bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter
Authors: Peter Martin F. , Ruland Jan A. , Depping Peer , Schneberger Niels , Severi Emmanuele , Moecking Jonas , Gatterdam Karl , Tindall Sarah , Durand Alexandre , Heinz Veronika , Siebrasse Jan Peter , Koenig Paul-Albert , Geyer Matthias , Ziegler Christine , Kubitscheck Ulrich , Thomas Gavin H. , Hagelueken Gregor 
Published: August 2022

AbstractTripartite ATP-independent periplasmic (TRAP) transporters are found widely in bacteria and archaea and consist of three structural domains, a soluble substrate-binding protein (P-domain), and two transmembrane domains (Q- and M-domains). HiSiaPQM and its homologs are TRAP transporters for sialic acid and are essential for host colonization by pathogenic bacteria. Here, we reconstitute HiSiaQM into lipid nanodiscs and use cryo-EM to reveal the structure of a TRAP transporter. It is composed of 16 transmembrane helices that are unexpectedly structurally related to multimeric elevator-type transporters. The idiosyncratic Q-domain of TRAP transporters enables the formation of a monomeric elevator architecture. A model of the tripartite PQM complex is experimentally validated and reveals the coupling of the substrate-binding protein to the transporter domains. We use single-molecule total internal reflection fluorescence (TIRF) microscopy in solid-supported lipid bilayers and surface plasmon resonance to study the formation of the tripartite complex and to investigate the impact of interface mutants. Furthermore, we characterize high-affinity single variable domains on heavy chain (VHH) antibodies that bind to the periplasmic side of HiSiaQM and inhibit sialic acid uptake, providing insight into how TRAP transporter function might be inhibited in vivo.
Generating experimentally unrelated target molecule-binding highly functionalized nucleic-acid polymers using machine learning
Authors: Chen Jonathan C. , Chen Jonathan P. , Shen Max W. , Wornow Michael , Bae Minwoo , Yeh Wei-Hsi , Hsu Alvin , Liu David R. 
Published: August 2022

AbstractIn vitro selection queries large combinatorial libraries for sequence-defined polymers with target binding and reaction catalysis activity. While the total sequence space of these libraries can extend beyond 1022 sequences, practical considerations limit starting sequences to ≤~1015 distinct molecules. Selection-induced sequence convergence and limited sequencing depth further constrain experimentally observable sequence space. To address these limitations, we integrate experimental and machine learning approaches to explore regions of sequence space unrelated to experimentally derived variants. We perform in vitro selections to discover highly side-chain-functionalized nucleic acid polymers (HFNAPs) with potent affinities for a target small molecule (daunomycin KD = 5–65 nM). We then use the selection data to train a conditional variational autoencoder (CVAE) machine learning model to generate diverse and unique HFNAP sequences with high daunomycin affinities (KD = 9–26 nM), even though they are unrelated in sequence to experimental polymers. Coupling in vitro selection with a machine learning model thus enables direct generation of active variants, demonstrating a new approach to the discovery of functional biopolymers.
Unjamming and emergent nonreciprocity in active ploughing through a compressible viscoelastic fluid
Authors: Banerjee Jyoti Prasad , Mandal Rituparno , Banerjee Deb Sankar , Thutupalli Shashi , Rao Madan 
Published: August 2022

AbstractA dilute suspension of active Brownian particles in a dense compressible viscoelastic fluid, forms a natural setting to study the emergence of nonreciprocity during a dynamical phase transition. At these densities, the transport of active particles is strongly influenced by the passive medium and shows a dynamical jamming transition as a function of activity and medium density. In the process, the compressible medium is actively churned up – for low activity, the active particle gets self-trapped in a cavity of its own making, while for large activity, the active particle ploughs through the medium, either accompanied by a moving anisotropic wake, or leaving a porous trail. A hydrodynamic approach makes it evident that the active particle generates a long-range density wake which breaks fore-aft symmetry, consistent with the simulations. Accounting for the back-reaction of the compressible medium leads to (i) dynamical jamming of the active particle, and (ii) a dynamical non-reciprocal attraction between two active particles moving along the same direction, with the trailing particle catching up with the leading one in finite time. We emphasize that these nonreciprocal effects appear only when the active particles are moving and so manifest in the vicinity of the jamming-unjamming transition.
An electronic nematic liquid in BaNi2As2
Authors: Yao Yi , Willa Roland , Lacmann Tom , Souliou Sofia-Michaela , Frachet Mehdi , Willa Kristin , Merz Michael , Weber Frank , Meingast Christoph , Heid Rolf , Haghighirad Amir-Abbas , Schmalian Jörg , Le Tacon Matthieu 
Published: August 2022

AbstractUnderstanding the organizing principles of interacting electrons and the emergence of novel electronic phases is a central endeavor of condensed matter physics. Electronic nematicity, in which the discrete rotational symmetry in the electron fluid is broken while the translational one remains unaffected, is a prominent example of such a phase. It has proven ubiquitous in correlated electron systems, and is of prime importance to understand Fe-based superconductors. Here, we find that fluctuations of such broken symmetry are exceptionally strong over an extended temperature range above phase transitions in$${{{{{\rm{Ba}}}}}}{{{{{{\rm{Ni}}}}}}}_{2}{({{{{{{\rm{As}}}}}}}_{1-x}{{{{{{\rm{P}}}}}}}_{x})}_{2}$$BaNi2(As1−xPx)2, the nickel homologue to the Fe-based systems. This lends support to a type of electronic nematicity, dynamical in nature, which exhibits a particularly strong coupling to the underlying crystal lattice. Fluctuations between degenerate nematic configurations cause splitting of phonon lines, without lifting degeneracies nor breaking symmetries, akin to spin liquids in magnetic systems.
Cingulate-motor circuits update rule representations for sequential choice decisions
Authors: Takeuchi Daigo , Roy Dheeraj , Muralidhar Shruti , Kawai Takashi , Bari Andrea , Lovett Chanel , Sullivan Heather A. , Wickersham Ian R. , Tonegawa Susumu 
Published: August 2022

AbstractAnterior cingulate cortex mediates the flexible updating of an animal’s choice responses upon rule changes in the environment. However, how anterior cingulate cortex entrains motor cortex to reorganize rule representations and generate required motor outputs remains unclear. Here, we demonstrate that chemogenetic silencing of the terminal projections of cingulate cortical neurons in secondary motor cortex in the rat disrupts choice performance in trials immediately following rule switches, suggesting that these inputs are necessary to update rule representations for choice decisions stored in the motor cortex. Indeed, the silencing of cingulate cortex decreases rule selectivity of secondary motor cortical neurons. Furthermore, optogenetic silencing of cingulate cortical neurons that is temporally targeted to error trials immediately after rule switches exacerbates errors in the following trials. These results suggest that cingulate cortex monitors behavioral errors and updates rule representations in motor cortex, revealing a critical role for cingulate-motor circuits in adaptive choice behaviors.
Poly(ADP) ribose polymerase promotes DNA polymerase theta-mediated end joining by activation of end resection
Authors: Luedeman Megan E. , Stroik Susanna , Feng Wanjuan , Luthman Adam J. , Gupta Gaorav P. , Ramsden Dale A. 
Published: August 2022

AbstractThe DNA polymerase theta (Polθ)-mediated end joining (TMEJ) pathway for repair of chromosomal double strand breaks (DSBs) is essential in cells deficient in other DSB repair pathways, including hereditary breast cancers defective in homologous recombination. Strand-break activated poly(ADP) ribose polymerase 1 (PARP1) has been implicated in TMEJ, but the modest specificity of existing TMEJ assays means the extent of effect and the mechanism behind it remain unclear. We describe here a series of TMEJ assays with improved specificity and show ablation of PARP activity reduces TMEJ activity 2-4-fold. The reduction in TMEJ is attributable to a reduction in the 5’ to 3’ resection of DSB ends that is essential for engagement of this pathway and is compensated by increased repair by the nonhomologous-end joining pathway. This limited role for PARP activity in TMEJ helps better rationalize the combined employment of inhibitors of PARP and Polθ in cancer therapy.
A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike
Authors: Claireaux Mathieu , Caniels Tom G. , de Gast Marlon , Han Julianna , Guerra Denise , Kerster Gius , van Schaik Barbera D. C. , Jongejan Aldo , Schriek Angela I. , Grobben Marloes , Brouwer Philip J. M. , van der Straten Karlijn , Aldon Yoann , Capella-Pujol Joan , Snitselaar Jonne L. , Olijhoek Wouter , Aartse Aafke , Brinkkemper Mitch , Bontjer Ilja , Burger Judith A. , Poniman Meliawati , Bijl Tom P. L. , Torres Jonathan L. , Copps Jeffrey , Martin Isabel Cuella , de Taeye Steven W. , de Bree Godelieve J. , Ward Andrew B. , Sliepen Kwinten , van Kampen Antoine H. C. , Moerland Perry D. , Sanders Rogier W. , van Gils Marit J. 
Published: August 2022

AbstractDelineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells share an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.
Nesting of multiple polyhedral plasmonic nanoframes into a single entity
Authors: Yoo Sungjae , Lee Jaewon , Hilal Hajir , Jung Insub , Park Woongkyu , Lee Joong Wook , Choi Soobong , Park Sungho 
Published: August 2022

AbstractThe development of plasmonic nanostructures with intricate nanoframe morphologies has attracted considerable interest for improving catalytic and optical properties. However, arranging multiple nanoframes in one nanostructure especially, in a solution phase remains a great challenge. Herein, we show complex nanoparticles by embedding various shapes of three-dimensional polyhedral nanoframes within a single entity through rationally designed synthetic pathways. This synthetic strategy is based on the selective deposition of platinum atoms on high surface energy facets and subsequent growth into solid platonic nanoparticles, followed by the etching of inner Au domains, leaving complex nanoframes. Our synthetic routes are rationally designed and executable on-demand with a high structural controllability. Diverse Au solid nanostructures (octahedra, truncated octahedra, cuboctahedra, and cubes) evolved into complex multi-layered nanoframes with different numbers/shapes/sizes of internal nanoframes. After coating the surface of the nanoframes with plasmonically active metal (like Ag), the materials exhibited highly enhanced electromagnetic near-field focusing embedded within the internal complicated rim architecture.
The association between adiposity and anti-proliferative response to neoadjuvant endocrine therapy with letrozole in post-menopausal patients with estrogen receptor positive breast cancer
Authors: Isnaldi Edoardo , Richard François , De Schepper Maxim , Leduc Sophia , Maetens Marion , Geukens Tatjana , Van Baelen Karen , Nguyen Ha-Linh , Rouas Ghizlane , Zoppoli Gabriele , Cardoso Fatima , Sotiriou Christos , Larsimont Denis , Floris Giuseppe , Biganzoli Elia , Desmedt Christine 
Published: August 2022

AbstractThe impact of adiposity on the efficacy of endocrine treatment in patients with estrogen receptor positive breast cancer is poorly investigated. Here, we retrospectively investigated in a cohort of 56 patients whether body mass index and/or mammary adiposity are associated with anti-proliferative response in the neoadjuvant setting. Anti-proliferative response was defined as high Ki67 at baseline (Ki67bl) and low Ki67 at surgery (Ki67srg), using the 14% cut-off. Mammary adipocyte size was assessed on hematoxylin and eosin slides from the surgical samples using digital pathology. A higher proportion of tumors with an anti-proliferative response was observed in patients with obesity (54.5%) as compared to patients with normal weight (9.0%) and patients with overweight (40.0%) (p = 0.031), confirmed by multivariable regression analysis adjusted for baseline Ki67 (OR, obese vs normal weight: 13.76, 95%CI: 1.49–207.63, p = 0.020). Larger adipocyte diameter was identified as predictor of anti-proliferative response (OR per increase in diameter of 5 μm for adipocytes distant from the tumor: 2.24, 95%CI: 1.01–14.32, p = 0.046). This study suggests that anti-proliferative response to neoadjuvant letrozole might be more frequent in patients with increased systemic or mammary adiposity.
Transcriptomic effects of propranolol and primidone converge on molecular pathways relevant to essential tremor
Authors: Castonguay Charles-Etienne , Liao Calwing , Khayachi Anouar , Liu Yumin , Medeiros Miranda , Houle Gabrielle , Ross Jay P. , Dion Patrick A. , Rouleau Guy A. 
Published: August 2022

AbstractEssential tremor (ET) is one of the most common movement disorders, affecting nearly 5% of individuals over 65 years old. Despite this, few genetic risk loci for ET have been identified. Recent advances in pharmacogenomics have previously been useful to identify disease related molecular targets. Notably, gene expression has proven to be quite successful for the inference of drug response in cell models. We sought to leverage this approach in the context of ET where many patients are responsive to two drugs: propranolol and primidone. In this study, cerebellar DAOY and neural progenitor cells were treated for 5 days with clinical concentrations of propranolol and primidone, after which RNA-sequencing was used to identify convergent differentially expressed genes across treatments. Propranolol was found to affect the expression of genes previously associated with ET and other movement disorders such as TRAPPC11. Pathway enrichment analysis of these convergent drug-targeted genes identified multiple terms related to calcium signaling, endosomal sorting, axon guidance, and neuronal morphology. Furthermore, genes targeted by ET drugs were enriched within cell types having high expression of ET-related genes in both cortical and cerebellar tissues. Altogether, our results highlight potential cellular and molecular mechanisms associated with tremor reduction and identify relevant genetic biomarkers for drug-responsiveness in ET.
Passive limitation of surface contamination by perFluoroDecylTrichloroSilane coatings in the ISS during the MATISS experiments
Authors: Lemelle Laurence , Rouquette Sébastien , Mottin Eléonore , Le Tourneau Denis , Marcoux Pierre R. , Thévenot Cécile , Maillet Alain , Nonglaton Guillaume , Place Christophe 
Published: August 2022

AbstractFuture long-duration human spaceflight will require developments to limit biocontamination of surface habitats. The MATISS (Microbial Aerosol Tethering on Innovative Surfaces in the international Space Station) experiments allowed for exposing surface treatments in the ISS (International Space Station) using a sample-holder developed to this end. Three campaigns of FDTS (perFluoroDecylTrichloroSilane) surface exposures were performed over monthly durations during distinct periods. Tile scanning optical microscopy (×3 and ×30 magnifications) showed a relatively clean environment with a few particles on the surface (0.8 to 7 particles per mm2). The varied densities and shapes in the coarse area fraction (50–1500 µm2) indicated different sources of contamination in the long term, while the bacteriomorph shapes of the fine area fraction (0.5–15 µm2) were consistent with microbial contamination. The surface contamination rates correlate to astronauts’ occupancy rates on board. Asymmetric particles density profiles formed throughout time along the air-flow. The higher density values were located near the flow entry for the coarse particles, while the opposite was the case for the fine particles, probably indicating the hydrophobic interaction of particles with the FDTS surface.
Global patterns and rates of habitat transitions across the eukaryotic tree of life
Authors: Jamy Mahwash , Biwer Charlie , Vaulot Daniel , Obiol Aleix , Jing Hongmei , Peura Sari , Massana Ramon , Burki Fabien 
Published: August 2022

AbstractThe successful colonization of new habitats has played a fundamental role during the evolution of life. Salinity is one of the strongest barriers for organisms to cross, which has resulted in the evolution of distinct marine and non-marine (including both freshwater and soil) communities. Although microbes represent by far the vast majority of eukaryote diversity, the role of the salt barrier in shaping the diversity across the eukaryotic tree is poorly known. Traditional views suggest rare and ancient marine/non-marine transitions but this view is being challenged by the discovery of several recently transitioned lineages. Here, we investigate habitat evolution across the tree of eukaryotes using a unique set of taxon-rich phylogenies inferred from a combination of long-read and short-read environmental metabarcoding data spanning the ribosomal DNA operon. Our results show that, overall, marine and non-marine microbial communities are phylogenetically distinct but transitions have occurred in both directions in almost all major eukaryotic lineages, with hundreds of transition events detected. Some groups have experienced relatively high rates of transitions, most notably fungi for which crossing the salt barrier has probably been an important aspect of their successful diversification. At the deepest phylogenetic levels, ancestral habitat reconstruction analyses suggest that eukaryotes may have first evolved in non-marine habitats and that the two largest known eukaryotic assemblages (TSAR and Amorphea) arose in different habitats. Overall, our findings indicate that the salt barrier has played an important role during eukaryote evolution and provide a global perspective on habitat transitions in this domain of life.
Male fathead minnow transcriptomes and associated chemical analytes in the Milwaukee estuary system
Authors: Garcia-Reyero Natàlia , Arick Mark A. , Woolard E. Alice , Wilbanks Mitchell , Mylroie John E. , Jensen Kathleen , Kahl Michael , Feifarek David , Poole Shane , Randolph Eric , Cavallin Jenna , Blackwell Brett R. , Villeneuve Daniel , Ankley Gerald T. , Perkins Edward J. 
Published: August 2022

AbstractContaminants of Emerging Concern (CECs) can be measured in waters across the United States, including the tributaries of the Great Lakes. The extent to which these contaminants affect gene expression in aquatic wildlife is unclear. This dataset presents the full hepatic transcriptomes of laboratory-reared fathead minnows (Pimephales promelas) caged at multiple sites within the Milwaukee Estuary Area of Concern and control sites. Following 4 days of in situ exposure, liver tissue was removed from males at each site for RNA extraction and sequencing, yielding a total of 116 samples from which libraries were prepared, pooled, and sequenced. For each exposure site, 179 chemical analytes were also assessed. These data were created with the intention of inviting research on possible transcriptomic changes observed in aquatic species exposed to CECs. Access to both full sequencing reads of animal samples as well as water contaminant data across multiple Great Lakes sites will allow others to explore the health of these ecosystems in support of the aims of the Great Lakes Restoration Initiative.
SeEn: Sequential enriched datasets for sequence-aware recommendations
Authors: Barros Marcia , Moitinho André , Couto Francisco M. 
Published: August 2022

AbstractThe recommendation of items based on the sequential past users’ preferences has evolved in the last few years, mostly due to deep learning approaches, such as BERT4Rec. However, in scientific fields, recommender systems for recommending the next best item are not widely used. The main goal of this work is to improve the results for the recommendation of the next best item in scientific domains using sequence aware datasets and algorithms. In the first part of this work, we present the adaptation of a previous method (LIBRETTI) for creating sequential recommendation datasets for scientific fields. The results were assessed in Astronomy and Chemistry. In the second part of this work, we propose a new approach to improve the datasets, not the algorithms, to obtain better recommendations. The new hybrid approach is called sequential enrichment (SeEn), which consists of adding to a sequence of items the n most similar items after each original item. The results show that the enriched sequences obtained better results than the original ones. The Chemistry dataset improved by approximately seven percentage points and the Astronomy dataset by 16 percentage points for Hit Ratio and Normalized Discounted Cumulative Gain.
Driving singing behaviour in songbirds using a multi-modal, multi-agent virtual environment
Authors: Larsen Leon Bonde , Adam Iris , Berman Gordon J. , Hallam John , Elemans Coen P. H. 
Published: August 2022

AbstractInteractive biorobotics provides unique experimental potential to study the mechanisms underlying social communication but is limited by our ability to build expressive robots that exhibit the complex behaviours of birds and small mammals. An alternative to physical robots is to use virtual environments. Here, we designed and built a modular, audio-visual 2D virtual environment that allows multi-modal, multi-agent interaction to study mechanisms underlying social communication. The strength of the system is an implementation based on event processing that allows for complex computation. We tested this system in songbirds, which provide an exceptionally powerful and tractable model system to study social communication. We show that pair-bonded zebra finches (Taeniopygia guttata) communicating through the virtual environment exhibit normal call timing behaviour, males sing female directed song and both males and females display high-intensity courtship behaviours to their mates. These results suggest that the environment provided is sufficiently natural to elicit these behavioral responses. Furthermore, as an example of complex behavioral annotation, we developed a fully unsupervised song motif detector and used it to manipulate the virtual social environment of male zebra finches based on the number of motifs sung. Our virtual environment represents a first step in real-time automatic behaviour annotation and animal–computer interaction using higher level behaviours such as song. Our unsupervised acoustic analysis eliminates the need for annotated training data thus reducing labour investment and experimenter bias.