bluuebunny/crossref_metadata_2025_split huggingface dataset:
The statistical geometry of material loops in turbulence
Authors: Bentkamp Lukas , Drivas Theodore D. , Lalescu Cristian C. , Wilczek Michael 
Published: April 2022

AbstractMaterial elements – which are lines, surfaces, or volumes behaving as passive, non-diffusive markers – provide an inherently geometric window into the intricate dynamics of chaotic flows. Their stretching and folding dynamics has immediate implications for mixing in the oceans or the atmosphere, as well as the emergence of self-sustained dynamos in astrophysical settings. Here, we uncover robust statistical properties of an ensemble of material loops in a turbulent environment. Our approach combines high-resolution direct numerical simulations of Navier-Stokes turbulence, stochastic models, and dynamical systems techniques to reveal predictable, universal features of these complex objects. We show that the loop curvature statistics become stationary through a dynamical formation process of high-curvature folds, leading to distributions with power-law tails whose exponents are determined by the large-deviations statistics of finite-time Lyapunov exponents of the flow. This prediction applies to advected material lines in a broad range of chaotic flows. To complement this dynamical picture, we confirm our theory in the analytically tractable Kraichnan model with an exact Fokker-Planck approach.
Double ridge formation over shallow water sills on Jupiter’s moon Europa
Authors: Culberg Riley , Schroeder Dustin M. , Steinbrügge Gregor 
Published: April 2022

AbstractJupiter’s moon Europa is a prime candidate for extraterrestrial habitability in our solar system. The surface landforms of its ice shell express the subsurface structure, dynamics, and exchange governing this potential. Double ridges are the most common surface feature on Europa and occur across every sector of the moon, but their formation is poorly understood, with current hypotheses providing competing and incomplete mechanisms for the development of their distinct morphology. Here we present the discovery and analysis of a double ridge in Northwest Greenland with the same gravity-scaled geometry as those found on Europa. Using surface elevation and radar sounding data, we show that this double ridge was formed by successive refreezing, pressurization, and fracture of a shallow water sill within the ice sheet. If the same process is responsible for Europa’s double ridges, our results suggest that shallow liquid water is spatially and temporally ubiquitous across Europa’s ice shell.
Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription
Authors: Lee Sang Bae , Garofano Luciano , Ko Aram , D’Angelo Fulvio , Frangaj Brulinda , Sommer Danika , Gan Qiwen , Kim KyeongJin , Cardozo Timothy , Iavarone Antonio , Lasorella Anna 
Published: April 2022

AbstractTissue-specific transcriptional activity is silenced in mitotic cells but it remains unclear whether the mitotic regulatory machinery interacts with tissue-specific transcriptional programs. We show that such cross-talk involves the controlled interaction between core subunits of the anaphase-promoting complex (APC) and the ID2 substrate. The N-terminus of ID2 is independently and structurally compatible with a pocket composed of core APC/C subunits that may optimally orient ID2 onto the APCCDH1 complex. Phosphorylation of serine-5 by CDK1 prevented the association of ID2 with core APC, impaired ubiquitylation and stabilized ID2 protein at the mitosis-G1 transition leading to inhibition of basic Helix-Loop-Helix (bHLH)-mediated transcription. The serine-5 phospho-mimetic mutant of ID2 that inefficiently bound core APC remained stable during mitosis, delayed exit from mitosis and reloading of bHLH transcription factors on chromatin. It also locked cells into a “mitotic stem cell” transcriptional state resembling the pluripotent program of embryonic stem cells. The substrates of APCCDH1 SKP2 and Cyclin B1 share with ID2 the phosphorylation-dependent, D-box-independent interaction with core APC. These results reveal a new layer of control of the mechanism by which substrates are recognized by APC.
Skeletal Ni electrode-catalyzed C-O cleavage of diaryl ethers entails direct elimination via benzyne intermediates
Authors: Zhou Yuting , Klinger Grace E. , Hegg Eric L. , Saffron Christopher M. , Jackson James E. 
Published: April 2022

AbstractDiaryl ethers undergo electrocatalytic hydrogenolysis (ECH) over skeletal Ni cathodes in a mild, aqueous process that achieves direct C-O cleavage without initial benzene ring saturation. Mechanistic studies find that aryl phenyl ethers with a single para or meta functional group (methyl, methoxy, or hydroxy) are selectively cleaved to the substituted benzene and phenol, in contrast to recently reported homogeneous catalytic cleavage processes. Ortho positioning of substituents reverses this C-O bond selectivity, except for the 2-phenoxyphenol case. Together with isotope labeling and co-solvent studies, these results point to two distinct cleavage mechanisms: (a) dual-ring coordination and C-H activation, leading to vicinal elimination to form phenol and a surface-bound aryne intermediate which is then hydrogenated and released as the arene; and (b) surface binding in keto form by the phenolic ring of the hydroxy-substituted substrates, followed by direct displacement of the departing phenol. Notably, acetone inhibits the well-known reduction of phenol to cyclohexanol, affording control of product ring saturation. A byproduct of this work is the discovery that the ECH treatment completely defluorinates substrates bearing aromatic C-F and C-CF3 groupings.
Trilobite-inspired neural nanophotonic light-field camera with extreme depth-of-field
Authors: Fan Qingbin , Xu Weizhu , Hu Xuemei , Zhu Wenqi , Yue Tao , Zhang Cheng , Yan Feng , Chen Lu , Lezec Henri J. , Lu Yanqing , Agrawal Amit , Xu Ting 
Published: April 2022

AbstractA unique bifocal compound eye visual system found in the now extinct trilobite, Dalmanitina socialis, may enable them to be sensitive to the light-field information and simultaneously perceive both close and distant objects in the environment. Here, inspired by the optical structure of their eyes, we demonstrate a nanophotonic light-field camera incorporating a spin-multiplexed bifocal metalens array capable of capturing high-resolution light-field images over a record depth-of-field ranging from centimeter to kilometer scale, simultaneously enabling macro and telephoto modes in a snapshot imaging. By leveraging a multi-scale convolutional neural network-based reconstruction algorithm, optical aberrations induced by the metalens are eliminated, thereby significantly relaxing the design and performance limitations on metasurface optics. The elegant integration of nanophotonic technology with computational photography achieved here is expected to aid development of future high-performance imaging systems.
Magic angle spinning NMR structure of human cofilin-2 assembled on actin filaments reveals isoform-specific conformation and binding mode
Authors: Kraus Jodi , Russell Ryan W. , Kudryashova Elena , Xu Chaoyi , Katyal Nidhi , Perilla Juan R. , Kudryashov Dmitri S. , Polenova Tatyana 
Published: April 2022

AbstractActin polymerization dynamics regulated by actin-binding proteins are essential for various cellular functions. The cofilin family of proteins are potent regulators of actin severing and filament disassembly. The structural basis for cofilin-isoform-specific severing activity is poorly understood as their high-resolution structures in complex with filamentous actin (F-actin) are lacking. Here, we present the atomic-resolution structure of the muscle-tissue-specific isoform, cofilin-2 (CFL2), assembled on ADP-F-actin, determined by magic-angle-spinning (MAS) NMR spectroscopy and data-guided molecular dynamics (MD) simulations. We observe an isoform-specific conformation for CFL2. This conformation is the result of a unique network of hydrogen bonding interactions within the α2 helix containing the non-conserved residue, Q26. Our results indicate F-site interactions that are specific between CFL2 and ADP-F-actin, revealing mechanistic insights into isoform-dependent F-actin disassembly.
Chemotherapy-induced COX-2 upregulation by cancer cells defines their inflammatory properties and limits the efficacy of chemoimmunotherapy combinations
Authors: Bell Charlotte R. , Pelly Victoria S. , Moeini Agrin , Chiang Shih-Chieh , Flanagan Eimear , Bromley Christian P. , Clark Christopher , Earnshaw Charles H. , Koufaki Maria A. , Bonavita Eduardo , Zelenay Santiago 
Published: April 2022

AbstractCytotoxic therapies, besides directly inducing cancer cell death, can stimulate immune-dependent tumor growth control or paradoxically accelerate tumor progression. The underlying mechanisms dictating these opposing outcomes are poorly defined. Here, we show that cytotoxic therapy acutely upregulates cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) production in cancer cells with pre-existing COX-2 activity. Screening a compound library of 1280 approved drugs, we find that all classes of chemotherapy drugs enhance COX-2 transcription whilst arresting cancer cell proliferation. Genetic manipulation of COX-2 expression or its gene promoter region uncover how augmented COX-2/PGE2 activity post-treatment profoundly alters the inflammatory properties of chemotherapy-treated cancer cells in vivo. Pharmacological COX-2 inhibition boosts the efficacy of the combination of chemotherapy and PD-1 blockade. Crucially, in a poorly immunogenic breast cancer model, only the triple therapy unleashes tumor growth control and significantly reduces relapse and spontaneous metastatic spread in an adjuvant setting. Our findings suggest COX-2/PGE2 upregulation by dying cancer cells acts as a major barrier to cytotoxic therapy-driven tumor immunity and uncover a strategy to improve the outcomes of immunotherapy and chemotherapy combinations.
A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation
Authors: Cohen S. , Guenolé A. , Lazar I. , Marnef A. , Clouaire T. , Vernekar D. V. , Puget N. , Rocher V. , Arnould C. , Aguirrebengoa M. , Genais M. , Firmin N. , Shamanna R. A. , Mourad R. , Bohr V. A. , Borde V. , Legube G. 
Published: April 2022

AbstractTranscriptionally active loci are particularly prone to breakage and mounting evidence suggests that DNA Double-Strand Breaks arising in active genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loop accumulation and dissolution. Here, we uncover a function for the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in an R-loop dissolution-deficient background, we find that BLM promotes cell death. We report that upon excessive RNA:DNA hybrid accumulation, DNA synthesis is enhanced at DSBs, in a manner that depends on BLM and POLD3. Altogether our work unveils a role for BLM at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at transcription-associated DSBs.
A fully automatic AI system for tooth and alveolar bone segmentation from cone-beam CT images
Authors: Cui Zhiming , Fang Yu , Mei Lanzhuju , Zhang Bojun , Yu Bo , Liu Jiameng , Jiang Caiwen , Sun Yuhang , Ma Lei , Huang Jiawei , Liu Yang , Zhao Yue , Lian Chunfeng , Ding Zhongxiang , Zhu Min , Shen Dinggang 
Published: April 2022

AbstractAccurate delineation of individual teeth and alveolar bones from dental cone-beam CT (CBCT) images is an essential step in digital dentistry for precision dental healthcare. In this paper, we present an AI system for efficient, precise, and fully automatic segmentation of real-patient CBCT images. Our AI system is evaluated on the largest dataset so far, i.e., using a dataset of 4,215 patients (with 4,938 CBCT scans) from 15 different centers. This fully automatic AI system achieves a segmentation accuracy comparable to experienced radiologists (e.g., 0.5% improvement in terms of average Dice similarity coefficient), while significant improvement in efficiency (i.e., 500 times faster). In addition, it consistently obtains accurate results on the challenging cases with variable dental abnormalities, with the average Dice scores of 91.5% and 93.0% for tooth and alveolar bone segmentation. These results demonstrate its potential as a powerful system to boost clinical workflows of digital dentistry.
A hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance
Authors: Filo Maurice , Kumar Sant , Khammash Mustafa 
Published: April 2022

AbstractProportional-Integral-Derivative (PID) feedback controllers are the most widely used controllers in industry. Recently, the design of molecular PID-controllers has been identified as an important goal for synthetic biology and the field of cybergenetics. In this paper, we consider the realization of PID-controllers via biomolecular reactions. We propose an array of topologies offering a compromise between simplicity and high performance. We first demonstrate that different biomolecular PI-controllers exhibit different performance-enhancing capabilities. Next, we introduce several derivative controllers based on incoherent feedforward loops acting in a feedback configuration. Alternatively, we show that differentiators can be realized by placing molecular integrators in a negative feedback loop, which can be augmented by PI-components to yield PID-controllers. We demonstrate that PID-controllers can enhance stability and dynamic performance, and can also reduce stochastic noise. Finally, we provide an experimental demonstration using a hybrid setup where in silico PID-controllers regulate a genetic circuit in single yeast cells.
Creating three-dimensional magnetic functional microdevices via molding-integrated direct laser writing
Authors: Liu Zemin , Li Meng , Dong Xiaoguang , Ren Ziyu , Hu Wenqi , Sitti Metin 
Published: April 2022

AbstractMagnetically driven wireless miniature devices have become promising recently in healthcare, information technology, and many other fields. However, they lack advanced fabrication methods to go down to micrometer length scales with heterogeneous functional materials, complex three-dimensional (3D) geometries, and 3D programmable magnetization profiles. To fill this gap, we propose a molding-integrated direct laser writing-based microfabrication approach in this study and showcase its advanced enabling capabilities with various proof-of-concept functional microdevice prototypes. Unique motions and functionalities, such as metachronal coordinated motion, fluid mixing, function reprogramming, geometrical reconfiguring, multiple degrees-of-freedom rotation, and wireless stiffness tuning are exemplary demonstrations of the versatility of this fabrication method. Such facile fabrication strategy can be applied toward building next-generation smart microsystems in healthcare, robotics, metamaterials, microfluidics, and programmable matter.
Salt marshes create more extensive channel networks than mangroves
Authors: Schwarz Christian , van Rees Floris , Xie Danghan , Kleinhans Maarten G. , van Maanen Barend 
Published: April 2022

AbstractCoastal wetlands fulfil important functions for biodiversity conservation and coastal protection, which are inextricably linked to typical morphological features like tidal channels. Channel network configurations in turn are shaped by bio-geomorphological feedbacks between vegetation, hydrodynamics and sediment transport. This study investigates the impact of two starkly different recruitment strategies between mangroves (fast/homogenous) and salt marshes (slow/patchy) on channel network properties. We first compare channel networks found in salt marshes and mangroves around the world and then demonstrate how observed channel patterns can be explained by vegetation establishment strategies using controlled experimental conditions. We find that salt marshes are dissected by more extensive channel networks and have shorter over-marsh flow paths than mangrove systems, while their branching patterns remain similar. This finding is supported by our laboratory experiments, which reveal that different recruitment strategies of mangroves and salt marshes hamper or facilitate channel development, respectively. Insights of our study are crucial to understand wetland resilience with rising sea-levels especially under climate-driven ecotone shifts.
Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells
Authors: Lohraseb Iman , McCarthy Peter , Secker Genevieve , Marchant Ceilidh , Wu Jianmin , Ali Naveid , Kumar Sharad , Daly Roger J. , Harvey Natasha L. , Kawabe Hiroshi , Kleifeld Oded , Wiszniak Sophie , Schwarz Quenten 
Published: April 2022

AbstractThe ubiquitin ligase NEDD4 promotes neural crest cell (NCC) survival and stem-cell like properties to regulate craniofacial and peripheral nervous system development. However, how ubiquitination and NEDD4 control NCC development remains unknown. Here we combine quantitative analysis of the proteome, transcriptome and ubiquitinome to identify key developmental signalling pathways that are regulated by NEDD4. We report 276 NEDD4 targets in NCCs and show that loss of NEDD4 leads to a pronounced global reduction in specific ubiquitin lysine linkages. We further show that NEDD4 contributes to the regulation of the NCC actin cytoskeleton by controlling ubiquitination and turnover of Profilin 1 to modulate filamentous actin polymerization. Taken together, our data provide insights into how NEDD4-mediated ubiquitination coordinates key regulatory processes during NCC development.
Development of NanoLuc-targeting protein degraders and a universal reporter system to benchmark tag-targeted degradation platforms
Authors: Grohmann Christoph , Magtoto Charlene M. , Walker Joel R. , Chua Ngee Kiat , Gabrielyan Anna , Hall Mary , Cobbold Simon A. , Mieruszynski Stephen , Brzozowski Martin , Simpson Daniel S. , Dong Hao , Dorizzi Bridget , Jacobsen Annette V. , Morrish Emma , Silke Natasha , Murphy James M. , Heath Joan K. , Testa Andrea , Maniaci Chiara , Ciulli Alessio , Lessene Guillaume , Silke John , Feltham Rebecca 
Published: April 2022

AbstractModulation of protein abundance using tag-Targeted Protein Degrader (tTPD) systems targeting FKBP12F36V (dTAGs) or HaloTag7 (HaloPROTACs) are powerful approaches for preclinical target validation. Interchanging tags and tag-targeting degraders is important to achieve efficient substrate degradation, yet limited degrader/tag pairs are available and side-by-side comparisons have not been performed. To expand the tTPD repertoire we developed catalytic NanoLuc-targeting PROTACs (NanoTACs) to hijack the CRL4CRBN complex and degrade NanoLuc tagged substrates, enabling rapid luminescence-based degradation screening. To benchmark NanoTACs against existing tTPD systems we use an interchangeable reporter system to comparatively test optimal degrader/tag pairs. Overall, we find the dTAG system exhibits superior degradation. To align tag-induced degradation with physiology we demonstrate that NanoTACs limit MLKL-driven necroptosis. In this work we extend the tTPD platform to include NanoTACs adding flexibility to tTPD studies, and benchmark each tTPD system to highlight the importance of comparing each system against each substrate.
A single-cell nanocoating of probiotics for enhanced amelioration of antibiotic-associated diarrhea
Authors: Pan Jiezhou , Gong Guidong , Wang Qin , Shang Jiaojiao , He Yunxiang , Catania Chelsea , Birnbaum Dan , Li Yifei , Jia Zhijun , Zhang Yaoyao , Joshi Neel S. , Guo Junling 
Published: April 2022

AbstractThe gut microbiota represents a large community of microorganisms that play an important role in immune regulation and maintenance of homeostasis. Living bacteria receive increasing interest as potential therapeutics for gut disorders, because they inhibit the colonization of pathogens and positively regulate the composition of bacteria in gut. However, these treatments are often accompanied by antibiotic administration targeting pathogens. In these cases, the efficacy of therapeutic bacteria is compromised by their susceptibility to antibiotics. Here, we demonstrate that a single-cell coating composed of tannic acids and ferric ions, referred to as ‘nanoarmor’, can protect bacteria from the action of antibiotics. The nanoarmor protects both Gram-positive and Gram-negative bacteria against six clinically relevant antibiotics. The multiple interactions between the nanoarmor and antibiotic molecules allow the antibiotics to be effectively absorbed onto the nanoarmor. Armored probiotics have shown the ability to colonize inside the gastrointestinal tracts of levofloxacin-treated rats, which significantly reduced antibiotic-associated diarrhea (AAD) resulting from the levofloxacin-treatment and improved some of the pre-inflammatory symptoms caused by AAD. This nanoarmor strategy represents a robust platform to enhance the potency of therapeutic bacteria in the gastrointestinal tracts of patients receiving antibiotics and to avoid the negative effects of antibiotics in the gastrointestinal tract.
Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population
Authors: Anjos-Afonso Fernando , Buettner Florian , Mian Syed A. , Rhys Hefin , Perez-Lloret Jimena , Garcia-Albornoz Manuel , Rastogi Namrata , Ariza-McNaughton Linda , Bonnet Dominique 
Published: April 2022

AbstractThe heterogeneous nature of human CD34+ hematopoietic stem cells (HSCs) has hampered our understanding of the cellular and molecular trajectories that HSCs navigate during lineage commitment. Using various platforms including single cell RNA-sequencing and extensive xenotransplantation, we have uncovered an uncharacterized human CD34+ HSC population. These CD34+EPCR+(CD38/CD45RA)− (simply as EPCR+) HSCs have a high repopulating and self-renewal abilities, reaching a stem cell frequency of ~1 in 3 cells, the highest described to date. Their unique transcriptomic wiring in which many gene modules associated with differentiated cell lineages confers their multilineage lineage output both in vivo and in vitro. At the single cell level, EPCR+ HSCs are the most transcriptomically and functionally homogenous human HSC population defined to date and can also be easily identified in post-natal tissues. Therefore, this EPCR+ population not only offers a high human HSC resolution but also a well-structured human hematopoietic hierarchical organization at the most primitive level.
Aeolian sediment transport on Io from lava–frost interactions
Authors: McDonald George D. , Méndez Harper Joshua , Ojha Lujendra , Corlies Paul , Dufek Josef , Ewing Ryan C. , Kerber Laura 
Published: April 2022

AbstractSurface modification on Jupiter’s volcanically active moon, Io, has to date been attributed almost exclusively to lava emplacement and volcanic plume deposits. Here we demonstrate that wind-blown transport of sediment may also be altering the Ionian surface. Specifically, shallow subsurface interactions between lava and Io’s widespread sulfur dioxide (SO2) frost can produce localized sublimation vapor flows with sufficient gas densities to enable particle saltation. We calculate anticipated outgassing velocities from lava–SO2 frost interactions, and compare these to the saltation thresholds predicted when accounting for the tenuous nature of the sublimated vapor. We find that saltation may occur if frost temperatures surpass 155 K. Finally we make the first measurements of the dimensions of linear features in images from the Galileo probe, previously termed “ridges”, which demonstrate certain similarities to dunes on other planetary bodies. Io joins a growing list of bodies with tenuous and transient atmospheres where aeolian sediment transport may be an important control on the landscape.