@article{15210, abstract = {The maximum mass of a star that can produce a white dwarf (WD) is an important astrophysical quantity. One of the best approaches to establishing this limit is to search for WDs in young star clusters in which only massive stars have had time to evolve and where the mass of the progenitor can be established from the cooling time of the WD together with the age of the cluster. Searches in young Milky Way clusters have not thus far yielded WD members more massive than about 1.1 M⊙, well below the Chandrasekhar mass of 1.38 M⊙, nor progenitors with masses in excess of about 6 M⊙. However, the hunt for potentially massive WDs that escaped their cluster environs is yielding interesting candidates. To expand the cluster sample further, we used HST to survey four young and massive star clusters in the Magellanic Clouds for bright WDs that could have evolved from stars as massive as 10 M⊙. We located five potential WD candidates in the oldest of the four clusters examined, the first extragalactic single WDs thus far discovered. As these hot WDs are very faint at optical wavelengths, final confirmation will likely have to await spectroscopy with 30 m class telescopes.}, author = {Richer, Harvey B. and Cohen, Roger E. and Heyl, Jeremy and Kalirai, Jason and Caiazzo, Ilaria and Correnti, Matteo and Cummings, Jeffrey and Goudfrooij, Paul and Hansen, Bradley M. S. and Peeples, Molly and Sabbi, Elena and Tremblay, Pier-Emmanuel and Williams, Benjamin}, issn = {2041-8213}, journal = {The Astrophysical Journal Letters}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {American Astronomical Society}, title = {{When do stars go boom?}}, doi = {10.3847/2041-8213/ac6585}, volume = {931}, year = {2022}, } @article{15211, abstract = {Over a dozen millisecond pulsars are ablating low-mass companions in close binary systems. In the original ‘black widow’, the eight-hour orbital period eclipsing pulsar PSR J1959+2048 (PSR B1957+20)1, high-energy emission originating from the pulsar2 is irradiating and may eventually destroy3 a low-mass companion. These systems are not only physical laboratories that reveal the interesting results of exposing a close companion star to the relativistic energy output of a pulsar, but are also believed to harbour some of the most massive neutron stars4, allowing for robust tests of the neutron star equation of state. Here we report observations of ZTF J1406+1222, a wide hierarchical triple hosting a 62-minute orbital period black widow candidate, the optical flux of which varies by a factor of more than ten. ZTF J1406+1222 pushes the boundaries of evolutionary models5, falling below the 80-minute minimum orbital period of hydrogen-rich systems. The wide tertiary companion is a rare low-metallicity cool subdwarf star, and the system has a Galactic halo orbit consistent with passing near the Galactic Centre, making it a probe of formation channels, neutron star kick physics6 and binary evolution.}, author = {Burdge, Kevin B. and Marsh, Thomas R. and Fuller, Jim and Bellm, Eric C. and Caiazzo, Ilaria and Chakrabarty, Deepto and Coughlin, Michael W. and De, Kishalay and Dhillon, V. S. and Graham, Matthew J. and Rodríguez-Gil, Pablo and Jaodand, Amruta D. and Kaplan, David L. and Kara, Erin and Kong, Albert K. H. and Kulkarni, S. R. and Li, Kwan-Lok and Littlefair, S. P. and Majid, Walid A. and Mróz, Przemek and Pearlman, Aaron B. and Phinney, E. S. and Roestel, Jan van and Simcoe, Robert A. and Andreoni, Igor and Drake, Andrew J. and Dekany, Richard G. and Duev, Dmitry A. and Kool, Erik C. and Mahabal, Ashish A. and Medford, Michael S. and Riddle, Reed and Prince, Thomas A.}, issn = {1476-4687}, journal = {Nature}, keywords = {Multidisciplinary}, number = {7908}, pages = {41--45}, publisher = {Springer Nature}, title = {{A 62-minute orbital period black widow binary in a wide hierarchical triple}}, doi = {10.1038/s41586-022-04551-1}, volume = {605}, year = {2022}, } @article{15212, abstract = {We determine the distribution of cooling ages of massive Gaia EDR3 white dwarfs identified with over 90 per cent probability within 200 pc and with mass in the range 0.95–1.25 M⊙. Using three sets of publicly available models, we consider sub-samples of these white dwarfs sorted into three equally spaced mass bins. Under the assumption of a constant white dwarf formation rate, we find an excess of white dwarfs, both along the Q branch and below it, corresponding respectively to stars that are in the process of freezing and those that are completely frozen. We compare the cooling age distributions for each of these bins to the recently determined time-varying star formation rate of Gaia DR2 main sequence stars. For white dwarfs in the two lightest mass bins, spanning the mass range 0.95–1.15 M⊙, we find that the cumulative cooling age distribution is statistically consistent with the expectation from the star formation rate. For white dwarfs in the heaviest mass bin, 1.15–1.25 M⊙, we find that their cumulative distribution is inconsistent with the star formation rate for all of the models considered; instead, we find that their cooling age distribution is well fitted by a linear combination of the distribution expected for single stellar evolution products and the distribution expected for double white dwarf merger products when approximately 40–50 per cent of the 1.15–1.25 M⊙ white dwarfs that formed over the past 4 Gyr are produced through double white dwarf mergers.}, author = {Fleury, Leesa and Caiazzo, Ilaria and Heyl, Jeremy}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {4}, pages = {5984--5993}, publisher = {Oxford University Press}, title = {{The cooling of massive white dwarfs from Gaia EDR3}}, doi = {10.1093/mnras/stac458}, volume = {511}, year = {2022}, } @article{15213, abstract = {We searched through the entire Gaia EDR3 candidate white dwarf catalog for stars with proper motions and positions that are consistent with them having escaped from the Alpha Persei cluster within the past 81 Myr, the age of the cluster. In this search we found five candidate white dwarf escapees from Alpha Persei and obtained spectra for all of them. We confirm that three are massive white dwarfs sufficiently young to have originated in the cluster. All these are more massive than any white dwarf previously associated with a cluster using Gaia astrometry, and possess some of the most massive progenitors. In particular, the white dwarf Gaia EDR3 4395978097863572, which lies within 25 pc of the cluster center, has a mass of about 1.20 solar masses and evolved from an 8.5 solar-mass star, pushing the upper limit for white dwarf formation from a single massive star, while still leaving a substantial gap between the resulting white dwarf mass and the Chandrasekhar mass.}, author = {Miller, David R. and Caiazzo, Ilaria and Heyl, Jeremy and Richer, Harvey B. and Tremblay, Pier-Emmanuel}, issn = {2041-8213}, journal = {The Astrophysical Journal Letters}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {American Astronomical Society}, title = {{The ultramassive white dwarfs of the Alpha Persei cluster}}, doi = {10.3847/2041-8213/ac50a5}, volume = {926}, year = {2022}, } @article{15214, abstract = {We search through an eight million cubic parsec volume surrounding the Pleiades star cluster and the Sun to identify both the current and past members of the Pleiades cluster within the Gaia EDR3 data set. We find nearly 1300 current cluster members and 289 former cluster candidates. Many of these candidates lie well in front of or behind the cluster from our point of view, so formerly they were considered cluster members, but their parallaxes put them more than 10 pc from the center of the cluster today. Over the past 100 Myr we estimate that the cluster has lost twenty percent of its mass including two massive white dwarf stars and the α2 Canum Venaticorum type variable star, 41 Tau. All three white dwarfs associated with the cluster are massive (1.01–1.06 M⊙) and have progenitors with main-sequence masses of about six solar masses. Although we did not associate any giant stars with the cluster, the cooling time of the oldest white dwarf of 60 Myr gives a firm lower limit on the age of the cluster.}, author = {Heyl, Jeremy and Caiazzo, Ilaria and Richer, Harvey B.}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {American Astronomical Society}, title = {{Reconstructing the Pleiades with Gaia EDR3}}, doi = {10.3847/1538-4357/ac45fc}, volume = {926}, year = {2022}, } @article{15268, abstract = {Apolipoprotein A‐I (apoA‐I) has a key function in the reverse cholesterol transport. However, aggregation of apoA‐I single point mutants can lead to hereditary amyloid pathology. Although several studies have tackled the biophysical and structural consequences introduced by these mutations, there is little information addressing the relationship between the evolutionary and structural features that contribute to the amyloid behavior of apoA‐I. We combined evolutionary studies, in silico mutagenesis and molecular dynamics (MD) simulations to provide a comprehensive analysis of the conservation and pathogenic role of the aggregation‐prone regions (APRs) present in apoA‐I. Sequence analysis demonstrated that among the four amyloidogenic regions described for human apoA‐I, only two (APR1 and APR4) are evolutionary conserved across different species of Sarcopterygii. Moreover, stability analysis carried out with the FoldX engine showed that APR1 contributes to the marginal stability of apoA‐I. Structural properties of full‐length apoA‐I models suggest that aggregation is avoided by placing APRs into highly packed and rigid portions of its native fold. Compared to silent variants extracted from the gnomAD database, the thermodynamic and pathogenic impact of amyloid mutations showed evidence of a higher destabilizing effect. MD simulations of the amyloid variant G26R evidenced the partial unfolding of the alpha‐helix bundle with the concomitant exposure of APR1 to the solvent, suggesting an insight into the early steps involved in its aggregation. Our findings highlight APR1 as a relevant component for apoA‐I structural integrity and emphasize a destabilizing effect of amyloid variants that leads to the exposure of this region.}, author = {Gisonno, Romina A. and Masson, Tomas and Ramella, Nahuel A. and Barrera, Exequiel E. and Romanowski, Víctor and Tricerri, M. Alejandra}, issn = {1097-0134}, journal = {Proteins: Structure, Function, and Bioinformatics}, keywords = {Molecular Biology, Biochemistry, Structural Biology}, number = {1}, pages = {258--269}, publisher = {Wiley}, title = {{Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid behavior}}, doi = {10.1002/prot.26217}, volume = {90}, year = {2022}, } @misc{17057, abstract = {Martin Loose studied chemistry at the University of Heidelberg, Germany. He then joined Petra Schwille's group at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, where he obtained his PhD degree in 2010 for work on self-organization and pattern formation in the bacterial Min protein system. He then moved to Tim Mitchison's lab at Harvard Medical School, Boston, USA for his postdoc, funded by Human Frontier Science Program (HSFP) and European Molecular Biology Organization (EMBO) long-term fellowships; there, he discovered that the bacterial cell division proteins FtsA and FtsZ self-organize into dynamic cytoskeletal patterns. Martin established his independent research group at the Institute of Science and Technology (IST) Austria in 2015, supported by an European Research Council (ERC) starting grant and HFSP Young Investigator Grant. His lab studies the self-organization of bacterial cell division and small GTPase networks.}, author = {Loose, Martin}, booktitle = {Journal of Cell Science}, issn = {1477-9137}, number = {2}, publisher = {The Company of Biologists}, title = {{Cell scientist to watch – Martin Loose}}, doi = {10.1242/jcs.259715}, volume = {135}, year = {2022}, } @inproceedings{17059, abstract = {The recent focus on the efficiency of deep neural networks (DNNs) has led to significant work on model compression approaches, of which weight pruning is one of the most popular. At the same time, there is rapidly-growing computational support for efficiently executing the unstructured-sparse models obtained via pruning. Yet, most existing pruning methods minimize just the number of remaining weights, i.e. the size of the model, rather than optimizing for inference time. We address this gap by introducing SPDY, a new compression method which automatically determines layer-wise sparsity targets achieving a desired inference speedup on a given system, while minimizing accuracy loss. SPDY is the composition of two new techniques. The first is an efficient and general dynamic programming algorithm for solving constrained layer-wise compression problems, given a set of layer-wise error scores. The second technique is a local search procedure for automatically determining such scores in an accurate and robust manner. Experiments across popular vision and language models show that SPDY guarantees speedups while recovering higher accuracy relative to existing strategies, both for one-shot and gradual pruning scenarios, and is compatible with most existing pruning approaches. We also extend our approach to the recently-proposed task of pruning with very little data, where we achieve the best known accuracy recovery when pruning to the GPU-supported 2:4 sparsity pattern.}, author = {Frantar, Elias and Alistarh, Dan-Adrian}, booktitle = {39th International Conference on Machine Learning}, location = {Baltimore, MD, United States}, pages = {6726--6743}, publisher = {ML Research Press}, title = {{SPDY: Accurate pruning with speedup guarantees}}, volume = {162}, year = {2022}, } @inproceedings{17060, abstract = {Payment channel networks (PCNs) are one of the most prominent solutions to the limited transaction throughput of blockchains. Nevertheless, PCNs suffer themselves from a throughput limitation due to the capital constraints of their channels. A similar dependence on high capital is also found in inter-bank payment settlements, where the so-called netting technique is used to mitigate liquidity demands. In this work, we alleviate this limitation by introducing the notion of transaction aggregation: instead of executing transactions sequentially through a PCN, we enable senders to aggregate multiple transactions and execute them simultaneously to benefit from several amounts that may "cancel out". Two direct advantages of our proposal is the decrease in intermediary fees paid by senders as well as the obfuscation of the transaction data from the intermediaries. We formulate the transaction aggregation as a computational problem, a generalization of the Bank Clearing Problem. We present a generic framework for the transaction aggregation execution, and thereafter we propose Wiser as an implementation of this framework in a specific hub-based setting. To overcome the NP-hardness of the transaction aggregation problem, in Wiser we propose a fixed-parameter linear algorithm for a special case of transaction aggregation as well as the Bank Clearing Problem. Wiser can also be seen as a modern variant of the Hawala money transfer system, as well as a decentralized implementation of the overseas remittance service of Wise.}, author = {Tiwari, Samarth and Yeo, Michelle X and Avarikioti, Zeta and Salem, Iosif and Pietrzak, Krzysztof Z and Schmid, Stefan}, booktitle = {Proceedings of the 4th ACM Conference on Advances in Financial Technologies}, isbn = {9781450398619}, location = {Cambridge, MA, United States}, pages = {217--231}, publisher = {Association for Computing Machinery}, title = {{Wiser: Increasing throughput in payment channel networks with transaction aggregation}}, doi = {10.1145/3558535.3559775}, year = {2022}, } @article{17061, abstract = {Across many domains of interaction, both natural and artificial, individuals use past experience to shape future behaviors. The results of such learning processes depend on what individuals wish to maximize. A natural objective is one’s own success. However, when two such “selfish” learners interact with each other, the outcome can be detrimental to both, especially when there are conflicts of interest. Here, we explore how a learner can align incentives with a selfish opponent. Moreover, we consider the dynamics that arise when learning rules themselves are subject to evolutionary pressure. By combining extensive simulations and analytical techniques, we demonstrate that selfish learning is unstable in most classical two-player repeated games. If evolution operates on the level of long-run payoffs, selection instead favors learning rules that incorporate social (other-regarding) preferences. To further corroborate these results, we analyze data from a repeated prisoner’s dilemma experiment. We find that selfish learning is insufficient to explain human behavior when there is a trade-off between payoff maximization and fairness.}, author = {McAvoy, Alex and Kates-Harbeck, Julian and Chatterjee, Krishnendu and Hilbe, Christian}, issn = {2752-6542}, journal = {PNAS Nexus}, number = {4}, publisher = {Oxford University Press}, title = {{Evolutionary instability of selfish learning in repeated games}}, doi = {10.1093/pnasnexus/pgac141}, volume = {1}, year = {2022}, } @article{17065, abstract = {Past work on optimizing fabrication plans given a carpentry design can provide Pareto-optimal plans trading off between material waste, fabrication time, precision, and other considerations. However, when developing fabrication plans, experts rarely restrict to a single design, instead considering families of design variations, sometimes adjusting designs to simplify fabrication. Jointly exploring the design and fabrication plan spaces for each design is intractable using current techniques. We present a new approach to jointly optimize design and fabrication plans for carpentered objects. To make this bi-level optimization tractable, we adapt recent work from program synthesis based on equality graphs (e-graphs), which encode sets of equivalent programs. Our insight is that subproblems within our bi-level problem share significant substructures. By representing both designs and fabrication plans in a new bag of parts (BOP) e-graph, we amortize the cost of optimizing design components shared among multiple candidates. Even using BOP e-graphs, the optimization space grows quickly in practice. Hence, we also show how a feedback-guided search strategy dubbed Iterative Contraction and Expansion on E-graphs (ICEE) can keep the size of the e-graph manageable and direct the search towards promising candidates. We illustrate the advantages of our pipeline through examples from the carpentry domain.}, author = {Zhao, Haisen and Willsey, Max and Zhu, Amy and Nandi, Chandrakana and Tatlock, Zachary and Solomon, Justin and Schulz, Adriana}, issn = {1557-7368}, journal = {ACM Transactions on Graphics}, number = {3}, publisher = {Association for Computing Machinery}, title = {{Co-optimization of design and fabrication plans for carpentry}}, doi = {10.1145/3508499}, volume = {41}, year = {2022}, } @article{17066, abstract = {A cell’s size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate “unwanted” cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical “lethal” size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the “cell death abnormal” phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell’s commitment to the cell death fate.}, author = {Sethi, Aditya and Wei, Hai and Mishra, Nikhil and Segos, Ioannis and Lambie, Eric J. and Zanin, Esther and Conradt, Barbara}, issn = {1545-7885}, journal = {PLOS Biology}, number = {10}, publisher = {Public Library of Science}, title = {{A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans}}, doi = {10.1371/journal.pbio.3001786}, volume = {20}, year = {2022}, } @article{17067, abstract = {Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. DCX is a microtubule-associated protein which plays a key role during neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO) mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons are also more excitable than wild-type (WT) cells. To further identify abnormalities, we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural levels. Severe defects were observed in mitochondria, affecting number and distribution. Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally organized. Transcriptome analyses from laser microdissected hippocampal tissue at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue showed that organelle defects are persistent throughout life. Locomotor activity and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently performed less well than WT littermates, with defects becoming more severe with age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can lead to permanent organelle anomalies contributing to abnormal adult behavior.}, author = {Stouffer, Melissa A and Khalaf-Nazzal, R. and Cifuentes-Diaz, C. and Albertini, G. and Bandet, E. and Grannec, G. and Lavilla, V. and Deleuze, J.-F. and Olaso, R. and Nosten-Bertrand, M. and Francis, F.}, issn = {0969-9961}, journal = {Neurobiology of Disease}, publisher = {Elsevier}, title = {{Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells}}, doi = {10.1016/j.nbd.2022.105702}, volume = {168}, year = {2022}, } @article{17068, abstract = {In plants, the antagonism between growth and defense is hardwired by hormonal signaling. The perception of pathogen-associated molecular patterns (PAMPs) from invading microorganisms inhibits auxin signaling and plant growth. Conversely, pathogens manipulate auxin signaling to promote disease, but how this hormone inhibits immunity is not fully understood. Ustilago maydis is a maize pathogen that induces auxin signaling in its host. We characterized a U. maydis effector protein, Naked1 (Nkd1), that is translocated into the host nucleus. Through its native ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, Nkd1 binds to the transcriptional co-repressors TOPLESS/TOPLESS-related (TPL/TPRs) and prevents the recruitment of a transcriptional repressor involved in hormonal signaling, leading to the de-repression of auxin and jasmonate signaling and thereby promoting susceptibility to (hemi)biotrophic pathogens. A moderate upregulation of auxin signaling inhibits the PAMP-triggered reactive oxygen species (ROS) burst, an early defense response. Thus, our findings establish a clear mechanism for auxin-induced pathogen susceptibility. Engineered Nkd1 variants with increased expression or increased EAR-mediated TPL/TPR binding trigger typical salicylic-acid-mediated defense reactions, leading to pathogen resistance. This implies that moderate binding of Nkd1 to TPL is a result of a balancing evolutionary selection process to enable TPL manipulation while avoiding host recognition.}, author = {Navarrete, Fernando and Gallei, Michelle C and Kornienko, Aleksandra E. and Saado, Indira and Khan, Mamoona and Chia, Khong-Sam and Darino, Martin A. and Bindics, Janos and Djamei, Armin}, issn = {2590-3462}, journal = {Plant Communications}, number = {2}, publisher = {Elsevier}, title = {{TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1}}, doi = {10.1016/j.xplc.2021.100269}, volume = {3}, year = {2022}, } @article{17069, abstract = {Fertilization of an egg by multiple sperm (polyspermy) leads to lethal genome imbalance and chromosome segregation defects. In Arabidopsis thaliana, the block to polyspermy is facilitated by a mechanism that prevents polytubey (the arrival of multiple pollen tubes to one ovule). We show here that FERONIA, ANJEA, and HERCULES RECEPTOR KINASE 1 receptor-like kinases located at the septum interact with pollen tube–specific RALF6, 7, 16, 36, and 37 peptide ligands to establish this polytubey block. The same combination of RALF (rapid alkalinization factor) peptides and receptor complexes controls pollen tube reception and rupture inside the targeted ovule. Pollen tube rupture releases the polytubey block at the septum, which allows the emergence of secondary pollen tubes upon fertilization failure. Thus, orchestrated steps in the fertilization process in Arabidopsis are coordinated by the same signaling components to guarantee and optimize reproductive success.}, author = {Zhong, Sheng and Li, Ling and Wang, Zhijuan and Ge, Zengxiang and Li, Qiyun and Bleckmann, Andrea and Wang, Jizong and Song, Zihan and Shi, Yihao and Liu, Tianxu and Li, Luhan and Zhou, Huabin and Wang, Yanyan and Zhang, Li and Wu, Hen-Ming and Lai, Luhua and Gu, Hongya and Dong, Juan and Cheung, Alice Y. and Dresselhaus, Thomas and Qu, Li-Jia}, issn = {1095-9203}, journal = {Science}, number = {6578}, pages = {290--296}, publisher = {American Association for the Advancement of Science}, title = {{RALF peptide signaling controls the polytubey block in Arabidopsis}}, doi = {10.1126/science.abl4683}, volume = {375}, year = {2022}, } @article{17070, abstract = {We investigate the formation of magnetic Bose polaron, an impurity atom dressed by spin-wave excitations, in a one-dimensional spinor Bose gas. Within an effective potential model, the impurity is strongly confined by the host excitations which can even overcome the impurity-medium repulsion leading to a self-localized quasi-particle state. The phase diagram of the attractive and self-bound repulsive magnetic polaron, repulsive non-magnetic (Fröhlich-type) polaron and impurity-medium phase-separation regimes is explored with respect to the Rabi-coupling between the spin components, spin–spin interactions and impurity-medium coupling. The residue of such magnetic polarons decreases substantially in both strong attractive and repulsive branches with strong impurity-spin interactions, illustrating significant dressing of the impurity. The impurity can be used to probe and maneuver the spin polarization of the magnetic medium while suppressing ferromagnetic spin–spin correlations. It is shown that mean-field theory fails as the spinor gas approaches immiscibility since the generated spin-wave excitations are prominent. Our findings illustrate that impurities can be utilized to generate controllable spin–spin correlations and magnetic polaron states which can be realized with current cold atom setups.}, author = {Mistakidis, S I and Koutentakis, Georgios and Grusdt, F and Schmelcher, P and Sadeghpour, H R}, issn = {1367-2630}, journal = {New Journal of Physics}, number = {8}, publisher = {IOP Publishing}, title = {{Inducing spin-order with an impurity: phase diagram of the magnetic Bose polaron}}, doi = {10.1088/1367-2630/ac836c}, volume = {24}, year = {2022}, } @article{17071, abstract = {The eukaryotic nucleus pro­tects the genome and is enclosed by the two membranes of the nuclear envelope. Nuclear pore complexes (NPCs) perforate the nuclear envelope to facilitate nucleocytoplasmic transport. With a molecular weight of ∼120 MDa, the human NPC is one of the larg­est protein complexes. Its ~1000 proteins are taken in multiple copies from a set of about 30 distinct nucleoporins (NUPs). They can be roughly categorized into two classes. Scaf­fold NUPs contain folded domains and form a cylindrical scaffold architecture around a central channel. Intrinsically disordered NUPs line the scaffold and extend into the central channel, where they interact with cargo complexes. The NPC architecture is highly dynamic. It responds to changes in nuclear envelope tension with conforma­tional breathing that manifests in dilation and constriction movements. Elucidating the scaffold architecture, ultimately at atomic resolution, will be important for gaining a more precise understanding of NPC function and dynamics but imposes a substantial chal­lenge for structural biologists. Considerable progress has been made toward this goal by a joint effort in the field. A synergistic combination of complementary approaches has turned out to be critical. In situ structural biology techniques were used to reveal the overall layout of the NPC scaffold that defines the spatial reference for molecular modeling. High-resolution structures of many NUPs were determined in vitro. Proteomic analysis and extensive biochemical work unraveled the interaction network of NUPs. Integra­tive modeling has been used to combine the different types of data, resulting in a rough outline of the NPC scaffold. Previous struc­tural models of the human NPC, however, were patchy and limited in accuracy owing to several challenges: (i) Many of the high-resolution structures of individual NUPs have been solved from distantly related species and, consequently, do not comprehensively cover their human counterparts. (ii) The scaf­fold is interconnected by a set of intrinsically disordered linker NUPs that are not straight­forwardly accessible to common structural biology techniques. (iii) The NPC scaffold intimately embraces the fused inner and outer nuclear membranes in a distinctive topol­ogy and cannot be studied in isolation. (iv) The conformational dynamics of scaffold NUPs limits the resolution achievable in structure determination. In this study, we used artificial intelligence (AI)–based prediction to generate an exten­sive repertoire of structural models of human NUPs and their subcomplexes. The resulting models cover various domains and interfaces that so far remained structurally uncharac­terized. Benchmarking against previous and unpublished x-ray and cryo–electron micros­copy structures revealed unprecedented accu­racy. We obtained well-resolved cryo–electron tomographic maps of both the constricted and dilated conformational states of the hu­man NPC. Using integrative modeling, we fit­ted the structural models of individual NUPs into the cryo–electron microscopy maps. We explicitly included several linker NUPs and traced their trajectory through the NPC scaf­fold. We elucidated in great detail how mem­brane-associated and transmembrane NUPs are distributed across the fusion topology of both nuclear membranes. The resulting architectural model increases the structural coverage of the human NPC scaffold by about twofold. We extensively validated our model against both earlier and new experimental data. The completeness of our model has enabled microsecond-long coarse-grained molecular dynamics simulations of the NPC scaffold within an explicit membrane en­vironment and solvent. These simulations reveal that the NPC scaffold prevents the constriction of the otherwise stable double-membrane fusion pore to small diameters in the absence of membrane tension Our 70-MDa atomically re­solved model covers >90% of the human NPC scaffold. It captures conforma­tional changes that occur during dilation and constriction. It also reveals the precise anchoring sites for intrinsically disordered NUPs, the identification of which is a prerequisite for a complete and dy­namic model of the NPC. Our study exempli­fies how AI-based structure prediction may accelerate the elucidation of subcellular ar­chitecture at atomic resolution.}, author = {Mosalaganti, Shyamal and Obarska-Kosinska, Agnieszka and Siggel, Marc and Taniguchi, Reiya and Turoňová, Beata and Zimmerli, Christian E. and Buczak, Katarzyna and Schmidt, Florian and Margiotta, Erica and Mackmull, Marie-Therese and Hagen, Wim J. H. and Hummer, Gerhard and Kosinski, Jan and Beck, Martin}, issn = {1095-9203}, journal = {Science}, number = {6598}, publisher = {American Association for the Advancement of Science}, title = {{AI-based structure prediction empowers integrative structural analysis of human nuclear pores}}, doi = {10.1126/science.abm9506}, volume = {376}, year = {2022}, } @article{17072, abstract = {The collapse of polypeptides is thought important to protein folding, aggregation, intrinsic disorder, and phase separation. However, whether polypeptide collapse is modulated in cells to control protein states is unclear. Here, using integrated protein manipulation and imaging, we show that the chaperonin GroEL-ES can accelerate the folding of proteins by strengthening their collapse. GroEL induces contractile forces in substrate chains, which draws them into the cavity and triggers a general compaction and discrete folding transitions, even for slow-folding proteins. This collapse enhancement is strongest in the nucleotide-bound states of GroEL and is aided by GroES binding to the cavity rim and by the amphiphilic C-terminal tails at the cavity bottom. Collapse modulation is distinct from other proposed GroEL-ES folding acceleration mechanisms, including steric confinement and misfold unfolding. Given the prevalence of collapse throughout the proteome, we conjecture that collapse modulation is more generally relevant within the protein quality control machinery.}, author = {Naqvi, Mohsin M. and Avellaneda Sarrió, Mario and Roth, Andrew and Koers, Eline J. and Roland, Antoine and Sunderlikova, Vanda and Kramer, Günter and Rye, Hays S. and Tans, Sander J.}, issn = {2375-2548}, journal = {Science Advances}, number = {9}, publisher = {American Association for the Advancement of Science}, title = {{Protein chain collapse modulation and folding stimulation by GroEL-ES}}, doi = {10.1126/sciadv.abl6293}, volume = {8}, year = {2022}, } @inbook{17075, abstract = {Disorders associated with the malfunction of amino acid transporters mainly affect the function of the intestine, kidney, brain, and liver. Mutations of brain amino acid transporters, for example, alter neuronal excitability (e.g., episodic ataxia due to SLC1A3 (EAAT1) defect and hyperekplexia due to SLC6A5 (GLYT2) deficiency) or brain development (SLC1A1 (EAAT3), SLC3A2/SLC7A5 (CD98hc/LAT1), and SLC1A4 (ASCT1) deficiencies). Mutations of renal and intestinal amino acid transporters SLC3A1/SLC7A9 (rBAT/b0,+AT) and SLC1A1 (EAAT3) cause renal problems (cystinuria and dicarboxylic aminoaciduria, respectively) and malabsorption that can affect whole-body homoeostasis (Hartnup disorder SLC6A19 (B0AT1), lysinuric protein intolerance SLC3A2/SLC7A7 (CD98hc/y+LAT1), and hyperdibasic aminoaciduria type 1). Mutations in the neuronal system A amino acid transporter SLC38A8 (SNAT8) cause eye developmental and visual defects. Inborn errors associated with mitochondrial SLC25 family members such as SLC25A12 (neuronal- and muscle-specific mitochondrial aspartate/glutamate transporter 1; AGC1) (global cerebral hypomyelination), SLC25A13 (aspartate/glutamate transporter 2) (citrin deficiency), SLC25A15 (ornithine-citrulline carrier 2) (homocitrullinuria, hyperornithinemia, and hyperammonemia syndrome), and SLC25A22 (mitochondrial glutamate/H+ symporter 1, GC1) (neonatal myoclonic epilepsy) will be dealt within Chap. 43 (defects of mitochondrial carriers).}, author = {Palacín, Manuel and Bröer, Stefan and Novarino, Gaia}, booktitle = {Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases}, editor = {Blau, Nenad and Vici, Carlo Dionisi and Ferreira, Carlos R. and Vianey-Saban, Christine and van Karnebeek, Clara D.M.}, isbn = {9783030677268}, pages = {291--312}, publisher = {Springer Nature}, title = {{Amino Acid Transport Defects}}, doi = {10.1007/978-3-030-67727-5_18}, year = {2022}, } @article{17077, abstract = {Resolving a conjecture of Füredi from 1988, we prove that with high probability, the random graph 𝔾(𝑛, 1/2) admits a friendly bisection of its vertex set, i.e., a partition of its vertex set into two parts whose sizes differ by at most one in which 𝑛 − 𝑜(𝑛) vertices have more neighbours in their own part as across. Our proof is constructive, and in the process, we develop a new method to study stochastic processes driven by degree information in random graphs; this involves combining enumeration techniques with an abstract second moment argument.}, author = {Ferber, Asaf and Kwan, Matthew Alan and Narayanan, Bhargav and Sah, Ashwin and Sawhney, Mehtaab}, issn = {2692-3688}, journal = {Communications of the American Mathematical Society}, number = {10}, pages = {380--416}, publisher = {American Mathematical Society}, title = {{Friendly bisections of random graphs}}, doi = {10.1090/cams/13}, volume = {2}, year = {2022}, }