bluuebunny/crossref_metadata_2025_split huggingface dataset:
The CHD Protein, Kismet, is Important for the Recycling of Synaptic Vesicles during Endocytosis
Authors: Latcheva Nina K. , Delaney Taylor L. , Viveiros Jennifer M. , Smith Rachel A. , Bernard Kelsey M. , Harsin Benjamin , Marenda Daniel R. , Liebl Faith L. W. 
Published: December 2019

AbstractChromatin remodeling proteins of the chromodomain DNA-binding protein family, CHD7 and CHD8, mediate early neurodevelopmental events including neural migration and differentiation. As such, mutations in either protein can lead to neurodevelopmental disorders. How chromatin remodeling proteins influence the activity of mature synapses, however, is relatively unexplored. A critical feature of mature neurons is well-regulated endocytosis, which is vital for synaptic function to recycle membrane and synaptic proteins enabling the continued release of synaptic vesicles. Here we show that Kismet, the Drosophila homolog of CHD7 and CHD8, regulates endocytosis. Kismet positively influenced transcript levels and bound to dap160 and endophilin B transcription start sites and promoters in whole nervous systems and influenced the synaptic localization of Dynamin/Shibire. In addition, kismet mutants exhibit reduced VGLUT, a synaptic vesicle marker, at stimulated but not resting synapses and reduced levels of synaptic Rab11. Endocytosis is restored at kismet mutant synapses by pharmacologically inhibiting the function of histone deacetyltransferases (HDACs). These data suggest that HDAC activity may oppose Kismet to promote synaptic vesicle endocytosis. A deeper understanding of how CHD proteins regulate the function of mature neurons will help better understand neurodevelopmental disorders.
Heregulin expression and its clinical implication for patients with EGFR-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors
Authors: Yonesaka Kimio , Iwama Eiji , Hayashi Hidetoshi , Suzuki Shinichiro , Kato Ryoji , Watanabe Satomi , Takahama Takayuki , Tanizaki Junko , Tanaka Kaoru , Takeda Masayuki , Sakai Kazuko , Azuma Koichi , Chiba Yasutaka , Atagi Shinji , Nishio Kazuto , Okamoto Isamu , Nakagawa Kazuhiko 
Published: December 2019

AbstractEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Preclinically, HER3 ligand heregulin induces resistance to EGFR-TKIs, whereas the pan-human EGFR family inhibitor afatinib remains effective. Here, we examined whether soluble heregulin levels have clinical implications for EGFR-mutant NSCLC treated with EGFR-TKIs. Soluble heregulin was immunologically measured in plasma from EGFR-mutant NSCLC patients. Cutoff values were determined by 1-year PFS ROC curve. The relationship between soluble heregulin and PFS following EGFR-TKI therapy was analyzed by Cox proportional hazards model. Seventy-three patients were enrolled: 44 were treated with 1st-generation and 29 with 2nd-generation EGFR-TKIs. Soluble heregulin levels varied (range: 274–7,138 pg/mL, median: 739 pg/mL). Among patients treated with 1st-generation EGFR-TKIs, those with high heregulin (n = 20, >800 pg/mL) had a tendency for shorter PFS than those with low heregulin (n = 24, <800 pg/mL), with median PFS of 322 and 671 days, respectively. Cox proportional hazards model also indicated a trend toward resistance against 1st-generation EGFR-TKIs (HR: 1.825, 95% CI: 0.865–4.318) but not against 2nd-generation EGFR-TKIs. Soluble heregulin potentially correlates with resistance to EGFR-TKIs but not 2nd-generation EGFR-TKIs in patients with EGFR-mutant NSCLC.
Farnesoid X receptor and bile acids regulate vitamin A storage
Authors: Saeed Ali , Yang Jing , Heegsma Janette , Groen Albert K. , van Mil Saskia W. C. , Paulusma Coen C. , Zhou Lu , Wang Bangmao , Faber Klaas Nico 
Published: December 2019

AbstractThe nuclear receptor Farnesoid X Receptor (FXR) is activated by bile acids and controls multiple metabolic processes, including bile acid, lipid, carbohydrate, amino acid and energy metabolism. Vitamin A is needed for proper metabolic and immune control and requires bile acids for efficient intestinal absorption and storage in the liver. Here, we analyzed whether FXR regulates vitamin A metabolism. Compared to control animals, FXR-null mice showed strongly reduced (>90%) hepatic levels of retinol and retinyl palmitate and a significant reduction in lecithin retinol acyltransferase (LRAT), the enzyme responsible for hepatic vitamin A storage. Hepatic reintroduction of FXR in FXR-null mice induced vitamin A storage in the liver. Hepatic vitamin A levels were normal in intestine-specific FXR-null mice. Obeticholic acid (OCA, 3 weeks) treatment rapidly reduced (>60%) hepatic retinyl palmitate levels in mice, concurrent with strongly increased retinol levels (>5-fold). Similar, but milder effects were observed in cholic acid (12 weeks)-treated mice. OCA did not change hepatic LRAT protein levels, but strongly reduced all enzymes involved in hepatic retinyl ester hydrolysis, involving mostly post-transcriptional mechanisms. In conclusion, vitamin A metabolism in the mouse liver heavily depends on the FXR and FXR-targeted therapies may be prone to cause vitamin A-related pathologies.
Interactions between earliest Linearbandkeramik farmers and central European hunter gatherers at the dawn of European Neolithization
Authors: Nikitin Alexey G. , Stadler Peter , Kotova Nadezhda , Teschler-Nicola Maria , Price T. Douglas , Hoover Jessica , Kennett Douglas J. , Lazaridis Iosif , Rohland Nadin , Lipson Mark , Reich David 
Published: December 2019

AbstractArchaeogenetic research over the last decade has demonstrated that European Neolithic farmers (ENFs) were descended primarily from Anatolian Neolithic farmers (ANFs). ENFs, including early Neolithic central European Linearbandkeramik (LBK) farming communities, also harbored ancestry from European Mesolithic hunter gatherers (WHGs) to varying extents, reflecting admixture between ENFs and WHGs. However, the timing and other details of this process are still imperfectly understood. In this report, we provide a bioarchaeological analysis of three individuals interred at the Brunn 2 site of the Brunn am Gebirge-Wolfholz archeological complex, one of the oldest LBK sites in central Europe. Two of the individuals had a mixture of WHG-related and ANF-related ancestry, one of them with approximately 50% of each, while the third individual had approximately all ANF-related ancestry. Stable carbon and nitrogen isotope ratios for all three individuals were within the range of variation reflecting diets of other Neolithic agrarian populations. Strontium isotope analysis revealed that the ~50% WHG-ANF individual was non-local to the Brunn 2 area. Overall, our data indicate interbreeding between incoming farmers, whose ancestors ultimately came from western Anatolia, and local HGs, starting within the first few generations of the arrival of the former in central Europe, as well as highlighting the integrative nature and composition of the early LBK communities.
Transcriptome analysis-identified long noncoding RNA CRNDE in maintaining endothelial cell proliferation, migration, and tube formation
Authors: Moran Matthew , Cheng Xiao , Shihabudeen Haider Ali Mohamed Sham , Wase Nishikant , Nguyen Nghi , Yang Weilong , Zhang Chi , DiRusso Concetta , Sun Xinghui 
Published: December 2019

AbstractObesity is a leading risk factor for type-2 diabetes. Diabetes often leads to the dysregulation of angiogenesis, although the mechanism is not fully understood. Previously, long noncoding RNAs (lncRNAs) have been found to modulate angiogenesis. In this study, we asked how the expression levels of lncRNAs change in endothelial cells in response to excessive palmitic acid treatment, an obesity-like condition. Bioinformatics analysis revealed that 305 protein-coding transcripts were upregulated and 70 were downregulated, while 64 lncRNAs were upregulated and 46 were downregulated. Gene ontology and pathway analysis identified endoplasmic reticulum stress, HIF-1 signaling, and Toll-like receptor signaling as enriched after palmitic acid treatment. Moreover, we newly report enrichment of AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling, and cysteine and methionine metabolism by palmitic acid. One lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE), was selected for further investigation. Palmitic acid induces CRNDE expression by 1.9-fold. We observed that CRNDE knockdown decreases endothelial cell proliferation, migration, and capillary tube formation. These decreases are synergistic under palmitic acid stress. These data demonstrated that lncRNA CRNDE is a regulator of endothelial cell proliferation, migration, and tube formation in response to palmitic acid, and a potential target for therapies treating the complications of obesity-induced diabetes.
Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis
Authors: Asakawa Masahiro , Itoh Michiko , Suganami Takayoshi , Sakai Takeru , Kanai Sayaka , Shirakawa Ibuki , Yuan Xunmei , Hatayama Tomomi , Shimada Shu , Akiyama Yoshimitsu , Fujiu Katsuhito , Inagaki Yutaka , Manabe Ichiro , Yamaoka Shoji , Yamada Tetsuya , Tanaka Shinji , Ogawa Yoshihiro 
Published: December 2019

AbstractNon-alcoholic steatohepatitis (NASH), characterized by chronic inflammation and fibrosis, is predicted to be the leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the next decade. Although recent evidence suggests the importance of fibrosis as the strongest determinant of HCC development, the molecular mechanisms underlying NASH-induced carcinogenesis still remain unclear. Here we performed RNA sequencing analysis to compare gene expression profiles of activated fibroblasts prepared from two distinct liver fibrosis models: carbon tetrachloride–induced fibrosis as a model without obesity and HCC and genetically obese melanocortin 4 receptor–deficient (MC4R-KO) mice fed Western diet, which develop steatosis, NASH, and eventually HCC. Our data showed that activated fibroblasts exhibited distinct gene expression patterns in each etiology, and that the ‘pathways in cancer’ were selectively upregulated in the activated fibroblasts from MC4R-KO mice. The most upregulated gene in these pathways was fibroblast growth factor 9 (FGF9), which was induced by metabolic stress such as palmitate. FGF9 exerted anti-apoptotic and pro-migratory effects in fibroblasts and hepatoma cells in vitro and accelerated tumor growth in a subcutaneous xenograft model. This study reveals upregulation of cancer-associated gene expression in activated fibroblasts in NASH, which would contribute to the progression from NASH to HCC.
Sighting acute myocardial infarction through platelet gene expression
Authors: Gobbi Giuliana , Carubbi Cecilia , Tagliazucchi Guidantonio Malagoli , Masselli Elena , Mirandola Prisco , Pigazzani Filippo , Crocamo Antonio , Notarangelo Maria Francesca , Suma Sergio , Paraboschi Elvezia , Maglietta Giuseppe , Nagalla Srikanth , Pozzi Giulia , Galli Daniela , Vaccarezza Mauro , Fortina Paolo , Addya Sankar , Ertel Adam , Bray Paul , Duga Stefano , Berzuini Carlo , Vitale Marco , Ardissino Diego 
Published: December 2019

AbstractAcute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs.
Period doubling as an indicator for ecosystem sensitivity to climate extremes
Authors: Tzuk Omer , Ujjwal Sangeeta Rani , Fernandez-Oto Cristian , Seifan Merav , Meron Ehud 
Published: December 2019

AbstractThe predictions for a warmer and drier climate and for increased likelihood of climate extremes raise high concerns about the possible collapse of dryland ecosystems, and about the formation of new drylands where native species are less tolerant to water stress. Using a dryland-vegetation model for plant species that display different tradeoffs between fast growth and tolerance to droughts, we find that ecosystems subjected to strong seasonal variability, typical for drylands, exhibit a temporal period-doubling route to chaos that results in early collapse to bare soil. We further find that fast-growing plants go through period doubling sooner and span wider chaotic ranges than stress-tolerant plants. We propose the detection of period-doubling signatures in power spectra as early indicators of ecosystem collapse that outperform existing indicators in their ability to warn against climate extremes and capture the heightened vulnerability of newly-formed drylands. The proposed indicator is expected to apply to other types of ecosystems, such as consumer–resource and predator–prey systems. We conclude by delineating the conditions ecosystems should meet in order for the proposed indicator to apply.
Metal-organic Framework-driven Porous Cobalt Disulfide Nanoparticles Fabricated by Gaseous Sulfurization as Bifunctional Electrocatalysts for Overall Water Splitting
Authors: Ahn In-Kyoung , Joo Wonhyo , Lee Ji-Hoon , Kim Hyoung Gyun , Lee So-Yeon , Jung Youngran , Kim Ji-Yong , Lee Gi-Baek , Kim Miyoung , Joo Young-Chang 
Published: December 2019

AbstractBoth high activity and mass production potential are important for bifunctional electrocatalysts for overall water splitting. Catalytic activity enhancement was demonstrated through the formation of CoS2 nanoparticles with mono-phase and extremely porous structures. To fabricate porous structures at the nanometer scale, Co-based metal-organic frameworks (MOFs), namely a cobalt Prussian blue analogue (Co-PBA, Co3[Co(CN)6]2), was used as a porous template for the CoS2. Then, controlled sulfurization annealing converted the Co-PBA to mono-phase CoS2 nanoparticles with ~ 4 nm pores, resulting in a large surface area of 915.6 m2 g−1. The electrocatalysts had high activity for overall water splitting, and the overpotentials of the oxygen evolution reaction and hydrogen evolution reaction under the operating conditions were 298 mV and −196 mV, respectively, at 10 mA cm−2.
Impact of interseismic deformation on phase transformations and rock properties in subduction zones
Authors: Cionoiu Sebastian , Moulas Evangelos , Tajčmanová Lucie 
Published: December 2019

AbstractPhase transformations greatly affect physical properties of rocks and impose a first-order control on geodynamic processes. Under high deformation rates, rheological heterogeneities cause large spatial variations of stress in materials. Until now, the impact of higher deformation rates, rock heterogeneity and stress build up on phase transformations and material properties is not well understood. Here we show, that phase transitions are controlled by the stress build-up during fast deformation. In a deformation experiment (600 °C, 1.47 GPa), rock heterogeneity was simulated by a strong elliptical alumina inclusion in a weak calcite matrix. Under deformation rates comparable to slow earthquakes, calcite transformed locally to aragonite matching the distribution of maximum principal stresses and pressure (mean stress) from mechanical models. This first systematic investigation documents that phase transformations occur in a dynamic system during deformation. The ability of rocks to react during fast deformation rates may have serious consequences on rock rheology and thus provide unique information on the processes leading to giant ruptures in subduction zones.
Conversion of methane to benzene in CVI by density functional theory study
Authors: Li Kun , Li Hejun , Yan Ningning , Wang Tiyuan , Li Wei , Song Qiang 
Published: December 2019

AbstractA density functional theory (DFT) study was employed to explore the mechanism of the conversion of methane to benzene in chemical vapor infiltration (CVI) based on the concluded reaction pathways from C1-species to C6-species. The geometry optimization and vibrational frequency analysis of all the chemical species and transition states (TS) were performed with B3LYP along with a basis set of 6–311 +G(d, p), and Gaussian 09 software was used to perform the study. The rate constants were calculated by KiSThelP according to the conventional transition state theory (TST), and the Wigner method was applied to acquire the tunneling correction factors. Then the rate constants were fitted to the modified Arrhenius expression in the temperature range of 800–2000 K. As for the barrierless reactions calculated in this paper, the rate constants were selected from the relating references. Through the energetic and kinetic calculations, the most favorable reaction pathway for benzene formation from methane was determined, which were mainly made of the unimolecular dissociation. The conversion trend from C1-species to C4-species is mainly guided by a strong tendency to dehydrogenation and the pathways from C4-species to C6-species are all presumed to be able to produce C6H6 molecule.
The Los Angeles Diversity Project: The Promotion of Cultural and Linguistic Competence via a University Community Learning Project
Authors: Greene Kai , Simon-Cereijido Gabriela 
Published: December 2019

Purpose
Community learning projects provide opportunities for students to become actively engaged in an educational process that extends beyond the classroom. The Los Angeles Diversity Project stems from a campus-based service learning program for undergraduate students enrolled in the Communication Disorders Program at California State University, Los Angeles. Although developed to specifically explore the cultural–linguistic diversity encountered in the Los Angeles metropolitan area, this project can be generalized to other large or small cities and urban or rural communities.

Conclusions
As a class assignment embedded in a requisite course on cultural and linguistic diversity and communication disorders, students learn how to develop an understanding of cultural competency skills applicable to our field. Furthermore, students find out how to integrate basic tenets of ethnographic research while exploring surrounding neighborhoods and local community resources. Additionally, implications aligned with the American Speech-Language-Hearing Association's cultural and linguistic competency requirements are addressed.
On‐board electric vehicle battery charger with improved power quality and reduced switching stress
Authors: Gupta Jyoti , Maurya Rakesh , Arya Sabha Raj 
Published: December 2019

Development of charging infrastructure is one of the key factors for the successful operation of electric vehicles. This study proposes a power converter for on‐board electric vehicle battery charger suitable with universal input voltage (85–265 V). The proposed converter is able to make better power quality by the reduction in total harmonic distortion (THD) of supply current, power factor correction and accurate output voltage regulation. System configuration includes diode bridge rectifier followed by three‐level DC–DC SEPIC converter which emphasises on the reduction of voltage stress and switching loss across switches, thereby reduces the switch rating and improves the overall efficiency of the converter. The converter employs a duty cycle feed‐forward controller scheme for charging the battery at constant voltage (CV) and constant current (CC) mode. Incorporating the above‐said controller scheme has benefits of low THD in supply current, make power factor unity and nearly no zero‐crossing detection. The proposed power factor correction converter system analysis is executed in continuous conduction mode. The system performance is evaluated with 400 V, 48 AH battery charging under CV and CC mode through MATLAB/Simulink and experimentation. To estimate the features of power quality indices like power factor and THD is recorded under the wide range of supply variations.
A solar filament disconnected by magnetic reconnection
Authors: Xue Zhike , Yan Xiaoli , Yang Liheng , Wang Jincheng , Li Qiaoling , Zhao Li 
Published: December 2019

Aims. We aim to study a high-resolution observation of an asymmetric inflow magnetic reconnection between a filament and its surrounding magnetic loops in active region NOAA 12436 on 2015 October 23.
Methods. We analyzed the multiband observations of the magnetic reconnection obtained by the New Vacuum Solar Telescope (NVST) and the Solar Dynamic Observatory. We calculated the NVST Hα Dopplergrams to determine the Doppler properties of the magnetic reconnection region and the rotation of a jet.
Results. The filament firstly becomes active and then approaches its southwestern surrounding magnetic loops (L1) with a velocity of 9.0 km s−1. During this period, the threads of the filament become loose in the reconnection region and then reconnect with L1 in turn. L1 is pressed backward by the filament with a velocity of 5.5 km s−1, and then the magnetic reconnection occurs between them. A set of newly formed loops are separated from the reconnection site with a mean velocity of 127.3 km s−1. In the middle stage, some threads of the filament return back first with a velocity of 20.1 km s−1, and others return with a velocity of 4.1 km s−1 after about 07:46 UT. Then, L1 also begins to return with a velocity of 3.5 km s−1 at about 07:47 UT. At the same time, magnetic reconnection continues to occur between them until 07:51 UT. During the reconnection, a linear typical current sheet forms with a length of 5.5 Mm and a width of 1.0 Mm, and a lot of hot plasma blobs are observed propagating from the typical current sheet. During the reconnection, the plasma in the reconnection region and the typical current sheet always shows redshifted feature. Furthermore, the material and twist of the filament are injected into the newly longer-formed magnetic loops by the magnetic reconnection, which leads to the formation of a jet, and its rotation.
Conclusions. The observational evidence for the asymmetric inflow magnetic reconnection is investigated. We conclude that the magnetic reconnection does occur in this event and results in the disconnection of the filament. The looseness of the filament may be due to the pressure imbalance between the inside and outside of the filament. The redshifted feature in the reconnection site can be explained by the expansion of the right flank of the filament to the lower atmosphere because of the complex magnetic configuration in this active region.