@misc{18895, abstract = {ISTAnt is a new ecological dataset for social immunity and represents the first real-world benchmark for causal inference downstream tasks on high-dimensional observations. It analyzes grooming behavior in the ant Lasius neglectus in groups of three worker ants. The workers for the experiment were obtained from their laboratory stock colony, which had been collected from the field in 2022 in the Botanical Garden Jena, Germany. Ant collection and all experimental work were performed in compliance with international, national and institutional regulations and ethical guidelines. For the experiment, the body surface of one of the three ants was treated with a suspension of either of two microparticle types (diameter ~5 µm) to induce grooming by the two nestmates, which were individually color-coded by application of a dot of blue or orange paint, respectively. The three ants were housed in small plastic containers (diameter 28mm, height 30mm) with moistened, plastered ground and the interior walls covered with PTFE (polytetrafluoroethane) to hamper climbing by the ants. Filming occurred in a temperature- and humidity-controlled room at 23°C within a custom-made filming box with controlled lighting and ventilation conditions. We set up nine ant groups at a time (always containing both treatments) and placed them randomly on positions 1-9 marked on the floor in a 3x3 grid, about 3mm from each other. The experiment was performed on two consecutive days. Videos were acquired using a USB camera (FLIR blackfly S BFS-U3-120S4C, Teledyne FLIR) with a high-performance lens (HP Series 25mm Focal Length, Edmund optics 86-572) in OBS studio 29.0.0 \citep{bailey2017obs} at a framerate of 30 FPS and a resolution of 2500x2500 pixels. From each original video (105x105 mm), we generated nine individual videos .mkv (each ~32x32 mm, 770x770 pixels) by determining exact coordinates per container from one frame in GIMP 2.10.36 and cropping of the videos with FFmpeg 6.1.1. Annotation was performed over two consecutive days by three observers who had not been involved in the experimental setup or recording and were unaware of the treatment assignments to ensure bias-free behavioral annotation. They annotated the behavior of the ants during video observations, using custom-made software that saves the start and end frames of behaviors marked in a .csv file (see 'annotations' folder). In one of the videos, one of the nestmates' legs got inadvertently stuck to its body surface during the color-coding, interfering with its behavior, so the video was discarded. This left 44 videos from 5 independent setups (n=24 of treatment 1 and n=20 of treatment 2) of 10 minutes each for a total of 792 000 annotated frames (see 'video' folder). For each video, we provide the following information: the number of the set to which it belongs (1-5); the number of the position within the set reflecting the position of the ant group under the camera (1-9), for which we also provide ‘coordinates’ in the 3x3 grid (taking values -1/0/1 for both X and Y axis); treatment (1 or 2); the hour of the day when the recording was started (in 24h CEST); experimental day (A or B); the top left coordinate of the cropping square from the original video (CropX/CropY); the person annotating the video (given as A, B, C); the date of annotation (1: first day, 2: second day) and in which order the videos were annotated by each person, both reflecting a possible training effect of the person (see 'experiments_settings.csv' file).}, author = {Cadei, Riccardo and Locatello, Francesco and Cremer, Sylvia M and Lindorfer, Lukas and Schmid, Cordelia}, publisher = {Institute of Science and Technology Austria}, title = {{ISTAnt}}, doi = {10.6084/M9.FIGSHARE.26484934.V2}, year = {2024}, } @inproceedings{18897, abstract = {Score-based generative models (SGMs) are powerful tools to sample from complex data distributions. Their underlying idea is to (i) run a forward process for time T1 by adding noise to the data, (ii) estimate its score function, and (iii) use such estimate to run a reverse process. As the reverse process is initialized with the stationary distribution of the forward one, the existing analysis paradigm requires T1→∞. This is however problematic: from a theoretical viewpoint, for a given precision of the score approximation, the convergence guarantee fails as T1 diverges; from a practical viewpoint, a large T1 increases computational costs and leads to error propagation. This paper addresses the issue by considering a version of the popular predictor-corrector scheme: after running the forward process, we first estimate the final distribution via an inexact Langevin dynamics and then revert the process. Our key technical contribution is to provide convergence guarantees which require to run the forward process only for a fixed finite time T1. Our bounds exhibit a mild logarithmic dependence on the input dimension and the subgaussian norm of the target distribution, have minimal assumptions on the data, and require only to control the L2 loss on the score approximation, which is the quantity minimized in practice.}, author = {Pedrotti, Francesco and Maas, Jan and Mondelli, Marco}, booktitle = {Transactions on Machine Learning Research}, issn = {2835-8856}, title = {{Improved convergence of score-based diffusion models via prediction-correction}}, year = {2024}, } @book{18899, abstract = {The flourishing theory of classical optimal transport concerns mass transportation at minimal cost. This book introduces the reader to optimal transport on quantum structures, i.e., optimal transportation between quantum states and related non-commutative concepts of mass transportation. It contains lecture notes on classical optimal transport and Wasserstein gradient flows dynamics and quantum optimal transport quantum couplings and many-body problems quantum channels and qubits These notes are based on lectures given by the authors at the "Optimal Transport on Quantum Structures" School held at the Erdös Center in Budapest in the fall of 2022. The lecture notes are complemented by two survey chapters presenting the state of the art in different research areas of non-commutative optimal transport.}, editor = {Maas, Jan and Rademacher, Simone Anna Elvira and Titkos, Tamás and Virosztek, Daniel}, isbn = {9783031504655}, issn = {2947-9460}, publisher = {Springer Nature}, title = {{Optimal Transport on Quantum Structures}}, doi = {10.1007/978-3-031-50466-2}, volume = {29}, year = {2024}, } @article{18900, abstract = {We prove that certain closable derivations on the GNS Hilbert space associated with a non-tracial weight on a von Neumann algebra give rise to GNS-symmetric semigroups of contractive completely positive maps on the von Neumann algebra.}, author = {Wirth, Melchior}, issn = {1687-0247}, journal = {International Mathematics Research Notices}, number = {14}, pages = {10597--10614}, publisher = {Oxford University Press}, title = {{Modular completely Dirichlet forms as squares of derivations}}, doi = {10.1093/imrn/rnae092}, volume = {2024}, year = {2024}, } @article{18902, author = {Zagorski, Marcin and Brandenberg, Nathalie and Lutolf, Matthias and Tkačik, Gašper and Bollenbach, Mark Tobias and Briscoe, James and Kicheva, Anna}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Assessing the precision of morphogen gradients in neural tube development}}, doi = {10.1038/s41467-024-45148-8}, volume = {15}, year = {2024}, } @inproceedings{18906, abstract = {Expander decompositions of graphs have significantly advanced the understanding of many classical graph problems and led to numerous fundamental theoretical results. However, their adoption in practice has been hindered due to their inherent intricacies and large hidden factors in their asymptotic running times. Here, we introduce the first practically efficient algorithm for computing expander decompositions and their hierarchies and demonstrate its effectiveness and utility by incorporating it as the core component in a novel solver for the normalized cut graph clustering objective. Our extensive experiments on a variety of large graphs show that our expander-based algorithm outperforms state-of-the-art solvers for normalized cut with respect to solution quality by a large margin on a variety of graph classes such as citation, e-mail, and social networks or web graphs while remaining competitive in running time.}, author = {Hanauer, Kathrin and Henzinger, Monika H and Münk, Robin and Räcke, Harald and Vötsch, Maximilian}, booktitle = {Proceedings of the 30th ACM SIGKDD Conference on Knowledge Discovery and Data Mining}, isbn = {9798400704901}, location = {Barcelona, Spain}, pages = {1016--1027}, publisher = {ACM}, title = {{Expander hierarchies for normalized cuts on graphs}}, doi = {10.1145/3637528.3671978}, year = {2024}, } @inproceedings{18913, abstract = {With the proliferation of blockchain technology in high-value sectors, consensus protocols are becoming critical infrastructures. The rapid innovation cycle in Byzantine fault tolerant (BFT) consensus protocols has culminated in HotStuff, which provides linear message complexity in the partially synchronous setting. To achieve this, HotStuff leverages a leader that collects, aggregates, and broadcasts the messages of other validators. This paper analyzes the security implications of such approaches in practice, from the perspective of liveness and availability. By implementing attacks in a globally-distributed testbed, we show that state-of-the-art leader-based protocols are vulnerable to denial-of-service (DoS) attacks on the leader. Our attacks, demonstrated on committees of up to 64 validators, manage to disrupt liveness within seconds, using only a few tens of Mbps of attack bandwidth per validator. Crucially, the cost and effectiveness of the attacks are independent of the committee size. Based on the outcome of these experiments, we then propose and test effective mitigations. Our findings show that advancements in both protocol design and network-layer defenses can greatly improve the practical resilience of BFT consensus protocols.}, author = {Giuliari, Giacomo and Sonnino, Alberto and Frei, Marc and Streun, Fabio and Kokoris Kogias, Eleftherios and Perrig, Adrian}, booktitle = {Proceedings of the 19th ACM Asia Conference on Computer and Communications Security}, isbn = {9798400704826}, location = {Singapore, Singapore}, pages = {1345--1360}, publisher = {ACM}, title = {{An empirical study of consensus protocols’ DoS resilience}}, doi = {10.1145/3634737.3656997}, year = {2024}, } @article{18919, abstract = {The integration of theory and experiment makes possible tracking the slow evolution of a photodoped Mott insulator to a distinct non-equilibrium metallic phase under the influence of electron-lattice coupling.}, author = {Baykusheva, Denitsa Rangelova}, issn = {1745-2481}, journal = {Nature Physics}, number = {5}, pages = {684--685}, publisher = {Springer Nature}, title = {{Through the slopes of a light-induced phase transition}}, doi = {10.1038/s41567-024-02401-7}, volume = {20}, year = {2024}, } @article{18920, abstract = {The globally distributed marine alga Emiliania huxleyi has cooling effect on the Earth’s climate. The population density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate, there is limited information about their structure and replication. Here, we show that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane. EhV-201 virions infect E. huxleyi by using fivefold vertices to bind to and fuse the virus’ inner membrane with the cell plasma membrane. Progeny virions assemble in the cytoplasm at the surface of endoplasmic reticulum–derived membrane segments. Genome packaging initiates synchronously with the capsid assembly and completes through an aperture in the forming capsid. The genome-filled capsids acquire an outer membrane by budding into intracellular vesicles. EhV-201 infection induces a loss of surface protective layers from E. huxleyi cells, which enables the continuous release of virions by exocytosis.}, author = {Homola, Miroslav and Büttner, Renate Carina and Füzik, Tibor and Křepelka, Pavel and Holbová, Radka and Nováček, Jiří and Chaillet, Marten L. and Žák, Jakub and Grybchuk, Danyil and Förster, Friedrich and Wilson, William H. and Schroeder, Declan C. and Plevka, Pavel}, issn = {2375-2548}, journal = {Science Advances}, number = {15}, publisher = {American Association for the Advancement of Science}, title = {{Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi}}, doi = {10.1126/sciadv.adk1954}, volume = {10}, year = {2024}, } @inproceedings{18922, abstract = {Let G be a directed graph with m edges and n vertices. We present a deterministic linear-time algorithm for computing the 3-edge-connected components of G. This is a significant improvement over the previous best bound by Georgiadis et al. [SODA 2023], which is Õ(m√{m}) and randomized. Our result is based on a novel characterization of 2-edge cuts in directed graphs and on a new technique that exploits the concept of divergent spanning trees and 2-connectivity-light graphs, and requires a careful modification of the minset-poset technique of Gabow [TALG 2016]. As a side result, our new technique yields also an oracle for providing in constant time a minimum edge-cut for any two vertices that are not 3-edge-connected. The oracle uses space O(n) and can be built in O(mlog n) time: given two query vertices, it determines in constant time whether they are 3-edge-connected, or provides a k-edge cut, with k≤ 2, that separates them.}, author = {Georgiadis, Loukas and Italiano, Giuseppe F. and Kosinas, Evangelos}, booktitle = {65th Annual Symposium on Foundations of Computer Science}, isbn = {9798331516741}, location = {Chicago, IL, United States}, pages = {62--85}, publisher = {IEEE}, title = {{Computing the 3-edge-connected components of directed graphs in linear time}}, doi = {10.1109/focs61266.2024.00015}, year = {2024}, } @inproceedings{18925, abstract = {Given the increasingly stringent requirements on the performance and efficiency of communication networks, over the last years, great efforts have been made to render networks more flexible and programmable. In particular, modern networks support a flexible rerouting of flows, e.g., depending on the dynamically changing traffic or network conditions. However, the underlying algorithmic problems are still not well-understood today.In this paper, we revisit the k-Network Flow Update problem that asks for a schedule to reroute k unsplittable flows from their current paths to the given new paths, in a congestion-free manner in a capacitated network. We show that the problem is already NP-hard for three acyclic flows on simple directed graphs. Our main contribution is an efficient algorithm for sparse networks; specifically the algorithm is fixed parameter tractable in the number of flows and the treewidth of a graph that is the union of all flows. Our results also settle the open complexity question in the literature.}, author = {Ceylan, Esra and Chatterjee, Krishnendu and Schmid, Stefan and Svoboda, Jakub}, booktitle = {NOMS 2024-2024 IEEE Network Operations and Management Symposium}, isbn = {9798350327946}, issn = {2374-9709}, location = {Seoul, Republic of Korea}, publisher = {IEEE}, title = {{Congestion-free rerouting of network flows: Hardness and an FPT algorithm}}, doi = {10.1109/noms59830.2024.10575579}, year = {2024}, } @article{18926, abstract = {We study weak solutions to mean curvature flow satisfying Young’s angle condition for general contact angles α ∈ (0, π). First, we construct BV solutions by using the Allen-Cahn approximation with boundary contact energy as proposed by Owen and Sternberg. Second, we prove the weak-strong uniqueness and stability for this solution concept. The main ingredient for both results is a relative energy, which can also be interpreted as a tilt excess. }, author = {Hensel, Sebastian and Laux, Tim}, issn = {0022-2518}, journal = {Indiana University Mathematics Journal}, number = {1}, pages = {111--148}, publisher = {Indiana University Mathematics Journal}, title = {{BV solutions for mean curvature flow with constant angle: Allen-Cahn approximation and weak-strong uniqueness}}, doi = {10.1512/iumj.2024.73.9701}, volume = {73}, year = {2024}, } @inproceedings{18928, abstract = {Algorithms with predictions is a new research direction that leverages machine learned predictions for algorithm design. So far a plethora of recent works have incorporated predictions to improve on worst-case bounds for online problems. In this paper, we initiate the study of complexity of dynamic data structures with predictions, including dynamic graph algorithms. Unlike online algorithms, the goal in dynamic data structures is to maintain the solution efficiently with every update. We investigate three natural models of prediction: (1) δ-accurate predictions where each predicted request matches the true request with probability δ, (2) list-accurate predictions where a true request comes from a list of possible requests, and (3) bounded delay predictions where the true requests are a permutation of the predicted requests. We give general reductions among the prediction models, showing that bounded delay is the strongest prediction model, followed by list-accurate, and δ-accurate. Further, we identify two broad problem classes based on lower bounds due to the Online Matrix Vector (OMv) conjecture. Specifically, we show that locally correctable dynamic problems have strong conditional lower bounds for list-accurate predictions that are equivalent to the non-prediction setting, unless list-accurate predictions are perfect. Moreover, we show that locally reducible dynamic problems have time complexity that degrades gracefully with the quality of bounded delay predictions. We categorize problems with known OMv lower bounds accordingly and give several upper bounds in the delay model that show that our lower bounds are almost tight. We note that concurrent work by v.d.Brand et al. [SODA '24] and Liu and Srinivas [arXiv:2307.08890] independently study dynamic graph algorithms with predictions, but their work is mostly focused on showing upper bounds.}, author = {Henzinger, Monika H and Saha, Barna and Seybold, Martin P. and Ye, Christopher}, booktitle = {15th Innovations in Theoretical Computer Science Conference}, isbn = {9783959773096}, issn = {1868-8969}, location = {Berkeley, CA, United States}, pages = {62:1--62:25}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{On the complexity of algorithms with predictions for dynamic graph problems}}, doi = {10.4230/LIPIcs.ITCS.2024.62}, volume = {287}, year = {2024}, } @article{18934, abstract = {The assembly of biomolecular condensate in eukaryotic cells and the accumulation of amyloid deposits in neurons are processes involving the nucleation and growth (NAG) of new protein phases. To therapeutically target protein phase separation, drug candidates are tested in in vitro assays that monitor the increase in the mass or size of the new phase. Limited mechanistic insight is, however, provided if empirical or untestable kinetic models are fitted to these progress curves. Here we present the web server NAGPKin that quantifies NAG rates using mass-based or size-based progress curves as the input data. A report is generated containing the fitted NAG parameters and elucidating the phase separation mechanisms at play. The NAG parameters can be used to predict particle size distributions of, for example, protein droplets formed by liquid-liquid phase separation (LLPS) or amyloid fibrils formed by protein aggregation. Because minimal intervention is required from the user, NAGPKin is a good platform for standardized reporting of LLPS and protein self-assembly data. NAGPKin is useful for drug discovery as well as for fundamental studies on protein phase separation. NAGPKin is freely available (no login required) at https://nagpkin.i3s.up.pt .}, author = {Sárkány, Zsuzsa and Figueiredo, Francisco and Macedo-Ribeiro, Sandra and Martins, Pedro M.}, issn = {1939-4586}, journal = {Molecular Biology of the Cell}, number = {3}, publisher = {American Society for Cell Biology}, title = {{NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation}}, doi = {10.1091/mbc.e23-07-0289}, volume = {35}, year = {2024}, } @article{18937, abstract = {A detailed structural, magnetic as well as dielectric dynamics study is carried out to investigate the influence of Bi3+ on YCrO3. All the samples crystalize in orthorhombic structure with Pnma symmetry and the grains are mostly stretched with Bi. A coexisting tunable fraction of both antiferromagnetic (AFM) and weak ferromagnetic (WFM) phases is acquired by the system down to Low-T. An abnormal negative magnetization in zero field is correlated to the competition among AFM and WFM phases. Maximum magnetization decreases while the coercivity first increases and then decreases with Bi is correlated to the competing effect between the local deformation and Cr–O–Cr exchange interaction. The magnetodielectric coupling with improved permittivity might be associated with the 6s2 lone pair electron of Bi3+. Furthermore, ac-conductivity increases with a decrease in activation energy (0.27–0.11 eV), is explained in the framework of structural model and charge carrier hopping between Cr3+ and Cr4+ ions.}, author = {Ray, Sujata Kumari and Pati, Anupama and Sahoo, Payala and Sahoo, A.K. and Singh, Saurabh and Takeuchi, Tsunehiro and Dash, S.}, issn = {0921-4526}, journal = {Physica B: Condensed Matter}, publisher = {Elsevier}, title = {{Tunable magnetoelectronic properties in Bi3+ substituted YCrO3}}, doi = {10.1016/j.physb.2024.416018}, volume = {685}, year = {2024}, } @article{18938, abstract = {The synthesis of proteins as encoded in the genome depends critically on translational fidelity. Nevertheless, errors inevitably occur, and those that result in reading frame shifts are particularly consequential because the resulting polypeptides are typically nonfunctional. Despite the generally maladaptive impact of such errors, the proper decoding of certain mRNAs, including many viral mRNAs, depends on a process known as programmed ribosomal frameshifting. The fact that these programmed events, commonly involving a shift to the –1 frame, occur at specific evolutionarily optimized “slippery” sites has facilitated mechanistic investigation. By contrast, less is known about the scope and nature of error (i.e., nonprogrammed) frameshifting. Here, we examine error frameshifting by monitoring spontaneous frameshift events that suppress the effects of single base pair deletions affecting two unrelated test proteins. To map the precise sites of frameshifting, we developed a targeted mass spectrometry–based method called “translational tiling proteomics” for interrogating the full set of possible –1 slippage events that could produce the observed frameshift suppression. Surprisingly, such events occur at many sites along the transcripts, involving up to one half of the available codons. Only a subset of these resembled canonical “slippery” sites, implicating alternative mechanisms potentially involving noncognate mispairing events. Additionally, the aggregate frequency of these events (ranging from 1 to 10% in our test cases) was higher than we might have anticipated. Our findings point to an unexpected degree of mechanistic diversity among ribosomal frameshifting events and suggest that frameshifted products may contribute more significantly to the proteome than generally assumed.}, author = {Springstein, Benjamin L and Paulo, Joao A. and Park, Hankum and Henry, Kemardo and Fleming, Eleanor and Feder, Zoë and Harper, J. Wade and Hochschild, Ann}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {6}, publisher = {National Academy of Sciences}, title = {{Systematic analysis of nonprogrammed frameshift suppression in E.coli via translational tiling proteomics}}, doi = {10.1073/pnas.2317453121}, volume = {121}, year = {2024}, } @article{18940, abstract = {BMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan Nematostella vectensis, several of which were conserved in Drosophila and Xenopus. Our ChIP-seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in Nematostella are directly controlled by BMP signaling. We identified several so far uncharacterized BMP-dependent transcription factors and signaling molecules, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules is zswim4-6, which encodes a novel nuclear protein that can modulate the pSMAD1/5 gradient and potentially promote BMP-dependent gene repression.}, author = {Knabl, Paul and Schauer, Alexandra and Pomreinke, Autumn P and Zimmermann, Bob and Rogers, Katherine W and Čapek, Daniel and Müller, Patrick and Genikhovich, Grigory}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator}}, doi = {10.7554/elife.80803}, volume = {13}, year = {2024}, } @article{18944, abstract = {Understanding connectivity patterns exhibited by endangered species living in fragmented habitats is fundamental to improving management and conservation actions. Such improvements can be particularly pressing at the trailing edges of these habitats, where populations are facing the greatest challenges from climate change, and appear even more crucial if the species is commercially harvested. Seascape genetics have been increasingly used to meet these needs. In this study, we examined connectivity patterns among 32 populations of the oarweed kelp Laminaria digitata located at the species’ southern range limit. The distance (or sampling gap) between neighboring populations ranged from a few km to a few 100s of km. By genotyping 11 microsatellite markers, we aimed to (1) refine analyses of population structure; (2) test whether on-shelf islands are genetically more differentiated than mainland populations; (3) evaluate the relative importance of various abiotic conditions in shaping the genetic structure; and (4) evaluate if the relative importance of each environmental factor varied according to sampling schemes. Our analyses revealed a positive relationship between connectivity links and genetic diversity: populations with high levels of connectivity were genetically enriched while isolated populations showed signs of genetic erosion. The genetically impoverished populations corresponded to the southernmost populations as well as populations along the northern coast of Brittany (Locquirec, Saint-Malo Bay) and the northernmost population in Pas-de-Calais. By performing distance-based redundancy analysis on various sampling schemes, geographic distance appeared as the dominant factor influencing connectivity between populations separated by great distances, while hydrodynamic processes were the main factor when analyzing at a final spatial resolution.}, author = {Fouqueau, Louise and Reynes, L and Tempera, F and Bajjouk, T and Blanfuné, A and Chevalier, C and Laurans, M and Mauger, S and Sourisseau, M and Assis, J and Lévêque, L and Valero, M}, issn = {1616-1599}, journal = {Marine Ecology Progress Series}, pages = {23--42}, publisher = {Inter-Research Science Center}, title = {{Seascape genetic study on Laminaria digitata underscores the critical role of sampling schemes}}, doi = {10.3354/meps14640}, volume = {740}, year = {2024}, } @article{18945, abstract = {Vaccinia-related kinase 1 (VRK1) and the δ and ε isoforms of casein kinase 1 (CK1) are linked to various disease-relevant pathways. However, the lack of tool compounds for these kinases has significantly hampered our understanding of their cellular functions and therapeutic potential. Here, we describe the structure-based development of potent inhibitors of VRK1, a kinase highly expressed in various tumor types and crucial for cell proliferation and genome integrity. Kinome-wide profiling revealed that our compounds also inhibit CK1δ and CK1ε. We demonstrate that dihydropteridinones 35 and 36 mimic the cellular outcomes of VRK1 depletion. Complementary studies with existing CK1δ and CK1ε inhibitors suggest that these kinases may play overlapping roles in cell proliferation and genome instability. Together, our findings highlight the potential of VRK1 inhibition in treating p53-deficient tumors and possibly enhancing the efficacy of existing cancer therapies that target DNA stability or cell division.}, author = {de Souza Gama, Fernando H. and Dutra, Luiz A. and Hawgood, Michael and dos Reis, Caio Vinícius and Serafim, Ricardo A. M. and Ferreira, Marcos A. and Teodoro, Bruno V. M. and Takarada, Jéssica Emi and Santiago, André S. and Balourdas, Dimitrios-Ilias and Nilsson, Ann-Sofie and Urien, Bruno and Almeida, Vitor M. and Gileadi, Carina and Ramos, Priscila Z. and Testa Salmazo, Anita P and Vasconcelos, Stanley N. S. and Cunha, Micael R. and Mueller, Susanne and Knapp, Stefan and Massirer, Katlin B. and Elkins, Jonathan M. and Gileadi, Opher and Mascarello, Alessandra and Lemmens, Bennie B. L. G. and Guimarães, Cristiano R. W. and Azevedo, Hatylas and Couñago, Rafael M.}, issn = {1520-4804}, journal = {Journal of Medicinal Chemistry}, number = {11}, pages = {8609--8629}, publisher = {American Chemical Society}, title = {{Novel dihydropteridinone derivatives as potent inhibitors of the understudied human kinases vaccinia-related kinase 1 and casein kinase 1δ/ε}}, doi = {10.1021/acs.jmedchem.3c02250}, volume = {67}, year = {2024}, } @article{18949, abstract = {Speciation research—the scientific field focused on understanding the origin and diversity of species—has a long and complex history. While relevant to one another, the specific goals and activities of speciation researchers are highly diverse, and scattered across a collection of different perspectives. Thus, our understanding of speciation will benefit from efforts to bridge scientific findings and the diverse people who do the work. In this paper, we outline two ways of integrating speciation research: (i) scientific integration, through the bringing together of ideas, data, and approaches; and (ii) social integration, by creating ways for a diversity of researchers to participate in the scientific process. We then discuss five challenges to integration: (i) the multidisciplinary nature of speciation research, (ii) the complex language of speciation; (iii) a bias toward certain study systems; (iv) the challenges of working across scales; and (v) inconsistent measures and reporting standards. We provide practical steps that individuals and groups can take to help overcome these challenges, and argue that integration is a team effort in which we all have a role to play.}, author = {Stankowski, Sean and Cutter, Asher D and Satokangas, Ina and Lerch, Brian A and Rolland, Jonathan and Smadja, Carole M and Segami Marzal, J Carolina and Cooney, Christopher R and Feulner, Philine G D and Domingos, Fabricius Maia Chaves Bicalho and North, Henry L and Yamaguchi, Ryo and Butlin, Roger K and Wolf, Jochen B W and Coughlan, Jenn and Heidbreder, Patrick and Hernández-Gutiérrez, Rebeca and Barnard-Kubow, Karen B and Peede, David and Rancilhac, Loïs and Salvador, Rodrigo Brincalepe and Thompson, Ken A and Stacy, Elizabeth A and Moyle, Leonie C and Garlovsky, Martin D and Maulana, Arif and Kantelinen, Annina and Cacho, N Ivalú and Schneemann, Hilde and Domínguez, Marisol and Dopman, Erik B and Lohse, Konrad and Rometsch, Sina J and Comeault, Aaron A and Merrill, Richard M and Scordato, Elizabeth S C and Singhal, Sonal and Pärssinen, Varpu and Lackey, Alycia C R and Kumar, Sanghamitra and Meier, Joana I and Barton, Nicholas H and Fraisse, Christelle and Ravinet, Mark and Kulmuni, Jonna}, issn = {2752-938X}, journal = {Evolutionary Journal of the Linnean Society}, number = {1}, publisher = {Oxford University Press}, title = {{Toward the integration of speciation research}}, doi = {10.1093/evolinnean/kzae001}, volume = {3}, year = {2024}, }