bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1
Authors: Zhang Yue , Soubias Olivier , Pant Shashank , Heinrich Frank , Vogel Alexander , Li Jess , Li Yifei , Clifton Luke A. , Daum Sebastian , Bacia Kirsten , Huster Daniel , Randazzo Paul A. , Lösche Mathias , Tajkhorshid Emad , Byrd R. Andrew 
Published: November 2023

AbstractADP-ribosylation factor 1 (Arf1) interacts with multiple cellular partners and membranes to regulate intracellular traffic, organelle structure and actin dynamics. Defining the dynamic conformational landscape of Arf1 in its active form, when bound to the membrane, is of high functional relevance and key to understanding how Arf1 can alter diverse cellular processes. Through concerted application of nuclear magnetic resonance (NMR), neutron reflectometry (NR) and molecular dynamics (MD) simulations, we show that, while Arf1 is anchored to the membrane through its N-terminal myristoylated amphipathic helix, the G domain explores a large conformational space, existing in a dynamic equilibrium between membrane-associated and membrane-distal conformations. These configurational dynamics expose different interfaces for interaction with effectors. Interaction with the Pleckstrin homology domain of ASAP1, an Arf-GTPase activating protein (ArfGAP), restricts motions of the G domain to lock it in what seems to be a conformation exposing functionally relevant regions.
Apparent nonlinear damping triggered by quantum fluctuations
Authors: Gely Mario F. , Sanz Mora Adrián , Yanai Shun , van der Spek Rik , Bothner Daniel , Steele Gary A. 
Published: November 2023

AbstractNonlinear damping, the change in damping rate with the amplitude of oscillations plays an important role in many electrical, mechanical and even biological oscillators. In novel technologies such as carbon nanotubes, graphene membranes or superconducting resonators, the origin of nonlinear damping is sometimes unclear. This presents a problem, as the damping rate is a key figure of merit in the application of these systems to extremely precise sensors or quantum computers. Through measurements of a superconducting resonator, we show that from the interplay of quantum fluctuations and the nonlinearity of a Josephson junction emerges a power-dependence in the resonator response which closely resembles nonlinear damping. The phenomenon can be understood and visualized through the flow of quasi-probability in phase space where it reveals itself as dephasing. Crucially, the effect is not restricted to superconducting circuits: we expect that quantum fluctuations or other sources of noise give rise to apparent nonlinear damping in systems with a similar conservative nonlinearity, such as nano-mechanical oscillators or even macroscopic systems.
Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing
Authors: Nguyen Lien D. , Wei Zhiyun , Silva M. Catarina , Barberán-Soler Sergio , Zhang Jiarui , Rabinovsky Rosalia , Muratore Christina R. , Stricker Jonathan M. S. , Hortman Colin , Young-Pearse Tracy L. , Haggarty Stephen J. , Krichevsky Anna M. 
Published: November 2023

AbstractMicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for miRNA modulation using oligonucleotides and gene therapies are challenging, especially for neurological diseases, and none have yet gained clinical approval. We explore a different approach by screening a biodiverse library of small molecule compounds for their ability to modulate hundreds of miRNAs in human induced pluripotent stem cell-derived neurons. We demonstrate the utility of the screen by identifying cardiac glycosides as potent inducers of miR-132, a key neuroprotective miRNA downregulated in Alzheimer’s disease and other tauopathies. Coordinately, cardiac glycosides downregulate known miR-132 targets, including Tau, and protect rodent and human neurons against various toxic insults. More generally, our dataset of 1370 drug-like compounds and their effects on the miRNome provides a valuable resource for further miRNA-based drug discovery.
PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling
Authors: Lin Yongfang , Yang Jing , Yang Qili , Zeng Sha , Zhang Jiayu , Zhu Yuanxiang , Tong Yuxin , Li Lin , Tan Weiqi , Chen Dahua , Sun Qinmiao 
Published: November 2023

AbstractTANK-binding kinase 1 (TBK1) is a key kinase in regulating antiviral innate immune responses. While the oligomerization of TBK1 is critical for its full activation, the molecular mechanism of how TBK1 forms oligomers remains unclear. Here, we show that protein tyrosine kinase 2 beta (PTK2B) acts as a TBK1-interacting protein and regulates TBK1 oligomerization. Functional assays reveal that PTK2B depletion reduces antiviral signaling in mouse embryonic fibroblasts, macrophages and dendritic cells, and genetic experiments show that Ptk2b-deficient mice are more susceptible to viral infection than control mice. Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation. In addition, we find that PTK2B also interacts with the stimulator of interferon genes (STING) and can promote its oligomerization in a kinase-independent manner. Collectively, PTK2B enhances the oligomerization of TBK1 and STING via different mechanisms, subsequently regulating STING-TBK1 activation to ensure efficient antiviral innate immune responses.
Cis-trans isomerization of peptoid residues in the collagen triple-helix
Authors: Qiu Rongmao , Li Xiaojing , Huang Kui , Bai Weizhe , Zhou Daoning , Li Gang , Qin Zhao , Li Yang 
Published: November 2023

AbstractCis-peptide bonds are rare in proteins, and building blocks less favorable to the trans-conformer have been considered destabilizing. Although proline tolerates the cis-conformer modestly among all amino acids, for collagen, the most prevalent proline-abundant protein, all peptide bonds must be trans to form its hallmark triple-helix structure. Here, using host-guest collagen mimetic peptides (CMPs), we discover that surprisingly, even the cis-enforcing peptoid residues (N-substituted glycines) form stable triple-helices. Our interrogations establish that these peptoid residues entropically stabilize the triple-helix by pre-organizing individual peptides into a polyproline-II helix. Moreover, noting that the cis-demanding peptoid residues drastically reduce the folding rate, we design a CMP whose triple-helix formation can be controlled by peptoid cis-trans isomerization, enabling direct targeting of fibrotic remodeling in myocardial infarction in vivo. These findings elucidate the principles of peptoid cis-trans isomerization in protein folding and showcase the exploitation of cis-amide-favoring residues in building programmable and functional peptidomimetics.
Axion insulator state in hundred-nanometer-thick magnetic topological insulator sandwich heterostructures
Authors: Zhuo Deyi , Yan Zi-Jie , Sun Zi-Ting , Zhou Ling-Jie , Zhao Yi-Fan , Zhang Ruoxi , Mei Ruobing , Yi Hemian , Wang Ke , Chan Moses H. W. , Liu Chao-Xing , Law K. T. , Chang Cui-Zu 
Published: November 2023

AbstractAn axion insulator is a three-dimensional (3D) topological insulator (TI), in which the bulk maintains the time-reversal symmetry or inversion symmetry but the surface states are gapped by surface magnetization. The axion insulator state has been observed in molecular beam epitaxy (MBE)-grown magnetically doped TI sandwiches and exfoliated intrinsic magnetic TI MnBi2Te4 flakes with an even number layer. All these samples have a thickness of ~ 10 nm, near the 2D-to-3D boundary. The coupling between the top and bottom surface states in thin samples may hinder the observation of quantized topological magnetoelectric response. Here, we employ MBE to synthesize magnetic TI sandwich heterostructures and find that the axion insulator state persists in a 3D sample with a thickness of ~ 106 nm. Our transport results show that the axion insulator state starts to emerge when the thickness of the middle undoped TI layer is greater than ~ 3 nm. The 3D hundred-nanometer-thick axion insulator provides a promising platform for the exploration of the topological magnetoelectric effect and other emergent magnetic topological states, such as the high-order TI phase.
Brain metastasis, EGFR mutation subtype and generation of EGFR-TKI jointly influence the treatment outcome of patient with EGFR-mutant NSCLC
Authors: Ju Jia-Shiuan , Huang Allen Chung-Cheng , Tung Pi-Hung , Huang Chi-Hsien , Chiu Tzu-Hsuan , Wang Chin-Chou , Ko How-Wen , Chung Fu-Tsai , Hsu Ping-Chih , Fang Yueh-Fu , Guo Yi-Ke , Kuo Chih-Hsi Scott , Yang Cheng-Ta 
Published: November 2023

AbstractNon-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation is brain metastasis (BM)-prone. We determined the impact of this hallmark, along with EGFR subtype and generation of tyrosine kinase inhibitor (TKI) treatment, on patients’ outcome. 553 metastatic EGFR-mutant NSCLC patients received front-line EGFR-TKI treatment. Progression-free survival (PFS), overall survival (OS) and secondary T790M rate were analysed. BM was observed in 211 (38.2%) patients. BM (HR 1.20 [95% CI 0.99–1.48]; p = 0.053), ECOG PS 0–1 (HR 0.71 [95% CI 0.54–0.93]; p = 0.014) and afatinib treatment (HR 0.81 [95% CI 0.66–0.99]; p = 0.045) were associated with PFS. Afatinib-treated patients without BM demonstrated a significantly longer PFS (16.3 months) compared to afatinib-treated patients with BM (13.7 months) and to gefitinib/erlotinib-treated patients with (11.1 months) or without BM (14.2 months; p < 0.001). CNS-only progression trended higher in afatinib-treated patients. ECOG PS 0–1 (HR 0.41 [95% CI 0.31–0.56]; p < 0.001) and EGFR L858R mutation (HR 1.46 [95% CI 1.13–1.88]; p = 0.003), but not BM, were the predictors for OS. BM (OR 2.02 [95% CI 1.02–4.08]; p = 0.040), afatinib treatment (OR 0.26 [95% CI 0.12–0.50]; p < 0.001) and EGFR L858R mutation (OR 0.55 [95% CI 0.28–1.05]; p = 0.070) were associated with secondary T790M rate. In BM patients, gefitinib/erlotinib-treated ones with 19 deletion mutation and afatinib-treated ones with L858R mutation had the highest and the lowest T790M rate (94.4% vs. 27.3%, p < 0.001), respectively. BM and generation of EGFR-TKI jointly impact PFS and secondary T790M rate in patients with EGFR-mutant NSCLC, whereas OS was mainly associated with EGFR subtype.
Economic implications of autonomous adaptation of firms and households in a resource-rich coastal city
Authors: Taberna Alessandro , Filatova Tatiana , Hochrainer-Stigler Stefan , Nikolic Igor , Noll Brayton 
Published: November 2023

AbstractClimate change intensifies the likelihood of extreme flood events worldwide, amplifying the potential for compound flooding. This evolving scenario represents an escalating risk, emphasizing the urgent need for comprehensive climate change adaptation strategies across society. Vital to effective response are models that evaluate damages, costs, and benefits of adaptation strategies, encompassing non-linearities and feedback between anthropogenic and natural systems. While flood risk modeling has progressed, limitations endure, including inadequate stakeholder representation and indirect risks such as business interruption and diminished tax revenues. To address these gaps, we propose an innovative version of the Climate-economy Regional Agent-Based model that integrates a dynamic, rapidly expanding agglomeration economy populated by interacting households and firms with extreme flood events. Through this approach, feedback loops and cascading effects generated by flood shocks are delineated within a socio-economic system of boundedly-rational agents. By leveraging extensive behavioral data, our model incorporates a risk layering strategy encompassing bottom-up and top-down adaptation, spanning individual risk reduction to insurance. Calibrated to resemble a research-rich coastal megacity in China, our model demonstrates how synergistic adaptation actions at all levels effectively combat the mounting climate threat. Crucially, the integration of localized risk management with top-down approaches offers explicit avenues to address both direct and indirect risks, providing significant insights for constructing climate-resilient societies.
A novel code generator for graphical user interfaces
Authors: Cai Bo , Luo Jian , Feng Zhen 
Published: November 2023

AbstractGraphical user interfaces (GUIs) are widely used in human–computer interaction, providing a convenient interface for operation. Automating the conversion of GUI design images into source code can significantly reduce the coding workload for front-end developers. Detecting elements in GUI images is a key challenge in achieving automatic GUI code generation and is crucial for tasks such as GUI automation and testing. However, current state-of-the-art methods do not fully consider the unique characteristics of GUI images and elements, and they lack the required high localization accuracy, resulting in low detection accuracy for GUI element boxes. In this paper, we propose GUICG, an automatic GUI code generator that combines deep neural networks with image processing techniques to efficiently detect GUI elements from GUI images and generate front-end code. We empirically investigate various deep learning approaches and image processing methods for GUI component detection. Based on a comprehensive understanding of their performance and characteristics, we design GUICG by fusing image processing with a deep learning-based target detection model, achieving state-of-the-art performance. GUICG outperforms existing methods in accuracy and F1 score for component detection tasks, while producing human-readable code with a logical structure. Furthermore, we conduct an ablation study to quantitatively assess the impact of each key element in GUICG.
Burden of diseases attributable to excess body weight in the Middle East and North Africa region, 1990–2019
Authors: Nejadghaderi Seyed Aria , Grieger Jessica A. , Karamzad Nahid , Kolahi Ali-Asghar , Sullman Mark J. M. , Safiri Saeid , Sabour Siamak 
Published: November 2023

AbstractHigh body mass index (BMI), or excess body weight (EBW), represents a significant risk factor for a range of diseases, including cardiovascular diseases and cancers. The study sought to determine the burden of diseases attributable to EBW in the Middle East and North Africa (MENA) region from 1990 and 2019. The analysis also included an exploration of this burden by age, sex, underlying cause, and sociodemographic index (SDI). We utilized publicly available data from the Global Burden of Disease (GBD) study 2019 to identify the deaths and disability-adjusted life-years (DALYs) of diseases associated with EBW in MENA, spanning the period from 1990 to 2019. The GBD estimated the mean BMI and the prevalence of EBW using hierarchical mixed-effects regression, followed by spatiotemporal Gaussian process regression to determine the most accurate BMI distribution through comparison with actual data. In 2019, there were an estimated 538.4 thousand deaths (95% UI 369.9–712.3) and 17.9 million DALYs (12.9–23.1) attributable to EBW in the region. The DALYs attributable to EBW were higher in men (9.3 million [6.5–12.4]) than in women (8.5 million [6.4–10.8]). The age-standardized death and DALY rates for the diseases associated with EBW increased by 5.1% (− 9.0–25.9) and 8.3% (− 6.5–28.8), respectively, during the study period which was not significant. Egypt had the highest age-standardized mortality rate due to EBW (217.7 [140.0, 307.8]), while Yemen (88.6 [45.9, 143.5]) had the lowest. In 2019, the highest number of DALYs occurred among individuals aged 60 to 64 years old. Furthermore, we found a positive association between a nation's SDI and the age-standardized DALY rate linked to EBW. Cardiovascular disease emerged as the leading contributor to the EBW burden in MENA. The disease burden attributable to EBW showed a non-significant increase in MENA from 1990 to 2019.
Molecular dynamics of JUNO-IZUMO1 complexation suggests biologically relevant mechanisms in fertilization
Authors: Pacak Paulina , Kluger Carleen , Vogel Viola 
Published: November 2023

AbstractJUNO-IZUMO1 binding is the first known physical link created between the sperm and egg membranes in fertilization, however, how this initiates sperm-egg fusion remains elusive. As advanced structural insights will help to combat the infertility crisis, or advance fertility control, we employed all-atom Molecular Dynamics (MD) to derive dynamic structural insights that are difficult to obtain experimentally. We found that the hydrated JUNO-IZUMO1 interface is composed of a large set of short-lived non-covalent interactions. The contact interface is destabilized by strategically located point mutations, as well as by Zn2+ ions, which shift IZUMO1 into the non-binding “boomerang” conformation. We hypothesize that the latter might explain how the transient zinc spark, as released after sperm entry into the oocyte, might contribute to block polyspermy. To address a second mystery, we performed another set of simulations, as it was previously suggested that JUNO in solution is unable to bind to folate despite it belonging to the folate receptor family. MD now suggests that JUNO complexation with IZUMO1 opens up the binding pocket thereby enabling folate insertion. Our MD simulations thus provide crucial new hypotheses how the dynamics of the JUNO-IZUMO1 complex upon solvation might regulate fertility.
Solanum lycopersicum heme-binding protein 2 as a potent antimicrobial weapon against plant pathogens
Authors: Farvardin Atefeh , Llorens Eugenio , Liu-Xu Luisa , Sánchez-Giménez Lorena , Wong Aloysius , Biosca Elena G. , Pedra José M. , Falomir Eva , Camañes Gemma , Scalschi Loredana , Vicedo Begonya 
Published: November 2023

AbstractThe rise in antibiotic-resistant bacteria caused by the excessive use of antibiotics has led to the urgent exploration of alternative antimicrobial solutions. Among these alternatives, antimicrobial proteins, and peptides (Apps) have garnered attention due to their wide-ranging antimicrobial effects. This study focuses on evaluating the antimicrobial properties of Solanum lycopersicum heme-binding protein 2 (SlHBP2), an apoplastic protein extracted from tomato plants treated with 1-Methyl tryptophan (1-MT), against Pseudomonas syringae pv. tomato DC3000 (Pst). Computational studies indicate that SlHBP2 is annotated as a SOUL heme-binding family protein. Remarkably, recombinant SlHBP2 demonstrated significant efficacy in inhibiting the growth of Pst within a concentration range of 3–25 μg/mL. Moreover, SlHBP2 exhibited potent antimicrobial effects against other microorganisms, including Xanthomonas vesicatoria (Xv), Clavibacter michiganensis subsp. michiganensis (Cmm), and Botrytis cinerea. To understand the mechanism of action employed by SlHBP2 against Pst, various techniques such as microscopy and fluorescence assays were employed. The results revealed that SlHBP2 disrupts the bacterial cell wall and causes leakage of intracellular contents. To summarize, the findings suggest that SlHBP2 has significant antimicrobial properties, making it a potential antimicrobial agent against a wide range of pathogens. Although further studies are warranted to explore the full potential of SlHBP2 and its suitability in various applications.
Multicenter observational survey on psychosocial and behavioral impacts of COVID-19 in people living with HIV in Northern Vietnam
Authors: Matsumoto Shoko , Nagai Moeko , Tran Linh Khanh , Yamaoka Kazue , Nguyen Hoai Dung Thi , Dinh Van Trang , Tanuma Junko , Pham Thach Ngoc , Oka Shinichi , Van Tran Giang 
Published: November 2023

AbstractSocially marginalized groups, including people living with HIV/AIDS (PLHIV), could be disproportionately affected by Coronavirus disease 2019 (COVID-19). Following an initial single-center survey conducted in 2020, we conducted a second survey of 11 antiretroviral therapy (ART) sites in Northern Vietnam between June 2021 and January 2022. We tested anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) nucleocapsid IgG antibodies and assessed prevention against COVID-19 and impacts of COVID-19 on access to ART, economic security, risky health behaviors, and mental health using self-reported questionnaires. In total, 7808 PLHIV on ART participated in the second survey. The overall prevalence of SARS-CoV-2 antibody was as low as 1.2%. There was no clear upward trend in COVID-19 infection among PLHIV compared with the rate of infection among the general population. HIV treatment was generally maintained and no increase in risky health behaviors was observed. The economic impacts were significant, with high unemployment rate, poorer economic security, and binge drinking strongly associated with depression. However, the prevalence of depression decreased by 11.2% compared with pre-COVID-19 levels. Social support, including for patients to continue HIV treatment and effective employment/financial assistance, may help to alleviate the negative socioeconomic impacts of COVID-19 and improve mental health among PLHIV.
Survey on chest CT findings in COVID-19 patients in Okinawa, Japan: differences between the delta and omicron variants
Authors: Tsuchiya Nanae , Yonamine Eri , Iraha Shoko , Takara Makoto , Oshiro Yasuji , Tetsuhiro Miyara , Murayama Sadayuki , Kinoshita Ryo , Sato Masaki , Nishikuramori Yukiko , Takara Hiroaki , Akamine Tamaki , Morita Hikaru , Matayoshi Takashi , Chinen Yuma , Nishie Akihiro 
Published: November 2023

AbstractTo investigate the frequency of pneumonia and chest computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) during the fifth Delta variant-predominant and sixth Omicron variant-predominant waves of the COVID-19 pandemic in Okinawa, Japan. A survey on chest CT examinations for patients with COVID-19 was conducted byhospitals with board-certified radiologists who provided treatment for COVID-19 pneumonia in Okinawa Prefecture. Data from 11 facilities were investigated. Indications for chest CT; number of COVID-19 patients undergoing chest CT; number of patients with late-onset pneumonia, tracheal intubation, and number of deaths; and COVID-19 Reporting and Data System classifications of initial chest CT scans were compared by the chi-squared test between the two pandemic waves (Delta vs. Omicron variants). A total of 1944 CT scans were performed during the fifth wave, and 1178 were performed during the sixth wave. CT implementation rates, which were the number of patients with COVID-19 undergoing CT examinations divided by the total number of COVID-19 cases in Okinawa Prefecture during the waves, were 7.1% for the fifth wave and 2.1% for the sixth wave. The rates of tracheal intubation and mortality were higher in the fifth wave. Differences between the distributions of the CO-RADS classifications were statistically significant for the fifth and sixth waves (p < 0.0001). In the fifth wave, CO-RADS 5 (typical of COVID-19) was most common (65%); in the sixth wave, CO-RADS 1 (no findings of pneumonia) was most common (50%). The finding of “typical for other infection but not COVID-19” was more frequent in the sixth than in the fifth wave (13.6% vs. 1.9%, respectively). The frequencies of pneumonia and typical CT findings were higher in the fifth Delta variant-predominant wave, and nontypical CT findings were more frequent in the sixth Omicron variant-predominant wave of the COVID-19 pandemic in Okinawa, Japan.