bluuebunny/crossref_metadata_2025_split huggingface dataset:
A robust approach for MicroED sample preparation of lipidic cubic phase embedded membrane protein crystals
Authors: Martynowycz Michael W. , Shiriaeva Anna , Clabbers Max T. B. , Nicolas William J. , Weaver Sara J. , Hattne Johan , Gonen Tamir 
Published: February 2023

AbstractCrystallizing G protein-coupled receptors (GPCRs) in lipidic cubic phase (LCP) often yields crystals suited for the cryogenic electron microscopy (cryoEM) method microcrystal electron diffraction (MicroED). However, sample preparation is challenging. Embedded crystals cannot be targeted topologically. Here, we use an integrated fluorescence light microscope (iFLM) inside of a focused ion beam and scanning electron microscope (FIB-SEM) to identify fluorescently labeled GPCR crystals. Crystals are targeted using the iFLM and LCP is milled using a plasma focused ion beam (pFIB). The optimal ion source for preparing biological lamellae is identified using standard crystals of proteinase K. Lamellae prepared using either argon or xenon produced the highest quality data and structures. MicroED data are collected from the milled lamellae and the structures are determined. This study outlines a robust approach to identify and mill membrane protein crystals for MicroED and demonstrates plasma ion-beam milling is a powerful tool for preparing biological lamellae.
BdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity
Authors: Shlyakhtina Yelyzaveta , Bloechl Bianca , Portal Maximiliano M. 
Published: February 2023

AbstractCell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thereby maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, here we develop a lineage-tracing technology termed Barcode decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. We show that cell transcriptome states are both inherited, and dynamically reshaped following constrained rules encoded within the cell lineage in basal growth conditions, upon oncogene activation and throughout the process of reversible resistance to therapeutic cues thus adjusting phenotypic output leading to intra-clonal non-genetic diversity.
Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1
Authors: Schmidpeter Philipp A. M. , Petroff John T. , Khajoueinejad Leila , Wague Aboubacar , Frankfater Cheryl , Cheng Wayland W. L. , Nimigean Crina M. , Riegelhaupt Paul M. 
Published: February 2023

AbstractTandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE). At the extracellular face of TREK1, a PA lipid inserts its hydrocarbon tail into a pocket behind the selectivity filter, causing a structural rearrangement that recapitulates mutations and pharmacology known to activate TREK1. At the cytoplasmic face, PA and PE lipids compete to modulate the conformation of the TREK1 TM4 gating helix. Our findings demonstrate two distinct pathways by which anionic lipids enhance TREK1 activity and provide a framework for a model that integrates lipid gating with the effects of other mechanosensitive K2P modulators.
Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response
Authors: Barczak Wojciech , Carr Simon M. , Liu Geng , Munro Shonagh , Nicastri Annalisa , Lee Lian Ni , Hutchings Claire , Ternette Nicola , Klenerman Paul , Kanapin Alexander , Samsonova Anastasia , La Thangue Nicholas B. 
Published: February 2023

AbstractProtein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine.
Softness of hydrated salt crystals under deliquescence
Authors: Wijnhorst Rozeline , Demmenie Menno , Jambon-Puillet Etienne , Ariese Freek , Bonn Daniel , Shahidzadeh Noushine 
Published: February 2023

AbstractDeliquescence is a first-order phase transition, happening when a salt absorbs water vapor. This has a major impact on the stability of crystalline powders that are important for example in pharmacology, food science and for our environment and climate. Here we show that during deliquescence, the abundant salt sodium sulfate decahydrate, mirabilite (Na2SO4·10H2O), behaves differently than anhydrous salts. Using various microscopy techniques combined with Raman spectroscopy, we show that mirabilite crystals not only lose their facets but also become soft and deformable. As a result, microcrystals of mirabilite simultaneously behave crystalline-like in the core bulk and liquid-like at the surface. Defects at the surface can heal at a speed much faster than the deliquescence rate by the mechanism of visco-capillary flow over the surface. While magnesium sulfate hexahydrate (MgSO4⋅6H2O) behaves similarly during deliquescence, a soft and deformable state is completely absent for the anhydrous salts sodium chloride (NaCl) and sodium sulfate thenardite (Na2SO4). The results highlight the effect of crystalline water, and its mobility in the crystalline structure on the observed softness during deliquescence. Controlled hydrated salts have potential applications such as thermal energy storage, where the key parameter is relative humidity rather than temperature.
Anion-enrichment interface enables high-voltage anode-free lithium metal batteries
Authors: Mao Minglei , Ji Xiao , Wang Qiyu , Lin Zejing , Li Meiying , Liu Tao , Wang Chengliang , Hu Yong-Sheng , Li Hong , Huang Xuejie , Chen Liquan , Suo Liumin 
Published: February 2023

AbstractAggressive chemistry involving Li metal anode (LMA) and high-voltage LiNi0.8Mn0.1Co0.1O2 (NCM811) cathode is deemed as a pragmatic approach to pursue the desperate 400 Wh kg−1. Yet, their implementation is plagued by low Coulombic efficiency and inferior cycling stability. Herein, we propose an optimally fluorinated linear carboxylic ester (ethyl 3,3,3-trifluoropropanoate, FEP) paired with weakly solvating fluoroethylene carbonate and dissociated lithium salts (LiBF4 and LiDFOB) to prepare a weakly solvating and dissociated electrolyte. An anion-enrichment interface prompts more anions’ decomposition in the inner Helmholtz plane and higher reduction potential of anions. Consequently, the anion-derived interface chemistry contributes to the compact and columnar-structure Li deposits with a high CE of 98.7% and stable cycling of 4.6 V NCM811 and LiCoO2 cathode. Accordingly, industrial anode-free pouch cells under harsh testing conditions deliver a high energy of 442.5 Wh kg−1 with 80% capacity retention after 100 cycles.
Single-molecular insights into the breakpoint of cellulose nanofibers assembly during saccharification
Authors: Zhang Ran , Hu Zhen , Wang Yanting , Hu Huizhen , Li Fengcheng , Li Mi , Ragauskas Arthur , Xia Tao , Han Heyou , Tang Jingfeng , Yu Haizhong , Xu Bingqian , Peng Liangcai 
Published: February 2023

AbstractPlant cellulose microfibrils are increasingly employed to produce functional nanofibers and nanocrystals for biomaterials, but their catalytic formation and conversion mechanisms remain elusive. Here, we characterize length-reduced cellulose nanofibers assembly in situ accounting for the high density of amorphous cellulose regions in the natural rice fragile culm 16 (Osfc16) mutant defective in cellulose biosynthesis using both classic and advanced atomic force microscopy (AFM) techniques equipped with a single-molecular recognition system. By employing individual types of cellulases, we observe efficient enzymatic catalysis modes in the mutant, due to amorphous and inner-broken cellulose chains elevated as breakpoints for initiating and completing cellulose hydrolyses into higher-yield fermentable sugars. Furthermore, effective chemical catalysis mode is examined in vitro for cellulose nanofibers conversion into nanocrystals with reduced dimensions. Our study addresses how plant cellulose substrates are digestible and convertible, revealing a strategy for precise engineering of cellulose substrates toward cost-effective biofuels and high-quality bioproducts.
Point process microstructural model of metallic thin films with implications for coarsening
Authors: Rickman J. M. , Barmak K. , Epshteyn Y. , Liu C. 
Published: February 2023

AbstractWe develop a thin-film microstructural model that represents structural markers (i.e., triple junctions in the two-dimensional projections of the structure of films with columnar grains) in terms of a stochastic, marked point process and the microstructure itself in terms of a grain-boundary network. The advantage of this representation is that it is conveniently applicable to the characterization of microstructures obtained from crystal orientation mapping, leading to a picture of an ensemble of interacting triple junctions, while providing results that inform grain-growth models with experimental data. More specifically, calculated quantities such as pair, partial pair and mark correlation functions, along with the microstructural mutual information (entropy), highlight effective triple junction interactions that dictate microstructural evolution. To validate this approach, we characterize microstructures from Al thin films via crystal orientation mapping and formulate an approach, akin to classical density functional theory, to describe grain growth that embodies triple-junction interactions.
PDGF gene expression and p53 alterations contribute to the biology of diffuse astrocytic gliomas
Authors: Kumar Mehul , Meode Mathieu , Blough Michael , Cairncross Gregory , Bose Pinaki 
Published: February 2023

AbstractDiffuse, histologically lower grade astrocytomas of adults (LGAs) are classified based on the mutational status of the isocitrate dehydrogenase (IDH) genes. While wild-type (WT) LGAs often evolve quickly to glioblastoma (GBM), mutant tumors typically follow an indolent course. To find possible effectors of these different behaviors, we compared their respective transcriptomes. Unlike mutant LGAs, platelet-derived growth factor (PDGF) signaling was significantly enriched in WT tumors, and PDGFA was the top overexpressed gene in the pathway. Moreover, methylation of the PDGFA and PDGFD promoters emerged as a possible mechanism for their low expression in mutant tumors. Copy number gain of chromosome 7 co-occurred with high expression of PDGFA in WT cases, and high expression of PDGFA was associated with aneuploidy, extracellular matrix (ECM)-related immunosuppressive features and poor prognosis. We also noted that high PDGFA expression in WT cases occurred irrespective of tumor grade and that multiple mechanisms of p53 pathway inactivation accompanied progression to GBM in PDGFA-overexpressing tumors. Conversely, TP53 point mutations were an early and constant feature of mutant LGAs. Our results suggest that members of the PDGF gene family, in concert with different p53 pathway alterations, underlie LGA behaviors.
A benchmarking procedure for quantum networks
Authors: Helsen Jonas , Wehner Stephanie 
Published: February 2023

AbstractWe propose network benchmarking: a procedure to efficiently benchmark the quality of a quantum network link connecting quantum processors in a quantum network. This procedure is based on the standard randomized benchmarking protocol and provides an estimate for the fidelity of a quantum network link. We provide statistical analysis of the protocol as well as a simulated implementation inspired by nitrogen-vacancy center systems using Netsquid, a special purpose simulator for noisy quantum networks.
Resting-state brain functional alterations and their genetic mechanisms in drug-naive first-episode psychosis
Authors: Li Qian , Xu Xiaotao , Qian Yinfeng , Cai Huanhuan , Zhao Wenming , Zhu Jiajia , Yu Yongqiang 
Published: February 2023

AbstractExtensive research has established the presence of resting-state brain functional damage in psychosis. However, the genetic mechanisms of such disease phenotype are yet to be unveiled. We investigated resting-state brain functional alterations in patients with drug-naive first-episode psychosis (DFP) by performing a neuroimaging meta-analysis of 8 original studies comprising 500 patients and 469 controls. Combined with the Allen Human Brain Atlas, we further conducted transcriptome-neuroimaging spatial correlations to identify genes whose expression levels were linked to brain functional alterations in DFP, followed by a range of gene functional characteristic analyses. Meta-analysis revealed a mixture of increased and decreased brain function in widespread areas including the default-mode, visual, motor, striatal, and cerebellar systems in DFP. Moreover, these brain functional alterations were spatially associated with the expression of 1662 genes, which were enriched for molecular functions, cellular components, and biological processes of the cerebral cortex, as well as psychiatric disorders including schizophrenia. Specific expression analyses demonstrated that these genes were specifically expressed in the brain tissue, in cortical neurons and immune cells, and during nearly all developmental periods. Concurrently, the genes could construct a protein-protein interaction network supported by hub genes and were linked to multiple behavioral domains including emotion, attention, perception, and motor. Our findings provide empirical evidence for the notion that brain functional damage in DFP involves a complex interaction of polygenes with various functional characteristics.
Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination
Authors: Holt Hayley , Jolliffe David A. , Talaei Mohammad , Faustini Sian , Vivaldi Giulia , Greenig Matthew , Richter Alex G. , Lyons Ronan A. , Griffiths Christopher J. , Kee Frank , Sheikh Aziz , Davies Gwyneth A. , Shaheen Seif O. , Martineau Adrian R. 
Published: February 2023

AbstractProspective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81–0.90), male vs. female sex (0.59, 0.53–0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26–0.32 for BNT162b2; 0.06, 0.01–0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78–2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81–1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12–1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.
A fast privacy-preserving patient record linkage of time series data
Authors: Soliman Ahmed , Rajasekaran Sanguthevar , Toman Patrick , Ravishanker Nalini 
Published: February 2023

AbstractRecent advances in technology have led to an explosion of data in virtually all domains of our lives. Modern biomedical devices can acquire a large number of physical readings from patients. Often, these readings are stored in the form of time series data. Such time series data can form the basis for important research to advance healthcare and well being. Due to several considerations including data size, patient privacy, etc., the original, full data may not be available to secondary parties or researchers. Instead, suppose that a subset of the data is made available. A fast and reliable record linkage algorithm enables us to accurately match patient records in the original and subset databases while maintaining privacy. The problem of record linkage when the attributes include time series has not been studied much in the literature. We introduce two main contributions in this paper. First, we propose a novel, very efficient, and scalable record linkage algorithm that is employed on time series data. This algorithm is 400× faster than the previous work. Second, we introduce a privacy preserving framework that enables health institutions to safely release their raw time series records to researchers with bare minimum amount of identifying information.
Removal of toxic lead from aqueous solution using a low-cost adsorbent
Authors: Dehghani Mohammad Hadi , Afsari Sardari Sahar , Afsharnia Mojtaba , Qasemi Mehdi , Shams Mahmoud 
Published: February 2023

AbstractValorization of waste materials and byproducts as adsorbents is a sustainable approach for water treatment systems. Pottery Granules (PG) without any chemical and thermal modification were used as a low-cost, abundant, and environmentally benign adsorbent against Pb(II), the toxic metal in drinking water. The porous structure and complex mineral composition of PG made it an efficient adsorbent material for Pb(II). The effect of key physicochemical factors was investigated to determine the significance of contact time, PG dose, pH, solution temperature, and coexisting ions, on the process. Pb(II) removal increased by PG dose in the range of 5–15 g/L, and agitation time from 5 to 60 min. Increasing Pb(II) concentration led to a drop in Pb(II) removal, however, adsorption capacity increased significantly as concentration elevated. Pb(II) removal also increased significantly from ~ 45% to ~ 97% by pH from 2 to 12. A ~ 20% improvement in Pb(II) adsorption after rising the solution temperature by 30˚C, indicated the endothermic nature of the process. The sorption was described to be a favorable process in which Pb(II) was adsorbed in a multilayer onto the heterogeneous PG surface. The qmax of 9.47 mg/g obtained by the Langmuir model was superior among many reported low-cost adsorbents. The Pb(II) adsorption was described well by the Pseudo- first-order kinetic model. Na+, Mg2+, Ca2+, Cd2+, and Zn2+ showed a negligible effect on Pb(II) adsorption. However, the presence of Mn2+ and Fe2+ significantly hindered the process efficacy. In conclusion, the use of waste material such as PG against Pb(II) is a viable option from the economic and effectiveness points of view.
Real-time automatic temperature regulation during in vivo MRI-guided laser-induced thermotherapy (MR-LITT)
Authors: Desclides Manon , Ozenne Valéry , Bour Pierre , Faller Thibaut , Machinet Guillaume , Pierre Christophe , Chemouny Stéphane , Quesson Bruno 
Published: February 2023

AbstractPrecise control of tissue temperature during Laser-Induced Thermotherapy (LITT) procedures has the potential to improve the clinical efficiency and safety of such minimally invasive therapies. We present a method to automatically regulate in vivo the temperature increase during LITT using real-time rapid volumetric Magnetic Resonance thermometry (8 slices acquired every second, with an in-plane resolution of 1.4 mmx1.4 mm and a slice thickness of 3 mm) using the proton-resonance frequency (PRF) shift technique. The laser output power is adjusted every second using a feedback control algorithm (proportional-integral-derivative controller) to force maximal tissue temperature in the targeted region to follow a predefined temperature–time profile. The root-mean-square of the difference between the target temperature and the measured temperature ranged between 0.5 °C and 1.4 °C, for temperature increases between + 5 °C to + 30 °C above body temperature and a long heating duration (up to 15 min), showing excellent accuracy and stability of the method. These results were obtained on a 1.5 T clinical MRI scanner, showing a potential immediate clinical application of such a temperature controller during MR-guided LITT.
Evidence for avoidance tendencies linked to anxiety about specific types of thinking
Authors: Daker Richard J. , Slipenkyj Michael S. , Green Adam E. , Lyons Ian M. 
Published: February 2023

AbstractAnxieties that are specific to a particular kind of thinking have been demonstrated for a variety of cognitive domains. One hypothesized consequence of these anxieties is reduced interest in pursuing activities and, consequentially, careers that involve the type of thinking in question in an effort to avoid engaging in that type of thinking. There is little research addressing this avoidance hypothesis, possibly because it is difficult to categorize pursuits as objectively “creative” or “spatial”. Here, we measured the perceptions that participants, themselves, hold about how much pursuits (careers and activities) involve different types of thinking. We developed a novel framework for calculating “affinity coefficients”, within-person associations between perceived cognitive involvement and interest across several pursuits. Having a negative creative affinity coefficient, for instance, means being less interested in pursuits the more they are perceived as involving creative thinking. Results across three separate cognitive domains (creativity, mathematics, and spatial reasoning) reliably showed that higher anxiety in a domain uniquely predicted a lower affinity coefficient in that domain, providing consistent evidence of avoidance tendencies linked to cognition-specific anxieties. These findings suggest that feeling anxious about particular types of thinking may play a significant role in shaping our interests, both big and small.