bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19
Authors: Radzikowska Urszula , Eljaszewicz Andrzej , Tan Ge , Stocker Nino , Heider Anja , Westermann Patrick , Steiner Silvio , Dreher Anita , Wawrzyniak Paulina , Rückert Beate , Rodriguez-Coira Juan , Zhakparov Damir , Huang Mengting , Jakiela Bogdan , Sanak Marek , Moniuszko Marcin , O’Mahony Liam , Jutel Marek , Kebadze Tatiana , Jackson David J. , Edwards Michael R. , Thiel Volker , Johnston Sebastian L. , Akdis Cezmi A. , Sokolowska Milena 
Published: April 2023

AbstractRhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.
Improved photovoltaic performance and robustness of all-polymer solar cells enabled by a polyfullerene guest acceptor
Authors: Yu Han , Wang Yan , Zou Xinhui , Yin Junli , Shi Xiaoyu , Li Yuhao , Zhao Heng , Wang Lingyuan , Ng Ho Ming , Zou Bosen , Lu Xinhui , Wong Kam Sing , Ma Wei , Zhu Zonglong , Yan He , Chen Shangshang 
Published: April 2023

AbstractFullerene acceptors typically possess excellent electron-transporting properties and can work as guest components in ternary organic solar cells to enhance the charge extraction and efficiencies. However, conventional fullerene small molecules typically suffer from undesirable segregation and dimerization, thus limiting their applications in organic solar cells. Herein we report the use of a poly(fullerene-alt-xylene) acceptor (PFBO-C12) as guest component enables a significant efficiency increase from 16.9% for binary cells to 18.0% for ternary all-polymer solar cells. Ultrafast optic and optoelectronic studies unveil that PFBO-C12 can facilitate hole transfer and suppress charge recombination. Morphological investigations show that the ternary blends maintain a favorable morphology with high crystallinity and smaller domain size. Meanwhile, the introduction of PFBO-C12 reduces voltage loss and enables all-polymer solar cells with excellent light stability and mechanical durability in flexible devices. This work demonstrates that introducing polyfullerenes as guest components is an effective approach to achieving highly efficient ternary all-polymer solar cells with good stability and mechanical robustness.
Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket
Authors: Schmidt Edward N. , Lamprinaki Dimitra , McCord Kelli A. , Joe Maju , Sojitra Mirat , Waldow Ayk , Nguyen Jasmine , Monyror John , Kitova Elena N. , Mozaneh Fahima , Guo Xue Yan , Jung Jaesoo , Enterina Jhon R. , Daskhan Gour C. , Han Ling , Krysler Amanda R. , Cromwell Christopher R. , Hubbard Basil P. , West Lori J. , Kulka Marianne , Sipione Simonetta , Klassen John S. , Derda Ratmir , Lowary Todd L. , Mahal Lara K. , Riddell Meghan R. , Macauley Matthew S. 
Published: April 2023

AbstractImmunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.
Observation of structural switch in nascent SAM-VI riboswitch during transcription at single-nucleotide and single-molecule resolution
Authors: Xue Yanyan , Li Jun , Chen Dian , Zhao Xizhu , Hong Liang , Liu Yu 
Published: April 2023

AbstractGrowing RNAs fold differently as they are transcribed, which modulates their finally adopted structures. Riboswitches regulate gene expression by structural change, which are sensitive to co-transcriptionally structural biology. Here we develop a strategy to track the structural change of RNAs during transcription at single-nucleotide and single-molecule resolution and use it to monitor individual transcripts of the SAM-VI riboswitch (riboSAM) as transcription proceeds, observing co-existence of five states in riboSAM. We report a bifurcated helix in one newly identified state from NMR and single-molecule FRET (smFRET) results, and its presence directs the translation inhibition in our cellular translation experiments. A model is proposed to illustrate the distinct switch patterns and gene-regulatory outcome of riboSAM when SAM is present or absent. Our strategy enables the precise mapping of RNAs’ conformational landscape during transcription, and may combine with detection methods other than smFRET for structural studies of RNAs in general.
IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings
Authors: Spínola-Amilibia Mercedes , Araújo-Bazán Lidia , de la Gándara Álvaro , Berger James M. , Arias-Palomo Ernesto 
Published: April 2023

AbstractTransposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transposase present in the widespread IS21 family of mobile elements, catalyzes efficient DNA transposition. Solution studies show that IstA engages the transposon terminal sequences to form a high-molecular weight complex and promote DNA integration. A 3.4 Å resolution structure of the transposase bound to transposon ends corroborates our biochemical findings and reveals that IstA self-assembles into a highly intertwined tetramer that synapses two supercoiled terminal inverted repeats. The three-dimensional organization of the IstA•DNA cleaved donor complex reveals remarkable similarities with retroviral integrases and classic transposase systems, such as Tn7 and bacteriophage Mu, and provides insights into IS21 transposition.
TransPolymer: a Transformer-based language model for polymer property predictions
Authors: Xu Changwen , Wang Yuyang , Barati Farimani Amir 
Published: April 2023

AbstractAccurate and efficient prediction of polymer properties is of great significance in polymer design. Conventionally, expensive and time-consuming experiments or simulations are required to evaluate polymer functions. Recently, Transformer models, equipped with self-attention mechanisms, have exhibited superior performance in natural language processing. However, such methods have not been investigated in polymer sciences. Herein, we report TransPolymer, a Transformer-based language model for polymer property prediction. Our proposed polymer tokenizer with chemical awareness enables learning representations from polymer sequences. Rigorous experiments on ten polymer property prediction benchmarks demonstrate the superior performance of TransPolymer. Moreover, we show that TransPolymer benefits from pretraining on large unlabeled dataset via Masked Language Modeling. Experimental results further manifest the important role of self-attention in modeling polymer sequences. We highlight this model as a promising computational tool for promoting rational polymer design and understanding structure-property relationships from a data science view.
Resistance to COVID-19 vaccination and the social contract: evidence from Italy
Authors: Kreps Sarah E. , Kriner Douglas L. 
Published: April 2023

AbstractConfronted with stalled vaccination efforts against COVID-19, many governments embraced mandates and other measures to incentivize vaccination that excluded the unvaccinated from aspects of social and economic life. Even still, many citizens remained unvaccinated. We advance a social contract framework for understanding who remains unvaccinated and why. We leverage both observational and individual-level survey evidence from Italy to study the relationship between vaccination status and social context, social trust, political partisanship, and adherence to core institutional structures such as the rule of law and collective commitments. We find that attitudes toward the rule of law and collective commitments outside the domain of vaccination are strongly associated with compliance with vaccine mandates and incentives. Partisanship also corresponds with vaccine behaviors, as supporters of parties whose leaders criticized aggressive policies to incentivize or mandate vaccination and emphasized individual liberty are least likely to comply. Our findings suggest appeals emphasizing individual benefits may be more effective than appeals emphasizing collective responsibility.
Extracting Group Velocity Dispersion values using quantum-mimic Optical Coherence Tomography and Machine Learning
Authors: Maliszewski Krzysztof A. , Urbańska Magdalena A. , Kolenderski Piotr , Vetrova Varvara , Kolenderska Sylwia M. 
Published: April 2023

AbstractQuantum-mimic Optical Coherence Tomography (Qm-OCT) images are cluttered with artefacts - parasitic peaks which emerge as a by-product of the algorithm used in this method. However, the shape and behaviour of an artefact are uniquely related to Group Velocity Dispersion (GVD) of the layer this artefact corresponds to and consequently, the GVD values can be inferred by carefully analysing them. Since for multi-layered objects the number of artefacts is too high to enable layer-specific analysis, we employ a solution based on Machine Learning. We train a neural network with Qm-OCT data as an input and dispersion profiles, i.e. depth distribution of GVD within an A-scan, as an output. By accounting for noise during training, we process experimental data and estimate the GVD values of BK7 and sapphire as well as provide a qualitative GVD value distribution in a grape and cucumber. Compared to other GVD-retrieving methods, our solution does not require user input, automatically provides dispersion values for all the visualised layers and is scalable. We analyse the factors affecting the accuracy of determining GVD: noise in the experimental data as well as general physical limitations of the detection of GVD-induced changes, and suggest possible solutions.
GATA6 coordinates cross-talk between BMP10 and oxidative stress axis in pulmonary arterial hypertension
Authors: Toyama Tetsuo , Kudryashova Tatiana V. , Ichihara Asako , Lenna Stefania , Looney Agnieszka , Shen Yuanjun , Jiang Lifeng , Teos Leyla , Avolio Theodore , Lin Derek , Kaplan Ulas , Marden Grace , Dambal Vrinda , Goncharov Dmitry , Delisser Horace , Lafyatis Robert , Seta Francesca , Goncharova Elena A. , Trojanowska Maria 
Published: April 2023

AbstractPulmonary arterial hypertension (PAH) is a life-threatening condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and often death. Here we report that deficiency of transcription factor GATA6 is a shared pathological feature of PA endothelial (PAEC) and smooth muscle cells (PASMC) in human PAH and experimental PH, which is responsible for maintenance of hyper-proliferative cellular phenotypes, pulmonary vascular remodeling and pulmonary hypertension. We further show that GATA6 acts as a transcription factor and direct positive regulator of anti-oxidant enzymes, and its deficiency in PAH/PH pulmonary vascular cells induces oxidative stress and mitochondrial dysfunction. We demonstrate that GATA6 is regulated by the BMP10/BMP receptors axis and its loss in PAECs and PASMC in PAH supports BMPR deficiency. In addition, we have established that GATA6-deficient PAEC, acting in a paracrine manner, increase proliferation and induce other pathological changes in PASMC, supporting the importance of GATA6 in pulmonary vascular cell communication. Treatment with dimethyl fumarate resolved oxidative stress and BMPR deficiency, reversed hemodynamic changes caused by endothelial Gata6 loss in mice, and inhibited proliferation and induced apoptosis in human PAH PASMC, strongly suggesting that targeting GATA6 deficiency may provide a therapeutic advance for patients with PAH.
Correlation between genotype and phenotype with special attention to hearing in 14 Japanese cases of NF2-related schwannomatosis
Authors: Oishi Naoki , Noguchi Masaru , Fujioka Masato , Nara Kiyomitsu , Wasano Koichiro , Mutai Hideki , Kawakita Rie , Tamura Ryota , Karatsu Kosuke , Morimoto Yukina , Toda Masahiro , Ozawa Hiroyuki , Matsunaga Tatsuo 
Published: April 2023

AbstractNF2-related schwannomatosis (NF2) is an autosomal dominant genetic disorder caused by variants in the NF2 gene. Approximately 50% of NF2 patients inherit pathogenic variants, and the remainder acquire de novo variants. NF2 is characterized by development of bilateral vestibular schwannomas. The genetic background of Japanese NF2 cases has not been fully investigated, and the present report performed a genetic analysis of 14 Japanese NF2 cases and examined genotype–phenotype correlations. DNA samples collected from peripheral blood were analyzed by next-generation sequencing, multiplex ligation-dependent probe amplification analysis, and in vitro electrophoresis. Ten cases had pathogenic or likely pathogenic variants in the NF2 gene, with seven truncating variants and three non-truncating variants. The age of onset in all seven cases with truncating variants was < 20 years. The age of onset significantly differed among cases with truncating NF2 variants, non-truncating NF2 variants, and no NF2 variants. However, the clinical course of tumor growth and hearing deterioration were not predicted only by germline pathogenic NF2 variants. The rate of truncating variants was higher in the present study than that of previous reports. Genotype–phenotype correlations in the age of onset were present in the analyzed Japanese NF2 cases.
Single-trajectory map equation
Authors: Kawamoto Tatsuro 
Published: April 2023

AbstractCommunity detection, the process of identifying module structures in complex systems represented on networks, is an effective tool in various fields of science. The map equation, which is an information-theoretic framework based on the random walk on a network, is a particularly popular community detection method. Despite its outstanding performance in many applications, the inner workings of the map equation have not been thoroughly studied. Herein, we revisit the original formulation of the map equation and address the existence of its “raw form,” which we refer to as the single-trajectory map equation. This raw form sheds light on many details behind the principle of the map equation that are hidden in the steady-state limit of the random walk. Most importantly, the single-trajectory map equation provides a more balanced community structure, naturally reducing the tendency of the overfitting phenomenon in the map equation.
Potential utility of risk stratification for multicancer screening with liquid biopsy tests
Authors: Kim Elle S. , Scharpf Robert B. , Garcia-Closas Montserrat , Visvanathan Kala , Velculescu Victor E. , Chatterjee Nilanjan 
Published: April 2023

AbstractOur proof-of-concept study reveals the potential of risk stratification by the combined effects of age, polygenic risk scores (PRS), and non-genetic risk factors in increasing the risk-benefit balance of rapidly emerging non-invasive multicancer early detection (MCED) liquid biopsy tests. We develop and validate sex-specific pan-cancer risk scores (PCRSs), defined by the combination of body mass index, smoking, family history of cancers, and cancer-specific polygenic risk scores (PRSs), to predict the absolute risk of developing at least one of the many common cancer types. We demonstrate the added value of PRSs in improving the predictive performance of the risk factors only model and project the positive and negative predictive values for two promising multicancer screening tests across risk strata defined by age and PCRS.
HaploCoV: unsupervised classification and rapid detection of novel emerging variants of SARS-CoV-2
Authors: Chiara Matteo , Horner David S. , Ferrandi Erika , Gissi Carmela , Pesole Graziano 
Published: April 2023

AbstractAccurate and timely monitoring of the evolution of SARS-CoV-2 is crucial for identifying and tracking potentially more transmissible/virulent viral variants, and implement mitigation strategies to limit their spread. Here we introduce HaploCoV, a novel software framework that enables the exploration of SARS-CoV-2 genomic diversity through space and time, to identify novel emerging viral variants and prioritize variants of potential epidemiological interest in a rapid and unsupervised manner. HaploCoV can integrate with any classification/nomenclature and incorporates an effective scoring system for the prioritization of SARS-CoV-2 variants. By performing retrospective analyses of more than 11.5 M genome sequences we show that HaploCoV demonstrates high levels of accuracy and reproducibility and identifies the large majority of epidemiologically relevant viral variants - as flagged by international health authorities – automatically and with rapid turn-around times.Our results highlight the importance of the application of strategies based on the systematic analysis and integration of regional data for rapid identification of novel, emerging variants of SARS-CoV-2. We believe that the approach outlined in this study will contribute to relevant advances to current and future genomic surveillance methods.
NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression
Authors: Sim Nicholas , Li Yinghui 
Published: April 2023

AbstractGliomas are highly invasive and chemoresistant cancers, making them challenging to treat. Chronic inflammation is a key driver of glioma progression as it promotes aberrant activation of inflammatory pathways such as NF-κB signalling, which drives cancer cell invasion and angiogenesis. NF-κB factors typically dimerise with its own family members, but emerging evidence of their promiscuous interactions with other oncogenic factors has been reported to promote transcription of new target genes and function. Here, we show that non-canonical NF-κB activation directly regulates p52 at the ETS1 promoter, activating its expression. This impacts the genomic and transcriptional landscape of ETS1 in a glioma-specific manner. We further show that enhanced non-canonical NF-κB signalling promotes the co-localisation of p52 and ETS1, resulting in transcriptional activation of non-κB and/or non-ETS glioma-promoting genes. We conclude that p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression.
Spontaneous tumor regression mediated by human T cells in a humanized immune system mouse model
Authors: Patel A. K. , Dhanik Ankur , Lim Wei Keat , Adler Christina , Ni Min , Wei Yi , Zhong Maggie , Nguyen Cindy , Zhong Jun , Lu Yi-Fen , Thurston Gavin , Macdonald Lynn , Murphy Andrew , Gurer Cagan , Frleta Davor 
Published: April 2023

AbstractImmunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice.
Search for a Grotthuss mechanism through the observation of proton transfer
Authors: Popov Ivan , Zhu Zhenghao , Young-Gonzales Amanda R. , Sacci Robert L. , Mamontov Eugene , Gainaru Catalin , Paddison Stephen J. , Sokolov Alexei P. 
Published: April 2023

AbstractThe transport of protons is critical in a variety of bio- and electro-chemical processes and technologies. The Grotthuss mechanism is considered to be the most efficient proton transport mechanism, generally implying a transfer of protons between ‘chains’ of host molecules via elementary reactions within the hydrogen bonds. Although Grotthuss proposed this concept more than 200 years ago, only indirect experimental evidence of the mechanism has been observed. Here we report the first experimental observation of proton transfer between the molecules in pure and 85% aqueous phosphoric acid. Employing dielectric spectroscopy, quasielastic neutron, and light scattering, and ab initio molecular dynamic simulations we determined that protons move by surprisingly short jumps of only ~0.5–0.7 Å, much smaller than the typical ion jump length in ionic liquids. Our analysis confirms the existence of correlations in these proton jumps. However, these correlations actually reduce the conductivity, in contrast to a desirable enhancement, as is usually assumed by a Grotthuss mechanism. Furthermore, our analysis suggests that the expected Grotthuss-like enhancement of conductivity cannot be realized in bulk liquids where ionic correlations always decrease conductivity.