bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of thyroid hormone signaling protects retinal pigment epithelium and photoreceptors from cell death in a mouse model of age-related macular degeneration
Authors: Ma Hongwei , Yang Fan , Ding Xi-Qin 
Published: January 2020

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Dry AMD is characterized by a progressive macular degeneration of the retinal pigment epithelium (RPE) and photoreceptors, and the RPE oxidative damage/dystrophy is at the core of the disease. Recent population/patients-based studies have shown an association of high free serum thyroid hormone (TH) levels with increased risk of AMD. This work investigated the effects of TH signaling inhibition on RPE and photoreceptor damage/cell death in an oxidative stress-induced mouse model of AMD. TH signaling inhibition was achieved by anti-thyroid drug treatment and oxidative stress was induced by sodium iodate (NaIO3) administration. Mice treated with NaIO3 showed severe RPE and photoreceptor cell death/necroptosis, destruction, oxidative damage, retinal stress, and reduced retinal function. Treatment with anti-thyroid drug protected RPE and photoreceptors from damage/cell death induced by NaIO3, reduced oxidative damage of RPE and photoreceptors, and preserved retinal function. Gene expression analysis showed that the NaIO3-induced RPE/photoreceptor damage/cell death involves multiple mechanisms, including cellular oxidative stress responses, activation of necroptosis/apoptosis signaling, and inflammatory responses. Treatment with anti-thyroid drug abolished these cellular stress/death responses. The findings of this study demonstrate a role of TH signaling in RPE and photoreceptor cell death after oxidative stress challenge, and support a role of TH signaling in the pathogenesis of AMD.
Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals
Authors: Segalés Jessica , Perdiguero Eusebio , Serrano Antonio L. , Sousa-Victor Pedro , Ortet Laura , Jardí Mercè , Budanov Andrei V. , Garcia-Prat Laura , Sandri Marco , Thomson David M. , Karin Michael , Hee Lee Jun , Muñoz-Cánoves Pura 
Published: January 2020

AbstractA unique property of skeletal muscle is its ability to adapt its mass to changes in activity. Inactivity, as in disuse or aging, causes atrophy, the loss of muscle mass and strength, leading to physical incapacity and poor quality of life. Here, through a combination of transcriptomics and transgenesis, we identify sestrins, a family of stress-inducible metabolic regulators, as protective factors against muscle wasting. Sestrin expression decreases during inactivity and its genetic deficiency exacerbates muscle wasting; conversely, sestrin overexpression suffices to prevent atrophy. This protection occurs through mTORC1 inhibition, which upregulates autophagy, and AKT activation, which in turn inhibits FoxO-regulated ubiquitin–proteasome-mediated proteolysis. This study reveals sestrin as a central integrator of anabolic and degradative pathways preventing muscle wasting. Since sestrin also protected muscles against aging-induced atrophy, our findings have implications for sarcopenia.
Distinct DNA repair pathways cause genomic instability at alternative DNA structures
Authors: McKinney Jennifer A. , Wang Guliang , Mukherjee Anirban , Christensen Laura , Subramanian Sai H. Sankara , Zhao Junhua , Vasquez Karen M. 
Published: January 2020

AbstractAlternative DNA structure-forming sequences can stimulate mutagenesis and are enriched at mutation hotspots in human cancer genomes, implicating them in disease etiology. However, the mechanisms involved are not well characterized. Here, we discover that Z-DNA is mutagenic in yeast as well as human cells, and that the nucleotide excision repair complex, Rad10-Rad1(ERCC1-XPF), and the mismatch repair complex, Msh2-Msh3, are required for Z-DNA-induced genetic instability in yeast and human cells. Both ERCC1-XPF and MSH2-MSH3 bind to Z-DNA-forming sequences, though ERCC1-XPF recruitment to Z-DNA is dependent on MSH2-MSH3. Moreover, ERCC1-XPF−dependent DNA strand-breaks occur near the Z-DNA-forming region in human cell extracts, and we model these interactions at the sub-molecular level. We propose a relationship in which these complexes recognize and process Z-DNA in eukaryotes, representing a mechanism of Z-DNA-induced genomic instability.
Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity
Authors: Kimura Shunsuke , Nakamura Yutaka , Kobayashi Nobuhide , Shiroguchi Katsuyuki , Kawakami Eiryo , Mutoh Mami , Takahashi-Iwanaga Hiromi , Yamada Takahiro , Hisamoto Meri , Nakamura Midori , Udagawa Nobuyuki , Sato Shintaro , Kaisho Tsuneyasu , Iwanaga Toshihiko , Hase Koji 
Published: January 2020

AbstractMicrofold cells (M cells) are responsible for antigen uptake to initiate immune responses in the gut-associated lymphoid tissue (GALT). Receptor activator of nuclear factor-κB ligand (RANKL) is essential for M cell differentiation. Follicle-associated epithelium (FAE) covers the GALT and is continuously exposed to RANKL from stromal cells underneath the FAE, yet only a subset of FAE cells undergoes differentiation into M cells. Here, we show that M cells express osteoprotegerin (OPG), a soluble inhibitor of RANKL, which suppresses the differentiation of adjacent FAE cells into M cells. Notably, OPG deficiency increases M cell number in the GALT and enhances commensal bacterium-specific immunoglobulin production, resulting in the amelioration of disease symptoms in mice with experimental colitis. By contrast, OPG-deficient mice are highly susceptible toSalmonellainfection. Thus, OPG-dependent self-regulation of M cell differentiation is essential for the balance between the infectious risk and the ability to perform immunosurveillance at the mucosal surface.
Direct asymmetric N-propargylation of indoles and carbazoles catalyzed by lithium SPINOL phosphate
Authors: Wang Yingcheng , Wang Sheng , Shan Wenyu , Shao Zhihui 
Published: January 2020

AbstractCatalytic asymmetric functionalization of the N–H groups of indoles and carbazoles constitutes an important but less developed class of reactions. Herein, we describe a propargylation protocol involving the use of a lithium SPINOL phosphate as the chiral catalyst and our recently developed C-alkynyl N,O-acetals as propargylating reagents. The direct asymmetric N-propargylation of indoles and carbazoles provides hitherto inaccessible N-functionalized products. Notably, the efficiency of the system allows reactions to be run at a very low catalyst loading (as low as 0.1 mol%). Mechanistic information about the titled reaction is also disclosed. This study represents an advance in the direct asymmetric functionalization of the N–H bonds of indoles and carbazoles, and additionally expands on the application of chiral alkali metal salts of chiral phosphoric acids in asymmetric catalysis.
Structural basis for the adaptation and function of chlorophyll f in photosystem I
Authors: Kato Koji , Shinoda Toshiyuki , Nagao Ryo , Akimoto Seiji , Suzuki Takehiro , Dohmae Naoshi , Chen Min , Allakhverdiev Suleyman I. , Shen Jian-Ren , Akita Fusamichi , Miyazaki Naoyuki , Tomo Tatsuya 
Published: January 2020

AbstractChlorophylls (Chl) play pivotal roles in energy capture, transfer and charge separation in photosynthesis. Among Chls functioning in oxygenic photosynthesis, Chl f is the most red-shifted type first found in a cyanobacterium Halomicronema hongdechloris. The location and function of Chl f in photosystems are not clear. Here we analyzed the high-resolution structures of photosystem I (PSI) core from H. hongdechloris grown under white or far-red light by cryo-electron microscopy. The structure showed that, far-red PSI binds 83 Chl a and 7 Chl f, and Chl f are associated at the periphery of PSI but not in the electron transfer chain. The appearance of Chl f is well correlated with the expression of PSI genes induced under far-red light. These results indicate that Chl f functions to harvest the far-red light and enhance uphill energy transfer, and changes in the gene sequences are essential for the binding of Chl f.
Climate econometric models indicate solar geoengineering would reduce inter-country income inequality
Authors: Harding Anthony R. , Ricke Katharine , Heyen Daniel , MacMartin Douglas G. , Moreno-Cruz Juan 
Published: January 2020

AbstractExploring heterogeneity in the economic impacts of solar geoengineering is a fundamental step towards understanding the risk tradeoff associated with a geoengineering option. To evaluate impacts of solar geoengineering and greenhouse gas-driven climate change on equal terms, we apply macroeconomic impact models that have been widely applied to climate change impacts assessment. Combining historical evidence with climate simulations of mean annual temperature and precipitation, we project socio-economic outcomes under high anthropogenic emissions for stylized climate scenarios in which global temperatures are stabilized or over-cooled by blocking solar radiation. We find impacts of climate changes on global GDP-per-capita by the end of the century are temperature-driven, highly dispersed, and model dependent. Across all model specifications, however, income inequality between countries is lower with solar geoengineering. Consistent reduction in inter-country inequality can inform discussions of the distribution of impacts of solar geoengineering, a topic of concern in geoengineering ethics and governance debates.
Antimicrobial resistant enteric bacteria are widely distributed amongst people, animals and the environment in Tanzania
Authors: Subbiah Murugan , Caudell Mark A. , Mair Colette , Davis Margaret A. , Matthews Louise , Quinlan Robert J. , Quinlan Marsha B. , Lyimo Beatus , Buza Joram , Keyyu Julius , Call Douglas R. 
Published: January 2020

AbstractAntibiotic use and bacterial transmission are responsible for the emergence, spread and persistence of antimicrobial-resistant (AR) bacteria, but their relative contribution likely differs across varying socio-economic, cultural, and ecological contexts. To better understand this interaction in a multi-cultural and resource-limited context, we examine the distribution of antimicrobial-resistant enteric bacteria from three ethnic groups in Tanzania. Household-level data (n = 425) was collected and bacteria isolated from people, livestock, dogs, wildlife and water sources (n = 62,376 isolates). The relative prevalence of different resistance phenotypes is similar across all sources. Multi-locus tandem repeat analysis (n = 719) and whole-genome sequencing (n = 816) of Escherichia coli demonstrate no evidence for host-population subdivision. Multivariate models show no evidence that veterinary antibiotic use increased the odds of detecting AR bacteria, whereas there is a strong association with livelihood factors related to bacterial transmission, demonstrating that to be effective, interventions need to accommodate different cultural practices and resource limitations.
The role of artificial intelligence in achieving the Sustainable Development Goals
Authors: Vinuesa Ricardo , Azizpour Hossein , Leite Iolanda , Balaam Madeline , Dignum Virginia , Domisch Sami , Felländer Anna , Langhans Simone Daniela , Tegmark Max , Fuso Nerini Francesco 
Published: January 2020

AbstractThe emergence of artificial intelligence (AI) and its progressively wider impact on many sectors requires an assessment of its effect on the achievement of the Sustainable Development Goals. Using a consensus-based expert elicitation process, we find that AI can enable the accomplishment of 134 targets across all the goals, but it may also inhibit 59 targets. However, current research foci overlook important aspects. The fast development of AI needs to be supported by the necessary regulatory insight and oversight for AI-based technologies to enable sustainable development. Failure to do so could result in gaps in transparency, safety, and ethical standards.
SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis
Authors: Zhou Jiyu , Cui Shuang , He Qingxian , Guo Yitong , Pan Xiaojie , Zhang Pengfei , Huang Ningning , Ge Chaoliang , Wang Guangji , Gonzalez Frank J. , Wang Hong , Hao Haiping 
Published: January 2020

AbstractFarnesoid X receptor (FXR) is a promising target for nonalcoholic steatohepatitis (NASH) and fibrosis. Although various FXR agonists have shown anti-fibrotic effects in diverse preclinical animal models, the response rate and efficacies in clinical trials were not optimum. Here we report that prophylactic but not therapeutic administration of obeticholic acid (OCA) prevents hepatic stellate cell (HSC) activation and fibrogenesis. Activated HSCs show limited response to OCA and other FXR agonists due to enhanced FXR SUMOylation. SUMOylation inhibitors rescue FXR signaling and thereby increasing the efficacy of OCA against HSC activation and fibrosis. FXR upregulates Perilipin-1, a direct target gene of FXR, to stabilize lipid droplets and thereby prevent HSC activation. Therapeutic coadministration of OCA and SUMOylation inhibitors drastically impedes liver fibrosis induced by CCl4, bile duct ligation, and more importantly NASH. In conclusion, we propose a promising therapeutic approach by combining SUMOylation inhibitors and FXR agonists for liver fibrosis.
Assembly and substrate recognition of curli biogenesis system
Authors: Yan Zhaofeng , Yin Meng , Chen Jianan , Li Xueming 
Published: January 2020

AbstractA major component of bacterial biofilms is curli amyloid fibrils secreted by the curli biogenesis system. Understanding the curli biogenesis mechanism is critical for developing therapeutic agents for biofilm-related infections. Here we report a systematic study of the curli biogenesis system, highlighted by structural, biochemical and functional analysis of the secretion channel complexes (CsgF-CsgG) with and without the curli substrate. The dual-pore architecture of the CsgF-CsgG complex was observed and used to develop an approach to inhibit the curli secretion by physically reducing the size of the CsgF pore. We further elucidated the assembly of the CsgFG complex with curli components (CsgA and CsgB) and curli-cell association through CsgF. Importantly, the recognition of the CsgA substrate by CsgG was uncovered. Nine crevices outside of the CsgG channel provide specific and highly-conserved recognition sites for CsgA N-terminus. Together with analysis of CsgE, our study provides comprehensive insights into curli biogenesis.
PIC, a paediatric-specific intensive care database
Authors: Zeng Xian , Yu Gang , Lu Yang , Tan Linhua , Wu Xiujing , Shi Shanshan , Duan Huilong , Shu Qiang , Li Haomin 
Published: January 2020

AbstractPIC (Paediatric Intensive Care) is a large paediatric-specific, single-centre, bilingual database comprising information relating to children admitted to critical care units at a large children’s hospital in China. The database is deidentified and includes vital sign measurements, medications, laboratory measurements, fluid balance, diagnostic codes, length of hospital stays, survival data, and more. The data are publicly available after registration, which includes completion of a training course on research with human subjects and signing of a data use agreement mandating responsible handling of the data and adherence to the principle of collaborative research. Although the PIC can be considered an extension of the widely used MIMIC (Medical Information Mart for Intensive Care) database in the field of paediatric critical care, it has many unique characteristics and can support database-based academic and industrial applications such as machine learning algorithms, clinical decision support tools, quality improvement initiatives, and international data sharing.
A database for global soil health assessment
Authors: Jian Jinshi , Du Xuan , Stewart Ryan D. 
Published: January 2020

AbstractField studies have been performed for decades to analyze effects of different management practices on agricultural soils and crop yields, but these data have never been combined together in a way that can inform current and future cropland management. Here, we collected, extracted, and integrated a database of soil health measurements conducted in the field from sites across the globe. The database, named SoilHealthDB, currently focuses on four main conservation management methods: cover crops, no-tillage, agro-forestry systems, and organic farming. These studies represent 354 geographic sites (i.e., locations with unique latitudes and longitudes) in 42 countries around the world. The SoilHealthDB includes 42 soil health indicators and 46 background indicators that describe factors such as climate, elevation, and soil type. A primary goal of this effort is to enable the research community to perform comprehensive analyses, e.g., meta-analyses, of soil health changes related to cropland conservation management. The database also provides a common framework for sharing soil health, and the scientific research community is encouraged to contribute their own measurements.
Rapid Response High Temperature Oxygen Sensor Based on Titanium Doped Gallium Oxide
Authors: Manandhar Sandeep , Battu Anil K. , Devaraj Arun , Shutthanandan V. , Thevuthasan S. , Ramana C. V. 
Published: January 2020

AbstractReal-time monitoring of combustion products and composition is critical to emission reduction and efficient energy production. The fuel efficiency in power plants and automobile engines can be dramatically improved by monitoring and controlling the combustion environment. However, the development of novel materials for survivability of oxygen sensors at extreme environments and demonstrated rapid response in chemical sensing is a major hindrance for further development in the field. Gallium oxide (Ga2O3), one among the wide band gap oxides, exhibit promising oxygen sensing properties in terms of reproducibility and long term stability. However, the oxygen sensors based on β-Ga2O3 and other existing materials lack in response time and stability at elevated temperatures. In this context, we demonstrate an approach to design materials based on Ti-doped Ga2O3, which exhibits a rapid response and excellent stability for oxygen sensing at elevated temperatures. We demonstrate that the nanocrystalline β-Ga2O3 films with 5% Ti significantly improves the response time (~20 times) while retaining the stability and repeatability in addition to enhancement in the sensitivity to oxygen. These extreme environment oxygen sensors with a rapid response time and sensitivity represent key advancement for integration into combustion systems for efficient energy conversion and emission reduction.
Revealing the mechanism of extraordinary hardness without compensating the toughness in a low alloyed high carbon steel
Authors: Hossain Rumana , Pahlevani Farshid , Sahajwalla Veena 
Published: January 2020

AbstractThere is a continuous quest for discovery of a steel grade which has better properties and lower production cost. To design steel with superior properties for industrial application, it is essential to understand the effect of microstructure and engineer it to fit the purpose. In this study, a counter intuitive strategy has used to reveal the mechanism of high carbon steel with ultrahard structure. High compact force has been used to produce a structure which has ceramic-like hardness without compensating the toughness significantly. The behaviour of high carbon low-alloy steel as the starting material under different stages of deformation has been studied to differentiate various deformation paths and microstructural transformation processes. Microscopy investigation by secondary electron microscopy, high-resolution electron backscattered diffraction (HR-EBSD) analysis and Transmission electron microscopy (TEM) showed that the key point to achieve ~75% increased hardness in this steel is through generation of nano-structured martensite of less than 50 nm grains size which can be formed due to high impact force. In this paper, we reveal a nano grained steel structure with excellent mechanical properties resulting from phase transformation, uniform dislocation distribution, grain refinement and recrystallization.
Blind information reconciliation with variable step sizes for quantum key distribution
Authors: Liu Zhihong , Wu Zhihao , Huang Anqi 
Published: January 2020

AbstractQuantum key distribution (QKD) generates symmetric keys between two authenticated parties with the guarantee of information-theoretically security. A vital step in QKD to obtain fully-matched key between two parties is information reconciliation. The blind reconciliation protocol provides a useful tool that corrects the mismatch in a wide range of qubit error rate (QBER) but without a prior error estimation. However, there is a contradiction between the reconciliation efficiency and the processing time in this protocol. In this work, we propose a blind reconciliation protocol with variable step sizes to relieve this contradiction. The analysis and simulation results show that the improved protocol inherits all the advantages of the original blind reconciliation protocol and can obtain better reconciliation efficiency with less operation time. The improved blind reconciliation protocol enhances the final secret key rate and accelerates the processing speed of a QKD system.
Newly emerged enterovirus-A71 C4 sublineage may be more virulent than B5 in the 2015–2016 hand-foot-and-mouth disease outbreak in northern Vietnam
Authors: Chu Son T. , Kobayashi Kyousuke , Bi Xiuqiong , Ishizaki Azumi , Tran Tu T. , Phung Thuy T. B. , Pham Chung T. T. , Nguyen Lam V. , Ta Tuan A. , Khu Dung T. K. , Agoh Masanobu , Pham An N. , Koike Satoshi , Ichimura Hiroshi 
Published: January 2020

AbstractEnterovirus-A71 (EV-A71) is a common cause of hand-foot-and-mouth disease (HFMD) and, rarely, causes severe neurological disease. This study aimed to elucidate the epidemiological and genetic characteristics and virulence of EV-A71 strains isolated from children diagnosed with HFMD. Rectal and throat swabs were collected from 488 children with HFMD in Hanoi, Vietnam, in 2015–2016. From 391 EV-positive patients, 15 EVs, including coxsackievirus A6 (CV-A6; 47.1%) and EV-A71 (32.5%, n = 127), were identified. Of the 127 EV-A71 strains, 117 (92.1%) were the B5 subgenotype and 10 (7.9%) were the C4 subgenotype. A whole-genome analysis of EV-A71 strains showed that seven of the eight C4a strains isolated in 2016 formed a new lineage, including two possible recombinants between EV-A71 C4 and CV-A8. The proportion of inpatients among C4-infected children was higher than among B5-infected children (80.0% vs. 27.4%; P = 0.002). The virulence of EV-A71 strains was examined in human scavenger receptor class B2 (hSCARB2)-transgenic mice, and EV-A71 C4 strains exhibited higher mortality than B5 strains (80.0% vs. 30.0%, P = 0.0001). Thus, a new EV-A71 C4a-lineage, including two possible recombinants between EV-A71 C4 and CV-A8, appeared in 2016 in Vietnam. The EV-A71 C4 subgenotype may be more virulent than the B5 subgenotype.