bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPrimary 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

AbstractProgrammed 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

AbstractAttachment 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

AbstractIn 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

AbstractFructose 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

AbstractLearning-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

AbstractAs 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

AbstractHalide 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

AbstractInfluenza 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

AbstractPreviously, 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

AbstractWe 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

AbstractPulmonary 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

AbstractThe 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

AbstractTo 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

AbstractThis 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.