@article{10202, abstract = {Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.}, author = {Pradhan, Saurabh J. and Reddy, Puli Chandramouli and Smutny, Michael and Sharma, Ankita and Sako, Keisuke and Oak, Meghana S. and Shah, Rini and Pal, Mrinmoy and Deshpande, Ojas and Dsilva, Greg and Tang, Yin and Mishra, Rakesh and Deshpande, Girish and Giraldez, Antonio J. and Sonawane, Mahendra and Heisenberg, Carl-Philipp J and Galande, Sanjeev}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis}}, doi = {10.1038/s41467-021-26234-7}, volume = {12}, year = {2021}, } @article{10271, abstract = {Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions.}, author = {Qi, Qin and Angermayr, S. Andreas and Bollenbach, Mark Tobias}, issn = {1664-302X}, journal = {Frontiers in Microbiology}, keywords = {microbiology}, publisher = {Frontiers}, title = {{Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli}}, doi = {10.3389/fmicb.2021.760017}, volume = {12}, year = {2021}, } @article{10221, abstract = {We prove that any deterministic matrix is approximately the identity in the eigenbasis of a large random Wigner matrix with very high probability and with an optimal error inversely proportional to the square root of the dimension. Our theorem thus rigorously verifies the Eigenstate Thermalisation Hypothesis by Deutsch (Phys Rev A 43:2046–2049, 1991) for the simplest chaotic quantum system, the Wigner ensemble. In mathematical terms, we prove the strong form of Quantum Unique Ergodicity (QUE) with an optimal convergence rate for all eigenvectors simultaneously, generalizing previous probabilistic QUE results in Bourgade and Yau (Commun Math Phys 350:231–278, 2017) and Bourgade et al. (Commun Pure Appl Math 73:1526–1596, 2020).}, author = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, number = {2}, pages = {1005–1048}, publisher = {Springer Nature}, title = {{Eigenstate thermalization hypothesis for Wigner matrices}}, doi = {10.1007/s00220-021-04239-z}, volume = {388}, year = {2021}, } @article{10224, abstract = {We investigate the Fröhlich polaron model on a three-dimensional torus, and give a proof of the second-order quantum corrections to its ground-state energy in the strong-coupling limit. Compared to previous work in the confined case, the translational symmetry (and its breaking in the Pekar approximation) makes the analysis substantially more challenging.}, author = {Feliciangeli, Dario and Seiringer, Robert}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, number = {3}, pages = {1835–1906}, publisher = {Springer Nature}, title = {{The strongly coupled polaron on the torus: Quantum corrections to the Pekar asymptotics}}, doi = {10.1007/s00205-021-01715-7}, volume = {242}, year = {2021}, } @article{10281, abstract = {Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems}, author = {Vasic, Verica and Jones, Mattson S.O. and Haslinger, Denise and Knaus, Lisa and Schmeisser, Michael J. and Novarino, Gaia and Chiocchetti, Andreas G.}, issn = {2073-4425}, journal = {Genes}, number = {11}, publisher = {MDPI}, title = {{Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment}}, doi = {10.3390/genes12111746}, volume = {12}, year = {2021}, } @article{10282, abstract = {Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development.}, author = {Kashkan, Ivan and Hrtyan, Mónika and Retzer, Katarzyna and Humpolíčková, Jana and Jayasree, Aswathy and Filepová, Roberta and Vondráková, Zuzana and Simon, Sibu and Rombaut, Debbie and Jacobs, Thomas B. and Frilander, Mikko J. and Hejátko, Jan and Friml, Jiří and Petrášek, Jan and Růžička, Kamil}, issn = {1469-8137}, journal = {New Phytologist}, pages = {329--343}, publisher = {Wiley}, title = {{Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana}}, doi = {10.1111/nph.17792}, volume = {233}, year = {2021}, } @article{10220, abstract = {We study conditions under which a finite simplicial complex K can be mapped to ℝd without higher-multiplicity intersections. An almost r-embedding is a map f: K → ℝd such that the images of any r pairwise disjoint simplices of K do not have a common point. We show that if r is not a prime power and d ≥ 2r + 1, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost r-embedding of the (d +1)(r − 1)-simplex in ℝd. This improves on previous constructions of counterexamples (for d ≥ 3r) based on a series of papers by M. Özaydin, M. Gromov, P. Blagojević, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If r ≥ 3 and if K is a finite 2(r − 1)-complex, then there exists an almost r-embedding K → ℝ2r if and only if there exists a general position PL map f: K → ℝ2r such that the algebraic intersection number of the f-images of any r pairwise disjoint simplices of K is zero. This result can be restated in terms of a cohomological obstruction and extends an analogous codimension 3 criterion by the second and fourth authors. As another application, we classify ornaments f: S3 ⊔ S3 ⊔ S3 → ℝ5 up to ornament concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for r = 2 is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.}, author = {Avvakumov, Sergey and Mabillard, Isaac and Skopenkov, Arkadiy B. and Wagner, Uli}, issn = {1565-8511}, journal = {Israel Journal of Mathematics}, pages = {501–534 }, publisher = {Springer Nature}, title = {{Eliminating higher-multiplicity intersections. III. Codimension 2}}, doi = {10.1007/s11856-021-2216-z}, volume = {245}, year = {2021}, } @misc{13061, abstract = {Infections early in life can have enduring effects on an organism’s development and immunity. In this study, we show that this equally applies to developing “superorganisms” – incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen’s immune system to suppress pathogen proliferation. Early-life queen pathogen-exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen’s pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism.}, author = {Casillas Perez, Barbara E and Pull, Christopher and Naiser, Filip and Naderlinger, Elisabeth and Matas, Jiri and Cremer, Sylvia}, publisher = {Dryad}, title = {{Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies}}, doi = {10.5061/DRYAD.7PVMCVDTJ}, year = {2021}, } @article{10301, abstract = {De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement.}, author = {Conde-Dusman, María J and Dey, Partha N and Elía-Zudaire, Óscar and Garcia Rabaneda, Luis E and García-Lira, Carmen and Grand, Teddy and Briz, Victor and Velasco, Eric R and Andero Galí, Raül and Niñerola, Sergio and Barco, Angel and Paoletti, Pierre and Wesseling, John F and Gardoni, Fabrizio and Tavalin, Steven J and Perez-Otaño, Isabel}, issn = {2050-084X}, journal = {eLife}, keywords = {general immunology and microbiology, general biochemistry, genetics and molecular biology, general medicine, general neuroscience}, publisher = {eLife Sciences Publications}, title = {{Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly}}, doi = {10.7554/elife.71575}, volume = {10}, year = {2021}, } @article{10283, abstract = {During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research.}, author = {Restivo, Leonardo and Gerlach, Björn and Tsoory, Michael and Bikovski, Lior and Badurek, Sylvia and Pitzer, Claudia and Kos-Braun, Isabelle C. and Mausset-Bonnefont, Anne Laure Mj and Ward, Jonathan and Schunn, Michael and Noldus, Lucas P.J.J. and Bespalov, Anton and Voikar, Vootele}, issn = {1469-3178}, journal = {EMBO Reports}, publisher = {EMBO Press}, title = {{Towards best practices in research: Role of academic core facilities}}, doi = {10.15252/embr.202153824}, volume = {22}, year = {2021}, } @article{10310, abstract = {A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.}, author = {Çoruh, Mehmet Orkun and Frank, Anna and Tanaka, Hideaki and Kawamoto, Akihiro and El-Mohsnawy, Eithar and Kato, Takayuki and Namba, Keiichi and Gerle, Christoph and Nowaczyk, Marc M. and Kurisu, Genji}, issn = {2399-3642}, journal = {Communications Biology}, keywords = {general agricultural and biological Sciences, general biochemistry, genetics and molecular biology, medicine (miscellaneous)}, number = {1}, publisher = {Springer }, title = {{Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster}}, doi = {10.1038/s42003-021-01808-9}, volume = {4}, year = {2021}, } @article{10270, abstract = {Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development.}, author = {Marconi, Marco and Gallemi, Marçal and Benková, Eva and Wabnik, Krzysztof}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{A coupled mechano-biochemical model for cell polarity guided anisotropic root growth}}, doi = {10.7554/elife.72132}, volume = {10}, year = {2021}, } @article{10299, abstract = {Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number.}, author = {Choueiri, George H and Lopez Alonso, Jose M and Varshney, Atul and Sankar, Sarath and Hof, Björn}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {multidisciplinary, elastoinertial turbulence, viscoelastic flows, elastic instability, drag reduction}, number = {45}, publisher = {National Academy of Sciences}, title = {{Experimental observation of the origin and structure of elastoinertial turbulence}}, doi = {10.1073/pnas.2102350118}, volume = {118}, year = {2021}, } @article{10280, abstract = {Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials.}, author = {Aubret, Antoine and Martinet, Quentin and Palacci, Jérémie A}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Metamachines of pluripotent colloids}}, doi = {10.1038/s41467-021-26699-6}, volume = {12}, year = {2021}, } @article{10322, abstract = {To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.}, author = {Chauve, Laetitia and Hodge, Francesca and Murdoch, Sharlene and Masoudzadeh, Fatemah and Mann, Harry Jack and Lopez-Clavijo, Andrea and Okkenhaug, Hanneke and West, Greg and Sousa, Bebiana C. and Segonds-Pichon, Anne and Li, Cheryl and Wingett, Steven and Kienberger, Hermine and Kleigrewe, Karin and De Bono, Mario and Wakelam, Michael and Casanueva, Olivia}, issn = {1545-7885}, journal = {PLoS Biology}, number = {11}, publisher = {Public Library of Science}, title = {{Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans}}, doi = {10.1371/journal.pbio.3001431}, volume = {19}, year = {2021}, } @article{10222, abstract = {Consider a random set of points on the unit sphere in ℝd, which can be either uniformly sampled or a Poisson point process. Its convex hull is a random inscribed polytope, whose boundary approximates the sphere. We focus on the case d = 3, for which there are elementary proofs and fascinating formulas for metric properties. In particular, we study the fraction of acute facets, the expected intrinsic volumes, the total edge length, and the distance to a fixed point. Finally we generalize the results to the ellipsoid with homeoid density.}, author = {Akopyan, Arseniy and Edelsbrunner, Herbert and Nikitenko, Anton}, issn = {1944-950X}, journal = {Experimental Mathematics}, pages = {1--15}, publisher = {Taylor and Francis}, title = {{The beauty of random polytopes inscribed in the 2-sphere}}, doi = {10.1080/10586458.2021.1980459}, year = {2021}, } @article{10323, abstract = {Molecular chaperones are central to cellular protein homeostasis. Dynamic disorder is a key feature of the complexes of molecular chaperones and their client proteins, and it facilitates the client release towards a folded state or the handover to downstream components. The dynamic nature also implies that a given chaperone can interact with many different client proteins, based on physico-chemical sequence properties rather than on structural complementarity of their (folded) 3D structure. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. Here, we review recent atomic-level descriptions of chaperones with client proteins, including chaperones in complex with intrinsically disordered proteins, with membrane-protein precursors, or partially folded client proteins. We focus hereby on chaperone-client interactions that are independent of ATP. The picture emerging from these studies highlights the importance of dynamics in these complexes, whereby several interaction types, not only hydrophobic ones, contribute to the complex formation. We discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity.}, author = {Sučec, Iva and Bersch, Beate and Schanda, Paul}, issn = {2296-889X}, journal = {Frontiers in Molecular Biosciences}, publisher = {Frontiers}, title = {{How do chaperones bind (partly) unfolded client proteins?}}, doi = {10.3389/fmolb.2021.762005}, volume = {8}, year = {2021}, } @article{10326, abstract = {Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants.}, author = {Xu, Enjun and Chai, Liang and Zhang, Shiqi and Yu, Ruixue and Zhang, Xixi and Xu, Chongyi and Hu, Yuxin}, issn = {2055-0278}, journal = {Nature Plants}, pages = {1495–1504 }, publisher = {Springer Nature}, title = {{Catabolism of strigolactones by a carboxylesterase}}, doi = {10.1038/s41477-021-01011-y}, volume = {7}, year = {2021}, } @misc{13069, abstract = {To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell-autonomous. We have discovered that, in Caenorhabditis elegans, neuronal Heat shock Factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR)- causes extensive fat remodelling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine, and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodelling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least six TAX-2/TAX-4 cGMP gated channel expressing sensory neurons and TGF-β/BMP are required for signalling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodelling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell non-autonomously coordinate membrane saturation and composition across tissues in a multicellular animal.}, author = {Chauve, Laetitia and Hodge, Francesca and Murdoch, Sharlene and Masoudzadeh, Fatemah and Mann, Harry-Jack and Lopez-Clavijo, Andrea and Okkenhaug, Hanneke and West, Greg and Sousa, Bebiana C. and Segonds-Pichon, Anne and Li, Cheryl and Wingett, Steven and Kienberger, Hermine and Kleigrewe, Karin and de Bono, Mario and Wakelam, Michael and Casanueva, Olivia}, publisher = {Zenodo}, title = {{Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans}}, doi = {10.5281/ZENODO.5519410}, year = {2021}, } @inproceedings{10325, abstract = {Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains.}, author = {Zamyatin, Alexei and Al-Bassam, Mustafa and Zindros, Dionysis and Kokoris Kogias, Eleftherios and Moreno-Sanchez, Pedro and Kiayias, Aggelos and Knottenbelt, William J.}, booktitle = {25th International Conference on Financial Cryptography and Data Security}, isbn = {9-783-6626-4330-3}, issn = {1611-3349}, location = {Virtual}, pages = {3--36}, publisher = {Springer Nature}, title = {{SoK: Communication across distributed ledgers}}, doi = {10.1007/978-3-662-64331-0_1}, volume = {12675 }, year = {2021}, } @inproceedings{10324, abstract = {Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee’s approval for the last valid state. Additionally, Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. We formally define and prove for Brick the properties a payment channel construction should fulfill. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity.}, author = {Avarikioti, Zeta and Kokoris Kogias, Eleftherios and Wattenhofer, Roger and Zindros, Dionysis}, booktitle = {25th International Conference on Financial Cryptography and Data Security}, isbn = {9-783-6626-4330-3}, issn = {1611-3349}, location = {Virtual}, pages = {209--230}, publisher = {Springer Nature}, title = {{Brick: Asynchronous incentive-compatible payment channels}}, doi = {10.1007/978-3-662-64331-0_11}, volume = {12675 }, year = {2021}, } @article{10363, abstract = {Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.}, author = {Lee, Jungmin and Vernet, Andyna and Gruber, Nathalie and Kready, Kasia M. and Burrill, Devin R. and Way, Jeffrey C. and Silver, Pamela A.}, issn = {1741-0134}, journal = {Protein Engineering, Design and Selection}, publisher = {Oxford University Press}, title = {{Rational engineering of an erythropoietin fusion protein to treat hypoxia}}, doi = {10.1093/protein/gzab025}, volume = {34}, year = {2021}, } @article{10366, author = {Heisenberg, Carl-Philipp J and Lennon, Ana Maria and Mayor, Roberto and Salbreux, Guillaume}, issn = {2667-2901}, journal = {Cells and Development}, number = {12}, publisher = {Elsevier}, title = {{Special rebranding issue: “Quantitative cell and developmental biology”}}, doi = {10.1016/j.cdev.2021.203758}, volume = {168}, year = {2021}, } @article{10402, abstract = {Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales.}, author = {Ucar, Mehmet C and Kamenev, Dmitrii and Sunadome, Kazunori and Fachet, Dominik C and Lallemend, Francois and Adameyko, Igor and Hadjab, Saida and Hannezo, Edouard B}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Theory of branching morphogenesis by local interactions and global guidance}}, doi = {10.1038/s41467-021-27135-5}, volume = {12}, year = {2021}, } @inproceedings{10407, abstract = {Digital hardware Trojans are integrated circuits whose implementation differ from the specification in an arbitrary and malicious way. For example, the circuit can differ from its specified input/output behavior after some fixed number of queries (known as “time bombs”) or on some particular input (known as “cheat codes”). To detect such Trojans, countermeasures using multiparty computation (MPC) or verifiable computation (VC) have been proposed. On a high level, to realize a circuit with specification F one has more sophisticated circuits F⋄ manufactured (where F⋄ specifies a MPC or VC of F ), and then embeds these F⋄ ’s into a master circuit which must be trusted but is relatively simple compared to F . Those solutions impose a significant overhead as F⋄ is much more complex than F , also the master circuits are not exactly trivial. In this work, we show that in restricted settings, where F has no evolving state and is queried on independent inputs, we can achieve a relaxed security notion using very simple constructions. In particular, we do not change the specification of the circuit at all (i.e., F=F⋄ ). Moreover the master circuit basically just queries a subset of its manufactured circuits and checks if they’re all the same. The security we achieve guarantees that, if the manufactured circuits are initially tested on up to T inputs, the master circuit will catch Trojans that try to deviate on significantly more than a 1/T fraction of the inputs. This bound is optimal for the type of construction considered, and we provably achieve it using a construction where 12 instantiations of F need to be embedded into the master. We also discuss an extremely simple construction with just 2 instantiations for which we conjecture that it already achieves the optimal bound.}, author = {Chakraborty, Suvradip and Dziembowski, Stefan and Gałązka, Małgorzata and Lizurej, Tomasz and Pietrzak, Krzysztof Z and Yeo, Michelle X}, isbn = {9-783-0309-0452-4}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {397--428}, publisher = {Springer Nature}, title = {{Trojan-resilience without cryptography}}, doi = {10.1007/978-3-030-90453-1_14}, volume = {13043}, year = {2021}, } @article{10403, abstract = {Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits.}, author = {Biane, Celia and Rückerl, Florian and Abrahamsson, Therese and Saint-Cloment, Cécile and Mariani, Jean and Shigemoto, Ryuichi and Digregorio, David A. and Sherrard, Rachel M. and Cathala, Laurence}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons}}, doi = {10.7554/eLife.65954}, volume = {10}, year = {2021}, } @article{10401, abstract = {Theoretical and experimental studies of the interaction between spins and temperature are vital for the development of spin caloritronics, as they dictate the design of future devices. In this work, we propose a two-terminal cold-atom simulator to study that interaction. The proposed quantum simulator consists of strongly interacting atoms that occupy two temperature reservoirs connected by a one-dimensional link. First, we argue that the dynamics in the link can be described using an inhomogeneous Heisenberg spin chain whose couplings are defined by the local temperature. Second, we show the existence of a spin current in a system with a temperature difference by studying the dynamics that follows the spin-flip of an atom in the link. A temperature gradient accelerates the impurity in one direction more than in the other, leading to an overall spin current similar to the spin Seebeck effect.}, author = {Barfknecht, Rafael E. and Foerster, Angela and Zinner, Nikolaj T. and Volosniev, Artem}, issn = {23993650}, journal = {Communications Physics}, number = {1}, publisher = {Springer Nature}, title = {{Generation of spin currents by a temperature gradient in a two-terminal device}}, doi = {10.1038/s42005-021-00753-7}, volume = {4}, year = {2021}, } @article{10404, abstract = {While convolutional neural networks (CNNs) have found wide adoption as state-of-the-art models for image-related tasks, their predictions are often highly sensitive to small input perturbations, which the human vision is robust against. This paper presents Perturber, a web-based application that allows users to instantaneously explore how CNN activations and predictions evolve when a 3D input scene is interactively perturbed. Perturber offers a large variety of scene modifications, such as camera controls, lighting and shading effects, background modifications, object morphing, as well as adversarial attacks, to facilitate the discovery of potential vulnerabilities. Fine-tuned model versions can be directly compared for qualitative evaluation of their robustness. Case studies with machine learning experts have shown that Perturber helps users to quickly generate hypotheses about model vulnerabilities and to qualitatively compare model behavior. Using quantitative analyses, we could replicate users’ insights with other CNN architectures and input images, yielding new insights about the vulnerability of adversarially trained models.}, author = {Sietzen, Stefan and Lechner, Mathias and Borowski, Judy and Hasani, Ramin and Waldner, Manuela}, issn = {1467-8659}, journal = {Computer Graphics Forum}, number = {7}, pages = {253--264}, publisher = {Wiley}, title = {{Interactive analysis of CNN robustness}}, doi = {10.1111/cgf.14418}, volume = {40}, year = {2021}, } @article{10406, abstract = {Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future.}, author = {Mishra, Nikhil and Heisenberg, Carl-Philipp J}, issn = {1545-2948}, journal = {Annual Review of Genetics}, keywords = {morphogenesis, forward genetics, high-resolution microscopy, biophysics, biochemistry, patterning}, pages = {209--233}, publisher = {Annual Reviews}, title = {{Dissecting organismal morphogenesis by bridging genetics and biophysics}}, doi = {10.1146/annurev-genet-071819-103748}, volume = {55}, year = {2021}, } @misc{13058, abstract = {The zip file includes source data used in the main text of the manuscript "Theory of branching morphogenesis by local interactions and global guidance", as well as a representative Jupyter notebook to reproduce the main figures. A sample script for the simulations of branching and annihilating random walks is also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary branched networks under external guidance. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt.}, author = {Ucar, Mehmet C}, publisher = {Zenodo}, title = {{Source data for the manuscript "Theory of branching morphogenesis by local interactions and global guidance"}}, doi = {10.5281/ZENODO.5257160}, year = {2021}, } @inproceedings{10408, abstract = {Key trees are often the best solution in terms of transmission cost and storage requirements for managing keys in a setting where a group needs to share a secret key, while being able to efficiently rotate the key material of users (in order to recover from a potential compromise, or to add or remove users). Applications include multicast encryption protocols like LKH (Logical Key Hierarchies) or group messaging like the current IETF proposal TreeKEM. A key tree is a (typically balanced) binary tree, where each node is identified with a key: leaf nodes hold users’ secret keys while the root is the shared group key. For a group of size N, each user just holds log(N) keys (the keys on the path from its leaf to the root) and its entire key material can be rotated by broadcasting 2log(N) ciphertexts (encrypting each fresh key on the path under the keys of its parents). In this work we consider the natural setting where we have many groups with partially overlapping sets of users, and ask if we can find solutions where the cost of rotating a key is better than in the trivial one where we have a separate key tree for each group. We show that in an asymptotic setting (where the number m of groups is fixed while the number N of users grows) there exist more general key graphs whose cost converges to the cost of a single group, thus saving a factor linear in the number of groups over the trivial solution. As our asymptotic “solution” converges very slowly and performs poorly on concrete examples, we propose an algorithm that uses a natural heuristic to compute a key graph for any given group structure. Our algorithm combines two greedy algorithms, and is thus very efficient: it first converts the group structure into a “lattice graph”, which is then turned into a key graph by repeatedly applying the algorithm for constructing a Huffman code. To better understand how far our proposal is from an optimal solution, we prove lower bounds on the update cost of continuous group-key agreement and multicast encryption in a symbolic model admitting (asymmetric) encryption, pseudorandom generators, and secret sharing as building blocks.}, author = {Alwen, Joel F and Auerbach, Benedikt and Baig, Mirza Ahad and Cueto Noval, Miguel and Klein, Karen and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z and Walter, Michael}, booktitle = {19th International Conference}, isbn = {9-783-0309-0455-5}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {222--253}, publisher = {Springer Nature}, title = {{Grafting key trees: Efficient key management for overlapping groups}}, doi = {10.1007/978-3-030-90456-2_8}, volume = {13044}, year = {2021}, } @article{10527, abstract = {We show that in a two-dimensional electron gas with an annular Fermi surface, long-range Coulomb interactions can lead to unconventional superconductivity by the Kohn-Luttinger mechanism. Superconductivity is strongly enhanced when the inner and outer Fermi surfaces are close to each other. The most prevalent state has chiral p-wave symmetry, but d-wave and extended s-wave pairing are also possible. We discuss these results in the context of rhombohedral trilayer graphene, where superconductivity was recently discovered in regimes where the normal state has an annular Fermi surface. Using realistic parameters, our mechanism can account for the order of magnitude of Tc, as well as its trends as a function of electron density and perpendicular displacement field. Moreover, it naturally explains some of the outstanding puzzles in this material, that include the weak temperature dependence of the resistivity above Tc, and the proximity of spin singlet superconductivity to the ferromagnetic phase.}, author = {Ghazaryan, Areg and Holder, Tobias and Serbyn, Maksym and Berg, Erez}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {24}, publisher = {American Physical Society}, title = {{Unconventional superconductivity in systems with annular Fermi surfaces: Application to rhombohedral trilayer graphene}}, doi = {10.1103/physrevlett.127.247001}, volume = {127}, year = {2021}, } @article{10534, abstract = {For many years, fullerene derivatives have been the main n-type material of organic electronics and optoelectronics. Recently, fullerene derivatives functionalized with ethylene glycol (EG) side chains have been showing important properties such as enhanced dielectric constants, facile doping and enhanced self-assembly capabilities. Here, we have prepared field-effect transistors using a series of these fullerene derivatives equipped with EG side chains of different lengths. Transport data show the beneficial effect of increasing the EG side chain. In order to understand the material properties, full structural determination of these fullerene derivatives has been achieved by coupling the X-ray data with molecular dynamics (MD) simulations. The increase in transport properties is paired with the formation of extended layered structures, efficient molecular packing and an increase in the crystallite alignment. The layer-like structure is composed of conducting layers, containing of closely packed C60 balls approaching the inter-distance of 1 nm, that are separated by well-defined EG layers, where the EG chains are rather splayed with the chain direction almost perpendicular to the layer normal. Such a layered structure appears highly ordered and highly aligned with the C60 planes oriented parallel to the substrate in the thin film configuration. The order inside the thin film increases with the EG chain length, allowing the systems to achieve mobilities as high as 0.053 cm2 V−1 s−1. Our work elucidates the structure of these interesting semiconducting organic molecules and shows that the synergistic use of X-ray structural analysis and MD simulations is a powerful tool to identify the structure of thin organic films for optoelectronic applications.}, author = {Dong, Jingjin and Sami, Selim and Balazs, Daniel and Alessandri, Riccardo and Jahani, Fatimeh and Qiu, Li and Marrink, Siewert J. and Havenith, Remco W.A. and Hummelen, Jan C. and Loi, Maria A. and Portale, Giuseppe}, issn = {2050-7526}, journal = {Journal of Materials Chemistry C}, number = {45}, pages = {16217--16225}, publisher = {Royal Society of Chemistry}, title = {{Fullerene derivatives with oligoethylene-glycol side chains: An investigation on the origin of their outstanding transport properties}}, doi = {10.1039/d1tc02753k}, volume = {9}, year = {2021}, } @article{10533, abstract = {Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin.}, author = {Choi, Jaemyung and Lyons, David B and Zilberman, Daniel}, issn = {2050-084X}, journal = {eLife}, keywords = {genetics and molecular biology}, publisher = {eLife Sciences Publications}, title = {{Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin}}, doi = {10.7554/elife.72676}, volume = {10}, year = {2021}, } @article{10536, abstract = {TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner.}, author = {Stefanescu, Cristina and Van Gogh, Merel and Roblek, Marko and Heikenwalder, Mathias and Borsig, Lubor}, issn = {2234-943X}, journal = {Frontiers in Oncology}, publisher = {Frontiers}, title = {{TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms}}, doi = {10.3389/fonc.2021.765151}, volume = {11}, year = {2021}, } @article{10537, abstract = {We consider the quantum many-body evolution of a homogeneous Fermi gas in three dimensions in the coupled semiclassical and mean-field scaling regime. We study a class of initial data describing collective particle–hole pair excitations on the Fermi ball. Using a rigorous version of approximate bosonization, we prove that the many-body evolution can be approximated in Fock space norm by a quasi-free bosonic evolution of the collective particle–hole excitations.}, author = {Benedikter, Niels P and Nam, Phan Thành and Porta, Marcello and Schlein, Benjamin and Seiringer, Robert}, issn = {1424-0637}, journal = {Annales Henri Poincaré}, publisher = {Springer Nature}, title = {{Bosonization of fermionic many-body dynamics}}, doi = {10.1007/s00023-021-01136-y}, year = {2021}, } @article{10549, abstract = {We derive optimal-order homogenization rates for random nonlinear elliptic PDEs with monotone nonlinearity in the uniformly elliptic case. More precisely, for a random monotone operator on \mathbb {R}^d with stationary law (that is spatially homogeneous statistics) and fast decay of correlations on scales larger than the microscale \varepsilon >0, we establish homogenization error estimates of the order \varepsilon in case d\geqq 3, and of the order \varepsilon |\log \varepsilon |^{1/2} in case d=2. Previous results in nonlinear stochastic homogenization have been limited to a small algebraic rate of convergence \varepsilon ^\delta . We also establish error estimates for the approximation of the homogenized operator by the method of representative volumes of the order (L/\varepsilon )^{-d/2} for a representative volume of size L. Our results also hold in the case of systems for which a (small-scale) C^{1,\alpha } regularity theory is available.}, author = {Fischer, Julian L and Neukamm, Stefan}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, keywords = {Mechanical Engineering, Mathematics (miscellaneous), Analysis}, number = {1}, pages = {343--452}, publisher = {Springer Nature}, title = {{Optimal homogenization rates in stochastic homogenization of nonlinear uniformly elliptic equations and systems}}, doi = {10.1007/s00205-021-01686-9}, volume = {242}, year = {2021}, } @inproceedings{10409, abstract = {We show that Yao’s garbling scheme is adaptively indistinguishable for the class of Boolean circuits of size S and treewidth w with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity. with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity.}, author = {Kamath Hosdurg, Chethan and Klein, Karen and Pietrzak, Krzysztof Z}, booktitle = {19th International Conference}, isbn = {9-783-0309-0452-4}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {486--517}, publisher = {Springer Nature}, title = {{On treewidth, separators and Yao’s garbling}}, doi = {10.1007/978-3-030-90453-1_17}, volume = {13043 }, year = {2021}, } @article{10545, abstract = {Classical models with complex energy landscapes represent a perspective avenue for the near-term application of quantum simulators. Until now, many theoretical works studied the performance of quantum algorithms for models with a unique ground state. However, when the classical problem is in a so-called clustering phase, the ground state manifold is highly degenerate. As an example, we consider a 3-XORSAT model defined on simple hypergraphs. The degeneracy of classical ground state manifold translates into the emergence of an extensive number of Z2 symmetries, which remain intact even in the presence of a quantum transverse magnetic field. We establish a general duality approach that restricts the quantum problem to a given sector of conserved Z2 charges and use it to study how the outcome of the quantum adiabatic algorithm depends on the hypergraph geometry. We show that the tree hypergraph which corresponds to a classically solvable instance of the 3-XORSAT problem features a constant gap, whereas the closed hypergraph encounters a second-order phase transition with a gap vanishing as a power-law in the problem size. The duality developed in this work provides a practical tool for studies of quantum models with classically degenerate energy manifold and reveals potential connections between glasses and gauge theories.}, author = {Medina Ramos, Raimel A and Serbyn, Maksym}, issn = {2469-9934}, journal = {Physical Review A}, number = {6}, publisher = {American Physical Society}, title = {{Duality approach to quantum annealing of the 3-variable exclusive-or satisfiability problem (3-XORSAT)}}, doi = {10.1103/physreva.104.062423}, volume = {104}, year = {2021}, } @inproceedings{10554, abstract = {We present DAG-Rider, the first asynchronous Byzantine Atomic Broadcast protocol that achieves optimal resilience, optimal amortized communication complexity, and optimal time complexity. DAG-Rider is post-quantum safe and ensures that all values proposed by correct processes eventually get delivered. We construct DAG-Rider in two layers: In the first layer, processes reliably broadcast their proposals and build a structured Directed Acyclic Graph (DAG) of the communication among them. In the second layer, processes locally observe their DAGs and totally order all proposals with no extra communication.}, author = {Keidar, Idit and Kokoris Kogias, Eleftherios and Naor, Oded and Spiegelman, Alexander}, booktitle = {Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing}, isbn = {978-1-4503-8548-0}, location = {Virtual, Italy}, pages = {165--175}, publisher = {Association for Computing Machinery}, title = {{All You Need is DAG}}, doi = {10.1145/3465084.3467905}, year = {2021}, } @article{10568, abstract = {Genetic adaptation and phenotypic plasticity facilitate the migration into new habitats and enable organisms to cope with a rapidly changing environment. In contrast to genetic adaptation that spans multiple generations as an evolutionary process, phenotypic plasticity allows acclimation within the life-time of an organism. Genetic adaptation and phenotypic plasticity are usually studied in isolation, however, only by including their interactive impact, we can understand acclimation and adaptation in nature. We aimed to explore the contribution of adaptation and plasticity in coping with an abiotic (salinity) and a biotic (Vibrio bacteria) stressor using six different populations of the broad-nosed pipefish Syngnathus typhle that originated from either high [14–17 Practical Salinity Unit (PSU)] or low (7–11 PSU) saline environments along the German coastline of the Baltic Sea. We exposed wild caught animals, to either high (15 PSU) or low (7 PSU) salinity, representing native and novel salinity conditions and allowed animals to mate. After male pregnancy, offspring was split and each half was exposed to one of the two salinities and infected with Vibrio alginolyticus bacteria that were evolved at either of the two salinities in a fully reciprocal design. We investigated life-history traits of fathers and expression of 47 target genes in mothers and offspring. Pregnant males originating from high salinity exposed to low salinity were highly susceptible to opportunistic fungi infections resulting in decreased offspring size and number. In contrast, no signs of fungal infection were identified in fathers originating from low saline conditions suggesting that genetic adaptation has the potential to overcome the challenges encountered at low salinity. Offspring from parents with low saline origin survived better at low salinity suggesting genetic adaptation to low salinity. In addition, gene expression analyses of juveniles indicated patterns of local adaptation, trans-generational plasticity and developmental plasticity. In conclusion, our study suggests that pipefish are locally adapted to the low salinity in their environment, however, they are retaining phenotypic plasticity, which allows them to also cope with ancestral salinity levels and prevailing pathogens.}, author = {Goehlich, Henry and Sartoris, Linda and Wagner, Kim-Sara and Wendling, Carolin C. and Roth, Olivia}, issn = {2296-701X}, journal = {Frontiers in Ecology and Evolution}, keywords = {ecology, evolution, behavior and systematics, trans-generational plasticity, genetic adaptation, local adaptation, phenotypic plasticity, Baltic Sea, climate change, salinity, syngnathids}, publisher = {Frontiers Media}, title = {{Pipefish locally adapted to low salinity in the Baltic Sea retain phenotypic plasticity to cope with ancestral salinity levels}}, doi = {10.3389/fevo.2021.626442}, volume = {9}, year = {2021}, } @article{10586, abstract = {A facile approach for developing an interfacial solar evaporator by heat localization of solar-thermal energy conversion at water-air liquid composed by in-situ polymerization of Fe2O3 nanoparticles (Fe2O3@PPy) deposited over a facial sponge is proposed. The demonstrated system consists of a floating solar receiver having a vertically cross-linked microchannel for wicking up saline water. The in situ polymerized Fe2O3@PPy interfacial layer promotes diffuse reflection and its rough black surface allows Omni-directional solar absorption (94%) and facilitates efficient thermal localization at the water/air interface and offers a defect-rich surface to promote heat localization (41.9 °C) and excellent thermal management due to cellulosic content. The self-floating composite foam reveals continuous vapors generation at a rate of 1.52 kg m−2 h−1 under one 1 kW m−2 and profound evaporating efficiency (95%) without heat losses that dissipates in its surroundings. Indeed, long-term evaporation experiments reveal the negligible disparity in continuous evaporation rate (33.84 kg m−2/8.3 h) receiving two sun solar intensity, and ensures the stability of the device under intense seawater conditions synchronized with excellent salt rejection potential. More importantly, Raman spectroscopy investigation validates the orange dye rejection via Fe2O3@PPy solar evaporator. The combined advantages of high efficiency, self-floating capability, multimedia rejection, low cost, and this configuration are promising for producing large-scale solar steam generating systems appropriate for commercial clean water yield due to their scalable fabrication.}, author = {Lu, Yuzheng and Arshad, Naila and Irshad, Muhammad Sultan and Ahmed, Iftikhar and Ahmad, Shafiq and Alshahrani, Lina Abdullah and Yousaf, Muhammad and Sayed, Abdelaty Edrees and Nauman, Muhammad}, issn = {2073-4352}, journal = {Crystals}, number = {12}, publisher = {MDPI}, title = {{Fe2O3 nanoparticles deposited over self-floating facial sponge for facile interfacial seawater solar desalination}}, doi = {10.3390/cryst11121509}, volume = {11}, year = {2021}, } @article{10569, abstract = {For animals to survive until reproduction, it is crucial that juveniles successfully detect potential predators and respond with appropriate behavior. The recognition of cues originating from predators can be innate or learned. Cues of various modalities might be used alone or in multi-modal combinations to detect and distinguish predators but studies investigating multi-modal integration in predator avoidance are scarce. Here, we used wild, naive tadpoles of the Neotropical poison frog Allobates femoralis ( Boulenger, 1884) to test their reaction to cues with two modalities from two different sympatrically occurring potential predators: heterospecific predatory Dendrobates tinctorius tadpoles and dragonfly larvae. We presented A. femoralis tadpoles with olfactory or visual cues, or a combination of the two, and compared their reaction to a water control in a between-individual design. In our trials, A. femoralis tadpoles reacted to multi-modal stimuli (a combination of visual and chemical information) originating from dragonfly larvae with avoidance but showed no reaction to uni-modal cues or cues from heterospecific tadpoles. In addition, visual cues from conspecifics increased swimming activity while cues from predators had no effect on tadpole activity. Our results show that A. femoralis tadpoles can innately recognize some predators and probably need both visual and chemical information to effectively avoid them. This is the first study looking at anti-predator behavior in poison frog tadpoles. We discuss how parental care might influence the expression of predator avoidance responses in tadpoles.}, author = {Szabo, B and Mangione, R and Rath, M and Pašukonis, A and Reber, SA and Oh, Jinook and Ringler, M and Ringler, E}, issn = {1477-9145}, journal = {Journal of Experimental Biology}, number = {24}, publisher = {The Company of Biologists}, title = {{Naïve poison frog tadpoles use bi-modal cues to avoid insect predators but not heterospecific predatory tadpoles}}, doi = {10.1242/jeb.243647}, volume = {224}, year = {2021}, } @article{10575, abstract = {The choice of the boundary conditions in mechanical problems has to reflect the interaction of the considered material with the surface. Still the assumption of the no-slip condition is preferred in order to avoid boundary terms in the analysis and slipping effects are usually overlooked. Besides the “static slip models”, there are phenomena that are not accurately described by them, e.g. at the moment when the slip changes rapidly, the wall shear stress and the slip can exhibit a sudden overshoot and subsequent relaxation. When these effects become significant, the so-called dynamic slip phenomenon occurs. We develop a mathematical analysis of Navier–Stokes-like problems with a dynamic slip boundary condition, which requires a proper generalization of the Gelfand triplet and the corresponding function space setting.}, author = {Abbatiello, Anna and Bulíček, Miroslav and Maringová, Erika}, issn = {1793-6314}, journal = {Mathematical Models and Methods in Applied Sciences}, number = {11}, pages = {2165--2212}, publisher = {World Scientific Publishing}, title = {{On the dynamic slip boundary condition for Navier-Stokes-like problems}}, doi = {10.1142/S0218202521500470}, volume = {31}, year = {2021}, } @article{10574, abstract = {The understanding of material appearance perception is a complex problem due to interactions between material reflectance, surface geometry, and illumination. Recently, Serrano et al. collected the largest dataset to date with subjective ratings of material appearance attributes, including glossiness, metallicness, sharpness and contrast of reflections. In this work, we make use of their dataset to investigate for the first time the impact of the interactions between illumination, geometry, and eight different material categories in perceived appearance attributes. After an initial analysis, we select for further analysis the four material categories that cover the largest range for all perceptual attributes: fabric, plastic, ceramic, and metal. Using a cumulative link mixed model (CLMM) for robust regression, we discover interactions between these material categories and four representative illuminations and object geometries. We believe that our findings contribute to expanding the knowledge on material appearance perception and can be useful for many applications, such as scene design, where any particular material in a given shape can be aligned with dominant classes of illumination, so that a desired strength of appearance attributes can be achieved.}, author = {Chen, Bin and Wang, Chao and Piovarci, Michael and Seidel, Hans Peter and Didyk, Piotr and Myszkowski, Karol and Serrano, Ana}, issn = {1432-2315}, journal = {Visual Computer}, number = {12}, pages = {2975--2987}, publisher = {Springer Nature}, title = {{The effect of geometry and illumination on appearance perception of different material categories}}, doi = {10.1007/s00371-021-02227-x}, volume = {37}, year = {2021}, } @article{10573, abstract = {How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.}, author = {Munjal, Akankshi and Hannezo, Edouard B and Tsai, Tony Y.C. and Mitchison, Timothy J. and Megason, Sean G.}, issn = {1097-4172}, journal = {Cell}, number = {26}, pages = {6313--6325.e18}, publisher = {Elsevier ; Cell Press}, title = {{Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis}}, doi = {10.1016/j.cell.2021.11.025}, volume = {184}, year = {2021}, } @article{10674, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets.}, author = {Aghajohari, Milad and Avni, Guy and Henzinger, Thomas A}, issn = {1860-5974}, journal = {Logical Methods in Computer Science}, keywords = {computer science, computer science and game theory, logic in computer science}, number = {1}, pages = {10:1--10:23}, publisher = {International Federation for Computational Logic}, title = {{Determinacy in discrete-bidding infinite-duration games}}, doi = {10.23638/LMCS-17(1:10)2021}, volume = {17}, year = {2021}, } @inproceedings{10609, abstract = {We study Multi-party computation (MPC) in the setting of subversion, where the adversary tampers with the machines of honest parties. Our goal is to construct actively secure MPC protocols where parties are corrupted adaptively by an adversary (as in the standard adaptive security setting), and in addition, honest parties’ machines are compromised. The idea of reverse firewalls (RF) was introduced at EUROCRYPT’15 by Mironov and Stephens-Davidowitz as an approach to protecting protocols against corruption of honest parties’ devices. Intuitively, an RF for a party P is an external entity that sits between P and the outside world and whose scope is to sanitize P ’s incoming and outgoing messages in the face of subversion of their computer. Mironov and Stephens-Davidowitz constructed a protocol for passively-secure two-party computation. At CRYPTO’20, Chakraborty, Dziembowski and Nielsen constructed a protocol for secure computation with firewalls that improved on this result, both by extending it to multi-party computation protocol, and considering active security in the presence of static corruptions. In this paper, we initiate the study of RF for MPC in the adaptive setting. We put forward a definition for adaptively secure MPC in the reverse firewall setting, explore relationships among the security notions, and then construct reverse firewalls for MPC in this stronger setting of adaptive security. We also resolve the open question of Chakraborty, Dziembowski and Nielsen by removing the need for a trusted setup in constructing RF for MPC. Towards this end, we construct reverse firewalls for adaptively secure augmented coin tossing and adaptively secure zero-knowledge protocols and obtain a constant round adaptively secure MPC protocol in the reverse firewall setting without setup. Along the way, we propose a new multi-party adaptively secure coin tossing protocol in the plain model, that is of independent interest.}, author = {Chakraborty, Suvradip and Ganesh, Chaya and Pancholi, Mahak and Sarkar, Pratik}, booktitle = {27th International Conference on the Theory and Application of Cryptology and Information Security}, isbn = {978-3-030-92074-6}, issn = {1611-3349}, location = {Virtual, Singapore}, pages = {335--364}, publisher = {Springer Nature}, title = {{Reverse firewalls for adaptively secure MPC without setup}}, doi = {10.1007/978-3-030-92075-3_12}, volume = {13091}, year = {2021}, } @article{10606, abstract = {Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s).}, author = {Godard, Benoit G and Dumollard, Remi and Heisenberg, Carl-Philipp J and Mcdougall, Alex}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Combined effect of cell geometry and polarity domains determines the orientation of unequal division}}, doi = {10.7554/eLife.75639}, volume = {10}, year = {2021}, } @article{10607, abstract = {The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders.}, author = {Venezia, Serena and Kaufmann, Walter and Wenning, Gregor K. and Stefanova, Nadia}, issn = {1873-5126}, journal = {Parkinsonism & Related Disorders}, pages = {59--65}, publisher = {Elsevier}, title = {{Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease}}, doi = {10.1016/j.parkreldis.2021.09.007}, volume = {91}, year = {2021}, }