bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis
Authors: Barros-Silva Daniela , Costa-Pinheiro Pedro , Duarte Henrique , Sousa Elsa Joana , Evangelista Adriane Feijó , Graça Inês , Carneiro Isa , Martins Ana Teresa , Oliveira Jorge , Carvalho André L. , Marques Márcia M. , Henrique Rui , Jerónimo Carmen 
Published: February 2018

AbstractUpregulation of MYC and miRNAs deregulation are common in prostate cancer (PCa). Overactive MYC may cause miRNAs’ expression deregulation through transcriptional and post-transcriptional mechanisms and epigenetic alterations are also involved in miRNAs dysregulation. Herein, we aimed to elucidate the role of regulatory network between MYC and miRNAs in prostate carcinogenesis. MYC expression was found upregulated in PCa cases and matched precursor lesions. MicroRNA’s microarray analysis of PCa samples with opposed MYC levels identified miRNAs significantly overexpressed in high-MYC PCa. However, validation of miR-27a-5p in primary prostate tissues disclosed downregulation in PCa, instead, correlating with aberrant promoter methylation. In a series of castration-resistant PCa (CRPC) cases, miR-27a-5p was upregulated, along with promoter hypomethylation. MYC and miR-27a-5p expression levels in LNCaP and PC3 cells mirrored those observed in hormone-naíve PCa and CRPC, respectively. ChIP analysis showed that miR-27a-5p expression is only regulated by c-Myc in the absence of aberrant promoter methylation. MiR-27a-5p knockdown in PC3 cells promoted cell growth, whereas miRNA forced expression in LNCaP and stable MYC-knockdown PC3 cells attenuated the malignant phenotype, suggesting a tumor suppressive role for miR-27a-5p. Furthermore, miR-27a-5p upregulation decreased EGFR/Akt1/mTOR signaling. We concluded that miR-27a-5p is positively regulated by MYC, and its silencing due to aberrant promoter methylation occurs early in prostate carcinogenesis, concomitantly with loss of MYC regulatory activity. Our results further suggest that along PCa progression, miR-27a-5p promoter becomes hypomethylated, allowing for MYC to resume its regulatory activity. However, the altered cellular context averts miR-27a-5p from successfully accomplishing its tumor suppressive function at this stage of disease.
LncRNA NCK1-AS1 promotes proliferation and induces cell cycle progression by crosstalk NCK1-AS1/miR-6857/CDK1 pathway
Authors: Li Haiyu , Jia Yongqin , Cheng Junning , Liu Geli , Song Fangzhou 
Published: February 2018

AbstractThe purpose of this study was to develop an lncRNA signature to improve the prediction of the prognosis of cervical cancer through integration bioinformatics and analysis of TCGA RNA sequencing data. In this study, we established a set of four lncRNA signatures that was significantly associated with recurrence-free survival using the Cox regression model. Functionally, we screened the CC-associated lncRNA NCK1-AS1 as a new candidate lncRNA and regulator which promotes development and progression in CC. qRT-PCR and RNA in situ hybridization (RISH) results showed that NCK1-AS1 was significantly up-regulated in 77.4% (24/31) of the CC tissue group compared with the normal group (P < 0.01). Interestingly, we demonstrated that transcription factor SP1 directly binds to the promoter to activate NCK1-AS1 expression in SiHa cells. In vitro and in vivo assays of silencing NCK1-AS1 significantly inhibited cell proliferation and invasion, with induction of cell arrest in S phase of the cell cycle. Furthermore, Human Transcriptome Array 2.0 analysis after NCK1-AS1 silencing highlighted alterations in cell proliferation and cell cycle pathways. NCK1-AS1 functioned as a molecular sponge for miR-6857, antagonizing its ability to repress CDK1/6 protein translation. In conclusion, these findings suggest that NCK1-AS1/miR-6857/CDK1 crosstalk serve as a critical effector in cervical cancer progression and may serve as a potential target in cervical cancer.
Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death
Authors: Thellung Stefano , Scoti Beatrice , Corsaro Alessandro , Villa Valentina , Nizzari Mario , Gagliani Maria Cristina , Porcile Carola , Russo Claudio , Pagano Aldo , Tacchetti Carlo , Cortese Katia , Florio Tullio 
Published: February 2018

AbstractAccording to the “gain-of-toxicity mechanism”, neuronal loss during cerebral proteinopathies is caused by accumulation of aggregation-prone conformers of misfolded cellular proteins, although it is still debated which aggregation state actually corresponds to the neurotoxic entity. Autophagy, originally described as a variant of programmed cell death, is now emerging as a crucial mechanism for cell survival in response to a variety of cell stressors, including nutrient deprivation, damage of cytoplasmic organelles, or accumulation of misfolded proteins. Impairment of autophagic flux in neurons often associates with neurodegeneration during cerebral amyloidosis, suggesting a role in clearing neurons from aggregation-prone misfolded proteins. Thus, autophagy may represent a target for innovative therapies. In this work, we show that alterations of autophagy progression occur in neurons following in vitro exposure to the amyloidogenic and neurotoxic prion protein-derived peptide PrP90-231. We report that the increase of autophagic flux represents a strategy adopted by neurons to survive the intracellular accumulation of misfolded PrP90-231. In particular, PrP90-231 internalization in A1 murine mesencephalic neurons occurs in acidic structures, showing electron microscopy hallmarks of autophagosomes and autophagolysosomes. However, these structures do not undergo resolution and accumulate in cytosol, suggesting that, in the presence of PrP90-231, autophagy is activated but its progression is impaired; the inability to clear PrP90-231 via autophagy induces cytotoxicity, causing impairment of lysosomal integrity and cytosolic diffusion of hydrolytic enzymes. Conversely, the induction of autophagy by pharmacological blockade of mTOR kinase or trophic factor deprivation restored autophagy resolution, reducing intracellular PrP90-231 accumulation and neuronal death. Taken together, these data indicate that PrP90-231 internalization induces an autophagic defensive response in A1 neurons, although incomplete and insufficient to grant survival; the pharmacological enhancement of this process exerts neuroprotection favoring the clearing of the internalized peptide and could represents a promising neuroprotective tool for neurodegenerative proteinopathies.
miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma
Authors: Jin Yun-Peng , Hu Yun-Ping , Wu Xiang-Song , Wu Yao-Shi , Ye Yuan-Yuan , Li Huai-Feng , Liu Yong-Chen , Jiang Lin , Liu Fa-Tao , Zhang Yi-Jian , Hao Ya-Juan , Liu Xi-Yong , Liu Ying-Bin 
Published: February 2018

AbstractGallbladder cancer (GBC) is the most common malignant tumour of the biliary track system. Angiogenesis plays a pivotal role in the development and progression of malignant tumours. miR-143-3p acts as a tumour suppressor in various cancers. Their role in GBC is however less well defined. Here we show that the expression levels of miR-143-3p were decreased in human GBC tissues compared with the non-tumour adjacent tissue (NAT) counterparts and were closely associated with overall survival. We discovered that miR-143-3p was a novel inhibitor of tumour growth and angiogenesis in vivo and in vitro. Our antibody array, ELISA and PLGF rescue analyses indicated that PLGF played an essential role in the antiangiogenic effect of miR-143-3p. Furthermore, we used miRNA target-prediction software and dual-luciferase assays to confirm that integrin α6 (ITGA6) acted as a direct target of miR-143-3p. Our ELISA and western blot analyses confirmed that the expression of PLGF was decreased via the ITGA6/PI3K/AKT pathway. In conclusion, miR-143-3p suppresses tumour angiogenesis and growth of GBC through the ITGA6/PI3K/AKT/PLGF pathways and may be a novel molecular therapeutic target for GBC.
NF-κB inhibition by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair
Authors: Deraska Peter V. , O’Leary Colin , Reavis Hunter D. , Labe Shelby , Dinh Tru-Khang , Lazaro Jean-Bernard , Sweeney Christopher , D’Andrea Alan D. , Kozono David 
Published: February 2018

AbstractDespite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization. Here we demonstrate that inhibition of the canonical NF-κB pathway by dimethylaminoparthenolide (DMAPT) radiosensitizes NSCLC by blocking DNA double-strand break (DSB) repair. NF-κB inhibition results in significant impairment of both homologous recombination (HR) and non-homologous end joining (NHEJ), as well as reductions in ionizing radiation (IR)-induced DNA repair biomarkers. NF-κB inhibition by DMAPT shows preclinical potential for further investigation as a NSCLC radiosensitizer.
Lithium induces mesenchymal-epithelial differentiation during human kidney development by activation of the Wnt signalling system
Authors: Price Karen L. , Kolatsi-Joannou Maria , Mari Chiara , Long David A. , Winyard Paul J. D. 
Published: February 2018

AbstractKidney function is directly linked to the number of nephrons which are generated until 32–36 weeks gestation in humans. Failure to make nephrons during development leads to congenital renal malformations, whilst nephron loss in adulthood occurs in progressive renal disease. Therefore, an understanding of the molecular processes which underlie human nephron development may help design new treatments for renal disease. Mesenchyme to epithelial transition (MET) is critical for forming nephrons, and molecular pathways which control rodent MET have been identified. However, we do not know whether they are relevant in human kidney development. In this study, we isolated mesenchymal cell lines derived from human first trimester kidneys in monolayer culture and investigated their differentiation potential. We found that the mesenchymal cells could convert into osteogenic, but not adipogenic or endothelial lineages. Furthermore, addition of lithium chloride led to MET which was accompanied by increases in epithelial (CDH1) and tubular (ENPEP) markers and downregulation of renal progenitor (SIX2, EYA1, CD133) and mesenchymal markers (HGF, CD24). Prior to phenotypic changes, lithium chloride altered Wnt signalling with elevations in AXIN2, GSK3β phosphorylation and β-catenin. Collectively, these studies provide the first evidence that lithium-induced Wnt activation causes MET in human kidneys. Therapies targeting Wnts may be critical in the quest to regenerate nephrons for human renal diseases.
Ecology and genomics of an important crop wild relative as a prelude to agricultural innovation
Authors: von Wettberg Eric J.B. , Chang Peter L. , Başdemir Fatma , Carrasquila-Garcia Noelia , Korbu Lijalem Balcha , Moenga Susan M. , Bedada Gashaw , Greenlon Alex , Moriuchi Ken S. , Singh Vasantika , Cordeiro Matilde A. , Noujdina Nina V. , Dinegde Kassaye Negash , Shah Sani Syed Gul Abbas , Getahun Tsegaye , Vance Lisa , Bergmann Emily , Lindsay Donna , Mamo Bullo Erena , Warschefsky Emily J. , Dacosta-Calheiros Emmanuel , Marques Edward , Yilmaz Mustafa Abdullah , Cakmak Ahmet , Rose Janna , Migneault Andrew , Krieg Christopher P. , Saylak Sevgi , Temel Hamdi , Friesen Maren L. , Siler Eleanor , Akhmetov Zhaslan , Ozcelik Huseyin , Kholova Jana , Can Canan , Gaur Pooran , Yildirim Mehmet , Sharma Hari , Vadez Vincent , Tesfaye Kassahun , Woldemedhin Asnake Fikre , Tar’an Bunyamin , Aydogan Abdulkadir , Bukun Bekir , Penmetsa R. Varma , Berger Jens , Kahraman Abdullah , Nuzhdin Sergey V. , Cook Douglas R. 
Published: February 2018

AbstractDomesticated species are impacted in unintended ways during domestication and breeding. Changes in the nature and intensity of selection impart genetic drift, reduce diversity, and increase the frequency of deleterious alleles. Such outcomes constrain our ability to expand the cultivation of crops into environments that differ from those under which domestication occurred. We address this need in chickpea, an important pulse legume, by harnessing the diversity of wild crop relatives. We document an extreme domestication-related genetic bottleneck and decipher the genetic history of wild populations. We provide evidence of ancestral adaptations for seed coat color crypsis, estimate the impact of environment on genetic structure and trait values, and demonstrate variation between wild and cultivated accessions for agronomic properties. A resource of genotyped, association mapping progeny functionally links the wild and cultivated gene pools and is an essential resource chickpea for improvement, while our methods inform collection of other wild crop progenitor species.
Understanding the plume dynamics of explosive super-eruptions
Authors: Costa Antonio , J. Suzuki Yujiro , Koyaguchi Takehiro 
Published: February 2018

AbstractExplosive super-eruptions can erupt up to thousands of km3 of magma with extremely high mass flow rates (MFR). The plume dynamics of these super-eruptions are still poorly understood. To understand the processes operating in these plumes we used a fluid-dynamical model to simulate what happens at a range of MFR, from values generating intense Plinian columns, as did the 1991 Pinatubo eruption, to upper end-members resulting in co-ignimbrite plumes like Toba super-eruption. Here, we show that simple extrapolations of integral models for Plinian columns to those of super-eruption plumes are not valid and their dynamics diverge from current ideas of how volcanic plumes operate. The different regimes of air entrainment lead to different shaped plumes. For the upper end-members can generate local up-lifts above the main plume (over-plumes). These over-plumes can extend up to the mesosphere. Injecting volatiles into such heights would amplify their impact on Earth climate and ecosystems.
Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging
Authors: Oh Gabriel , Ebrahimi Sasha , Carlucci Matthew , Zhang Aiping , Nair Akhil , Groot Daniel E. , Labrie Viviane , Jia Peixin , Oh Edward S. , Jeremian Richie H. , Susic Miki , Shrestha Tenjin C. , Ralph Martin R. , Gordevičius Juozas , Koncevičius Karolis , Petronis Art 
Published: February 2018

AbstractCircadian rhythmicity governs a remarkable array of fundamental biological functions and is mediated by cyclical transcriptomic and proteomic activities. Epigenetic factors are also involved in this circadian machinery; however, despite extensive efforts, detection and characterization of circadian cytosine modifications at the nucleotide level have remained elusive. In this study, we report that a large proportion of epigenetically variable cytosines show a circadian pattern in their modification status in mice. Importantly, the cytosines with circadian epigenetic oscillations significantly overlap with the cytosines exhibiting age-related changes in their modification status. Our findings suggest that evolutionary advantageous processes such as circadian rhythmicity can also contribute to an organism’s deterioration.
Effects of diversity in olfactory environment on children’s sense of smell
Authors: Martinec Nováková Lenka , Fialová Jitka , Havlíček Jan 
Published: February 2018

AbstractDiversity in children’s everyday olfactory environment may affect the development of their olfactory abilities and odor awareness. To test this, we collected data on olfactory abilities using the Sniffin’ Sticks and odor awareness with Children’s Olfactory Behaviors in Everyday Life Questionnaire in 153 preschool children and retested them one and a half year later. Parents completed an inventory on children’s exposure to a variety of odors and on their own odor awareness using the Odor Awareness Scale. We controlled for the effects of age and verbal fluency on the children’s performance. We found that the children’s odor identification and discrimination scores differed as a function of parental odor awareness. Although these effects were rather small, they were commensurate in size with those of gender and age. To the best of our knowledge, this study is the first to present evidence that diversity in children’s olfactory environment affects variation in their olfactory abilities and odor awareness. We suggest that future studies consider the long-term impact of perceptual learning out of the laboratory and its consequences for olfactory development.
Abnormal optical anisotropy in correlated disorder KTa1−xNbxO3:Cu with refractive index gradient
Authors: Zhang Xin , He Shan , Zhao Zhuan , Wu Pengfei , Wang Xuping , Liu Hongliang 
Published: February 2018

AbstractIn this report, an abnormal optical anisotropy in KTa1−xNbxO3:Cu (Cu:KTN) crystals with refractive index gradient is presented. Contrary to general regulation in a cross-polarization setup, the transmitted intensity of both TE (horizontally polarized) and TM (vertically polarized) lasers aligned with the basic crystallographic directions can be modulated quasiperiodically. The mechanism is supposed to be based on the polarization induced by the temperature gradient and the refractive index gradient. Meanwhile, the correlated disorder property of the crystals in the range of the freezing temperature (Tf) and the intermediate temperature (T *) also plays an important role. With the results verified both theoretically and experimentally, we believe this work is not only beneficial for the development of the theory associated with the correlated disorder structures in relaxor ferroelectrics, but also significant for the exploitation of numerous optical functional devices.
Concise N-doped Carbon Nanosheets/Vanadium Nitride Nanoparticles Materials via Intercalative Polymerization for Supercapacitors
Authors: Tan Yongtao , Liu Ying , Tang Zhenghua , Wang Zhe , Kong Lingbin , Kang Long , Liu Zhen , Ran Fen 
Published: February 2018

AbstractN-doped carbon nanosheets/vanadium nitride nanoparticles (N-CNS/VNNPs) are synthesized via a novel method combining surface-initiated in-situ intercalative polymerization and thermal-treatment process in NH3/N2 atmosphere. The pH value of the synthesis system plays a critical role in constructing the structure and enhancing electrochemical performance for N-CNS/VNNPs, which are characterized by SEM, TEM, XRD, and XPS, and measured by electrochemical station, respectively. The results show that N-CNS/VNNPs materials consist of 2D N-doped carbon nanosheets and 0D VN nanoparticles. With the pH value decreasing from 2 to 0, the sizes of both carbon nanosheets and VN nanoparticles decreased to smaller in nanoscale. The maximum specific capacitance of 280 F g−1 at the current density of 1 A g−1 for N-CNS/VNNPs is achieved in three-electrode configuration. The asymmetric energy device of Ni(OH)2||N-CNS/VNNPs offers a specific capacitance of 89.6 F g−1 and retention of 60% at 2.7 A g−1 after 5000 cycles. The maximum energy density of Ni(OH)2 ||N-CNS/VNNPs asymmetric energy device is as high as 29.5 Wh kg−1.
Vascular dysfunction in obese diabetic db/db mice involves the interplay between aldosterone/mineralocorticoid receptor and Rho kinase signaling
Authors: Nguyen Dinh Cat Aurelie , Callera Glaucia E. , Friederich-Persson Malou , Sanchez Ana , Dulak-Lis Maria Gabriela , Tsiropoulou Sofia , Montezano Augusto C. , He Ying , Briones Ana M. , Jaisser Frederic , Touyz Rhian M. 
Published: February 2018

AbstractActivation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+. This was associated with enhanced vascular MR signaling. Norepinephrine (NE)-induced contraction was increased in arteries from db/db mice. These responses were attenuated in mice treated with canrenoate or fasudil. Db/db mice displayed hypertrophic remodeling and increased arterial stiffness, improved by MR blockade. Vascular calcium sensitivity was similar between depolarized arteries from db/+ and db/db. Vascular hypercontractility in db/db mice was associated with increased myosin light chain phosphorylation and reduced expression of PKG-1α. Vascular RhoA/ROCK signaling and expression of pro-inflammatory and pro-fibrotic markers were exaggerated in db/db mice, effects that were attenuated by MRA. Fasudil, but not MRA, improved vascular insulin sensitivity in db/db mice, evidenced by normalization of Irs1 phosphorylation. Our data identify novel pathways involving MR-RhoA/ROCK-PKG-1 that underlie vascular dysfunction and injury in diabetic mice.
Rpb9-deficient cells are defective in DNA damage response and require histone H3 acetylation for survival
Authors: Sein Henel , Reinmets Kristina , Peil Kadri , Kristjuhan Kersti , Värv Signe , Kristjuhan Arnold 
Published: February 2018

AbstractRpb9 is a non-essential subunit of RNA polymerase II that is involved in DNA transcription and repair. In budding yeast, deletion of RPB9 causes several phenotypes such as slow growth and temperature sensitivity. We found that simultaneous mutation of multiple N-terminal lysines within histone H3 was lethal in rpb9Δ cells. Our results indicate that hypoacetylation of H3 leads to inefficient repair of DNA double-strand breaks, while activation of the DNA damage checkpoint regulators γH2A and Rad53 is suppressed in Rpb9-deficient cells. Combination of H3 hypoacetylation with the loss of Rpb9 leads to genomic instability, aberrant segregation of chromosomes in mitosis, and eventually to cell death. These results indicate that H3 acetylation becomes essential for efficient DNA repair and cell survival if a DNA damage checkpoint is defective.
Combined aptamer and transcriptome sequencing of single cells
Authors: Delley Cyrille L. , Liu Leqian , Sarhan Maen F. , Abate Adam R. 
Published: February 2018

AbstractThe transcriptome and proteome encode distinct information that is important for characterizing heterogeneous biological systems. We demonstrate a method to simultaneously characterize the transcriptomes and proteomes of single cells at high throughput using aptamer probes and droplet-based single cell sequencing. With our method, we differentiate distinct cell types based on aptamer surface binding and gene expression patterns. Aptamers provide advantages over antibodies for single cell protein characterization, including rapid, in vitro, and high-purity generation via SELEX, and the ability to amplify and detect them with PCR and sequencing.