bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-synuclein is involved in manganese-induced spatial memory and synaptic plasticity impairments via TrkB/Akt/Fyn-mediated phosphorylation of NMDA receptors
Authors: Ma Zhuo , Liu Kuan , Li Xin-Ru , Wang Can , Liu Chang , Yan Dong-Ying , Deng Yu , Liu Wei , Xu Bin 
Published: October 2020

AbstractManganese (Mn) overexposure produces long-term cognitive deficits and reduces brain-derived neurotrophic factor (BDNF) in the hippocampus. However, it remains elusive whether Mn-dependent enhanced alpha-synuclein (α-Syn) expression, suggesting a multifaceted mode of neuronal toxicities, accounts for interference with BDNF/TrkB signaling. In this study, we used C57BL/6J WT and α-Syn knockout (KO) mice to establish a model of manganism and found that Mn-induced impairments in spatial memory and synaptic plasticity were related to the α-Syn protein. In addition, consistent with the long-term potentiation (LTP) impairments that were observed, α-Syn KO relieved Mn-induced degradation of PSD95, phosphorylated CaMKIIα, and downregulated SynGAP protein levels. We transfected HT22 cells with lentivirus (LV)-α-Syn shRNA, followed by BDNF and Mn stimulation. In vitro experiments indicated that α-Syn selectively interacted with TrkB receptors and inhibited BDNF/TrkB signaling, leading to phosphorylation and downregulation of GluN2B. The binding of α-Syn to TrkB and Fyn-mediated phosphorylation of GluN2B were negatively regulated by BDNF. Together, these findings indicate that Mn-dependent enhanced α-Syn expression contributes to further exacerbate BDNF protein-level reduction and to inhibit TrkB/Akt/Fyn signaling, thereby disturbing Fyn-mediated phosphorylation of the NMDA receptor GluN2B subunit at tyrosine. In KO α-Syn mice treated with Mn, spatial memory and LTP impairments were less pronounced than in WT mice. However, the same robust neuronal death was observed as a result of Mn-induced neurotoxicity.
Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle
Authors: Theparambil Shefeeq M. , Hosford Patrick S. , Ruminot Iván , Kopach Olga , Reynolds James R. , Sandoval Pamela Y. , Rusakov Dmitri A. , Barros L. Felipe , Gourine Alexander V. 
Published: October 2020

AbstractBrain cells continuously produce and release protons into the extracellular space, with the rate of acid production corresponding to the levels of neuronal activity and metabolism. Efficient buffering and removal of excess H+ is essential for brain function, not least because all the electrogenic and biochemical machinery of synaptic transmission is highly sensitive to changes in pH. Here, we describe an astroglial mechanism that contributes to the protection of the brain milieu from acidification. In vivo and in vitro experiments conducted in rodent models show that at least one third of all astrocytes release bicarbonate to buffer extracellular H+ loads associated with increases in neuronal activity. The underlying signalling mechanism involves activity-dependent release of ATP triggering bicarbonate secretion by astrocytes via activation of metabotropic P2Y1 receptors, recruitment of phospholipase C, release of Ca2+ from the internal stores, and facilitated outward HCO3− transport by the electrogenic sodium bicarbonate cotransporter 1, NBCe1. These results show that astrocytes maintain local brain extracellular pH homeostasis via a neuronal activity-dependent release of bicarbonate. The data provide evidence of another important metabolic housekeeping function of these glial cells.
Reconstructing the electrical structure of dust storms from locally observed electric field data
Authors: Zhang Huan , Zhou You-He 
Published: October 2020

AbstractWhile the electrification of dust storms is known to substantially affect the lifting and transport of dust particles, the electrical structure of dust storms and its underlying charge separation mechanisms are largely unclear. Here we present an inversion method, which is based on the Tikhonov regularization for inverting the electric field data collected in a near-ground observation array, to reconstruct the space-charge density and electric field in dust storms. After verifying the stability, robustness, and accuracy of the inversion procedure, we find that the reconstructed space-charge density exhibits a universal three-dimensional mosaic pattern of oppositely charged regions, probably due to the charge separation by turbulence. Furthermore, there are significant linear relationships between the reconstructed space-charge densities and measured PM10 dust concentrations at each measurement point, suggesting a multi-point large-scale charge equilibrium phenomenon in dust storms. These findings refine our understanding of charge separation mechanisms and particle transport in dust storms.
Structural basis for energy transfer in a huge diatom PSI-FCPI supercomplex
Authors: Xu Caizhe , Pi Xiong , Huang Yawen , Han Guangye , Chen Xiaobo , Qin Xiaochun , Huang Guoqiang , Zhao Songhao , Yang Yanyan , Kuang Tingyun , Wang Wenda , Sui Sen-Fang , Shen Jian-Ren 
Published: October 2020

AbstractDiatom is an important group of marine algae and contributes to around 20% of the global photosynthetic carbon fixation. Photosystem I (PSI) of diatoms is associated with a large number of fucoxanthin-chlorophyll a/c proteins (FCPIs). We report the structure of PSI-FCPI from a diatom Chaetoceros gracilis at 2.38 Å resolution by single-particle cryo-electron microscopy. PSI-FCPI is a monomeric supercomplex consisting of 12 core and 24 antenna subunits (FCPIs), and 326 chlorophylls a, 34 chlorophylls c, 102 fucoxanthins, 35 diadinoxanthins, 18 β-carotenes and some electron transfer cofactors. Two subunits designated PsaR and PsaS were found in the core, whereas several subunits were lost. The large number of pigments constitute a unique and huge network ensuring efficient energy harvesting, transfer and dissipation. These results provide a firm structural basis for unraveling the mechanisms of light-energy harvesting, transfer and quenching in the diatom PSI-FCPI, and also important clues to evolutionary changes of PSI-LHCI.
In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells
Authors: Martinez-Lage M. , Torres-Ruiz R. , Puig-Serra P. , Moreno-Gaona P. , Martin M. C. , Moya F. J. , Quintana-Bustamante O. , Garcia-Silva S. , Carcaboso A. M. , Petazzi P. , Bueno C. , Mora J. , Peinado H. , Segovia J. C. , Menendez P. , Rodriguez-Perales S. 
Published: October 2020

AbstractFusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.
Significant increase of global anomalous moisture uptake feeding landfalling Atmospheric Rivers
Authors: Algarra Iago , Nieto Raquel , Ramos Alexandre M. , Eiras-Barca Jorge , Trigo Ricardo M. , Gimeno Luis 
Published: October 2020

AbstractOne of the most robust signals of climate change is the relentless rise in global mean surface temperature, which is linked closely with the water-holding capacity of the atmosphere. A more humid atmosphere will lead to enhanced moisture transport due to, among other factors, an intensification of atmospheric rivers (ARs) activity, which are an important mechanism of moisture advection from subtropical to extra-tropical regions. Here we show an enhanced evapotranspiration rates in association with landfalling atmospheric river events. These anomalous moisture uptake (AMU) locations are identified on a global scale. The interannual variability of AMU displays a significant increase over the period 1980-2017, close to the Clausius-Clapeyron (CC) scaling, at 7 % per degree of surface temperature rise. These findings are consistent with an intensification of AR predicted by future projections. Our results also reveal generalized significant increases in AMU at the regional scale and an asymmetric supply of oceanic moisture, in which the maximum values are located over the region known as the Western Hemisphere Warm Pool (WHWP) centred on the Gulf of Mexico and the Caribbean Sea.
Al2O3-modified PS-PVD 7YSZ thermal barrier coatings for advanced gas-turbine engines
Authors: Zhang Xiaofeng , Deng Ziqian , Li Hong , Mao Jie , Deng Chunming , Deng Changguang , Niu Shaopeng , Chen Wenlong , Song Jinbing , Fan Jiafeng , Liu Min , Zhou Kesong 
Published: October 2020

AbstractPlasma spray-physical vapor deposition (PS-PVD), called the third-generation method for thermal barrier coatings (TBCs) fabrication, has great potential for their using in gas-turbine engines. Compared to atmospheric plasma spray (APS), called the first-generation TBCs, and electron beam-PVD (EB-PVD), called the second generation, PS-PVD has many interesting features, including non-line sight deposition, high deposition rate, and microstructural flexibility, among others. Such advantages make them a promising approach to prepare thermal barrier coatings for advanced gas-turbine engines. Using PS-PVD, feather-like columnar TBCs with good strain tolerance and low thermal conductivity can be fabricated. However, prior to their application in gas-turbine engines, some disadvantages, such as CMAS (CaO–MgO–Al2O3–SiO2, etc.) corrosion and oxidation resistance, need to be addressed. In this work, a method to develop Al2O3-modified PS-PVD 7YSZ TBCs was proposed. The experimental results demonstrate that the Al2O3-modification process is an effective approach to address the aforementioned weaknesses of traditional PS-PVD 7YSZ TBCs.
Synergy of pandemics-social isolation is associated with worsened Parkinson severity and quality of life
Authors: Subramanian Indu , Farahnik Joshua , Mischley Laurie K. 
Published: October 2020

AbstractSocial isolation and its deleterious effects on health increases with age in the general population. People with Parkinson’s Disease (PWP) are no exception. Social isolation is a risk factor for worsened health outcomes and increased mortality. Symptoms such as depression and sleep dysfunction are adversely affected by loneliness. There is a paucity of research on social isolation in Parkinson’s disease (PD), which is all the more critical now in the setting of social distancing due to COVID-19. The goal of this study was to survey individuals with PD to evaluate whether social isolation is associated with PD symptom severity and quality of life. Only individuals reporting a diagnosis of idiopathic PD were included in this analysis. The primary outcome measures were the Patient-Reported Outcomes in PD (PRO-PD) and questions from PROMIS Global related to social health. PRO-PD scores increased as social performance and social satisfaction scores diminished. Individuals who reported being lonely experienced a 55% greater symptom severity than those who were not lonely (P < 0.01). Individuals who documented having a lot of friends had 21% fewer symptoms than those with few or no friends (P < 0.01). Social isolation was associated with greater patient-reported PD severity and lower quality of life, although it is unclear whether this is the cause and/or a consequence of the disease. In essence, the Parkinson pandemic and the pandemic of social isolation have been further compounded by the recent COVID-19 pandemic. The results emphasize the need to keep PWP socially connected and prevent loneliness in this time of social distancing. Proactive use of virtual modalities for support groups and social prescribing should be explored.
Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
Authors: Atcheson Erwan , Cabral-Miranda Gustavo , Salman Ahmed M. , Reyes-Sandoval Arturo 
Published: October 2020

AbstractMalaria remains one of the world’s most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an effective vaccine; but the leading P. falciparum and P. vivax vaccine candidates, RTS,S and VMP001, show only modest to low field efficacy. New antigens and improved ways for screening antigens for protective efficacy will be required. This study exploits the potential of Virus-Like Particles (VLP) to enhance immune responses to antigens, the ease of coupling peptides to the Q beta (Qβ) VLP and the existing murine malaria challenge to screen B-cell epitopes for protective efficacy. We screened P. vivax TRAP (PvTRAP) immune sera against individual 20-mer PvTRAP peptides. The most immunogenic peptides associated with protection were loaded onto Qβ VLPs to assess protective efficacy in a malaria sporozoite challenge. A second approach focused on identifying conserved regions within known sporozoite invasion proteins and assessing them as part of the Qβ. Using this VLP as a peptide scaffold, four new protective B-cell epitopes were discovered: three from the disordered region of PvTRAP and one from Thrombospondin-related sporozoite protein (TRSP). Antigenic interference between these and other B-cell epitopes was also explored using the virus-like particle/peptide platform. This approach demonstrates the utility of VLPs to help identifying new B-cell epitopes for inclusion in next-generation malaria vaccines.
Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
Authors: Pai Chen-Hsueh , Lin Shu-Rung , Liu Chia-Hao , Pan Szu-Yu , Hsu Hao , Chen Yi-Ting , Yen Ching-Tzu , Yu I-Shing , Wu Hua-Lin , Lin Shuei-Liong , Lin Shu-Wha 
Published: October 2020

AbstractThe role of fibroblasts in tissue fibrosis has been extensively studied. Activated fibroblasts, namely myofibroblasts, produce pathological extracellular matrix. CD248, a type I transmembrane glycoprotein, is expressed in fibroblasts after birth. In human chronic kidney disease, upregulated CD248 in myofibroblasts is linked to poor renal survival. In this study, we demonstrated a novel interaction between CD248 and macrophages to be a key step in mediating tissue fibrosis. CD248 was upregulated in myofibroblasts in murine models of renal and peritoneal fibrosis. Cd248 knockout (Cd248–/–) could attenuate both renal and peritoneal fibrosis. By parabiosis of GFP reporter mice and Cd248–/– mice, we showed that attenuation of renal fibrosis was associated with a decrease of macrophage infiltration in Cd248–/– mice. Moreover, decrease of chemokine (C–C motif) ligand 17 and Ccl22 was found in macrophages isolated from the fibrotic kidneys of Cd248–/– mice. Because galectin-3-deficient macrophages showed decreased Ccl17 and Ccl22 in fibrotic kidneys, we further demonstrated that CD248 interacted specifically with galectin-3 of macrophages who then expressed CCL17 to activate collagen production in myofibroblasts. Mice with DNA vaccination targeting CD248 showed decreased fibrosis. We thus propose that CD248 targeting should be studied in the clinical tissue fibrosis setting.
Plasmid diversity among genetically related Klebsiella pneumoniae blaKPC-2 and blaKPC-3 isolates collected in the Dutch national surveillance
Authors: Hendrickx Antoni P. A. , Landman Fabian , de Haan Angela , Borst Dyogo , Witteveen Sandra , van Santen-Verheuvel Marga G. , van der Heide Han G. J. , Schouls Leo M. ,   The Dutch CPE surveillance Study Group, Halaby T. , Steingrover R. , Cohen Stuart J. W. T. , Melles D. C. , van Dijk K. , Spijkerman I. J. B. , Notermans D. W. , Oudbier J. H. , van Ogtrop M. L. , van Dam A. , den Reijer M. , Kluytmans J. A. J. W. , van der Linden M. P. M. , Mattsson E. E. , van der Vusse M. , de Jong E. , Maijer-Reuwer A. , van Trijp M. , van Griethuysen A. J. , Ott A. , Bathoorn E. , Sinnige J. C. , Heikens E. , de Brauwer E. I. G. B. , Stals F. S. , Silvis W. , Dorigo-Zetsma J. W. , Waar K. , van Mens S. P. , Roescher N. , Voss A. , Wertheim H. , Slingerland B. C. G. C. , Frenay H. M. E. , Schulin T. , Diederen B. M. W. , Bode L. , van Rijn M. , Dinant S. , Damen M. , de Man P. , Leversteijn-van Hall M. A. , van Elzakker E. P. M. , Muller A. E. , Schneeberger P. , van Dam D. W. , Buiting A. G. M. , Vlek A. L. M. , Stam A. , Troelstra A. , Overdevest I. T. M. A. , Bosboom R. W. , Trienekens T. A. M. , Wolfhagen M. J. H. M. , Paltansing S. 
Published: October 2020

AbstractCarbapenemase-producing Klebsiella pneumoniae emerged as a nosocomial pathogen causing morbidity and mortality in patients. For infection prevention it is important to track the spread of K. pneumoniae and its plasmids between patients. Therefore, the major aim was to recapitulate the contents and diversity of the plasmids of genetically related K. pneumoniae strains harboring the beta-lactamase gene blaKPC-2 or blaKPC-3 to determine their dissemination in the Netherlands and the former Dutch Caribbean islands from 2014 to 2019. Next-generation sequencing was combined with long-read third-generation sequencing to reconstruct 22 plasmids. wgMLST revealed five genetic clusters comprised of K. pneumoniae blaKPC-2 isolates and four clusters consisted of blaKPC-3 isolates. KpnCluster-019 blaKPC-2 isolates were found both in the Netherlands and the Caribbean islands, while blaKPC-3 cluster isolates only in the Netherlands. Each K. pneumoniae blaKPC-2 or blaKPC-3 cluster was characterized by a distinct resistome and plasmidome. However, the large and medium plasmids contained a variety of antibiotic resistance genes, conjugation machinery, cation transport systems, transposons, toxin/antitoxins, insertion sequences and prophage-related elements. The small plasmids carried genes implicated in virulence. Thus, implementing long-read plasmid sequencing analysis for K. pneumoniae surveillance provided important insights in the transmission of a KpnCluster-019 blaKPC-2 strain between the Netherlands and the Caribbean.
Two ways to overcome the three social dilemmas of indirect reciprocity
Authors: Okada Isamu 
Published: October 2020

AbstractIndirect reciprocity is one of the main principles of evolving cooperation in a social dilemma situation. In reciprocity, a positive score is given to cooperative behaviour while a negative score is given to non-cooperative behaviour, and the dilemma is resolved by selectively cooperating only with those with positive scores. However, many studies have shown that non-cooperation with those who have not cooperated also downgrades one's reputation; they have called this situation the scoring dilemma. To address this dilemma, the notion of justified punishments has been considered. The notion of justified punishment allows good individuals who defect against bad co-players to keep their standing. Despite numerous studies on justified punishment, it is unknown whether this solution leads to a new type of dilemma because reputations may be downgraded when the intent of punishment is not correctly communicated. The dilemma of punishment has so far been rarely analysed, and thus, the complete solution of the mechanism for evolving cooperation using the principle of indirect reciprocity has not been found yet. Here, we identify sufficient conditions to overcome each of the three dilemmas including the dilemma of punishment to maintain stable cooperation by using the framework of evolutionary game theory. This condition includes the principle of detecting free riders, which resolves the social dilemma, the principle of justification, which resolves the scoring dilemma, and the principle of generosity, which resolves the dilemma of punishment. A norm that satisfies these principles can stably maintain social cooperation. Our insights may offer a general assessment principle that applies to a wide range of subjects, from individual actions to national decisions.
Data mining and model-predicting a global disease reservoir for low-pathogenic Avian Influenza (AI) in the wider pacific rim using big data sets
Authors: Gulyaeva Marina , Huettmann Falk , Shestopalov Alexander , Okamatsu Masatoshi , Matsuno Keita , Chu Duc-Huy , Sakoda Yoshihiro , Glushchenko Alexandra , Milton Elaina , Bortz Eric 
Published: October 2020

AbstractAvian Influenza (AI) is a complex but still poorly understood disease; specifically when it comes to reservoirs, co-infections, connectedness and wider landscape perspectives. Low pathogenic (Low-path LP) AI in chickens caused by less virulent strains of AI viruses (AIVs)—when compared with highly pathogenic AIVs (HPAIVs)—are not even well-described yet or known how they contribute to wider AI and immune system issues. Co-circulation of LPAIVs with HPAIVs suggests their interactions in their ecological aspects. Here we show for the Pacific Rim an international approach how to data mine and model-predict LP AI and its ecological niche with machine learning and open access data sets and geographic information systems (GIS) on a 5 km pixel size for best-possible inference. This is based on the best-available data on the issue (~ 40,827 records of lab-analyzed field data from Japan, Russia, Vietnam, Mongolia, Alaska and Influenza Research Database (IRD) and U.S. Department of Agriculture (USDA) database sets, as well as 19 GIS data layers). We sampled 157 hosts and 110 low-path AIVs with 32 species as drivers. The prevalence across low-path AIV subtypes is dominated by Muscovy ducks, Mallards, Whistling Swans and gulls also emphasizing industrial impacts for the human-dominated wildlife contact zone. This investigation sets a good precedent for the study of reservoirs, big data mining, predictions and subsequent outbreaks of HPAI and other pandemics.