bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Dust‐Induced Direct Radiative Forcing Over the Arabian Peninsula Based on High‐Resolution WRF‐Chem Simulations
Authors: Karumuri Rama Krishna , Dasari Hari Prasad , Gandham Harikishan , Kunchala Ravi Kumar , Attada Raju , Ashok Karumuri , Hoteit Ibrahim 
Published: July 2024

AbstractThis study investigates the impact of dust on radiation over the Arabian Peninsula (AP) during the reported high, low, and normal dust seasons (March–August) of 2012, 2014, and 2015, respectively. Simulations were performed using the Weather Research and Forecasting model coupled to a Chemistry module (WRF‐Chem). The simulated seasonal horizontal and vertical dust concentrations, and their interannual distinctions, match well with those from two ground‐based AERONET observations, and measurements from MODIS and CALIOP satellites. The maximum dust concentrations over the dust‐source regions in the southern AP reach vertically upto 700 hPa during the high dust season, but only upto 900–950 hPa during the low/normal dust seasons. Stronger incoming low‐level winds along the southern Red Sea and those from Iraq bring in higher‐than‐normal dust during the high dust summers. We conducted a sensitivity experiment by switching‐off the dust module to assess the radiative perturbations due to dust. The results suggest that active dust‐module improved the fidelity of simulated radiation fluxes distributions at the surface and top of the atmosphere vis‐à‐vis Clouds and the Earth's Radiant Energy System (CERES) measurements. Dust results in a 26 Wm−2 short‐wave (SW) radiative forcing in the tropospheric‐column over the AP. The SW radiative forcing increases by another 6–8 Wm−2 during the high dust season due to the increased number of extreme dust days, which also amplifies atmospheric heating. During extreme dust days, the heating rate exhibits a dipolar structure, with cooling over the Iraq region and warming of 40%–60% over the southern‐AP.
Network properties determine neural network performance
Authors: Jiang Chunheng , Huang Zhenhan , Pedapati Tejaswini , Chen Pin-Yu , Sun Yizhou , Gao Jianxi 
Published: July 2024

AbstractMachine learning influences numerous aspects of modern society, empowers new technologies, from Alphago to ChatGPT, and increasingly materializes in consumer products such as smartphones and self-driving cars. Despite the vital role and broad applications of artificial neural networks, we lack systematic approaches, such as network science, to understand their underlying mechanism. The difficulty is rooted in many possible model configurations, each with different hyper-parameters and weighted architectures determined by noisy data. We bridge the gap by developing a mathematical framework that maps the neural network’s performance to the network characters of the line graph governed by the edge dynamics of stochastic gradient descent differential equations. This framework enables us to derive a neural capacitance metric to universally capture a model’s generalization capability on a downstream task and predict model performance using only early training results. The numerical results on 17 pre-trained ImageNet models across five benchmark datasets and one NAS benchmark indicate that our neural capacitance metric is a powerful indicator for model selection based only on early training results and is more efficient than state-of-the-art methods.
Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells
Authors: Lai Rocky , Williams Travis , Rakib Tasfia , Lee Jinhee , Behar Samuel M. 
Published: July 2024

AbstractFollowing Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminate M. tuberculosis infection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.
Ocean iron cycle feedbacks decouple atmospheric CO2 from meridional overturning circulation changes
Authors: Lauderdale Jonathan Maitland 
Published: July 2024

AbstractThe ocean’s Meridional Overturning Circulation (MOC) brings carbon- and nutrient-rich deep waters to the surface around Antarctica. Limited by light and dissolved iron, photosynthetic microbes incompletely consume these nutrients, the extent of which governs the escape of inorganic carbon into the atmosphere. Changes in MOC upwelling may have regulated Southern Ocean outgassing, resulting in glacial-interglacial atmospheric CO2 oscillations. However, numerical models that explore this positive relationship do not typically include a feedback between biological activity and abundance of organic chelating ligands that control dissolved iron availability. Here, I show that incorporating a dynamic ligand parameterization inverts the modelled MOC-atmospheric CO2 relationship: reduced MOC nutrient upwelling decreases biological activity, resulting in scant ligand production, enhanced iron limitation, incomplete nutrient usage, and ocean carbon outgassing, and vice versa. This first-order response suggests iron cycle feedbacks may be a critical driver of the ocean’s response to climate changes, independent of external iron supply.
Ube3a unsilencer for the potential treatment of Angelman syndrome
Authors: Vihma Hanna , Li Kelin , Welton-Arndt Anna , Smith Audrey L. , Bettadapur Kiran R. , Gilmore Rachel B. , Gao Eric , Cotney Justin L. , Huang Hsueh-Cheng , Collins Jon L. , Chamberlain Stormy J. , Lee Hyeong-Min , Aubé Jeffrey , Philpot Benjamin D. 
Published: July 2024

AbstractDeletion of the maternal UBE3A allele causes Angelman syndrome (AS); because paternal UBE3A is epigenetically silenced by a long non-coding antisense (UBE3A-ATS) in neurons, this nearly eliminates UBE3A protein in the brain. Reactivating paternal UBE3A holds promise for treating AS. We previously showed topoisomerase inhibitors can reactivate paternal UBE3A, but their therapeutic challenges prompted our search for small molecule unsilencers with a different mechanism of action. Here, we found that (S)-PHA533533 acts through a novel mechanism to significantly increase paternal Ube3a mRNA and UBE3A protein levels while downregulating Ube3a-ATS in primary neurons derived from AS model mice. Furthermore, peripheral delivery of (S)-PHA533533 in AS model mice induces widespread neuronal UBE3A expression. Finally, we show that (S)-PHA533533 unsilences paternal UBE3A in AS patient-derived neurons, highlighting its translational potential. Our findings provide a lead for developing a small molecule treatment for AS that could be safe, non-invasively delivered, and capable of brain-wide unsilencing of paternal UBE3A.
Copy number variation introduced by a massive mobile element facilitates global thermal adaptation in a fungal wheat pathogen
Authors: Tralamazza Sabina Moser , Gluck-Thaler Emile , Feurtey Alice , Croll Daniel 
Published: July 2024

AbstractCopy number variation (CNV) can drive rapid evolution in changing environments. In microbial pathogens, such adaptation is a key factor underpinning epidemics and colonization of new niches. However, the genomic determinants of such adaptation remain poorly understood. Here, we systematically investigate CNVs in a large genome sequencing dataset spanning a worldwide collection of 1104 genomes from the major wheat pathogen Zymoseptoria tritici. We found overall strong purifying selection acting on most CNVs. Genomic defense mechanisms likely accelerated gene loss over episodes of continental colonization. Local adaptation along climatic gradients was likely facilitated by CNVs affecting secondary metabolite production and gene loss in general. One of the strongest loci for climatic adaptation is a highly conserved gene of the NAD-dependent Sirtuin family. The Sirtuin CNV locus localizes to an ~68-kb Starship mobile element unique to the species carrying genes highly expressed during plant infection. The element has likely lost the ability to transpose, demonstrating how the ongoing domestication of cargo-carrying selfish elements can contribute to selectable variation within populations. Our work highlights how standing variation in gene copy numbers at the global scale can be a major factor driving climatic and metabolic adaptation in microbial species.
An experimentally validated approach to automated biological evidence generation in drug discovery using knowledge graphs
Authors: Sudhahar Saatviga , Ozer Bugra , Chang Jiakang , Chadwick Wayne , O’Donovan Daniel , Campbell Aoife , Tulip Emma , Thompson Neil , Roberts Ian 
Published: July 2024

AbstractExplaining predictions for drug repositioning with biological knowledge graphs is a challenging problem. Graph completion methods using symbolic reasoning predict drug treatments and associated rules to generate evidence representing the therapeutic basis of the drug. Yet the vast amounts of generated paths that are biologically irrelevant or not mechanistically meaningful within the context of disease biology can limit utility. We use a reinforcement learning based knowledge graph completion model combined with an automatic filtering approach that produces the most relevant rules and biological paths explaining the predicted drug’s therapeutic connection to the disease. In this work we validate the approach against preclinical experimental data for Fragile X syndrome demonstrating strong correlation between automatically extracted paths and experimentally derived transcriptional changes of selected genes and pathways of drug predictions Sulindac and Ibudilast. Additionally, we show it reduces the number of generated paths in two case studies, 85% for Cystic fibrosis and 95% for Parkinson’s disease.
Egg multivesicular bodies elicit an LC3-associated phagocytosis-like pathway to degrade paternal mitochondria after fertilization
Authors: Ben-Hur Sharon , Sernik Shoshana , Afar Sara , Kolpakova Alina , Politi Yoav , Gal Liron , Florentin Anat , Golani Ofra , Sivan Ehud , Dezorella Nili , Morgenstern David , Pietrokovski Shmuel , Schejter Eyal , Yacobi-Sharon Keren , Arama Eli 
Published: July 2024

AbstractMitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination after fertilization are far less clear. Using Drosophila, we show that special egg-derived multivesicular body vesicles promote paternal mitochondrial elimination by activating an LC3-associated phagocytosis-like pathway, a cellular defense pathway commonly employed against invading microbes. Upon fertilization, these egg-derived vesicles form extended vesicular sheaths around the sperm flagellum, promoting degradation of the sperm mitochondrial derivative and plasma membrane. LC3-associated phagocytosis cascade of events, including recruitment of a Rubicon-based class III PI(3)K complex to the flagellum vesicular sheaths, its activation, and consequent recruitment of Atg8/LC3, are all required for paternal mitochondrial elimination. Finally, lysosomes fuse with strings of large vesicles derived from the flagellum vesicular sheaths and contain degrading fragments of the paternal mitochondrial derivative. Given reports showing that in some mammals, the paternal mitochondria are also decorated with Atg8/LC3 and surrounded by multivesicular bodies upon fertilization, our findings suggest that a similar pathway also mediates paternal mitochondrial elimination in other flagellated sperm-producing organisms.
Network mechanisms of ongoing brain activity’s influence on conscious visual perception
Authors: Wu Yuan-hao , Podvalny Ella , Levinson Max , He Biyu J. 
Published: July 2024

AbstractSensory inputs enter a constantly active brain, whose state is always changing from one moment to the next. Currently, little is known about how ongoing, spontaneous brain activity participates in online task processing. We employed 7 Tesla fMRI and a threshold-level visual perception task to probe the effects of prestimulus ongoing brain activity on perceptual decision-making and conscious recognition. Prestimulus activity originating from distributed brain regions, including visual cortices and regions of the default-mode and cingulo-opercular networks, exerted a diverse set of effects on the sensitivity and criterion of conscious recognition, and categorization performance. We further elucidate the mechanisms underlying these behavioral effects, revealing how prestimulus activity modulates multiple aspects of stimulus processing in highly specific and network-dependent manners. These findings reveal heretofore unknown network mechanisms underlying ongoing brain activity’s influence on conscious perception, and may hold implications for understanding the precise roles of spontaneous activity in other brain functions.
Metal-ligand dual-site single-atom nanozyme mimicking urate oxidase with high substrates specificity
Authors: Wang Kaiyuan , Hong Qing , Zhu Caixia , Xu Yuan , Li Wang , Wang Ying , Chen Wenhao , Gu Xiang , Chen Xinghua , Fang Yanfeng , Shen Yanfei , Liu Songqin , Zhang Yuanjian 
Published: July 2024

AbstractIn nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.
CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation
Authors: Xu Nana , Jiang Jiebang , Jiang Fei , Dong Guokai , Meng Li , Wang Meng , Chen Jing , Li Cong , Shi Yongping , He Sisi , Li Rongpeng 
Published: July 2024

AbstractThe circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)−165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.
Donor-acceptor bulk-heterojunction sensitizer for efficient solid-state infrared-to-visible photon up-conversion
Authors: Bi Pengqing , Zhang Tao , Guo Yuanyuan , Wang Jianqiu , Chua Xian Wei , Chen Zhihao , Goh Wei Peng , Jiang Changyun , Chia Elbert E. M. , Hou Jianhui , Yang Le 
Published: July 2024

AbstractSolid-state infrared-to-visible photon up-conversion is important for spectral-tailoring applications. However, existing up-conversion systems not only suffer from low efficiencies and a need for high excitation intensity, but also exhibit a limited selection of materials and complex fabrication processes. Herein, we propose a sensitizer with a bulk-heterojunction structure, comprising both an energy donor and an energy acceptor, for triplet-triplet annihilation up-conversion devices. The up-conversion occurs through charge separation at the donor-acceptor interface, followed by the formation of charge transfer state between the energy donor and annihilator following the spin statistics. The bulk-heterojunction sensitizer ensures efficient charge generation and low charge recombination. Hence, we achieve a highly efficient solid-state up-conversion device with 2.20% efficiency and low excitation intensity (10 mW cm−2) through a one-step solution method. We also demonstrate bright up-conversion devices on highly-flexible large-area substrates. This study introduces a simple and scalable platform strategy for fabricating efficient up-conversion devices.
Efficient and rapid digestion of proteins with a dual-enzyme microreactor featuring 3-D pores formed by dopamine/polyethyleneimine/acrylamide-coated KIT-6 molecular sieve
Authors: Yuan Fang-Fang , Wang Pei , Han Xiao-Jie , Qin Ting-Ting , Lu Xin , Bai Hai-Jiao 
Published: July 2024

AbstractThe microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.
Dietary nanocomposite of vitamin C and vitamin E enhanced the performance of Nile tilapia
Authors: Sherif Ahmed H. , Khalil Riad H. , Talaat Talaat S. , Baromh Mohamed Z. , Elnagar Mahmoud A. 
Published: July 2024

AbstractNowadays, nanomaterials enter high numbers of daily used products and drug manufacture. A nanocomposite of vitamins C (VC) and vitamin E (VE) with chitosan as a vehicle and protector was used in a comparative eight-week feeding study, Nile tilapia weighing 31.2 ± 0.36 g distributed in seven groups and fed (G1) basal diet, (G2) bulk VC, (G3) VC- nanoparticles (NPs), (G4) bulk VE, (G5) VE-NPs, bulk VCE (G6), and (G7) VC plus VE (VCE)-NPs, respectively. The Nile tilapia-fed nanocomposite vitamins had significantly higher growth performance compared to the control; VCE-NPs had the superiority among tested supplementations where total weight gain (63.6 g), daily weight gain (1.13 g), relative growth rate (206.1%) with lower feed conversion rate (1.6) and insignificant feed intake (101.5 g). Overall, the level of liver enzymes was significantly decreased in fish serum after eight-week nanocomposite supplementation, and dietary VCE-NPs caused a significant reduction of serum AST (18.45 IU/L) and ALT (14.77 IU/L) compared to the control 25.5 IU/L and 17.6 IU/L, respectively. Fish fed dietary VCE-NPs, VC-NPs, and VE-NPs had significant enhancement of RBCs 4.2 × 106/μL, 3.8 × 106/μL, and 3.55 × 106/μL; WBCs 46.15 × 103, 42.9 × 103, and 44 × 103/μL, respectively, Also TP was significantly higher 6.38 g/dL in VCE-NPs group compared to the control and the other treatments. Over all, the dietary nanocomposite vitamins boost the innate immunity of the experimental Nile tilapia, the oxidative burst activity (OBA), phagocytic activity (PA), phagocytic index (PI), and serum antibacterial (SAA) were significantly increased compared to those received bulk vitamins and the control. The activity of antioxidant biomarkers in fish serum including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), glutathione reductase (GR), and myeloperoxidase (MPO) showed a rise in the serum of Nile tilapia received nano- and bulk-form of VC and VCE compared to the control and both forms of VE. Furthermore, the level of malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG) were significantly increased in the fish serum following the trend of antioxidants enzymes. In conclusion, a dietary nanocomposite of vitamin C and vitamin E enhanced Nile tilapia's growth performance and feed utilization. It could also improve health status and immune response. The values of antioxidant biomarkers indicated that the nanocomposite could help the fish body scavenge the generated reactive oxidative species (ROS).
Non-invasive fractional flow reserve estimation in coronary arteries using angiographic images
Authors: Edrisnia Hadis , Sarkhosh Mohammad Hossein , Mohebbi Bahram , Parhizgar Seyed Ehsan , Alimohammadi Mona 
Published: July 2024

AbstractCoronary artery disease is the leading global cause of mortality and Fractional Flow Reserve (FFR) is widely regarded as the gold standard for assessing coronary artery stenosis severity. However, due to the limitations of invasive FFR measurements, there is a pressing need for a highly accurate virtual FFR calculation framework. Additionally, it’s essential to consider local haemodynamic factors such as time-averaged wall shear stress (TAWSS), which play a critical role in advancement of atherosclerosis. This study introduces an innovative FFR computation method that involves creating five patient-specific geometries from two-dimensional coronary angiography images and conducting numerical simulations using computational fluid dynamics with a three-element Windkessel model boundary condition at the outlet to predict haemodynamic distribution. Furthermore, four distinct boundary condition methodologies are applied to each geometry for comprehensive analysis. Several haemodynamic features, including velocity, pressure, TAWSS, and oscillatory shear index are investigated and compared for each case. Results show that models with average boundary conditions can predict FFR values accurately and observed errors between invasive FFR and virtual FFR are found to be less than 5%.