bluuebunny/crossref_metadata_2025_split huggingface dataset:
circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment
Authors: Piras Roberta , Ko Emily Y. , Barrett Connor , De Simone Marco , Lin Xianzhi , Broz Marina T. , Tessaro Fernando H. G. , Castillo-Martin Mireia , Cordon-Cardo Carlos , Goodridge Helen S. , Di Vizio Dolores , Batish Mona , Lawrenson Kate , Chen Y. Grace , Chan Keith Syson , Guarnerio Jlenia 
Published: November 2022

AbstractExonic circular RNAs (circRNAs) produce predominantly non-coding RNA species that have been recently profiled in many tumors. However, their functional contribution to cancer progression is still poorly understood. Here, we identify the circRNAs expressed in soft tissue sarcoma cells and explore how the circRNAs regulate sarcoma growth in vivo. We show that circCsnk1g3 and circAnkib1 promote tumor growth by shaping a pro-tumorigenic microenvironment, possibly due to their capabilities to regulate tumor-promoting elements extrinsic to the tumor cells. Accordingly, circCsnk1g3 and circAnkib1 can control the expression of interferon-related genes and pro-inflammatory factors in the sarcoma cells, thus directing immune cell recruitment into the tumor mass, and hence their activation. Mechanistically, circRNAs may repress pro-inflammatory elements by buffering activation of the pathways mediated by RIG-I, the cytosolic viral RNA sensor. The current findings suggest that the targeting of specific circRNAs could augment the efficacy of tumor and immune response to mainstay therapies.
CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease
Authors: Pierson Sheila K. , Katz Laura , Williams Reece , Mumau Melanie , Gonzalez Michael , Guzman Stacy , Rubenstein Ayelet , Oromendia Ana B. , Beineke Philip , Fosså Alexander , van Rhee Frits , Fajgenbaum David C. 
Published: November 2022

AbstractIdiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N = 42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD.
Holocene hydroclimatic variability in the tropical Pacific explained by changing ENSO diversity
Authors: Karamperidou Christina , DiNezio Pedro N. 
Published: November 2022

AbstractUnderstanding El Niño-Southern Oscillation (ENSO) response to past climate forcings is hindered by conflicting paleoclimate evidence. Records from the eastern Pacific show an intensification of ENSO variability from early to late Holocene, while records from the central Pacific show highly variable ENSO throughout the Holocene without an obvious relation to insolation forcing, which is the main climate driver during this interval. Here, we show via climate model simulations that conflicting Holocene records can be reconciled by considering changes in the relative frequency of the three preferred spatial patterns in which El Niño events occur (Eastern Pacific, Central Pacific, and Coastal) and in the strength of their hydroclimatic impacts. The relationship between ENSO diversity and variance is not only crucial for interpreting paleo-ENSO records and understanding ENSO response to external forcings but can also be used across climate model simulations to help evaluate the realism of ENSO projections in a changing climate.
AlphaPeptDeep: a modular deep learning framework to predict peptide properties for proteomics
Authors: Zeng Wen-Feng , Zhou Xie-Xuan , Willems Sander , Ammar Constantin , Wahle Maria , Bludau Isabell , Voytik Eugenia , Strauss Maximillian T. , Mann Matthias 
Published: November 2022

AbstractMachine learning and in particular deep learning (DL) are increasingly important in mass spectrometry (MS)-based proteomics. Recent DL models can predict the retention time, ion mobility and fragment intensities of a peptide just from the amino acid sequence with good accuracy. However, DL is a very rapidly developing field with new neural network architectures frequently appearing, which are challenging to incorporate for proteomics researchers. Here we introduce AlphaPeptDeep, a modular Python framework built on the PyTorch DL library that learns and predicts the properties of peptides (https://github.com/MannLabs/alphapeptdeep). It features a model shop that enables non-specialists to create models in just a few lines of code. AlphaPeptDeep represents post-translational modifications in a generic manner, even if only the chemical composition is known. Extensive use of transfer learning obviates the need for large data sets to refine models for particular experimental conditions. The AlphaPeptDeep models for predicting retention time, collisional cross sections and fragment intensities are at least on par with existing tools. Additional sequence-based properties can also be predicted by AlphaPeptDeep, as demonstrated with a HLA peptide prediction model to improve HLA peptide identification for data-independent acquisition (https://github.com/MannLabs/PeptDeep-HLA).
Insights into protein post-translational modification landscapes of individual human cells by trapped ion mobility time-of-flight mass spectrometry
Authors: Orsburn Benjamin C. , Yuan Yuting , Bumpus Namandjé N. 
Published: November 2022

AbstractSingle cell proteomics is a powerful tool with potential for markedly enhancing understanding of cellular processes. Here we report the development and application of multiplexed single cell proteomics using trapped ion mobility time-of-flight mass spectrometry. When employing a carrier channel to improve peptide signal, this method allows over 40,000 tandem mass spectra to be acquired in 30 min. Using a KRASG12C model human-derived cell line, we demonstrate the quantification of over 1200 proteins per cell with high relative sequence coverage permitting the detection of multiple classes of post-translational modifications in single cells. When cells were treated with a KRASG12C covalent inhibitor, this approach revealed cell-to-cell variability in the impact of the drug, providing insight missed by traditional proteomics. We provide multiple resources necessary for the application of single cell proteomics to drug treatment studies including tools to reduce cell cycle linked proteomic effects from masking pharmacological phenotypes.
Global landscape of replicative DNA polymerase usage in the human genome
Authors: Koyanagi Eri , Kakimoto Yoko , Minamisawa Tamiko , Yoshifuji Fumiya , Natsume Toyoaki , Higashitani Atsushi , Ogi Tomoo , Carr Antony M. , Kanemaki Masato T. , Daigaku Yasukazu 
Published: November 2022

AbstractThe division of labour among DNA polymerase underlies the accuracy and efficiency of replication. However, the roles of replicative polymerases have not been directly established in human cells. We developed polymerase usage sequencing (Pu-seq) in HCT116 cells and mapped Polε and Polα usage genome wide. The polymerase usage profiles show Polε synthesises the leading strand and Polα contributes mainly to lagging strand synthesis. Combining the Polε and Polα profiles, we accurately predict the genome-wide pattern of fork directionality plus zones of replication initiation and termination. We confirm that transcriptional activity contributes to the pattern of initiation and termination and, by separately analysing the effect of transcription on co-directional and converging forks, demonstrate that coupled DNA synthesis of leading and lagging strands is compromised by transcription in both co-directional and convergent forks. Polymerase uncoupling is particularly evident in the vicinity of large genes, including the two most unstable common fragile sites, FRA3B and FRA3D, thus linking transcription-induced polymerase uncoupling to chromosomal instability. Together, our result demonstrated that Pu-seq in human cells provides a powerful and straightforward methodology to explore DNA polymerase usage and replication fork dynamics.
Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter
Authors: Yamagata Atsushi , Murata Yoshiko , Namba Kosuke , Terada Tohru , Fukai Shuya , Shirouzu Mikako 
Published: November 2022

AbstractCalcareous soils cover one-third of all land and cause severe growth defects in plants due to the poor water solubility of iron at high pH. Poaceae species use a unique chelation strategy, whereby plants secrete a high-affinity metal chelator, known as phytosiderophores (mugineic acids), and reabsorb the iron-phytosiderophore complex by the yellow stripe 1/yellow stripe 1-like (YS1/YSL) transporter for efficient uptake of iron from the soil. Here, we present three cryo-electron microscopy structures of barley YS1 (HvYS1) in the apo state, in complex with an iron-phytosiderophore complex, Fe(III)-deoxymugineic acid (Fe(III)–DMA), and in complex with the iron-bound synthetic DMA analog (Fe(III)–PDMA). The structures reveal a homodimeric assembly mediated through an anti-parallel β-sheet interaction with cholesterol hemisuccinate. Each protomer adopts an outward open conformation, and Fe(III)–DMA is bound near the extracellular space in the central cavity. Fe(III)–PDMA occupies the same binding site as Fe(III)–DMA, demonstrating that PDMA can function as a potent fertilizer in an essentially identical manner to DMA. Our results provide a structural framework for iron-phytosiderophore recognition and transport by YS1/YSL transporters, which will enable the rational design of new, high-potency fertilizers.
Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death
Authors: Scur Michal , Mahmoud Ahmad Bakur , Dey Sayanti , Abdalbarri Farah , Stylianides Iona , Medina-Luna Daniel , Gamage Gayani S. , Woblistin Aaron , Wilson Alexa N. M. , Zein Haggag S. , Stueck Ashley , Wight Andrew , Aguilar Oscar A. , Di Cara Francesca , Parsons Brendon D. , Rahim Mir Munir A. , Carlyle James R. , Makrigiannis Andrew P. 
Published: November 2022

AbstractAlveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming.Nkrp1b−/−mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM ofNkrp1b−/−mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.
The molecular organization of differentially curved caveolae indicates bendable structural units at the plasma membrane
Authors: Matthaeus Claudia , Sochacki Kem A. , Dickey Andrea M. , Puchkov Dmytro , Haucke Volker , Lehmann Martin , Taraska Justin W. 
Published: November 2022

AbstractCaveolae are small coated plasma membrane invaginations with diverse functions. Caveolae undergo curvature changes. Yet, it is unclear which proteins regulate this process. To address this gap, we develop a correlative stimulated emission depletion (STED) fluorescence and platinum replica electron microscopy imaging (CLEM) method to image proteins at single caveolae. Caveolins and cavins are found at all caveolae, independent of curvature. EHD2 is detected at both low and highly curved caveolae. Pacsin2 associates with low curved caveolae and EHBP1 with mostly highly curved caveolae. Dynamin is absent from caveolae. Cells lacking dynamin show no substantial changes to caveolae, suggesting that dynamin is not directly involved in caveolae curvature. We propose a model where caveolins, cavins, and EHD2 assemble as a cohesive structural unit regulated by intermittent associations with pacsin2 and EHBP1. These coats can flatten and curve to enable lipid traffic, signaling, and changes to the surface area of the cell.
High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers
Authors: Ouyang Ruochen , Costa Ana Rita , Cassidy C. Keith , Otwinowska Aleksandra , Williams Vera C. J. , Latka Agnieszka , Stansfeld Phill J. , Drulis-Kawa Zuzanna , Briers Yves , Pelt Daniël M. , Brouns Stan J. J. , Briegel Ariane 
Published: November 2022

AbstractThe Klebsiella jumbo myophage ϕKp24 displays an unusually complex arrangement of tail fibers interacting with a host cell. In this study, we combine cryo-electron microscopy methods, protein structure prediction methods, molecular simulations, microbiological and machine learning approaches to explore the capsid, tail, and tail fibers of ϕKp24. We determine the structure of the capsid and tail at 4.1 Å and 3.0 Å resolution. We observe the tail fibers are branched and rearranged dramatically upon cell surface attachment. This complex configuration involves fourteen putative tail fibers with depolymerase activity that provide ϕKp24 with the ability to infect a broad panel of capsular polysaccharide (CPS) types of Klebsiella pneumoniae. Our study provides structural and functional insight into how ϕKp24 adapts to the variable surfaces of capsulated bacterial pathogens, which is useful for the development of phage therapy approaches against pan-drug resistant K. pneumoniae strains.
Water induced ultrathin Mo2C nanosheets with high-density grain boundaries for enhanced hydrogen evolution
Authors: Yang Yang , Qian Yumin , Luo Zhaoping , Li Haijing , Chen Lanlan , Cao Xumeng , Wei Shiqiang , Zhou Bo , Zhang Zhenhua , Chen Shuai , Yan Wenjun , Dong Juncai , Song Li , Zhang Wenhua , Feng Renfei , Zhou Jigang , Du Kui , Li Xiuyan , Zhang Xian-Ming , Fan Xiujun 
Published: November 2022

AbstractGrain boundary controlling is an effective approach for manipulating the electronic structure of electrocatalysts to improve their hydrogen evolution reaction performance. However, probing the direct effect of grain boundaries as highly active catalytic hot spots is very challenging. Herein, we demonstrate a general water-assisted carbothermal reaction strategy for the construction of ultrathin Mo2C nanosheets with high-density grain boundaries supported on N-doped graphene. The polycrystalline Mo2C nanosheets are connected with N-doped graphene through Mo–C bonds, which affords an ultra-high density of active sites, giving excellent hydrogen evolution activity and superior electrocatalytic stability. Theoretical calculations reveal that the dz2 orbital energy level of Mo atoms is controlled by the MoC3 pyramid configuration, which plays a vital role in governing the hydrogen evolution activity. The dz2 orbital energy level of metal atoms exhibits an intrinsic relationship with the catalyst activity and is regarded as a descriptor for predicting the hydrogen evolution activity.
Comparison of antibody responses to SARS-CoV-2 variants in Australian children
Authors: Toh Zheng Quan , Mazarakis Nadia , Nguyen Jill , Higgins Rachel A. , Anderson Jeremy , Do Lien Anh Ha , Burgner David P. , Curtis Nigel , Steer Andrew C. , Mulholland Kim , Crawford Nigel W. , Tosif Shidan , Licciardi Paul V. 
Published: November 2022

AbstractThere is limited understanding of antibody responses in children across different SARS-CoV-2 variants. As part of an ongoing household cohort study, we assessed the antibody response among unvaccinated children infected with Wuhan, Delta, or Omicron variants, as well as vaccinated children with breakthrough Omicron infection, using a SARS-CoV-2 S1-specific IgG assay and surrogate virus neutralization test (% inhibition). Most children infected with Delta (100%, 35/35) or Omicron (81.3%, 13/16) variants seroconverted by one month following infection. In contrast, 37.5% (21/56) children infected with Wuhan seroconverted, as previously reported. However, Omicron-infected children (geometric mean concentration 46.4 binding antibody units/ml; % inhibition = 16.3%) mounted a significantly lower antibody response than Delta (435.5 binding antibody untis/mL, % inhibition = 76.9%) or Wuhan (359.0 binding antibody units/mL, % inhibition = 74.0%). Vaccinated children with breakthrough Omicron infection mounted the highest antibody response (2856 binding antibody units/mL, % inhibition = 96.5%). Our findings suggest that despite a high seropositivity rate, Omicron infection in children results in lower antibody levels and function compared with Wuhan or Delta infection or with vaccinated children with breakthrough Omicron infection. Our data have important implications for public health measures and vaccination strategies to protect children.
Unexpectedly efficient ion desorption of graphene-based materials
Authors: Xia Xinming , Zhou Feng , Xu Jing , Wang Zhongteng , Lan Jian , Fan Yan , Wang Zhikun , Liu Wei , Chen Junlang , Feng Shangshen , Tu Yusong , Yang Yizhou , Chen Liang , Fang Haiping 
Published: November 2022

AbstractIon desorption is extremely challenging for adsorbents with superior performance, and widely used conventional desorption methods involve high acid or base concentrations and large consumption of reagents. Here, we experimentally demonstrate the rapid and efficient desorption of ions on magnetite-graphene oxide (M-GO) by adding low amounts of Al3+. The corresponding concentration of Al3+ used is reduced by at least a factor 250 compared to conventional desorption method. The desorption rate reaches ~97.0% for the typical radioactive and bivalent ions Co2+, Mn2+, and Sr2+ within ~1 min. We achieve effective enrichment of radioactive 60Co and reduce the volume of concentrated 60Co solution by approximately 10 times compared to the initial solution. The M-GO can be recycled and reused easily without compromising its adsorption efficiency and magnetic performance, based on the unique hydration anionic species of Al3+ under alkaline conditions. Density functional theory calculations show that the interaction of graphene with Al3+ is stronger than with divalent ions, and that the adsorption probability of Al3+ is superior than that of Co2+, Mn2+, and Sr2+ ions. This suggests that the proposed method could be used to enrich a wider range of ions in the fields of energy, biology, environmental technology, and materials science.
Active matter in space
Authors: Volpe Giorgio , Bechinger Clemens , Cichos Frank , Golestanian Ramin , Löwen Hartmut , Sperl Matthias , Volpe Giovanni 
Published: November 2022

AbstractIn the last 20 years, active matter has been a highly dynamic field of research, bridging fundamental aspects of non-equilibrium thermodynamics with applications to biology, robotics, and nano-medicine. Active matter systems are composed of units that can harvest and harness energy and information from their environment to generate complex collective behaviours and forms of self-organisation. On Earth, gravity-driven phenomena (such as sedimentation and convection) often dominate or conceal the emergence of these dynamics, especially for soft active matter systems where typical interactions are of the order of the thermal energy. In this review, we explore the ongoing and future efforts to study active matter in space, where low-gravity and microgravity conditions can lift some of these limitations. We envision that these studies will help unify our understanding of active matter systems and, more generally, of far-from-equilibrium physics both on Earth and in space. Furthermore, they will also provide guidance on how to use, process and manufacture active materials for space exploration and colonisation.
Estimating the randomness of quantum circuit ensembles up to 50 qubits
Authors: Liu Minzhao , Liu Junyu , Alexeev Yuri , Jiang Liang 
Published: November 2022

AbstractRandom quantum circuits have been utilized in the contexts of quantum supremacy demonstrations, variational quantum algorithms for chemistry and machine learning, and blackhole information. The ability of random circuits to approximate any random unitaries has consequences on their complexity, expressibility, and trainability. To study this property of random circuits, we develop numerical protocols for estimating the frame potential, the distance between a given ensemble and the exact randomness. Our tensor-network-based algorithm has polynomial complexity for shallow circuits and is high-performing using CPU and GPU parallelism. We study 1. local and parallel random circuits to verify the linear growth in complexity as stated by the Brown–Susskind conjecture, and; 2. hardware-efficient ansätze to shed light on its expressibility and the barren plateau problem in the context of variational algorithms. Our work shows that large-scale tensor network simulations could provide important hints toward open problems in quantum information science.
Enviroscore: normalization, weighting, and categorization algorithm to evaluate the relative environmental impact of food and drink products
Authors: Ramos Saioa , Segovia Lucia , Melado-Herreros Angela , Cidad Maite , Zufía Jaime , Vranken Liesbet , Matthys Christophe 
Published: November 2022

AbstractA 5-scale label that relativizes the environmental impact of a given product referred to the impact of the European food basket is proposed. It was developed based on the Product Environmental Footprint methodology with the following stepwise approach. First, a set of normalization and weighting factors were defined to aggregate all the environmental impact categories into a single dimensionless index referred to as the European food basket, coined the European Food Environmental Footprint Single Index (EFSI). Next, the effectiveness of the EFSI index was evaluated by assessing the distribution of the EFSI results on 149 hypothetical food items and comparing it with the results obtained with EC Single Score. Finally, the thresholds to translate the EFSI index into the 5-scale Enviroscore (A, B, C, D, and E) were established and validated using the Delphi method. Results indicated that both, Enviroscore and EFSI, were able to account for impact variability between and within food products. Differences on the final score were observed due to the type of products (vegetables vs. animal products), the country of origin and the mean of transportation. Regarding country of origin, results indicated that differences in water stress impact category were better captured by the EFSI index (r = 0.624) than by the EC Single Score (r = 0.228). Finally, good agreement achieved with the Delphi method (weighted Kappa 0.642; p = 0.0025), ensures the acceptability of the Enviroscore. In conclusion, this study developed a method to communicate environmental impact assessment in a front-of-packaging label.