bluuebunny/crossref_metadata_2025_split huggingface dataset:
M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity
Authors: Zhao Hong-Yan , Zhang Yuan-Yuan , Xing Tong , Tang Shu-Qian , Wen Qi , Lyu Zhong-Shi , Lv Meng , Wang Yu , Xu Lan-Ping , Zhang Xiao-Hui , Kong Yuan , Huang Xiao-Jun 
Published: June 2021

AbstractDysfunctional megakaryopoiesis hampers platelet production, which is closely associated with thrombocytopenia (PT). Macrophages (MФs) are crucial cellular components in the bone marrow (BM) microenvironment. However, the specific effects of M1 MФs or M2 MФs on regulating megakaryocytes (MKs) are largely unknown. In the current study, aberrant BM-M1/M2 MФ polarization, characterized by increased M1 MФs and decreased M2 MФs and accompanied by impaired megakaryopoiesis-supporting abilities, was found in patients with PT post-allotransplant. RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MФs of PT patients. Moreover, in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MФs from PT patients. Furthermore, we found M1 MФs suppress, whereas M2 MФs support MK maturation and platelet formation in humans. Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MФs, as indicated by decreased MK count, colony-forming unit number, high-ploidy distribution, and platelet count. Importantly, genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MФs both in vitro and in a MФ-specific PI3K-knockdown murine model, indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 MФs. Furthermore, our preliminary data indicated that TGF-β released by M2 MФs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs. Taken together, our data reveal that M1 and M2 MФs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner, which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.
Evidence for increased thermogenesis in female C57BL/6J mice housed aboard the international space station
Authors: Wong Carmen P. , Iwaniec Urszula T. , Turner Russell T. 
Published: June 2021

AbstractSixteen-week-old female C57BL/6J mice were sacrificed aboard the International Space Station after 37 days of flight (RR-1 mission) and frozen carcasses returned to Earth. RNA was isolated from interscapular brown adipose tissue (BAT) and gonadal white adipose tissue (WAT). Spaceflight resulted in differential expression of genes in BAT consistent with increased non-shivering thermogenesis and differential expression of genes in WAT consistent with increased glucose uptake and metabolism, adipogenesis, and β-oxidation.
Nobel Turing Challenge: creating the engine for scientific discovery
Authors: Kitano Hiroaki 
Published: June 2021

AbstractScientific discovery has long been one of the central driving forces in our civilization. It uncovered the principles of the world we live in, and enabled us to invent new technologies reshaping our society, cure diseases, explore unknown new frontiers, and hopefully lead us to build a sustainable society. Accelerating the speed of scientific discovery is therefore one of the most important endeavors. This requires an in-depth understanding of not only the subject areas but also the nature of scientific discoveries themselves. In other words, the “science of science” needs to be established, and has to be implemented using artificial intelligence (AI) systems to be practically executable. At the same time, what may be implemented by “AI Scientists” may not resemble the scientific process conducted by human scientist. It may be an alternative form of science that will break the limitation of current scientific practice largely hampered by human cognitive limitation and sociological constraints. It could give rise to a human-AI hybrid form of science that shall bring systems biology and other sciences into the next stage. The Nobel Turing Challenge aims to develop a highly autonomous AI system that can perform top-level science, indistinguishable from the quality of that performed by the best human scientists, where some of the discoveries may be worthy of Nobel Prize level recognition and beyond.
Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
Authors: Mallory Katherine L. , Taylor Justin A. , Zou Xiaoyan , Waghela Ishita N. , Schneider Cosette G. , Sibilo Michael Q. , Punde Neeraja M. , Perazzo Leah C. , Savransky Tatyana , Sedegah Martha , Dutta Sheetij , Janse Chris J. , Pardi Norbert , Lin Paulo J. C. , Tam Ying K. , Weissman Drew , Angov Evelina 
Published: June 2021

AbstractHuman malaria affects the vast majority of the world’s population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research. As the immunodominant coat protein of the invasive stage of the malaria parasite, circumsporozoite protein (PfCSP) was selected as the antigen of choice to assess the immunogenic and protective potential of an mRNA malaria vaccine. In mammalian cell transfection experiments, PfCSP mRNA was well expressed and cell associated. In the transition to an in vivo murine model, lipid nanoparticle (LNP) encapsulation was applied to protect and deliver the mRNA to the cell translation machinery and supply adjuvant activity. The immunogenic effect of an array of factors was explored, such as formulation, dose, number, and interval of immunizations. PfCSP mRNA-LNP achieved sterile protection against infection with two P. berghei PfCSP transgenic parasite strains, with mRNA dose and vaccination interval having a greater effect on outcome. This investigation serves as the assessment of pre-erythrocytic malaria, PfCSP mRNA vaccine candidate resulting in sterile protection, with numerous factors affecting protective efficacy, making it a compelling candidate for further investigation.
Diagnosis and management of migraine in ten steps
Authors: Eigenbrodt Anna K. , Ashina Håkan , Khan Sabrina , Diener Hans-Christoph , Mitsikostas Dimos D. , Sinclair Alexandra J. , Pozo-Rosich Patricia , Martelletti Paolo , Ducros Anne , Lantéri-Minet Michel , Braschinsky Mark , del Rio Margarita Sanchez , Daniel Oved , Özge Aynur , Mammadbayli Ayten , Arons Mihails , Skorobogatykh Kirill , Romanenko Vladimir , Terwindt Gisela M. , Paemeleire Koen , Sacco Simona , Reuter Uwe , Lampl Christian , Schytz Henrik W. , Katsarava Zaza , Steiner Timothy J. , Ashina Messoud 
Published: June 2021

AbstractMigraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.
Scenario simulation of land use and land cover change in mining area
Authors: Chang Xiaoyan , Zhang Feng , Cong Kanglin , Liu Xiaojun 
Published: June 2021

AbstractIn this study, we selected 11 townships with severe ground subsidence located in Weishan County as the study area. Based on the interpretation data of Landsat images, the Binary logistic regression model was used to explore the relationship between land use and land cover (LULC) change and the related 7 driving factors at a resolution of 60 m. Using the CLUE-S model, combined with Markov model, the simulation of LULC under three scenarios—namely, natural development scenario, ecological protection scenario and farmland protection scenario—were explored. Firstly, using LULC map in 2005 as input data, we predicted the land use spatial distribution pattern in 2016. By comparing the actual LULC map in 2016 with the simulated map in 2016, the prediction accuracy was evaluated based on the Kappa index. Then, after validation, the spatial distribution pattern of LULC in 2025 under the three scenarios was simulated. The results showed the following: (1) The driving factors had satisfactory explanatory power for LULC changes. The Kappa index was 0.82, which indicated good simulation accuracy of the CLUE-S model. (2) Under the three scenarios, the area of other agricultural land and water body showed an increasing trend; while the area of farmland, urban and rural construction land, subsided land with water accumulation, and tidal wetland showed a decreasing trend, and the area of urban and rural construction land and tidal wetland decreased the fastest. (3) Under the ecological protection scenario, the farmland decreased faster than the other two scenarios, and most of the farmland was converted to ecological land such as garden land and water body. Under the farmland protection scenario, the area of tidal wetland decreased the fastest, followed by urban and rural construction land. We anticipate that our study results will provide useful information for decision-makers and planners to take appropriate land management measures in the mining area.
Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice
Authors: Mizoguchi Akira , Banno Ryoichi , Sun Runan , Yaginuma Hiroshi , Taki Keigo , Kobayashi Tomoko , Sugiyama Mariko , Tsunekawa Taku , Onoue Takeshi , Takagi Hiroshi , Hagiwara Daisuke , Ito Yoshihiro , Iwama Shintaro , Suga Hidetaka , Nagai Taku , Yamada Kiyofumi , Arima Hiroshi 
Published: June 2021

AbstractThe reward system, which consists of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens and caudate-putamen in the striatum, has an important role in the pathogenesis of not only drug addiction but also diet-induced obesity. In the present study, we examined whether signaling through glucocorticoid receptors (GRs) in the reward system affects the rewarding value of a high-fat diet (HFD). To do so, we generated mice that lack functional GRs specifically in dopaminergic neurons (D-KO mice) or corticostriatal neurons (CS-KO mice), subjected the mice to caloric restriction stress conditions, and evaluated the rewarding value of a HFD by conditioned place preference (CPP) test. Caloric restriction induced increases in serum corticosterone to similar levels in all genotypes. While CS-KO as well as WT mice exhibited a significant preference for HFD in the CPP test, D-KO mice exhibited no such preference. There were no differences between WT and D-KO mice in consumption of HFD after fasting or cognitive function evaluated by a novel object recognition test. These data suggest that glucocorticoid signaling in the VTA increases the rewarding value of a HFD under restricted caloric stress.
Anxiety disturbs the blood plasma metabolome in acute coronary syndrome patients
Authors: Wei HongYan , Gu JunYuan , Jiang XueYao , Deng Nan , Wu Jing , Zou LianHong , Zhu YiMin , Tan BoYu 
Published: June 2021

AbstractCoronary heart disease (CHD) is the result of a complex metabolic disorder caused by various environmental and genetic factors, and often has anxiety as a comorbidity. Rupture of atherosclerotic plaque in CHD patients can lead to acute coronary syndrome (ACS). Anxiety is a known independent risk factor for the adverse cardiovascular events and mortality in ACS, but it remains unclear how stress-induced anxiety behavior impacts their blood plasma metabolome and contributes to worsening of CHD. The present study aimed to determine the effect of anxiety on the plasma metabolome in ACS patients. After receiving ethical approval 26 ACS patients comorbid anxiety were recruited and matched 26 ACS patients. Blood plasma samples were collected from the patients and stored at − 80 °C until metabolome profiling. Metabolome analysis was performed by liquid chromatography mass spectrometry (LC–MS), and the data were subjected to multivariate analysis. Disturbance of 39 plasma metabolites was noted in the ACS with comorbid anxiety group compared to the ACS group. These disturbed metabolites were mainly involved in tryptophan metabolism, pyrimidine metabolism, glycerophospholipid metabolism, pentose phosphate pathway, and pentose and glucuronate interconversions. The most significantly affected pathway was tryptophan metabolism including the down-regulation of tryptophan and serotonin. Glycerophospholipids metabolism, pentose and glucuronate interconversions, and pentose phosphate pathway were also greatly affected. These results suggest that anxiety can disturb three translation of material in ACS patients. Besides the above metabolism pathways pyrimidine metabolism was significantly disturbed. Based on the present findings the plasma metabolites monitoring can be recommended and may be conducive to early biomarkers detection for personalized treatment anxiety in CHD patients in future.
Kitchen elbow sign predicts surgical outcomes in adults with spinal deformity: a retrospective cohort study
Authors: Murata Shizumasa , Hashizume Hiroshi , Nagata Keiji , Yukawa Yasutsugu , Minamide Akihito , Iwasaki Hiroshi , Tsutsui Shunji , Takami Masanari , Taiji Ryo , Kozaki Takuhei , Yamada Hiroshi 
Published: June 2021

AbstractKitchen elbow sign (KE-Sign) is a skin abnormality on the extensor side of the elbow and forearm that is often observed in patients with adult spinal deformity (ASD). The significance of KE-Sign in surgical cases was investigated. Overall, 114 patients with ASD treated with long spinal fusion were reviewed and divided into KE-Sign positive and negative groups. The preoperative and 1-year follow-up evaluations included radiographic parameters [C7 sagittal vertical axis (SVA), pelvic incidence (PI) and lumbar lordosis (LL)], the Oswestry Disability Index (ODI), visual analogue scales (VASs) for low back pain, leg pain, and satisfaction, and Short Form 36 questionnaire (SF-36). Multi-regression analysis was performed to identify patient satisfaction predictors and improvement in the ODI as dependent variables and preoperative background factors as independent variables. Preoperative characteristics showed no significant difference between both groups. Improvement in the ODI and VAS for satisfaction were significantly superior in the KE-Sign positive group. In multiple regression analysis, KE-Sign and preoperative ODI were significantly associated with improvement in the ODI; age, KE-Sign, preoperative low back pain VAS, and leg pain VAS were significantly associated with satisfaction. KE-Sign can be a predictor of better surgical outcomes in ASD patients.
Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages
Authors: Zeeshan Mohammad , Pandey Rajan , Subudhi Amit Kumar , Ferguson David J. P. , Kaur Gursimran , Rashpa Ravish , Nugmanova Raushan , Brady Declan , Bottrill Andrew R. , Vaughan Sue , Brochet Mathieu , Bollen Mathieu , Pain Arnab , Holder Anthony A. , Guttery David S. , Tewari Rita 
Published: June 2021

AbstractPP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the malaria parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes. Using real-time live-cell and ultrastructural imaging, conditional gene knockdown, RNA-seq and proteomic approaches, we show that Plasmodium PP1 is implicated in both mitotic exit and, potentially, establishing cell polarity during zygote development in the mosquito midgut, suggesting that small molecule inhibitors of PP1 should be explored for blocking parasite transmission.
Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors
Authors: Gao Yuen , Duque-Wilckens Natalia , Aljazi Mohammad B. , Wu Yan , Moeser Adam J. , Mias George I. , Robison Alfred J. , He Jin 
Published: June 2021

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.
Predicting the probability of death using proteomics
Authors: Eiriksdottir Thjodbjorg , Ardal Steinthor , Jonsson Benedikt A. , Lund Sigrun H. , Ivarsdottir Erna V. , Norland Kristjan , Ferkingstad Egil , Stefansson Hreinn , Jonsdottir Ingileif , Holm Hilma , Rafnar Thorunn , Saemundsdottir Jona , Norddahl Gudmundur L. , Thorgeirsson Gudmundur , Gudbjartsson Daniel F. , Sulem Patrick , Thorsteinsdottir Unnur , Stefansson Kari , Ulfarsson Magnus O. 
Published: June 2021

AbstractPredicting all-cause mortality risk is challenging and requires extensive medical data. Recently, large-scale proteomics datasets have proven useful for predicting health-related outcomes. Here, we use measurements of levels of 4,684 plasma proteins in 22,913 Icelanders to develop all-cause mortality predictors both for short- and long-term risk. The participants were 18-101 years old with a mean follow up of 13.7 (sd. 4.7) years. During the study period, 7,061 participants died. Our proposed predictor outperformed, in survival prediction, a predictor based on conventional mortality risk factors. We could identify the 5% at highest risk in a group of 60-80 years old, where 88% died within ten years and 5% at the lowest risk where only 1% died. Furthermore, the predicted risk of death correlates with measures of frailty in an independent dataset. Our results show that the plasma proteome can be used to assess general health and estimate the risk of death.
Lifetime stability of social traits in bottlenose dolphins
Authors: Evans Taylor , Krzyszczyk Ewa , Frère Céline , Mann Janet 
Published: June 2021

AbstractBehavioral phenotypic traits or “animal personalities” drive critical evolutionary processes such as fitness, disease and information spread. Yet the stability of behavioral traits, essential by definition, has rarely been measured over developmentally significant periods of time, limiting our understanding of how behavioral stability interacts with ontogeny. Based on 32 years of social behavioral data for 179 wild bottlenose dolphins, we show that social traits (associate number, time alone and in large groups) are stable from infancy to late adulthood. Multivariate analysis revealed strong relationships between these stable metrics within individuals, suggesting a complex behavioral syndrome comparable to human extraversion. Maternal effects (particularly vertical social learning) and sex-specific reproductive strategies are likely proximate and ultimate drivers for these patterns. We provide rare empirical evidence to demonstrate the persistence of social behavioral traits over decades in a non-human animal.
Origin and control of ionic hydration patterns in nanopores
Authors: Barabash Miraslau L. , Gibby William A. T. , Guardiani Carlo , Smolyanitsky Alex , Luchinsky Dmitry G. , McClintock Peter V. E. 
Published: June 2021

AbstractIn order to permeate a nanopore, an ion must overcome a dehydration energy barrier caused by the redistribution of surrounding water molecules. The redistribution is inhomogeneous, anisotropic and strongly position-dependent, resulting in complex patterns that are routinely observed in molecular dynamics simulations. Here, we study the physical origin of these patterns and of how they can be predicted and controlled. We introduce an analytic model able to predict the patterns in a graphene nanopore in terms of experimentally accessible radial distribution functions, giving results that agree well with molecular dynamics simulations. The patterns are attributable to a complex interplay of ionic hydration shells with water layers adjacent to the graphene membrane and with the hydration cloud of the nanopore rim atoms, and we discuss ways of controlling them. Our findings pave the way to designing required transport properties into nanoionic devices by optimising the structure of the hydration patterns.
The moment of initial crystallization captured on functionalized nanoparticles
Authors: Machida Hironobu , Sugahara Takeshi , Hirasawa Izumi 
Published: June 2021

AbstractEven if a liquid is cooled below its melting point, the liquid state can be maintained under certain conditions. This state is called supercooling. Spraying fine particles of dry ice or silver iodide induces a phase change from supercooled droplets to ice grains. However, the mechanism by which crystallization seeds diminish supercooling is not well understood. Here, we captured the moment when a cluster, which is the smallest structural unit of a crystal, envelops a silver nanoparticle. As a result of observing the structure of a supercooled aqueous solution of a clathrate hydrate, we found that silver nanoparticles accelerate the formation of clusters, whereas the noble metals palladium, gold and iridium likewise form nanoparticles but do not promote crystallization. Our discoveries elucidate the mechanism of heterogeneous nucleation during a phase change in clathrate hydrates. We anticipate our discovery to be the starting point for the control of supercooling, a technique that can be applied to enhance the production efficiency and quality of manufactured products.
Injectable silanized hyaluronic acid hydrogel/biphasic calcium phosphate granule composites with improved handling and biodegradability promote bone regeneration in rabbits
Authors: Flegeau Killian , Gauthier Olivier , Rethore Gildas , Autrusseau Florent , Schaefer Aurélie , Lesoeur Julie , Veziers Joëlle , Brésin Anthony , Gautier Hélène , Weiss Pierre 
Published: June 2021

In situ forming Si-HA/BCP are potent injectable bone substitutes to regenerate bone defects.