bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electoral incentives, policy compromise, and coalition durability: Japan's LDP–Komeito Government in a mixed electoral system
Authors: Liff Adam P. , Maeda Ko 
Published: December 2018

AbstractPolitical parties’ behavior in coalition formation is commonly explained by their policy-, vote-, and office-seeking incentives. From these perspectives, the 20-year partnership of Japan's ruling conservative Liberal Democratic Party (LDP) and its pacifistic Komeito junior coalition partner is an anomalous case. The longevity, closeness, and nature of their unlikely partnership challenges core assumptions in existing theories of coalition politics. LDP–Komeito cooperation has sustained for two decades despite vastly different support bases and ideological differences on fundamental policy issues. LDP leaders also show no signs of abandoning the much smaller Komeito despite enjoying a single-party majority. We argue that the remarkable durability of this puzzling partnership results primarily from the two parties’ electoral incentives and what has effectively become codependence under Japan's mixed electoral system. Our analysis also demonstrates that being in a coalition can induce significant policy compromises, even from amuchlarger senior partner. Beyond theoretical implications, these phenomena yield important real-world consequences for Japanese politics: especially, a far less dominant LDP than the party's Diet seat total suggests, and Komeito's remarkable ability to punch significantly above its weight and constrain its far larger senior partner, even on the latter's major national security policy priorities.
New insights into the morphology of the Carboniferous tetrapodCrassigyrinus scoticusfrom computed tomography
Authors: HERBST Eva C. , HUTCHINSON John R. 
Published: December 2018

ABSTRACTThe Carboniferous tetrapodCrassigyrinus scoticusis an enigmatic animal in terms of its morphology and its phylogenetic position.Crassigyrinushad extremely reduced forelimbs, and was aquatic, perhaps secondarily. Recent phylogenetic analyses tentatively placeCrassigyrinusclose to the whatcheeriids. Many Carboniferous tetrapods exhibit several characteristics associated with terrestrial locomotion, and much research has focused on how this novel locomotor mode evolved. However, to estimate the selective pressures and constraints during this important time in vertebrate evolution, it is also important to study early tetrapods likeCrassigyrinusthat either remained aquatic or secondarily became aquatic. We used computed tomographic scanning to search for more data about the skeletal morphology ofCrassigyrinusand discovered several elements previously hidden by the matrix. These elements include more ribs, another neural arch, potential evidence of an ossified pubis and maybe of pleurocentra. We also discovered several additional metatarsals with interesting asymmetrical morphology that may have functional implications. Finally, we reclassify what was previously thought to be a left sacral rib as a left fibula and show previously unknown aspects of the morphology of the radius. These discoveries are examined in functional and phylogenetic contexts.
Thermal Evolution of the Impact‐Induced Cryomagma Chamber Beneath Occator Crater on Ceres
Authors: Hesse M. A. , Castillo‐Rogez J. C. 
Published: December 2018

AbstractThe faculae in Occator Crater on dwarf planet Ceres are an accumulation of salts that have been interpreted as cryovolcanic products. Current age estimates from crater counting suggest a maximum 18‐Ma difference between the crater forming impact and the formation of Cerealia Facula, the central and most recent region in the crater. Here we model the thermal evolution of the potential impact‐induced cryomagma chamber beneath Occator Crater and show that it cools in less than 12 Ma. To reach cooling times of 18 Ma requires initial melt volumes exceeding 11,000 km3. However, simulations suggest that smaller initial cryomagma chambers may lead to partial melting of the lower crust. This may allow recharge of the magma chamber by deep brines located in the porous upper mantle of Ceres and may extend the longevity of cryovolcanic activity.
Fault Reactivation by Fluid Injection: Controls From Stress State and Injection Rate
Authors: Passelègue François. X. , Brantut Nicolas , Mitchell Thomas M. 
Published: December 2018

AbstractWe studied the influence of stress state and fluid injection rate on the reactivation of faults. We conducted experiments on a saw cut Westerly granite sample under triaxial stress conditions. Fault reactivation was triggered by injecting fluids through a borehole directly connected to the fault. Our results show that the peak fluid pressure at the borehole leading to reactivation increases with injection rate. Elastic wave velocity measurements along‐fault strike highlight that high injection rates induce significant fluid pressure heterogeneities, which explains that in such cases, the onset of fault reactivation is not determined by a conventional Coulomb law and effective stress principle, but rather by a nonlocal rupture initiation criterion. Our results demonstrate that increasing the injection rate enhances the transition from drained to locally undrained conditions, where local but intense fluid pressures perturbations can reactivate large faults, and contribute to continuing seismicity beyond the period of injection.
A framework for estimating the US mortality burden of fine particulate matter exposure attributable to indoor and outdoor microenvironments
Authors: Azimi Parham , Stephens Brent 
Published: December 2018

AbstractExposure to fine particulate matter (PM2.5) is associated with increased mortality. Although epidemiology studies typically use outdoor PM2.5 concentrations as surrogates for exposure, the majority of PM2.5 exposure in the US occurs in microenvironments other than outdoors. We develop a framework for estimating the total US mortality burden attributable to exposure to PM2.5 of both indoor and outdoor origin in the primary non-smoking microenvironments in which people spend most of their time. The framework utilizes an exposure-response function combined with adjusted mortality effect estimates that account for underlying exposures to PM2.5 of outdoor origin that likely occurred in the original epidemiology populations from which effect estimates are derived. We demonstrate the framework using several different scenarios to estimate the potential magnitude and bounds of the US mortality burden attributable to total PM2.5 exposure across all non-smoking environments under a variety of assumptions. Our best estimates of the US mortality burden associated with total PM2.5 exposure in the year 2012 range from ~230,000 to ~300,000 deaths. Indoor exposure to PM2.5 of outdoor origin is typically the largest total exposure, accounting for ~40–60% of total mortality, followed by residential exposure to indoor PM2.5 sources, which also drives the majority of variability in each scenario.
Temporal proteomic profiling of postnatal human cortical development
Authors: Breen Michael S. , Ozcan Sureyya , Ramsey Jordan M. , Wang Zichen , Ma’ayan Avi , Rustogi Nitin , Gottschalk Michael G. , Webster Maree J. , Weickert Cynthia Shannon , Buxbaum Joseph D. , Bahn Sabine 
Published: December 2018

AbstractHealthy cortical development depends on precise regulation of transcription and translation. However, the dynamics of how proteins are expressed, function and interact across postnatal human cortical development remain poorly understood. We surveyed the proteomic landscape of 69 dorsolateral prefrontal cortex samples across seven stages of postnatal life and integrated these data with paired transcriptome data. We detected 911 proteins by liquid chromatography-mass spectrometry, and 83 were significantly associated with postnatal age (FDR < 5%). Network analysis identified three modules of co-regulated proteins correlated with age, including two modules with increasing expression involved in gliogenesis and NADH metabolism and one neurogenesis-related module with decreasing expression throughout development. Integration with paired transcriptome data revealed that these age-related protein modules overlapped with RNA modules and displayed collinear developmental trajectories. Importantly, RNA expression profiles that are dynamically regulated throughout cortical development display tighter correlations with their respective translated protein expression compared to those RNA profiles that are not. Moreover, the correspondence between RNA and protein expression significantly decreases as a function of cortical aging, especially for genes involved in myelination and cytoskeleton organization. Finally, we used this data resource to elucidate the functional impact of genetic risk loci for intellectual disability, converging on gliogenesis, myelination and ATP-metabolism modules in the proteome and transcriptome. We share all data in an interactive, searchable companion website. Collectively, our findings reveal dynamic aspects of protein regulation and provide new insights into brain development, maturation, and disease.
CREPT/RPRD1B associates with Aurora B to regulate Cyclin B1 expression for accelerating the G2/M transition in gastric cancer
Authors: Ding Lidan , Yang Liu , He Yuqi , Zhu Bingtao , Ren Fangli , Fan Xuanzi , Wang Yinyin , Li Mengdi , Li Jun , Kuang Yanshen , Liu Sihan , Zhai Wanli , Ma Danhui , Ju Yanfang , Liu Quentin , Jia Baoqing , Sheng Jianqiu , Chang Zhijie 
Published: December 2018

AbstractGastric cancer, like most of other cancers, has an uncontrolled cell cycle regulated by cyclins and cyclin-dependent kinases (CDKs). In this study, we reported that gastric cancer cells showed an accelerated G2/M transition promoted by CREPT/RPRD1B and Aurora kinase B (Aurora B). We found that CREPT/RPRD1B and Aurora B were coordinately expressed during the cell cycle in gastric cancer cells. Deletion of CREPT/RPRD1B disturbed the cell progression and extended the length of cell cycle, leading to a significant accumulation of mitotic cells. Mechanistically, we revealed that CREPT/RPRD1B interacted with Aurora B to regulate the expression of Cyclin B1 in gastric cancer cells. Interestingly, Aurora B phosphorylates S145 in a well-conserved motif of CREPT/RPRD1B. We proposed that phosphorylation of CREPT/RPRD1B by Aurora B is required for promoting the transcription of Cyclin B1, which is critical for the regulation of gastric tumorigenesis. Our study provides a mechanism by which gastric tumor cells maintain their high proliferation rate via coordination of Aurora B and CREPT/RPRD1B on the expression of Cyclin B1. Targeting the interaction of Aurora B and CREPT/RPRD1B might be a strategy for anti-gastric cancer therapy in the future.
Ferritin heavy subunit enhances apoptosis of non-small cell lung cancer cells through modulation of miR-125b/p53 axis
Authors: Biamonte Flavia , Battaglia Anna Martina , Zolea Fabiana , Oliveira Duarte Mendes , Aversa Ilenia , Santamaria Gianluca , Giovannone Emilia Dora , Rocco Gaetano , Viglietto Giuseppe , Costanzo Francesco 
Published: December 2018

AbstractFerritin is a nanocage protein composed by the variable assembly of 24 heavy and light subunits. As major intracellular iron storage protein, ferritin has been studied for many years in the context of iron metabolism. However, recent evidences have highlighted its role, in particular that of the heavy subunit (FHC), in pathways related to cancer development and progression, such as cell proliferation, growth suppressor evasion, cell death inhibition, and angiogenesis. At least partly, the involvement in these pathways is due to the ability of FHC to control the expression of a repertoire of oncogenes and oncomiRNAs. Moreover, the existence of a feedback loop between FHC and the tumor suppressor p53 has been demonstrated in different cell types. Here, we show that ectopic over-expression of FHC induces the promoter hypermethylation and the down-regulation of miR-125b that, in turn, enhances p53 protein expression in non-small cell lung cancer (NSCLC) cell lines. Notably, analysis by absolute quantitative RT-PCR of FHC, miR-125b, and p53 strongly suggests that this axis might be active in human NSCLC tissue specimens. In vitro, FHC over-expression attenuates survival of NSCLC cells by inducing p53-mediated intrinsic apoptosis that is partially abrogated upon miR-125b re-expression. Overall, our findings demonstrate that FHC acts as a tumor suppressor gene, thus providing a potential molecular strategy for induction of NSCLC apoptotic cell death.
m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression
Authors: Zhang Panpan , He Qiuping , Lei Yuan , Li Yingqin , Wen Xin , Hong Mengzhi , Zhang Jian , Ren Xianyue , Wang Yaqin , Yang Xiaojing , He Qingmei , Ma Jun , Liu Na 
Published: December 2018

AbstractNasopharyngeal carcinoma (NPC) progression is regulated by genetic, epigenetic, and epitranscript modulation. As one of the epitranscript modifications, the role of N6-Methyladenosine (m6A) has not been elucidated in NPC. In the present study, we found that the poorly methylated gene ZNF750 (encoding zinc finger protein 750) was downregulated in NPC tumor tissues and cell lines. Ectopic expression of ZNF750 blocked NPC growth in vitro and in vivo. Further studies revealed that m6A modifications maintained the low expression level of ZNF750 in NPC. Chromatin immunoprecipitation sequencing identified that ZNF750 directly regulated FGF14 (encoding fibroblast growth factor 14), ablation of which reversed ZNF750’s tumor repressor effect. Moreover, the ZNF750-FGF14 signaling axis inhibited NPC growth by promoting cell apoptosis. These findings uncovered the critical role of m6A in NPC, and stressed the regulatory function of the ZNF750-FGF14 signaling axis in modulating NPC progression, which provides theoretical guidance for the clinical treatment of NPC.
Proteasomal degradation of BRAHMA promotes Boron tolerance in Arabidopsis
Authors: Sakamoto Takuya , Tsujimoto-Inui Yayoi , Sotta Naoyuki , Hirakawa Takeshi , Matsunaga Tomoko M. , Fukao Yoichiro , Matsunaga Sachihiro , Fujiwara Toru 
Published: December 2018

AbstractHigh levels of boron (B) induce DNA double-strand breaks (DSBs) in eukaryotes, including plants. Here we show a molecular pathway of high B-induced DSBs by characterizing Arabidopsis thaliana hypersensitive to excess boron mutants. Molecular analysis of the mutants revealed that degradation of a SWItch/Sucrose Non-Fermentable subunit, BRAHMA (BRM), by a 26S proteasome (26SP) with specific subunits is a key process for ameliorating high-B-induced DSBs. We also found that high-B treatment induces histone hyperacetylation, which increases susceptibility to DSBs. BRM binds to acetylated histone residues and opens chromatin. Accordingly, we propose that the 26SP limits chromatin opening by BRM in conjunction with histone hyperacetylation to maintain chromatin stability and avoid DSB formation under high-B conditions. Interestingly, a positive correlation between the extent of histone acetylation and DSB formation is evident in human cultured cells, suggesting that the mechanism of DSB induction is also valid in animals.
Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization
Authors: Bedewitz Matthew A. , Jones A. Daniel , D’Auria John C. , Barry Cornelius S. 
Published: December 2018

AbstractTropinone is the first intermediate in the biosynthesis of the pharmacologically important tropane alkaloids that possesses the 8-azabicyclo[3.2.1]octane core bicyclic structure that defines this alkaloid class. Chemical synthesis of tropinone was achieved in 1901 but the mechanism of tropinone biosynthesis has remained elusive. In this study, we identify a root-expressed type III polyketide synthase from Atropa belladonna (AbPYKS) that catalyzes the formation of 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This catalysis proceeds through a non-canonical mechanism that directly utilizes an unconjugated N-methyl-Δ1-pyrrolinium cation as the starter substrate for two rounds of malonyl-Coenzyme A mediated decarboxylative condensation. Subsequent formation of tropinone from 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid is achieved through cytochrome P450-mediated catalysis by AbCYP82M3. Silencing of AbPYKS and AbCYP82M3 reduces tropane levels in A. belladonna. This study reveals the mechanism of tropinone biosynthesis, explains the in planta co-occurrence of pyrrolidines and tropanes, and demonstrates the feasibility of tropane engineering in a non-tropane producing plant.
Reversible and selective ion intercalation through the top surface of few-layer MoS2
Authors: Zhang Jinsong , Yang Ankun , Wu Xi , van de Groep Jorik , Tang Peizhe , Li Shaorui , Liu Bofei , Shi Feifei , Wan Jiayu , Li Qitong , Sun Yongming , Lu Zhiyi , Zheng Xueli , Zhou Guangmin , Wu Chun-Lan , Zhang Shou-Cheng , Brongersma Mark L. , Li Jia , Cui Yi 
Published: December 2018

AbstractElectrochemical intercalation of ions into the van der Waals gap of two-dimensional (2D) layered materials is a promising low-temperature synthesis strategy to tune their physical and chemical properties. It is widely believed that ions prefer intercalation into the van der Waals gap through the edges of the 2D flake, which generally causes wrinkling and distortion. Here we demonstrate that the ions can also intercalate through the top surface of few-layer MoS2 and this type of intercalation is more reversible and stable compared to the intercalation through the edges. Density functional theory calculations show that this intercalation is enabled by the existence of natural defects in exfoliated MoS2 flakes. Furthermore, we reveal that sealed-edge MoS2 allows intercalation of small alkali metal ions (e.g., Li+ and Na+) and rejects large ions (e.g., K+). These findings imply potential applications in developing functional 2D-material-based devices with high tunability and ion selectivity.
Design Optimization of Tumor Vasculature-Bound Nanoparticles
Authors: Chamseddine Ibrahim M. , Frieboes Hermann B. , Kokkolaras Michael 
Published: December 2018

AbstractNanotherapy may constitute a promising approach to target tumors with anticancer drugs while minimizing systemic toxicity. Computational modeling can enable rapid evaluation of nanoparticle (NP) designs and numerical optimization. Here, an optimization study was performed using an existing tumor model to find NP size and ligand density that maximize tumoral NP accumulation while minimizing tumor size. Optimal NP avidity lies at lower bound of feasible values, suggesting reduced ligand density to prolong NP circulation. For the given set of tumor parameters, optimal NP diameters were 288 nm to maximize NP accumulation and 334 nm to minimize tumor diameter, leading to uniform NP distribution and adequate drug load. Results further show higher dependence of NP biodistribution on the NP design than on tumor morphological parameters. A parametric study with respect to drug potency was performed. The lower the potency of the drug, the bigger the difference is between the maximizer of NP accumulation and the minimizer of tumor size, indicating the existence of a specific drug potency that minimizes the differential between the two optimal solutions. This study shows the feasibility of applying optimization to NP designs to achieve efficacious cancer nanotherapy, and offers a first step towards a quantitative tool to support clinical decision making.
Development of a novel RANKL-based peptide, microglial healing peptide1-AcN (MHP1-AcN), for treatment of ischemic stroke
Authors: Shimamura Munehisa , Nakagami Hironori , Shimizu Hideo , Mukai Hideyuki , Watanabe Ryosuke , Okuzono Takeshi , Kawano Tomohiro , Ikeda Yuka , Hayashi Hiroki , Yoshida Shota , Ju Nan , Mochizuki Hideki , Morishita Ryuichi 
Published: December 2018

AbstractAlthough the regulation of post-ischemic inflammation is an important strategy to treat ischemic stroke, all clinical trials have failed to show its efficacy. To solve the problem, we previously developed a novel partial peptide of RANKL, microglial healing peptide 1 (MHP1), which could reduce ischemic injury by inhibiting Toll-like receptor (TLR) induced inflammation. However, optimization of the peptide was necessary to increase the stability and efficacies for clinical use. According to information gathered through HPLC/MS in serum, we have newly designed a series of modified MHP1 peptides and have found that N-terminal acetylation and C-terminal amidation in MHP1 (MHP1-AcN), can strengthen its anti-inflammatory effects and increase its stability with anti-osteoclastogenic effects. Anti-TLR activity was reported to be reduced in MHP1 when incubated at 37 °C for 24 hrs, but MHP1-AcN could keep the activity under the same condition. The therapeutic effect of MHP1-AcN was observed in transient ischemic stroke model at lower dose than MHP1. Importantly, MHP1-AcN did not affect thrombolytic effects of tissue plasminogen activator (tPA) and inhibited tPA-induced hemorrhagic transformation. These findings indicated that MHP1-AcN was stable and effective anti-TLR signal peptide and could be a promising agent for treating stroke patients receiving tPA and endovascular therapy.
Developmental Shifts in Detection and Attention for Auditory, Visual, and Audiovisual Speech
Authors: Jerger Susan , Damian Markus F. , Karl Cassandra , Abdi Hervé 
Published: December 2018

PurposeSuccessful speech processing depends on our ability to detect and integrate multisensory cues, yet there is minimal research on multisensory speech detection and integration by children. To address this need, we studied the development of speech detection for auditory (A), visual (V), and audiovisual (AV) input.MethodParticipants were 115 typically developing children clustered into age groups between 4 and 14 years. Speech detection (quantified by response times [RTs]) was determined for 1 stimulus, /buh/, presented in A, V, and AV modes (articulating vs. static facial conditions). Performance was analyzed not only in terms of traditional mean RTs but also in terms of the faster versus slower RTs (defined by the 1st vs. 3rd quartiles of RT distributions). These time regions were conceptualized respectively as reflecting optimal detection with efficient focused attention versus less optimal detection with inefficient focused attention due to attentional lapses.ResultsMean RTs indicated better detection (a) of multisensory AV speech than A speech only in 4- to 5-year-olds and (b) of A and AV inputs than V input in all age groups. The faster RTs revealed that AV input did not improve detection in any group. The slower RTs indicated that (a) the processing of silent V input was significantly faster for the articulating than static face and (b) AV speech or facial input significantly minimized attentional lapses in all groups except 6- to 7-year-olds (a peaked U-shaped curve). Apparently, the AV benefit observed for mean performance in 4- to 5-year-olds arose from effects of attention.ConclusionsThe faster RTs indicated that AV input did not enhance detection in any group, but the slower RTs indicated that AV speech and dynamic V speech (mouthing) significantly minimized attentional lapses and thus did influence performance. Overall, A and AV inputs were detected consistently faster than V input; this result endorsed stimulus-bound auditory processing by these children.