bluuebunny/crossref_metadata_2025_split huggingface dataset:
Present Day Endogenic and Exogenic Activity on Mercury
Authors: Speyerer E. J. , Robinson M. S. , Sonke A. J. 
Published: August 2022

AbstractExogenic and endogenic activities dictate how planetary surfaces evolve. However, the present‐day influence of each of these activities is not well constrained. MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) temporal imaging recorded surface changes associated with these activities between 2011 and 2015. Here we present the results of a temporal investigation that identified 20 reflectance changes. One change exhibited bright rays extending from the site, consistent with the aftermath of an impact event. If all changes result from impact events, the present flux rate is 1,000 times higher than models predict. Consequently, we also report changes on slopes in areas with concentrations of tectonic landforms and identify a subset of changes that are on or adjacent to hollows, consistent with present‐day endogenic activities. Therefore, we conclude that these observations captured endogenic and exogenic modifications to the surface.
Carbon Dioxide (CO2) Dissolution Efficiency During Geological Carbon Sequestration (GCS) in Randomly Stratified Formations
Authors: Wang Yufei , Fernàndez‐Garcia Daniel , Saaltink Maarten W. 
Published: August 2022

AbstractGeological carbon sequestration mitigates climate change by capturing and storing carbon dioxide (CO2) emissions in deep geologic formations. Dissolution trapping is one mechanism by which CO2 can be trapped in a deep formation. However, heterogeneity can significantly affect the dissolution efficiency. This work addresses the injection of CO2 in perfectly stratified saline formations under uncertainty. Monte Carlo two‐phase flow compositional simulations involving the dissolution of CO2 into brine and evaporation of water into the CO2‐rich phase are presented. We systematically analyzed the interplay between heterogeneity and gravity factor (G), which is shown to control the migration of the CO2 plume as well as the temporal evolution of dissolution efficiency. Results show that when G is important, vertical segregation controls the overall behavior of CO2, diminishing the influence of small‐scale heterogeneity on dissolution. However, when G is relatively small compared to , CO2 migrates preferentially through high permeability layers and dissolution efficiency increases with due to the stretching of the CO2 plume that enhances mixing. As a result, in this situation, the upscaling of permeability leads to an underestimation of the dissolution efficiency. A review of field sites shows that dissolution is heterogeneity‐controlled in most real systems. Knowing that most numerical models cannot afford to represent heterogeneity at an adequate scale, results indicate that dissolution efficiency can be typically underestimated by a factor close to 1.5.
Unconfined Plunging of a Hyperpycnal River Plume Over a Sloping Bed and Its Lateral Spreading: Laboratory Experiments and Numerical Modeling
Authors: Shi H. , Negretti M. E. , Chauchat J. , Blanckaert K. , Lemmin U. , Barry D. A. 
Published: August 2022

AbstractHyperpycnal (negatively buoyant) river inflow into lakes and oceans often develops three‐dimensional (3D) plunging flow patterns when laterally unconfined. To determine the 3D flow pattern characteristics, laboratory experiments of laterally unconfined plunging on a sloping bed were carried out using salinity to control the density difference. The experiments were complemented by numerical modeling based on a high‐resolution computational fluid dynamics model. As is the case for confined plunging plumes, it was found that in unconfined plunging, the inflow densimetric Froude number Frd−0 at the river mouth and the bed slope of the receiving water body β are the dominant control parameters. However, the results documented that the hydrodynamics of laterally unconfined plunging are fundamentally different: The hyperpycnal plume in unconfined configurations forms a triangle on the surface in the plunge zone due to its convergence near the surface and lateral spreading near the bottom. The triangular pattern extends further into the receiving water when Frd−0 increases or the bottom slope decreases. The unconfined entrainment coefficient, which quantifies the amount of ambient water entrained into the plunging plume, also increases with increasing Frd−0. In general, entrainment is much higher in unconfined than in confined plunging. The plunging densimetric Froude number Frd−p takes a constant value of ∼0.5 in confined plunging, whereas it increases with increasing Frd−0 and can be ≫1 in unconfined plunging. Complex patterns of secondary currents occur in the plunging plume. A low‐velocity zone whose size increases with Frd−0 is observed near the centerline above the bed.
GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization, mitochondria-targeting and -activating properties of human salivary histatin 1
Authors: Ma Dandan , Sun Wei , Fu Cuicui , Nazmi Kamran , Veerman Enno C. I. , Jaspers Richard T. , Bolscher Jan G. M. , Bikker Floris J. , Wu Gang 
Published: August 2022

AbstractHuman salivary histatin 1 (Hst1) exhibits a series of cell-activating properties, such as promoting cell spreading, migration, and metabolic activity. We recently have shown that fluorescently labeled Hst1 (F-Hst1) targets and activates mitochondria, presenting an important molecular mechanism. However, its regulating signaling pathways remain to be elucidated. We investigated the influence of specific inhibitors of G protein-coupled receptors (GPCR), endocytosis pathways, extracellular signal-regulated kinases 1/2 (ERK1/2) signaling, p38 signaling, mitochondrial respiration and Na+/K+-ATPase activity on the uptake, mitochondria-targeting and -activating properties of F-Hst1. We performed a siRNA knockdown (KD) to assess the effect of Sigma-2 receptor (S2R) /Transmembrane Protein 97 (TMEM97)—a recently identified target protein of Hst1. We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1. Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1. The inhibitors of GPCR, ERK1/2, phagocytosis, and clathrin-mediated endocytosis (CME) as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake, which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity. Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1. We further showed the intracellular trafficking and targeting process of F-Hst1, in which early endosome plays an important role. Overall, phagocytosis, CME, GPCR, ERK signaling, and S2R/TMEM97 are involved in the internalization of Hst1, while only CME and S2R/TMEM97 are critical for its subcellular targeting. The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.
A novel mutation located in the intermembrane space domain of AFG3L2 causes dominant optic atrophy through decreasing the stability of the encoded protein
Authors: Yang Lin , Jin Xiuxiu , Li Ya , Guo Qingge , Yang Mingzhu , You Ya , Yao Shun , Zhang Xiaoli , Wang Zhongfeng , Lei Bo 
Published: August 2022

AbstractDominant optic atrophy (DOA) is the most common hereditary optic neuropathy. Although DOA is caused by mutations in several genes, there are still many cases that have not been diagnosed or misdiagnosed. Herein, we present a large family of 11 patients with DOA. To identify potential pathogenic mutations, whole exome sequencing (WES) was performed on the proband, a 35-year-old woman. WES revealed a novel pathogenic mutation (c.524T>C, p.F175S) in the AFG3L2 intermembrane space domain, rather than in the ATPase domain, which is the hot mutation region associated with most of the previously reported DOA cases. Functional studies on skin fibroblasts generated from patients and HEK293T cells showed that the mutation may impair mitochondrial function and decrease the ability of AFG3L2 protein to enter the mitochondrial inner membrane. In addition, this novel mutation led to protein degradation and reduced the stability of the AFG3L2 protein, which appeared to be associated with the proteasome-ubiquitin pathway.
Structures of UBA6 explain its dual specificity for ubiquitin and FAT10
Authors: Truongvan Ngoc , Li Shurong , Misra Mohit , Kuhn Monika , Schindelin Hermann 
Published: August 2022

AbstractThe covalent modification of target proteins with ubiquitin or ubiquitin-like modifiers is initiated by E1 activating enzymes, which typically transfer a single modifier onto cognate conjugating enzymes. UBA6 is an unusual E1 since it activates two highly distinct modifiers, ubiquitin and FAT10. Here, we report crystal structures of UBA6 in complex with either ATP or FAT10. In the UBA6-FAT10 complex, the C-terminal domain of FAT10 binds to where ubiquitin resides in the UBA1-ubiquitin complex, however, a switch element ensures the alternate recruitment of either modifier. Simultaneously, the N-terminal domain of FAT10 interacts with the 3-helix bundle of UBA6. Site-directed mutagenesis identifies residues permitting the selective activation of either ubiquitin or FAT10. These results pave the way for studies investigating the activation of either modifier by UBA6 in physiological and pathophysiological settings.
Second-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland
Authors: Simpson Colin R. , Kerr Steven , Katikireddi Srinivasa Vittal , McCowan Colin , Ritchie Lewis D. , Pan Jiafeng , Stock Sarah J. , Rudan Igor , Tsang Ruby S. M. , de Lusignan Simon , Hobbs F. D. Richard , Akbari Ashley , Lyons Ronan A. , Robertson Chris , Sheikh Aziz 
Published: August 2022

AbstractWe investigated thrombocytopenic, thromboembolic and hemorrhagic events following a second dose of ChAdOx1 and BNT162b2 using a self-controlled case series analysis. We used a national prospective cohort with 2.0 million(m) adults vaccinated with two doses of ChAdOx or 1.6 m with BNT162b2. The incidence rate ratio (IRR) for idiopathic thrombocytopenic purpura (ITP) 14–20 days post-ChAdOx1 second dose was 2.14, 95% confidence interval (CI) 0.90–5.08. The incidence of ITP post-second dose ChAdOx1 was 0.59 (0.37–0.89) per 100,000 doses. No evidence of an increased risk of CVST was found for the 0–27 day risk period (IRR 0.83, 95% CI 0.16 to 4.26). However, few (≤5) events arose within this risk period. It is perhaps noteworthy that these events all clustered in the 7–13 day period (IRR 4.06, 95% CI 0.94 to 17.51). No other associations were found for second dose ChAdOx1, or any association for second dose BNT162b2 vaccination. Second dose ChAdOx1 vaccination was associated with increased borderline risks of ITP and CVST events. However, these events were rare thus providing reassurance about the safety of these vaccines. Further analyses including more cases are required to determine more precisely the risk profile for ITP and CVST after a second dose of ChAdOx1 vaccine.
A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness
Authors: Antonica Francesco , Santomaso Lucia , Pernici Davide , Petrucci Linda , Aiello Giuseppe , Cutarelli Alessandro , Conti Luciano , Romanel Alessandro , Miele Evelina , Tebaldi Toma , Tiberi Luca 
Published: August 2022

AbstractPediatric and adult high-grade gliomas are the most common primary malignant brain tumors, with poor prognosis due to recurrence and tumor infiltration after therapy. Quiescent cells have been implicated in tumor recurrence and treatment resistance, but their direct visualization and targeting remain challenging, precluding their mechanistic study. Here, we identify a population of malignant cells expressing Prominin-1 in a non-proliferating state in pediatric high-grade glioma patients. Using a genetic tool to visualize and ablate quiescent cells in mouse brain cancer and human cancer organoids, we reveal their localization at both the core and the edge of the tumors, and we demonstrate that quiescent cells are involved in infiltration of brain cancer cells. Finally, we find that Harmine, a DYRK1A/B inhibitor, partially decreases the number of quiescent and infiltrating cancer cells. Our data point to a subpopulation of quiescent cells as partially responsible of tumor invasiveness, one of the major causes of brain cancer morbidity.
Structural basis for Sarbecovirus ORF6 mediated blockage of nucleocytoplasmic transport
Authors: Gao Xiaopan , Tian Huabin , Zhu Kaixiang , Li Qing , Hao Wei , Wang Linyue , Qin Bo , Deng Hongyu , Cui Sheng 
Published: August 2022

AbstractThe emergence of heavily mutated SARS-CoV-2 variants of concern (VOCs) place the international community on high alert. In addition to numerous mutations that map in the spike protein of VOCs, expression of the viral accessory proteins ORF6 and ORF9b also elevate; both are potent interferon antagonists. Here, we present the crystal structures of Rae1-Nup98 in complex with the C-terminal tails (CTT) of SARS-CoV-2 and SARS-CoV ORF6 to 2.85 Å and 2.39 Å resolution, respectively. An invariant methionine (M) 58 residue of ORF6 CTT extends its side chain into a hydrophobic cavity in the Rae1 mRNA binding groove, resembling a bolt-fitting-hole; acidic residues flanking M58 form salt-bridges with Rae1. Our mutagenesis studies identify key residues of ORF6 important for its interaction with Rae1-Nup98 in vitro and in cells, of which M58 is irreplaceable. Furthermore, we show that ORF6-mediated blockade of mRNA and STAT1 nucleocytoplasmic transport correlate with the binding affinity between ORF6 and Rae1-Nup98. Finally, binding of ORF6 to Rae1-Nup98 is linked to ORF6-induced interferon antagonism. Taken together, this study reveals the molecular basis for the antagonistic function of Sarbecovirus ORF6, and implies a strategy of using ORF6 CTT-derived peptides for immunosuppressive drug development.
Confinement-induced accumulation and de-mixing of microscopic active-passive mixtures
Authors: Williams Stephen , Jeanneret Raphaël , Tuval Idan , Polin Marco 
Published: August 2022

AbstractUnderstanding the out-of-equilibrium properties of noisy microscale systems and the extent to which they can be modulated externally, is a crucial scientific and technological challenge. It holds the promise to unlock disruptive new technologies ranging from targeted delivery of chemicals within the body to directed assembly of new materials. Here we focus on how active matter can be harnessed to transport passive microscopic systems in a statistically predictable way. Using a minimal active-passive system of weakly Brownian particles and swimming microalgae, we show that spatial confinement leads to a complex non-monotonic steady-state distribution of colloids, with a pronounced peak at the boundary. The particles’ emergent active dynamics is well captured by a space-dependent Poisson process resulting from the space-dependent motion of the algae. Based on our findings, we then realise experimentally the de-mixing of the active-passive suspension, opening the way for manipulating colloidal objects via controlled activity fields.
Three-dimensional electron ptychography of organic–inorganic hybrid nanostructures
Authors: Ding Zhiyuan , Gao Si , Fang Weina , Huang Chen , Zhou Liqi , Pei Xudong , Liu Xiaoguo , Pan Xiaoqing , Fan Chunhai , Kirkland Angus I. , Wang Peng 
Published: August 2022

AbstractThree dimensional scaffolded DNA origami with inorganic nanoparticles has been used to create tailored multidimensional nanostructures. However, the image contrast of DNA is poorer than those of the heavy nanoparticles in conventional transmission electron microscopy at high defocus so that the biological and non-biological components in 3D scaffolds cannot be simultaneously resolved using tomography of samples in a native state. We demonstrate the use of electron ptychography to recover high contrast phase information from all components in a DNA origami scaffold without staining. We further quantitatively evaluate the enhancement of contrast in comparison with conventional transmission electron microscopy. In addition, We show that for ptychography post-reconstruction focusing simplifies the workflow and reduces electron dose and beam damage.
Cell clusters softening triggers collective cell migration in vivo
Authors: Marchant Cristian L. , Malmi-Kakkada Abdul N. , Espina Jaime A. , Barriga Elias H. 
Published: August 2022

AbstractEmbryogenesis, tissue repair and cancer metastasis rely on collective cell migration. In vitro studies propose that cells are stiffer while migrating in stiff substrates, but softer when plated in compliant surfaces which are typically considered as non-permissive for migration. Here we show that cells within clusters from embryonic tissue dynamically decrease their stiffness in response to the temporal stiffening of their native substrate to initiate collective cell migration. Molecular and mechanical perturbations of embryonic tissues reveal that this unexpected mechanical response involves a mechanosensitive pathway relying on Piezo1-mediated microtubule deacetylation. We further show that decreasing microtubule acetylation and consequently cluster stiffness is sufficient to trigger collective cell migration in soft non-permissive substrates. This suggests that reaching an optimal cluster-to-substrate stiffness ratio is essential to trigger the onset of this collective process. Overall, these in vivo findings challenge the current understanding of collective cell migration and its physiological and pathological roles.
Antibiotic resistance genes of public health importance in livestock and humans in an informal urban community in Nepal
Authors: Young Cristin C. W. , Karmacharya Dibesh , Bista Manisha , Sharma Ajay N. , Goldstein Tracey , Mazet Jonna A. K. , Johnson Christine K. 
Published: August 2022

AbstractEfforts to mitigate the increasing emergence of antimicrobial resistance (AMR) will benefit from a One Health perspective, as over half of animal antimicrobials are also considered medically important in humans, and AMR can be maintained in the environment. This is especially pertinent to low- and middle-income countries and in community settings, where an estimated 80% of all antibiotics are used. This study features AMR genes found among humans, animals, and water at an urban informal settlement in Nepal with intensifying livestock production. We sampled humans, chickens, ducks, swine, and water clustered by household, as well as rodents and shrews near dwellings, concurrently in time in July 2017 in southeastern Kathmandu along the Manohara river. Real-time qualitative PCR was performed to screen for 88 genes. Our results characterize the animal-human-environmental interfaces related to the occurrence of specific resistance genes (blaSHV-1 (SHV(238G240E) strain), QnrS, ermC, tetA, tetB, aacC2, aadA1) associated with antibiotics of global health importance that comprise several drug classes, including aminoglycosides, beta-lactams, tetracyclines, macrolides, and fluoroquinolones. By characterizing risk factors across AMR genes of public health importance, this research highlights potential transmission pathways for further investigation and provides prioritization of community-based prevention and intervention efforts for disrupting AMR transmission of critically important antibiotics used in both humans and animals in Nepal.
Investigating the effect of N-doping on carbon quantum dots structure, optical properties and metal ion screening
Authors: Nguyen Kiem Giap , Baragau Ioan-Alexandru , Gromicova Radka , Nicolaev Adela , Thomson Stuart A. J. , Rennie Alistair , Power Nicholas P. , Sajjad Muhammad Tariq , Kellici Suela 
Published: August 2022

AbstractCarbon quantum dots (CQDs) derived from biomass, a suggested green approach for nanomaterial synthesis, often possess poor optical properties and have low photoluminescence quantum yield (PLQY). This study employed an environmentally friendly, cost-effective, continuous hydrothermal flow synthesis (CHFS) process to synthesise efficient nitrogen-doped carbon quantum dots (N-CQDs) from biomass precursors (glucose in the presence of ammonia). The concentrations of ammonia, as nitrogen dopant precursor, were varied to optimise the optical properties of CQDs. Optimised N-CQDs showed significant enhancement in fluorescence emission properties with a PLQY of 9.6% compared to pure glucose derived-CQDs (g-CQDs) without nitrogen doping which have PLQY of less than 1%. With stability over a pH range of pH 2 to pH 11, the N-CQDs showed excellent sensitivity as a nano-sensor for the highly toxic highly-pollutant chromium (VI), where efficient photoluminescence (PL) quenching was observed. The optimised nitrogen-doping process demonstrated effective and efficient tuning of the overall electronic structure of the N-CQDs resulting in enhanced optical properties and performance as a nano-sensor.
The role of traditional obesity parameters in predicting the number of stenosed coronary arteries (≥ 60%) among patients undergoing cardiac catheterization
Authors: Hayajneh Audai A. , Alhusban Islam M. , Rababa Mohammad 
Published: August 2022

AbstractThe correlation between obesity and coronary artery disease (CAD) has been well-documented in the literature. Body mass index, waist–height ratio, waist–hip ratio, body adiposity index, body shape index, waist circumference, and hip circumference are traditional obesity parameters used to measure obesity. This study aimed to investigate the role of these traditional obesity parameters in the prediction of the number of stenosed coronary arteries (≥ 60%) among patients undergoing cardiac catheterization. A descriptive cross-sectional study was conducted among 220 hospitalized patients undergoing cardiac catheterization in two hospitals in Jordan. Bivariate Pearson’s correlation and forward linear regression analysis were used in the current study. Hip circumference was identified as being the best predictor of CAD (r = 0.5), with the best cut-off value of 103 cm (sensitivity = 0.92, specificity = 0.58). Hip circumference had significant regression levels with the number of stented coronary arteries (P = 0.002) and the number of severe stenosed coronary arteries (P = 0.04). The second-best obesity parameter in predicting CAD was waist circumference (r = 0.4), with a cut-off value of 0.95 m (sensitivity = 0.76, specificity = 0.68). High-sensitivity C-reactive protein (HS-CRP), triglycerides, and smoking had significant positive correlations with the number of stented coronary arteries (P < 0.05). Hip circumference of ≥ 103 cm, increased serum level of triglycerides, HS-CRP, and being a smoker are all factors which can predict CAD or the risk of developing it.