@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 = {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{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{5770, abstract = {Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA subsequently assembles into the mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is the prototypical γ-retrovirus and serves as the basis of retroviral vectors, but the structure of the MLV CA layer is unknown. Here we have combined X-ray crystallography with cryoelectron tomography to determine the structures of immature and mature MLV CA layers within authentic viral particles. This reveals the structural changes associated with maturation, and, by comparison with HIV-1, uncovers conserved and variable features. In contrast to HIV-1, most MLV CA is used for assembly of the mature core, which adopts variable, multilayered morphologies and does not form a closed structure. Unlike in HIV-1, there is similarity between protein–protein interfaces in the immature MLV CA layer and those in the mature CA layer, and structural maturation of MLV could be achieved through domain rotations that largely maintain hexameric interactions. Nevertheless, the dramatic architectural change on maturation indicates that extensive disassembly and reassembly are required for mature core growth. The core morphology suggests that wrapping of the genome in CA sheets may be sufficient to protect the MLV ribonucleoprotein during cell entry.}, author = {Qu, Kun and Glass, Bärbel and Doležal, Michal and Schur, Florian and Murciano, Brice and Rein, Alan and Rumlová, Michaela and Ruml, Tomáš and Kräusslich, Hans-Georg and Briggs, John A. G.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {50}, pages = {E11751--E11760}, publisher = {National Academy of Sciences}, title = {{Structure and architecture of immature and mature murine leukemia virus capsids}}, doi = {10.1073/pnas.1811580115}, volume = {115}, year = {2018}, } @article{5780, abstract = {Bioluminescence is found across the entire tree of life, conferring a spectacular set of visually oriented functions from attracting mates to scaring off predators. Half a dozen different luciferins, molecules that emit light when enzymatically oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis has been described in full, which is found only in bacteria. Here, we report identification of the fungal luciferase and three other key enzymes that together form the biosynthetic cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite. Introduction of the identified genes into the genome of the yeast Pichia pastoris along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis cycle and found that fungal bioluminescence emerged through a series of events that included two independent gene duplications. The retention of the duplicated enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication was followed by functional sequence divergence of enzymes of at least one gene in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence proceeded through several closely related stepping stone nonluminescent biochemical reactions with adaptive roles. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering.}, author = {Kotlobay, Alexey A. and Sarkisyan, Karen and Mokrushina, Yuliana A. and Marcet-Houben, Marina and Serebrovskaya, Ekaterina O. and Markina, Nadezhda M. and Gonzalez Somermeyer, Louisa and Gorokhovatsky, Andrey Y. and Vvedensky, Andrey and Purtov, Konstantin V. and Petushkov, Valentin N. and Rodionova, Natalja S. and Chepurnyh, Tatiana V. and Fakhranurova, Liliia and Guglya, Elena B. and Ziganshin, Rustam and Tsarkova, Aleksandra S. and Kaskova, Zinaida M. and Shender, Victoria and Abakumov, Maxim and Abakumova, Tatiana O. and Povolotskaya, Inna S. and Eroshkin, Fedor M. and Zaraisky, Andrey G. and Mishin, Alexander S. and Dolgov, Sergey V. and Mitiouchkina, Tatiana Y. and Kopantzev, Eugene P. and Waldenmaier, Hans E. and Oliveira, Anderson G. and Oba, Yuichi and Barsova, Ekaterina and Bogdanova, Ekaterina A. and Gabaldón, Toni and Stevani, Cassius V. and Lukyanov, Sergey and Smirnov, Ivan V. and Gitelson, Josef I. and Kondrashov, Fyodor and Yampolsky, Ilia V.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {50}, pages = {12728--12732}, publisher = {National Academy of Sciences}, title = {{Genetically encodable bioluminescent system from fungi}}, doi = {10.1073/pnas.1803615115}, 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{6109, abstract = {Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. Unlike synaptic vesicles, which can be recycled and refilled close to release sites, DCVs must be replenished by de novo synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a Caenorhabditis elegans sensory neuron whose tonic activity we can control using a natural stimulus. We express fluorescently tagged neuropeptides in the neuron and define parameters that describe their subcellular distribution. We measure these parameters at high and low neural activity in 187 mutants defective in proteins implicated in membrane traffic, neuroendocrine secretion, and neuronal or synaptic activity. Using unsupervised hierarchical clustering methods, we analyze these data and identify 62 groups of genes with similar mutant phenotypes. We explore the function of a subset of these groups. We recapitulate many previous findings, validating our paradigm. We uncover a large battery of proteins involved in recycling DCV membrane proteins, something hitherto poorly explored. We show that the unfolded protein response promotes DCV production, which may contribute to intertissue communication of stress. We also find evidence that different mechanisms of priming and exocytosis may operate at high and low neural activity. Our work provides a defined framework to study DCV biology at different neural activity levels.}, author = {Laurent, Patrick and Ch’ng, QueeLim and Jospin, Maëlle and Chen, Changchun and Lorenzo, Ramiro and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {29}, pages = {E6890--E6899}, publisher = {National Academy of Sciences}, title = {{Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron}}, doi = {10.1073/pnas.1714610115}, volume = {115}, 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{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{7724, abstract = {Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.}, author = {Sanjak, Jaleal S. and Sidorenko, Julia and Robinson, Matthew Richard and Thornton, Kevin R. and Visscher, Peter M.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {1}, pages = {151--156}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Evidence of directional and stabilizing selection in contemporary humans}}, doi = {10.1073/pnas.1707227114}, volume = {115}, year = {2018}, } @article{9135, abstract = {Idealized simulations of tropical moist convection have revealed that clouds can spontaneously clump together in a process called self-aggregation. This results in a state where a moist cloudy region with intense deep convection is surrounded by extremely dry subsiding air devoid of deep convection. Because of the idealized settings of the simulations where it was discovered, the relevance of self-aggregation to the real world is still debated. Here, we show that self-aggregation feedbacks play a leading-order role in the spontaneous genesis of tropical cyclones in cloud-resolving simulations. Those feedbacks accelerate the cyclogenesis process by a factor of 2, and the feedbacks contributing to the cyclone formation show qualitative and quantitative agreement with the self-aggregation process. Once the cyclone is formed, wind-induced surface heat exchange (WISHE) effects dominate, although we find that self-aggregation feedbacks have a small but nonnegligible contribution to the maintenance of the mature cyclone. Our results suggest that self-aggregation, and the framework developed for its study, can help shed more light into the physical processes leading to cyclogenesis and cyclone intensification. In particular, our results point out the importance of the longwave radiative cooling outside the cyclone.}, author = {Muller, Caroline J and Romps, David M.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {12}, pages = {2930--2935}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Acceleration of tropical cyclogenesis by self-aggregation feedbacks}}, doi = {10.1073/pnas.1719967115}, 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{38, abstract = {Genomes of closely-related species or populations often display localized regions of enhanced relative sequence divergence, termed genomic islands. It has been proposed that these islands arise through selective sweeps and/or barriers to gene flow. Here, we genetically dissect a genomic island that controls flower color pattern differences between two subspecies of Antirrhinum majus, A.m.striatum and A.m.pseudomajus, and relate it to clinal variation across a natural hybrid zone. We show that selective sweeps likely raised relative divergence at two tightly-linked MYB-like transcription factors, leading to distinct flower patterns in the two subspecies. The two patterns provide alternate floral guides and create a strong barrier to gene flow where populations come into contact. This barrier affects the selected flower color genes and tightlylinked loci, but does not extend outside of this domain, allowing gene flow to lower relative divergence for the rest of the chromosome. Thus, both selective sweeps and barriers to gene flow play a role in shaping genomic islands: sweeps cause elevation in relative divergence, while heterogeneous gene flow flattens the surrounding "sea," making the island of divergence stand out. By showing how selective sweeps establish alternative adaptive phenotypes that lead to barriers to gene flow, our study sheds light on possible mechanisms leading to reproductive isolation and speciation.}, author = {Tavares, Hugo and Whitley, Annabel and Field, David and Bradley, Desmond and Couchman, Matthew and Copsey, Lucy and Elleouet, Joane and Burrus, Monique and Andalo, Christophe and Li, Miaomiao and Li, Qun and Xue, Yongbiao and Rebocho, Alexandra B and Barton, Nicholas H and Coen, Enrico}, issn = {0027-8424}, journal = {PNAS}, number = {43}, pages = {11006 -- 11011}, publisher = {National Academy of Sciences}, title = {{Selection and gene flow shape genomic islands that control floral guides}}, doi = {10.1073/pnas.1801832115}, volume = {115}, year = {2018}, } @article{43, abstract = {The initial amount of pathogens required to start an infection within a susceptible host is called the infective dose and is known to vary to a large extent between different pathogen species. We investigate the hypothesis that the differences in infective doses are explained by the mode of action in the underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms tend to have smaller infective doses than pathogens with distantly acting mechanisms. While empirical evidence tends to support the hypothesis, a formal theoretical explanation has been lacking. We give simple analytical models to gain insight into this phenomenon and also investigate a stochastic, spatially explicit, mechanistic within-host model for toxin-dependent bacterial infections. The model shows that pathogens secreting locally acting toxins have smaller infective doses than pathogens secreting diffusive toxins, as hypothesized. While local pathogenetic mechanisms require smaller infective doses, pathogens with distantly acting toxins tend to spread faster and may cause more damage to the host. The proposed model can serve as a basis for the spatially explicit analysis of various virulence factors also in the context of other problems in infection dynamics.}, author = {Rybicki, Joel and Kisdi, Eva and Anttila, Jani}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {42}, pages = {10690 -- 10695}, publisher = {National Academy of Sciences}, title = {{Model of bacterial toxin-dependent pathogenesis explains infective dose}}, doi = {10.1073/pnas.1721061115}, volume = {115}, year = {2018}, } @article{15157, abstract = {The basic helix–loop–helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ∼24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here we show that CRY1 binds directly to the PAS domain core of CLOCK:BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.}, author = {Michael, Alicia Kathleen and Fribourgh, Jennifer L. and Chelliah, Yogarany and Sandate, Colby R. and Hura, Greg L. and Schneidman-Duhovny, Dina and Tripathi, Sarvind M. and Takahashi, Joseph S. and Partch, Carrie L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {7}, pages = {1560--1565}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1}}, doi = {10.1073/pnas.1615310114}, volume = {114}, year = {2017}, } @article{6113, author = {Oda, Shigekazu and Toyoshima, Yu and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {23}, pages = {E4658--E4665}, publisher = {National Academy of Sciences}, title = {{Modulation of sensory information processing by a neuroglobin in Caenorhabditis elegans}}, doi = {10.1073/pnas.1614596114}, volume = {114}, year = {2017}, } @article{6115, abstract = {Animals adjust their behavioral priorities according to momentary needs and prior experience. We show that Caenorhabditis elegans changes how it processes sensory information according to the oxygen environment it experienced recently. C. elegans acclimated to 7% O2 are aroused by CO2 and repelled by pheromones that attract animals acclimated to 21% O2. This behavioral plasticity arises from prolonged activity differences in a circuit that continuously signals O2 levels. A sustained change in the activity of O2-sensing neurons reprograms the properties of their postsynaptic partners, the RMG hub interneurons. RMG is gap-junctionally coupled to the ASK and ADL pheromone sensors that respectively drive pheromone attraction and repulsion. Prior O2 experience has opposite effects on the pheromone responsiveness of these neurons. These circuit changes provide a physiological correlate of altered pheromone valence. Our results suggest C. elegans stores a memory of recent O2 experience in the RMG circuit and illustrate how a circuit is flexibly sculpted to guide behavioral decisions in a context-dependent manner.}, author = {Fenk, Lorenz A. and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {16}, pages = {4195--4200}, publisher = {National Academy of Sciences}, title = {{Memory of recent oxygen experience switches pheromone valence inCaenorhabditis elegans}}, doi = {10.1073/pnas.1618934114}, 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{7729, abstract = {Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in ∼140,000 participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between −2.3 and −5.2 phenotypic SDs for complete inbreeding; P<0.001). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.}, author = {Yengo, Loic and Zhu, Zhihong and Wray, Naomi R. and Weir, Bruce S. and Yang, Jian and Robinson, Matthew Richard and Visscher, Peter M.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {32}, pages = {8602--8607}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Detection and quantification of inbreeding depression for complex traits from SNP data}}, doi = {10.1073/pnas.1621096114}, volume = {114}, year = {2017}, } @article{7757, abstract = {Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.}, author = {Rocks, Jason W. and Pashine, Nidhi and Bischofberger, Irmgard and Goodrich, Carl Peter and Liu, Andrea J. and Nagel, Sidney R.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {10}, pages = {2520--2525}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Designing allostery-inspired response in mechanical networks}}, doi = {10.1073/pnas.1612139114}, volume = {114}, year = {2017}, }