bluuebunny/crossref_metadata_2025 huggingface dataset:
S‐Velocity Mantle Structure of East Asia From Teleseismic Traveltime Tomography: Inferred Mechanisms for the Cenozoic Intraplate Volcanoes
Authors: Kim Yong‐Woo , Chang Sung‐Joon , Witek Michael , Ning Jieyuan , Wen Jingchong
Published: February 2021

Clusters of Cenozoic volcanoes are found in Korea and Northeast China away from plate boundaries, but the mechanisms responsible for their formation is still unknown. To resolve this issue, we derive an S‐wave velocity model of the upper mantle structure beneath East Asia using 131,947 S‐wave relative traveltimes from 974 earthquakes recorded at 1,948 seismic stations in China, Korea, Taiwan, and Japan. Our results show that low‐velocity anomalies beneath Mt. Baekdu (Changbaishan) and Jeju Island extend to the bottom of the mantle transition zone (MTZ) through slab gaps in the stagnant Pacific slab. On the other hand, low‐velocity anomalies beneath the Datong volcanic field are observed to connect to the edge of the stagnant Pacific slab, which may be attributed to subduction‐triggered upwelling or deep dehydration from the hydrous MTZ perturbed by subducting slabs. Furthermore, tilted high‐velocity anomalies are found all the way down to the MTZ beneath the Great Xing'an Range and the Songliao basin, which may indicate delaminated lithosphere. The intraplate volcanoes north of the Songliao basin, such as the Wudalianchi and Halaha volcanoes, are located just above the delaminated bodies, thereby implying that decompression melting after delamination may be responsible for the intraplate volcanoes. Therefore, the dominant origin of intraplate volcanoes in East Asia may be subduction‐related hot upwelling, complemented by shallow origins such as edge‐driven convection and lithospheric delamination.
Spatial Variations of Upper Crustal Anisotropy Along the San Jacinto Fault Zone in Southern California: Constraints From Shear Wave Splitting Analysis
Authors: Jiang Enyuan , Liu Kelly H. , Gao Yuan , Fu Xiaofei , Gao Stephen S.
Published: February 2021

To discern spatial and explore possible existence of temporal variations of upper crustal anisotropy in an ∼15 km section of the San Jacinto Fault Zone (SJFZ) that is composed of the Buck Ridge and Clark faults in southern California, we conduct a systematic shear wave splitting investigation using local S‐wave data recorded by three broadband seismic stations located near the surface expression of the SJFZ. An automatic data selection and splitting measurement procedure is first applied, and the resulting splitting measurements are then manually screened to ensure reliability of the results. Strong spatial variations in crustal anisotropy are revealed by 1,694 pairs of splitting parameters (fast polarization orientation and splitting delay time), as reflected by the dependence of the resulting splitting parameters on the location and geometry of the raypaths. For raypaths traveling through the fault zones, the fast orientations are dominantly WNW‐ESE which is parallel to the faults and may be attributed to fluid‐filled fractures in the fault zones. For non‐fault‐zone crossing raypaths, the fast orientations are dominantly N–S which are consistent with the orientation of the regional maximum compressive stress. A three‐dimensional model of upper crustal anisotropy is constructed based on the observations. An increase in the raypath length normalized splitting times is observed after the 03/11/2013 M4.7 earthquake, which is probably attributable to changes in the spatial distribution of earthquakes before and after the M4.7 earthquake rather than reflecting temporal changes of upper crustal anisotropy.
Seismic Moment Accumulation Response to Lateral Crustal Variations of the San Andreas Fault System
Authors: Ward Lauren A. , Smith‐Konter Bridget R. , Xu Xiaohua , Sandwell David T.
Published: February 2021

Rheologic variations in the Earth's crust (like elastic plate thickness [EPT] or crustal rigidity) modulate the rate at which seismic moment accumulates for potentially hazardous faults of the San Andreas Fault System (SAFS). To quantify rates of seismic moment accumulation, Global Navigation Satellite Systems, and Interferometric Synthetic Aperture Radar data were used to constrain surface deformation rates of a four‐dimensional viscoelastic deformation model that incorporates rheological variations spanning a 900 km section of the SAFS. Lateral variations in EPT, estimated from surface heat flow and seismic depth to the lithosphere‐asthenosphere boundary, were converted to lateral variations in rigidity and then used to solve for seismic moment accumulation rates on 32 fault segments. We find a cluster of elevated seismic moment rates (11–20 × 1015 Nm year−1 km−1) along the main SAFS trace spanning the historical Mw 7.9 1857 Fort Tejon earthquake rupture length; present‐day seismic moment magnitude on these segments ranges from Mw 7.2–7.6. We also find that the average plate thickness in the Salton Trough is reduced to only 60% of the regional average, which results in a ∼60% decrease in moment accumulation rate along the Imperial fault. Likewise, a 30% increase of average plate thickness results in at least a ∼30% increase in moment rate and even larger increases are identified in regions of complex plate heterogeneity. These results emphasize the importance of considering rheological variations when estimating seismic hazard, suggesting that meaningful changes in seismic moment accumulation are revealed when considering spatial variations in crustal rheology.
Scale‐Aware Space‐Time Stochastic Parameterization of Subgrid‐Scale Velocity Enhancement of Sea Surface Fluxes
Authors: Bessac Julie , Christensen Hannah M. , Endo Kota , Monahan Adam H. , Weitzel Nils
Published: February 2021

Stochastic representation of the influence of the subgrid‐scales on the resolved scales in weather and climate models has been shown to improve ensemble spread and resolved variability. We propose a statistical scale‐aware space‐time model to characterize the contribution of mesoscale wind variability to air‐sea exchanges. In an earlier study, we analyzed the difference between “true” fluxes computed from a high resolution simulation and “resolved” fluxes obtained by coarse graining. This discrepancy is modeled in space and time, conditioned on the coarse‐grained wind and precipitation fields, to parameterize the enhancement of fluxes by mesoscale velocity variations. Stochastic parameterization models have traditionally been developed for particular model resolutions without the explicit capability to adapt to model resolution. We present an approach to develop stochastic models that adapt to resolution in a scale‐aware fashion. The scale‐aware parameterization is developed from empirical results for systematically coarse‐grained high‐resolution numerical model output. The statistical model is fit from numerical model output at three different coarsening resolutions. From this scale‐aware parameterization, we derive a stochastic parameterization of flux enhancement by subgrid velocity variations for arbitrary resolutions and characterize the conditional distributions and space‐time structures of the flux enhancement across model resolutions.
Absolute Age and Temperature Constraints on Deformation Along the Basal Décollement of the Jura Fold‐and‐Thrust Belt From Carbonate U‐Pb Dating and Clumped Isotopes
Authors: Looser N. , Madritsch H. , Guillong M. , Laurent O. , Wohlwend S. , Bernasconi S. M.
Published: February 2021

During its late‐stage evolution, the European Alpine orogen witnessed a northwest‐directed propagation of its deformation front along an evaporitic basal décollement into the foreland. This resulted in the decoupling of the northern Alpine Molasse Basin from its basement and the formation of the Jura fold‐and‐thrust belt. Here, we present the first absolute age and temperature constraints on deformation along this basal décollement using carbonate U‐Pb LA‐ICP‐MS dating and clumped isotope thermometry. We analyzed calcite veins associated with a thrust fault branching off from the basal décollement in the distal Molasse Basin and slickenfibers from thrusts and strike‐slip faults in the eastern Jura Mountains. Our U‐Pb data provide evidence for tectonic activity related to Alpine contraction between 14.3 and 4.5 Ma ago. According to the oldest deformation ages, the propagation of Alpine deformation into the distal foreland along the basal décollement occurred earlier than previously inferred by biostratigraphy, at Middle Miocene (Langhian) times at the latest. Younger deformation ages between 11.3 and 4.5 Ma correspond very well in time with shortening in the Subalpine Molasse and the Central Alps, proving simultaneous tectonic activity along both thrust fronts; i.e., the Jura Mountains and the Subalpine Molasse. Clumped isotopes reveal vein calcite precipitation at temperatures between 53 and 104 °C from fluids with oxygen isotope compositions between −6.2‰ and +9.5‰ reflecting distinct burial settings. Combined, our U‐Pb and clumped isotope data show that the burial conditions in the studied area remained constant between 14.3 and 4.5 Ma indicating that large‐scale foreland erosion did not initiate before 4.5 Ma.
Rainfall Washoff of Spores From Concrete and Asphalt Surfaces
Authors: Mikelonis Anne M. , Calfee M. W. , Lee Sang Don , Touati Abderrahmane , Ratliff Katherine
Published: February 2021

After a biological terrorist attack, understanding the migration of agents such as Bacillus anthracis is critical due to their deadly nature. This is important in urban settings with higher likelihood of human exposure and a large fraction of impervious materials contributing to pollutant washoff. The study goals were to understand the removal of spores from urban surfaces under different rainfall conditions, to compare washoff of two B. anthracis surrogate spores, and to compare two empirical fits for the first flush of spores from small areas. Concrete and asphalt were inoculated with either Bacillus atrophaeus or Bacillus thuringiensis kurstaki spores and exposed to simulated rainfall. The study assessed goodness‐of‐fit for the Storm Water Management Model (SWMM)'s exponential washoff function compared to an alternative two‐stage exponential function. The highest average washoff of spores was 15% for an hour‐long experiment. Spore washoff was not significantly different for the two spore types, but there were significant differences in washoff from asphalt versus concrete with more occurring from asphalt. Average kinetic energy of the storm event impacted washoff from asphalt, but not concrete. The two‐stage function had a better goodness‐of‐fit than the SWMM exponential function. As such, emergency responders should be aware that the spread of contamination is impacted by the droplet characteristics of the storm event and the surface material type in the contaminated area; modelers should be aware that different data‐fitting approaches may be more appropriate for first‐flush calculations of small washoff areas than those used for continuous long‐term simulation of large subcatchments.
A Cognitive-Behavioral Group Intervention for Parents of Youth with Chronic Pain: Development, Feasibility, and Preliminary Effectiveness
Authors: Lee Soeun , Edwards Kim , McMurtry C. Meghan
Published: February 2021

Background: Caregiving for a youth with chronic pain is associated with unique stressors. Parents can play important roles for youth coping and functional outcomes, although parents often report uncertainty about how to support their youth and may benefit from learning evidence-based strategies. However, few parent-targeted interventions for pediatric chronic pain exist, particularly delivered within a group format. Objectives: The aims of this study were to describe the development of a parent-targeted group intervention within an outpatient interdisciplinary pediatric chronic pain clinic and to assess preliminary feasibility and effectiveness. Method: The development and content of the intervention are described in detail. Feasibility was assessed via enrollment, attendance, and attrition. Effectiveness was assessed via parent self-reported responses to pain and psychological flexibility (PF) before and after treatment. Results: Seventy parents consented and participated in the 5-week group intervention (2 hr/session). Preliminary results demonstrated adequate feasibility, with attendance rates at 61.4% and attrition rates at 24.3%. After treatment, there were significant moderate- to large-sized decreases in 3 of 4 parent behaviors assessed (protectiveness, monitoring, minimizing) and large-sized increases in PF. Conclusions: This group intervention for parents can produce positive changes in self-reported parent behavior and PF and may be a feasible way to intervene within an outpatient interdisciplinary setting.

Implications for Impact Statement

Parents play important roles for supporting coping and functional outcomes in youth with chronic pain, although parents report uncertainty over how to best support their youth and may benefit from learning evidence-based strategies. This study suggests that a relatively brief parent-targeted group intervention (5 weeks, 2 hr/week) may help promote psychological flexibility and reduce unhelpful parent behaviours that may reinforce pain.
Specific inactivation of an antifungal bacterial siderophore by a fungal plant pathogen
Authors: Ho Ying-Ning , Hoo Sin Yong , Wang Bo-Wei , Hsieh Chi-Ting , Lin Ching-Chih , Sun Chi-Hui , Peng Chia-Chi , Lin Chih , Yang Yu-Liang
Published: February 2021

Bacteria and fungi secrete many natural products that inhibit each other’s growth and development. The dynamic changes in secreted metabolites that occur during interactions between bacteria and fungi are complicated. Pyochelin is a siderophore produced by many Pseudomonas and Burkholderia species that induces systemic resistance in plants and has been identified as an antifungal agent. Through imaging mass spectrometry and metabolomics analysis, we found that Phellinus noxius, a plant pathogen, can modify pyochelin and ent-pyochelin to an esterification product, resulting in reduced iron-chelation and loss of antifungal activity. We also observed that dehydroergosterol peroxide, the fungal metabolite, is only accumulated in the presence of pyochelin produced through bacteria–fungi interactions. For the first time, we show the fungal transformation of pyochelin in the microbial interaction. Our findings highlight the importance of understanding the dynamic changes of metabolites in microbial interactions and their influences on microbial communities.
Improved model simulation of soil carbon cycling by representing the microbially derived organic carbon pool
Authors: Fan Xianlei , Gao Decai , Zhao Chunhong , Wang Chao , Qu Ying , Zhang Jing , Bai Edith
Published: February 2021

During the decomposition process of soil organic carbon (SOC), microbial products such as microbial necromass and microbial metabolites may form an important stable carbon (C) pool, called microbially derived C, which has different decomposition patterns from plant-derived C. However, current Earth System Models do not simulate this microbially derived C pool separately. Here, we incorporated the microbial necromass pool to the first-order kinetic model and the Michaelis–Menten model, respectively, and validated model behaviors against previous observation data from the decomposition experiments of 13C-labeled necromass. Our models showed better performance than existing models and the Michaelis–Menten model was better than the first-order kinetic model. Microbial necromass C was estimated to be 10–27% of total SOC in the study soils by our models and therefore should not be ignored. This study provides a novel modification to process-based models for better simulation of soil organic C under the context of global changes.
Massive Southern Ocean phytoplankton bloom fed by iron of possible hydrothermal origin
Authors: Schine Casey M. S. , Alderkamp Anne-Carlijn , van Dijken Gert , Gerringa Loes J. A. , Sergi Sara , Laan Patrick , van Haren Hans , van de Poll Willem H. , Arrigo Kevin R.
Published: February 2021

Primary production in the Southern Ocean (SO) is limited by iron availability. Hydrothermal vents have been identified as a potentially important source of iron to SO surface waters. Here we identify a recurring phytoplankton bloom in the high-nutrient, low-chlorophyll waters of the Antarctic Circumpolar Current in the Pacific sector of the SO, that we argue is fed by iron of hydrothermal origin. In January 2014 the bloom covered an area of ~266,000 km2with depth-integrated chlorophylla > 300 mg m−2, primary production rates >1 g C m−2d−1, and a mean CO2flux of −0.38 g C m−2d−1. The elevated iron supporting this bloom is likely of hydrothermal origin based on the recurrent position of the bloom relative to two active hydrothermal vent fields along the Australian Antarctic Ridge and the association of the elevated iron with a distinct water mass characteristic of a nonbuoyant hydrothermal vent plume.
Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1
Authors: Park Jang-June , Thi Emily P. , Carpio Victor H. , Bi Yingzhi , Cole Andrew G. , Dorsey Bruce D. , Fan Kristi , Harasym Troy , Iott Christina L. , Kadhim Salam , Kim Jin Hyang , Lee Amy C. H. , Nguyen Duyan , Paratala Bhavna S. , Qiu Ruiqing , White Andre , Lakshminarasimhan Damodharan , Leo Christopher , Suto Robert K. , Rijnbrand Rene , Tang Sunny , Sofia Michael J. , Moore Chris B.
Published: February 2021

Programmed death-ligand 1 is a glycoprotein expressed on antigen presenting cells, hepatocytes, and tumors which upon interaction with programmed death-1, results in inhibition of antigen-specific T cell responses. Here, we report a mechanism of inhibiting programmed death-ligand 1 through small molecule-induced dimerization and internalization. This represents a mechanism of checkpoint inhibition, which differentiates from anti-programmed death-ligand 1 antibodies which function through molecular disruption of the programmed death 1 interaction. Testing of programmed death ligand 1 small molecule inhibition in a humanized mouse model of colorectal cancer results in a significant reduction in tumor size and promotes T cell proliferation. In addition, antigen-specific T and B cell responses from patients with chronic hepatitis B infection are significantly elevated upon programmed death ligand 1 small molecule inhibitor treatment. Taken together, these data identify a mechanism of small molecule-induced programmed death ligand 1 internalization with potential therapeutic implications in oncology and chronic viral infections.
RING domains act as both substrate and enzyme in a catalytic arrangement to drive self-anchored ubiquitination
Authors: Kiss Leo , Clift Dean , Renner Nadine , Neuhaus David , James Leo C.
Published: February 2021

Attachment of ubiquitin (Ub) to proteins is one of the most abundant and versatile of all posttranslational modifications and affects outcomes in essentially all physiological processes. RING E3 ligases target E2 Ub-conjugating enzymes to the substrate, resulting in its ubiquitination. However, the mechanism by which a ubiquitin chain is formed on the substrate remains elusive. Here we demonstrate how substrate binding can induce a specific RING topology that enables self-ubiquitination. By analyzing a catalytically trapped structure showing the initiation of TRIM21 RING-anchored ubiquitin chain elongation, and in combination with a kinetic study, we illuminate the chemical mechanism of ubiquitin conjugation. Moreover, biochemical and cellular experiments show that the topology found in the structure can be induced by substrate binding. Our results provide insights into ubiquitin chain formation on a structural, biochemical and cellular level with broad implications for targeted protein degradation.
A space hurricane over the Earth’s polar ionosphere
Authors: Zhang Qing-He , Zhang Yong-Liang , Wang Chi , Oksavik Kjellmar , Lyons Larry R. , Lockwood Michael , Yang Hui-Gen , Tang Bin-Bin , Moen Jøran Idar , Xing Zan-Yang , Ma Yu-Zhang , Wang Xiang-Yu , Ning Ya-Fei , Xia Li-Dong
Published: February 2021

In Earth’s low atmosphere, hurricanes are destructive due to their great size, strong spiral winds with shears, and intense rain/precipitation. However, disturbances resembling hurricanes have not been detected in Earth’s upper atmosphere. Here, we report a long-lasting space hurricane in the polar ionosphere and magnetosphere during low solar and otherwise low geomagnetic activity. This hurricane shows strong circular horizontal plasma flow with shears, a nearly zero-flow center, and a coincident cyclone-shaped aurora caused by strong electron precipitation associated with intense upward magnetic field-aligned currents. Near the center, precipitating electrons were substantially accelerated to ~10 keV. The hurricane imparted large energy and momentum deposition into the ionosphere despite otherwise extremely quiet conditions. The observations and simulations reveal that the space hurricane is generated by steady high-latitude lobe magnetic reconnection and current continuity during a several hour period of northward interplanetary magnetic field and very low solar wind density and speed.
Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation
Authors: Jones Nicholas , Blagih Julianna , Zani Fabio , Rees April , Hill David G. , Jenkins Benjamin J. , Bull Caroline J. , Moreira Diana , Bantan Azari I. M. , Cronin James G. , Avancini Daniele , Jones Gareth W. , Finlay David K. , Vousden Karen H. , Vincent Emma E. , Thornton Catherine A.
Published: February 2021

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.
Causal role for sleep-dependent reactivation of learning-activated sensory ensembles for fear memory consolidation
Authors: Clawson Brittany C. , Pickup Emily J. , Ensing Amy , Geneseo Laura , Shaver James , Gonzalez-Amoretti John , Zhao Meiling , York A. Kane , Kuhn Femke Roig , Swift Kevin , Martinez Jessy D. , Wang Lijing , Jiang Sha , Aton Sara J.
Published: February 2021

Learning-activated engram neurons play a critical role in memory recall. An untested hypothesis is that these same neurons play an instructive role in offline memory consolidation. Here we show that a visually-cued fear memory is consolidated during post-conditioning sleep in mice. We then use TRAP (targeted recombination in active populations) to genetically label or optogenetically manipulate primary visual cortex (V1) neurons responsive to the visual cue. Following fear conditioning, mice respond to activation of this visual engram population in a manner similar to visual presentation of fear cues. Cue-responsive neurons are selectively reactivated in V1 during post-conditioning sleep. Mimicking visual engram reactivation optogenetically leads to increased representation of the visual cue in V1. Optogenetic inhibition of the engram population during post-conditioning sleep disrupts consolidation of fear memory. We conclude that selective sleep-associated reactivation of learning-activated sensory populations serves as a necessary instructive mechanism for memory consolidation.
Water enables mild oxidation of methane to methanol on gold single-atom catalysts
Authors: Luo Laihao , Luo Jie , Li Hongliang , Ren Fangning , Zhang Yifei , Liu Andong , Li Wei-Xue , Zeng Jie
Published: February 2021

As a 100% atom-economy process, direct oxidation of methane into methanol remains as a grand challenge due to the dilemma between activation of methane and over-oxidation of methanol. Here, we report that water enabled mild oxidation of methane into methanol with >99% selectivity over Au single atoms on black phosphorus (Au1/BP) nanosheets under light irradiation. The mass activity of Au1/BP nanosheets reached 113.5 μmol gcatal−1 in water pressured with 33 bar of mixed gas (CH4:O2 = 10:1) at 90 °C under light irradiation (1.2 W), while the activation energy was 43.4 kJ mol−1. Mechanistic studies revealed that water assisted the activation of O2 to generate reactive hydroxyl groups and •OH radicals under light irradiation. Hydroxyl groups reacted with methane at Au single atoms to form water and CH3* species, followed by oxidation of CH3* via •OH radicals into methanol. Considering the recycling of water during the whole process, we can also regard water as a catalyst.
Surface passivated halide perovskite single-crystal for efficient photoelectrochemical synthesis of dimethoxydihydrofuran
Authors: Wang Xu-Dong , Huang Yu-Hua , Liao Jin-Feng , Wei Ze-Feng , Li Wen-Guang , Xu Yang-Fan , Chen Hong-Yan , Kuang Dai-Bin
Published: February 2021

Halide perovskite single-crystals have recently been widely highlighted to possess high light harvesting capability and superior charge transport behaviour, which further enable their attractive performance in photovoltaics. However, their application in photoelectrochemical cells has not yet been reported. Here, a methylammonium lead bromide MAPbBr3 single-crystal thin film is reported as a photoanode with potential application in photoelectrochemical organic synthesis, 2,5-dimethoxy-2,5-dihydrofuran. Depositing an ultrathin Al2O3 layer is found to effectively passivate perovskite surface defects. Thus, the nearly 5-fold increase in photoelectrochemical performance with the saturated current being increased from 1.2 to 5.5 mA cm−2 is mainly attributed to suppressed trap-assisted recombination for MAPbBr3 single-crystal thin film/Al2O3. In addition, Ti3+-species-rich titanium deposition has been introduced not only as a protective film but also as a catalytic layer to further advance performance and stability. As an encouraging result, the photoelectrochemical performance and stability of MAPbBr3 single-crystal thin film/Al2O3/Ti-based photoanode have been significantly improved for 6 h continuous dimethoxydihydrofuran evolution test with a high Faraday efficiency of 93%.
Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus
Authors: Bullard Brianna L. , Corder Brigette N. , DeBeauchamp Jennifer , Rubrum Adam , Korber Bette , Webby Richard J. , Weaver Eric A.
Published: February 2021

Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential. Here, we utilize epigraph, a computational algorithm, to design a universal swine H3 influenza vaccine. The epigraph hemagglutinin proteins are delivered using an Adenovirus type 5 vector and are compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination leads to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduces weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, show stronger levels of cross-reactive antibodies and T-cell responses after immunization with the epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination shows superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.
Laparoscopic isolated caudate lobe resection
Authors: Parikh Maulik , Han Ho-Seong , Cho Jai Young , D’Silva Mizelle
Published: February 2021

Previously, isolated caudate lobectomy was rarely performed and the caudate lobe was usually resected along with other segments. Isolated caudate lobe resection is a challenging procedure even for an experienced surgeon. Our aim was to evaluate the feasibility, safety and outcomes of laparoscopic isolated caudate lobectomy and to compare these with the open technique. We retrospectively analyzed 21 patients who underwent isolated caudate lobectomy between January 2005 and December 2018 at Seoul National University Bundang Hospital. Patients who underwent either anatomical or non-anatomical resection of the caudate lobe were included. Patients were divided into two groups according to whether they underwent laparoscopic or open surgery. Intra-operative and postoperative outcomes were compared with a median follow-up of 43 months (4–149). A total of 21 patients were included in the study. Of these, 12 (57.14%) underwent laparoscopic and nine (42.85%) underwent open caudate lobectomy. Median operation time (204.5 vs. 200 minutes, p = 0.397), estimated blood loss (250 vs. 400 ml, p = 0.214) and hospital stay (4 vs. 7 days, p = 0.298) were comparable between laparoscopy and open group. The overall post operative complication rate was similar in both groups (p = 0.375). The 5-year disease free survival rate (42.9% vs 60.0%, p = 0.700) and the 5-year overall survival rate (76.2% vs 64.8%, p = 0.145) was similar between laparoscopy and open group. Our findings demonstrate that with increasing surgical expertise and technological advances, laparoscopic isolated caudate lobectomy can become a feasible and safe in selected patients.
Severe hypoglycemia and the risk of end stage renal disease in type 2 diabetes
Authors: Yun Jae-Seung , Park Yong-Moon , Han Kyungdo , Kim Hyung-Wook , Cha Seon-Ah , Ahn Yu-Bae , Ko Seung-Hyun
Published: February 2021

We investigated the association between the incidence of severe hypoglycemia and the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes. Baseline and follow-up data for 988,333 participants with type 2 diabetes were retrieved from the National Health Insurance System database. The number of severe hypoglycemia episodes experienced from 2007 to 2009 was determined. The primary outcome was the development of ESRD after the baseline evaluation. Participants were followed from the baseline until death or December 31, 2016, during this period 14,545 participants (1.5%) developed ESRD. In the crude model, compared with those who experienced no severe hypoglycemia, the hazard ratios (95% confidential intervals) for developing ESRD were 4.96 (4.57–5.39), 6.84 (5.62–8.32), and 9.51 (7.14–12.66) in participants who experienced one, two, and three or more episodes of severe hypoglycemia, respectively. Further adjustment for various confounding factors attenuated the association between severe hypoglycemia and ESRD; the significance of the association between severe hypoglycemia and ESRD was maintained. Having three or more severe hypoglycemia episodes was associated with a nearly two-fold increased risk of developing ESRD. Prior episodes of severe hypoglycemia were associated with an increased risk of ESRD among Korean adults with type 2 diabetes.
Studies on metal–organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension
Authors: Mohamed Nura A. , Abou-Saleh Haissam , Kameno Yu , Marei Isra , de Nucci Gilberto , Ahmetaj-Shala Blerina , Shala Fisnik , Kirkby Nicholas S. , Jennings Lewis , Al-Ansari Dana E. , Davies Robert P. , Lickiss Paul D. , Mitchell Jane A.
Published: February 2021

Pulmonary arterial hypertension (PAH) is an incurable disease, although symptoms are treated with a range of dilator drugs. Despite their clinical benefits, these drugs are limited by systemic side-effects. It is, therefore, increasingly recognised that using controlled drug-release nanoformulation, with future modifications for targeted drug delivery, may overcome these limitations. This study presents the first evaluation of a promising nanoformulation (highly porous iron-based metal–organic framework (MOF); nanoMIL-89) as a carrier for the PAH-drug sildenafil, which we have previously shown to be relatively non-toxic in vitro and well-tolerated in vivo. In this study, nanoMIL-89 was prepared and charged with a payload of sildenafil (generating Sil@nanoMIL-89). Sildenafil release was measured by Enzyme-Linked Immunosorbent Assay (ELISA), and its effect on cell viability and dilator function in mouse aorta were assessed. Results showed that Sil@nanoMIL-89 released sildenafil over 6 h, followed by a more sustained release over 72 h. Sil@nanoMIL-89 showed no significant toxicity in human blood outgrowth endothelial cells for concentrations up to100µg/ml; however, it reduced the viability of the human pulmonary artery smooth muscle cells (HPASMCs) at concentrations > 3 µg/ml without inducing cellular cytotoxicity. Finally, Sil@nanoMIL-89 induced vasodilation of mouse aorta after a lag phase of 2–4 h. To our knowledge, this study represents the first demonstration of a novel nanoformulation displaying delayed drug release corresponding to vasodilator activity. Further pharmacological assessment of our nanoformulation, including in PAH models, is required and constitutes the subject of ongoing investigations.
Three-dimensional structure of human cyclooxygenase (hCOX)-1
Authors: Miciaccia Morena , Belviso Benny Danilo , Iaselli Mariaclara , Cingolani Gino , Ferorelli Savina , Cappellari Marianna , Loguercio Polosa Paola , Perrone Maria Grazia , Caliandro Rocco , Scilimati Antonio
Published: February 2021

The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined to an R/Rfree of 20.82/26.37, at 3.36 Å resolution. hCOX-1 structure provides a detailed picture of the enzyme active site and the residues crucial for inhibitor/substrate binding and catalytic activity. We compared hCOX-1 crystal structure with the ovine COX-1 and human COX-2 structures by using metrics based on Cartesian coordinates, backbone dihedral angles, and solvent accessibility coupled with multivariate methods. Differences and similarities among structures are discussed, with emphasis on the motifs responsible for the diversification of the various enzymes (primary structure, stability, catalytic activity, and specificity). The structure of hCOX-1 represents an essential step towards the development of new and more selective COX-1 inhibitors of enhanced therapeutic potential.
Correlation between early features and prognosis of symptomatic COVID-19 discharged patients in Hunan, China
Authors: Cai Yeyu , Liu Jiayi , Yang Haitao , Chen Taili , Yu Qizhi , Chen Juan , Huang Deng , Chen Zhu , Shang Quan-Liang , Ma Cong , Chen Xiangyu , Xiao Enhua
Published: February 2021

To determine the correlation between the clinical, laboratory, and radiological findings and the hospitalization days in Coronavirus Infectious Disease-19 (COVID-19) discharged patients. We retrospectively identified 172 discharged patients with COVID-19 pneumonia from January 10, 2020, to February 28, 2020, in Hunan province. The patients were categorized into group 1 (≤ 19 days) and group 2 (> 19 days) based on the time from symptom onset to discharge. Cough during admission occurred more commonly in group 2 (68.4%) than in group 1 (53.1%, p = 0.042). White blood cell (p = 0.045), neutrophil counts (p = 0.023), Alanine aminotransferase (p = 0.029), Aspartate aminotransferase (p = 0.027) and Lactate dehydrogenase (p = 0.021) that were above normal were more common in group 2. Patients with single lesions were observed more in group 1(17.7%, p = 0.018) and multiple lesions observed more in group 2(86.8%, p = 0.012). The number of lobes involved (p = 0.008) in the CT score (p = 0.001) for each patient was all differences between the two groups with a statistically significant difference. Mixed ground-glass opacity (GGO) and consolidation appearances were observed in most patients. GGO components > consolidation appearance was more common in group 1 (25.0%) than in group 2 (8.0%) with a significant difference (0.015), GGO < consolidation was more common in group 2(71.1%, p = 0.012). From the logistic regression analysis, the CT score (OR, 1.223; 95% CI, 1.004 to 1.491, p = 0.046) and the appearance of GGO > consolidation (OR, 0.150; 95% CI, 0.034 to 0.660, p = 0.012) were independently associated with the hospitalization days. Thus, special attention should be paid to the role of radiological features in monitoring the disease prognosis.
Osseointegration of a novel dental implant in canine
Authors: Wang Lingxiao , Gao Zhenhua , Su Yucheng , Liu Qian , Ge Yi , Shan Zhaochen
Published: February 2021

This study aimed to compare and verify the osseointegration performance of a novel implant (NI) in vivo, which could provide a useful scientific basis for the further development of NIs. Thirty-two NIs treated with hydrofluoric acid and anodization and sixteen control implants (CIs) were placed in the mandibles of 8 beagles. Micro-CT showed that the trabecular number (Tb.N) significantly increased and trabecular separation (Tb.Sp) significantly decreased in the NIs at 2 weeks. Significant differences were found in the trabecular thickness, Tb.N, Tb.Sp, bone surface/bone volume ratio, and bone volume/total volume ratio between the two groups from the 2nd–4th weeks. However, there were no significant differences between the two groups in the bone volume density at 2, 4, 8, or 12 weeks or bone-implant contact at 2 or 4 weeks, but the BIC in the CIs was higher than that in the NIs at the 8th and 12th weeks. Meanwhile, the histological staining showed a similar osseointegration process between the two groups over time. Overall, the NIs could be used as new potential implants after further improvement.
Examining Neanderthal and carnivore occupations of Teixoneres Cave (Moià, Barcelona, Spain) using archaeostratigraphic and intra-site spatial analysis
Authors: Zilio Leandro , Hammond Heidi , Karampaglidis Theodoros , Sánchez-Romero Laura , Blasco Ruth , Rivals Florent , Rufà Anna , Picin Andrea , Chacón M. Gema , Demuro Martina , Arnold Lee J. , Rosell Jordi
Published: February 2021

Teixoneres Cave (Moià, Barcelona, Spain) is a reference site for Middle Palaeolithic studies of the Iberian Peninsula. The cave preserves an extensive stratigraphic sequence made up of eight units, which is presented in depth in this work. The main goal of this study is to undertake an initial spatial examination of Unit III, formed during Marine Isotope Stage 3, with the aim of understanding spatial organization and past activities developed by Neanderthals and carnivores (bears, hyenas and smaller carnivores). The total sample analysed includes 38,244 archaeological items and 5888 limestone blocks. The application of GIS tools allows us to clearly distinguish three geologically-defined stratigraphic subunits. Unit III has been previously interpreted as a palimpsest resulting from alternating occupation of the cave by human groups and carnivores. The distribution study shows that faunal specimens, lithic artefacts, hearths and charcoal fragments are significantly concentrated at the entrance of the cave where, it is inferred, hominins carried out different activities, while carnivores preferred the sheltered zones in the inner areas of the cave. The results obtained reveal a spatial pattern characterized by fire use related zones, and show that the site was occupied by Neanderthals in a similar and consistent way throughout the ˃ 7000 years range covered by the analysed subunits. This spatial pattern is interpreted as resulting from repeated short-term human occupations.
Nanocomposite-based dual enzyme system for broad-spectrum scavenging of reactive oxygen species
Authors: Pavlovic Marko , Muráth Szabolcs , Katona Xénia , Alsharif Nizar B. , Rouster Paul , Maléth József , Szilagyi Istvan
Published: February 2021

A broad-spectrum reactive oxygen species (ROS)-scavenging hybrid material (CASCADE) was developed by sequential adsorption of heparin (HEP) and poly(L-lysine) (PLL) polyelectrolytes together with superoxide dismutase (SOD) and horseradish peroxidase (HRP) antioxidant enzymes on layered double hydroxide (LDH) nanoclay support. The synthetic conditions were optimized so that CASCADE possessed remarkable structural (no enzyme leakage) and colloidal (excellent resistance against salt-induced aggregation) stability. The obtained composite was active in decomposition of both superoxide radical anions and hydrogen peroxide in biochemical assays revealing that the strong electrostatic interaction with the functionalized support led to high enzyme loadings, nevertheless, it did not interfere with the native enzyme conformation. In vitro tests demonstrated that ROS generated in human cervical adenocarcinoma cells were successfully consumed by the hybrid material. The cellular uptake was not accompanied with any toxicity effects, which makes the developed CASCADE a promising candidate for treatment of oxidative stress-related diseases.
Transcriptome analysis reveals differentially expressed MYB transcription factors associated with silicon response in wheat
Authors: Hao Lidong , Shi Shubing , Guo Haibin , Zhang Jinshan , Li Peng , Feng Yanfei
Published: February 2021

Silicon plays a vital role in plant growth. However, molecular mechanisms in response to silicon have not previously been studied in wheat. In this study, we used RNA-seq technology to identify differentially expressed genes (DEGs) in wheat seedlings treated with silicon. Results showed that many wheat genes responded to silicon treatment, including 3057 DEGs, of which 6.25% (191/3057) were predicted transcription factors (TFs). Approximately 14.67% (28 out of 191) of the differentially expressed TFs belonged to the MYB TF family. Gene ontology (GO) enrichment showed that the highly enriched DEGs were responsible for secondary biosynthetic processes. According to KEGG pathway analysis, the DEGs were related to chaperones and folding catalysts, phenylpropanoid biosynthesis, and protein processing in the endoplasmic reticulum. Moreover, 411 R2R3-MYB TFs were identified in the wheat genome, all of which were classified into 15 groups and accordingly named S1–S15. Among them, 28 were down-regulated under silicon treatment. This study revealed the essential role of MYB TFs in the silicon response mechanism of plants, and provides important genetic resources for breeding silicon-tolerant wheat.
Magmatic flare-up causes crustal thickening at the transition from subduction to continental collision
Authors: Ganade Carlos E. , Lanari Pierre , Rubatto Daniela , Hermann Joerg , Weinberg Roberto F. , Basei Miguel A. S. , Tesser Lucas R. , Caby Renaud , Agbossoumondé Yao , Ribeiro Caroline M.
Published: February 2021

Above subduction zones, magma production rate and crustal generation can increase by an order of magnitude during narrow time intervals known as magmatic flare-ups. However, the consequences of these events in the deep arc environment remain poorly understood. Here we use petrological and in-situ zircon dating techniques to investigate the root of a continental arc within the collisional West Gondwana Orogen that is now exposed in the Kabyé Massif, Togo. We show that gabbros intruded 670 million years ago at 20–25 km depth were transformed to eclogites by 620 million years ago at 65–70 km depth. This was coeval with extensive magmatism at 20–40 km depth, indicative of a flare-up event which peaked just prior to the subduction of the continental margin. We propose that increased H2O flux from subduction of serpentinized mantle in the hyper-extended margin of the approaching continent was responsible for the increased magma productivity and crustal thickening.
Recent advances in bioanalytical methods to measure proteome stability in cells
Authors: Zhang Shouxiang , Greening David W. , Hong Yuning
Published: February 2021

This review summarizes recent bioanalytical methods for measuring and profiling protein stability in cells on a proteome-wide scale, which can provide insights for proteostasis and associated diseases.
Investigation of the biological functions of heparan sulfate using a chemoenzymatic synthetic approach
Authors: Wang Zhangjie , Arnold Katelyn , Dhurandhare Vijay Manohar , Xu Yongmei , Liu Jian
Published: February 2021

Heparan sulfate (HS) is a highly sulfated polysaccharide playing essential physiological and pathophysiological roles in the animal kingdom.
Tuning the electronic transition energy of indoleviasubstitution: application to identify tryptophan-based chromophores that absorb and emit visible light
Authors: Micikas Robert J. , Ahmed Ismail A. , Acharyya Arusha , Smith Amos B. , Gai Feng
Published: February 2021

The unnatural amino acids 4CHO-tryptophan and 4NO2-tryptophan can be excited by visible light and could afford useful application as biological chromophores.
A copper(ii)-based porous metal–organic framework for the efficient and rapid capture of toxic oxo-anion pollutants from water
Authors: Li Yang , Yang Jin , Ma Jian-Fang
Published: February 2021

A porous cationic metal–organic framework was rationally achieved with nanosized channels, and it exhibited the capability to efficiently capture environmentally toxic Cr2O72− and MnO4− anions.
Oxygen vacancy modulated interface chemistry: identifying iron(iv) in heterogeneous Fenton reaction
Authors: Yu Yaqin , Chen Haoze , Yan Li , Jing Chuanyong
Published: February 2021

WO3−x switched the reaction of FeII with H2O2 from the formation of FeIII towards the direct generation of FeIV. FeIV was reduced to FeIII/FeII by electrons localized in the t2g orbitals of WO3−x, which favored the generation of ˙O2−, ˙OH, and 1O2.
Volatilome changes during probiotic fermentation of combined soy and rice drinks
Authors: Nissen Lorenzo , Casciano Flavia , Gianotti Andrea
Published: February 2021

Probiotic fermentation of combined plant-based drinks in comparison with single drinks gives a superior final product with higher bacterial growth, more health-related and nice flavoring compounds, and less undesirable ones.
Investigating the remediation potential of iron oxide nanoparticles in Cu-polluted soil–plant systems: coupled geochemical, geophysical and biological approaches
Authors: Demangeat E. , Pédrot M. , Dia A. , Bouhnik-Le-Coz M. , Roperch P. , Compaoré G. , Cabello-Hurtado F.
Published: February 2021

Introduction of iron oxide nanoparticles (NPs) and/or copper (Cu) in soil-plant columns.
The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery
Authors: Baroud Milad , Lepeltier Elise , Thepot Sylvain , El-Makhour Yolla , Duval Olivier
Published: February 2021

Nucleoside and nucleotide analogs are essential tools in our limited arsenal in the fight against cancer.
Removal of emulsified oil by ferrite-coated ceramic membranes
Authors: Xie Liyuan , Coffie Ernestine Sefakor , Li Peng , Zhang Bo
Published: February 2021

This research was conducted to investigate the removal effect and mechanisms of emulsified oil by ferrite-coated ceramic membranes.