bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal cancer cells respond differentially to autophagy inhibition in vivo
Authors: Lauzier Annie , Normandeau-Guimond Josiann , Vaillancourt-Lavigueur Vanessa , Boivin Vincent , Charbonneau Martine , Rivard Nathalie , Scott Michelle S. , Dubois Claire M. , Jean Steve 
Published: August 2019

AbstractAutophagy has both tumor-promoting and -suppressing effects in cancer, including colorectal cancer (CRC), with transformed cells often exhibiting high autophagic flux. In established tumors, autophagy inhibition can lead to opposite responses resulting in either tumor cell death or hyperproliferation. The functional mechanisms underlying these differences are poorly understood. The present study aimed to investigate the relationship between the autophagic capacities of CRC cells and their sensitivities to autophagy inhibition. All studied CRC cell lines showed high basal autophagic flux. However, only HCT116 and Caco-2/15 cells displayed regulated autophagic flux upon starvation. Knockdown of ATG5 (which disrupts autophagosome elongation) or RAB21 (which decreases autophagosome/lysosome fusion) had little effect on CRC cell proliferation in vitro. Nonetheless, inhibition of autophagy in vivo had a substantial cell line-dependent impact on tumor growth, with some cells displaying decreased (HCT116 and Caco-2/15) or increased (SW480 and LoVo) proliferation. RNA sequencing and Western blot analyses in hyperproliferative SW480 tumors revealed that the mTORC2 and AKT pathways were hyperactivated following autophagy impairment. Inhibition of either mTOR or AKT activities rescued the observed hyperproliferation in autophagy-inhibited SW480 and reduced tumor growth. These results highlight that autophagy inhibition can lead, in specific cellular contexts, to compensatory mechanisms promoting tumor growth.
A comparative study of curated contents by knowledge-based curation system in cancer clinical sequencing
Authors: Sakai Kazuko , Takeda Masayuki , Shimizu Shigeki , Takahama Takayuki , Yoshida Takeshi , Watanabe Satomi , Iwasa Tsutomu , Yonesaka Kimio , Suzuki Shinichiro , Hayashi Hidetoshi , Kawakami Hisato , Nonagase Yoshikane , Tanaka Kaoru , Tsurutani Junji , Saigoh Kazumasa , Ito Akihiko , Mitsudomi Tetsuya , Nakagawa Kazuhiko , Nishio Kazuto 
Published: August 2019

AbstractMedical oncologists are challenged to personalize medicine with scientific evidence, drug approvals, and treatment guidelines based on sequencing of clinical samples using next generation sequencer (NGS). Knowledge-based curation systems have the potential to help address this challenge. We report here the results of examining the level of evidence regarding treatment approval and clinical trials between recommendations made by Watson for Genomics (WfG), QIAGEN Clinical Insight Interpret (QCII), and Oncomine knowledge-based reporter (OKR). The tumor samples obtained from the solid cancer patients between May to June 2018 at Kindai University Hospital. The formalin-fixed paraffin-embedded tumor samples (n = 31) were sequenced using Oncomine Comprehensive Assay v3. Variants including copy number alteration and gene fusions identified by the Ion reporter software were used commonly on three curation systems. Curation process of data were provided for 25 solid cancers using three curation systems independently. Concordance and distribution of curated evidence levels of variants were analyzed. As a result of sequencing analysis, nonsynonymous mutation (n = 58), gene fusion (n = 2) or copy number variants (n = 12) were detected in 25 cases, and subsequently subjected to knowledge-based curation systems (WfG, OKR, and QCII). The number of curated information in any systems was 51/72 variants. Concordance of evidence levels was 65.3% between WfG and OKR, 56.9% between WfG and QCII, and 66.7% between OKR and QCII. WfG provided great number of clinical trials for the variants. The annotation of resistance information was also observed. Larger differences were observed in clinical trial matching which could be due to differences in the filtering process among three curation systems. This study demonstrates knowledge-based curation systems (WfG, OKR, and QCII) could be helpful tool for solid cancer treatment decision making. Difference in non-concordant evidence levels was observed between three curation systems, especially in the information of clinical trials. This point will be improved by standardized filtering procedure and enriched database of clinical trials in Japan.
Seismic loading of fault-controlled fluid seepage systems by great subduction earthquakes
Authors: Bonini Marco 
Published: August 2019

AbstractVarious types of fluid expulsion features (mud volcanoes, pockmarks, authigenic carbonate mounds and associated gas pipes, etc.) are often found above subduction zones, which have the highest seismic potential on Earth. Faults potentially control the liberation of deep-seated greenhouse gases into the feeder systems of seepage features located above subduction thrusts. These feeder systems could be stressed by large earthquakes, yet the mechanisms that can drive episodic mobilization of stored hydrocarbon gases remain poorly understood. Here I address the potential stress loading on fluid expulsion systems created by past earthquakes nucleated at both accretionary and erosive subduction margins. The most significant effects occur in the epicentral area where subduction earthquakes can produce normal stress changes as high as 20–100 bar, although these are generally restricted to relatively small regions. Coseismic normal stress changes and elastic strain relaxation upon a ruptured subduction thrust could increase crustal permeability by dilating fault-controlled conduits, and channelling fluids to the seafloor. Fluid pressure pulses released during subduction earthquakes can greatly contribute to the rupture of fluid pathways that have been brought closer to failure from coseismic static stress changes, although the inaccessible location of most submarine seepage systems has so far hampered probing these relationships.
Unnatural spirocyclic oxindole alkaloids biosynthesis in Uncaria guianensis
Authors: Lopes Adriana A. , Chioca Bianca , Musquiari Bruno , Crevelin Eduardo J. , França Suzelei de C. , Fernandes da Silva Maria Fatima das G. , Pereira Ana Maria S. 
Published: August 2019

AbstractSpiro-oxindole scaffolds have been studied due to their promising therapeutic potential. In the Amazon rainforest there are two important Uncaria species known as “cat’s claw”, which biosynthesize spirocyclic oxindole alkaloids; Uncaria tomentosa (Willd. ex Schult.) DC. and Uncaria guianensis (Aublet) Gmell. We carried out a precursor-directed biosynthesis approach with U. guianensis and successfully obtained oxindole alkaloid analogues with molecular mass corresponding to the addition of a methyl or fluorine group on the oxindole ring using tryptamine analogue precursors. Two of these novel oxindole alkaloid analogues (3b-7-methyl-isomitraphylline and 3c-6-fluoro-isomitraphylline) were isolated and characterized by NMR spectroscopy and ESI-QTOF-MS/MS. Having established a substrate feeding protocol for these plantlets, the biosynthetic route for mitraphylline (1), rhynchophylline (2), isomitraphylline (3) and isorhynchophylline (4) was also investigated using 13C-precursors (1-13C-D-glucose, 2-13C-tryptophan, 1-13C-DL-glyceraldehyde, and methyl-13C-D-methionine).
Niclosamide reverses adipocyte induced epithelial-mesenchymal transition in breast cancer cells via suppression of the interleukin-6/STAT3 signalling axis
Authors: Gyamfi Jones , Lee Yun-Hee , Min Byung Soh , Choi Junjeong 
Published: August 2019

AbstractThe microenvironment of breast cancer comprises predominantly of adipocytes. Adipocytes drive cancer progression through the secretion adipocytokines. Adipocytes induce epithelial mesenchymal transition of breast cancer cells through paracrine IL-6/Stat3 signalling. Treatment approaches that can target adipocytes in the microenvironment and abrogate paracrine signals that drive breast cancer growth and metastasis are urgently needed. Repositioning of old drugs has become an effective approach for discovering new cancer drugs. In this study, niclosamide, an FDA approved anthelminthic drug was evaluated for its anti-breast cancer activity and its ability to inhibit adipocytes induced EMT. Niclosamide potently inhibited proliferation, migration and invasion at low concentration and induced significant apoptosis at high concentrations in human breast cancer cell lines MDA-MB-468 and MCF-7. Additionally, niclosamide reversed adipocyte-induced EMT with a correlated inhibition of IL-6/Stat3 activation and downregulation of EMT-TFs TWIST and SNAIL. Moreover, niclosamide markedly impaired MDA-MB-468 and MCF-7 migration and invasion. We further found that the inhibitory effects of niclosamide on MDA-MB-468 and MCF-7 motility was closely related to destabilization of focal adhesion complex formation. With decreased co-localization of focal adhesion kinase (FAK) and phosphorylated paxillin (pPAX). Collectively, these results demonstrate that niclosamide could be used to inhibit adipocyte-induced breast cancer growth and metastasis.
Association between grandparent co-residence, socioeconomic status and dental caries among early school-aged children in Japan: A population-based prospective study
Authors: Morita Ayako , Matsuyama Yusuke , Isumi Aya , Doi Satomi , Ochi Manami , Fujiwara Takeo 
Published: August 2019

AbstractGlobally many children are living with grandparents, and it has been suggested that grandparent co-residence may be associated with dental caries in infants and toddlers possibly through passive parenting style, accompanied by children’s cariogenic behaviors such as feeding sugary sweets. However, little is known about this association in schoolchildren, adjusted for socioeconomic status. Therefore, this study investigates the association between grandparent co-residence, socioeconomic status, and dental caries among schoolchildren. All caregivers of first-grade children (age 6–7 years) in Adachi City, Tokyo, were administered a questionnaire about children’s grandparent co-residence status and oral health-related behaviors, and responses were linked with dental examination records conducted by school dentists (N = 3,578). Multilevel Poisson regression analysis was applied to examine the association between grandparent co-residence, socioeconomic status, and dental caries status for each individual tooth, adjusting for potential covariates. The percentage of dental caries experience was higher among children living with grandparents (48.9%) than among children living without grandparents (44.0%). The risk for caries, however, did not differ according to grandparent co-residence status when tooth type, child’s age and sex, and parental socio-economic status and structure were adjusted (PR, 1.13; 95%CI, 0.90, 1.42). The association between grandparent co-residence and dental caries among early school-aged children in urban Japan was confounded by socioeconomic status.
The association between frailty and MRI features of cerebral small vessel disease
Authors: Kant Ilse M. J. , Mutsaerts Henri J. M. M. , van Montfort Simone J. T. , Jaarsma-Coes Myriam G. , Witkamp Theodoor D. , Winterer Georg , Spies Claudia D. , Hendrikse Jeroen , Slooter Arjen J. C. , de Bresser Jeroen ,   BioCog Consortium, Armbruster Franz Paul , Böcher Axel , Boraschi Diana , Borchers Friedrich , Della Camera Giacomo , van Dellen Edwin , Diehl Ina , Dschietzig Thomas Bernd , Feinkohl Insa , Fillmer Ariane , Gallinat Jürgen , Hafen Bettina , Hartmann Katarina , Heidtke Karsten , Helmschrodt Anja , Italiani Paola , Ittermann Bernd , Krause Roland , Kronabel Marion , Kühn Simone , Lachmann Gunnar , Melillo Daniela , Menon David K. , Moreno-López Laura , Mörgeli Rudolf , Nürnberg Peter , Ofosu Kwaku , Olbert Maria , Pietzsch Malte , Pischon Tobias , Preller Jacobus , Ruppert Jana , Schneider Reinhard , Stamatakis Emmanuel A. , Weber Simon , Weyer Marius , Winzeck Stefan , Wolf Alissa , Yürek Fatima , Zacharias Norman 
Published: August 2019

AbstractFrailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype.
Defining a Core Genome for the Herpesvirales and Exploring their Evolutionary Relationship with the Caudovirales
Authors: Andrade-Martínez Juan S. , Moreno-Gallego J. Leonardo , Reyes Alejandro 
Published: August 2019

AbstractThe order Herpesvirales encompasses a wide variety of important and broadly distributed human pathogens. During the last decades, similarities in the viral cycle and the structure of some of their proteins with those of the order Caudovirales, the tailed bacterial viruses, have brought speculation regarding the existence of an evolutionary relationship between these clades. To evaluate such hypothesis, we used over 600 Herpesvirales and 2000 Caudovirales complete genomes to search for the presence or absence of clusters of orthologous protein domains and constructed a dendrogram based on their compositional similarities. The results obtained strongly suggest an evolutionary relationship between the two orders. Furthermore, they allowed to propose a core genome for the Herpesvirales, composed of 4 proteins, including the ATPase subunit of the DNA-packaging terminase, the only protein with previously verified conservation. Accordingly, a phylogenetic tree constructed with sequences derived from the clusters associated to these proteins grouped the Herpesvirales strains accordingly to the established families and subfamilies. Overall, this work provides results supporting the hypothesis that the two orders are evolutionarily related and contributes to the understanding of the history of the Herpesvirales.
Neoceroplatus betaryiensis nov. sp. (Diptera: Keroplatidae) is the first record of a bioluminescent fungus-gnat in South America
Authors: Falaschi Rafaela L. , Amaral Danilo T. , Santos Isaias , Domingos Adão H. R. , Johnson Grant A. , Martins Ana G. S. , Viroomal Imran B. , Pompéia Sérgio L. , Mirza Jeremy D. , Oliveira Anderson G. , Bechara Etelvino J. H. , Viviani Vadim R. , Stevani Cassius V. 
Published: August 2019

AbstractBlue shining fungus gnats (Diptera) had been long reported in the Waitomo caves of New Zealand (Arachnocampa luminosaSkuse), in stream banks of the American Appalachian Mountains (Orfelia fultoniFisher) in 1939 and in true spore eating EurasiaticKeroplatusBosc species. This current report observes that similar blue light emitting gnat larvae also occur nearby the Betary river in the buffer zone of High Ribeira River State Park (PETAR) in the Atlantic Forest of Brazil, where the larvae were found when on fallen branches or trunks enveloped in their own secreted silk. The new species is namedNeoceroplatus betaryiensisnov. sp. (Diptera: Keroplatidae: Keroplatinae: Keroplatini) based on a morphological analysis.Neoceroplatus betaryiensisnov. sp. larvae emit blue bioluminescence that can be seen from their last abdominal segment and from two photophores located laterally on the first thoracic segment. When touched, the larvae can actively stop its luminescence, which returns when it is no longer being agitated. Thein vitrobioluminescence spectrum ofN.betaryiensisnov. sp. peaks at 472 nm, and cross-reactivity of hot and cold extracts with the luciferin-luciferase fromOrfelia fultoniindicate significant similarity in both enzyme and substrate of the two species, and that the bioluminescence system in the subfamily Keroplatinae is conserved.
Salivary glands require Aurora Kinase B for regeneration after transient innate immune-mediated injury
Authors: Shaalan Abeer , Proctor Gordon 
Published: August 2019

AbstractSevere, irreversible salivary gland disease and oral dryness is experienced by sufferers of Sjögren’s syndrome and those treated with irradiation for head and neck cancer. Therefore, major efforts have been made in the last decade to unravel key molecular signals that can drive salivary gland (SG) regeneration and functional restoration. However, the earliest molecular determinants that accompany SG regeneration remain incompletely defined. The present study examined the initial mitogenic events marking the regenerative response of the murine submandibular gland (SMG), following innate immune-mediated injury. Local intraductal administration of the synthetic double stranded (ds) RNA polyinosinic-polycytidylic acid (poly (I:C)) widely, but transiently, depleted the acinar and progenitor cells, 24 hours post poly (I:C) introduction. While the progenitor and duct cells started to proliferate and expand at 72 hours, the Mist1-positve acinar cells did not re-appear until 96 hours post poly (I:C) injury. The cellular replenishment during regeneration involved significant upregulation of the cell cycle promoter Aurora kinase B (AURKB). AURKB, which is expressed in healthy proliferating and cancerous cells, is a serine/threonine protein kinase, well known to orchestrate key events in cell division and cytokinesis. However, the expression and role of AURKB in regeneration of post mitotic salivary gland cells has not been previously explored. In vivo inhibition of AURKB using the selective inhibitor Barasertib (AZD1152-HQPA) interfered with SMG recovery from the transient, but severe poly (I:C)-mediated injury and cellular depletion. AURKB deficiency during regeneration of the injured tissues: disrupted cell cycle progression, repressed renewal of Mist1-positive acinar cells and prevented recovery of salivary secretion. The knowledge gained in this study may be utilized in the development of therapeutic targets for irreversible salivary gland disease.
Tunable diameter and spacing of double Ge quantum dots using highly-controllable spacers and selective oxidation of SiGe
Authors: Huang Tsung-Lin , Peng Kang-Ping , Chen Ching-Lun , Lin Horng-Chih , George Tom , Li Pei-Wen 
Published: August 2019

AbstractWe report the novel tunability of the diameters and spacings of paired Ge double quantum dots (DQDs) using nano-spacer technology in combination with selective oxidation of Si0.85Ge0.15 at high temperature. Pairs of spherical-shaped Ge QDs were formed by the selective oxidation of poly-SiGe spacer islands at each sidewall corner of the nano-patterned Si3N4/poly-Si ridges. The diameters of the Ge spherical QDs are essentially determined by geometrical conditions (height, width, and length) of the nano-patterned spacer islands of poly-SiGe, which are tunable by adjusting the process times of deposition and etch back for poly-SiGe spacer layers in combination with the exposure dose of electron-beam lithography. Most importantly, the separations between the Ge DQDs are controllable by adjusting the widths of the poly-Si/Si3N4 ridges and the thermal oxidation times. Our self-organization and self-alignment approach achieved high symmetry within the Ge DQDs in terms of the individual QD diameters as well as the coupling barriers between the QDs and external electrodes in close proximity.
Influence of Roasting Condition on Flavor Profile of Sunflower Seeds: A flavoromics approach
Authors: Guo Shuangshuang , Na Jom Kriskamol , Ge Yan 
Published: August 2019

AbstractSunflower see/ds (Helianthus annuus L.) were roasted in an electric forced air oven for 15, 30, 45, and 60 min at 125, 135 and 145 °C. The effect of temperature and time on the flavor profile of the samples were evaluated by headspace solid-phase microextraction coupled with gas chromatography-mass spectroscopy (HS-SPME-GC-MS). Unsupervised Principle Component Analysis (PCA) and Agglomerative Hierarchical Clustering (AHC) multivariate statistical methods were used to visualize, group and classify the samples. 114 volatiles were identified in the roasted sunflower seeds (RSF), with terpenes (α-pinene, β-pinene), heterocyclic compounds (2-ethyl-3-methylpyrazine, 2,5-dimethylpyrazine, 2-ethyl-3,5-dimethylpyrazine, pyridine), aldehydes (2-methylbutanal, furfural, hexanal, phenylacetaldehyde), hydrocarbons (octane, 2-isobutyl-1,4-dimethylcyclohexane, 6,6-dimethylundecane), alcohol (3-methyl-2-propyl-1-pentanol), and γ-butyrolactone being dominant compounds. The content of most volatile compounds increased with increase in roasting temperature and time, such as esters, terpenes, pyrazines, aldehydes, ketones, and alcohols. 2,3-dimethylpyrazine, 2,5-dimethylpyrazine, 2-ethyl-3-methylpyrazine, and 2-ethyl-3,5-dimethylpyrazine contributed to be the major role in roast and nutty flavor of the roasted sunflower seeds. Roasting at 125 °C for 45 min was found to be the better condition for roasted sunflower seeds, which gave the lowest off-flavor and burnt tastes.
Fast-switching laterally virtual-moving microlens array for enhancing spatial resolution in light-field imaging system without degradation of angular sampling resolution
Authors: Park Min-Kyu , Park Heewon , Joo Kyung-Il , Lee Tae-Hyun , Kwon Ki-Chul , Erdenebat Munkh-Uchral , Lim Young-Tae , Kim Nam , Kim Hak-Rin 
Published: August 2019

AbstractWe present an electrically controllable fast-switching virtual-moving microlens array (MLA) consisting of a stacked structure of two polarization-dependent microlens arrays (PDMLAs) with optical orthogonality, where the position of the two stacked PDMLAs is shifted by half the elemental pitch in the diagonal direction. By controlling the polarization of the incident light without the physical movement of the molecules comprising the virtual-moving MLA, the periodic sampling position of the MLA can be switched fast using a polarization-switching layer based on a fast-switching liquid crystal cell. Using the fast-switching virtual-moving MLA, the spatial-resolution-enhanced light-field (LF) imaging system was demonstrated without a decrease in the angular sampling resolution as compared to the conventional LF imaging system comprising a passive MLA; two sets of elemental image arrays were captured quickly owing to the short switching time of the virtual-moving MLA of 450 μs. From the two captured sets of the elemental array image, four-times resolution-enhanced reconstruction images of the directional-view and depth-slice images could be obtained.