonstrate how enhanced interlayer hopping in the Te-based material drives a band inversion within the antibonding 𝑝-orbital manifold well above the Fermi level. We show how this mediates spin-polarized topological surface states which form rich multivalley Fermi surfaces with complex spin textures. Scanning tunneling spectroscopy reveals type-II superconductivity at the surface, and moreover shows no evidence for an unconventional component of its superconducting order parameter, despite the presence of topological surface states.}, author = {Clark, O. J. and Neat, M. J. and Okawa, K. and Bawden, L. and Marković, I. and Mazzola, F. and Feng, J. and Sunko, Veronika and Riley, J. M. and Meevasana, W. and Fujii, J. and Vobornik, I. and Kim, T. K. and Hoesch, M. and Sasagawa, T. and Wahl, P. and Bahramy, M. S. and King, P. D. C.}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {15}, publisher = {American Physical Society}, title = {{Fermiology and superconductivity of topological surface states in PdTe2}}, doi = {10.1103/physrevlett.120.156401}, volume = {120}, year = {2018}, } @article{19819, abstract = {The ability to modulate the collective properties of correlated electron systems at their interfaces and surfaces underpins the burgeoning field of “designer” quantum materials. Here, we show how an electronic reconstruction driven by surface polarity mediates a Stoner-like magnetic instability to itinerant ferromagnetism at the Pd-terminated surface of the nonmagnetic delafossite oxide metal PdCoO2. Combining angle-resolved photoemission spectroscopy and density-functional theory calculations, we show how this leads to a rich multiband surface electronic structure. We find similar surface state dispersions in PdCrO2, suggesting surface ferromagnetism persists in this sister compound despite its bulk antiferromagnetic order.}, author = {Mazzola, Federico and Sunko, Veronika and Khim, Seunghyun and Rosner, Helge and Kushwaha, Pallavi and Clark, Oliver J. and Bawden, Lewis and Marković, Igor and Kim, Timur K. and Hoesch, Moritz and Mackenzie, Andrew P. and King, Phil D. C.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {51}, pages = {12956--12960}, publisher = {National Academy of Sciences}, title = {{Itinerant ferromagnetism of the Pd-terminated polar surface of PdCoO2}}, doi = {10.1073/pnas.1811873115}, volume = {115}, year = {2018}, } @article{199, abstract = {Sex-biased genes are central to the study of sexual selection, sexual antagonism, and sex chromosome evolution. We describe a comprehensive de novo assembled transcriptome in the common frog Rana temporaria based on five developmental stages and three adult tissues from both sexes, obtained from a population with karyotypically homomorphic but genetically differentiated sex chromosomes. This allows the study of sex-biased gene expression throughout development, and its effect on the rate of gene evolution while accounting for pleiotropic expression, which is known to negatively correlate with the evolutionary rate. Overall, sex-biased genes had little overlap among developmental stages and adult tissues. Late developmental stages and gonad tissues had the highest numbers of stage-or tissue-specific genes. We find that pleiotropic gene expression is a better predictor than sex bias for the evolutionary rate of genes, though it often interacts with sex bias. Although genetically differentiated, the sex chromosomes were not enriched in sex-biased genes, possibly due to a very recent arrest of XY recombination. These results extend our understanding of the developmental dynamics, tissue specificity, and genomic localization of sex-biased genes.}, author = {Ma, Wen and Veltsos, Paris and Toups, Melissa A and Rodrigues, Nicolas and Sermier, Roberto and Jeffries, Daniel and Perrin, Nicolas}, journal = {Genes}, number = {6}, publisher = {MDPI}, title = {{Tissue specificity and dynamics of sex biased gene expression in a common frog population with differentiated, yet homomorphic, sex chromosomes}}, doi = {10.3390/genes9060294}, volume = {9}, year = {2018}, } @article{20, abstract = {Background: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level. Results: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses. Conclusions: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function.}, author = {Higareda Almaraz, Juan and Karbiener, Michael and Giroud, Maude and Pauler, Florian and Gerhalter, Teresa and Herzig, Stephan and Scheideler, Marcel}, issn = {1471-2164}, journal = {BMC Genomics}, number = {1}, publisher = {BioMed Central}, title = {{Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes}}, doi = {10.1186/s12864-018-5173-0}, volume = {19}, year = {2018}, } @phdthesis{200, abstract = {This thesis is concerned with the inference of current population structure based on geo-referenced genetic data. The underlying idea is that population structure affects its spatial genetic structure. Therefore, genotype information can be utilized to estimate important demographic parameters such as migration rates. These indirect estimates of population structure have become very attractive, as genotype data is now widely available. However, there also has been much concern about these approaches. Importantly, genetic structure can be influenced by many complex patterns, which often cannot be disentangled. Moreover, many methods merely fit heuristic patterns of genetic structure, and do not build upon population genetics theory. Here, I describe two novel inference methods that address these shortcomings. In Chapter 2, I introduce an inference scheme based on a new type of signal, identity by descent (IBD) blocks. Recently, it has become feasible to detect such long blocks of genome shared between pairs of samples. These blocks are direct traces of recent coalescence events. As such, they contain ample signal for inferring recent demography. I examine sharing of IBD blocks in two-dimensional populations with local migration. Using a diffusion approximation, I derive formulas for an isolation by distance pattern of long IBD blocks and show that sharing of long IBD blocks approaches rapid exponential decay for growing sample distance. I describe an inference scheme based on these results. It can robustly estimate the dispersal rate and population density, which is demonstrated on simulated data. I also show an application to estimate mean migration and the rate of recent population growth within Eastern Europe. Chapter 3 is about a novel method to estimate barriers to gene flow in a two dimensional population. This inference scheme utilizes geographically localized allele frequency fluctuations - a classical isolation by distance signal. The strength of these local fluctuations increases on average next to a barrier, and there is less correlation across it. I again use a framework of diffusion of ancestral lineages to model this effect, and provide an efficient numerical implementation to fit the results to geo-referenced biallelic SNP data. This inference scheme is able to robustly estimate strong barriers to gene flow, as tests on simulated data confirm.}, author = {Ringbauer, Harald}, issn = {2663-337X}, pages = {146}, publisher = {Institute of Science and Technology Austria}, title = {{Inferring recent demography from spatial genetic structure}}, doi = {10.15479/AT:ISTA:th_963}, year = {2018}, } @article{2015, abstract = {We consider the problem of learning a Bayesian network or directed acyclic graph model from observational data. A number of constraint‐based, score‐based and hybrid algorithms have been developed for this purpose. Statistical consistency guarantees of these algorithms rely on the faithfulness assumption, which has been shown to be restrictive especially for graphs with cycles in the skeleton. We here propose the sparsest permutation (SP) algorithm, showing that learning Bayesian networks is possible under strictly weaker assumptions than faithfulness. This comes at a computational price, thereby indicating a statistical‐computational trade‐off for causal inference algorithms. In the Gaussian noiseless setting, we prove that the SP algorithm boils down to finding the permutation of the variables with the sparsest Cholesky decomposition of the inverse covariance matrix, which is equivalent to ℓ0‐penalized maximum likelihood estimation. We end with a simulation study showing that in line with the proven stronger consistency guarantees, and the SP algorithm compares favourably to standard causal inference algorithms in terms of accuracy for a given sample size.}, author = {Raskutti, Garvesh and Uhler, Caroline}, journal = {STAT}, number = {1}, publisher = {Wiley}, title = {{Learning directed acyclic graphs based on sparsest permutations}}, doi = {10.1002/sta4.183}, volume = {7}, year = {2018}, } @article{203, abstract = {Asymmetric auxin distribution is instrumental for the differential growth that causes organ bending on tropic stimuli and curvatures during plant development. Local differences in auxin concentrations are achieved mainly by polarized cellular distribution of PIN auxin transporters, but whether other mechanisms involving auxin homeostasis are also relevant for the formation of auxin gradients is not clear. Here we show that auxin methylation is required for asymmetric auxin distribution across the hypocotyl, particularly during its response to gravity. We found that loss-of-function mutants in Arabidopsis IAA CARBOXYL METHYLTRANSFERASE1 (IAMT1) prematurely unfold the apical hook, and that their hypocotyls are impaired in gravitropic reorientation. This defect is linked to an auxin-dependent increase in PIN gene expression, leading to an increased polar auxin transport and lack of asymmetric distribution of PIN3 in the iamt1 mutant. Gravitropic reorientation in the iamt1 mutant could be restored with either endodermis-specific expression of IAMT1 or partial inhibition of polar auxin transport, which also results in normal PIN gene expression levels. We propose that IAA methylation is necessary in gravity-sensing cells to restrict polar auxin transport within the range of auxin levels that allow for differential responses.}, author = {Abbas, Mohamad and Hernández, García J and Pollmann, Stephan and Samodelov, Sophia L and Kolb, Martina and Friml, Jirí and Hammes, Ulrich Z and Zurbriggen, Matias D and Blázquez, Miguel and Alabadí, David}, journal = {PNAS}, number = {26}, pages = {6864--6869}, publisher = {National Academy of Sciences}, title = {{Auxin methylation is required for differential growth in Arabidopsis}}, doi = {10.1073/pnas.1806565115}, volume = {115}, year = {2018}, } @article{10357, abstract = {The misfolding and aggregation of proteins into linear fibrils is widespread in human biology, for example, in connection with amyloid formation and the pathology of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. The oligomeric species that are formed in the early stages of protein aggregation are of great interest, having been linked with the cellular toxicity associated with these conditions. However, these species are not characterized in any detail experimentally, and their properties are not well understood. Many of these species have been found to have approximately spherical morphology and to be held together by hydrophobic interactions. We present here an analytical statistical mechanical model of globular oligomer formation from simple idealized amphiphilic protein monomers and show that this correlates well with Monte Carlo simulations of oligomer formation. We identify the controlling parameters of the model, which are closely related to simple quantities that may be fitted directly from experiment. We predict that globular oligomers are unlikely to form at equilibrium in many polypeptide systems but instead form transiently in the early stages of amyloid formation. We contrast the globular model of oligomer formation to a well-established model of linear oligomer formation, highlighting how the differing ensemble properties of linear and globular oligomers offer a potential strategy for characterizing oligomers from experimental measurements.}, author = {Dear, Alexander J. and Šarić, Anđela and Michaels, Thomas C. T. and Dobson, Christopher M. and Knowles, Tuomas P. J.}, issn = {1520-5207}, journal = {The Journal of Physical Chemistry B}, keywords = {materials chemistry}, number = {49}, pages = {11721--11730}, publisher = {American Chemical Society}, title = {{Statistical mechanics of globular oligomer formation by protein molecules}}, doi = {10.1021/acs.jpcb.8b07805}, volume = {122}, year = {2018}, } @article{10358, abstract = {Probing reaction mechanisms of supramolecular processes in soft and biological matter, such as protein aggregation, is inherently challenging. This is because these processes involve multiple molecular mechanisms that are associated with the rearrangement of large numbers of weak bonds, resulting in complex free energy landscapes with many kinetic barriers. Reaction rate measurements at different temperatures can offer unprecedented insights into the underlying molecular mechanisms. However, to be able to interpret such measurements, a key challenge is to establish which properties of the complex free energy landscapes are probed by the reaction rate. Here, we present a reaction rate theory for supramolecular kinetics based on Kramers theory of diffusive reactions over multiple kinetic barriers. We find that reaction rates for protein aggregation are of the Arrhenius–Eyring type and that the associated activation energies probe only one relevant barrier along the respective free energy landscapes. We apply this advancement to interpret, in experiments and in coarse-grained computer simulations, reaction rates of amyloid aggregation in terms of molecular mechanisms and associated thermodynamic signatures. These results suggest a practical extension of the concept of rate-determining steps for complex supramolecular processes and establish a general platform for probing the underlying energy landscape using kinetic measurements.}, author = {Michaels, Thomas C. T. and Liu, Lucie X. and Curk, Samo and Bolhuis, Peter G. and Šarić, Anđela and Knowles, Tuomas P. J.}, issn = {1362-3028}, journal = {Molecular Physics}, keywords = {physical chemistry}, number = {21-22}, pages = {3055--3065}, publisher = {Taylor & Francis}, title = {{Reaction rate theory for supramolecular kinetics: application to protein aggregation}}, doi = {10.1080/00268976.2018.1474280}, volume = {116}, year = {2018}, } @article{10359, abstract = {Biological membranes typically contain a large number of different components dispersed in small concentrations in the main membrane phase, including proteins, sugars, and lipids of varying geometrical properties. Most of these components do not bind the cargo. Here, we show that such “inert” components can be crucial for the precise control of cross-membrane trafficking. Using a statistical mechanics model and molecular dynamics simulations, we demonstrate that the presence of inert membrane components of small isotropic curvatures dramatically influences cargo endocytosis, even if the total spontaneous curvature of such a membrane remains unchanged. Curved lipids, such as cholesterol, as well as asymmetrically included proteins and tethered sugars can, therefore, actively participate in the control of the membrane trafficking of nanoscopic cargo. We find that even a low-level expression of curved inert membrane components can determine the membrane selectivity toward the cargo size and can be used to selectively target membranes of certain compositions. Our results suggest a robust and general method of controlling cargo trafficking by adjusting the membrane composition without needing to alter the concentration of receptors or the average membrane curvature. This study indicates that cells can prepare for any trafficking event by incorporating curved inert components in either of the membrane leaflets.}, author = {Curk, Tine and Wirnsberger, Peter and Dobnikar, Jure and Frenkel, Daan and Šarić, Anđela}, issn = {1530-6992}, journal = {Nano Letters}, keywords = {mechanical engineering, condensed matter physics}, number = {9}, pages = {5350--5356}, publisher = {American Chemical Society}, title = {{Controlling cargo trafficking in multicomponent membranes}}, doi = {10.1021/acs.nanolett.8b00786}, volume = {18}, year = {2018}, } @article{10360, abstract = {Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer’s disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.}, author = {Cohen, Samuel I. A. and Cukalevski, Risto and Michaels, Thomas C. T. and Šarić, Anđela and Törnquist, Mattias and Vendruscolo, Michele and Dobson, Christopher M. and Buell, Alexander K. and Knowles, Tuomas P. J. and Linse, Sara}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {general chemical engineering, general chemistry}, number = {5}, pages = {523--531}, publisher = {Springer Nature}, title = {{Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide}}, doi = {10.1038/s41557-018-0023-x}, volume = {10}, year = {2018}, }