bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II
Authors: Steurer Barbara , Janssens Roel C. , Geijer Marit E. , Aprile-Garcia Fernando , Geverts Bart , Theil Arjan F. , Hummel Barbara , van Royen Martin E. , Evers Bastiaan , Bernards René , Houtsmuller Adriaan B. , Sawarkar Ritwick , Marteijn Jurgen 
Published: June 2022

AbstractThe precise regulation of RNA Polymerase II (Pol II) transcription after genotoxic stress is crucial for proper execution of the DNA damage-induced stress response. While stalling of Pol II on transcription-blocking lesions (TBLs) blocks transcript elongation and initiates DNA repair in cis, TBLs additionally elicit a response in trans that regulates transcription genome-wide. Here we uncover that, after an initial elongation block in cis, TBLs trigger the genome-wide VCP-mediated proteasomal degradation of promoter-bound, P-Ser5-modified Pol II in trans. This degradation is mechanistically distinct from processing of TBL-stalled Pol II, is signaled via GSK3, and contributes to the TBL-induced transcription block, even in transcription-coupled repair-deficient cells. Thus, our data reveal the targeted degradation of promoter-bound Pol II as a critical pathway that allows cells to cope with DNA damage-induced transcription stress and enables the genome-wide adaptation of transcription to genotoxic stress.
Toggle-like current-induced Bloch point dynamics of 3D skyrmion strings in a room temperature nanowire
Authors: Birch M. T. , Cortés-Ortuño D. , Litzius K. , Wintz S. , Schulz F. , Weigand M. , Štefančič A. , Mayoh D. A. , Balakrishnan G. , Hatton P. D. , Schütz G. 
Published: June 2022

AbstractResearch into practical applications of magnetic skyrmions, nanoscale solitons with interesting topological and transport properties, has traditionally focused on two dimensional (2D) thin-film systems. However, the recent observation of novel three dimensional (3D) skyrmion-like structures, such as hopfions, skyrmion strings (SkS), skyrmion bundles, and skyrmion braids, motivates the investigation of new designs, aiming to exploit the third spatial dimension for more compact and higher performance spintronic devices in 3D or curvilinear geometries. A crucial requirement of such device schemes is the control of the 3D magnetic structures via charge or spin currents, which has yet to be experimentally observed. In this work, we utilise real-space imaging to investigate the dynamics of a 3D SkS within a nanowire of Co8Zn9Mn3 at room temperature. Utilising single current pulses, we demonstrate current-induced nucleation of a single SkS, and a toggle-like positional switching of an individual Bloch point at the end of a SkS. The observations highlight the possibility to locally manipulate 3D topological spin textures, opening up a range of design concepts for future 3D spintronic devices.
Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
Authors: Comba Andrea , Faisal Syed M. , Dunn Patrick J. , Argento Anna E. , Hollon Todd C. , Al-Holou Wajd N. , Varela Maria Luisa , Zamler Daniel B. , Quass Gunnar L. , Apostolides Pierre F. , Abel Clifford , Brown Christine E. , Kish Phillip E. , Kahana Alon , Kleer Celina G. , Motsch Sebastien , Castro Maria G. , Lowenstein Pedro R. 
Published: June 2022

AbstractIntra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment.
Cross-cutting scenarios and strategies for designing decarbonization pathways in the transport sector toward carbon neutrality
Authors: Zhang Runsen , Hanaoka Tatsuya 
Published: June 2022

AbstractThe transport sector will play a pivotal role in achieving China’s carbon neutrality goal by 2060. This study develops a regional transport-energy integrated model to analyze the long-term pathways and strategies toward the carbon-neutral ground transport sector in China. A set of scenarios are created to identify the effectiveness and feasibility of low-carbon policy measures based on the well-known transport strategies within the Avoid–Shift–Improve framework. Our simulations shed light on synergistic coupling and trade-offs among different strategies and instruments for prescribing a desirable mix of policy measures that maximize the synergies and minimize the trade-offs. Here, we show that a region-specific policy package designed from a balanced perspective under the Avoid–Shift–Improve framework has the potential to realize a deep decarbonization in the transport sector and will greatly assist in achieving China’s carbon neutrality by 2060.
Coordination of metal center biogenesis in human cytochrome c oxidase
Authors: Nývltová Eva , Dietz Jonathan V. , Seravalli Javier , Khalimonchuk Oleh , Barrientos Antoni 
Published: June 2022

AbstractMitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the CuA and CuB sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates.
Seasonal influenza vaccination expands hemagglutinin-specific antibody breadth to older and future A/H3N2 viruses
Authors: Ertesvåg Nina Urke , Cox Rebecca Jane , Lartey Sarah Larteley , Mohn Kristin G-I , Brokstad Karl Albert , Trieu Mai-Chi 
Published: June 2022

AbstractHistory of influenza A/H3N2 exposure, especially childhood infection, shape antibody responses after influenza vaccination and infection, but have not been extensively studied. We investigated the breadth and durability of influenza A/H3N2-specific hemagglutinin-inhibition antibodies after live-attenuated influenza vaccine in children (aged 3-17 years, n = 42), and after inactivated influenza vaccine or infection in adults (aged 22-61 years, n = 42) using 14 antigenically distinct A/H3N2 viruses circulating from 1968 to 2018. We found that vaccination and infection elicited cross-reactive antibody responses, predominantly directed against newer or future strains. Childhood H3-priming increased the breadth and magnitude of back-boosted A/H3N2-specific antibodies in adults. Broader and more durable A/H3N2-specific antibodies were observed in repeatedly vaccinated adults than in children and previously unvaccinated adults. Our findings suggest that early A/H3N2 exposure and frequent seasonal vaccination could increase the breadth and seropositivity of antibody responses, which may improve vaccine protection against future viruses.
A potent estrogen receptor and microtubule specific purine-benzothiazole-based fluorescent molecular probe induces apoptotic death of breast cancer cells
Authors: Barman Surajit , Ghosh Subhajit , Roy Rajsekhar , Gupta Varsha , Ghosh Satyajit , Ghosh Surajit 
Published: June 2022

AbstractBreast cancer is the most common malignancy in women and is a heterogeneous disease at molecular level. Early detection and specificity are the key prerequisite for the treatment of this deadly cancer. To address these issues attention on the breast cancer specific receptor protein(s) is the most realistic option. Herein estrogen (E) and progesterone (Pg) receptors(R) were considered to design fluorescent molecular probes with possible therapeutic option. We adopted QSAR technique to design a library of benzothiazole-purine hybrid molecules. Molecular docking offers us three screened molecules as most potential. Among these molecules one abbreviated as “CPIB” showed blue fluorescence and detected ER positive cancer cells at 1 nM concentration. At elevated concentration, CPIB induces apoptotic deaths of same cancer cells through targeting intracellular microtubules without affecting normal cells or ER negative cells. CPIB is one of its kind with two-in-one potential of “Detection and Destroy” ability targeting ER positive breast cancer cells.
Prediction of difficulty in direct laryngoscopy
Authors: Kharrat Ines , Achour Imen , Trabelsi Jihene Jdidi , Trigui Majdi , Thabet Wadii , Mnejja Malek , Hammami Bouthaina , Chakroun Amine , Charfeddine Ilhem 
Published: June 2022

AbstractTo establish easily measurable and reproducible preoperative parameters predicting difficult laryngeal exposure in direct laryngoscopy. A prospective study including 71 patients who underwent transoral microsurgery for benign or malignant lesions of the larynx was performed in our department from January 2021 to November 2021. Physical assessment included the Mallampati score, weight, height, body mass index and measurements of seven parameters in the cervical region. Eleven parameters were measured on the cervical radiography film. Among our patients, 19 were included in the difficult laryngeal exposure (DLE) group. High Mallampati and Cormack scores were significantly associated with DLE (p = 0.005 and p < 0.0001). Limited mouth opening, direct thyromental distance (DTMD) < 67 mm in neutral position, DTMD < 82 mm and sternomental distance < 157 mm at full head extension were statistically related to DLE. For radiological assessment, the effective length of the maxilla and the atlanto-occipital distance were related to DLE. Using stepwise logistic regression, only the effective length of the maxilla and atlanto-occipital distance were selected as independent predictors for DLE (p: 0.015 and 0.001). Preoperative prediction of DLE is useful for both surgeons and patients. The length of the maxilla and the atlanto-occipital distance were found to be independent risk factors for DLE. This highlights the effect of overgrowth of the maxilla, protrusion of the upper teeth and limited extension of the cervical spine as the major risk factors for difficult laryngeal exposure.
Disentangling the critical signatures of neural activity
Authors: Mariani Benedetta , Nicoletti Giorgio , Bisio Marta , Maschietto Marta , Vassanelli Stefano , Suweis Samir 
Published: June 2022

AbstractThe critical brain hypothesis has emerged as an attractive framework to understand neuronal activity, but it is still widely debated. In this work, we analyze data from a multi-electrodes array in the rat’s cortex and we find that power-law neuronal avalanches satisfying the crackling-noise relation coexist with spatial correlations that display typical features of critical systems. In order to shed a light on the underlying mechanisms at the origin of these signatures of criticality, we introduce a paradigmatic framework with a common stochastic modulation and pairwise linear interactions inferred from our data. We show that in such models power-law avalanches that satisfy the crackling-noise relation emerge as a consequence of the extrinsic modulation, whereas scale-free correlations are solely determined by internal interactions. Moreover, this disentangling is fully captured by the mutual information in the system. Finally, we show that analogous power-law avalanches are found in more realistic models of neural activity as well, suggesting that extrinsic modulation might be a broad mechanism for their generation.
Bio-acceptability of wearable sensors: a mechanistic study towards evaluating ionic leaching induced cellular inflammation
Authors: Bhushan Pulak , Kamat Vivek , Abrol Ishita , Kaushik Ajeet , Bhansali Shekhar 
Published: June 2022

AbstractThe recent need for remote health wellness monitoring has led to the extensive use of wearable sensors. Owing to their increased use, these sensors are required to exhibit both functionality and safety to the user. A major component in the fabrication of these sensors and their associated circuitry is the use of metallic/organic conductive inks. However, very less is known about the interfacial and molecular interactions of these inks with biological matter as they can result in an inflammatory reaction to the user. Significant efforts are thus needed to explore and improve the bio-acceptability of such conductive ink-based wearable sensors. The present study investigates the biocompatibility of encapsulated and non-encapsulated wearable electrochemical sensors used for sensing uric acid as a biomarker for wound healing fabricated using screen-printing technique. Ionic release of metallic ions was investigated first to understand the susceptibility of the conductive inks towards ionic leaching when in contact with a fluid. Time-lapse investigation using ICPS (inductive couple plasma spectroscopy) shows a high concentration (607.31 ppb) of leached silver (Ag+) ions from the non-encapsulated sensors. The cell viability data suggests a 2.5-fold improvement in the sensor biocompatibility for an encapsulated sensor. While the carbon ink shows negligible effect on cell viability, the silver ink elicits significant decrease (< 50%) in cell viability at concentrations higher than 2 mg ml-1. The toxicity pathway of these sensors was further determined to be through the generation of reactive oxygen species resulting in over 20% apoptotic cell death. Our results show that the lower biocompatibility of the non-encapsulated sensor attributes to the higher leaching of Ag+ ions from the printed inks which elicits several different inflammatory pathways. This work highlights the importance biocompatibility evaluation of the material used in sensor fabrication to develop safe and sustainable sensors for long-term applications.
A comparative genomic analysis of lichen-forming fungi reveals new insights into fungal lifestyles
Authors: Song Hyeunjeong , Kim Ki-Tae , Park Sook-Young , Lee Gir-Won , Choi Jaeyoung , Jeon Jongbum , Cheong Kyeongchae , Choi Gobong , Hur Jae-Seoun , Lee Yong-Hwan 
Published: June 2022

AbstractLichen-forming fungi are mutualistic symbionts of green algae or cyanobacteria. We report the comparative analysis of six genomes of lichen-forming fungi in classes Eurotiomycetes and Lecanoromycetes to identify genomic information related to their symbiotic lifestyle. The lichen-forming fungi exhibited genome reduction via the loss of dispensable genes encoding plant-cell-wall-degrading enzymes, sugar transporters, and transcription factors. The loss of these genes reflects the symbiotic biology of lichens, such as the absence of pectin in the algal cell wall and obtaining specific sugars from photosynthetic partners. The lichens also gained many lineage- and species-specific genes, including those encoding small secreted proteins. These genes are primarily induced during the early stage of lichen symbiosis, indicating their significant roles in the establishment of lichen symbiosis.Our findings provide comprehensive genomic information for six lichen-forming fungi and novel insights into lichen biology and the evolution of symbiosis.
The network nature of language endangerment hotspots
Authors: Lee Nala H. , Siew Cynthia S. Q. , Ng Nadine H. N. 
Published: June 2022

AbstractLanguage endangerment is one of the most urgent issues of the twenty-first century. Languages are disappearing at unprecedented rates, with dire consequences that affect speaker communities, scientific community and humanity. There is impetus for understanding the nature of language endangerment, and we investigate where language endangerment occurs by performing network analysis on 3423 languages at various levels of risk. Macro-level analysis shows evidence of positive assortative mixing of endangerment statuses—critically endangered languages are surrounded by similarly endangered languages, indicating the prevalence of linguistic hotspots throughout the world. Meso-level analysis using community detection returned 13 communities experiencing different levels of threat. Micro-level analysis of closeness centrality shows that more geographically isolated languages tend to be more critically endangered. Even after accounting for the statistical contributions of linguistic diversity, the structural properties of the spatial network were still significantly associated with endangerment outcomes. Findings support that the notion of hotspots is useful when accounting for language endangerment but go beyond that to establish that quantifying spatial structure is crucial. Language preservation in these hotspots and understanding why endangered languages pattern the way they do in their environments becomes more vital than ever.
Trends in maintenance status and usability of public automated external defibrillators during a 5-year on-site inspection
Authors: Kim Tae Youn , Jung Yun-kyoung , Yoon Sun Hwa , Kim Sun Ju , Cha Kyoung-chul , Jung Woo Jin , Roh Young Il , Kim Soyeong , Kim Sung Hwa , Kang Dae Ryong , Hwang Sung Oh 
Published: June 2022

AbstractThis study aimed to assess the trend of the maintenance status and usability of public automated external defibrillators (AEDs). Public AEDs installed in Seoul from 2013 to 2017 were included. An inspector checked the maintenance status and usability of the AEDs annually using a checklist. During the study period, 23,619 AEDs were inspected. Access to the AEDs was improved, including the absence of obstacles near the AEDs (from 90.2% in 2013 to 99.1% in 2017, p < 0.0001) and increased AED signs (from 34.3% in 2013 to 91.3% in 2017, p < 0.0001). The rate of AEDs in normal operation (from 94.0% in 2013 to 97.6% in 2017, p < 0.0001), good battery status (from 95.6% in 2013 to 96.8% in 2017, p = 0.0016), and electrode availability increased (from 97.1% in 2013 to 99.0% in 2017, p < 0.0001); the rate of electrode validity decreased (from 90.0% in 2013 to 87.2% in 2017, p < 0.0001). The overall rate of the non-ready-to-use AEDs and AEDs with less than 24-h usability accounted for 15.4% and 44.1% of the total number of AEDs, respectively. Although most AEDs had a relatively good maintenance status, a significant proportion of public AEDs were not available for 24-h use. Invalid electrodes and less than 24-h accessibility were the main reasons that limited the 24-h usability of public AEDs.
A phase-field model by an Ising machine and its application to the phase-separation structure of a diblock polymer
Authors: Endo Katsuhiro , Matsuda Yoshiki , Tanaka Shu , Muramatsu Mayu 
Published: June 2022

AbstractA novel model to be applied to next-generation accelerators, Ising machines, is formulated on the basis of the phase-field model of the phase-separation structure of a diblock polymer. Recently, Ising machines including quantum annealing machines, attract overwhelming attention as a technology that opens up future possibilities. On the other hand, the phase-field model has demonstrated its high performance in material development, though it takes a long time to achieve equilibrium. Although the convergence time problem might be solved by the next-generation accelerators, no solution has been proposed. In this study, we show the calculation of the phase-separation structure of a diblock polymer as the equilibrium state using phase-field model by an actual Ising machine. The proposed new model brings remarkable acceleration in obtaining the phase-separation structure. Our model can be solved on a large-scale quantum annealing machine. The significant acceleration of the phase-field simulation by the quantum technique pushes the material development to the next stage.
In-frame editing of transcription factor gene RDD1 to suppress miR166 recognition influences nutrient uptake, photosynthesis, and grain quality in rice
Authors: Iwamoto Masao 
Published: June 2022

AbstractThe transcription factor-encoding gene RDD1 increases the uptake of nutrient ions, photosynthetic activity under ambient and high CO2 conditions, and grain productivity, and microRNA166 (miR166) regulates its transcript levels. This study found that CRISPR/Cas9 genome editing of rice plants to inhibit miR166–RDD1 transcript pairing (R1-Cas plants) increased RDD1 transcript levels, NH4+ and PO43− uptake, and photosynthetic activity under high CO2 conditions in rice. However, the panicle weight of the R1-Cas plants decreased compared with the wild-type (WT) plants. Adversely, changes in environmental conditions, such as high CO2 or high temperatures, showed insignificant differences in the panicle weight between the WT and R1-Cas plants despite a largely increased panicle weight observed in the transgenic RDD1-overexpressing plants. Moreover, both the R1-Cas and transgenic RDD1-overexpressing plants that were matured in a growth chamber demonstrated an improved grain appearance quality or a decrease in the number of chalky grains compared with the WT plants. These results suggest that the in-frame mutagenesis of RDD1 to suppress miR166–RDD1 transcript pairing contributes to the improved grain appearance of rice.
Magnetic dynamics of ferromagnetic long range order in icosahedral quasicrystal
Authors: Watanabe Shinji 
Published: June 2022

AbstractQuasicrystals lack translational symmetry and have unique lattice structures with rotational symmetry forbidden in periodic crystals. The electric state and physical property are far from complete understanding, which are the frontiers of modern matter physics. Recent discovery of the ferromagnetic long-range order in the rare-earth based icosahedral quasicrystal has made the breakthrough. Here, we first reveal the dynamical as well as static magnetic structure in the ferromagnetic long-range order in the terbium-based quasicrystal. The dynamical structure factor exhibits highly structured energy and wavenumber dependences beyond the crystalline-electric-field excitation. We find the presence of the magnetic excitation mode analog to magnon with unique hierarchical structure as well as the localized magnetic excitation with high degeneracy in the quasicrystal. Non-collinear and non-coplanar magnetic structure on the icosahedron is discovered to give rise to non-reciprocal magnetic excitation in the quasicrystal as well as non-reciprocal magnon in the periodic cubic 1/1 approximant. These findings afford illuminating insight into the magnetic dynamics in the broad range of the rare-earth-based quasicrystals and approximants.