bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational engineering of minimally immunogenic nucleases for gene therapy
Authors: Raghavan Rumya , Friedrich Mirco J. , King Indigo , Chau-Duy-Tam Vo Samuel , Strebinger Daniel , Lash Blake , Kilian Michael , Platten Michael , Macrae Rhiannon K. , Song Yifan , Nivon Lucas , Zhang Feng 
Published: January 2025

AbstractGenome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a. Through MHC-associated peptide proteomics (MAPPs) analysis, we identify putative immunogenic epitopes on each nuclease. Using computational modeling, we rationally design these proteins to evade the immune response. SaCas9 and AsCas12a Redi variants are substantially less recognized by adaptive immune components, including reduced binding affinity to MHC molecules and attenuated generation of cytotoxic T cell responses, yet maintain wild-type levels of activity and specificity. In vivo editing of PCSK9 with SaCas9.Redi.1 is comparable in efficiency to wild-type SaCas9, but significantly reduces undesired immune responses. This demonstrates the utility of this approach in engineering proteins to evade immune detection.
Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A2 α for targeted cancer therapy
Authors: Ashcroft Felicity J. , Bourboula Asimina , Mahammad Nur , Barbayianni Efrosini , Feuerherm Astrid J. , Nguyen Thanh Thuy , Hayashi Daiki , Kokotou Maroula G. , Alevizopoulos Konstantinos , Dennis Edward A. , Kokotos George , Johansen Berit 
Published: January 2025

AbstractEicosanoids are key players in inflammatory diseases and cancer. Targeting their production by inhibiting Group IVA cytosolic phospholipase A2 (cPLA2α) offers a promising approach for cancer therapy. In this study, we synthesize a second generation of thiazolyl ketone inhibitors of cPLA2α starting with compound GK470 (AVX235) and test their in vitro and cellular activities. We identify a more potent and selective lead molecule, GK420 (AVX420), which we test in parallel with AVX235 and a structurally unrelated compound, AVX002 for inhibition of cell viability across a panel of cancer cell lines. From this, we show that activity of polycomb group repressive complex 2 is a key molecular determinant of sensitivity to cPLA2α inhibition, while resistance depends on antioxidant response pathways. Consistent with these results, we show that elevated intracellular reactive oxygen species and activating transcription factor 4 target gene expression precede cell death in AVX420-sensitive T-cell acute lymphoblastic leukemia cells. Our findings imply cPLA2α may support cancer by mitigating oxidative stress and inhibiting tumor suppressor expression and suggest that AVX420 has potential for treating acute leukemias and other cancers that are susceptible to oxidative cell death.
TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen
Authors: Albuquerque-Wendt Andreia , McCoy Ciaran , Neish Rachel , Dobramysl Ulrich , Alagöz Çağla , Beneke Tom , Cowley Sally A. , Crouch Kathryn , Wheeler Richard J. , Mottram Jeremy C. , Gluenz Eva 
Published: January 2025

AbstractFor the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L. mexicana transportome. A total of 312 protein components of small molecule carriers, ion channels and pumps were identified and targeted in a CRISPR-Cas9 gene deletion screen in the promastigote form, yielding 188 viable null mutants. Forty transporter deletions caused significant loss of fitness in macrophage and mouse infections. A striking example is the Vacuolar H+ ATPase (V-ATPase), which, unexpectedly, was dispensable for promastigote growth in vitro but essential for survival of the disease-causing amastigotes.
Structural insights into the regulation of monomeric and dimeric apelin receptor
Authors: Yue Yang , Liu Lier , Wu Lijie , Xu Chanjuan , Na Man , Liu Shenhui , Liu Yuxuan , Li Fei , Liu Junlin , Shi Songting , Lei Hui , Zhao Minxuan , Yang Tianjie , Ji Wei , Wang Arthur , Hanson Michael A. , Stevens Raymond C. , Liu Jianfeng , Xu Fei 
Published: January 2025

AbstractThe apelin receptor (APJR) emerges as a promising drug target for cardiovascular health and muscle regeneration. While prior research unveiled the structural versatility of APJR in coupling to Gi proteins as a monomer or dimer, the dynamic regulation within the APJR dimer during activation remains poorly understood. In this study, we present the structures of the APJR dimer and monomer complexed with its endogenous ligand apelin-13. In the dimeric structure, apelin-13 binds exclusively to one protomer that is coupled with Gi proteins, revealing a distinct ligand-binding behavior within APJR homodimers. Furthermore, binding of an antagonistic antibody induces a more compact dimerization by engaging both protomers. Notably, structural analyses of the APJR dimer complexed with an agonistic antibody, with or without Gi proteins, suggest that G protein coupling may promote the dissociation of the APJR dimer during activation. These findings underscore the intricate interplay between ligands, dimerization, and G protein coupling in regulating APJR signaling pathways.
Surface remodeling and inversion of cell-matrix interactions underlie community recognition and dispersal in Vibrio cholerae biofilms
Authors: Moreau Alexis , Nguyen Danh T. , Hinbest Alexander J. , Zamora Anthony , Weerasekera Ranjuna , Matej Katherine , Zhou Xuening , Sanchez Sandra , Rodriguez Brenes Ignacio , Tai Jung-Shen Benny , Nadell Carey D. , Ng Wai-Leung , Gordon Vernita , Komarova Natalia L. , Olson Rich , Li Ying , Yan Jing 
Published: January 2025

AbstractBiofilms are ubiquitous surface-associated bacterial communities embedded in an extracellular matrix. It is commonly assumed that biofilm cells are glued together by the matrix; however, how the specific biochemistry of matrix components affects the cell-matrix interactions and how these interactions vary during biofilm growth remain unclear. Here, we investigate cell-matrix interactions in Vibrio cholerae, the causative agent of cholera. We combine genetics, microscopy, simulations, and biochemical analyses to show that V. cholerae cells are not attracted to the main matrix component (Vibrio polysaccharide, VPS), but can be attached to each other and to the VPS network through surface-associated VPS and crosslinks formed by the protein Bap1. Downregulation of VPS production and surface trimming by the polysaccharide lyase RbmB cause surface remodeling as biofilms age, shifting the nature of cell-matrix interactions from attractive to repulsive and facilitating cell dispersal as aggregated groups. Our results shed light on the dynamics of diverse cell-matrix interactions as drivers of biofilm development.
2.5-dimensional covalent organic frameworks
Authors: Kitano Tomoki , Goto Syunto , Wang Xiaohan , Kamihara Takayuki , Sei Yoshihisa , Kondo Yukihito , Sannomiya Takumi , Uekusa Hidehiro , Murakami Yoichi 
Published: January 2025

AbstractCovalently bonded crystalline substances with micropores have broad applications. Covalent organic frameworks (COFs) are representative of such substances. They have so far been classified into two-dimensional (2D) and three-dimensional (3D) COFs. 2D-COFs have planar shapes useful for broad purposes, but obtaining good crystals of 2D-COFs with sizes larger than 10 μm is significantly challenging, whereas yielding 3D-COFs with high crystallinity and larger sizes is easier. Here, we show COFs with 2.5-dimensional (2.5D) skeletons, which are microscopically constructed with 3D bonds but have macroscopically 2D planar shapes. The 2.5D-COFs shown herein achieve large single-crystal sizes above 0.1 mm and ultrahigh-density primary amines regularly allocated on and pointing perpendicular to the covalently-bonded network plane. Owing to the latter nature, the COFs are promising as CO2 adsorbents that can simultaneously achieve high CO2/N2 selectivity and low heat of adsorption, which are usually in a mutually exclusive relationship. 2.5D-COFs are expected to broaden the frontier and application of covalently bonded microporous crystalline systems.
Mitochondrial-cytochrome c oxidase II promotes glutaminolysis to sustain tumor cell survival upon glucose deprivation
Authors: Yi Yong , Wang Guoqiang , Zhang Wenhua , Yu Shuhan , Fei Junjie , An Tingting , Yi Jianqiao , Li Fengtian , Huang Ting , Yang Jian , Niu Mengmeng , Wang Yang , Xu Chuan , Xiao Zhi-Xiong Jim 
Published: January 2025

AbstractGlucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA. Elevated MT-CO2 increases flavin adenosine dinucleotide (FAD) levels in activating lysine-specific demethylase 1 (LSD1) to epigenetically upregulate JUN transcription, consequently promoting glutaminase-1 (GLS1) and glutaminolysis for tumor cell survival. Furthermore, MT-CO2 is indispensable for oncogenic Ras-induced glutaminolysis and tumor growth, and elevated expression of MT-CO2 is associated with poor prognosis in lung cancer patients. Together, these findings reveal a role for MT-CO2 in adapting to metabolic stress and highlight MT-CO2 as a putative therapeutic target for Ras-driven cancers.
A dataset of gridded precipitation intensity-duration-frequency curves in Qinghai-Tibet Plateau
Authors: Ren Zhihui , Sang Yan-Fang , Cui Peng , Chen Fei , Chen Deliang 
Published: January 2025

AbstractThe Qinghai-Tibet Plateau (QTP), a high mountain area prone to destructive rainstorm hazards and inducing natural disasters, underscores the importance of developing precipitation intensity-duration-frequency (IDF) curves for estimating extreme precipitation characteristics. Here we introduce the Qinghai-Tibet Plateau Precipitation Intensity-Duration-Frequency Curves (QTPPIDFC) dataset, the first gridded dataset tailored for estimating extreme precipitation characteristics in QTP. The generalized extreme value distribution is chosen to fit the annual maximum precipitation samples at 203 weather stations, based on which the at-site IDF curves are estimated; then, principal component analysis is done to identify the southeast-northwest spatial pattern of at-site IDF curves, and its first principal component gives a 96% explained variance; finally, spatial interpolation is done to estimate gridded IDF curves by using the random forest model with geographical and climatic variables as predictors. The dataset provides precipitation information within 1, 2, 3, 6, 12, 24 hours and 5, 10, 20, 50,100 return years, with a 1/30° spatial resolution. The QTPPIDFC dataset can solidly serve for hydrometeorological-related risk management and hydraulic/hydrologic engineering design in QTP.
Carboxylated nanocellulose from quinoa husk for enhanced protease immobilization and stability of protease in biotechnological applications
Authors: Ariaeenejad Shohreh , Motamedi Elaheh 
Published: January 2025

AbstractHerein, an efficient and feasible approach was developed to oxidize low-cost agricultural waste (quinoa husk, QS) for the synthesis of carboxylated nanocellulose (CNC). The as-prepared rod-like CNCs (average diameter of 10 nm and length of 103 nm) with a high specific surface area (173 m2/g) were utilized for the immobilization of a model protease enzyme (PersiProtease1) either physically or via covalent attachment. For chemical immobilization, CNCs were firstly functionalized with N, N′-dicyclohexylcarbodiimide (DCC) to provide DCNCs nanocarrier which could covalently bond to enzyme trough nucleophilic substitution reaction and formation of the amide bond between DCNCs and enzyme. The immobilization efficiency, activity, stability, kinetic parameters, and reusability of covalently attached and physically immobilized PersiProtease1 were similar to those of the free enzyme. Enzyme immobilization resulted in higher thermal stability of the enzyme at elevated temperatures (> 80 °C), and the covalently immobilized enzyme displayed higher reusability than its physically immobilized form (56% vs. 37% activity, after 15 consecutive cycles), which would be rooted in a more tightly attached and less leached enzyme in the case of PersiProtease1/DCNCs. This study demonstrates the significance of using agricultural by-products and the enhanced performance and stability of immobilized proteases.
Affordability of family foods is associated with Nutritional Status of women with pre-school children in Addis Ababa, Ethiopia
Authors: Abdelmenan Semira , Worku Alemayehu , Berhane Hanna Y. , Berhane Yemane , Ekström Eva-Charlotte 
Published: January 2025

AbstractMalnutrition among women of reproductive age is a critical public health issue in LMICs, where undernutrition coexists with rising overweight and obesity rates. In Ethiopia, particularly among urban women, maternal and child undernutrition remains high despite efforts to combat poverty and food insecurity. This study examined the relationship between food affordability and the nutritional status of 4797 women in Addis Ababa. Using repeated cross-sectional surveys, body mass index was calculated, and women’s nutritional status was categorized. Data on the affordability of 11 healthy family food groups were collected and categorized into terciles. Multinomial logistic regression models analyzed the association between food affordability and nutritional status, adjusting for confounding factors. The prevalence of underweight among women was 7.3%, while 39.1% were overweight or obese. On average, families could afford 6.1 out of the 11 food groups. Women with higher food affordability had increased odds of being overweight (AOR: 1.32; 95% CI 1.09, 1.60) or obese (AOR: 1.50; 95% CI 1.14, 1.97). The findings highlight that two out of five women are either overweight or obese, with obesity more likely in those with greater perceived food affordability. Addressing food choices as food affordability improves is crucial, as better food affordability is associated with an increased risk of becoming overweight and obese.
Effect of gabapentin on solution surface properties and micellization behavior of betaine-based surfactant ionic liquids
Authors: Ghasemzadeh Shima , Bagheri Mohammad , Shekaari Hemayat , Golmohammadi Behrang 
Published: January 2025

AbstractThis study investigates the surface properties, micellization, and electrical conductivity of betaine-based ionic liquids (ILs) composed of [R-bet][Br] where R represents the C4, C6 and C8 (specifically [C4bet][Br], [C6bet][Br], and [C8bet][Br]) in aqueous gabapentin solutions at concentrations of (0.0000, 0.0100, 0.0300, and 0.0500) mol kg−1 at 298.15 K. The surface tension measurements revealed that increasing gabapentin concentration and alkyl chain length decrease surface tension, indicating significant hydrophobic and hydrophilic interactions. The related thermophysical micellization parameters, including critical micelle concentration (CMC) and minimum surface area per molecule (Amin), exhibited improved micellization and interfacial efficiency with longer alkyl chains. Thermodynamic analysis confirm the spontaneous nature of micelle formation, with more negative Gibbs free energy values for SAILs with longer alkyl chains. The electrical conductivity studies indicate lower limiting molar conductivity (Λ0) at higher gabapentin concentrations, due to increased viscosity and ion-ion interactions. Ion association constants (KA) and DFT-COSMO calculations support stronger hydrophobic interactions and molecular packing influenced by alkyl chain length and gabapentin.
Validation of musculoskeletal segmentation model with uncertainty estimation for bone and muscle assessment in hip-to-knee clinical CT images
Authors: Soufi Mazen , Otake Yoshito , Iwasa Makoto , Uemura Keisuke , Hakotani Tomoki , Hashimoto Masahiro , Yamada Yoshitake , Yamada Minoru , Yokoyama Yoichi , Jinzaki Masahiro , Kusano Suzushi , Takao Masaki , Okada Seiji , Sugano Nobuhiko , Sato Yoshinobu 
Published: January 2025

AbstractDeep learning-based image segmentation has allowed for the fully automated, accurate, and rapid analysis of musculoskeletal (MSK) structures from medical images. However, current approaches were either applied only to 2D cross-sectional images, addressed few structures, or were validated on small datasets, which limit the application in large-scale databases. This study aimed to validate an improved deep learning model for volumetric MSK segmentation of the hip and thigh with uncertainty estimation from clinical computed tomography (CT) images. Databases of CT images from multiple manufacturers/scanners, disease status, and patient positioning were used. The segmentation accuracy, and accuracy in estimating the structures volume and density, i.e., mean HU, were evaluated. An approach for segmentation failure detection based on predictive uncertainty was also investigated. The model has improved all segmentation accuracy and structure volume/density evaluation metrics compared to a shallower baseline model with a smaller training database (N = 20). The predictive uncertainty yielded large areas under the receiver operating characteristic (AUROC) curves (AUROCs ≥ .95) in detecting inaccurate and failed segmentations. Furthermore, the study has shown an impact of the disease severity status on the model’s predictive uncertainties when applied to a large-scale database. The high segmentation and muscle volume/density estimation accuracy and the high accuracy in failure detection based on the predictive uncertainty exhibited the model’s reliability for analyzing individual MSK structures in large-scale CT databases.
Study of the spatial strength distribution patterns and microstructure characteristics of ultra-fine tailings cemented paste backfill
Authors: Tan Yuye , Li Yiding , Yu Xin , Deng Yuchao , Song Zepu , Kou Yunpeng 
Published: January 2025

AbstractIn this study, the spatial distribution of the mechanical strength of ultra-fine tailings cemented paste backfill (UCPB) in underground stopes was examined, and the micro-mechanism responsible for differences in spatial strength performance via changes in particle deposition was elucidated. To better understand this phenomenon, we constructed a similar backfilling stope model using the ultra-fine tailings of a gold mine. We manufactured specimens at different spatial locations and conducted a novel series of tests, including uniaxial compressive strength, shear strength, and conventional triaxial tests, to obtain the strength parameters in different spatial distributions. The strength parameters for the different UCPB locations in this model were revealed and examined along with the original pore and particle size distributions. Computer tomography (CT) and scanning electron microscopy (SEM) observations before and after the UCPB failed revealed that the particle deposition effect at different positions was the primary cause of the size effect. The strength distribution pattern demonstrated that the UCPB material has an apparent spatial effect. Consequently, considering the position relationship between the stope and filling mouth is crucial when designing the strength of adjacent mining rooms. This research may guide both backfill study and design.
Risk factors for photic phenomena in two different multifocal diffractive intraocular lenses
Authors: Ukai Yuki , Mito Tsuyoshi , Nakatsugawa Yui , Seki Yusuke , Mita Norihiro , Shibuya Eri , Yamazaki Mai , Kubo Eri , Sasaki Hiroshi 
Published: January 2025

AbstractPhotic phenomena are more pronounced in presbyopia-corrected than in monofocal intraocular lens (IOL), causing dissatisfaction after cataract surgery. Photic Phenomena Test (PPT) quantifies photic phenomena in eyes with two types of presbyopia-corrected IOL. We examined the relationship between preoperative eye shape and pupil diameter. We included patients with PanOptix IOLs (PanOptix group, n = 38; 65.7 ± 9.2 years old) and Synergy IOLs (Synergy group, n = 39; 61.9 ± 9.6 years old), who underwent the PPT between 1 and 3 months after cataract surgery, from January 2021 to April 2023. The relationships between age, sex, pupil diameter, and higher-order corneal aberrations were examined and mean values for PPT measurements were compared between the groups. There was no difference in glare between the two groups. The halo was larger and thicker, and the starburst was larger and stronger in the Synergy group (P < 0.01). Postoperative halo brightness was positively correlated with the corneal coma aberration in the PanOptix group (P < 0.05). The Synergy group showed a positive correlation between the size and brightness of the postoperative halo and starburst and pupil diameter (P < 0.01). PPT, thus, revealed risk factors in eyes with two types of presbyopia-corrected IOL, which can be examined before cataract surgery to provide critical information for IOL selection.
Raiding nature’s genetic toolbox for UV-C resistance by functional metagenomics
Authors: Roberts Kingman Garrett A. , Kipness Justin L. , Rothschild Lynn J. 
Published: January 2025

AbstractAs we assess the habitability of other worlds, we are limited by being able to only study terrestrial life adapted to terrestrial conditions. The environments found on Earth, though tremendously diverse, do not approach the multitude of potentially habitable environments beyond Earth, and so limited terrestrial adaptive capabilities tell us little about the fundamental biochemical boundaries of life. One approach to this problem is to use experimental laboratory evolution to adapt microbes to these novel environmental conditions. This approach can be dramatically improved through functional metagenomics, large-scale introduction of foreign genetic material to screen for phenotypes in a new host organism. This takes advantage of Earth’s immense biological diversity with high-throughput screening for genetic tools that can facilitate adaptation. We address a key gap in functional metagenomics work by exploring the impact of the experimental parameters chosen for functional metagenomics libraries. Experimental design dictates both fragment size and copy number, and we show that both can have outsized effects on the resultant phenotypes in non-intuitive ways. These results highlight the potential of functional metagenomics for adapting life rapidly to challenging new environments, with important implications in both astrobiology and bioindustry, while also emphasizing the impacts of decisions in experimental design.