bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein‐based materials
Authors: Italia Valeria , Jons Amanda , Kaparthi Bhavika , Faulk Britt , Maccarini Marco , Bertoncello Paolo , Meissner Ken , Martin Donald K. , Bondos Sarah E. 
Published: January 2025

AbstractThe Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment. We discovered that in low salt buffers, we can generate a new type of Ubx material from early coacervates using 5‐fold less protein, and 100‐fold less assembly time. Comparison of the new materials with standard Ubx fibers also revealed differences in the extent of wrinkling on the fiber surface. A new image analysis technique based on autocorrelation of scanning electron microscopy (SEM) images was developed to quantify these structural differences. These differences extend to the molecular level: new materials form more dityrosine covalent cross‐links per monomer, but without requiring the specific tyrosine residues necessary for crosslinking previously established materials. We conclude that varying the assembly conditions represents a facile and inexpensive process for creating new materials. Most new biopolymers are created by changing the composition of the monomers or the method used to drive assembly. In contrast, in this study we used the same monomers and assembly approach, but altered the assembly time and chemical environment to create a new material with unique properties.
α‐N‐Methyltransferase regiospecificity is mediated by proximal, redundant enzyme–substrate interactions
Authors: Crone Kathryn K. , Labonte Jason W. , Elias Mikael H. , Freeman Michael F. 
Published: January 2025

AbstractN‐Methylation of the peptide backbone confers pharmacologically beneficial characteristics to peptides that include greater membrane permeability and resistance to proteolytic degradation. The borosin family of ribosomally synthesized and post‐translationally modified peptides offer a post‐translational route to install amide backbone α‐N‐methylations. Previous work has elucidated the substrate scope and engineering potential of two examples of type I borosins, which feature autocatalytic precursors that encode N‐methyltransferases that methylate their own C‐termini in trans. We recently reported the first discrete N‐methyltransferase and precursor peptide from Shewanella oneidensis MR‐1, a minimally iterative, type IV borosin that allowed the first detailed kinetic analyses of borosin N‐methyltransferases. Herein, we characterize the substrate scope and resilient regiospecificity of this discrete N‐methyltransferase by comparison of relative rates and methylation patterns of over 40 precursor peptide variants along with structure analyses of nine enzyme–substrate complexes. Sequences critical to methylation are identified and demonstrated in assaying minimal peptide substrates and non‐native peptide sequences for assessment of secondary structure requirements and engineering potential. This work grants understanding towards the mechanism of substrate recognition and iterative activity by discrete borosin N‐methyltransferases.
Loop engineering of enzymes to control their immobilization and ultimately fabricate more efficient heterogeneous biocatalysts
Authors: Zeballos Nicoll , Ginés‐Alcober Irene , Macías‐León Javier , Andrés‐Sanz Daniel , González‐Ramírez Andrés Manuel , Sánchez‐Costa Mercedes , Merino Pedro , Hurtado‐Guerrero Ramón , López‐Gallego Fernando 
Published: January 2025

AbstractEnzyme immobilization is indispensable for enhancing enzyme performance in various industrial applications. Typically, enzymes require specific spatial arrangements for optimal functionality, underscoring the importance of correct orientation. Despite well‐known N‐ or C‐terminus tailoring techniques, alternatives for achieving orientation control are limited. Here, we propose a novel approach that tailors the enzyme surface with engineered His‐rich loops. To that aim, we first solve the X‐ray crystal structure of a hexameric alcohol dehydrogenase from Thermus thermophilus HB27 (TtHBDH) (PDB: 9FBD). Guided by this 3D structure, we engineer the enzyme surface with a new loop enriched with six His residues to control enzyme orientation. Molecular dynamics simulations reveal that the engineered loop's imidazole rings have greater solvent accessibility than those in native His residues, allowing for more efficient enzyme immobilization on certain metal chelate‐functionalized carriers. Using carriers functionalized with iron (III)‐catechol, the apparent Vmax of the immobilized loop variant doubles the immobilized His‐tagged one, and vice versa when both variants are immobilized on carriers functionalized with copper (II)‐imidodiacetic acid. His‐tagged and loop‐engineered TtHBDH show high operational stability reaching 100% bioconversion after 10 reaction cycles, yet the loop variant is faster than the His‐tagged one.
Allosteric modulation of NF1 GAP: Differential distributions of catalytically competent populations in loss‐of‐function and gain‐of‐function mutants
Authors: Xu Liang , Jang Hyunbum , Nussinov Ruth 
Published: January 2025

AbstractNeurofibromin (NF1), a Ras GTPase‐activating protein (GAP), catalyzes Ras‐mediated GTP hydrolysis and thereby negatively regulates the Ras/MAPK pathway. NF1 mutations can cause neurofibromatosis type 1 manifesting tumors, and neurodevelopmental disorders. Exactly how the missense mutations in the GAP‐related domain of NF1 (NF1GRD) allosterically impact NF1 GAP to promote these distinct pathologies is unclear. Especially tantalizing is the question of how same‐domain, same‐residue NF1GRD variants exhibit distinct clinical phenotypes. Guided by clinical data, we take up this dilemma. We sampled the conformational ensembles of NF1GRD in complex with GTP‐bound K‐Ras4B by performing molecular dynamics simulations. Our results show that mutations in NF1GRD retain the active conformation of K‐Ras4B but with biased propensities of the catalytically competent populations of K‐Ras4B–NF1GRD complex. In agreement with clinical depiction and experimental tagging, compared to the wild type, NF1GRD E1356A and E1356V mutants effectively act through loss‐of‐function and gain‐of‐function mechanisms, leading to neurofibromatosis and developmental disorders, respectively. Allosteric modulation of NF1GRD GAP activity through biasing the conformational ensembles in the different states is further demonstrated by the diminished GAP activity by NF1GRD isoform 2, further manifesting propensities of conformational ensembles as powerful predictors of protein function. Taken together, our work identifies a NF1GRD hotspot that could allosterically tune GAP function, suggests targeting Ras oncogenic mutations by restoring NF1 catalytic activity, and offers a molecular mechanism for NF1 phenotypes determined by their distinct conformational propensities.
Combining computational modeling and experimental library screening to affinity‐mature VEEV‐neutralizing antibody F5
Authors: Sumner Christopher A. , Schwedler Jennifer L. , McCoy Katherine Maia , Holland Jack , Duva Valerie , Gelperin Daniel , Busygina Valeria , Stefan Maxwell A. , Martinez Daniella V. , Juarros Miranda A. , Phillips Ashlee M. , Weilhammer Dina R. , Grigoryan Gevorg , Kent Michael S. , Harmon Brooke N. 
Published: January 2025

AbstractEngineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand‐up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen. We modeled the F5/E1E2 binding interface and generated predictions for mutations to improve binding using a Rosetta‐based approach and dTERMen, an informatics approach. The modeling was complicated by the fact that a high‐resolution structure of F5 is not available and the H3 loop of F5 exceeds the length for which current modeling approaches can determine a unique structure. A subset of the predicted mutations from both methods were incorporated into a phage display library of scFvs. This library and a library generated by error‐prone PCR were screened for binding affinity to the recombinant antigen. Results from the screens identified favorable mutations which were incorporated into 12 human‐IgG1 variants. The best variant, containing eight mutations, improved KD from 0.63 nM (parental) to 0.01 nM. While this did not improve neutralization or therapeutic potency of F5 against IAB, it did increase cross‐reactivity to other closely related VEEV epizootic and enzootic strains, demonstrating the potential of this method to rapidly adapt existing therapeutics to emerging viral strains.
PET/CT Imaging of the Right Heart Perfusion and Glucose Metabolism Depending on a Risk Status in Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Goncharova Natalia , Ryzhkova Daria , Lapshin Kirill , Ryzhkov Anton , Malanova Aryana , Andreeva Elizaveta , Moiseeva Olga 
Published: January 2025

ABSTRACTRight ventricular heart failure (RV HF) is the leading cause of death in pulmonary arterial hypertension (PAH). Relevance of the low‐risk status assessment using available diagnostic tools requires a reliable confirmation. The study aimed to evaluate right ventricular perfusion and glucose metabolism using positron emission tomography (PET)/computed tomography (CT) with [13N]‐ammonia and [18F]‐fluorodeoxyglucose ([18F]‐FDG) in 30 IPAH patients (33.8 ± 9.4 years) according to ESC/ERS 2022 risk status. The ratio of SUVmaxRV/LV metabolism and SUVmaxRV/LV perfusion showed significant positive correlation with pulmonary artery pressure, right heart dilatation, NT‐proBNP level and negative correlation with the RV ejection fraction. The SUVmaxRV/LV perfusion and SUVmaxRV/LV metabolism ratios differed significantly according to risk status. Low risk patients had a SUVmaxRV/LV metabolism comparable to the controls without PH. The SUVmaxRV/LV perfusion ratio was elevated in low‐risk IPAH patients compared with controls. Increased SUVmaxRV/LV perfusion may be an early marker of coronary flow adaptation to RV pressure overload in low‐risk IPAH patients and requires further evaluation. Further long‐term studies are needed to determine the clinical relevance and cut‐off values for the RV/LV PET/CT with [13N]‐ammonia and [18F]‐fluorodeoxyglucose ([18F]‐FDG) uptake in different IPAH risk groups.
C‐type natriuretic peptide promotes human granulosa cell growth and estradiol production: Implications for early follicle development
Authors: Sato Yorino , Kawamura Kazuhiro 
Published: January 2025

AbstractPurposeTo investigate the effects of C‐type natriuretic peptide (CNP) on human granulosa cell growth and elucidate its regulatory mechanisms.MethodsA human non‐luteinizing granulosa cell line (HGrC) developed from small antral follicles was used to assess the impact of CNP on cell proliferation and estrogen synthesis. cGMP production via the guanylate cyclase domain of the CNP receptor, natriuretic peptide receptor 2 (NPR2), was confirmed. The regulation of CNP encoding natriuretic peptide C (NPPC) and NPR2 by estradiol and oocyte‐derived factors (ODFs) was examined.ResultsBesides detecting both NPPC and NPR2, CNP increased cellular proliferation. The specific action of CNP on cell proliferation was confirmed using siRNA transfection. CNP stimulated cGMP production, whereas a guanylate‐cyclase inhibitor suppressed CNP‐induced cell proliferation. Estradiol production was elevated by CNP treatment, accompanied by increased expression of estrogen synthetic enzymes. Furthermore, CNP upregulated NPR2 expression in cooperation with estradiol and ODFs, while estradiol increased NPPC expression.ConclusionThis study demonstrates CNP stimulation of human granulosa cell growth and suggests potential cross‐talk between these cells and oocytes. Further research on the simultaneous administration of CNP and estradiol may offer a promising approach for promoting early‐stage follicle development in infertility treatments for patients with poor ovarian reserve.
Incorporating Deep Learning Into System Dynamics: Amortized Bayesian Inference for Scalable Likelihood‐Free Parameter Estimation
Authors: Rahmandad Hazhir , Akhavan Ali , Jalali Mohammad S. 
Published: January 2025

ABSTRACTEstimating parameters and their credible intervals for complex system dynamics models is challenging but critical to continuous model improvement and reliable communication with an increasing fraction of audiences. The purpose of this study is to integrate Amortized Bayesian Inference (ABI) methods with system dynamics. Utilizing Neural Posterior Estimation (NPE), we train neural networks using synthetic data (pairs of ground truth parameters and outcome time series) to estimate parameters of system dynamics models. We apply this method to two example models: a simple Random Walk model and a moderately complex SEIRb model. We show that the trained neural networks can output the posterior for parameters instantly given new unseen time series data. Our analysis highlights the potential of ABI to facilitate a principled, scalable, and likelihood‐free inference workflow that enhance the integration of models of complex systems with data. Accompanying code streamlines application to diverse system dynamics models.
In Situ Slow‐Release Hydrogen Sulfide Therapeutics for Advanced Disease Treatments
Authors: Chen Yiqing , Chen Zhishan , Chen Xingzhong , Zhang Shizhen , Zhang Shaoan , Kang Qiyun , Sharafudeen Kaniyarakkal , Lian Huiwang , Saravanakumar Subramanian , Zhang Xinyue , Xu Jialong , Zhu Xiaoqin , Zhang Qingbin , Han Gang , Li Yang 
Published: January 2025

AbstractHydrogen sulfide (H2S) gas therapygarners significant attention for its potential to improve outcomes in various disease treatments. The quantitative control of H2S release is crucial for effective the rapeutic interventions; however, traditional researchon H2S therapy frequently utilizes static release models and neglects the dynamic nature of blood flow. In this study, we propose a novel slow‐release in‐situ H2S release model that leverages the dynamic hydrolysis of H2S donorswithin the bloodstream. Calcium sulfide nanoparticles (CaS NPs) withmicrosolubility characteristics exhibit continuous H2S release, surpassing 24 h at normal blood flow velocities. The extended‐release profile demonstrates superior potential in aligning with the bell‐shapedpharmacological effect of H2S, compared to NaHS. Moreover, we synthesisedrare earth‐doped CaS NPs (CaS: Eu2+, Sm3+ NPs) tha texhibit persistent luminescence, enabling visualisation of the continuous H2S release in trials. Our results demonstrate that lowdose CaS: Eu2+, Sm3+ NPs significantly reduces seizureduration to 1.2 ± 0.7 minutes, while high dose effectively suppresses colontumor growth with a tumor inhibition rate of 54%. Remarkably, these findings closely resemble endogenous H2S levels in treating epilepsy and tumors. This innovative slow‐release, in‐situ H2S the rapeutic approach via hydrolysis rejuvenates the development of H2S‐basedtherapeutics.
Toward Green and Sustainable Zinc‐Ion Batteries: The Potential of Natural Solvent‐Based Electrolytes
Authors: Yaman Uzunoglu Gulsah , Yuksel Recep 
Published: January 2025

AbstractZinc‐ion batteries (ZIBs) are emerged as a promising alternative for sustainable energy storage, offering advantages such as safety, low cost, and environmental friendliness. However, conventional aqueous electrolytes in ZIBs face significant challenges, including hydrogen evolution reaction (HER) and zinc dendrite formation, compromising their cycling stability and safety. These limitations necessitate innovative electrolyte solutions to enhance ZIB performance while maintaining sustainability. This review explores the potential of natural solvent‐based electrolytes derived from renewable and biodegradable resources. Natural deep eutectic solvents (DES), bio‐ionic liquids, and biomass‐derived organic compounds present unique advantages, including a wider electrochemical stability window, reduced HER activity, and controlled zinc deposition. Examples include DESs based on choline chloride (ChCl), glycerol‐based systems, and biomass‐derived solvents such as γ‐valerolactone (GVL) and aloe vera, demonstrating improved cycling stability and dendrite suppression. Despite their promise, challenges such as high viscosity, cost, and scalability remain critical barriers to commercialization. This review underscores the need for further research to optimize natural solvent formulations, enhance Zn anode compatibility, and integrate these systems into practical applications. By addressing these challenges, natural solvent‐based electrolytes can pave the way for safer, high‐performance, and environmentally sustainable ZIBs, particularly large‐scale energy storage systems.
Semi‐Confinement Effect Enhances CH4 and C2H4 Production in CO2 Electrocatalytic Reduction
Authors: Song Jiahao , Sun Hanlei , Yao Shuo , Liu Ziyong , Lv Ming , Li Fuli , Lv Zhihui , Hu Xinming , Wang Hongzhi , Liu Licheng 
Published: January 2025

AbstractAchieving fast conversion and precise regulation of product selectivity in electrochemical CO2 reduction reaction (CO2RR) remains a challenge. The space confinement effect provides a theoretical basis for the design of catalysts of different morphology and sizes and reveals the physical phenomena caused by the confinement of electrons and other particles at the nanoscale. In this work, a semi‐confinement concept is introduced and a mesoporous silica nanosphere supported Cu catalyst (Cu‐MSN) is prepared as a typical example to realize CO2RR enhancement and product selectivity regulation (methane vs ethylene). The semi‐confined structure partially solves the mass transfer problem of classical confined catalysis. Cu‐MSN allows flexible controls aggregation form of Cu species by loading amount, which achieves a free switch from methane Faraday efficiency of 71.1% to ethylene Faraday efficiency of 66.4%. Various characterizations confirm that the fast adsorption behavior and local coordination structure transformation of Cu (from Cu─O─Si to Cu─O─Cu), which can stabilize key intermediates *CHO and *CO*COH for generating respective methane and ethylene.
Sonographic Anatomy and Imaging of the Dorsal Thumb Tendons
Authors: Fenech Michelle , Walkley Daniel , Carmody Deborah , Roots Jacqueline , Obrien Sophie , Diep Susan , Winnett Craig , Grant Andrew , Yeoh Sean , Roche Bridie 
Published: January 2025

ABSTRACTInjuries to the dorsal thumb tendons and related structures can result in impairment to thumb motion. Ultrasound imaging is useful in diagnosing structural change in the dorsal thumb tendons, branches of the superficial radial nerve, and the dorsal hood. A detailed knowledge of the anatomy, sonographic technique, and normal and abnormal sonographic appearances is required to appropriately identify pertinent findings to guide patient management.
Probabilistic model for ultimate displacement of reinforced concrete columns with flexural failure
Authors: Wang Haoyu , Zhang Pengfei , Li Shaonan , Yu Bo 
Published: January 2025

AbstractIn order to describe the probabilistic characteristics of the ultimate displacement, a probabilistic model for ultimate displacement of reinforced concrete columns with flexural failure was proposed based on the Bayesian theory and the Markov Chain Monte Carlo (MCMC) method. An analytical model for probabilistic ultimate displacement was established first according to the plane cross‐section assumption and the equivalent plastic hinge theory. Then probabilistic model parameters were determined based on the Bayesian theory and the MCMC method. Finally, the proposed model was verified by comparison with 252 sets of experimental data and existing ultimate displacement models. Comparisons show that the proposed model not only provides reasonable prediction accuracy but also describes the probability distribution of ultimate displacement realistically. Furthermore, the proposed model is useful for the validation of the accuracy and applicability of available deterministic ultimate displacement models, which provide probabilistic validation methods based on the confidence interval and probability density function.
Natural Flood Risk Management in Tropical Southeast Asia: Prospects in the Biodiverse Archipelagic Nation of the Philippines
Authors: Tolentino Pamela Louise M. , Williams Richard D. , Hurst Martin D. 
Published: January 2025

ABSTRACTNatural flood management (NFM) has gained prominence as a flood risk management approach in temperate settings but lacks extensive applied examples and evidence in tropical settings, despite significant ecosystem degradation and high flood risk exposure. Tropical river catchments often experience highly variable hydrographs (i.e., prone to flash floods) and intense rainfall from monsoon and typhoon‐dominated weather systems that can cause landslides and sediment‐transporting river flows. These conditions provide a backdrop to the prospects for NFM in tropical Southeast Asia, of which the Philippines is representative. Catchments in the country are typically small and thus associated with short hydrological response times. They are also characterized by diversity of river types, high rates of lateral mobility, extensive downstream urbanization, and complex land use mosaics at the coast. Consideration of NFM as a conceptual framework in the Philippines may enable conversations about adapting existing flood risk management approaches. To explore these NFM alternatives, we conceptualize opportunities in a typical catchment that we divide into four nested, connected parts: managing headwaters as sponges; conserving and restoring river and floodplain width; blue‐green infrastructure in urban areas; and maintaining and creating space for water in fluvial‐coastal settings. There is potential in countries such as the Philippines to adopt NFM strategies that have shown promise in temperate regions and select Southeast Asian countries, where emerging evidence supports their effectiveness. Monitoring tropical NFM interventions remains crucial to gather evidence supporting broader application of nature‐based solutions for flood risk mitigation and biodiversity loss in tropical Southeast Asia.