bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo design of α-helical peptide channels with designer stoichiometry
Authors: Niitsu Ai , Thomson Andrew R , Scott Alistair J , Sengel Jason T , Jung Jaewoon , Mahendran Kozhinjampara R , Sodeoka Mikiko , Bayley Hagan , Sugita Yuji , Woolfson Derek N , Wallace Mark I 
Published: October 2024

AbstractDespite advances in peptide and protein design, the rational design of membrane-spanning peptides that form conducting channels remains challenging due to our imperfect understanding of the sequence-to-structure relationships that drive membrane insertion, assembly, and conductance. Here, we describe the design and computational and experimental characterization of a series of coiled coil-based peptides that form transmembrane α-helical barrels.Through a combination of rational and computational design, we obtain barrels with 5 to 7 helices, as characterized in detergent micelles. In lipid bilayers, these peptide assemblies exhibit two conductance states with relative populations dependent on the applied potential: (i) a low-conductance states that correlate with variations in the modeled coiled-coil barrel geometries, indicating stable transmembrane α-helical barrels; and (ii) high-conductance states in which single pores change size in discrete steps. Notably, the high-conductance states are similar for all peptides in contrast to the low-conductance states. This indicates the formation of large, dynamic pores through the recruitment and expulsion of peptides, as observed in natural barrel-stave peptide pores. These findings establish rational routes to design and tune functional membrane-spanning peptide channels with specific conductance and geometry.
Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4′-fluorouridine
Authors: Schrell Leon , Fuchs Hannah L. , Dickmanns Antje , Scheibner David , Olejnik Judith , Hume Adam J. , Reineking Wencke , Störk Theresa , Müller Martin , Graaf-Rau Annika , Diederich Sandra , Finke Stefan , Baumgärtner Wolfgang , Mühlberger Elke , Balkema-Buschmann Anne , Dobbelstein Matthias 
Published: October 2024

ABSTRACTRNA viruses present a constant threat to human health, often with limited options for vaccination or therapy. Notable examples include influenza viruses and coronaviruses, which have pandemic potential. Filo- and henipaviruses cause more limited outbreaks, but with high case fatality rates. All RNA viruses rely on the activity of a virus-encoded RNA-dependent RNA polymerase (RdRp). An antiviral nucleoside analogue, 4′-Fluorouridine (4′-FlU), targets RdRp and diminishes the replication of several RNA viruses, including influenza A virus and SARS-CoV-2, through incorporation into nascent viral RNA and delayed chain termination. However, the effective concentration of 4′-FlU varied among different viruses, raising the need to fortify its efficacy. Here we show that inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme essential for pyrimidine biosynthesis, can synergistically enhance the antiviral effect of 4′-FlU against influenza A viruses, SARS-CoV-2, henipaviruses, and Ebola virus. Even 4′-FlU-resistant mutant influenza A virus was re-sensitized towards 4′-FlU by DHODH inhibition. The addition of uridine rescued influenza A virus replication, strongly suggesting uridine depletion as a mechanism of this synergy. 4′-FlU was also highly effective against SARS-CoV-2 in a hamster model of COVID. We propose that the impairment of endogenous uridine synthesis by DHODH inhibition enhances the incorporation of 4′-FlU into viral RNAs. This strategy may be broadly applicable to enhance the efficacy of pyrimidine nucleoside analogues for antiviral therapy.Graphical AbstractHIGHLIGHTSStrong synergy of DHODH inhibitors with 4′-FlUActivity of the combination against previously resistant influenza virusBroadly active combination against a diverse set of RNA virusesSuccessful targets include highly pathogenic Ebola and Nipah viruses
Single-Cell RNA-Seq Reveals Adventitial Fibroblast Alterations during Mouse Atherosclerosis
Authors: Fries Lauren E. , Chung Allen , Chang Hyun K. , Yuan Timothy L. , Bauer Robert C. 
Published: October 2024

AbstractBackgroundAtherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in the western world despite the success of lipid lowering therapies, highlighting the need for novel lipid-independent therapeutic strategies. Genome-wide association studies (GWAS) have identified numerous genes associated with ASCVD that function in the vessel wall, suggesting that vascular cells mediate ASCVD, and that the genes and pathways essential for this vascular cell function may be novel therapeutic targets for the treatment of ASCVD. Furthermore, some of these implicated genes appear to function in the adventitial layer of the vasculature, suggesting these cells are able to potentiate ASCVD.MethodsTo investigate the role of adventitial cells in atherosclerosis, we conducted single-cell RNA sequencing (scRNA-seq) of the aortic adventitia during atherogenesis in maleLdlr-/-mice via pools of three mice, two samples per condition. We cross-referenced the scRNA-seq data with human ASCVD GWAS to identify regulators of adventitial responses in ASCVD. These regulators were then validatedin vitroin human adventitial fibroblasts.ResultsWe identified four adventitial fibroblast populations, all of which displayed shifts in population size and gene expression over the course of atherogenesis.SERPINH1, an ASCVD-linked GWAS gene, was differentially expressed in adventitial fibroblasts during atherogenesis. Knockdown ofSERPINH1 in vitroreduced fibroblast migration and altered subcluster marker gene expression.ConclusionsThese findings reveal dynamic changes in adventitial fibroblasts during atherosclerosis and suggest that reducedSERPINH1expression disrupts adventitial fibroblast function, contributing to ASCVD progression.
Computational Insights into the Allosteric Behavior of Mini Proinsulin Driven by C Peptide Mobility
Authors: Ayan Esra 
Published: October 2024

AbstractBackground/aimThe production of recombinant insulin remains challenging, particularly in enhancing refolding efficiency and bioactivity. Mini-proinsulin analogs, which involve reducing the length of the C-peptide, offer potential improvements in insulin production. This study aims to evaluate mini-proinsulin analogs’ design and receptor binding dynamics to optimize recombinant insulin production inE. coli.Materials and methodsMini-proinsulin analogs were engineered by replacing the 33-residue C-peptide with a pentapeptide sequence to improve refolding. The three-dimensional structure of mini-proinsulin was predicted using AlphaFold and performed docking analysis of mini-proinsulin analogs to the insulin receptor using AutoDock Tools, with comparisons made to previously available NMR-determined analog and the native insulin-insulin receptor complex. Normal Mode Analyses (GNM and ANM) were performed in detail to assess binding dynamics.ResultsIn silicoanalyses revealed that mini-proinsulin analogs closely replicate the structural features of native insulin and display receptor binding dynamics similar to native insulin, though they follow distinct receptor interaction paths.ConclusionAll analysis suggests that C-peptide mobility may contribute to the allosteric behavior observed in mini-proinsulin analogs during receptor interaction.
High aspect ratio graphene oxide: a highly efficient plasmid DNA deliverer for plant seed
Authors: Jiang Cheng , Pan Yue , Li Xinyu , Yang Zhongzhu 
Published: October 2024

AbstractPlant genetic engineering plays a central role in crop improvement and the biosynthesis of natural products. However, the plant cell wall serves as a natural barrier that restricts the efficient delivery of exogenous biomolecules, particularly the direct transfer of plasmid DNA into plant seeds. Here, we introduce a novel form of graphene oxide characterized by a high aspect ratio, synthesized through low-voltage, low-current, and prolonged electrochemical oxidation in a 0.5 mol/L NaOH aqueous solution. The high aspect ratio graphene oxide (HARGO) can effectively deliver plasmid DNA toPoa crymophilaKeng seeds, achieving a 90% success rate. Furthermore, it is effective for both wheat and rice seeds. The underlying mechanism of this efficient delivery is that HARGO can physically absorb plasmid DNA and transport the adsorbed plasmid DNA into plant cells and deeper tissues through passive transport, eliminating the need for chemical modification of polyethylene glycol (PEG) and polyethyleneimine (PEI). These findings offer a dependable non-integrating plasmid DNA delivery tool for plant genetic engineering, which will significantly impact the advancement of plant biotechnology.
Extracellular vesicles from a novel chordoma cell line, ARF-8, promote tumorigenic microenvironmental changes when incubated with the parental cells and with human osteoblasts
Authors: Nguyen Khoa N , Graner Arin N , Fringuello Anthony R , Zizzo Zoe , Valenzuela Lorena , Anyanwu Kamara , Lillehei Kevin O , Youssef A Samy , Guzman Samuel , Coughlan Christina , Graner Michael W 
Published: October 2024

ABSTRACTChordomas are rare, generally slow-growing spinal tumors that nonetheless exhibit progressive characteristics over time, leading to malignant phenotypes and high recurrence rates, despite maximal therapeutic interventions. The tumors are notoriously resistant to therapies and are often in locations that make gross total resections difficult. Here, we describe a new chordoma cell line (ARF-8) derived from an extensive clival chordoma that extended back to the cervical spine. From the cultured cell line we characterized the ARF-8 cellular and extracellular vesicle (EV) proteomes, as well as the impacts of ARF-8 EVs on proteomes and secretomes of recipient cells (both ARF-8 and human osteoblasts) in autocrine and paracrine settings. All the characteristics associated with chordomas as cancers – migration and invasion, therapeutic resistance, metastatic potential – can be driven by tumor EVs. Our proteomic analyses suggested roles for transforming growth factor beta (TGFB) and cell-matrix interactions involving the epithelial-to-mesenchymal transition (EMT), and cell/extracellular matrix interactions in cell migration, consistent with a metastatic tumor phenotype. Our results demonstrated that ARF-8 tumor cell migration was dependent on general (arginine-glycine-aspartic acid [RGD]-based) integrin activity, and ARF-8 EVs could promote such migration. ARF-8 EVs also prompted proteomic/secretomic changes in human osteoblast cells, again with indications that cell-cell and cell-extracellular matrix interactions would be activated. Overall, the EVs promoted predicted tumorigenic phenotypes in recipient cells.
Multiple context discrimination in adult rats: sex variability and dynamics of time-dependent generalization of an aversive memory
Authors: Lotz Fernanda Nogueira , Guerra Kétlyn Talise Knak , Crestani Ana Paula , Quillfeldt Jorge Alberto 
Published: October 2024

ABSTRACTMemory generalization can be defined as the transference of conditioned fear responses to novel contexts. It happens in systems consolidation, a time-dependent reduction of discrimination precision due to the rearrangement of brain regions supporting memory retrieval. To better understand the fine temporal structure of this process in different sexes, young adult female and male rats were trained in a contextual fear conditioning task and tested in the conditioning or in three novel contexts either 2, 28 or 45 days later. A set of neutral contexts was selected and graded levels of fear expression compared to the training context was obtained, albeit observed only in males, not females, in a recent memory test - the first of a number of sexual dimorphisms detected. This asymmetry, however, disappeared over time due to partial generalization, with fear converging to similar, higher values, grouped in two levels, in both sexes. In all experiments, females were better discriminators and displayed lower fear responses than males, apparently valuing different sensory modalities. This is the first study to compare fear responses between adult female and male rats retrieving recent or remote memories in multiple neutral contexts, allowing several dimorphic findings.
Separate timescales for spatial and anatomical information processing during action observation
Authors: Waltzing B.M. , McAteer S. , Moreno-Verdú M. , Van Caenegem E.E. , Du Yue , Hardwick R.M. 
Published: October 2024

AbstractIntroductionObserving actions primes us to perform similar movements. Prior work indicates this effect is influenced by factors such as spatial congruence, perspective, and presenting biological/non-biological stimuli. We hypothesized that the influence of these factors would vary depending on the amount of time that participants had to process visual stimuli.MethodExperiment 1 was a reaction time task (n=29) with stimuli varying in spatial congruence (congruent, incongruent, neutral), perspective (first- or third-person) and stimulus type (biological or non-biological). Experiment 2 (n=50) used the same stimuli in a “Forced Response” paradigm, which controlled the time participants had to prepare a response. This allowed us to assess responses as a function of preparation time.ResultsExperiment 1 showed effects of spatial congruence, with longer reaction times and more errors for spatially incongruent stimuli. This effect was greater for biological stimuli. Experiment 2 showed that spatial information was processed faster than anatomical information, inducing incorrect responses at short preparation times for spatially incongruent biological stimuli. There was little-to-no corresponding effect for non-biological stimuli. Both experiments also showed weak-to-no effects of perspective, which appear to have been driven by spatial congruence.DiscussionOur results indicate that spatial information is processed faster than anatomical information during action observation. These data are consistent with the dual visual streams hypothesis, whereby spatial information would be processed rapidly via the dorsal stream, while anatomical processing would occur later via the ventral stream. These data also indicate differences in processing between biological and non-biological stimuli.Public significance statementsThis study provides novel insight into the time-course of information processing, showing that spatial information is processed faster than anatomical information during action observation. The results also challenge the established view that visual perspective is critical to action observation effects, demonstrating that this may instead result from lower-level effects of spatial congruence.
Flux qubit based detector of microwave photons
Authors: Ilinskaya O. A. , Ryzhov A. I. , Shevchenko S. N. 
Published: October 2024

A theory of detection of microwave photons with a flux qubit based detector is presented. We consider a semiclassical approximation with the electromagnetic field being in a coherent state. The flux qubit is considered as a multilevel quantum system (qudit). By solving the Lindblad equation, we describe the time evolution of occupations of the qudit's levels for readout and reset stages of detection. When considering the reset stage, the time evolution is described by multiple avoided-level crossings, thus providing a multilevel Landau-Zener-Stückelberg-Majorana (LZSM) problem. In addition to numerical calculations, we present an approximate solution for the description of the reset stage dynamics based on the adiabatic-impulse approximation and rate equation approach. Our theory may be useful for the theoretical description of driven-dissipative dynamics of qudits, including applications such as single-photon detection.

Published by the American Physical Society
2024
Nuclear suppression of coherent
J/ψ
photoproduction in heavy-ion ultraperipheral collisions and leading twist nuclear shadowing
Authors: Guzey V. , Strikman M. 
Published: October 2024

We determine the nuclear suppression factor SPb(x), where x=MJ/ψ2/Wγp2 with MJ/ψ the J/ψ mass and Wγp the photon-nucleon energy, for the cross section of coherent J/ψ photoproduction in heavy-ion ultraperipheral collisions at the Large Hadron Collider and Relativistic Heavy Ion Collider by performing the χ2 fit to all available data on the cross section dσAA→J/ψAA/dy as a function of the J/ψ rapidity y and the photoproduction cross section σγA→J/ψA(Wγp) as a function of Wγp. We find that while the dσAA→J/ψAA/dy data alone constrain SPb(x) for x≥10−3, the combined dσAA→J/ψAA/dy and σγA→J/ψA(Wγp) data allow us to determine SPb(x) in the wide interval 10−5<x<0.05. In particular, the data favor SPb(x), which decreases with a decrease of x in the 10−4<x<0.01 interval and can be both decreasing or constant for x<10−4. Identifying SPb(x) with the ratio of the gluon distributions in Pb and the proton Rg(x,Q02)=gA(x,Q02)/[Agp(x,Q02)], we demonstrate that the leading twist approximation for nuclear shadowing provides a good description of all the data on dσAA→J/ψAA/dy and σγA→J/ψA(Wγp) as well as on the experimental values for SPb(x) derived from σγA→J/ψA(Wγp). We also show that modern nuclear parton distributions reasonably reproduce SPb(x) as well.

Published by the American Physical Society
2024
EMhub: a web platform for data management and on-the-fly processing in scientific facilities
Authors: de la Rosa-Trevin Jose M. , Sharov Grigory , Fleischmann Stefan , Morado Dustin , Bollinger John C. , Miller Darcie J. , Terry Daniel S. , Blanchard Scott C. , Fernandez Israel S. , Carroni Marta 
Published: October 2024

Most scientific facilities produce large amounts of heterogeneous data at a rapid pace. Managing users, instruments, reports and invoices presents additional challenges. To address these challenges, EMhub, a web platform designed to support the daily operations and record-keeping of a scientific facility, has been introduced. EMhub enables the easy management of user information, instruments, bookings and projects. The application was initially developed to meet the needs of a cryoEM facility, but its functionality and adaptability have proven to be broad enough to be extended to other data-generating centers. The expansion of EMHub is enabled by the modular nature of its core functionalities. The application allows external processes to be connected via a REST API, automating tasks such as folder creation, user and password generation, and the execution of real-time data-processing pipelines. EMhub has been used for several years at the Swedish National CryoEM Facility and has been installed in the CryoEM center at the Structural Biology Department at St. Jude Children's Research Hospital. A fully automated single-particle pipeline has been implemented for on-the-fly data processing and analysis. At St. Jude, the X-Ray Crystallography Center and the Single-Molecule Imaging Center have already expanded the platform to support their operational and data-management workflows.
Roles of cognition demand and advertising literacy in advergames
Authors: Vashisht Devika 
Published: October 2024

PurposeTo determine the impact of advergame specific factors on players’ brand recall and brand attitude by conducting two experimental studies.Design/methodology/approachTwo 2 × 2 × 2 experiments were conducted in this study.FindingsIndividuals with high-cognition-demand reported superior brand recall for an advergame with prominent brand placements and low game-product analogy and a more favorable brand attitude for a prominently placed game with high game-product analogy than the low-cognition-demand individuals. Individuals with high advertising literacy reported higher brand recall but less favorable brand attitude for games with less game-rapidity but high product-involvement than those with low advertising literacy.Practical implicationsThe research outcomes are highly significant for the marketing specialists, as choosing a communication tool that best fits the advertised product with regard to the content of the media is a planning stratagem that has been broadly used by the media designers.Originality/valueThis research mainly adds to the literature of online advertising, exclusively the advergames by probing the impact of game-specific and gamer-specific factors on brand recall and brand attitude. Also, this study supports comprehending the moderating roles of cognitive demand and advertising literacy on players’ cognitive and affective brand responses.
Frozen food purchasing and home freezing of fresh foods: associations with household food waste
Authors: Xu Lei , Li Ran , Roe Brian 
Published: October 2024

PurposeFreezing extends the shelf life of food. Home freezing of fresh foods and the purchase of frozen foods have been advocated as approaches to reduce food waste in US households. This paper discusses how commonly US households apply these practices, quantifies frozen food waste and relates these practices to food waste.Design/methodology/approachWe add questions to the summer 2022 wave of the US Household Food Waste Tracking Survey. The novel survey data provide important baseline information and household behaviours, such as food waste, home freezing of fresh food and the purchase of frozen foods. We analyse the association among these behaviours from more than 1,000 US households.FindingsWe find that US household wastes about 26 g per person per week of food that was once frozen, which is about 6% of all household food waste. The finding indicates that a small portion of food waste in US households comes from frozen food. Vegetables and meats are the most commonly discarded frozen foods. Among the frozen items reported as discarded, about 30% were purchased as frozen rather than purchased fresh and then frozen at home by the consumer and about 30% more were reported as discarded from the refrigerator rather than directly from the freezer. The findings are important for informing strategies to reduce household food waste.Research limitations/implicationsWhile the data provide important baseline information and correlate the use of freezing with lower waste levels, more work is needed to understand if interventions encouraging frozen food purchase or home freezing would reduce household food waste.Originality/valueWe provide unique, detailed information about the quantity of frozen food waste in US households and the relationships between consumer food waste and the practices of frozen food purchasing and home freezing.
To take a stand or not: effects of company-issue fit and perceived motivations for CSA on consumer response
Authors: Kim Seoyeon , Austin Lucinda L. , Gaither Barbara Miller 
Published: October 2024

PurposeThis study examined how consumer response to corporations that take a stand (or not) on social/political issues – varied by “fit” between the company and the advocated issue – was mediated by perceptions of the motives for the advocacy.Design/methodology/approachA 2 (corporate stand: stand v. no stand) × 2 (company-issue fit: high v. low) experiment was conducted with a nationally representative sample of 1,204 U.S. adult consumers.FindingsThe study found that the effect of corporate stand taking on perceived corporate hypocrisy was moderated by company-issue fit. Also, companies were viewed as more hypocritical when taking a stand on an issue that was less relevant to the company’s business, despite the CSA being seen as being values-driven.Originality/valueThe study provides guidelines for companies to determine when and whether to take a stand on a CSA issue. Particularly, the results suggest that values promotion is not the sole determinant of successful CSA and that company-issue fit should be taken into account for a more comprehensive assessment of the given CSA.