bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
Authors: Scaramuzza Shaun , Jones Rebecca M. , Sadurni Martina Muste , Reynolds-Winczura Alicja , Poovathumkadavil Divyasree , Farrell Abigail , Natsume Toyoaki , Rojas Patricia , Cuesta Cyntia Fernandez , Kanemaki Masato T. , Saponaro Marco , Gambus Agnieszka 
Published: August 2023

AbstractCell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin ligase has been shown to play a role in various cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability, and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells and to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We conclude that upon rapid TRAIP degradation, specifically in S-phase, cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. Our findings reveal that TRAIP works in S-phase to prevent DNA damage at transcription start sites, caused by replication-transcription conflicts.
Crystal structure and functional implications of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases
Authors: Yang Chia-Shin , Ko Tzu-Ping , Chen Chao-Jung , Hou Mei-Hui , Wang Yu-Chuan , Chen Yeh 
Published: August 2023

AbstractPurine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states. A conserved (R/Q)xW motif controlling the pyrimidine specificity of donor nucleotide is identified. Mutation of Trp or Arg from the (R/Q)xW motif to Ala rewires its specificity to purine nucleotides, producing mixed purine-pyrimidine cyclic dinucleotides (CDNs). Preferential binding of uracil over cytosine bases explains the product specificity of cyclic di-pyrimidine-synthesizing CdnE to cyclic di-UMP (cUU). Based on the intermediate-bound structures, a synthetic pathway for cUU containing a unique 2’3’-phosphodiester linkage through intermediate pppU[3’−5’]pU is deduced. Our results provide a framework for pyrimidine selection and establish the importance of conserved residues at the C-terminal loop for the specificity determination of CD-NTases.
Redox driven B12-ligand switch drives CarH photoresponse
Authors: Poddar Harshwardhan , Rios-Santacruz Ronald , Heyes Derren J. , Shanmugam Muralidharan , Brookfield Adam , Johannissen Linus O. , Levy Colin W. , Jeffreys Laura N. , Zhang Shaowei , Sakuma Michiyo , Colletier Jacques-Philippe , Hay Sam , Schirò Giorgio , Weik Martin , Scrutton Nigel S. , Leys David 
Published: August 2023

AbstractCarH is a coenzyme B12-dependent photoreceptor involved in regulating carotenoid biosynthesis. How light-triggered cleavage of the B12 Co-C bond culminates in CarH tetramer dissociation to initiate transcription remains unclear. Here, a series of crystal structures of the CarH B12-binding domain after illumination suggest formation of unforeseen intermediate states prior to tetramer dissociation. Unexpectedly, in the absence of oxygen, Co-C bond cleavage is followed by reorientation of the corrin ring and a switch from a lower to upper histidine-Co ligation, corresponding to a pentacoordinate state. Under aerobic conditions, rapid flash-cooling of crystals prior to deterioration upon illumination confirm a similar B12-ligand switch occurs. Removal of the upper His-ligating residue prevents monomer formation upon illumination. Combined with detailed solution spectroscopy and computational studies, these data demonstrate the CarH photoresponse integrates B12 photo- and redox-chemistry to drive large-scale conformational changes through stepwise Co-ligation changes.
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis
Authors: Tang Zihan , Xu Yanyan , Tan Yun , Shi Hui , Jin Peipei , Li Yunqi , Teng Jialin , Liu Honglei , Pan Haoyu , Hu Qiongyi , Cheng Xiaobing , Ye Junna , Su Yutong , Sun Yue , Meng Jianfen , Zhou Zhuochao , Chi Huihui , Wang Xuefeng , Liu Junling , Lu Yong , Liu Feng , Dai Jing , Yang Chengde , Chen Saijuan , Liu Tingting 
Published: August 2023

AbstractAberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.
NFIB facilitates replication licensing by acting as a genome organizer
Authors: Zhang Wenting , Wang Yue , Liu Yongjie , Liu Cuifang , Wang Yizhou , He Lin , Cheng Xiao , Peng Yani , Xia Lu , Wu Xiaodi , Wu Jiajing , Zhang Yu , Sun Luyang , Chen Ping , Li Guohong , Tu Qiang , Liang Jing , Shang Yongfeng 
Published: August 2023

AbstractThe chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.
At-home wearables and machine learning sensitively capture disease progression in amyotrophic lateral sclerosis
Authors: Gupta Anoopum S. , Patel Siddharth , Premasiri Alan , Vieira Fernando 
Published: August 2023

AbstractAmyotrophic lateral sclerosis causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment in motor function. Promising drug development efforts have accelerated in amyotrophic lateral sclerosis, but are constrained by a lack of objective, sensitive, and accessible outcome measures. Here we investigate the use of wearable sensors, worn on four limbs at home during natural behavior, to quantify motor function and disease progression in 376 individuals with amyotrophic lateral sclerosis. We use an analysis approach that automatically detects and characterizes submovements from passively collected accelerometer data and produces a machine-learned severity score for each limb that is independent of clinical ratings. We show that this approach produces scores that progress faster than the gold standard Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (−0.86 ± 0.70 SD/year versus −0.73 ± 0.74 SD/year), resulting in smaller clinical trial sample size estimates (N = 76 versusN = 121). This method offers an ecologically valid and scalable measure for potential use in amyotrophic lateral sclerosis trials and clinical care.
Heat is associated with short-term increases in household food insecurity in 150 countries and this is mediated by income
Authors: Kroeger Carolin 
Published: August 2023

AbstractRising temperatures are expected to stall progress on food insecurity by reducing agricultural yields in the coming decades. But hot periods may also increase food insecurity within days when it gets too hot to work and earn an income, thus limiting households’ capability to purchase food. Here I exploit variations in heat levels during a household survey spanning 150 countries in a quasi-natural experiment to show that particularly hot weeks are associated with higher chances of food insecurity among households (0.5767, 95% confidence interval 0.2958–0.8576, t = 4.024, d.f. = 427,816, P < 0.001). This association is mediated by reductions in income and health for households and the effects are stronger in countries with lower incomes and more agricultural or precarious forms of employment. The results highlight the importance of labour market disruptions for food insecurity and suggest integration of these concerns into heat action plans and food programmes.
Postacute sequelae of COVID-19 at 2 years
Authors: Bowe Benjamin , Xie Yan , Al-Aly Ziyad 
Published: August 2023

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively. Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6–89.6) and 642.8 (95% CI: 596.9–689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9–31.0%) and 21.3% (18.2–24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year. In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection.
DUO-GAIT: A gait dataset for walking under dual-task and fatigue conditions with inertial measurement units
Authors: Zhou Lin , Fischer Eric , Brahms Clemens Markus , Granacher Urs , Arnrich Bert 
Published: August 2023

AbstractIn recent years, there has been a growing interest in developing and evaluating gait analysis algorithms based on inertial measurement unit (IMU) data, which has important implications, including sports, assessment of diseases, and rehabilitation. Multi-tasking and physical fatigue are two relevant aspects of daily life gait monitoring, but there is a lack of publicly available datasets to support the development and testing of methods using a mobile IMU setup. We present a dataset consisting of 6-minute walks under single- (only walking) and dual-task (walking while performing a cognitive task) conditions in unfatigued and fatigued states from sixteen healthy adults. Especially, nine IMUs were placed on the head, chest, lower back, wrists, legs, and feet to record under each of the above-mentioned conditions. The dataset also includes a rich set of spatio-temporal gait parameters that capture the aspects of pace, symmetry, and variability, as well as additional study-related information to support further analysis. This dataset can serve as a foundation for future research on gait monitoring in free-living environments.
Body mass trajectory from diagnosis to the end of treatment in a pediatric acute lymphoblastic leukemia cohort
Authors: Galati Paula Cristina , Rocha Priscilla Roberta Silva , Gruezo Nádia Dias , Amato Angélica Amorim 
Published: August 2023

AbstractThe advances in pediatric acute lymphoblastic leukemia (ALL) care have substantially increased survival, and the late effects of treatment are a growing concern. Obesity development is frequent following ALL therapy and may significantly contribute to long-term morbidity and mortality. We examined the body mass trajectory of 208 children with ALL, from the diagnosis to the completion of therapy. We found that 7.2% of children were overweight or obese at diagnosis, which increased to 19.7% at the end of induction therapy and 20.8% after completion of treatment. In a multivariable linear regression model, age at ALL diagnosis, the type of chemotherapy regimen, and body mass index (BMI) z-score at diagnosis were significant predictors of BMI z-score after induction therapy, whereas BMI z-score at diagnosis was the only significant predictor of BMI z-score at the completion of treatment. In a subgroup of 120 children, we found no association between nutrition status at diagnosis and the risk of ALL relapse or poorer overall survival. Our findings indicate that weight gain occurs early during ALL therapy and is predicted by weight status at diagnosis. Therefore, nutritional status should be assessed throughout treatment, and weight management interventions should be considered early, particularly for patients with higher weight at diagnosis.
Modeling abundance and risk impact of Vespa velutina nigrithorax (Hymenoptera: Vespidae) in Korea: application of a species abundance model
Authors: Kim Min-Jung , Bak Seongbin , Jung Chuleui 
Published: August 2023

AbstractThe Asian yellow-legged hornet, Vespa velutina nigrithorax, is native to Southeast Asia. However, it has invaded many countries in temperate regions, causing serious threats to honeybees and human health. With a growing demand for estimating the potential distribution of this species, multiple studies have resorted to occurrence-based models. However, they are less informative for predicting local abundance patterns associated with the species’ impact. Thus, we aimed to develop an abundance-based distribution model for V. v. nigrithorax in Korea to support the forecast of its impact and associated management strategies. The abundance data of V. v. nigrithorax were collected from 254 sites for 4 years covering the country and used to develop a model with bioclimatic and land composition variables. Along with the abundance model, the classical occurrence model was tested to determine whether it could provide a reasonable prediction on the estimation of local abundance. As a result, the abundance model provided higher discriminative power and accuracy than the occurrence model to evaluate the impacts caused by V. v. nigrithorax. On the other hand, the occurrence model was not able to discriminate abundance in the areas occupied by V. v. nigrithorax, indicating an unclear occurrence-abundance relationship or oversimplification of the estimated niche created by the occurrence model. Based on the final abundance model, risk indices for human health and honeybee losses were suggested. These results could help to provide support for risk management of V. v. nigrithorax in Korea and to give biological information to other countries where this species has already become established or which it is likely to invade in the near future.
Effect of the isotiazole adjuvants in combination with cisplatin in chemotherapy of neuroepithelial tumors: experimental results and modeling
Authors: Potkin Vladimir , Pushkarchuk Aliaxandr , Zamaro Alexandra , Zhou Hongwei , Kilin Sergey , Petkevich Sergey , Kolesnik Irina , Michels Dominik L. , Lyakhov Dmitry A. , Kulchitsky Vladimir A. 
Published: August 2023

AbstractChemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for the selection of the optimal agent. Here we examine the system drug-adjuvant to explain the observed effect in practice. We used the first line drug cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of the cisplatin-adjuvant system was carried out by quantum chemical modeling using DFT. It turned out that adjuvants form conjugates with cisplatin that lead to the relocation of frontier molecular orbitals as well as increase of conjugate’s dipole moment. It resulted in change of the interaction character with DNA and increase of the bioactivity of the system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use “classical” chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such a treatment because of pronounced toxic side effects.
Stabilization and racetrack application of asymmetric Néel skyrmions in hybrid nanostructures
Authors: Zelent Mateusz , Moalic Mathieu , Mruczkiewicz Michal , Li Xiaoguang , Zhou Yan , Krawczyk Maciej 
Published: August 2023

AbstractMagnetic skyrmions, topological quasiparticles, are small stable magnetic textures that possess intriguing properties and potential for data storage applications. Hybrid nanostructures comprised of skyrmions and soft magnetic material can offer additional advantages for developing skyrmion-based spintronic and magnonic devices. We show that a Néel-type skyrmion confined within a nanodot placed on top of a ferromagnetic in-plane magnetized stripe produces a unique and compelling platform for exploring the mutual coupling between magnetization textures. The skyrmion induces an imprint upon the stripe, which, in turn, asymmetrically squeezes the skyrmion in the dot, increasing their size and the range of skyrmion stability at small values of Dzyaloshinskii–Moriya interaction, as well as introducing skyrmion bi-stability. Finally, by exploiting the properties of the skyrmion in a hybrid system, we demonstrate unlimited skyrmion transport along a racetrack, free of the skyrmion Hall effect.
Supply chain management with uncertainty in consumer perception of product greenness under an eco-label policy
Authors: Gao Jingzhe , Wei Haixiao 
Published: August 2023

AbstractThe urgency of environmental preservation necessitates green manufacturing and supply chain advancements. This research examines a green supply chain problem influenced by eco-label policies, focusing on two prevalent market eco-label types. One allows the manufacturer to determine product greenness, while the other requires compliance with standards set by a non-governmental organization (NGO). We also explore the variability in consumer comprehension of eco-label implications and purchasing behaviors with different eco-labeled products. Through consumer utility and manufacturer profit models, we discover that the manufacturer's production and pricing choices significantly impact consumer behavior. Increased investigation costs may enhance consumer utility through improved product greenness, potentially boosting manufacturer profit via price hikes. However, if investigation costs are minimal, the NGO-label may be rejected due to decreased utility and profit. These insights could help direct supply chains by providing a theoretical foundation for green production decisions and future eco-label policies, whether determined by an NGO or the manufacturer.
A content analysis of YouTube videos on tinnitus in South Korea
Authors: Seo Hee Won , Ha Jung Woo , Kwak Jin Hye , Kim Moo Keon , Byun Hayoung , Lee Seung Hwan , Chung Jae Ho 
Published: August 2023

AbstractMore people use the internet for medical information, especially YouTube. Nevertheless, no study has been conducted to analyze the quality of YouTube videos about tinnitus in Korea. This study aims to review the contents and quality of YouTube videos on tinnitus. The top 100 Korean YouTube videos on tinnitus were reviewed by a tinnitus expert. This study assessed video details: title, creator, length, and popularity indicators—subscribers, views, and likes. The contents of the video clips were analyzed to determine the relevance, understandability, actionability, and quality of information. Out of 100 tinnitus videos, 27 were created by otolaryngologists, 25 by traditional Korean medicine doctors, 25 by other medical professionals, and 3 by lay persons. Sensorineural tinnitus was frequently dealt, and hearing loss, stress, and noise were introduced as main causes of tinnitus. Otolaryngologists' videos covered verified treatments, but others suggested unproven therapies including herbal medicine or acupressure. Otolaryngologists' videos showed significantly higher understandability and quality of information compared to others (p < 0.001). This study found that tinnitus YouTube videos frequently present low-quality and incorrect material, which could have an adverse effect on patients. Results highlight the need for tinnitus specialists to provide accurate information.
Site-specific phosphorylations of the Arf activator GBF1 differentially regulate GBF1 function in Golgi homeostasis and secretion versus cytokinesis
Authors: Walton Kendall , Nawara Tomasz J. , Angermeier Allyson R. , Rosengrant Hadley , Lee Eunjoo , Wynn Bridge , Victorova Ekaterina , Belov George , Sztul Elizabeth 
Published: August 2023

AbstractDiverse cellular processes, including membrane traffic, lipid homeostasis, cytokinesis, mitochondrial positioning, and cell motility are critically dependent on the Sec7 domain guanine nucleotide exchange factor GBF1. Yet, how the participation of GBF1 in a particular cellular function is regulated is unknown. Here, we show that the phosphorylation of specific highly conserved serine and tyrosine residues within the N-terminal domain of GBF1 differentially regulates its function in maintaining Golgi homeostasis and facilitating secretion versus its role in cytokinesis. Specifically, GBF1 mutants containing single amino acid substitutions that mimic a stably phosphorylated S233, S371, Y377, and Y515 or the S233A mutant that can’t be phosphorylated are fully able to maintain Golgi architecture and support cargo traffic through the secretory pathway when assessed in multiple functional assays. However, the same mutants cause multi-nucleation when expressed in cells, and appear to inhibit the progression through mitosis and the resolution of cytokinetic bridges. Thus, GBF1 participates in distinct interactive networks when mediating Golgi homeostasis and secretion versus facilitating cytokinesis, and GBF1 integration into such networks is differentially regulated by the phosphorylation of specific GBF1 residues.