bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCAPH, ubiquitinated by TRIM21, promotes cell proliferation by inhibiting autophagy of cervical cancer through AKT/mTOR dependent signaling
Authors: Wang Shiqi , Qiao Xiaowen , Cui Yaqi , Liu Liang , Cooper Tamara , Hu Yingxin , Lin Jiaxiang , Liu Haiting , Wang Meng , Hayball John , Wang Xiao 
Published: August 2024

AbstractAutophagy is closely related to the occurrence and development of human malignancies; however, the detailed mechanisms underlying autophagy in cervical cancer require further investigation. Previously, we found that the ectopic expression of NCAPH, a regulatory subunit of condensed protein complexes, significantly enhanced the proliferation of tumor cells; however, the underlying mechanisms were unclear. Here, we revealed that NCAPH is a novel autophagy-associated protein in cervical cancer that promotes cell proliferation by inhibiting autophagosome formation and reducing autophagy, with no effect on the cell cycle, apoptosis, or aging. Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in inflammation, autoimmunity and cancer, mainly via its E3 ubiquitin ligase activity. Mass spectrometry and immunoprecipitation assays showed that TRIM21 interacted with NCAPH and decreased the protein stability of NCAPH via ubiquitination at the K11 lysine residue. Structural domain mutation analysis revealed that TRIM21 combined with NCAPH through its PRY/SPRY and CC domains and accelerated the degradation of NCAPH through the RING domain. Furthermore, TRIM21 promoted autophagosome formation and reduced cell proliferation by inhibiting NCAPH expression and the downstream AKT/mTOR pathway in cervical cancer cells. Immunohistochemical staining revealed that the protein expression of TRIM21 was negatively correlated with that of NCAPH and positively correlated with that of beclin-1 in cervical cancer tissues. Therefore, we provide evidence for the role of the TRIM21-NCAPH axis in cervical cancer autophagy and proliferation and the involvement of the AKT/mTOR signaling pathway in this process. These results deepen our understanding of the carcinogenesis of cervical cancer, broaden the understanding of the molecular mechanisms of TRIM21 and NCAPH, and provide guidance for individualized treatment of cervical cancer in the future.
Barcoded overexpression screens in gut Bacteroidales identify genes with roles in carbon utilization and stress resistance
Authors: Huang Yolanda Y. , Price Morgan N. , Hung Allison , Gal-Oz Omree , Tripathi Surya , Smith Christopher W. , Ho Davian , Carion Héloïse , Deutschbauer Adam M. , Arkin Adam P. 
Published: August 2024

AbstractA mechanistic understanding of host-microbe interactions in the gut microbiome is hindered by poorly annotated bacterial genomes. While functional genomics can generate large gene-to-phenotype datasets to accelerate functional discovery, their applications to study gut anaerobes have been limited. For instance, most gain-of-function screens of gut-derived genes have been performed in Escherichia coli and assayed in a small number of conditions. To address these challenges, we develop Barcoded Overexpression BActerial shotgun library sequencing (Boba-seq). We demonstrate the power of this approach by assaying genes from diverse gut Bacteroidales overexpressed in Bacteroides thetaiotaomicron. From hundreds of experiments, we identify new functions and phenotypes for 29 genes important for carbohydrate metabolism or tolerance to antibiotics or bile salts. Highlights include the discovery of a d-glucosamine kinase, a raffinose transporter, and several routes that increase tolerance to ceftriaxone and bile salts through lipid biosynthesis. This approach can be readily applied to develop screens in other strains and additional phenotypic assays.
Bidirectional pilus processing in the Tad pilus system motor CpaF
Authors: Hohl Michael , Banks Emma J. , Manley Max P. , Le Tung B. K. , Low Harry H. 
Published: August 2024

AbstractThe bacterial tight adherence pilus system (TadPS) assembles surface pili essential for adhesion and colonisation in many human pathogens. Pilus dynamics are powered by the ATPase CpaF (TadA), which drives extension and retraction cycles in Caulobacter crescentus through an unknown mechanism. Here we use cryogenic electron microscopy and cell-based light microscopy to characterise CpaF mechanism. We show that CpaF assembles into a hexamer with C2 symmetry in different nucleotide states. Nucleotide cycling occurs through an intra-subunit clamp-like mechanism that promotes sequential conformational changes between subunits. Moreover, a comparison of the active sites with different nucleotides bound suggests a mechanism for bidirectional motion. Conserved CpaF residues, predicted to interact with platform proteins CpaG (TadB) and CpaH (TadC), are mutated in vivo to establish their role in pilus processing. Our findings provide a model for how CpaF drives TadPS pilus dynamics and have broad implications for how other ancient type 4 filament family members power pilus assembly.
Proteostasis perturbation of N-Myc leveraging HSP70 mediated protein turnover improves treatment of neuroendocrine prostate cancer
Authors: Xu Pengfei , Yang Joy C. , Chen Bo , Ning Shu , Zhang Xiong , Wang Leyi , Nip Christopher , Shen Yuqiu , Johnson Oleta T. , Grigorean Gabriela , Phinney Brett , Liu Liangren , Wei Qiang , Corey Eva , Tepper Clifford G. , Chen Hong-Wu , Evans Christopher P. , Dall’Era Marc A. , Gao Allen C. , Gestwicki Jason E. , Liu Chengfei 
Published: August 2024

AbstractN-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved “SELILKR” motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70’s dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.
Fiber-optic seismic sensing of vadose zone soil moisture dynamics
Authors: Shen Zhichao , Yang Yan , Fu Xiaojing , Adams Kyra H. , Biondi Ettore , Zhan Zhongwen 
Published: August 2024

AbstractVadose zone soil moisture is often considered a pivotal intermediary water reservoir between surface and groundwater in semi-arid regions. Understanding its dynamics in response to changes in meteorologic forcing patterns is essential to enhance the climate resiliency of our ecological and agricultural system. However, the inability to observe high-resolution vadose zone soil moisture dynamics over large spatiotemporal scales hinders quantitative characterization. Here, utilizing pre-existing fiber-optic cables as seismic sensors, we demonstrate a fiber-optic seismic sensing principle to robustly capture vadose zone soil moisture dynamics. Our observations in Ridgecrest, California reveal sub-seasonal precipitation replenishments and a prolonged drought in the vadose zone, consistent with a zero-dimensional hydrological model. Our results suggest a significant water loss of 0.25 m/year through evapotranspiration at our field side, validated by nearby eddy-covariance based measurements. Yet, detailed discrepancies between our observations and modeling highlight the necessity for complementary in-situ validations. Given the escalated regional drought risk under climate change, our findings underscore the promise of fiber-optic seismic sensing to facilitate water resource management in semi-arid regions.
Removing development incentives in risky areas promotes climate adaptation
Authors: Druckenmiller Hannah , Liao Yanjun , Pesek Sophie , Walls Margaret , Zhang Shan 
Published: August 2024

AbstractAs natural disasters grow in frequency and intensity with climate change, limiting the populations and properties in harm’s way will be key to adaptation. This study evaluates one approach to discouraging development in risky areas—eliminating public incentives for development, such as infrastructure investments, disaster assistance and federal flood insurance. Using machine learning and matching techniques, we examine the Coastal Barrier Resources System (CBRS), a set of lands where these federal incentives have been removed. We find that the policy leads to lower development densities inside designated areas, increases development in neighbouring areas, reduces flood damages and alters local demographics. Our results suggest that the CBRS generates substantial savings for the federal government by reducing flood claims in the National Flood Insurance Program, while increasing the property tax base in coastal counties.
Nine months of daily LiDAR, orthophotos and MetOcean data from the eroding soft cliff coast at Happisburgh, UK
Authors: Pennington Catherine , Shaw Matthew , Brooks Thomas , Briganti Riccardo , Gómez-Pazo Alejandro , Ruffini Gioele , Appleton Matthew , Payo Andres 
Published: August 2024

AbstractThe dynamic interaction between cliff, beach and shore-platform is key to assessing the sediment balance for coastal erosion risk assessments, but this is poorly understood. We present a dataset containing daily, 3D,colour LiDAR scans of a 450 m coastal section at Happisburgh, Norfolk, UK. This previously para-glaciated region comprises mixed sand-gravel sediments, which are less well-understood and well-studied than sandy beaches. From Apr-Dec 2019, 236 daily surveys were carried out. The dataset presented includes: survey areas, transects LiDAR scans, georeferenced orthophotos, meteorological- and oceanographical conditions during the Apr-Dec observation period. Full LiDAR point-clouds are available for 67 scans (Oct-Dec). Hourly time-series of offshore sea-state parameters (significant wave height, mean propagation direction, selected spectral periods) were obtained by downscaling the ERA5 global reanalysis data (global atmosphere, land surface and ocean waves) using the numerical model Simulating Waves Nearshore (SWAN). We indicate how to obtain hourly precipitation time-series by interpolating ERA5 data. This dataset is important for researchers understanding the interaction between cliff, beach and shore-platform in open-coast mixed-sand-gravel environments.
Machine learning-assisted discovery of flow reactor designs
Authors: Savage Tom , Basha Nausheen , McDonough Jonathan , Krassowski James , Matar Omar , del Rio Chanona Ehecatl Antonio 
Published: August 2024

AbstractAdditive manufacturing has enabled the fabrication of advanced reactor geometries, permitting larger, more complex design spaces. Identifying promising configurations within such spaces presents a significant challenge for current approaches. Furthermore, existing parameterizations of reactor geometries are low dimensional with expensive optimization, limiting more complex solutions. To address this challenge, we have established a machine learning-assisted approach for the design of new chemical reactors, combining the application of high-dimensional parameterizations, computational fluid dynamics and multi-fidelity Bayesian optimization. We associate the development of mixing-enhancing vortical flow structures in coiled reactors with performance and used our approach to identify the key characteristics of optimal designs. By appealing to the principles of fluid dynamics, we rationalized the selection of design features that lead to experimental plug flow performance improvements of ~60% compared with conventional designs. Our results demonstrate that coupling advanced manufacturing techniques with ‘augmented intelligence’ approaches can give rise to reactor designs with enhanced performance.
Real-time assessment of mitochondrial DNA heteroplasmy dynamics at the single-cell level
Authors: Roussou Rodaria , Metzler Dirk , Padovani Francesco , Thoma Felix , Schwarz Rebecca , Shraiman Boris , Schmoller Kurt M , Osman Christof 
Published: August 2024

AbstractMitochondrial DNA (mtDNA) is present in multiple copies within cells and is required for mitochondrial ATP generation. Even within individual cells, mtDNA copies can differ in their sequence, a state known as heteroplasmy. The principles underlying dynamic changes in the degree of heteroplasmy remain incompletely understood, due to the inability to monitor this phenomenon in real time. Here, we employ mtDNA-based fluorescent markers, microfluidics, and automated cell tracking, to follow mtDNA variants in live heteroplasmic yeast populations at the single-cell level. This approach, in combination with direct mtDNA tracking and data-driven mathematical modeling reveals asymmetric partitioning of mtDNA copies during cell division, as well as limited mitochondrial fusion and fission frequencies, as critical driving forces for mtDNA variant segregation. Given that our approach also facilitates assessment of segregation between intact and mutant mtDNA, we anticipate that it will be instrumental in elucidating the mechanisms underlying the purifying selection of mtDNA.
Experimental vaccination by single dose sporozoite injection of blood-stage attenuated malaria parasites
Authors: Sattler Julia M , Keiber Lukas , Abdelrahim Aiman , Zheng Xinyu , Jäcklin Martin , Zechel Luisa , Moreau Catherine A , Steinbrück Smilla , Fischer Manuel , Janse Chris J , Hoffmann Angelika , Hentzschel Franziska , Frischknecht Friedrich 
Published: August 2024

AbstractMalaria vaccination approaches using live Plasmodium parasites are currently explored, with either attenuated mosquito-derived sporozoites or attenuated blood-stage parasites. Both approaches would profit from the availability of attenuated and avirulent parasites with a reduced blood-stage multiplication rate. Here we screened gene-deletion mutants of the rodent parasite P. berghei and the human parasite P. falciparum for slow growth. Furthermore, we tested the P. berghei mutants for avirulence and resolving blood-stage infections, while preserving sporozoite formation and liver infection. Targeting 51 genes yielded 18 P. berghei gene-deletion mutants with several mutants causing mild infections. Infections with the two most attenuated mutants either by blood stages or by sporozoites were cleared by the immune response. Immunization of mice led to protection from disease after challenge with wild-type sporozoites. Two of six generated P. falciparum gene-deletion mutants showed a slow growth rate. Slow-growing, avirulent P. falciparum mutants will constitute valuable tools to inform on the induction of immune responses and will aid in developing new as well as safeguarding existing attenuated parasite vaccines.
Solving Boltzmann optimization problems with deep learning
Authors: Knoll Fiona , Daly John , Meyer Jess 
Published: August 2024

AbstractDecades of exponential scaling in high-performance computing (HPC) efficiency is coming to an end. Transistor-based logic in complementary metal-oxide semiconductor (CMOS) technology is approaching physical limits beyond which further miniaturization will be impossible. Future HPC efficiency gains will necessarily rely on new technologies and paradigms of computing. The Ising model shows particular promise as a future framework for highly energy-efficient computation. Ising systems are able to operate at energies approaching thermodynamic limits for energy consumption of computation. Ising systems can function as both logic and memory. Thus, they have the potential to significantly reduce energy costs inherent to CMOS computing by eliminating costly data movement. The challenge in creating Ising-based hardware is in optimizing useful circuits that produce correct results on fundamentally nondeterministic hardware. The contribution of this paper is a novel machine learning approach, a combination of deep neural networks and random forests, for efficiently solving optimization problems that minimize sources of error in the Ising model. In addition, we provide a process to express a Boltzmann probability optimization problem as a supervised machine learning problem.
Cinnamon extracts, trans-cinnamaldehyde and trans-cinnamic acid inhibit HDAC 1 activity
Authors: Koyu Halil , Istanbullu Huseyin , Turunc Ozoglu Sinem Ezgi , Kaya Temiz Tijen 
Published: August 2024

Essential oil and 70% ethanol extract of Cinnamomum cassia bark can be evaluated to be used in products against HDAC 1 related diseases.
An analytical approach for power system frequency stability evaluation
Authors: Li Zhenyao , Li Jing , Gan Deqiang 
Published: August 2024

AbstractRecent years have seen high penetration of renewable energies, which have significantly reduced the inertia of bulk power systems. As a result, the frequency behaviour of power systems is becoming more complex. To resolve this technical challenge, there is a particularly strong interest in developing analytical solutions for frequency dynamics studies. This study first describes a second‐order frequency dynamics model for power systems with renewable energies. A non‐linear perturbation approach is suggested to drive the analytical solution of the model. It is shown that, under many circumstances, frequency dynamics can be effectively approximated using a linear model. Subsequently, the article describes a fourth‐order linear frequency dynamics model that takes into account governor‐turbines. A polynomial eigenvalue method is proposed to identify the dominant and non‐dominant modes of the solution of the four‐order model. It is demonstrated that the dominant mode has a decisive impact on frequency behaviour, while the non‐dominant modes influence the relative frequency oscillations only. Finally, the study derives the analytical expressions of the standard frequency performance metrics and examines the impact of damping and inertia parameters. The introduced results are verified using two test systems, demonstrating the accuracy and effectiveness of the suggested method.
Road user opinions and needs regarding small modular autonomous electric vehicles: Differences between elderly and non‐elderly in Norway
Authors: Moscoso Claudia , Roche‐Cerasi Isabelle 
Published: August 2024

AbstractThis study examines road user opinions regarding small modular autonomous electric vehicles, focusing on the differences between the elderly and non‐elderly populations in Norway. The data allowed for a comparison between 193 respondents under 65 years old and 208 respondents over 65 years old. The results highlighted significant differences between the two groups about the vehicles, their usability, and the likeliness of using them as public transport if implemented in the future. Traffic safety and personal security were found to be decisive aspects, for respondents over 65 years old being more worried about safety and security than their counterparts. Trust that the authorities will ensure the safe implementation of such vehicles in the current transportation system was also significantly different between the two groups, with the younger generations having more trust in the authorities than the older group. The results shed light on road user opinions about a small modular transport mode, particularly on those over 65 years old, indicating a need for research efforts to better identify how this new form of public transport should be implemented in the future to improve the mobility of all travellers and meet the needs of the seniors.
Posterior Cruciate Ligament Preservation versus Posterior Cruciate Ligament Sacrifice: Comparing Patient Outcomes in Medial Congruent Total Knee Arthroplasty
Authors: Guild George N. , McConnell Mary J. , Najafi Farideh , Naylor Brandon H. , DeCook Charles A. , Bradbury Thomas L. 
Published: August 2024

AbstractThis study aimed to compare outcomes and complication rates between posterior cruciate ligament (PCL) retention and excision utilizing a medial congruent (MC) polyethylene insert in total knee arthroplasty (TKA) in a specialized ambulatory surgery center (ASC) dedicated to hip and knee arthroplasty. A retrospective review was performed between May 2023 and October 2023 analyzing 398 patients who underwent primary MC TKA by high-volume joint arthroplasty surgeons (n = 9) with either PCL preservation (n = 264) or sacrifice (n = 134) in a single free-standing ASC. Patients were matched chronologically on a 2:1 basis. Demographics, baseline function, 90-day complications, and patient-reported outcomes were recorded for each patient. There were no differences in preoperative baseline function or patient-reported outcome measures, Charlson Comorbidity Index, or American Society of Anesthesiologists class among patient groups. The PCL-preserve and PCL-sacrifice cohorts showed significant variation in 12-week postoperative Knee Injury and Osteoarthritis Outcome, Junior (KOOS, JR.) scores. Specifically, the number of patients who achieved the minimal clinically important difference (MCID) in KOOS, JR. scores was higher in the PCL-sacrifice group (p < 0.05). Yet, no complications within the 90-day period were associated with PCL status and other patient-reported outcomes. This study comparing outcomes between MC TKAs with PCL retention and sacrifice suggests that both techniques are viable options with similar functional outcomes, pain scores, and complication rates, which may have benefits in an ASC setting. The PCL-sacrifice group exhibited a statistically significant increase in patients who achieved the MCID in KOOS, JR. score compared with the PCL-preserving at early follow-up. Future research should employ prospective, randomized designs to further validate these findings and explore long-term implications.