bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA GAS5 acts as proliferation “brakes” in CD133+ cells responsible for tumor recurrence
Authors: Sharma Nikita S. , Gnamlin Prisca , Durden Brittany , Gupta Vineet K. , Kesh Kousik , Garrido Vanessa T. , Dudeja Vikas , Saluja Ashok , Banerjee Sulagna 
Published: November 2019

AbstractPresence of quiescent, therapy evasive population often described as cancer stem cells (CSC) or tumor initiating cells (TIC) is often attributed to extreme metastasis and tumor recurrence. This population is typically enriched in a tumor as a result of microenvironment or chemotherapy induced stress. The TIC population adapts to this stress by turning on cell cycle arrest programs that is a “fail-safe” mechanism to prevent expansion of malignant cells to prevent further injury. Upon removal of the “stress” conditions, these cells restart their cell cycle and regain their proliferative nature thereby resulting in tumor relapse. Growth Arrest Specific 5 (GAS5) is a long-non-coding RNA that plays a vital role in this process. In pancreatic cancer, CD133+ population is a typical representation of the TIC population that is responsible for tumor relapse. In this study, we show for the first time that emergence of CD133+ population coincides with upregulation of GAS5, that reprograms the cell cycle to slow proliferation by inhibiting GR mediated cell cycle control. The CD133+ population further routed metabolites like glucose to shunt pathways like pentose phosphate pathway, that were predominantly biosynthetic in spite of being quiescent in nature but did not use it immediately for nucleic acid synthesis. Upon inhibiting GAS5, these cells were released from their growth arrest and restarted the nucleic acid synthesis and proliferation. Our study thus showed that GAS5 acts as a molecular switch for regulating quiescence and growth arrest in CD133+ population, that is responsible for aggressive biology of pancreatic tumors.
Chemical compound cinobufotalin potently induces FOXO1-stimulated cisplatin sensitivity by antagonizing its binding partner MYH9
Authors: Li YongHao , Liu Xiong , Lin Xian , Zhao Menyang , Xiao Yanyi , Liu Chen , Liang Zixi , Lin Zelong , Yi Renhui , Tang Zibo , Liu Jiahao , Li Xin , Jiang Qingping , Li Libo , Xie Yinyin , Liu Zhen , Fang Weiyi 
Published: November 2019

AbstractIn this study, we present novel molecular mechanisms by which FOXO1 functions as a tumor suppressor to prevent the pathogenesis of nasopharyngeal carcinoma (NPC). First, we observed that FOXO1 not only controlled tumor stemness and metastasis, but also sensitized NPC cells to cisplatin (DDP) in vitro and in vivo. Mechanistic studies demonstrated that FOXO1-induced miR-200b expression through the GSK3β/β-catenin/TCF4 network-mediated stimulation of ZEB1, which reduced tumor stemness and the epithelial–mesenchymal transition (EMT) signal. Furthermore, we observed FOXO1 interaction with MYH9 and suppression of MYH9 expression by modulating the PI3K/AKT/c-Myc/P53/miR-133a-3p pathway. Decreased MYH9 expression not only reduced its interactions with GSK3β, but also attenuated TRAF6 expression, which then decreased the ubiquitin-mediated degradation of GSK3β protein. Increased GSK3β expression stimulated the β-catenin/TCF4/ZEB1/miR-200b network, which increased the downstream tumor stemness and EMT signals. Subsequently, we observed that chemically synthesized cinobufotalin (CB) strongly increased FOXO1-induced DDP chemosensitivity by reducing MYH9 expression, and the reduction in MYH9 modulated GSK3β/β-catenin and its downstream tumor stemness and EMT signal in NPC. In clinical samples, the combination of low FOXO1 expression and high MYH9 expression indicated the worst overall survival rates. Our studies demonstrated that CB potently induced FOXO1-mediated DDP sensitivity by antagonizing its binding partner MYH9 to modulate tumor stemness in NPC.
Prenatal nicotine sex-dependently alters adolescent dopamine system development
Authors: Dwyer Jennifer B. , Cardenas Anjelica , Franke Ryan M. , Chen YiLing , Bai Yu , Belluzzi James D. , Lotfipour Shahrdad , Leslie Frances M. 
Published: November 2019

AbstractDespite persistent public health initiatives, many women continue to smoke during pregnancy. Since maternal smoking has been linked to persisting sex-dependent neurobehavioral deficits in offspring, some consider nicotine to be a safer alternative to tobacco during pregnancy, and the use of electronic nicotine delivery systems is on the rise. We presently show, however, that sustained exposure to low doses of nicotine during fetal development, approximating plasma levels seen clinically with the nicotine patch, produces substantial changes in developing corticostriatal dopamine systems in adolescence. Briefly, pregnant dams were implanted on gestational day 4 with an osmotic minipump that delivered either saline (GS) or nicotine (3 mg/kg/day) (GN) for two weeks. At birth, pups were cross-fostered with treatment naïve dams and were handled daily. Biochemical analyses, signaling assays, and behavioral responses to cocaine were assessed on postnatal day 32, representative of adolescence in the rodent. GN treatment had both sex-dependent and sex-independent effects on prefrontal dopamine systems, altering Catechol-O-methyl transferase (COMT)-dependent dopamine turnover in males and norepinephrine transporter (NET) binding expression in both sexes. GN enhanced cocaine-induced locomotor activity in females, concomitant with GN-induced reductions in striatal dopamine transporter (DAT) binding. GN enhanced ventral striatal D2-like receptor expression and G-protein coupling, while altering the roles of D2 and D3 receptors in cocaine-induced behaviors. These data show that low-dose prenatal nicotine treatment sex-dependently alters corticostriatal dopamine system development, which may underlie clinical deficits seen in adolescents exposed to tobacco or nicotine in utero.
Individual differences in human fear generalization—pattern identification and implications for anxiety disorders
Authors: Stegmann Y. , Schiele M. A. , Schümann D. , Lonsdorf T. B. , Zwanzger P. , Romanos M. , Reif A. , Domschke K. , Deckert J. , Gamer M. , Pauli P. 
Published: November 2019

AbstractPrevious research indicates that anxiety disorders are characterized by an overgeneralization of conditioned fear as compared with healthy participants. Therefore, fear generalization is considered a key mechanism for the development of anxiety disorders. However, systematic investigations on the variance in fear generalization are lacking. Therefore, the current study aims at identifying distinctive phenotypes of fear generalization among healthy participants. To this end, 1175 participants completed a differential fear conditioning phase followed by a generalization test. To identify patterns of fear generalization, we used a k-means clustering algorithm based on individual arousal generalization gradients. Subsequently, we examined the reliability and validity of the clusters and phenotypical differences between subgroups on the basis of psychometric data and markers of fear expression. Cluster analysis reliably revealed five clusters that systematically differed in mean responses, differentiation between conditioned threat and safety, and linearity of the generalization gradients, though mean response levels accounted for most variance. Remarkably, the patterns of mean responses were already evident during fear acquisition and corresponded most closely to psychometric measures of anxiety traits. The identified clusters reliably described subgroups of healthy individuals with distinct response characteristics in a fear generalization test. Following a dimensional view of psychopathology, these clusters likely delineate risk factors for anxiety disorders. As crucial group characteristics were already evident during fear acquisition, our results emphasize the importance of average fear responses and differentiation between conditioned threat and safety as risk factors for anxiety disorders.
Idebenone has preventative and therapeutic effects on pulmonary fibrosis via preferential suppression of fibroblast activity
Authors: Sugizaki Toshifumi , Tanaka Ken-ichiro , Asano Teita , Kobayashi Daisuke , Hino Yuuki , Takafuji Ayaka , Shimoda Mikako , Mogushi Kaoru , Kawahara Masahiro , Mizushima Tohru 
Published: November 2019

AbstractAlveolar epithelial injury induced by reactive oxygen species (ROS) and abnormal collagen production by activated fibroblasts (myofibroblasts) is involved in the onset and exacerbation of idiopathic pulmonary fibrosis (IPF). Compared with alveolar epithelial cells, lung fibroblasts, especially myofibroblasts, exhibit an apoptosis-resistance phenotype (apoptosis paradox) that appears to be involved in IPF pathogenesis. Thus, we screened for chemicals eliciting preferential cytotoxicity of LL29 cells (lung fibroblasts from an IPF patient) compared with A549 cells (human lung alveolar epithelial cell line) from medicines already in clinical use. We identified idebenone, a synthetic analogue of coenzyme Q10 (CoQ10, an antioxidant) that has been used clinically as a brain metabolic stimulant. Idebenone induced cell growth inhibition and cell death in LL29 cells at a lower concentration than in A549 cells, a feature that was not observed for other antioxidant molecules (such as CoQ10) and two IPF drugs (pirfenidone and nintedanib). Administration of idebenone prevented bleomycin-induced pulmonary fibrosis and increased pulmonary ROS levels. Importantly, idebenone also improved pulmonary fibrosis and lung function when administered after the development of fibrosis, whereas administration of CoQ10 similarly prevented bleomycin-induced pulmonary fibrosis, but had no effect after its development. Administration of idebenone, but not CoQ10, suppressed bleomycin-induced increases in lung myofibroblasts. In vitro, treatment of LL29 cells with idebenone, but not CoQ10, suppressed TGF-β–induced collagen production. These results suggest that in addition to antioxidant activity, idebenone exerts inhibitory activity on the function of lung fibroblasts, with the former activity being preventative and the latter therapeutic for bleomycin-induced fibrosis. Thus, we propose that idebenone may be more therapeutically beneficial for IPF patients than current treatments.
Geodynamic evolution of southwestern North America since the Late Eocene
Authors: Bahadori Alireza , Holt William E. 
Published: November 2019

AbstractSlab rollback, lithospheric body forces, or evolution of plate boundary conditions are strongly debated as possible lithospheric driving mechanisms for Cenozoic extension in southwestern North America. By incorporating paleo-topography, lithospheric structure, and paleo-boundary conditions, we develop a complete geodynamic model that quantifies lithospheric deviatoric stresses and predicts extension and shear history since Late Eocene. We show that lithospheric body forces together with influence of change-over from subduction to transtensional boundary conditions from Late Eocene to Early Miocene were the primary driving factors controlling direction and magnitude of extensional deviatoric stresses that produced topographic collapse. After paleo-highlands collapsed, influence of Pacific-North America plate motion and associated deformation style along the plate boundary became increasingly important from Middle Miocene to present. Smaller-scale convection stress effects from slab rollback and associated mantle flow played only a minor role. However, slab rollback guided deformation rate through introduction of melts and fluids that impacted rheology.
Key drivers of cloud response to surface-active organics
Authors: Lowe S. J. , Partridge D. G. , Davies J. F. , Wilson K. R. , Topping D. , Riipinen I. 
Published: November 2019

AbstractAerosol-cloud interactions constitute the largest source of uncertainty in global radiative forcing estimates, hampering our understanding of climate evolution. Recent empirical evidence suggests surface tension depression by organic aerosol to significantly influence the formation of cloud droplets, and hence cloud optical properties. In climate models, however, surface tension of water is generally assumed when predicting cloud droplet concentrations. Here we show that the sensitivity of cloud microphysics, optical properties and shortwave radiative effects to the surface phase are dictated by an interplay between the aerosol particle size distribution, composition, water availability and atmospheric dynamics. We demonstrate that accounting for the surface phase becomes essential in clean environments in which ultrafine particle sources are present. Through detailed sensitivity analysis, quantitative constraints on the key drivers – aerosol particle number concentrations, organic fraction and fixed updraft velocity – are derived for instances of significant cloud microphysical susceptibilities to the surface phase.
Interspecific introgression mediates adaptation to whole genome duplication
Authors: Marburger Sarah , Monnahan Patrick , Seear Paul J. , Martin Simon H. , Koch Jordan , Paajanen Pirita , Bohutínská Magdalena , Higgins James D. , Schmickl Roswitha , Yant Levi 
Published: November 2019

AbstractAdaptive gene flow is a consequential phenomenon across all kingdoms. Although recognition is increasing, there is no study showing that bidirectional gene flow mediates adaptation at loci that manage core processes. We previously discovered concerted molecular changes among interacting members of the meiotic machinery controlling crossover number upon adaptation to whole-genome duplication (WGD) in Arabidopsis arenosa. Here we conduct a population genomic study to test the hypothesis that adaptation to WGD has been mediated by adaptive gene flow between A. arenosa and A. lyrata. We find that A. lyrata underwent WGD more recently than A. arenosa, suggesting that pre-adapted alleles have rescued nascent A. lyrata, but we also detect gene flow in the opposite direction at functionally interacting loci under the most extreme levels of selection. These data indicate that bidirectional gene flow allowed for survival after WGD, and that the merger of these species is greater than the sum of their parts.
Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing
Authors: Kim Hyunsuk , Park Hayne Cho , Ryu Hyunjin , Kim Hyunho , Lee Hyun-Seob , Heo Jongho , Lee Chung , Kim Nayoung K. D. , Park Woong-Yang , Hwang Young-Hwan , Lee Kyu Beck , Oh Kook-Hwan , Oh Yun kyu , Ahn Curie 
Published: November 2019

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of PKD1/2 were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the PKD1 gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel. PKD1 protein-truncating (PKD1-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to PKD1 non-truncating and PKD2 genotypes. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect, PKD2 genotype had 0.2 times lower risk for reaching ESRD than PKD1-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans.
Single-Shot Readout Performance of Two Heterojunction-Bipolar-Transistor Amplification Circuits at Millikelvin Temperatures
Authors: Curry M. J. , Rudolph M. , England T. D. , Mounce A. M. , Jock R. M. , Bureau-Oxton C. , Harvey-Collard P. , Sharma P. A. , Anderson J. M. , Campbell D. M. , Wendt J. R. , Ward D. R. , Carr S. M. , Lilly M. P. , Carroll M. S. 
Published: November 2019

AbstractHigh-fidelity single-shot readout of spin qubits requires distinguishing states much faster than the T1 time of the spin state. One approach to improving readout fidelity and bandwidth (BW) is cryogenic amplification, where the signal from the qubit is amplified before noise sources are introduced and room-temperature amplifiers can operate at lower gain and higher BW. We compare the performance of two cryogenic amplification circuits: a current-biased heterojunction bipolar transistor circuit (CB-HBT), and an AC-coupled HBT circuit (AC-HBT). Both circuits are mounted on the mixing-chamber stage of a dilution refrigerator and are connected to silicon metal oxide semiconductor (Si-MOS) quantum dot devices on a printed circuit board (PCB). The power dissipated by the CB-HBT ranges from 0.1 to 1 μW whereas the power of the AC-HBT ranges from 1 to 20 μW. Referred to the input, the noise spectral density is low for both circuits, in the 15 to 30 fA/$$\sqrt{{\bf{Hz}}}$$

Hz

range. The charge sensitivity for the CB-HBT and AC-HBT is 330 μe/$$\sqrt{{\bf{Hz}}}$$

Hz

and 400 μe/$$\sqrt{{\bf{Hz}}}$$

Hz

, respectively. For the single-shot readout performed, less than 10 μs is required for both circuits to achieve bit error rates below 10−3, which is a putative threshold for quantum error correction.
Non-deforestation drivers of fires are increasingly important sources of aerosol and carbon dioxide emissions across Amazonia
Authors: Morgan William T. , Darbyshire Eoghan , Spracklen Dominick V. , Artaxo Paulo , Coe Hugh 
Published: November 2019

AbstractDeforestation rates have declined substantially across the Brazilian Legal Amazon (BLA) over the period from 2000–2017. However, reductions in fire, aerosol and carbon dioxide have been far less significant than deforestation, even when accounting for inter-annual variability in precipitation. Our observations and analysis support a decoupling between fire and deforestation that has exacerbated forest degradation in the BLA. Basing aerosol and carbon dioxide emissions on deforestation rates, without accounting for forest degradation will bias these important climate and ecosystem-health parameters low, both now and in the future. Recent increases in deforestation rate since 2014 will enhance such degradation, particularly during drought-conditions, increasing emissions of aerosol and greenhouse gases. Given Brazil’s committed Nationally Determined Contribution under the Paris Agreement, failure to account for forest degradation fires will paint a false picture of prior progress and potentially have profound implications for both regional and global climate.
Epigenetic regulation of AURKA by miR-4715-3p in upper gastrointestinal cancers
Authors: Gomaa Ahmed , Peng Dunfa , Chen Zheng , Soutto Mohammed , Abouelezz Khaled , Corvalan Alejandro , El-Rifai Wael 
Published: November 2019

AbstractAurora kinase A (AURKA) is frequently overexpressed in several cancers. miRNA sequencing and bioinformatics analysis indicated significant downregulation of miR-4715-3p. We found that miR-4715-3p has putative binding sites on the 3UTR region of AURKA. Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Luciferase reporter assays confirmed binding of miR-4715-3p on the 3UTR region of AURKA. miR-4715-3p mediated a reduction in AURKA levels leading to G2/M delay, chromosomal polyploidy, and cell death. We also detected a remarkable decrease in GPX4, an inhibitor of ferroptosis, with an increase in cleaved PARP and caspase-3. Inhibition of AURKA using siRNA produced similar results, suggesting a possible link between AURKA and GPX4. Analysis of UGC samples and cell models demonstrated increased methylation levels of several CpG nucleotides upstream of miR-4715-3p. 5-Aza-2′-deoxycytidine induced demethylation of several CpG nucleotides, restoring miR-4715-3p expression, leading to downregulation of AURKA. In conclusion, our data identified a novel epigenetic mechanism mediating silencing of miR-4715-3p and induction of AURKA in UGCs. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis.
Vanadium Phosphorus Oxide/Siliceous Mesostructured Cellular Foams: efficient and selective for sustainable acrylic acid production via condensation route
Authors: Liu Jun , Xu Peiwen , Wang Pengcheng , Xu Zhijia , Feng Xinzhen , Ji Weijie , Au Chak-Tong 
Published: November 2019

AbstractA new type of supported vanadium phosphorus oxide (VPO) with self-phase regulation was simply fabricated (organic solvent free) for the first time by depositing the specific VPO precursor NH4(VO2)HPO4 onto the Siliceous Mesostructured Cellular Foams (MCF) with controlled activation. The resulting materials were found to be highly efficient and selective for sustainable acrylic acid (AA) plus methyl acrylate (MA) production via a condensation route between acetic acid (HAc) and formaldehyde (HCHO). A (AA + MA) yield of 83.7% (HCHO input-based) or a (AA + MA) selectivity of 81.7% (converted HAc-based) are achievable at 360 °C. The systematic characterizations and evaluations demonstrate a unique surface regulation occurring between the MCF and the NH4(VO2)HPO4 precursor. NH3 release upon activation of NH4(VO2)HPO4 precursor together with adsorption of NH3 by MCF automatically induces partial reduction of V5+ whose content is fine-tunable by the VPO loading. Such a functionalization simultaneously modifies phase constitution and surface acidity/basicity of catalyst, hence readily controls catalytic performance.
Precise determination of surface band bending in Ga-polar n-GaN films by angular dependent X-Ray photoemission spectroscopy
Authors: Zhao Yanfei , Gao Hongwei , Huang Rong , Huang Zengli , Li Fangsen , Feng Jiagui , Sun Qian , Dingsun An , Yang Hui 
Published: November 2019

AbstractWe present a systematic study of surface band bending in Ga-polar n-GaN with different Si doping concentrations by angular dependent X-ray photoelectron spectroscopy (ADXPS). The binding energies of Ga 3d and N 1 s core levels in n-GaN films increase with increasing the emission angle, i. e., the probing depth, suggesting an upward surface band bending. By fitting the Ga 3d core level spectra at different emission angles and considering the integrated effect of electrostatic potential, the core level energy at the topmost surface layer is well corrected, therefore, the surface band bending is precisely evaluated. For moderately doped GaN, the electrostatic potential can be reflected by the simply linear potential approximation. However, for highly doped GaN samples, in which the photoelectron depth is comparable to the width of the space charge region, quadratic depletion approximation was used for the electrostatic potential to better understand the surface band bending effect. Our work improves the knowledge of surface band bending determination by ADXPS and also paves the way for studying the band bending effect in the interface of GaN based heterostructures.