bluuebunny/crossref_metadata_2025_split huggingface dataset:
Δ133p53α, a natural p53 isoform, contributes to conditional reprogramming and long-term proliferation of primary epithelial cells
Authors: Mondal Abdul M. , Zhou Hua , Horikawa Izumi , Suprynowicz Frank A. , Li Guangzhao , Dakic Aleksandra , Rosenthal Bernard , Ye Lin , Harris Curtis C. , Schlegel Richard , Liu Xuefeng 
Published: July 2018

AbstractWe previously developed the technique of conditional reprogramming (CR), which allows primary epithelial cells from fresh or cryopreserved specimens to be propagated long-term in vitro, while maintaining their genetic stability and differentiation potential. This method requires a combination of irradiated fibroblast feeder cells and a Rho-associated kinase (ROCK) inhibitor. In the present study, we demonstrate increased levels of full-length p53 and its natural isoform, Δ133p53α, in conditionally reprogrammed epithelial cells from primary prostate, foreskin, ectocervical, and mammary tissues. Increased Δ133p53α expression is critical for CR since cell proliferation is rapidly inhibited following siRNA knockdown of endogenous Δ133p53α. Importantly, overexpression of Δ133p53α consistently delays the onset of cellular senescence of primary cells when cultured under non-CR conditions in normal keratinocyte growth medium (KGM). More significantly, the combination of Δ133p53α overexpression and ROCK inhibitor, without feeder cells, enables primary epithelial cells to be propagated long-term in vitro. We also show that Δ133p53α overexpression induces hTERT expression and telomerase activity and that siRNA knockdown of hTERT causes rapid inhibition of cell proliferation, indicating a critical role of hTERT for mediating the effects of Δ133p53α. Altogether, these data demonstrate a functional and regulatory link between p53 pathways and hTERT expression during the conditional reprogramming of primary epithelial cells.
Epigenetic silencing of tumor suppressor gene CDKN1A by oncogenic long non-coding RNA SNHG1 in cholangiocarcinoma
Authors: Yu Yang , Zhang Mingjiong , Wang Ni , Li Quanpeng , Yang Jian , Yan Shuai , He Xuezhi , Ji Guozhong , Miao Lin 
Published: July 2018

AbstractCholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.
Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells
Authors: Zhang Yingshi , Li Dandan , Jiang Qiyu , Cao Shuang , Sun Huiwei , Chai Yantao , Li Xiaojuan , Ren Tianshu , Yang Ruichuang , Feng Fan , Li Bo-an , Zhao Qingchun 
Published: July 2018

AbstractHepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial–mesenchymal transition (EMT), and also participate in the induction of multi-drug resistance (MDR). In the present study, we demonstrated the discovery of a novel inhibitor for Notch activating/cleaving enzyme ADAM-17, named ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins. ZLDI-8 treatment enhanced the susceptibility of HCC cells to a small molecular kinase inhibitor Sorafenib, and chemotherapy agents Etoposide and Paclitaxel. ZLDI-8 treatment enhanced the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model. These results suggest that ZLDI-8 can be a promising therapeutic agent to enhance Sorafenib’s anti-tumor effect and to overcome the MDR of HCC patients.
k-space imaging of anisotropic 2D electron gas in GaN/GaAlN high-electron-mobility transistor heterostructures
Authors: Lev L. L. , Maiboroda I. O. , Husanu M.-A. , Grichuk E. S. , Chumakov N. K. , Ezubchenko I. S. , Chernykh I. A. , Wang X. , Tobler B. , Schmitt T. , Zanaveskin M. L. , Valeyev V. G. , Strocov V. N. 
Published: July 2018

AbstractNanostructures based on buried interfaces and heterostructures are at the heart of modern semiconductor electronics as well as future devices utilizing spintronics, multiferroics, topological effects, and other novel operational principles. Knowledge of electronic structure of these systems resolved in electron momentum k delivers unprecedented insights into their physics. Here we explore 2D electron gas formed in GaN/AlGaN high-electron-mobility transistor heterostructures with an ultrathin barrier layer, key elements in current high-frequency and high-power electronics. Its electronic structure is accessed with angle-resolved photoelectron spectroscopy whose probing depth is pushed to a few nanometers using soft-X-ray synchrotron radiation. The experiment yields direct k-space images of the electronic structure fundamentals of this system—the Fermi surface, band dispersions and occupancy, and the Fourier composition of wavefunctions encoded in the k-dependent photoemission intensity. We discover significant planar anisotropy of the electron Fermi surface and effective mass connected with relaxation of the interfacial atomic positions, which translates into nonlinear (high-field) transport properties of the GaN/AlGaN heterostructures as an anisotropy of the saturation drift velocity of the 2D electrons.
Microtubule minus-end aster organization is driven by processive HSET-tubulin clusters
Authors: Norris Stephen R. , Jung Seungyeon , Singh Prashant , Strothman Claire E. , Erwin Amanda L. , Ohi Melanie D. , Zanic Marija , Ohi Ryoma 
Published: July 2018

AbstractHigher-order structures of the microtubule (MT) cytoskeleton are comprised of two architectures: bundles and asters. Although both architectures are critical for cellular function, the molecular pathways that drive aster formation are poorly understood. Here, we study aster formation by human minus-end-directed kinesin-14 (HSET/KIFC1). We show that HSET is incapable of forming asters from preformed, nongrowing MTs, but rapidly forms MT asters in the presence of soluble (non-MT) tubulin. HSET binds soluble (non-MT) tubulin via its N-terminal tail domain to form heterogeneous HSET-tubulin clusters containing multiple motors. Cluster formation induces motor processivity and rescues the formation of asters from nongrowing MTs. We then show that excess soluble (non-MT) tubulin stimulates aster formation in HeLa cells overexpressing HSET during mitosis. We propose a model where HSET can toggle between MT bundle and aster formation in a manner governed by the availability of soluble (non-MT) tubulin.
Crystal and melt inclusion timescales reveal the evolution of magma migration before eruption
Authors: Ruth Dawn C. S. , Costa Fidel , Bouvet de Maisonneuve Caroline , Franco Luis , Cortés Joaquin A. , Calder Eliza S. 
Published: July 2018

AbstractVolatile element concentrations measured in melt inclusions are a key tool used to understand magma migration and degassing, although their original values may be affected by different re-equilibration processes. Additionally, the inclusion-bearing crystals can have a wide range of origins and ages, further complicating the interpretation of magmatic processes. To clarify some of these issues, here we combined olivine diffusion chronometry and melt inclusion data from the 2008 eruption of Llaima volcano (Chile). We found that magma intrusion occurred about 4 years before the eruption at a minimum depth of approximately 8 km. Magma migration and reaction became shallower with time, and about 6 months before the eruption magma reached 3–4 km depth. This can be linked to reported seismicity and ash emissions. Although some ambiguities of interpretation still remain, crystal zoning and melt inclusion studies allow a more complete understanding of magma ascent, degassing, and volcano monitoring data.
Radio-frequency current drive for thermonuclear fusion reactors
Authors: Cardinali A. , Castaldo C. , Cesario R. , Amicucci L. , Galli A. , Napoli F. , Panaccione L. , Riccardi C. , Santini F. , Schettini G. , Tuccillo A. A. 
Published: July 2018

AbstractPrincipal research on energy from thermonuclear fusion uses Deuterium-Tritium plasmas magnetically trapped in toroidal devices. As major scientific problem for an economic (i.e., really feasible) reactor, we must understand how to lead strongly heated plasmas to sustain a high fusion gain while large fraction of current is self-produced via the presence of strong pressure gradient. To suppress turbulent eddies that impair thermal insulation and pressure tight of the plasma, current drive (CD) is necessary. However, tools envisaged so far in ITER (International Thermonuclear Experiment Rector) are unable accomplishing this task that requires efficiently and flexibly matching the natural current profiles of plasma. Consequently, viability of a thermonuclear reactor should be problematic. Multi-megawatt radio-frequency (RF) power coupled to plasma would produce the necessary CD, but modelling results based on previous understanding found difficult the extrapolation of this CD concept to reactor conditions of high temperature plasma, and greater flexibility of method would also be required. Here we present new model results based on standard quasilinear (QL) theory that allow establish conditions to drive efficiently and flexibly the RF-driven current at large radii of the plasma column, as necessary for the goal of a reactor.
Environmental DNA reveals quantitative patterns of fish biodiversity in large rivers despite its downstream transportation
Authors: Pont Didier , Rocle Mathieu , Valentini Alice , Civade Raphaël , Jean Pauline , Maire Anthony , Roset Nicolas , Schabuss Michael , Zornig Horst , Dejean Tony 
Published: July 2018

AbstractDespite the ecological and societal importance of large rivers, fish sampling remains costly and limited to specific habitats (e.g., river banks). Using an eDNA metabarcoding approach, we regularly sampled 500 km of a large river (Rhône River). Comparisons with long-term electrofishing surveys demonstrated the ability of eDNA metabarcoding to qualitatively and quantitatively reveal fish assemblage structures (relative species abundance) but eDNA integrated a larger space than the classical sampling location. Combination of a literature review and field data showed that eDNA behaves in the water column like fine particulate organic matter. Its detection distance varied from a few km in a small stream to more than 100 km in a large river. To our knowledge, our results are the first demonstration of the capacity of eDNA metabarcoding to describe longitudinal fish assemblage patterns in a large river, and metabarcoding appears to be a reliable, cost-effective method for future monitoring.
Prolonged phloem ingestion by Diaphorina citri nymphs compared to adults is correlated with increased acquisition of citrus greening pathogen
Authors: George Justin , Ammar El-Desouky , Hall David G. , Shatters Robert G. , Lapointe Stephen L. 
Published: July 2018

AbstractCitrus greening disease (huanglongbing), currently the most destructive citrus disease worldwide, is putatively caused by Candidatus Liberibacter asiaticus (CLas), a phloem-limited bacterium transmitted by the Asian citrus psyllid Diaphorina citri. Electrical penetration graph (EPG) recordings over 42 h were performed to compare the feeding behavior of D. citri adults and 4th or 5th instar nymphs feeding on CLas-infected or healthy citron plants. Nymphs performed more individual bouts of phloem ingestion (E2) and recorded longer phloem ingestion total time compared with adults, whereas adults performed more bouts of xylem ingestion (G) and recorded greater total time of xylem ingestion compared with nymphs. Quantitative polymerase chain reaction tests indicated that 58% of nymphs and 6% of adults acquired CLas during the 42 h EPG-recorded feeding on infected plants. In a histological study, a greater proportion of salivary sheaths produced by nymphs were branched compared to those of the adults. Our results strongly suggest that more bouts and longer feeding time in the phloem by nymphs may explain their more efficient CLas acquisition from infected plants compared to adults. This is the first EPG study comparing nymphs and adults of D. citri on healthy and infected citrus plants in relation to CLas acquisition.
Optimization of a MT1-MMP-targeting Peptide and Its Application in Near-infrared Fluorescence Tumor Imaging
Authors: Ren Li , Wang Ye , Zhu Lei , Shen Liqiao , Zhang Jinrui , Wang Jingjing , Li Haolong , Zheng Qingchuan , Yu Dahai , Fang Xuexun 
Published: July 2018

AbstractMembrane type 1 metalloproteinase (MT1-MMP) is an important regulator of cancer invasion, growth and angiogenesis, thus making it an attractive target for cancer imaging and therapy. A non-substrate peptide (MT1-AF7p) that bonded to the “MT-Loop” region of MT1-MMP was identified by using a phage-displayed peptide library and was used to image the MT1-MMP expression in vivo through optical imaging. However, the substrate in the screening did not have a 3D structure, thus resulting in a loose bonding of MT1-AF7p. To simulate the real conformation of the “MT-Loop” and improve the performance of MT1-AF7p, molecular simulations were performed, because this strategy provides multiple methods for predicting the conformation and interaction of proteinase in 3D. In view of the binding site of the receptor–ligand interactions, histidine 4 was selected for mutation to achieve an increased affinity effect. The optimized peptides were further identified and conformed by atomic force microscopy, isothermal titration calorimetry, cell fluorescence imaging in vitro, and near-infrared fluorescence tumor optical imaging in vivo. The results revealed that the optimized peptide with a mutation of histidine 4 to arginine has the highest affinity and specificity, and exhibited an increased fluorescence intensity in the tumor site in optical imaging.
Cancer mortality does not differ by antiarrhythmic drug use: A population-based cohort of Finnish men
Authors: Kaapu Kalle J. , Rantaniemi Lauri , Talala Kirsi , Taari Kimmo , Tammela Teuvo L. J. , Auvinen Anssi , Murtola Teemu J. 
Published: July 2018

AbstractIn-vitro studies have suggested that the antiarrhythmic drug digoxin might restrain the growth of cancer cells by inhibiting Na+/K+-ATPase. We evaluated the association between cancer mortality and digoxin, sotalol and general antiarrhythmic drug use in a retrospective cohort study. The study population consists of 78,615 men originally identified for the Finnish Randomized Study of Screening for Prostate Cancer. Information on antiarrhythmic drug purchases was collected from the national prescription database. We used the Cox regression method to analyze separately overall cancer mortality and mortality from the most common types of cancer. During the median follow-up of 17.0 years after the baseline 28,936 (36.8%) men died, of these 8,889 due to cancer. 9,023 men (11.5%) had used antiarrhythmic drugs. Overall cancer mortality was elevated among antiarrhythmic drug users compared to non-users (HR 1.43, 95% CI 1.34–1.53). Similar results were observed separately for digoxin and for sotalol. However, the risk associations disappeared in long-term use and were modified by background co-morbidities. All in all, cancer mortality was elevated among antiarrhythmic drug users. This association is probably non-causal as it was related to short-term use and disappeared in long-term use. Our results do not support the anticancer effects of digoxin or any other antiarrhythmic drug.
AMPA receptor trafficking and its role in heterosynaptic plasticity
Authors: Antunes G. , Simoes-de-Souza F. M. 
Published: July 2018

AbstractHistorically, long-term potentiation (LTP) and long-term depression (LTD), the best-characterized forms of long-term synaptic plasticity, are viewed as experience-dependent and input-specific processes. However, cumulative experimental and theoretical data have demonstrated that LTP and LTD can promote compensatory alterations in non-stimulated synapses. In this work, we have developed a computational model of a tridimensional spiny dendritic segment to investigate the role of AMPA receptor (AMPAR) trafficking during synaptic plasticity at specific synapses and its consequences for the populations of AMPAR at nearby synapses. Our results demonstrated that the mechanisms of AMPAR trafficking involved with LTP and LTD can promote heterosynaptic plasticity at non-stimulated synapses. These alterations are compensatory and arise from molecular competition. Moreover, the heterosynaptic changes observed in our model can modulate further activity-driven inductions of synaptic plasticity.
Preservation of explicit learning of visuomotor sequences during Parkinson’s disease progression
Authors: Kitahara Eriko , Shimo Yasushi , Mori Hideo , Nagaoka Masanori 
Published: July 2018

AbstractWhile motor learning approaches are effective in rehabilitating Parkinson’s disease (PD) patients, many studies reported deficits in sequential motor learning in these patients. We hypothesised that preserved explicit learning of visuomotor sequences in PD patients contributed to the effectiveness of motor learning approaches. However, there are very few studies analysing explicit learning of visuomotor sequences during the progression of PD. We investigated this phenomenon in 23 patients with moderate to severe PD (Hoehn–Yahr stages II-IV) and 17 age-matched controls using sequential button-press tasks (2 × 5 task). We found (1) no significant differences in numbers of errors in the 2 × 5 task among control and PD groups. (2) There was a significant difference in response times while exploring correct sequences (ERT) among control and PD groups; ERTs in stage-IV patients tended to be longer than those of control and stage-II groups. (3) All four groups significantly improved their performance (i.e., reduced ERTs in the 2 × 5 task) with sequence repetition, although stage-III:IV patients were slower. Thus, even patients with severe PD can learn visual sequences and can translate them into visuomotor sequences (explicit visuomotor sequence learning), albeit slower than controls, providing evidence for effective motor learning approaches during rehabilitation of patients with advanced PD.
Knockdown Indian Hedgehog (Ihh) does not delay Fibular Fracture Healing in genetic deleted Ihh mice and pharmaceutical inhibited Ihh Mice
Authors: Li Shengchun , Xiang Chuan , Wei Xiaochun , Li Hongbin , Li Kai , Sun Xiaojuan , Wang Shaowei , Zhang Min , Deng Jin , Wang Xiaodu , Li Pengcui , Li Ruifang , Zhang Yanxiang , Wei Lei 
Published: July 2018

AbstractThe objective of this study was to determine if Ihh is required for fracture healing. Fibular fracture was created in adult Col2a1-CreERT2; Ihhfl/fl mice. Ihhfl/fl mice received Tamoxifen (TM) to delete Ihh. WT mice received Cyclopamine to inhibit Hh pathway. Callus tissue properties and Ihh pathway were analyzed at 1, 2, and 3 weeks post-fracture by X-ray, micro-CT, mechanical test, RT-PCR and immunohistochemistry. Deleted Ihh was evidenced by the occurrence of growth plate closure in the Ihhfl/fl mice by X-ray 3 weeks after TM treatment. All mice showed fracture healing at 3 weeks post-operation. Histology analysis indicated that, compared to the control, cartilage area was less in fracture sites from Ihh deficient animals by either genetic deletion or drug inhibition at 1 and 2 weeks post-fracture. Ihh immunostaining and its mRNA level were diminished in the fracture callus in Ihh reduced mice. There was no significant difference in BV/TV, BMD and mechanical test. Interruption to Ihh pathway by either genetic or pharmaceutical approach didn’t affect fibular fracture healing in these mice. This surprised finding implicates that the deleted Ihh does not affect fracture healing in this model.
Data-driven analysis of motor activity implicates 5-HT2A neurons in backward locomotion of larval Drosophila
Authors: Park Jeonghyuk , Kondo Shu , Tanimoto Hiromu , Kohsaka Hiroshi , Nose Akinao 
Published: July 2018

AbstractRhythmic animal behaviors are regulated in part by neural circuits called the central pattern generators (CPGs). Classifying neural population activities correlated with body movements and identifying the associated component neurons are critical steps in understanding CPGs. Previous methods that classify neural dynamics obtained by dimension reduction algorithms often require manual optimization which could be laborious and preparation-specific. Here, we present a simpler and more flexible method that is based on the pre-trained convolutional neural network model VGG-16 and unsupervised learning, and successfully classifies the fictive motor patterns in Drosophila larvae under various imaging conditions. We also used voxel-wise correlation mapping to identify neurons associated with motor patterns. By applying these methods to neurons targeted by 5-HT2A-GAL4, which we generated by the CRISPR/Cas9-system, we identified two classes of interneurons, termed Seta and Leta, which are specifically active during backward but not forward fictive locomotion. Optogenetic activation of Seta and Leta neurons increased backward locomotion. Conversely, thermogenetic inhibition of 5-HT2A-GAL4 neurons or application of a 5-HT2 antagonist decreased backward locomotion induced by noxious light stimuli. This study establishes an accelerated pipeline for activity profiling and cell identification in larval Drosophila and implicates the serotonergic system in the modulation of backward locomotion.