bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actin polymerization promotes invagination of flat clathrin-coated lattices in mammalian cells by pushing at lattice edges
Authors: Yang Changsong , Colosi Patricia , Hugelier Siewert , Zabezhinsky Daniel , Lakadamyali Melike , Svitkina Tatyana 
Published: October 2022

AbstractClathrin-mediated endocytosis (CME) requires energy input from actin polymerization in mechanically challenging conditions. The roles of actin in CME are poorly understood due to inadequate knowledge of actin organization at clathrin-coated structures (CCSs). Using platinum replica electron microscopy of mammalian cells, we show that Arp2/3 complex-dependent branched actin networks, which often emerge from microtubule tips, assemble along the CCS perimeter, lack interaction with the apical clathrin lattice, and have barbed ends oriented toward the CCS. This structure is hardly compatible with the widely held “apical pulling” model describing actin functions in CME. Arp2/3 complex inhibition or epsin knockout produce large flat non-dynamic CCSs, which split into invaginating subdomains upon recovery from Arp2/3 inhibition. Moreover, epsin localization to CCSs depends on Arp2/3 activity. We propose an “edge pushing” model for CME, wherein branched actin polymerization promotes severing and invagination of flat CCSs in an epsin-dependent manner by pushing at the CCS boundary, thus releasing forces opposing the intrinsic curvature of clathrin lattices.
Anaerobic oxidation of propane coupled to nitrate reduction by a lineage within the class Symbiobacteriia
Authors: Wu Mengxiong , Li Jie , Leu Andy O. , Erler Dirk V. , Stark Terra , Tyson Gene W. , Yuan Zhiguo , McIlroy Simon J. , Guo Jianhua 
Published: October 2022

AbstractAnaerobic microorganisms are thought to play a critical role in regulating the flux of short-chain gaseous alkanes (SCGAs; including ethane, propane and butane) from terrestrial and aquatic ecosystems to the atmosphere. Sulfate has been confirmed to act as electron acceptor supporting microbial anaerobic oxidation of SCGAs, yet several other energetically more favourable acceptors co-exist with these gases in anaerobic environments. Here, we show that a bioreactor seeded with biomass from a wastewater treatment facility can perform anaerobic propane oxidation coupled to nitrate reduction to dinitrogen gas and ammonium. The bioreactor was operated for more than 1000 days, and we used13C- and15N-labelling experiments, metagenomic, metatranscriptomic, metaproteomic and metabolite analyses to characterize the microbial community and the metabolic processes. The data collectively suggest that a species representing a novel order within the bacterial class Symbiobacteriia is responsible for the observed nitrate-dependent propane oxidation. The closed genome of this organism, which we designate as ‘CandidatusAlkanivorans nitratireducens’, encodes pathways for oxidation of propane to CO2via fumarate addition, and for nitrate reduction, with all the key genes expressed during nitrate-dependent propane oxidation. Our results suggest that nitrate is a relevant electron sink for SCGA oxidation in anaerobic environments, constituting a new microbially-mediated link between the carbon and nitrogen cycles.
Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile
Authors: Kawamoto Akihiro , Yamada Tomohito , Yoshida Toru , Sato Yusui , Kato Takayuki , Tsuge Hideaki 
Published: October 2022

AbstractSome bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically important bacterium with such a system is Clostridioides difficile (formerly Clostridium). The CDTa and CDTb proteins from its system represent important therapeutic targets. CDTb has been proposed to be a di-heptamer, but its physiological heptameric structure has not yet been reported. Here, we report the cryo-EM structure of CDTa bound to the CDTb-pore, which reveals that CDTa binding induces partial unfolding and tilting of the first CDTa α-helix. In the CDTb-pore, an NSS-loop exists in ‘in’ and ‘out’ conformations, suggesting its involvement in substrate translocation. Finally, 3D variability analysis revealed CDTa movements from a folded to an unfolded state. These dynamic structural information provide insights into drug design against hypervirulent C. difficile strains.
Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability
Authors: Wang Hao-Lian , Chen Yan , Wang Yun-Qian , Tao En-Wei , Tan Juan , Liu Qian-Qian , Li Chun-Min , Tong Xue-Mei , Gao Qin-Yan , Hong Jie , Chen Ying-Xuan , Fang Jing-Yuan 
Published: October 2022

AbstractIn our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD+-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.
Organic radicals stabilization above 300 °C in Eu-based coordination polymers for solar steam generation
Authors: Ye Xinhe , Chung Lai-Hon , Li Kedi , Zheng Saili , Wong Yan-Lung , Feng Zihao , He Yonghe , Chu Dandan , Xu Zhengtao , Yu Lin , He Jun 
Published: October 2022

AbstractOrganic radicals feature unpaired electrons, and these compounds may have applications in biomedical technology and as materials for solar energy conversion. However, unpaired electrons tend to pair up (to form chemical bonds), making radicals unstable and hampering their applications. Here we report an organic radical system that is stable even at 350 °C, surpassing the upper temperature limit (200 °C) observed for other organic radicals. The system reported herein features a sulfur-rich organic linker that facilitates the formation of the radical centers; on the solid-state level, the molecules are crystallized with Eu(III) ions to form a 3D framework featuring stacks of linker molecules. The stacking is, however, somewhat loose and allows the molecules to wiggle and transform into sulfur-stabilized radicals at higher temperatures. In addition, the resulting solid framework remains crystalline, and it is stable to water and air. Moreover, it is black and features strong broad absorption in the visible and near IR region, thereby enhancing both photothermal conversion and solar-driven water evaporation.
On-site colorimetric detection of Salmonella typhimurium
Authors: Wei Shengnan , Su Zhenyue , Bu Xiangong , Shi Xuening , Pang Bo , Zhang Liang , Li Juan , Zhao Chao 
Published: October 2022

AbstractRapid qualitative and quantitative detection ofSalmonella typhimurium(S. typhimurium) takes an important role in ensuring food safety. Herein, a colorimetric assay aptasensor forS. typhimuriumutilizing intrinsic peroxidase-like activity of gold nanoparticles embedded spherical covalent organic framework and the affinity and specificity ofS. typhimurium-aptamer has been explored. This aptasensor can capture theS. typhimuriumvia the selective binding effect of aptamer, and the catalytically active sites were shielded. As a result, the colorimetric signals of the 3,3′,5,5′-tetramethylbenzidine-H2O2system were turned off. Under optimum conditions, the aptasensor gave a linear response over the range of 10 to 107CFU/mL forS. typhimurium. The detection limit of 7 CFU/mL was obtained within 45 min and was effectively applied to detectS. typhimuriumin milk and lake water samples with recoveries in the range from 96.4 to 101.0%. More importantly, combined with a self-developed smartphone-based image analysis system, the proposed aptasensor can be used for point-of-care testing applications.
Estimation of skeletal kinematics in freely moving rodents
Authors: Monsees Arne , Voit Kay-Michael , Wallace Damian J. , Sawinski Juergen , Charyasz Edyta , Scheffler Klaus , Macke Jakob H. , Kerr Jason N. D. 
Published: October 2022

AbstractForming a complete picture of the relationship between neural activity and skeletal kinematics requires quantification of skeletal joint biomechanics during free behavior; however, without detailed knowledge of the underlying skeletal motion, inferring limb kinematics using surface-tracking approaches is difficult, especially for animals where the relationship between the surface and underlying skeleton changes during motion. Here we developed a videography-based method enabling detailed three-dimensional kinematic quantification of an anatomically defined skeleton in untethered freely behaving rats and mice. This skeleton-based model was constrained using anatomical principles and joint motion limits and provided skeletal pose estimates for a range of body sizes, even when limbs were occluded. Model-inferred limb positions and joint kinematics during gait and gap-crossing behaviors were verified by direct measurement of either limb placement or limb kinematics using inertial measurement units. Together we show that complex decision-making behaviors can be accurately reconstructed at the level of skeletal kinematics using our anatomically constrained model.
Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation
Authors: Cutler Kevin J. , Stringer Carsen , Lo Teresa W. , Rappez Luca , Stroustrup Nicholas , Brook Peterson S. , Wiggins Paul A. , Mougous Joseph D. 
Published: October 2022

AbstractAdvances in microscopy hold great promise for allowing quantitative and precise measurement of morphological and molecular phenomena at the single-cell level in bacteria; however, the potential of this approach is ultimately limited by the availability of methods to faithfully segment cells independent of their morphological or optical characteristics. Here, we present Omnipose, a deep neural network image-segmentation algorithm. Unique network outputs such as the gradient of the distance field allow Omnipose to accurately segment cells on which current algorithms, including its predecessor, Cellpose, produce errors. We show that Omnipose achieves unprecedented segmentation performance on mixed bacterial cultures, antibiotic-treated cells and cells of elongated or branched morphology. Furthermore, the benefits of Omnipose extend to non-bacterial subjects, varied imaging modalities and three-dimensional objects. Finally, we demonstrate the utility of Omnipose in the characterization of extreme morphological phenotypes that arise during interbacterial antagonism. Our results distinguish Omnipose as a powerful tool for characterizing diverse and arbitrarily shaped cell types from imaging data.
CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease
Authors: Qiang Qiang , Skudder-Hill Loren , Toyota Tomoko , Wei Wenshi , Adachi Hiroaki 
Published: October 2022

AbstractTo test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) concentration is elevated in Alzheimer’s disease (AD) dementia and its associations with other hallmarks of AD, we examined the CSF GAP-43 measurements of 787 participants (245 cognitively normal (CN), 415 individuals with mild cognitive impairment (MCI) and 127 individuals with AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Associations were investigated between CSF GAP-43 and clinical diagnosis, Aβ/tau/neurodegeneration (AT(N)) status, CSF and blood biomarkers of AD, cognitive measurements and brain neuroimaging findings. CSF GAP-43 levels were increased in patients with AD dementia (mean, 6331.05 pg/ml) compared with the CN (mean, 5001.05 pg/ml) and MCI (mean, 5118.8 pg/ml) (P < 0.001) groups. CSF GAP-43 correlated with CSF phosphorylated tau 181(p-tau) (r = 0.768, P < 0.001), and had high diagnostic accuracy in differentiating tau positive status vs. tau negative status (area under the receiver operating characteristic curve, 0.8606). CSF GAP-43 was particularly elevated among individuals with tau positive status. High CSF GAP-43 was associated with longitudinal deterioration of cognitive scores and brain neuroimaging findings. CSF GAP-43 was associated with a clinical diagnosis of AD dementia and with an individual’s tau status, cognitive measurements and findings from neuroimaging. This study implies that CSF GAP-43 as a biomarker of synaptic dysfunction could predict the disease progression of AD patients.
A digital platform for the design of patient-centric supply chains
Authors: Triantafyllou Niki , Bernardi Andrea , Lakelin Matthew , Shah Nilay , Papathanasiou Maria M. 
Published: October 2022

AbstractChimeric Antigen Receptor (CAR) T cell therapies have received increasing attention, showing promising results in the treatment of acute lymphoblastic leukaemia and aggressive B cell lymphoma. Unlike typical cancer treatments, autologous CAR T cell therapies are patient-specific; this makes them a unique therapeutic to manufacture and distribute. In this work, we focus on the development of a computer modelling tool to assist the design and assessment of supply chain structures that can reliably and cost-efficiently deliver autologous CAR T cell therapies. We focus on four demand scales (200, 500, 1000 and 2000 patients annually) and we assess the tool’s capabilities with respect to the design of responsive supply chain candidate solutions while minimising cost.
An 80-million-year sulphur isotope record of pyrite burial over the Permian–Triassic
Authors: Salisbury Jack , Gröcke Darren R. , Cheung H. D. R. Ashleigh , Kump Lee R. , McKie Tom , Ruffell Alastair 
Published: October 2022

AbstractDespite the extensive use of sulphur isotope ratios (δ34S) for understanding ancient biogeochemical cycles, many studies focus on specific time-points of interest, such as the end-Permian mass extinction (EPME). We have generated an 80 million-year Permian–Triassic δ34Sevap curve from the Staithes S-20 borehole, Yorkshire, England. The Staithes δ34Sevap record replicates the major features of the global curve, while confirming a new excursion at the Olenekian/Anisian boundary at ~ 247 million years ago. We incorporate the resultant δ34Sevap curve into a sulphur isotope box model. Our modelling approach reveals three significant pyrite burial events (i.e. PBEs) in the Triassic. In particular, it predicts a significant biogeochemical response across the EPME, resulting in a substantial increase in pyrite burial, possibly driven by Siberian Traps volcanism. Our model suggests that after ~ 10 million years pyrite burial achieves relative long-term stability until the latest Triassic.
Characterizing the composition of iPSC derived cells from bulk transcriptomics data with CellMap
Authors: Ouyang Zhengyu , Bourgeois-Tchir Nathanael , Lyashenko Eugenia , Cundiff Paige E. , Cullen Patrick F. , Challa Ravi , Li Kejie , Zhang Xinmin , Casey Fergal , Engle Sandra J. , Zhang Baohong , Zavodszky Maria I. 
Published: October 2022

AbstractInduced pluripotent stem cell (iPSC) derived cell types are increasingly employed as in vitro model systems for drug discovery. For these studies to be meaningful, it is important to understand the reproducibility of the iPSC-derived cultures and their similarity to equivalent endogenous cell types. Single-cell and single-nucleus RNA sequencing (RNA-seq) are useful to gain such understanding, but they are expensive and time consuming, while bulk RNA-seq data can be generated quicker and at lower cost. In silico cell type decomposition is an efficient, inexpensive, and convenient alternative that can leverage bulk RNA-seq to derive more fine-grained information about these cultures. We developed CellMap, a computational tool that derives cell type profiles from publicly available single-cell and single-nucleus datasets to infer cell types in bulk RNA-seq data from iPSC-derived cell lines.
Comparing three types of data-driven models for monthly evapotranspiration prediction under heterogeneous climatic conditions
Authors: Aghelpour Pouya , Varshavian Vahid , Khodamorad Pour Mehraneh , Hamedi Zahra 
Published: October 2022

AbstractEvapotranspiration is one of the most important hydro-climatological components which directly affects agricultural productions. Therefore, its forecasting is critical for water managers and irrigation planners. In this study, adaptive neuro-fuzzy inference system (ANFIS) model has been hybridized by differential evolution (DE) optimization algorithm as a novel approach to forecast monthly reference evapotranspiration (ET0). Furthermore, this model has been compared with the classic stochastic time series model. For this, the ET0 rates were calculated on a monthly scale during 1995–2018, based on FAO-56 Penman–Monteith equation and meteorological data including minimum air temperature, maximum air temperature, mean air temperature, minimum relative humidity, maximum relative humidity & sunshine duration. The investigation was performed on 6 stations in different climates of Iran, including Bandar Anzali & Ramsar (per-humid), Gharakhil (sub-humid), Shiraz (semi-arid), Ahwaz (arid), and Yazd (extra-arid). The models’ performances were evaluated by the criteria percent bias (PB), root mean squared error (RMSE), normalized RMSE (NRMSE), and Nash-Sutcliff (NS) coefficient. Surveys confirm the high capability of the hybrid ANFIS-DE model in monthly ET0 forecasting; so that the DE algorithm was able to improve the accuracy of ANFIS, by 16% on average. Seasonal autoregressive integrated moving average (SARIMA) was the most suitable pattern among the time series stochastic models and superior to its competitors, ANFIS and ANFIS-DE. Consequently, the SARIMA was suggested more appropriate for monthly ET0 forecasting in all the climates, due to its simplicity and parsimony. Comparison between the different climates confirmed that the climate type significantly affects the forecasting accuracies: it’s revealed that all the models work better in extra-arid, arid and semi-arid climates, than the humid and per-humid areas.
Finite element analysis and optimization of tractor gearbox body under various kinds of working conditions
Authors: Dong Sihui , Li Shiqun , Fu Shenghui , Wang Kang 
Published: October 2022

AbstractAs the main component of the tractor gearbox, the box has the functions of shifting operation and carrying the cab, it also carries part of the framework function. If the strength, stiffness, or vibration characteristics of the box do not meet the allowable requirements, large vibration and noise may occur, and even there is the possibility of fracture in some limiting conditions. To solve this problem, according to the structural parameters of a gearbox, the three-dimensional model of the box was established by using the three-dimensional modeling software Creo. According to the dangerous degree of the transmission load when the tractor is working normally, three vehicle working conditions are selected: a round of suspension conditions, farm tool lifting conditions, and emergency turning conditions. In addition, according to the transmission ratio of each gear meshing inside the gearbox, two gear conditions are selected: gear condition one and reverse gear condition one. The forces of the box under these extreme conditions are analyzed. The static analysis and modal analysis of the tractor gearbox are carried out by using the Static Structural module of ANSYS Workbanch. The deformation, equivalent stress distribution, and modal vibration frequency of the gearbox are tested. The topology optimization method is used to improve structural defects and reduce box quality. The results show that the weight of the optimized box reduces by 8.44%, the deformation decreased by 15.89%, and the equivalent stress decreased by 18.34%. The strength and stiffness of the box are improved, the quality is lightweight, the waste of resources is reduced, and the heat dissipation performance and fracture resistance of the box are enhanced.
Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
Authors: Jackson Edwin K. , Kitsios Georgios D. , Lu Michael Y. , Schaefer Caitlin M. , Kessinger Cathy J. , McVerry Bryan J. , Morris Alison , Macatangay Bernard J. C. 
Published: October 2022

AbstractAcute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patients supporting the possibility that abnormally low kidney levels of adenosine, inosine and guanosine contribute to AKI. Here, we addressed the question as to whether these renoprotective purines are altered in the urine of COVID-19 patients with AKI. Purines were measured by employing ultra-high-performance liquid chromatography-tandem mass spectrometry with stable-isotope-labeled internal standards for each purine of interest. Compared with COVID-19 patients without AKI (n = 23), COVID-19 patients with AKI (n = 20) had significantly lower urine levels of adenosine (P < 0.0001), inosine (P = 0.0008), and guanosine (P = 0.0008) (medians reduced by 85%, 48% and 61%, respectively) and lower levels (P = 0.0003; median reduced by 67%) of the 2nd messenger for A2A and A2B adenosine receptors, i.e., 3’,5’-cAMP. Moreover, in COVID-19 patients with AKI, urine levels of 8-aminoguanine (endogenous inhibitor of inosine and guanosine metabolism) were nearly abolished (P < 0.0001). In contrast, the “upstream” precursors of renoprotective purines, namely 5’-AMP and 5’-GMP, were not significantly altered in COVID-19 patients with AKI, suggesting defective conversion of these precursors by CD73 (converts 5’-AMP to adenosine and 5’-GMP to guanosine). These findings imply that an imbalance in renoprotective purines may contribute to AKI in COVID-19 patients and that pharmacotherapy targeted to restore levels of renoprotective purines may attenuate the risk of AKI in susceptible patients with COVID-19.