bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/β-catenin signal pathway in hepatocellular carcinoma
Authors: Wang Yufeng , Sun Liankang , Wang Liang , Liu Zhikui , Li Qing , Yao Bowen , Wang Cong , Chen Tianxiang , Tu Kangsheng , Liu Qingguang 
Published: August 2018

AbstractPrevious evidences reveal that long non-coding RNA (lncRNA) down syndrome critical region 8 (DSCR8) involves in the progression of multiple cancers. However, the exact expression, function, and mechanism of DSCR8 in hepatocellular carcinoma (HCC) remain uncovered. In this study, real-time PCR in HCC tissues and cell lines indicated that DSCR8 expression was upregulated, while miR-485-5p was downregulated. MTT assay, plate clone formation, Edu assay, flow cytometry, and in vivo experiments indicated that DSCR8 promoted HCC cell proliferation and cycle, whereas accelerated cell apoptosis. Luciferase reporter gene assay, RIP assay, and rescue experiments demonstrated that DSCR8 functioned as a competing endogenous RNA (ceRNA) by sponging miR-485-5p in HCC cells. Furthermore, gain- and loss-of-function studies showed that miR-485-5p activated Wnt/β-catenin signal pathway by targeting Frizzled-7 (FZD7). Moreover, DSCR8 activated Wnt/β-catenin signal pathway to promote HCC progression by DSCR8/miR-485-5p/FZD7 axis. Statistical analysis revealed that DSCR8 and miR-485-5p were closely related to some malignant clinicopathological features and 5-year survival rates of HCC patients. Taken together, the present study reports for the first time that DSCR8 activates Wnt/β-catenin signal pathway to promote HCC progression by DSCR8/miR-485-5p/FZD7 axis. The findings provide promising and valuable strategies for targeted therapy of HCC.
JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling
Authors: Wang Yunchuan , Zheng Jianping , Han Yue , Zhang Yijie , Su Linlin , Hu Dahai , Fu Xiaobing 
Published: August 2018

AbstractJunctional adhesion molecule-A (JAM-A) belongs to the immunoglobulin superfamily, it predominantly exists at the tight junctions of epithelial and endothelial cells. JAM-A is known to regulate leukocyte trans-endothelial migration, however, how it affects the proliferation and migration of keratinocytes, the two essential steps during wound healing, has less been explored. In this study, we showed that JAM-A was significantly expressed in normal skin epidermis. RNAi-mediated JAM-A knockdown remarkably promoted the proliferation and migration of keratinocytes. We also found that loss of JAM-A increased the protein levels of p-FAK, p-Erk1/2, and p-JNK; however, FAK inhibitor PF-562271 restrained the expression of p-FAK and p-Erk1/2 elevated by JAM-A RNAi, but not p-JNK, and also slowed down keratinocyte proliferation and migration. Finally, in a rat wound model we showed that absence of JAM-A significantly promoted the wound healing process, while the use of PF-562271 or Erk1/2 inhibitor PD98059 repressed those effects. These data collectively demonstrate that suppressing JAM-A expression could promote the proliferation and migration of keratinocytes and accelerate the healing process of rat skin wounds, potentially via FAK/Erk pathway, indicating that JAM-A might serve as a potential therapeutic target for the treatment of chronic refractory wounds.
Tolerance to sustained activation of the cAMP/Creb pathway activity in osteoblastic cells is enabled by loss of p53
Authors: Walia Mannu K. , Taylor Scott , Ho Patricia W. M. , Martin T. John , Walkley Carl R. 
Published: August 2018

AbstractThe loss of p53 function is a central event in the genesis of osteosarcoma (OS). How mutation of p53 enables OS development from osteoblastic lineage cells is poorly understood. We and others have reported a key role for elevated and persistent activation of the cAMP/PKA/Creb1 pathway in maintenance of OS. In view of the osteoblast lineage being the cell of origin of OS, we sought to determine how these pathways interact within the context of the normal osteoblast. Normal osteoblasts (p53 WT) rapidly underwent apoptosis in response to acute elevation of cAMP levels or activity, whereas p53-deficient osteoblasts tolerated this aberrant cAMP/Creb level and activity. Using the p53 activating small-molecule Nutlin-3a and cAMP/Creb1 activator forskolin, we addressed the question of how p53 responds to the activation of cAMP. We observed that p53 acts dominantly to protect cells from excessive cAMP accumulation. We identify a Creb1-Cbp complex that functions together with and interacts with p53. Finally, translating these results we find that a selective small-molecule inhibitor of the Creb1-Cbp interaction demonstrates selective toxicity to OS cells where this pathway is constitutively active. This highlights the cAMP/Creb axis as a potentially actionable therapeutic vulnerability in p53-deficient tumors such as OS. These results define a mechanism through which p53 protects normal osteoblasts from excessive or abnormal cAMP accumulation, which becomes fundamentally compromised in OS.
Disentangling astroglial physiology with a realistic cell model in silico
Authors: Savtchenko Leonid P. , Bard Lucie , Jensen Thomas P. , Reynolds James P. , Kraev Igor , Medvedev Nikolay , Stewart Michael G. , Henneberger Christian , Rusakov Dmitri A. 
Published: August 2018

AbstractElectrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+and generate Ca2+signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+hotspots. We show how intracellular Ca2+buffers affect Ca2+waves and why the classical Ca2+sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+imaging.
Inducing drop to bubble transformation via resonance in ultrasound
Authors: Zang Duyang , Li Lin , Di Wenli , Zhang Zehui , Ding Changlin , Chen Zhen , Shen Wei , Binks Bernard P. , Geng Xingguo 
Published: August 2018

AbstractBubble formation plays an important role in industries concerned with mineral flotation, food, cosmetics, and materials, which requires additional energy to produce the liquid–gas interfaces. A naturally observed fact is, owing to the effect of surface tension, a bubble film tends to retract to reduce its surface area. Here we show a “reverse” phenomenon whereby a drop is transformed into a bubble using acoustic levitation via acoustic resonance. Once the volume of the cavity encapsulated by the buckled film reaches a critical value V*, resonance occurs and an abrupt inflation is triggered, leading to the formation of a closed bubble. Experiments and simulations both reveal that V* decreases with increasing acoustic frequency, which agrees well with acoustic resonance theory. The results afford enlightening insights into acoustic resonance and highlight its role in manipulating buckled fluid–fluid interfaces, providing a reference for fabricating unique core–shell-like materials.
Single reach plans in dorsal premotor cortex during a two-target task
Authors: Dekleva Brian M. , Kording Konrad P. , Miller Lee E. 
Published: August 2018

AbstractIn many situations, we are faced with multiple potential actions, but must wait for more information before knowing which to perform. Movement scientists have long asked whether in these delayed-response situations the brain plans both potential movements simultaneously, or if it simply chooses one and then switches later if necessary. To answer this question, we used simultaneously recorded activity from populations of neurons in macaque dorsal premotor cortex to track moment-by-moment deliberation between two potential reach targets. We found that the neural activity only ever indicated a single-reach plan (with some targets favored more than others), and that initial plans often predicted the monkeys’ behavior on both Free-Choice trials and incorrect Cued trials. Our results suggest that premotor cortex plans only one option at a time, and that decisions are strongly influenced by the initial response to the available set of movement options.
Dynamic earthquake rupture preserved in a creeping serpentinite shear zone
Authors: Tarling Matthew S. , Smith Steven A. F. , Viti Cecilia , Scott James M. 
Published: August 2018

AbstractLaboratory experiments on serpentinite suggest that extreme dynamic weakening at earthquake slip rates is accompanied by amorphisation, dehydration and possible melting. However, hypotheses arising from experiments remain untested in nature, because earthquake ruptures have not previously been recognised in serpentinite shear zones. Here we document the progressive formation of high-temperature reaction products that formed by coseismic amorphisation and dehydration in a plate boundary-scale serpentinite shear zone. The highest-temperature products are aggregates of nanocrystalline olivine and enstatite, indicating minimum peak coseismic temperatures of ca. 925 ± 60 °C. Modelling suggests that frictional heating during earthquakes of magnitude 2.7–4 can satisfy the petrological constraints on the coseismic temperature profile, assuming that coseismic fluid storage capacity and permeability are increased by the development of reaction-enhanced porosity. Our results indicate that earthquake ruptures can propagate through serpentinite shear zones, and that the signatures of transient frictional heating can be preserved in the fault rock record.
Ap4 is rate limiting for intestinal tumor formation by controlling the homeostasis of intestinal stem cells
Authors: Jaeckel Stephanie , Kaller Markus , Jackstadt Rene , Götz Ursula , Müller Susanna , Boos Sophie , Horst David , Jung Peter , Hermeking Heiko 
Published: August 2018

AbstractThe gene encoding the transcription factor TFAP4/AP4 represents a direct target of the c-MYC oncoprotein. Here, we deleted Ap4 in ApcMin mice, a preclinical model of inherited colorectal cancer. Ap4 deficiency extends their average survival by 110 days and decreases the formation of intestinal adenomas and tumor-derived organoids. The effects of Ap4 deletion are presumably due to the reduced number of functional intestinal stem cells (ISCs) amenable to adenoma-initiating mutational events. Deletion of Ap4 also decreases the number of colonic stem cells and increases the number of Paneth cells. Expression profiling revealed that ISC signatures, as well as the Wnt/β-catenin and Notch signaling pathways are downregulated in Ap4-deficient adenomas and intestinal organoids. AP4-associated signatures are conserved between murine adenomas and human colorectal cancer samples. Our results establish Ap4 as rate-limiting mediator of adenoma initiation, as well as regulator of intestinal and colonic stem cell and Paneth cell homeostasis.
The mitotic spindle is chiral due to torques within microtubule bundles
Authors: Novak Maja , Polak Bruno , Simunić Juraj , Boban Zvonimir , Kuzmić Barbara , Thomae Andreas W. , Tolić Iva M. , Pavin Nenad 
Published: August 2018

AbstractMitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins. Forces are required for the congression of chromosomes to the metaphase plate and their separation in anaphase. However, besides forces, torques may exist in the spindle, yet they have not been investigated. Here we show that the spindle is chiral. Chirality is evident from the finding that microtubule bundles in human spindles follow a left-handed helical path, which cannot be explained by forces but rather by torques. Kinesin-5 (Kif11/Eg5) inactivation abolishes spindle chirality. Our theoretical model predicts that bending and twisting moments may generate curved shapes of bundles. We found that bundles turn by about −2 deg µm−1 around the spindle axis, which we explain by a twisting moment of roughly −10 pNµm. We conclude that torques, in addition to forces, exist in the spindle and determine its chiral architecture.
A hexagon in Saturn’s northern stratosphere surrounding the emerging summertime polar vortex
Authors: Fletcher L. N. , Orton G. S. , Sinclair J. A. , Guerlet S. , Read P. L. , Antuñano A. , Achterberg R. K. , Flasar F. M. , Irwin P. G. J. , Bjoraker G. L. , Hurley J. , Hesman B. E. , Segura M. , Gorius N. , Mamoutkine A. , Calcutt S. B. 
Published: August 2018

AbstractSaturn’s polar stratosphere exhibits the seasonal growth and dissipation of broad, warm vortices poleward of ~75° latitude, which are strongest in the summer and absent in winter. The longevity of the exploration of the Saturn system by Cassini allows the use of infrared spectroscopy to trace the formation of the North Polar Stratospheric Vortex (NPSV), a region of enhanced temperatures and elevated hydrocarbon abundances at millibar pressures. We constrain the timescales of stratospheric vortex formation and dissipation in both hemispheres. Although the NPSV formed during late northern spring, by the end of Cassini’s reconnaissance (shortly after northern summer solstice), it still did not display the contrasts in temperature and composition that were evident at the south pole during southern summer. The newly formed NPSV was bounded by a strengthening stratospheric thermal gradient near 78°N. The emergent boundary was hexagonal, suggesting that the Rossby wave responsible for Saturn’s long-lived polar hexagon—which was previously expected to be trapped in the troposphere—can influence the stratospheric temperatures some 300 km above Saturn’s clouds.
Understanding 6th-century barbarian social organization and migration through paleogenomics
Authors: Amorim Carlos Eduardo G. , Vai Stefania , Posth Cosimo , Modi Alessandra , Koncz István , Hakenbeck Susanne , La Rocca Maria Cristina , Mende Balazs , Bobo Dean , Pohl Walter , Baricco Luisella Pejrani , Bedini Elena , Francalacci Paolo , Giostra Caterina , Vida Tivadar , Winger Daniel , von Freeden Uta , Ghirotto Silvia , Lari Martina , Barbujani Guido , Krause Johannes , Caramelli David , Geary Patrick J. , Veeramah Krishna R. 
Published: August 2018

AbstractDespite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data are consistent with the proposed long-distance migration from Pannonia to Northern Italy.
Comparing frontal eye field and superior colliculus contributions to covert spatial attention
Authors: Bollimunta Anil , Bogadhi Amarender R. , Krauzlis Richard J. 
Published: August 2018

AbstractThe causal roles of the frontal eye fields (FEF) and superior colliculus (SC) in spatial selective attention have not been directly compared. Reversible inactivation is an established method for testing causality but comparing results between FEF and SC is complicated by differences in size and morphology of the two brain regions. Here we exploited the fact that inactivation of FEF and SC also changes the metrics of saccadic eye movements, providing an independent benchmark for the strength of the causal manipulation. Using monkeys trained to covertly perform a visual motion-change detection task, we found that inactivation of either FEF or SC could cause deficits in attention task performance. However, SC-induced attention deficits were found with saccade changes half the size needed to get FEF-induced attention deficits. Thus, performance in visual attention tasks is vulnerable to loss of signals from either structure, but suppression of SC activity has a more devastating effect.
Image analysis with deep learning to predict breast cancer grade, ER status, histologic subtype, and intrinsic subtype
Authors: Couture Heather D. , Williams Lindsay A. , Geradts Joseph , Nyante Sarah J. , Butler Ebonee N. , Marron J. S. , Perou Charles M. , Troester Melissa A. , Niethammer Marc 
Published: August 2018

AbstractRNA-based, multi-gene molecular assays are available and widely used for patients with ER-positive/HER2-negative breast cancers. However, RNA-based genomic tests can be costly and are not available in many countries. Methods for inferring molecular subtype from histologic images may identify patients most likely to benefit from further genomic testing. To identify patients who could benefit from molecular testing based on H&E stained histologic images, we developed an image analysis approach using deep learning. A training set of 571 breast tumors was used to create image-based classifiers for tumor grade, ER status, PAM50 intrinsic subtype, histologic subtype, and risk of recurrence score (ROR-PT). The resulting classifiers were applied to an independent test set (n = 288), and accuracy, sensitivity, and specificity of each was assessed on the test set. Histologic image analysis with deep learning distinguished low-intermediate vs. high tumor grade (82% accuracy), ER status (84% accuracy), Basal-like vs. non-Basal-like (77% accuracy), Ductal vs. Lobular (94% accuracy), and high vs. low-medium ROR-PT score (75% accuracy). Sampling considerations in the training set minimized bias in the test set. Incorrect classification of ER status was significantly more common for Luminal B tumors. These data provide proof of principle that molecular marker status, including a critical clinical biomarker (i.e., ER status), can be predicted with accuracy >75% based on H&E features. Image-based methods could be promising for identifying patients with a greater need for further genomic testing, or in place of classically scored variables typically accomplished using human-based scoring.
Promoter Usage and Dynamics in Vascular Smooth Muscle Cells Exposed to Fibroblast Growth Factor-2 or Interleukin-1β
Authors: Alhendi Ahmad M. N. , Patrikakis Margaret , Daub Carsten O. , Kawaji Hideya , Itoh Masayoshi , de Hoon Michiel , Carninci Piero , Hayashizaki Yoshihide , Arner Erik , Khachigian Levon M. 
Published: August 2018

AbstractSmooth muscle cells (SMC) in blood vessels are normally growth quiescent and transcriptionally inactive. Our objective was to understand promoter usage and dynamics in SMC acutely exposed to a prototypic growth factor or pro-inflammatory cytokine. Using cap analysis gene expression (FANTOM5 project) we report differences in promoter dynamics for immediate-early genes (IEG) and other genes when SMC are exposed to fibroblast growth factor-2 or interleukin-1β. Of the 1871 promoters responding to FGF2 or IL-1β considerably more responded to FGF2 (68.4%) than IL-1β (18.5%) and 13.2% responded to both. Expression clustering reveals sets of genes induced, repressed or unchanged. Among IEG responding rapidly to FGF2 or IL-1β were FOS, FOSB and EGR-1, which mediates human SMC migration. Motif activity response analysis (MARA) indicates most transcription factor binding motifs in response to FGF2 were associated with a sharp induction at 1 h, whereas in response to IL-1β, most motifs were associated with a biphasic change peaking generally later. MARA revealed motifs for FOS_FOS{B,L1}_JUN{B,D} and EGR-1..3 in the cluster peaking 1 h after FGF2 exposure whereas these motifs were in clusters peaking 1 h or later in response to IL-1β. Our findings interrogating CAGE data demonstrate important differences in promoter usage and dynamics in SMC exposed to FGF2 or IL-1β.
Epigenetic modulator UVI5008 inhibits MRSA by interfering with bacterial gyrase
Authors: Franci Gianluigi , Folliero Veronica , Cammarota Marcella , Zannella Carla , Sarno Federica , Schiraldi Chiara , de Lera Angel R. , Altucci Lucia , Galdiero Massimiliano 
Published: August 2018

AbstractThe impact of multi-drug resistant bacterial strains on human health is reaching worrisome levels. Over 2 million people are infected by resistant bacteria, and more than 700,000 people die each year because of the continuous spread of resistant strains. The development of new antibiotics and the prudent use of existing ones to prolong their lifespan require a constant effort by drug industries and healthcare workers. The re-purposing of existing drugs for use as antimicrobial agents would streamline the development of new antibacterial strategies. As part of this effort, we screened a panel of drugs previously characterized to be epigenetic modulators/pro-apoptotic/differentiative drugs. We selected a few compounds that alter Gram-positive growth. Among these, UVI5008, a derivative of the natural compound psammaplin A (Psa_A), was identified. The interaction of Psa_A with the DNA gyrase enzyme has been shown, and here, we hypothesized and confirmed the gyrase-specific activity by biochemical assays. UVI5008 exhibited growth inhibition activity against Staphylococcus aureus via structural modification of the cell wall, which was observed by SEM electron microscopy. Based on our findings, we propose UVI5008 as an alternative antibacterial compound against methicillin-resistant (Met.R) S. aureus strains.
Regulating exopolysaccharide gene wcaF allows control of Escherichia coli biofilm formation
Authors: Zhang Jingyun , Poh Chueh Loo 
Published: August 2018

AbstractWhile biofilms are known to cause problems in many areas of human health and the industry, biofilms are important in a number of engineering applications including wastewater management, bioremediation, and bioproduction of valuable chemicals. However, excessive biofilm growth remains a key challenge in the use of biofilms in these applications. As certain amount of biofilm growth is required for efficient use of biofilms, the ability to control and maintain biofilms at desired thickness is vital. To this end, we developed synthetic gene circuits to control E. coli MG1655 biofilm formation by using CRISPRi/dCas9 to regulate a gene (wcaF) involved in the synthesis of colanic acid (CA), a key polysaccharide in E. coli biofilm extracellular polymeric substance (EPS). We showed that the biofilm formation was inhibited when wcaF was repressed and the biofilms could be maintained at a different thickness over a period of time. We also demonstrated that it is also possible to control the biofilm thickness spatially by inhibiting wcaF gene using a genetic light switch. The results demonstrate that the approach has great potential as a new means to control and maintain biofilm thickness in biofilm related applications.