@article{9887, abstract = {Clathrin-mediated endocytosis is the major route of entry of cargos into cells and thus underpins many physiological processes. During endocytosis, an area of flat membrane is remodeled by proteins to create a spherical vesicle against intracellular forces. The protein machinery which mediates this membrane bending in plants is unknown. However, it is known that plant endocytosis is actin independent, thus indicating that plants utilize a unique mechanism to mediate membrane bending against high-turgor pressure compared to other model systems. Here, we investigate the TPLATE complex, a plant-specific endocytosis protein complex. It has been thought to function as a classical adaptor functioning underneath the clathrin coat. However, by using biochemical and advanced live microscopy approaches, we found that TPLATE is peripherally associated with clathrin-coated vesicles and localizes at the rim of endocytosis events. As this localization is more fitting to the protein machinery involved in membrane bending during endocytosis, we examined cells in which the TPLATE complex was disrupted and found that the clathrin structures present as flat patches. This suggests a requirement of the TPLATE complex for membrane bending during plant clathrin–mediated endocytosis. Next, we used in vitro biophysical assays to confirm that the TPLATE complex possesses protein domains with intrinsic membrane remodeling activity. These results redefine the role of the TPLATE complex and implicate it as a key component of the evolutionarily distinct plant endocytosis mechanism, which mediates endocytic membrane bending against the high-turgor pressure in plant cells.}, author = {Johnson, Alexander J and Dahhan, Dana A and Gnyliukh, Nataliia and Kaufmann, Walter and Zheden, Vanessa and Costanzo, Tommaso and Mahou, Pierre and Hrtyan, Mónika and Wang, Jie and Aguilera Servin, Juan L and van Damme, Daniël and Beaurepaire, Emmanuel and Loose, Martin and Bednarek, Sebastian Y and Friml, Jiří}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {51}, publisher = {National Academy of Sciences}, title = {{The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis}}, doi = {10.1073/pnas.2113046118}, volume = {118}, year = {2021}, } @article{7580, abstract = {The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell.}, author = {Bezeljak, Urban and Loya, Hrushikesh and Kaczmarek, Beata M and Saunders, Timothy E. and Loose, Martin}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {12}, pages = {6504--6549}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Stochastic activation and bistability in a Rab GTPase regulatory network}}, doi = {10.1073/pnas.1921027117}, volume = {117}, year = {2020}, } @article{8002, abstract = {Wound healing in plant tissues, consisting of rigid cell wall-encapsulated cells, represents a considerable challenge and occurs through largely unknown mechanisms distinct from those in animals. Owing to their inability to migrate, plant cells rely on targeted cell division and expansion to regenerate wounds. Strict coordination of these wound-induced responses is essential to ensure efficient, spatially restricted wound healing. Single-cell tracking by live imaging allowed us to gain mechanistic insight into the wound perception and coordination of wound responses after laser-based wounding in Arabidopsis root. We revealed a crucial contribution of the collapse of damaged cells in wound perception and detected an auxin increase specific to cells immediately adjacent to the wound. This localized auxin increase balances wound-induced cell expansion and restorative division rates in a dose-dependent manner, leading to tumorous overproliferation when the canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure changes together also spatially define the activation of key components of regeneration, such as the transcription regulator ERF115. Our observations suggest that the wound signaling involves the sensing of collapse of damaged cells and a local auxin signaling activation to coordinate the downstream transcriptional responses in the immediate wound vicinity.}, author = {Hörmayer, Lukas and Montesinos López, Juan C and Marhavá, Petra and Benková, Eva and Yoshida, Saiko and Friml, Jiří}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {26}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots}}, doi = {10.1073/pnas.2003346117}, volume = {117}, year = {2020}, } @article{15061, abstract = {The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.}, author = {Pinotsis, Nikos and Zielinska, Karolina and Babuta, Mrigya and Arolas, Joan L. and Kostan, Julius and Khan, Muhammad Bashir and Schreiner, Claudia and Testa Salmazo, Anita P and Ciccarelli, Luciano and Puchinger, Martin and Gkougkoulia, Eirini A. and Ribeiro, Euripedes de Almeida and Marlovits, Thomas C. and Bhattacharya, Alok and Djinovic-Carugo, Kristina}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {36}, pages = {22101--22112}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin}}, doi = {10.1073/pnas.1917269117}, volume = {117}, year = {2020}, } @article{10336, abstract = {Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.}, author = {Krausser, Johannes and Knowles, Tuomas P. J. and Šarić, Anđela}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {52}, pages = {33090--33098}, publisher = {National Academy of Sciences}, title = {{Physical mechanisms of amyloid nucleation on fluid membranes}}, doi = {10.1073/pnas.2007694117}, volume = {117}, year = {2020}, } @article{10347, abstract = {Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors.}, author = {Michaels, Thomas C. T. and Šarić, Anđela and Meisl, Georg and Heller, Gabriella T. and Curk, Samo and Arosio, Paolo and Linse, Sara and Dobson, Christopher M. and Vendruscolo, Michele and Knowles, Tuomas P. J.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {multidisciplinary}, number = {39}, pages = {24251--24257}, publisher = {National Academy of Sciences}, title = {{Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors}}, doi = {10.1073/pnas.2006684117}, volume = {117}, year = {2020}, } @article{6999, abstract = {Plasmodesmata (PD) are plant-specific membrane-lined channels that create cytoplasmic and membrane continuities between adjacent cells, thereby facilitating cell–cell communication and virus movement. Plant cells have evolved diverse mechanisms to regulate PD plasticity in response to numerous environmental stimuli. In particular, during defense against plant pathogens, the defense hormone, salicylic acid (SA), plays a crucial role in the regulation of PD permeability in a callose-dependent manner. Here, we uncover a mechanism by which plants restrict the spreading of virus and PD cargoes using SA signaling by increasing lipid order and closure of PD. We showed that exogenous SA application triggered the compartmentalization of lipid raft nanodomains through a modulation of the lipid raft-regulatory protein, Remorin (REM). Genetic studies, superresolution imaging, and transmission electron microscopy observation together demonstrated that Arabidopsis REM1.2 and REM1.3 are crucial for plasma membrane nanodomain assembly to control PD aperture and functionality. In addition, we also found that a 14-3-3 epsilon protein modulates REM clustering and membrane nanodomain compartmentalization through its direct interaction with REM proteins. This study unveils a molecular mechanism by which the key plant defense hormone, SA, triggers membrane lipid nanodomain reorganization, thereby regulating PD closure to impede virus spreading.}, author = {Huang, D and Sun, Y and Ma, Z and Ke, M and Cui, Y and Chen, Z and Chen, C and Ji, C and Tran, TM and Yang, L and Lam, SM and Han, Y and Shu, G and Friml, Jiří and Miao, Y and Jiang, L and Chen, X}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {42}, pages = {21274--21284}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Salicylic acid-mediated plasmodesmal closure via Remorin-dependent lipid organization}}, doi = {10.1073/pnas.1911892116}, volume = {116}, year = {2019}, } @article{196, abstract = {The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. }, author = {Lang, Moritz and Shkolnikov, Mikhail}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {8}, pages = {2821--2830}, publisher = {National Academy of Sciences}, title = {{Harmonic dynamics of the Abelian sandpile}}, doi = {10.1073/pnas.1812015116}, volume = {116}, year = {2019}, } @article{14001, abstract = {Chiral molecules interact and react differently with other chiral objects, depending on their handedness. Therefore, it is essential to understand and ultimately control the evolution of molecular chirality during chemical reactions. Although highly sophisticated techniques for the controlled synthesis of chiral molecules have been developed, the observation of chirality on the natural femtosecond time scale of a chemical reaction has so far remained out of reach in the gas phase. Here, we demonstrate a general experimental technique, based on high-harmonic generation in tailored laser fields, and apply it to probe the time evolution of molecular chirality during the photodissociation of 2-iodobutane. These measurements show a change in sign and a pronounced increase in the magnitude of the chiral response over the first 100 fs, followed by its decay within less than 500 fs, revealing the photodissociation to achiral products. The observed time evolution is explained in terms of the variation of the electric and magnetic transition-dipole moments between the lowest electronic states of the cation as a function of the reaction coordinate. These results open the path to investigations of the chirality of molecular-reaction pathways, light-induced chirality in chemical processes, and the control of molecular chirality through tailored laser pulses.}, author = {Baykusheva, Denitsa Rangelova and Zindel, Daniel and Svoboda, Vít and Bommeli, Elias and Ochsner, Manuel and Tehlar, Andres and Wörner, Hans Jakob}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {48}, pages = {23923--23929}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Real-time probing of chirality during a chemical reaction}}, doi = {10.1073/pnas.1907189116}, volume = {116}, year = {2019}, } @article{9460, abstract = {Epigenetic reprogramming is required for proper regulation of gene expression in eukaryotic organisms. In Arabidopsis, active DNA demethylation is crucial for seed viability, pollen function, and successful reproduction. The DEMETER (DME) DNA glycosylase initiates localized DNA demethylation in vegetative and central cells, so-called companion cells that are adjacent to sperm and egg gametes, respectively. In rice, the central cell genome displays local DNA hypomethylation, suggesting that active DNA demethylation also occurs in rice; however, the enzyme responsible for this process is unknown. One candidate is the rice REPRESSOR OF SILENCING 1a (ROS1a) gene, which is related to DME and is essential for rice seed viability and pollen function. Here, we report genome-wide analyses of DNA methylation in wild-type and ros1a mutant sperm and vegetative cells. We find that the rice vegetative cell genome is locally hypomethylated compared with sperm by a process that requires ROS1a activity. We show that many ROS1a target sequences in the vegetative cell are hypomethylated in the rice central cell, suggesting that ROS1a also demethylates the central cell genome. Similar to Arabidopsis, we show that sperm non-CG methylation is indirectly promoted by DNA demethylation in the vegetative cell. These results reveal that DNA glycosylase-mediated DNA demethylation processes are conserved in Arabidopsis and rice, plant species that diverged 150 million years ago. Finally, although global non-CG methylation levels of sperm and egg differ, the maternal and paternal embryo genomes show similar non-CG methylation levels, suggesting that rice gamete genomes undergo dynamic DNA methylation reprogramming after cell fusion.}, author = {Kim, M. Yvonne and Ono, Akemi and Scholten, Stefan and Kinoshita, Tetsu and Zilberman, Daniel and Okamoto, Takashi and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {19}, pages = {9652--9657}, publisher = {National Academy of Sciences}, title = {{DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm}}, doi = {10.1073/pnas.1821435116}, volume = {116}, year = {2019}, } @article{9689, abstract = {A central goal of computational physics and chemistry is to predict material properties by using first-principles methods based on the fundamental laws of quantum mechanics. However, the high computational costs of these methods typically prevent rigorous predictions of macroscopic quantities at finite temperatures, such as heat capacity, density, and chemical potential. Here, we enable such predictions by marrying advanced free-energy methods with data-driven machine-learning interatomic potentials. We show that, for the ubiquitous and technologically essential system of water, a first-principles thermodynamic description not only leads to excellent agreement with experiments, but also reveals the crucial role of nuclear quantum fluctuations in modulating the thermodynamic stabilities of different phases of water.}, author = {Cheng, Bingqing and Engel, Edgar A. and Behler, Jörg and Dellago, Christoph and Ceriotti, Michele}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {4}, pages = {1110--1115}, publisher = {National Academy of Sciences}, title = {{Ab initio thermodynamics of liquid and solid water}}, doi = {10.1073/pnas.1815117116}, volume = {116}, year = {2019}, } @article{12607, abstract = {Supraglacial ice cliffs exist on debris-covered glaciers worldwide, but despite their importance as melt hot spots, their life cycle is little understood. Early field observations had advanced a hypothesis of survival of north-facing and disappearance of south-facing cliffs, which is central for predicting the contribution of cliffs to total glacier mass losses. Their role as windows of energy transfer suggests they may explain the anomalously high mass losses of debris-covered glaciers in High Mountain Asia (HMA) despite the insulating debris, currently at the center of a debated controversy. We use a 3D model of cliff evolution coupled to very high-resolution topographic data to demonstrate that ice cliffs facing south (in the Northern Hemisphere) disappear within a few months due to enhanced solar radiation receipts and that aspect is the key control on cliffs evolution. We reproduce continuous flattening of south-facing cliffs, a result of their vertical gradient of incoming solar radiation and sky view factor. Our results establish that only north-facing cliffs are recurrent features and thus stable contributors to the melting of debris-covered glaciers. Satellite observations and mass balance modeling confirms that few south-facing cliffs of small size exist on the glaciers of Langtang, and their contribution to the glacier volume losses is very small (∼1%). This has major implications for the mass balance of HMA debris-covered glaciers as it provides the basis for new parameterizations of cliff evolution and distribution to constrain volume losses in a region where glaciers are highly relevant as water sources for millions of people.}, author = {Buri, Pascal and Pellicciotti, Francesca}, issn = {1091-6490}, journal = {PNAS}, number = {17}, pages = {4369--4374}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Aspect controls the survival of ice cliffs on debris-covered glaciers}}, doi = {10.1073/pnas.1713892115}, volume = {115}, year = {2018}, } @article{13376, abstract = {Efficient molecular switching in confined spaces is critical for the successful development of artificial molecular machines. However, molecular switching events often entail large structural changes and therefore require conformational freedom, which is typically limited under confinement conditions. Here, we investigated the behavior of azobenzene—the key building block of light-controlled molecular machines—in a confined environment that is flexible and can adapt its shape to that of the bound guest. To this end, we encapsulated several structurally diverse azobenzenes within the cavity of a flexible, water-soluble coordination cage, and investigated their light-responsive behavior. Using UV/Vis absorption spectroscopy and a combination of NMR methods, we showed that each of the encapsulated azobenzenes exhibited distinct switching properties. An azobenzene forming a 1:1 host–guest inclusion complex could be efficiently photoisomerized in a reversible fashion. In contrast, successful switching in inclusion complexes incorporating two azobenzene guests was dependent on the availability of free cages in the system, and it involved reversible trafficking of azobenzene between the cages. In the absence of extra cages, photoswitching was either suppressed or it involved expulsion of azobenzene from the cage and consequently its precipitation from the solution. This finding was utilized to develop an information storage medium in which messages could be written and erased in a reversible fashion using light.}, author = {Samanta, Dipak and Gemen, Julius and Chu, Zonglin and Diskin-Posner, Yael and Shimon, Linda J. W. and Klajn, Rafal}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {38}, pages = {9379--9384}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Reversible photoswitching of encapsulated azobenzenes in water}}, doi = {10.1073/pnas.1712787115}, volume = {115}, year = {2018}, } @article{6010, abstract = {The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity.}, author = {Garrido-Charad, Florencia and Vega Zuniga, Tomas A and Gutiérrez-Ibáñez, Cristián and Fernandez, Pedro and López-Jury, Luciana and González-Cabrera, Cristian and Karten, Harvey J. and Luksch, Harald and Marín, Gonzalo J.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {32}, pages = {E7615--E7623}, publisher = {National Academy of Sciences}, title = {{“Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network}}, doi = {10.1073/pnas.1804517115}, volume = {115}, year = {2018}, } @article{9471, abstract = {The DEMETER (DME) DNA glycosylase catalyzes genome-wide DNA demethylation and is required for endosperm genomic imprinting and embryo viability. Targets of DME-mediated DNA demethylation reside in small, euchromatic, AT-rich transposons and at the boundaries of large transposons, but how DME interacts with these diverse chromatin states is unknown. The STRUCTURE SPECIFIC RECOGNITION PROTEIN 1 (SSRP1) subunit of the chromatin remodeler FACT (facilitates chromatin transactions), was previously shown to be involved in the DME-dependent regulation of genomic imprinting in Arabidopsis endosperm. Therefore, to investigate the interaction between DME and chromatin, we focused on the activity of the two FACT subunits, SSRP1 and SUPPRESSOR of TY16 (SPT16), during reproduction in Arabidopsis. We found that FACT colocalizes with nuclear DME in vivo, and that DME has two classes of target sites, the first being euchromatic and accessible to DME, but the second, representing over half of DME targets, requiring the action of FACT for DME-mediated DNA demethylation genome-wide. Our results show that the FACT-dependent DME targets are GC-rich heterochromatin domains with high nucleosome occupancy enriched with H3K9me2 and H3K27me1. Further, we demonstrate that heterochromatin-associated linker histone H1 specifically mediates the requirement for FACT at a subset of DME-target loci. Overall, our results demonstrate that FACT is required for DME targeting by facilitating its access to heterochromatin.}, author = {Frost, Jennifer M. and Kim, M. Yvonne and Park, Guen Tae and Hsieh, Ping-Hung and Nakamura, Miyuki and Lin, Samuel J. H. and Yoo, Hyunjin and Choi, Jaemyung and Ikeda, Yoko and Kinoshita, Tetsu and Choi, Yeonhee and Zilberman, Daniel and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {20}, pages = {E4720--E4729}, publisher = {National Academy of Sciences}, title = {{FACT complex is required for DNA demethylation at heterochromatin during reproduction in Arabidopsis}}, doi = {10.1073/pnas.1713333115}, volume = {115}, year = {2018}, } @article{8018, abstract = {Nervous systems use excitatory cell assemblies to encode and represent sensory percepts. Similarly, synaptically connected cell assemblies or "engrams" are thought to represent memories of past experience. Multiple lines of recent evidence indicate that brain systems create and use inhibitory replicas of excitatory representations for important cognitive functions. Such matched "inhibitory engrams" can form through homeostatic potentiation of inhibition onto postsynaptic cells that show increased levels of excitation. Inhibitory engrams can reduce behavioral responses to familiar stimuli, thereby resulting in behavioral habituation. In addition, by preventing inappropriate activation of excitatory memory engrams, inhibitory engrams can make memories quiescent, stored in a latent form that is available for context-relevant activation. In neural networks with balanced excitatory and inhibitory engrams, the release of innate responses and recall of associative memories can occur through focused disinhibition. Understanding mechanisms that regulate the formation and expression of inhibitory engrams in vivo may help not only to explain key features of cognition but also to provide insight into transdiagnostic traits associated with psychiatric conditions such as autism, schizophrenia, and posttraumatic stress disorder. }, author = {Barron, Helen C. and Vogels, Tim P and Behrens, Timothy E. and Ramaswami, Mani}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {26}, pages = {6666--6674}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Inhibitory engrams in perception and memory}}, doi = {10.1073/pnas.1701812114}, volume = {114}, year = {2017}, } @article{10373, abstract = {Electric charges are conserved. The same would be expected to hold for magnetic charges, yet magnetic monopoles have never been observed. It is therefore surprising that the laws of nonequilibrium thermodynamics, combined with Maxwell’s equations, suggest that colloidal particles heated or cooled in certain polar or paramagnetic solvents may behave as if they carry an electric/magnetic charge. Here, we present numerical simulations that show that the field distribution around a pair of such heated/cooled colloidal particles agrees quantitatively with the theoretical predictions for a pair of oppositely charged electric or magnetic monopoles. However, in other respects, the nonequilibrium colloidal particles do not behave as monopoles: They cannot be moved by a homogeneous applied field. The numerical evidence for the monopole-like fields around heated/cooled colloidal particles is crucial because the experimental and numerical determination of forces between such colloidal particles would be complicated by the presence of other effects, such as thermophoresis.}, author = {Wirnsberger, Peter and Fijan, Domagoj and Lightwood, Roger A. and Šarić, Anđela and Dellago, Christoph and Frenkel, Daan}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {multidisciplinary}, number = {19}, pages = {4911--4914}, publisher = {National Academy of Sciences}, title = {{Numerical evidence for thermally induced monopoles}}, doi = {10.1073/pnas.1621494114}, volume = {114}, year = {2017}, } @article{12618, abstract = {Mountain ranges are the world’s natural water towers and provide water resources for millions of people. However, their hydrological balance and possible future changes in river flow remain poorly understood because of high meteorological variability, physical inaccessibility, and the complex interplay between climate, cryosphere, and hydrological processes. Here, we use a state-of-the art glacio-hydrological model informed by data from high-altitude observations and the latest climate change scenarios to quantify the climate change impact on water resources of two contrasting catchments vulnerable to changes in the cryosphere. The two study catchments are located in the Central Andes of Chile and in the Nepalese Himalaya in close vicinity of densely populated areas. Although both sites reveal a strong decrease in glacier area, they show a remarkably different hydrological response to projected climate change. In the Juncal catchment in Chile, runoff is likely to sharply decrease in the future and the runoff seasonality is sensitive to projected climatic changes. In the Langtang catchment in Nepal, future water availability is on the rise for decades to come with limited shifts between seasons. Owing to the high spatiotemporal resolution of the simulations and process complexity included in the modeling, the response times and the mechanisms underlying the variations in glacier area and river flow can be well constrained. The projections indicate that climate change adaptation in Central Chile should focus on dealing with a reduction in water availability, whereas in Nepal preparedness for flood extremes should be the policy priority.}, author = {Ragettli, Silvan and Immerzeel, Walter W. and Pellicciotti, Francesca}, issn = {1091-6490}, journal = {PNAS}, keywords = {Multidisciplinary}, number = {33}, pages = {9222--9227}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Contrasting climate change impact on river flows from high-altitude catchments in the Himalayan and Andes Mountains}}, doi = {10.1073/pnas.1606526113}, volume = {113}, year = {2016}, } @article{14304, abstract = {Despite the recent rapid progress in cryo-electron microscopy (cryo-EM), there still exist ample opportunities for improvement in sample preparation. Macromolecular complexes may disassociate or adopt nonrandom orientations against the extended air–water interface that exists for a short time before the sample is frozen. We designed a hollow support structure using 3D DNA origami to protect complexes from the detrimental effects of cryo-EM sample preparation. For a first proof-of-principle, we concentrated on the transcription factor p53, which binds to specific DNA sequences on double-stranded DNA. The support structures spontaneously form monolayers of preoriented particles in a thin film of water, and offer advantages in particle picking and sorting. By controlling the position of the binding sequence on a single helix that spans the hollow support structure, we also sought to control the orientation of individual p53 complexes. Although the latter did not yet yield the desired results, the support structures did provide partial information about the relative orientations of individual p53 complexes. We used this information to calculate a tomographic 3D reconstruction, and refined this structure to a final resolution of ∼15 Å. This structure settles an ongoing debate about the symmetry of the p53 tetramer bound to DNA.}, author = {Martin, Thomas G. and Bharat, Tanmay A. M. and Joerger, Andreas C. and Bai, Xiao-chen and Praetorius, Florian M and Fersht, Alan R. and Dietz, Hendrik and Scheres, Sjors H. W.}, issn = {1091-6490}, journal = {PNAS}, number = {47}, pages = {E7456--E7463}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Design of a molecular support for cryo-EM structure determination}}, doi = {10.1073/pnas.1612720113}, volume = {113}, year = {2016}, } @article{9473, abstract = {Cytosine DNA methylation regulates the expression of eukaryotic genes and transposons. Methylation is copied by methyltransferases after DNA replication, which results in faithful transmission of methylation patterns during cell division and, at least in flowering plants, across generations. Transgenerational inheritance is mediated by a small group of cells that includes gametes and their progenitors. However, methylation is usually analyzed in somatic tissues that do not contribute to the next generation, and the mechanisms of transgenerational inheritance are inferred from such studies. To gain a better understanding of how DNA methylation is inherited, we analyzed purified Arabidopsis thaliana sperm and vegetative cells-the cell types that comprise pollen-with mutations in the DRM, CMT2, and CMT3 methyltransferases. We find that DNA methylation dependency on these enzymes is similar in sperm, vegetative cells, and somatic tissues, although DRM activity extends into heterochromatin in vegetative cells, likely reflecting transcription of heterochromatic transposons in this cell type. We also show that lack of histone H1, which elevates heterochromatic DNA methylation in somatic tissues, does not have this effect in pollen. Instead, levels of CG methylation in wild-type sperm and vegetative cells, as well as in wild-type microspores from which both pollen cell types originate, are substantially higher than in wild-type somatic tissues and similar to those of H1-depleted roots. Our results demonstrate that the mechanisms of methylation maintenance are similar between pollen and somatic cells, but the efficiency of CG methylation is higher in pollen, allowing methylation patterns to be accurately inherited across generations.}, author = {Hsieh, Ping-Hung and He, Shengbo and Buttress, Toby and Gao, Hongbo and Couchman, Matthew and Fischer, Robert L. and Zilberman, Daniel and Feng, Xiaoqi}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {52}, pages = {15132--15137}, publisher = {National Academy of Sciences}, title = {{Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues}}, doi = {10.1073/pnas.1619074114}, volume = {113}, year = {2016}, }