bluuebunny/crossref_metadata_2025_split huggingface dataset:
The political motivations for the reform of urban policy during the rapid economic growth period in Japan: a closer look
Authors: Hasegawa Junichi 
Published: December 2019

AbstractUrban policy in Japan gained greater significance in the late 1960s. In 1968, a new City Planning Law was enacted, and urban policy was a prominent issue in that year's House of Councillors election. Scholars have regarded the ruling conservative party's fear of a threat to its hegemony as the primary force driving this increased attention to urban policy. This article examines the political factors surrounding the reforms enacted, concluding that politicians actually underestimated the degree of public interest in urban policy and made largely empty political gestures to appease urban dwellers while responding more readily to agricultural interests.
The Representation of Föhn Events to the East of the Antarctic Peninsula in Simulations by the Antarctic Mesoscale Prediction System
Authors: Kirchgaessner Amélie , King John , Gadian Alan 
Published: December 2019

AbstractFöhn winds are warm, strong, downslope winds on the leeside of mountains, which can last from several hours to a few days. The years 1995 and 2002 saw the dramatic breakup of huge parts of the Larsen Ice Shelf (LIS) on the east of the Antarctic Peninsula. It is widely accepted that hydrofracturing, the widening of crevasses due to the excess hydrostatic pressure exerted by meltwater which accumulates inside them, is the mechanism behind the breakup of the Larsen A and Larsen B ice shelves. On the LIS, in the lee of the mountain range that runs along the spine of the Antarctic Peninsula, Föhn winds are thought to provide the atmospheric conditions for significant warming over the ice shelf, leading to the initial firn densification, and subsequently providing the melt water for hydrofracturing. Measurements provide evidence that in some cases Föhn events reach an Automatic Weather Station on the LIS at over 100 km distance. In this paper, we examine the representation of Föhn events during 2011 as they were observed in measurements by an Automatic Weather Station and in simulations with the Weather Research and Forecasting Model as run for the Antarctic Mesoscale Prediction System (AMPS). We find that, while the model generally simulates meteorological parameters very well and shows good skill in capturing the occurrence, frequency, and duration of Föhn events, it underestimates the temperature increase and humidity decrease during the Föhn significantly and may thus underestimate the contribution of Föhn to driving surface melt on LIS.
A Global Survey of Apparent Aerosol‐Cloud Interaction Signals
Authors: Oreopoulos Lazaros , Cho Nayeong , Lee Dongmin 
Published: December 2019

AbstractWe update and expand analysis of the apparent responses to aerosol variations of the planet's cloud regimes seen by the Moderate Resolution Imaging Spectroradiometer (MODIS). We distinguish between morning aerosol loadings and afternoon clouds and consider local scales explicitly. Aerosol loading is represented by gridded aerosol optical depth (AOD) from either MODIS or a reanalysis data set, while cloud information comes exclusively from MODIS. The afternoon cloud affected quantities (CAQs) examined in conjunction with morning AOD include precipitation and cloud radiative effect, in addition to cloud properties. One analysis thrust focuses on calculating global means distinguished by morning cloud regime, of afternoon CAQs, for distinct percentiles of grid cell seasonal morning AOD distributions. When the dependence of these global means on AOD is examined, we find persistent increases in cloud radiative fluxes with AOD as predicted by classic aerosol‐cloud interaction paradigms, and also deviations from expected cloud responses, especially for precipitation. The other analysis thrust involves calculations at 1° scales of logarithmic CAQ sensitivities to AOD perturbations, approximated by linear regression slopes for distinct morning cloud regime groups. While the calculations are fundamentally local, we concentrate on the prevailing sensitivity signs in statistics of the slopes at global scales. Results from this second analysis approach indicate CAQ directions of change with AOD that are largely consistent with the first approach. When using a rather simple methodology where meteorological variables are treated as if they were CAQs, no conclusive results on the potential influence of meteorology on our findings are inferred.
Model‐Based Properties of the Dayside Open/Closed Boundary: Is There a UT‐Dependent Variation?
Authors: Smith David A. , Sojka Jan J. 
Published: December 2019

AbstractThe open‐closed boundary (OCB) defines a region of significant transformation in Earth's protective magnetic shield. Principle among these changes is the transition of magnetic field lines from having two foot points, one in each hemisphere, to one foot point at Earth, the other mapping to the solar wind. Charged particles in the solar wind are able to follow these open field lines into Earth's upper atmosphere. The OCB also defines the polar cap boundary. Being able to identify and track the OCB allows study of several components of the geomagnetic system. Among them are the electrodynamics of the geomagnetic field and the reconnection balance between the dayside and nightside of the geomagnetic field. Furthermore, the OCB can provide insights into the precipitation of energetic protons into the ionosphere. Using the Tsyganenko model of the geomagnetic field (T96), we demonstrate a diurnal fluctuation which we call the Universal Time (UT) effect of the OCB. This UT effect is independent of all other inputs. We anticipate this UT effect to have important consequences in modeling the OCB and other polar cap‐associated structures, especially polar cap absorption events that adversely affect high‐frequency radio wave propagation in polar regions.
Yes-associated protein regulates podocyte cell cycle re-entry and dedifferentiation in adriamycin-induced nephropathy
Authors: Xie Kewei , Xu Chenqi , Zhang Minfang , Wang Minzhou , Min Lulin , Qian Cheng , Wang Qin , Ni Zhaohui , Mou Shan , Dai Huili , Pang Huihua , Gu Leyi 
Published: December 2019

AbstractPodocytes are terminally differentiated cells with little proliferative capacity. The high expression levels of cell cycle inhibitory proteins, including p21, p27, and p57, play an important role in maintaining the low level of proliferation of mature podocytes. In the present study, we aimed to explore the role of yes-associated protein (YAP) signalling in adriamycin-induced podocyte re-entry into the cell cycle and dedifferentiation. Proliferating cell nuclear antigen (PCNA)-, cyclin-dependent kinase 4 (CDK4)-, and Cyclin D1-positive podocytes were found in mice with adriamycin-induced nephropathy. In vitro, adriamycin administration increased the percentage of cells in S phase and the upregulation of mesenchymal-related marker proteins. CDK4 and cyclin D1 were significantly up-regulated after incubation with adriamycin. Overexpression of YAP in podocytes promoted their entry into the cell cycle; up-regulated cyclin D1, desmin, and snail2 expression and down-regulated Wilms’ tumour 1 (WT1) and nephrin production. Recombinant murine FGF-basic induced podocytes to re-enter the cell cycle, inhibited WT1 and nephrin, and increased desmin and snail2 expression. Pretreating podocytes with verteporfin, an inhibitor of YAP/ TEA domain transcription factor (TEAD), decreased the adriamycin-induced overexpression of cyclin D1 and reduced the ratio of S-phase podocytes. This result was further verified by knocking down YAP expression using RNA interference. In conclusion, adriamycin induced podocytes to re-enter the cell cycle via upregulation of CDK4 and cyclin D1 expression, which was at least partly mediated by YAP signalling. Re-entry into the cell cycle induced the over-expression of mesenchymal markers in podocytes.
Extensive protein S-nitrosylation associated with human pancreatic ductal adenocarcinoma pathogenesis
Authors: Tan Chaochao , Li Yunfeng , Huang Xiahe , Wei Meijin , Huang Ying , Tang Zhouqin , Huang He , Zhou Wen , Wang Yingchun , Hu Jiliang 
Published: December 2019

AbstractNO (nitric oxide)-mediated protein S-nitrosylation has been established as one major signaling mechanism underlying cancer initiation and development, but its roles in PDAC (pancreatic ductal adenocarcinoma) pathogenesis still remain largely unexplored. In this study, we identified 585 unique S-nitrosylation sites among 434 proteins in PDAC patients and PANC-1 cell line by a site-specific proteomics. Larger number of S-nitrosylated proteins were identified in PDAC tissues and PANC-1 cells than adjacent non-cancerous tissues. These S-nitrosylated proteins are significantly enriched in a multitude of biological processes associated with tumorigenesis, including carbohydrate metabolism, cytoskeleton regulation, cell cycle, focal adhesion, adherent junctions, and cell migration. Components of the pancreatic cancer pathway were extensively S-nitrosylated, such as v-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) and Signal transducer and activator of transcription 3 (STAT3). Moreover, NOS (NO synthase) inhibitor significantly repressed STAT3 S-nitrosylation in PANC-1 cells, which caused significant increase of STAT3 phosphorylation and PANC-1 cell viability, suggesting important roles of protein S-nitrosylation in PDAC development. These results revealed extensive protein S-nitrosylation associated with PDAC pathogenesis, which provided a basis for protein modification-based cancer diagnosis and targeted therapy.
Side-by-side comparison of BH3-mimetics identifies MCL-1 as a key therapeutic target in AML
Authors: Ewald Larissa , Dittmann Jessica , Vogler Meike , Fulda Simone 
Published: December 2019

AbstractDespite advances in the treatment of acute myeloid leukemia (AML), prognosis of AML patients is still dismal and better treatment options are required. B-cell Lymphoma 2 (BCL-2) homology domain 3 (BH3)-mimetics are emerging as a novel class of apoptosis-inducing agents that are currently being tested for the treatment of different hematological malignancies including AML. Particularly, the selective BCL-2 inhibitor ABT-199/Venetoclax is demonstrating clinical responses and has recently been approved in combination for the treatment of AML. Compounds targeting the related protein MCL-1 have recently entered clinical trials, highlighting the urgency to compare the different BH3-mimetics and identify the most promising antiapoptotic target in AML. We performed a side-by-side comparison of different highly selective and potent BH3-mimetics targeting BCL-2 (ABT-199), MCL-1 (S63845) or BCL-xL (A1331852) in a panel of AML cell lines and primary patient cells. Gene knockdown using siRNAs was utilized to investigate the functional relevance of BCL-2 proteins. Western blotting and immunoprecipitations were used to explore the influence of BH3-mimetics on interactions between pro- and antiapoptotic BCL-2 proteins. A1331852 induced apoptosis only in selected cases, indicating that BCL-xL is not a very promising therapeutic target in AML. However, S63845 displayed higher potency than ABT-199, with more cell lines and primary cells responding to S63845 than to ABT-199. MCL-1 dependency in AML cells was confirmed by siRNA-mediated knockdown of MCL-1, which was sufficient to induce apoptosis. S63845-induced cell death was accompanied by a displacement of the BH3-only protein BIM as well as BAK, resulting in BAK-dependent apoptosis. In contrast, ABT-199-induced cell death was mediated by BAX rather than BAK, indicating distinct non-redundant molecular functions of BCL-2 and MCL-1 in AML. Our study reveals that MCL-1 may be a more prevalent therapeutic target than BCL-2 in AML and identifies BIM and BAK as important mediators of S63845-induced apoptosis in AML.
Cell death following the loss of ADAR1 mediated A-to-I RNA editing is not effected by the intrinsic apoptosis pathway
Authors: Walkley Carl R. , Kile Benjamin T. 
Published: December 2019

AbstractModifications of RNA, collectively termed as the epitranscriptome, are widespread, evolutionarily conserved and contribute to gene regulation and protein diversity in healthy and disease states. There are >160 RNA modifications described, greatly exceeding the number of modifications to DNA. Of these, adenosine-to-inosine (A-to-I) RNA editing is one of the most common. There are tens of thousands of A-to-I editing sites in mouse, and millions in humans. Upon translation or sequencing an inosine base is decoded as guanosine, leading to A-to-G mismatches between the RNA and DNA. Inosine has different base pairing properties to adenosine and as a result editing not only alters the RNA code but can also change the RNA structure. In mammals A-to-I editing is performed by ADAR1 and ADAR2. A feature of murine loss of function ADAR1 alleles is cell death and a failure to survive embryogenesis. Adar1−/− and editing deficient (Adar1E861A/E861A) mice die between E11.75–13.5 of failed hematopoiesis. Strikingly this phenotype is rescued by the deletion of the cytosolic dsRNA sensor MDA5 or its downstream adaptor MAVS, a mechanism conserved in human and mouse. Current literature indicates that the loss of ADAR1 leads to cell death via apoptosis, yet this has not been genetically established. We report that blockade of the intrinsic (mitochondrial) apoptosis pathway, through the loss of both BAK and BAX, does not rescue or modify the cellular phenotype of the fetal liver or extend the lifespan of ADAR1 editing deficient embryos. We had anticipated that the loss of BAK and BAX would rescue, or at least significantly extend, the gestational viability of Adar1E861A/E861A embryos. However, the triple mutant Adar1E861A/E861ABak−/−Bax−/− embryos that were recovered at E13.5 were indistinguishable from the Adar1E861A/E861A embryos with BAK and BAX. The results indicate that cell death processes not requiring the intrinsic apoptosis pathway are triggered by MDA5 following the loss of ADAR1.
CD40 induces renal cell carcinoma-specific differential regulation of TRAF proteins, ASK1 activation and JNK/p38-mediated, ROS-dependent mitochondrial apoptosis
Authors: Ibraheem Khalidah , Yhmed Albashir M. A. , Qayyum Tahir , Bryan Nicolas P. , Georgopoulos Nikolaos T. 
Published: December 2019

AbstractA unique feature of CD40 among the TNF receptor (TNFR) superfamily is its exquisitely contextual effects, as originally demonstrated in normal and malignant B-lymphocytes. We studied renal cell carcinoma (RCC) in comparison to normal (human renal proximal tubule) cells, as a model to better understand the role of CD40 in epithelial cells. CD40 ligation by membrane-presented CD40 ligand (mCD40L), but not soluble CD40 agonist, induced extensive apoptosis in RCC cells; by contrast, normal cells were totally refractory to mCD40L. These findings underline the importance of CD40 ‘signal-quality’ on cell fate and explain the lack of pro-apoptotic effects in RCC cells previously, while confirming the tumour specificity of CD40 in epithelial cells. mCD40L differentially regulated TRAF expression, causing sustained TRAF2/TRAF3 induction in RCC cells, yet downregulation of TRAF2 and no TRAF3 induction in normal cells, observations strikingly reminiscent of TRAF modulation in B-lymphocytes. mCD40L triggered reactive oxygen species (ROS) production, critical in apoptosis, and NADPH oxidase (Nox)-subunit p40phox phosphorylation, with Nox blockade abrogating apoptosis thus implying Nox-dependent initial ROS release. mCD40L mediated downregulation of Thioredoxin-1 (Trx-1), ASK1 phosphorylation, and JNK and p38 activation. Although both JNK/p38 were essential in apoptosis, p38 activation was JNK-dependent, which is the first report of such temporally defined JNK-p38 interplay during an apoptotic programme. CD40-killing entrained Bak/Bax induction, controlled by JNK/p38, and caspase-9-dependent mitochondrial apoptosis, accompanied by pro-inflammatory cytokine secretion, the repertoire of which also depended on CD40 signal quality. Previous reports suggested that, despite the ability of soluble CD40 agonist to reduce RCC tumour size in vivo via immunocyte activation, RCC could be targeted more effectively by combining CD40-mediated immune activation with direct tumour CD40 signalling. Since mCD40L represents a potent tumour cell-specific killing signal, our work not only offers insights into CD40’s biology in normal and malignant epithelial cells, but also provides an avenue for a ‘double-hit’ approach for inflammatory, tumour cell-specific CD40-based therapy.
Type I-F CRISPR-Cas resistance against virulent phages results in abortive infection and provides population-level immunity
Authors: Watson Bridget N. J. , Vercoe Reuben B. , Salmond George P. C. , Westra Edze R. , Staals Raymond H. J , Fineran Peter C. 
Published: December 2019

AbstractType I CRISPR-Cas systems are abundant and widespread adaptive immune systems in bacteria and can greatly enhance bacterial survival in the face of phage infection. Upon phage infection, some CRISPR-Cas immune responses result in bacterial dormancy or slowed growth, which suggests the outcomes for infected cells may vary between systems. Here we demonstrate that type I CRISPR immunity of Pectobacterium atrosepticum leads to suppression of two unrelated virulent phages, ɸTE and ɸM1. Immunity results in an abortive infection response, where infected cells do not survive, but viral propagation is severely decreased, resulting in population protection due to the reduced phage epidemic. Our findings challenge the view of CRISPR-Cas as a system that protects the individual cell and supports growing evidence of abortive infection by some types of CRISPR-Cas systems.
Synthesis of higher carboxylic acids from ethers, CO2 and H2
Authors: Wang Ying , Qian Qingli , Zhang Jingjing , Bediako Bernard Baffour Asare , Wang Zhenpeng , Liu Huizhen , Han Buxing 
Published: December 2019

AbstractSynthesis of higher carboxylic acids using CO2 and H2 is of great importance, because CO2 is an attractive renewable C1 resource and H2 is a cheap and clean reductant. Herein we report a route to produce higher carboxylic acids via reaction of ethers with CO2 and H2. We show that the reaction can be efficiently catalyzed by an IrI4 catalyst with LiI as promoter at 170 °C, 5 MPa of CO2 and 2 MPa of H2. The catalytic system applies to various ether substrates. The mechanistic study indicates that the ethers are converted to olefins, which are further transformed into alkyl iodides. The higher carboxylic acids are produced by carbonylation of alkyl iodides with CO generated in situ via RWGS reaction. This report offers an alternative strategy of higher carboxylic acid synthesis and CO2 transformation.
The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant
Authors: Bogdanow Boris , Wang Xi , Eichelbaum Katrin , Sadewasser Anne , Husic Immanuel , Paki Katharina , Budt Matthias , Hergeselle Martha , Vetter Barbara , Hou Jingyi , Chen Wei , Wiebusch Lüder , Meyer Irmtraud M. , Wolff Thorsten , Selbach Matthias 
Published: December 2019

AbstractPandemic influenza A virus (IAV) outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular basis of this species barrier is incompletely understood. Here we combine metabolic pulse labeling and quantitative proteomics to monitor protein synthesis upon infection of human cells with a human- and a bird-adapted IAV strain and observe striking differences in viral protein synthesis. Most importantly, the matrix protein M1 is inefficiently produced by the bird-adapted strain. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Strain-specific M segment splicing is controlled by the 3′ splice site and functionally important for permissive infection. In silico and biochemical evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, we identify M segment RNA splicing as a viral host range determinant.
Cerebral oxygenation during locomotion is modulated by respiration
Authors: Zhang Qingguang , Roche Morgane , Gheres Kyle W. , Chaigneau Emmanuelle , Kedarasetti Ravi T. , Haselden William D. , Charpak Serge , Drew Patrick J. 
Published: December 2019

AbstractIn the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animal remains unclear. We investigated to what extent cerebral oxygenation varies during locomotion. We measured oxygen levels in the cortex of awake, head-fixed mice during locomotion using polarography, spectroscopy, and two-photon phosphorescence lifetime measurements of oxygen sensors. We find that locomotion significantly and globally increases cerebral oxygenation, specifically in areas involved in locomotion, as well as in the frontal cortex and the olfactory bulb. The oxygenation increase persists when neural activity and functional hyperemia are blocked, occurred both in the tissue and in arteries feeding the brain, and is tightly correlated with respiration rate and the phase of respiration cycle. Thus, breathing rate is a key modulator of cerebral oxygenation and should be monitored during hemodynamic imaging, such as in BOLD fMRI.
Epidemic dynamics of respiratory syncytial virus in current and future climates
Authors: Baker Rachel E. , Mahmud Ayesha S. , Wagner Caroline E. , Yang Wenchang , Pitzer Virginia E. , Viboud Cecile , Vecchi Gabriel A. , Metcalf C. Jessica E. , Grenfell Bryan T. 
Published: December 2019

AbstractA key question for infectious disease dynamics is the impact of the climate on future burden. Here, we evaluate the climate drivers of respiratory syncytial virus (RSV), an important determinant of disease in young children. We combine a dataset of county-level observations from the US with state-level observations from Mexico, spanning much of the global range of climatological conditions. Using a combination of nonlinear epidemic models with statistical techniques, we find consistent patterns of climate drivers at a continental scale explaining latitudinal differences in the dynamics and timing of local epidemics. Strikingly, estimated effects of precipitation and humidity on transmission mirror prior results for influenza. We couple our model with projections for future climate, to show that temperature-driven increases to humidity may lead to a northward shift in the dynamic patterns observed and that the likelihood of severe outbreaks of RSV hinges on projections for extreme rainfall.