@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{10285, abstract = {We study the overlaps between right and left eigenvectors for random matrices of the spherical ensemble, as well as truncated unitary ensembles in the regime where half of the matrix at least is truncated. These two integrable models exhibit a form of duality, and the essential steps of our investigation can therefore be performed in parallel. In every case, conditionally on all eigenvalues, diagonal overlaps are shown to be distributed as a product of independent random variables with explicit distributions. This enables us to prove that the scaled diagonal overlaps, conditionally on one eigenvalue, converge in distribution to a heavy-tail limit, namely, the inverse of a γ2 distribution. We also provide formulae for the conditional expectation of diagonal and off-diagonal overlaps, either with respect to one eigenvalue, or with respect to the whole spectrum. These results, analogous to what is known for the complex Ginibre ensemble, can be obtained in these cases thanks to integration techniques inspired from a previous work by Forrester & Krishnapur.}, author = {Dubach, Guillaume}, issn = {1083-6489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{On eigenvector statistics in the spherical and truncated unitary ensembles}}, doi = {10.1214/21-EJP686}, volume = {26}, 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{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{10321, abstract = {Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).}, author = {Amberg, Nicole and Hippenmeyer, Simon}, issn = {2666-1667}, journal = {STAR Protocols}, number = {4}, publisher = {Cell Press}, title = {{Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers}}, doi = {10.1016/j.xpro.2021.100939}, volume = {2}, 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{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}, } @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{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}, } @article{10337, abstract = {The T cell receptor (TCR) pathway receives, processes, and amplifies the signal from pathogenic antigens to the activation of T cells. Although major components in this pathway have been identified, the knowledge on how individual components cooperate to effectively transduce signals remains limited. Phase separation emerges as a biophysical principle in organizing signaling molecules into liquid-like condensates. Here, we report that phospholipase Cγ1 (PLCγ1) promotes phase separation of LAT, a key adaptor protein in the TCR pathway. PLCγ1 directly cross-links LAT through its two SH2 domains. PLCγ1 also protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK activation and SLP76 phosphorylation. Intriguingly, a nonmonotonic effect of PLCγ1 on LAT clustering was discovered. Computer simulations, based on patchy particles, revealed how the cluster size is regulated by protein compositions. Together, these results define a critical function of PLCγ1 in promoting phase separation of the LAT complex and TCR signal transduction.}, author = {Zeng, Longhui and Palaia, Ivan and Šarić, Anđela and Su, Xiaolei}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {cell biology}, number = {6}, publisher = {Rockefeller University Press}, title = {{PLCγ1 promotes phase separation of T cell signaling components}}, doi = {10.1083/jcb.202009154}, volume = {220}, year = {2021}, } @article{10338, abstract = {In the nuclear pore complex, intrinsically disordered proteins (FG Nups), along with their interactions with more globular proteins called nuclear transport receptors (NTRs), are vital to the selectivity of transport into and out of the cell nucleus. Although such interactions can be modeled at different levels of coarse graining, in vitro experimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, in which the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and noncohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity in a minimal fashion and compare them with experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs does play a role in determining equilibrium binding properties but is of much greater significance when it comes to unbinding and binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.}, author = {Davis, Luke K. and Šarić, Anđela and Hoogenboom, Bart W. and Zilman, Anton}, issn = {0006-3495}, journal = {Biophysical Journal}, keywords = {biophysics}, number = {9}, pages = {1565--1577}, publisher = {Elsevier}, title = {{Physical modeling of multivalent interactions in the nuclear pore complex}}, doi = {10.1016/j.bpj.2021.01.039}, volume = {120}, year = {2021}, } @article{10339, abstract = {We study the effects of osmotic shocks on lipid vesicles via coarse-grained molecular dynamics simulations by explicitly considering the solute in the system. We find that depending on their nature (hypo- or hypertonic) such shocks can lead to bursting events or engulfing of external material into inner compartments, among other morphology transformations. We characterize the dynamics of these processes and observe a separation of time scales between the osmotic shock absorption and the shape relaxation. Our work consequently provides an insight into the dynamics of compartmentalization in vesicular systems as a result of osmotic shocks, which can be of interest in the context of early proto-cell development and proto-cell compartmentalisation.}, author = {Vanhille-Campos, Christian and Šarić, Anđela}, issn = {1744-6848}, journal = {Soft Matter}, keywords = {condensed matter physics, general chemistry}, number = {14}, pages = {3798--3806}, publisher = {Royal Society of Chemistry}, title = {{Modelling the dynamics of vesicle reshaping and scission under osmotic shocks}}, doi = {10.1039/d0sm02012e}, volume = {17}, year = {2021}, } @article{10340, abstract = {The cell membrane is an inhomogeneous system composed of phospholipids, sterols, carbohydrates, and proteins that can be directly attached to underlying cytoskeleton. The protein linkers between the membrane and the cytoskeleton are believed to have a profound effect on the mechanical properties of the cell membrane and its ability to reshape. Here, we investigate the role of membrane-cortex linkers on the extrusion of membrane tubes using computer simulations and experiments. In simulations, we find that the force for tube extrusion has a nonlinear dependence on the density of membrane-cortex attachments: at a range of low and intermediate linker densities, the force is not significantly influenced by the presence of the membrane-cortex attachments and resembles that of the bare membrane. For large concentrations of linkers, however, the force substantially increases compared with the bare membrane. In both cases, the linkers provided membrane tubes with increased stability against coalescence. We then pulled tubes from HEK cells using optical tweezers for varying expression levels of the membrane-cortex attachment protein Ezrin. In line with simulations, we observed that overexpression of Ezrin led to an increased extrusion force, while Ezrin depletion had a negligible effect on the force. Our results shed light on the importance of local protein rearrangements for membrane reshaping at nanoscopic scales.}, author = {Paraschiv, Alexandru and Lagny, Thibaut J. and Campos, Christian Vanhille and Coudrier, Evelyne and Bassereau, Patricia and Šarić, Anđela}, issn = {0006-3495}, journal = {Biophysical Journal}, keywords = {biophysics}, number = {4}, pages = {598--606}, publisher = {Cell Press}, title = {{Influence of membrane-cortex linkers on the extrusion of membrane tubes}}, doi = {10.1016/j.bpj.2020.12.028}, volume = {120}, year = {2021}, } @article{10365, abstract = {The early development of many organisms involves the folding of cell monolayers, but this behaviour is difficult to reproduce in vitro; therefore, both mechanistic causes and effects of local curvature remain unclear. Here we study epithelial cell monolayers on corrugated hydrogels engineered into wavy patterns, examining how concave and convex curvatures affect cellular and nuclear shape. We find that substrate curvature affects monolayer thickness, which is larger in valleys than crests. We show that this feature generically arises in a vertex model, leading to the hypothesis that cells may sense curvature by modifying the thickness of the tissue. We find that local curvature also affects nuclear morphology and positioning, which we explain by extending the vertex model to take into account membrane–nucleus interactions, encoding thickness modulation in changes to nuclear deformation and position. We propose that curvature governs the spatial distribution of yes-associated proteins via nuclear shape and density changes. We show that curvature also induces significant variations in lamins, chromatin condensation and cell proliferation rate in folded epithelial tissues. Together, this work identifies active cell mechanics and nuclear mechanoadaptation as the key players of the mechanistic regulation of epithelia to substrate curvature.}, author = {Luciano, Marine and Xue, Shi-lei and De Vos, Winnok H. and Redondo-Morata, Lorena and Surin, Mathieu and Lafont, Frank and Hannezo, Edouard B and Gabriele, Sylvain}, issn = {1745-2481}, journal = {Nature Physics}, number = {12}, pages = {1382–1390}, publisher = {Springer Nature}, title = {{Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation}}, doi = {10.1038/s41567-021-01374-1}, volume = {17}, 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}, } @inproceedings{10367, abstract = {How information is created, shared and consumed has changed rapidly in recent decades, in part thanks to new social platforms and technologies on the web. With ever-larger amounts of unstructured and limited labels, organizing and reconciling information from different sources and modalities is a central challenge in machine learning. This cutting-edge tutorial aims to introduce the multimodal entailment task, which can be useful for detecting semantic alignments when a single modality alone does not suffice for a whole content understanding. Starting with a brief overview of natural language processing, computer vision, structured data and neural graph learning, we lay the foundations for the multimodal sections to follow. We then discuss recent multimodal learning literature covering visual, audio and language streams, and explore case studies focusing on tasks which require fine-grained understanding of visual and linguistic semantics question answering, veracity and hatred classification. Finally, we introduce a new dataset for recognizing multimodal entailment, exploring it in a hands-on collaborative section. Overall, this tutorial gives an overview of multimodal learning, introduces a multimodal entailment dataset, and encourages future research in the topic.}, author = {Ilharco, Cesar and Shirazi, Afsaneh and Gopalan, Arjun and Nagrani, Arsha and Bratanič, Blaž and Bregler, Chris and Liu, Christina and Ferreira, Felipe and Barcik, Gabriek and Ilharco, Gabriel and Osang, Georg F and Bulian, Jannis and Frank, Jared and Smaira, Lucas and Cao, Qin and Marino, Ricardo and Patel, Roma and Leung, Thomas and Imbrasaite, Vaiva}, booktitle = {59th Annual Meeting of the Association for Computational Linguistics and the 11th International Joint Conference on Natural Language Processing, Tutorial Abstracts}, isbn = {9-781-9540-8557-2}, location = {Bangkok, Thailand}, pages = {29--30}, publisher = {Association for Computational Linguistics}, title = {{Recognizing multimodal entailment}}, doi = {10.18653/v1/2021.acl-tutorials.6}, 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 = {2399-3650}, 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{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}, } @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{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}, }