bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of gemcitabine sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells by RUNX2 depletion-mediated augmentation of TAp73-dependent cell death
Authors: Nakamura M , Sugimoto H , Ogata T , Hiraoka K , Yoda H , Sang M , Sang M , Zhu Y , Yu M , Shimozato O , Ozaki T 
Published: June 2016

AbstractPancreatic cancer exhibits the worst prognostic outcome among human cancers. Recently, we have described that depletion of RUNX2 enhances gemcitabine (GEM) sensitivity of p53-deficient pancreatic cancer AsPC-1 cells through the activation of TAp63-mediated cell death pathway. These findings raised a question whether RUNX2 silencing could also improve GEM efficacy on pancreatic cancer cells bearing p53 mutation. In the present study, we have extended our study to p53-mutated pancreatic cancer MiaPaCa-2 cells. Based on our current results, MiaPaCa-2 cells were much more resistant to GEM as compared with p53-proficient pancreatic cancer SW1990 cells, and there existed a clear inverse relationship between the expression levels of TAp73 and RUNX2 in response to GEM. Forced expression of TAp73α in MiaPaCa-2 cells significantly promoted cell cycle arrest and/or cell death, indicating that a large amount of TAp73 might induce cell death even in the presence of mutant p53. Consistent with this notion, overexpression of TAp73α stimulated luciferase activity driven by p53/TAp73-target gene promoters in MiaPaCa-2 cells. Similar to AsPC-1 cells, small interfering RNA-mediated knockdown of RUNX2 remarkably enhanced GEM sensitivity of MiPaCa-2 cells. Under our experimental conditions, TAp73 further accumulated in RUNX2-depleted MiaPaCa-2 cells exposed to GEM relative to GEM-treated non-silencing control cells. As expected, silencing of p73 reduced GEM sensitivity of MiPaCa-2 cells. Moreover, GEM-mediated Tyr phosphorylation level of TAp73 was much more elevated in RUNX2-depleted MiaPaCa-2 cells. Collectively, our present findings strongly suggest that knockdown of RUNX2 contributes to a prominent enhancement of GEM sensitivity of p53-mutated pancreatic cancer cells through the activation of TAp73-mediated cell death pathway, and also provides a promising strategy for the treatment of patients with pancreatic cancer bearing p53 mutation.
High-Throughput Single-Cell Derived Sphere Formation for Cancer Stem-Like Cell Identification and Analysis
Authors: Chen Yu-Chih , Ingram Patrick N. , Fouladdel Shamileh , McDermott Sean P. , Azizi Ebrahim , Wicha Max S. , Yoon Euisik 
Published: June 2016

AbstractConsiderable evidence suggests that many malignancies are driven by a cellular compartment that displays stem cell properties. Cancer stem-like cells (CSCs) can be identified by expression of cell surface markers or enzymatic activity, but these methods are limited by phenotypic heterogeneity and plasticity of CSCs. An alternative phenotypic methodology based on in-vitro sphere formation has been developed, but it is typically labor-intensive and low-throughput. In this work, we present a 1,024-microchamber microfluidic platform for single-cell derived sphere formation. Utilizing a hydrodynamic capturing scheme, more than 70% of the microchambers capture only one cell, allowing for monitoring of sphere formation from heterogeneous cancer cell populations for identification of CSCs. Single-cell derived spheres can be retrieved and dissociated for single-cell analysis using a custom 96-gene panel to probe heterogeneity within the clonal CSC spheres. This microfluidic platform provides reliable and high-throughput sphere formation for CSC identification and downstream clonal analysis.
Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling
Authors: Frolov Antonina , Evans Ian M. , Li Ningning , Sidlauskas Kastytis , Paliashvili Ketevan , Lockwood Nicola , Barrett Angela , Brandner Sebastian , Zachary Ian C. , Frankel Paul 
Published: June 2016

AbstractImatinib was the first targeted tyrosine kinase inhibitor to be approved for clinical use and remains first-line therapy for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. We show that treatment of human glioblastoma multiforme (GBM) tumour cells with imatinib and the closely-related drug, nilotinib, strikingly increases tyrosine phosphorylation of p130Cas, focal adhesion kinase (FAK) and the downstream adaptor protein paxillin (PXN), resulting in enhanced cell migration and invasion. Imatinib and nilotinib-induced tyrosine phosphorylation was dependent on expression of p130Cas and FAK activity and was independent of known imatinib targets including Abl, platelet derived growth factor receptor beta (PDGFRβ) and the collagen receptor DDR1. Imatinib and nilotinib treatment increased two dimensional cell migration and three dimensional radial spheroid invasion in collagen. In addition, silencing of p130Cas and inhibition of FAK activity both strongly reduced imatinib and nilotinib stimulated invasion. Importantly, imatinib and nilotinib increased tyrosine phosphorylation of p130Cas, FAK, PXN and radial spheroid invasion in stem cell lines isolated from human glioma biopsies. These findings identify a novel mechanism of action in GBM cells for two well established front line therapies for cancer resulting in enhanced tumour cell motility.
Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
Authors: Warrilow Andrew G. S. , Price Claire L. , Parker Josie E. , Rolley Nicola J. , Smyrniotis Christopher J. , Hughes David D. , Thoss Vera , Nes W. David , Kelly Diane E. , Holman Theodore R. , Kelly Steven L. 
Published: June 2016

AbstractMalassezia globosa cytochromes P450 CYP51 and CYP5218 are sterol 14α-demethylase (the target of azole antifungals) and a putative fatty acid metabolism protein (and a potential azole drug target), respectively. Lanosterol, eburicol and obtusifoliol bound to CYP51 with Kd values of 32, 23 and 28 μM, respectively, catalyzing sterol 14α-demethylation with respective turnover numbers of 1.7 min−1, 5.6 min−1 and 3.4 min−1. CYP5218 bound a range of fatty acids with linoleic acid binding strongest (Kd 36 μM), although no metabolism could be detected in reconstitution assays or role in growth on lipids. Clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole and ketaminazole bound tightly to CYP51 (Kd ≤ 2 to 11 nM). In contrast, fluconazole did not bind to CYP5218, voriconazole and ketaminazole bound weakly (Kd ~107 and ~12 μM), whereas ketoconazole, clotrimazole and itraconazole bound strongest to CYP5218 (Kd ~1.6, 0.5 and 0.4 μM) indicating CYP5218 to be only a secondary target of azole antifungals. IC50 determinations confirmed M. globosa CYP51 was strongly inhibited by azole antifungals (0.15 to 0.35 μM). MIC100 studies showed itraconazole should be considered as an alternative to ketoconazole given the potency and safety profiles and the CYP51 assay system can be used in structure-activity studies in drug development.
A novel way to detect correlations on multi-time scales, with temporal evolution and for multi-variables
Authors: Yuan Naiming , Xoplaki Elena , Zhu Congwen , Luterbacher Juerg 
Published: June 2016

AbstractIn this paper, two new methods, Temporal evolution of Detrended Cross-Correlation Analysis (TDCCA) and Temporal evolution of Detrended Partial-Cross-Correlation Analysis (TDPCCA), are proposed by generalizing DCCA and DPCCA. Applying TDCCA/TDPCCA, it is possible to study correlations on multi-time scales and over different periods. To illustrate their properties, we used two climatological examples: i) Global Sea Level (GSL) versus North Atlantic Oscillation (NAO); and ii) Summer Rainfall over Yangtze River (SRYR) versus previous winter Pacific Decadal Oscillation (PDO). We find significant correlations between GSL and NAO on time scales of 60 to 140 years, but the correlations are non-significant between 1865–1875. As for SRYR and PDO, significant correlations are found on time scales of 30 to 35 years, but the correlations are more pronounced during the recent 30 years. By combining TDCCA/TDPCCA and DCCA/DPCCA, we proposed a new correlation-detection system, which compared to traditional methods, can objectively show how two time series are related (on which time scale, during which time period). These are important not only for diagnosis of complex system, but also for better designs of prediction models. Therefore, the new methods offer new opportunities for applications in natural sciences, such as ecology, economy, sociology and other research fields.
Facile and Scale Up Synthesis of Red Phosphorus-Graphitic Carbon Nitride Heterostructures for Energy and Environment Applications
Authors: Ansari Sajid Ali , Ansari Mohammad Omaish , Cho Moo Hwan 
Published: June 2016

AbstractThe development of heterostructured materials for efficient solar energy conversion and energy storage devices are essential for practical applications. In this study, a simple and relatively inexpensive method was used to improve the visible light-driven photocatalytic activity and electrochemical supercapacitor behavior of the graphitic carbon nitride (g-C3N4) by elemental red phosphorus (RPh). The as-prepared RPh-g-C3N4 was characterized in detail using a range of spectroscopic techniques to understand the structure, morphology, chemical interaction and chemical state of the materials. The visible light-driven photocatalytic activity and supercapacitive electrode performance were assessed by the photodegradation of model colored, non-colored organic pollutants and electrochemical half-cell measurements, respectively. The RPh-g-C3N4 heterostructure with 30 weight percent of RPh exhibited remarkably high photocatalytic activity for the degradation of pollutants compared to the bare constituent materials, which was further confirmed by the photoelectrochemical study under similar visible photoirradiation conditions. The RPh-g-C3N4 heterostructure supercapacitor electrode displayed a high capacitance of 465 F/g and excellent cyclic stability with capacitance retention of 90% after 1000 cycles at a current of 10 A/g. The superior performance was attributed mainly to the narrow band gap, high surface area, capacitive nature of RPh and nitrogen-rich skeleton of g-C3N4.
Phylogenomic analyses of bat subordinal relationships based on transcriptome data
Authors: Lei Ming , Dong Dong 
Published: June 2016

AbstractBats, order Chiroptera, are one of the largest monophyletic clades in mammals. Based on morphology and behaviour bats were once differentiated into two suborders Megachiroptera and Microchiroptera Recently, researchers proposed alternative views of chiropteran classification (suborders Yinpterochiroptera and Yangochiroptera) based on morphological, molecular and fossil evidence. Since genome-scale data can significantly increase the number of informative characters for analysis, transcriptome RNA-seq data for 12 bat taxa were generated in an attempt to resolve bat subordinal relationships at the genome level. Phylogenetic reconstructions were conducted using up to 1470 orthologous genes and 634,288 aligned sites. We found strong support for the Yinpterochiroptera-Yangochiroptera classification. Next, we built expression distance matrices for each species and reconstructed gene expression trees. The tree is highly consistent with sequence-based phylogeny. We also examined the influence of taxa sampling on the performance of phylogenetic methods, and found that the topology is robust to sampling. Relaxed molecular clock estimates the divergence between Yinpterochiroptera and Yangochiroptera around 63 million years ago. The most recent common ancestor of Yinpterochiroptera, corresponding to the split between Rhinolophoidea and Pteropodidae (Old World Fruit bats), is estimated to have occurred 60 million years ago. Our work provided a valuable resource to further explore the evolutionary relationship within bats.
Bodily ownership modulation in defensive responses: physiological evidence in brain-damaged patients with pathological embodiment of other’s body parts
Authors: Fossataro C. , Gindri P. , Mezzanato T. , Pia L. , Garbarini F. 
Published: June 2016

AbstractDo conscious beliefs about the body affect defensive mechanisms within the body? To answer this question we took advantage from a monothematic delusion of bodily ownership, in which brain-damaged patients misidentify alien limbs as their own. We investigated whether the delusional belief that an alien hand is their own hand modulates a subcortical defensive response, such as the hand-blink reflex. The blink, dramatically increases when the threated hand is inside the defensive peripersonal-space of the face. In our between-subjects design, including patients and controls, the threat was brought near the face either by the own hand or by another person’s hand. Our results show an ownership-dependent modulation of the defensive response. In controls, as well as in the patients’ intact-side, the response enhancement is significantly greater when the threat was brought near the face by the own than by the alien hand. Crucially, in the patients’ affected-side (where the pathological embodiment occurs), the alien (embodied) hand elicited a response enhancement comparable to that found when the threat is brought near the face by the real hand. These findings suggest the existence of a mutual interaction between our conscious beliefs about the body and the physiological mechanisms within the body.
The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts
Authors: Kemler Denise , Dahley Oliver , Roßwag Sven , Litfin Margarethe , Kassel Olivier 
Published: June 2016

AbstractThe transcription factor Myocyte enhancer factor 2C (MEF2C) plays a key role in the late differentiation of skeletal muscle progenitor cells, the so-called myoblasts. During myoblast differentiation, both MEF2C expression and transcriptional activity are regulated. We have reported that nTRIP6, the nuclear isoform of the focal adhesion LIM domain protein TRIP6, acts as an adaptor transcriptional co-activator for several transcription factors. It interacts with the promoter-bound transcription factors and consequently mediates the recruitment of other co-activators. Based on a described interaction between MEF2C and TRIP6 in a yeast-two-hybrid screen, we hypothesised a co-regulatory function of nTRIP6 for MEF2C. In proliferating myoblasts, nTRIP6 interacted with MEF2C and was recruited together with MEF2C to the MEF2-binding regions of the MEF2C target genes Myom2, Mb, Tnni2 and Des. Silencing nTRIP6 or preventing its interaction with MEF2C increased MEF2C transcriptional activity and increased the expression of these MEF2C target genes. Thus, nTRIP6 acts as a co-repressor for MEF2C. Mechanistically, nTRIP6 mediated the recruitment of the class IIa histone deacetylase HDAC5 to the MEF2C-bound promoters. In conclusion, our results unravel a transcriptional co-repressor function for nTRIP6. This adaptor co-regulator can thus exert either co-activator or co-repressor functions, depending on the transcription factor it interacts with.
Harvest locations of goose barnacles can be successfully discriminated using trace elemental signatures
Authors: Albuquerque Rui , Queiroga Henrique , Swearer Stephen E. , Calado Ricardo , Leandro Sérgio M. 
Published: June 2016

AbstractEuropean Union regulations state that consumers must be rightfully informed about the provenance of fishery products to prevent fraudulent practices. However, mislabeling of the geographical origin is a common practice. It is therefore paramount to develop forensic methods that allow all players involved in the supply chain to accurately trace the origin of seafood. In this study, trace elemental signatures (TES) of the goose barnacle Pollicipes pollicipes, collected from ten sites along the Portuguese coast, were employed to discriminate individual’s origin. Barium (Ba), boron (B), cadmium (Cd), chromium (Cr), lithium (Li), magnesium (Mg), manganese (Mn), phosphorous (P), lead (Pb), strontium (Sr) and zinc (Zn) - were quantified using Inductively Coupled Plasma−Mass Spectrometry (ICP-MS). Significant differences were recorded among locations for all elements. A regularized discriminant analysis (RDA) revealed that 83% of all individuals were correctly assigned. This study shows TES can be a reliable tool to confirm the geographic origin of goose barnacles at fine spatial resolution. Although additional studies are required to ascertain the reliability of TES on cooked specimens and the temporal stability of the signature, the approach holds great promise for the management of goose barnacles fisheries, enforcement of conservation policies and assurance in accurate labeling.
PiggyBac transposon-based polyadenylation-signal trap for genome-wide mutagenesis in mice
Authors: Li Limei , Liu Peng , Sun Liangliang , Bin Zhou  , Fei Jian 
Published: June 2016

AbstractWe designed a new type of polyadenylation-signal (PAS) trap vector system in living mice, the piggyBac (PB) (PAS-trapping (EGFP)) gene trapping vector, which takes advantage of the efficient transposition ability of PB and efficient gene trap and insertional mutagenesis of PAS-trapping. The reporter gene of PB(PAS-trapping (EGFP)) is an EGFP gene with its own promoter, but lacking a poly(A) signal. Transgenic mouse lines carrying PB(PAS-trapping (EGFP)) and protamine 1 (Prm1) promoter-driven PB transposase transgenes (Prm1-PBase) were generated by microinjection. Male mice doubly positive for PB(PAS-trapping (EGFP)) and Prm1-PBase were crossed with WT females, generating offspring with various insertion mutations. We found that 44.8% (26/58) of pups were transposon-positive progenies. New transposon integrations comprised 26.9% (7/26) of the transposon-positive progenies. We found that 100% (5/5) of the EGFP fluorescence-positive mice had new trap insertions mediated by a PB transposon in transcriptional units. The direction of the EGFP gene in the vector was consistent with the direction of the endogenous gene reading frame. Furthermore, mice that were EGFP-PCR positive, but EGFP fluorescent negative, did not show successful gene trapping. Thus, the novel PB(PAS-trapping (EGFP)) system is an efficient genome-wide gene-trap mutagenesis in mice.
Deciphering the Counterplay of Aspergillus fumigatus Infection and Host Inflammation by Evolutionary Games on Graphs
Authors: Pollmächer Johannes , Timme Sandra , Schuster Stefan , Brakhage Axel A. , Zipfel Peter F. , Figge Marc Thilo 
Published: June 2016

AbstractMicrobial invaders are ubiquitously present and pose the constant risk of infections that are opposed by various defence mechanisms of the human immune system. A tight regulation of the immune response ensures clearance of microbial invaders and concomitantly limits host damage that is crucial for host viability. To investigate the counterplay of infection and inflammation, we simulated the invasion of the human-pathogenic fungus Aspergillus fumigatus in lung alveoli by evolutionary games on graphs. The layered structure of the innate immune system is represented by a sequence of games in the virtual model. We show that the inflammatory cascade of the immune response is essential for microbial clearance and that the inflammation level correlates with the infection-dose. At low infection-doses, corresponding to daily inhalation of conidia, the resident alveolar macrophages may be sufficient to clear infections, however, at higher infection-doses their primary task shifts towards recruitment of neutrophils to infection sites.
Formation of functional CENP-B boxes at diverse locations in repeat units of centromeric DNA in New World monkeys
Authors: Kugou Kazuto , Hirai Hirohisa , Masumoto Hiroshi , Koga Akihiko 
Published: June 2016

AbstractCentromere protein B, which is involved in centromere formation, binds to centromeric repetitive DNA by recognizing a nucleotide motif called the CENP-B box. Humans have large numbers of CENP-B boxes in the centromeric repetitive DNA of their autosomes and X chromosome. The current understanding is that these CENP-B boxes are located at identical positions in the repeat units of centromeric DNA. Great apes also have CENP-B boxes in locations that are identical to humans. The purpose of the present study was to examine the location of CENP-B box in New World monkeys. We recently identified CENP-B box in one species of New World monkeys (marmosets). In this study, we found functional CENP-B boxes in CENP-A-assembled repeat units of centromeric DNA in 2 additional New World monkeys (squirrel monkeys and tamarins) by immunostaining and ChIP-qPCR analyses. The locations of the 3 CENP-B boxes in the repeat units differed from one another. The repeat unit size of centromeric DNA of New World monkeys (340–350 bp) is approximately twice that of humans and great apes (171 bp). This might be, associated with higher-order repeat structures of centromeric DNA, a factor for the observed variation in the CENP-B box location in New World monkeys.
A potential panel of six-long non-coding RNA signature to improve survival prediction of diffuse large-B-cell lymphoma
Authors: Sun Jie , Cheng Liang , Shi Hongbo , Zhang Zhaoyue , Zhao Hengqiang , Wang Zhenzhen , Zhou Meng 
Published: June 2016

AbstractLong non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology and have been implicated in the development and progression of cancers. However, the prognostic significance of lncRNAs in diffuse large-B-cell lymphoma (DLBCL) remains unclear and needs to be systematically investigated. In this study, we obtained and analyzed lncRNA expression profiles in three cohorts of 1043 DLBCL patients by repurposing the publicly available microarray datasets from the Gene Expression Omnibus (GEO) database. In the discovery series of 207 patients, we identified a set of six lncRNAs that was significantly associated with patients’ overall survival (OS) using univariate Cox regression analysis. The six prognostic lncRNAs were combined to form an expression-based six-lncRNA signature which classified patients of the discovery series into the high-risk group and low-risk group with significantly different survival outcome (HR = 2.31, 95% CI = 1.8 to 2.965, p < 0.001). The six-lncRNA signature was further confirmed in the internal testing series and two additional independent datasets with different array platform. Moreover, the prognostic value of the six-lncRNA signature is independent of conventional clinical factors. Functional analysis suggested that six-lncRNA signature may be involved with DLBCL through exerting their regulatory roles in known cancer-related pathways, immune system and signaling molecules interaction.
Impact of climate change on larch budmoth cyclic outbreaks
Authors: Iyengar Sudharsana V. , Balakrishnan Janaki , Kurths Jürgen 
Published: June 2016

AbstractPeriodic outbreaks of the larch budmoth Zeiraphera diniana population (and the massive forest defoliation they engender) have been recorded in the Alps over the centuries and are known for their remarkable regularity. But these have been conspicuously absent since 1981. On the other hand, budmoth outbreaks have been historically unknown in the larches of the Carpathian Tatra mountains. To resolve this puzzle, we propose here a model which includes the influence of climate and explains both the 8–9 year periodicity in the budmoth cycle and the variations from this, as well as the absence of cycles. We successfully capture the observed trend of relative frequencies of outbreaks, reproducing the dominant periodicities seen. We contend that the apparent collapse of the cycle in 1981 is due to changing climatic conditions following a tipping point and propose the recurrence of the cycle with a changed periodicity of 40 years – the next outbreak could occur in 2021. Our model also predicts longer cycles.