@article{18216,
abstract = {Protein structure, both at the global and local level, dictates function. Proteins fold from chains of amino acids, forming secondary structures, α-helices and β-strands, that, at least for globular proteins, subsequently fold into a three-dimensional structure. Here, we show that a Ramachandran-type plot focusing on the two dihedral angles separated by the peptide bond, and entirely contained within an amino acid pair, defines a local structural unit. We further demonstrate the usefulness of this cross-peptide-bond Ramachandran plot by showing that it captures β-turn conformations in coil regions, that traditional Ramachandran plot outliers fall into occupied regions of our plot, and that thermophilic proteins prefer specific amino acid pair conformations. Further, we demonstrate experimentally that the effect of a point mutation on backbone conformation and protein stability depends on the amino acid pair context, i.e., the identity of the adjacent amino acid, in a manner predictable by our method.},
author = {Rosenberg, Aviv A. and Yehishalom, Nitsan and Marx, Ailie and Bronstein, Alexander},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences},
number = {44},
publisher = {National Academy of Sciences},
title = {{An amino-domino model described by a cross-peptide-bond Ramachandran plot defines amino acid pairs as local structural units}},
doi = {10.1073/pnas.2301064120},
volume = {120},
year = {2023},
}
@article{13201,
abstract = {As a crucial nitrogen source, nitrate (NO3−) is a key nutrient for plants. Accordingly, root systems adapt to maximize NO3− availability, a developmental regulation also involving the phytohormone auxin. Nonetheless, the molecular mechanisms underlying this regulation remain poorly understood. Here, we identify low-nitrate-resistant mutant (lonr) in Arabidopsis (Arabidopsis thaliana), whose root growth fails to adapt to low-NO3− conditions. lonr2 is defective in the high-affinity NO3− transporter NRT2.1. lonr2 (nrt2.1) mutants exhibit defects in polar auxin transport, and their low-NO3−-induced root phenotype depends on the PIN7 auxin exporter activity. NRT2.1 directly associates with PIN7 and antagonizes PIN7-mediated auxin efflux depending on NO3− levels. These results reveal a mechanism by which NRT2.1 in response to NO3− limitation directly regulates auxin transport activity and, thus, root growth. This adaptive mechanism contributes to the root developmental plasticity to help plants cope with changes in NO3− availability.},
author = {Wang, Yalu and Yuan, Zhi and Wang, Jinyi and Xiao, Huixin and Wan, Lu and Li, Lanxin and Guo, Yan and Gong, Zhizhong and Friml, Jiří and Zhang, Jing},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {25},
publisher = {National Academy of Sciences},
title = {{The nitrate transporter NRT2.1 directly antagonizes PIN7-mediated auxin transport for root growth adaptation}},
doi = {10.1073/pnas.2221313120},
volume = {120},
year = {2023},
}
@article{10888,
abstract = {Despite the growing interest in using chemical genetics in plant research, small molecule target identification remains a major challenge. The cellular thermal shift assay coupled with high-resolution mass spectrometry (CETSA MS) that monitors changes in the thermal stability of proteins caused by their interactions with small molecules, other proteins, or posttranslational modifications, allows the discovery of drug targets or the study of protein–metabolite and protein–protein interactions mainly in mammalian cells. To showcase the applicability of this method in plants, we applied CETSA MS to intact Arabidopsis thaliana cells and identified the thermal proteome of the plant-specific glycogen synthase kinase 3 (GSK3) inhibitor, bikinin. A comparison between the thermal and the phosphoproteomes of bikinin revealed the auxin efflux carrier PIN-FORMED1 (PIN1) as a substrate of the Arabidopsis GSK3s that negatively regulate the brassinosteroid signaling. We established that PIN1 phosphorylation by the GSK3s is essential for maintaining its intracellular polarity that is required for auxin-mediated regulation of vascular patterning in the leaf, thus revealing cross-talk between brassinosteroid and auxin signaling.},
author = {Lu, Qing and Zhang, Yonghong and Hellner, Joakim and Giannini, Caterina and Xu, Xiangyu and Pauwels, Jarne and Ma, Qian and Dejonghe, Wim and Han, Huibin and Van De Cotte, Brigitte and Impens, Francis and Gevaert, Kris and De Smet, Ive and Friml, Jiří and Molina, Daniel Martinez and Russinova, Eugenia},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {11},
publisher = {National Academy of Sciences},
title = {{Proteome-wide cellular thermal shift assay reveals unexpected cross-talk between brassinosteroid and auxin signaling}},
doi = {10.1073/pnas.2118220119},
volume = {119},
year = {2022},
}
@article{11702,
abstract = {When Mendel’s work was rediscovered in 1900, and extended to establish classical genetics, it was initially seen in opposition to Darwin’s theory of evolution by natural selection on continuous variation, as represented by the biometric research program that was the foundation of quantitative genetics. As Fisher, Haldane, and Wright established a century ago, Mendelian inheritance is exactly what is needed for natural selection to work efficiently. Yet, the synthesis remains unfinished. We do not understand why sexual reproduction and a fair meiosis predominate in eukaryotes, or how far these are responsible for their diversity and complexity. Moreover, although quantitative geneticists have long known that adaptive variation is highly polygenic, and that this is essential for efficient selection, this is only now becoming appreciated by molecular biologists—and we still do not have a good framework for understanding polygenic variation or diffuse function.},
author = {Barton, Nicholas H},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {30},
publisher = {National Academy of Sciences},
title = {{The "New Synthesis"}},
doi = {10.1073/pnas.2122147119},
volume = {119},
year = {2022},
}
@article{11723,
abstract = {Plant cell growth responds rapidly to various stimuli, adapting architecture to environmental changes. Two major endogenous signals regulating growth are the phytohormone auxin and the secreted peptides rapid alkalinization factors (RALFs). Both trigger very rapid cellular responses and also exert long-term effects [Du et al., Annu. Rev. Plant Biol. 71, 379–402 (2020); Blackburn et al., Plant Physiol. 182, 1657–1666 (2020)]. However, the way, in which these distinct signaling pathways converge to regulate growth, remains unknown. Here, using vertical confocal microscopy combined with a microfluidic chip, we addressed the mechanism of RALF action on growth. We observed correlation between RALF1-induced rapid Arabidopsis thaliana root growth inhibition and apoplast alkalinization during the initial phase of the response, and revealed that RALF1 reversibly inhibits primary root growth through apoplast alkalinization faster than within 1 min. This rapid apoplast alkalinization was the result of RALF1-induced net H+ influx and was mediated by the receptor FERONIA (FER). Furthermore, we investigated the cross-talk between RALF1 and the auxin signaling pathways during root growth regulation. The results showed that RALF-FER signaling triggered auxin signaling with a delay of approximately 1 h by up-regulating auxin biosynthesis, thus contributing to sustained RALF1-induced growth inhibition. This biphasic RALF1 action on growth allows plants to respond rapidly to environmental stimuli and also reprogram growth and development in the long term.},
author = {Li, Lanxin and Chen, Huihuang and Alotaibi, Saqer S. and Pěnčík, Aleš and Adamowski, Maciek and Novák, Ondřej and Friml, Jiří},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
keywords = {Multidisciplinary},
number = {31},
publisher = {National Academy of Sciences},
title = {{RALF1 peptide triggers biphasic root growth inhibition upstream of auxin biosynthesis}},
doi = {10.1073/pnas.2121058119},
volume = {119},
year = {2022},
}
@article{11733,
abstract = {Genetically informed, deep-phenotyped biobanks are an important research resource and it is imperative that the most powerful, versatile, and efficient analysis approaches are used. Here, we apply our recently developed Bayesian grouped mixture of regressions model (GMRM) in the UK and Estonian Biobanks and obtain the highest genomic prediction accuracy reported to date across 21 heritable traits. When compared to other approaches, GMRM accuracy was greater than annotation prediction models run in the LDAK or LDPred-funct software by 15% (SE 7%) and 14% (SE 2%), respectively, and was 18% (SE 3%) greater than a baseline BayesR model without single-nucleotide polymorphism (SNP) markers grouped into minor allele frequency–linkage disequilibrium (MAF-LD) annotation categories. For height, the prediction accuracy R2 was 47% in a UK Biobank holdout sample, which was 76% of the estimated h2SNP. We then extend our GMRM prediction model to provide mixed-linear model association (MLMA) SNP marker estimates for genome-wide association (GWAS) discovery, which increased the independent loci detected to 16,162 in unrelated UK Biobank individuals, compared to 10,550 from BoltLMM and 10,095 from Regenie, a 62 and 65% increase, respectively. The average χ2 value of the leading markers increased by 15.24 (SE 0.41) for every 1% increase in prediction accuracy gained over a baseline BayesR model across the traits. Thus, we show that modeling genetic associations accounting for MAF and LD differences among SNP markers, and incorporating prior knowledge of genomic function, is important for both genomic prediction and discovery in large-scale individual-level studies.},
author = {Orliac, Etienne J. and Trejo Banos, Daniel and Ojavee, Sven E. and Läll, Kristi and Mägi, Reedik and Visscher, Peter M. and Robinson, Matthew Richard},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {31},
publisher = {National Academy of Sciences},
title = {{Improving GWAS discovery and genomic prediction accuracy in biobank data}},
doi = {10.1073/pnas.2121279119},
volume = {119},
year = {2022},
}
@article{11734,
abstract = {Mineral nutrition is one of the key environmental factors determining plant development and growth. Nitrate is the major form of macronutrient nitrogen that plants take up from the soil. Fluctuating availability or deficiency of this element severely limits plant growth and negatively affects crop production in the agricultural system. To cope with the heterogeneity of nitrate distribution in soil, plants evolved a complex regulatory mechanism that allows rapid adjustment of physiological and developmental processes to the status of this nutrient. The root, as a major exploitation organ that controls the uptake of nitrate to the plant body, acts as a regulatory hub that, according to nitrate availability, coordinates the growth and development of other plant organs. Here, we identified a regulatory framework, where cytokinin response factors (CRFs) play a central role as a molecular readout of the nitrate status in roots to guide shoot adaptive developmental response. We show that nitrate-driven activation of NLP7, a master regulator of nitrate response in plants, fine tunes biosynthesis of cytokinin in roots and its translocation to shoots where it enhances expression of CRFs. CRFs, through direct transcriptional regulation of PIN auxin transporters, promote the flow of auxin and thereby stimulate the development of shoot organs.},
author = {Abualia, Rashed and Ötvös, Krisztina and Novák, Ondřej and Bouguyon, Eleonore and Domanegg, Kevin and Krapp, Anne and Nacry, Philip and Gojon, Alain and Lacombe, Benoit and Benková, Eva},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {31},
publisher = {National Academy of Sciences},
title = {{Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses}},
doi = {10.1073/pnas.2122460119},
volume = {119},
year = {2022},
}
@article{11841,
abstract = {Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer’s and Parkinson’s diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physicochemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process.},
author = {Toprakcioglu, Zenon and Kamada, Ayaka and Michaels, Thomas C.T. and Xie, Mengqi and Krausser, Johannes and Wei, Jiapeng and Šarić, Anđela and Vendruscolo, Michele and Knowles, Tuomas P.J.},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {31},
publisher = {National Academy of Sciences},
title = {{Adsorption free energy predicts amyloid protein nucleation rates}},
doi = {10.1073/pnas.2109718119},
volume = {119},
year = {2022},
}
@article{12081,
abstract = {Selection accumulates information in the genome—it guides stochastically evolving populations toward states (genotype frequencies) that would be unlikely under neutrality. This can be quantified as the Kullback–Leibler (KL) divergence between the actual distribution of genotype frequencies and the corresponding neutral distribution. First, we show that this population-level information sets an upper bound on the information at the level of genotype and phenotype, limiting how precisely they can be specified by selection. Next, we study how the accumulation and maintenance of information is limited by the cost of selection, measured as the genetic load or the relative fitness variance, both of which we connect to the control-theoretic KL cost of control. The information accumulation rate is upper bounded by the population size times the cost of selection. This bound is very general, and applies across models (Wright–Fisher, Moran, diffusion) and to arbitrary forms of selection, mutation, and recombination. Finally, the cost of maintaining information depends on how it is encoded: Specifying a single allele out of two is expensive, but one bit encoded among many weakly specified loci (as in a polygenic trait) is cheap.},
author = {Hledik, Michal and Barton, Nicholas H and Tkačik, Gašper},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {36},
publisher = {National Academy of Sciences},
title = {{Accumulation and maintenance of information in evolution}},
doi = {10.1073/pnas.2123152119},
volume = {119},
year = {2022},
}
@article{12577,
abstract = {Glaciers are key components of the mountain water towers of Asia and are vital for downstream domestic, agricultural, and industrial uses. The glacier mass loss rate over the southeastern Tibetan Plateau is among the highest in Asia and has accelerated in recent decades. This acceleration has been attributed to increased warming, but the mechanisms behind these glaciers’ high sensitivity to warming remain unclear, while the influence of changes in precipitation over the past decades is poorly quantified. Here, we reconstruct glacier mass changes and catchment runoff since 1975 at a benchmark glacier, Parlung No. 4, to shed light on the drivers of recent mass losses for the monsoonal, spring-accumulation glaciers of the Tibetan Plateau. Our modeling demonstrates how a temperature increase (mean of 0.39∘C ⋅dec−1since 1990) has accelerated mass loss rates by altering both the ablation and accumulation regimes in a complex manner. The majority of the post-2000 mass loss occurred during the monsoon months, caused by simultaneous decreases in the solid precipitation ratio (from 0.70 to 0.56) and precipitation amount (–10%), leading to reduced monsoon accumulation (–26%). Higher solid precipitation in spring (+18%) during the last two decades was increasingly important in mitigating glacier mass loss by providing mass to the glacier and protecting it from melting in the early monsoon. With bare ice exposed to warmer temperatures for longer periods, icemelt and catchment discharge have unsustainably intensified since the start of the 21st century, raising concerns for long-term water supply and hazard occurrence in the region.},
author = {Jouberton, Achille and Shaw, Thomas E. and Miles, Evan and McCarthy, Michael and Fugger, Stefan and Ren, Shaoting and Dehecq, Amaury and Yang, Wei and Pellicciotti, Francesca},
issn = {1091-6490},
journal = {PNAS},
keywords = {Multidisciplinary},
number = {37},
publisher = {Proceedings of the National Academy of Sciences},
title = {{Warming-induced monsoon precipitation phase change intensifies glacier mass loss in the southeastern Tibetan Plateau}},
doi = {10.1073/pnas.2109796119},
volume = {119},
year = {2022},
}
@article{10766,
abstract = {Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact.},
author = {Slovakova, Jana and Sikora, Mateusz K and Arslan, Feyza N and Caballero Mancebo, Silvia and Krens, Gabriel and Kaufmann, Walter and Merrin, Jack and Heisenberg, Carl-Philipp J},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {8},
publisher = {National Academy of Sciences},
title = {{Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells}},
doi = {10.1073/pnas.2122030119},
volume = {119},
year = {2022},
}
@article{12667,
abstract = {Unlike crystalline atomic and ionic solids, texture development due to crystallographically preferred growth in colloidal crystals is less studied. Here we investigate the underlying mechanisms of the texture evolution in an evaporation-induced colloidal assembly process through experiments, modeling, and theoretical analysis. In this widely used approach to obtain large-area colloidal crystals, the colloidal particles are driven to the meniscus via the evaporation of a solvent or matrix precursor solution where they close-pack to form a face-centered cubic colloidal assembly. Via two-dimensional large-area crystallographic mapping, we show that the initial crystal orientation is dominated by the interaction of particles with the meniscus, resulting in the expected coalignment of the close-packed direction with the local meniscus geometry. By combining with crystal structure analysis at a single-particle level, we further reveal that, at the later stage of self-assembly, however, the colloidal crystal undergoes a gradual rotation facilitated by geometrically necessary dislocations (GNDs) and achieves a large-area uniform crystallographic orientation with the close-packed direction perpendicular to the meniscus and parallel to the growth direction. Classical slip analysis, finite element-based mechanical simulation, computational colloidal assembly modeling, and continuum theory unequivocally show that these GNDs result from the tensile stress field along the meniscus direction due to the constrained shrinkage of the colloidal crystal during drying. The generation of GNDs with specific slip systems within individual grains leads to crystallographic rotation to accommodate the mechanical stress. The mechanistic understanding reported here can be utilized to control crystallographic features of colloidal assemblies, and may provide further insights into crystallographically preferred growth in synthetic, biological, and geological crystals.},
author = {Li, Ling and Goodrich, Carl Peter and Yang, Haizhao and Phillips, Katherine R. and Jia, Zian and Chen, Hongshun and Wang, Lifeng and Zhong, Jinjin and Liu, Anhua and Lu, Jianfeng and Shuai, Jianwei and Brenner, Michael P. and Spaepen, Frans and Aizenberg, Joanna},
issn = {1091-6490},
journal = {PNAS},
number = {32},
publisher = {Proceedings of the National Academy of Sciences},
title = {{Microscopic origins of the crystallographically preferred growth in evaporation-induced colloidal crystals}},
doi = {10.1073/pnas.2107588118},
volume = {118},
year = {2021},
}
@article{15139,
abstract = {Rotavirus genomes are distributed between 11 distinct RNA molecules, all of which must be selectively copackaged during virus assembly. This likely occurs through sequence-specific RNA interactions facilitated by the RNA chaperone NSP2. Here, we report that NSP2 autoregulates its chaperone activity through its C-terminal region (CTR) that promotes RNA–RNA interactions by limiting its helix-unwinding activity. Unexpectedly, structural proteomics data revealed that the CTR does not directly interact with RNA, while accelerating RNA release from NSP2. Cryo–electron microscopy reconstructions of an NSP2–RNA complex reveal a highly conserved acidic patch on the CTR, which is poised toward the bound RNA. Virus replication was abrogated by charge-disrupting mutations within the acidic patch but completely restored by charge-preserving mutations. Mechanistic similarities between NSP2 and the unrelated bacterial RNA chaperone Hfq suggest that accelerating RNA dissociation while promoting intermolecular RNA interactions may be a widespread strategy of RNA chaperone recycling.},
author = {Bravo, Jack Peter Kelly and Bartnik, Kira and Venditti, Luca and Acker, Julia and Gail, Emma H. and Colyer, Alice and Davidovich, Chen and Lamb, Don C. and Tuma, Roman and Calabrese, Antonio N. and Borodavka, Alexander},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences},
number = {41},
publisher = {Proceedings of the National Academy of Sciences},
title = {{Structural basis of rotavirus RNA chaperone displacement and RNA annealing}},
doi = {10.1073/pnas.2100198118},
volume = {118},
year = {2021},
}
@article{18236,
abstract = {Despite their great promise, artificial intelligence (AI) systems have yet to become ubiquitous in the daily practice of medicine largely due to several crucial unmet needs of healthcare practitioners. These include lack of explanations in clinically meaningful terms, handling the presence of unknown medical conditions, and transparency regarding the system’s limitations, both in terms of statistical performance as well as recognizing situations for which the system’s predictions are irrelevant. We articulate these unmet clinical needs as machine-learning (ML) problems and systematically address them with cutting-edge ML techniques. We focus on electrocardiogram (ECG) analysis as an example domain in which AI has great potential and tackle two challenging tasks: the detection of a heterogeneous mix of known and unknown arrhythmias from ECG and the identification of underlying cardio-pathology from segments annotated as normal sinus rhythm recorded in patients with an intermittent arrhythmia. We validate our methods by simulating a screening for arrhythmias in a large-scale population while adhering to statistical significance requirements. Specifically, our system 1) visualizes the relative importance of each part of an ECG segment for the final model decision; 2) upholds specified statistical constraints on its out-of-sample performance and provides uncertainty estimation for its predictions; 3) handles inputs containing unknown rhythm types; and 4) handles data from unseen patients while also flagging cases in which the model’s outputs are not usable for a specific patient. This work represents a significant step toward overcoming the limitations currently impeding the integration of AI into clinical practice in cardiology and medicine in general.},
author = {Elul, Yonatan and Rosenberg, Aviv A. and Schuster, Assaf and Bronstein, Alexander and Yaniv, Yael},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences},
number = {24},
publisher = {National Academy of Sciences},
title = {{Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis}},
doi = {10.1073/pnas.2020620118},
volume = {118},
year = {2021},
}
@article{8988,
abstract = {The differentiation of cells depends on a precise control of their internal organization, which is the result of a complex dynamic interplay between the cytoskeleton, molecular motors, signaling molecules, and membranes. For example, in the developing neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP] with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite branching by regulating the small GTPase ARF6. Together with the motor protein KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity. However, what defines the function of ADAP1 and how its different roles are coordinated are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions. We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well as PI(3,4)P2 act as stop signals for this transport instead of being transported. We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity to catalyze GTP hydrolysis by ARF6. Together, our results support a model for the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates from the motor to inactivate ARF6, promoting dendrite branching.},
author = {Düllberg, Christian F and Auer, Albert and Canigova, Nikola and Loibl, Katrin and Loose, Martin},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {1},
publisher = {National Academy of Sciences},
title = {{In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1}},
doi = {10.1073/pnas.2010054118},
volume = {118},
year = {2021},
}
@article{8993,
abstract = {N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is still being debated, with prevailing mechanistic schemes describing only indirect connections between NPA and the main transporters responsible for directional transport, namely PIN auxin exporters. Here we present data supporting a model in which NPA associates with PINs in a more direct manner than hitherto postulated. We show that NPA inhibits PIN activity in a heterologous oocyte system and that expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to specific saturable NPA binding. We thus propose that PINs are a bona fide NPA target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent auxin transport and a logical parsimonious explanation for the known physiological effects of NPA on plant growth, as well as an alternative hypothesis to interpret past and future results. We also introduce PIN dimerization and describe an effect of NPA on this, suggesting that NPA binding could be exploited to gain insights into structural aspects of PINs related to their transport mechanism.},
author = {Abas, Lindy and Kolb, Martina and Stadlmann, Johannes and Janacek, Dorina P. and Lukic, Kristina and Schwechheimer, Claus and Sazanov, Leonid A and Mach, Lukas and Friml, Jiří and Hammes, Ulrich Z.},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {1},
publisher = {National Academy of Sciences},
title = {{Naphthylphthalamic acid associates with and inhibits PIN auxin transporters}},
doi = {10.1073/pnas.2020857118},
volume = {118},
year = {2021},
}
@article{9257,
abstract = {The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely designed by directly differentiating through statistical physics models, namely free energy calculations and molecular dynamics simulations. We consider two systems that are crucial to our understanding of structural self-assembly: bulk crystallization and small nanoclusters. In each case, we are able to assemble precise dynamical features. Using gradient information, we manipulate interactions among constituent particles to tune the rate at which these systems yield specific structures of interest. Moreover, we use this approach to learn nontrivial features about the high-dimensional design space, allowing us to accurately predict when multiple kinetic features can be simultaneously and independently controlled. These results provide a concrete and generalizable foundation for studying nonstructural self-assembly, including kinetic properties as well as other complex emergent properties, in a vast array of systems.},
author = {Goodrich, Carl Peter and King, Ella M. and Schoenholz, Samuel S. and Cubuk, Ekin D. and Brenner, Michael P.},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {10},
publisher = {National Academy of Sciences},
title = {{Designing self-assembling kinetics with differentiable statistical physics models}},
doi = {10.1073/pnas.2024083118},
volume = {118},
year = {2021},
}
@article{9301,
abstract = {Electrodepositing insulating lithium peroxide (Li2O2) is the key process during discharge of aprotic Li–O2 batteries and determines rate, capacity, and reversibility. Current understanding states that the partition between surface adsorbed and dissolved lithium superoxide governs whether Li2O2 grows as a conformal surface film or larger particles, leading to low or high capacities, respectively. However, better understanding governing factors for Li2O2 packing density and capacity requires structural sensitive in situ metrologies. Here, we establish in situ small- and wide-angle X-ray scattering (SAXS/WAXS) as a suitable method to record the Li2O2 phase evolution with atomic to submicrometer resolution during cycling a custom-built in situ Li–O2 cell. Combined with sophisticated data analysis, SAXS allows retrieving rich quantitative structural information from complex multiphase systems. Surprisingly, we find that features are absent that would point at a Li2O2 surface film formed via two consecutive electron transfers, even in poorly solvating electrolytes thought to be prototypical for surface growth. All scattering data can be modeled by stacks of thin Li2O2 platelets potentially forming large toroidal particles. Li2O2 solution growth is further justified by rotating ring-disk electrode measurements and electron microscopy. Higher discharge overpotentials lead to smaller Li2O2 particles, but there is no transition to an electronically passivating, conformal Li2O2 coating. Hence, mass transport of reactive species rather than electronic transport through a Li2O2 film limits the discharge capacity. Provided that species mobilities and carbon surface areas are high, this allows for high discharge capacities even in weakly solvating electrolytes. The currently accepted Li–O2 reaction mechanism ought to be reconsidered.},
author = {Prehal, Christian and Samojlov, Aleksej and Nachtnebel, Manfred and Lovicar, Ludek and Kriechbaum, Manfred and Amenitsch, Heinz and Freunberger, Stefan Alexander},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
keywords = {small-angle X-ray scattering, oxygen reduction, disproportionation, Li-air battery},
number = {14},
publisher = {National Academy of Sciences},
title = {{In situ small-angle X-ray scattering reveals solution phase discharge of Li–O2 batteries with weakly solvating electrolytes}},
doi = {10.1073/pnas.2021893118},
volume = {118},
year = {2021},
}
@article{9330,
abstract = {In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density.},
author = {Schöpf, Clemens L. and Ablinger, Cornelia and Geisler, Stefanie M. and Stanika, Ruslan I. and Campiglio, Marta and Kaufmann, Walter and Nimmervoll, Benedikt and Schlick, Bettina and Brockhaus, Johannes and Missler, Markus and Shigemoto, Ryuichi and Obermair, Gerald J.},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {14},
publisher = {National Academy of Sciences},
title = {{Presynaptic α2δ subunits are key organizers of glutamatergic synapses}},
doi = {10.1073/pnas.1920827118},
volume = {118},
year = {2021},
}
@article{9877,
abstract = {Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.},
author = {Rodrigues, Jessica A. and Hsieh, Ping-Hung and Ruan, Deling and Nishimura, Toshiro and Sharma, Manoj K. and Sharma, Rita and Ye, XinYi and Nguyen, Nicholas D. and Nijjar, Sukhranjan and Ronald, Pamela C. and Fischer, Robert L. and Zilberman, Daniel},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {29},
publisher = {National Academy of Sciences},
title = {{Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting}},
doi = {10.1073/pnas.2104445118},
volume = {118},
year = {2021},
}