bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered purinergic receptor‐Ca2+ signaling associated with hypoxia‐induced epithelial‐mesenchymal transition in breast cancer cells
Authors: Azimi Iman , Beilby Hannah , Davis Felicity M. , Marcial Daneth L. , Kenny Paraic A. , Thompson Erik W. , Roberts-Thomson Sarah J. , Monteith Gregory R. 
Published: September 2015

Hypoxia is a feature of the microenvironment of many cancers and can trigger epithelial‐mesenchymal transition (EMT), a process by which cells acquire a more invasive phenotype with enriched survival. A remodeling of adenosine 5′‐triphosphate (ATP)‐induced Ca2+ signaling via purinergic receptors is associated with epidermal growth factor (EGF)‐induced EMT in MDA‐MB‐468 breast cancer cells. Here, we assessed ATP‐mediated Ca2+ signaling in a model of hypoxia‐induced EMT in MDA‐MB‐468 cells. Like EGF, hypoxia treatment (1% O2) was also associated with a significant reduction in the sensitivity of MDA‐MB‐468 cells to ATP (EC50 of 0.5 μM for normoxic cells versus EC50 of 5.8 μM for hypoxic cells). Assessment of mRNA levels of a panel of P2X and P2Y purinergic receptors following hypoxia revealed a change in levels of a suite of purinergic receptors. P2X4, P2X5, P2X7, P2Y1 and P2Y11 mRNAs decreased with hypoxia, whereas P2Y6 mRNA increased. Up‐regulation of P2Y6 was a common feature of both growth factor‐ and hypoxia‐induced models of EMT. P2Y6 levels were also significantly increased in basal‐like breast tumors compared to other subtypes and breast cancer patients with higher P2Y6 levels showed reduced overall survival rates. P2Y6 siRNA‐mediated silencing and the P2Y6 pharmacological inhibitor MRS2578 reduced hypoxia‐induced vimentin protein expression in MDA‐MB‐468 cells. P2Y6 inhibition also reduced the migration of mesenchymal‐like MDA‐MB‐231 breast cancer cells. The up‐regulation of P2Y6 appears to be a common feature of the mesenchymal phenotype of breast cancer cells and inhibition of this receptor may represent a novel therapeutic target in breast cancer metastasis.
Personalised pathway analysis reveals association between DNA repair pathway dysregulation and chromosomal instability in sporadic breast cancer
Authors: Liu Chao , Srihari Sriganesh , Lal Samir , Gautier Benoît , Simpson Peter T. , Khanna Kum Kum , Ragan Mark A. , Lê Cao Kim-Anh 
Published: September 2015

The Homologous Recombination (HR) pathway is crucial for the repair of DNA double‐strand breaks (DSBs) generated during DNA replication. Defects in HR repair have been linked to the initiation and development of a wide variety of human malignancies, and exploited in chemical, radiological and targeted therapies. In this study, we performed a personalised pathway analysis independently for four large sporadic breast cancer cohorts to investigate the status of HR pathway dysregulation in individual sporadic breast tumours, its association with HR repair deficiency and its impact on tumour characteristics. Specifically, we first manually curated a list of HR genes according to our recent review on this pathway (Liu et al., 2014), and then applied a personalised pathway analysis method named Pathifier (Drier et al., 2013) on the expression levels of the curated genes to obtain an HR score quantifying HR pathway dysregulation in individual tumours. Based on the score, we observed a great diversity in HR dysregulation between and within gene expression‐based breast cancer subtypes, and by using two published HR‐defect signatures, we found HR pathway dysregulation reflects HR repair deficiency. Furthermore, we identified a novel association between HR pathway dysregulation and chromosomal instability (CIN) in sporadic breast cancer. Although CIN has long been considered as a hallmark of most solid tumours, with recent extensive studies highlighting its importance in tumour evolution and drug resistance, the molecular basis of CIN in sporadic cancers remains poorly understood. Our results imply that HR pathway dysregulation might contribute to CIN in sporadic breast cancer.
Boundedness of the velocity derivative skewness in various turbulent flows
Authors: Antonia R. A. , Tang S. L. , Djenidi L. , Danaila L. 
Published: September 2015

The variation of$S$, the velocity derivative skewness, with the Taylor microscale Reynolds number$\mathit{Re}_{{\it\lambda}}$is examined for different turbulent flows by considering the locally isotropic form of the transport equation for the mean energy dissipation rate$\overline{{\it\epsilon}}_{iso}$. In each flow, the equation can be expressed in the form$S+2G/\mathit{Re}_{{\it\lambda}}=C/\mathit{Re}_{{\it\lambda}}$, where$G$is a non-dimensional rate of destruction of$\overline{{\it\epsilon}}_{iso}$and$C$is a flow-dependent constant. Since$2G/\mathit{Re}_{{\it\lambda}}$is found to be very nearly constant for$\mathit{Re}_{{\it\lambda}}\geqslant 70$,$S$should approach a universal constant when$\mathit{Re}_{{\it\lambda}}$is sufficiently large, but the way this constant is approached is flow dependent. For example, the approach is slow in grid turbulence and rapid along the axis of a round jet. For all the flows considered, the approach is reasonably well supported by experimental and numerical data. The constancy of$S$at large$\mathit{Re}_{{\it\lambda}}$has obvious ramifications for small-scale turbulence research since it violates the modified similarity hypothesis introduced by Kolmogorov (J. Fluid Mech., vol. 13, 1962, pp. 82–85) but is consistent with the original similarity hypothesis (Kolmogorov,Dokl. Akad. Nauk SSSR, vol. 30, 1941, pp. 299–303).
Absorption and initial metabolism of 75Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data
Authors: Große Ruse Mareile , Søndergaard Lasse R. , Ditlevsen Susanne , Damgaard Morten , Fuglsang Stefan , Ottesen Johnny T. , Madsen Jan L. 
Published: September 2015

AbstractSelenomethionine (SeMet) is an important organic nutritional source of Se, but the uptake and metabolism of SeMet are poorly characterised in humans. Dynamic gamma camera images of the abdominal region were acquired from eight healthy young men after the ingestion of radioactive 75Se-l-SeMet (75Se-SeMet). Scanning started simultaneously to the ingestion of 75Se-SeMet and lasted 120 min. We generated time-activity curves from two-dimensional regions of interest in the stomach, small intestine and liver. During scanning, blood samples were collected at 10-min intervals to generate plasma time-activity curves. A four-compartment model, augmented with a delay between the liver and plasma, was fitted to individual participants’ data. The mean rate constant for 75Se-SeMet transport was 2·63 h–1 from the stomach to the small intestine, 13·2 h–1 from the small intestine to the liver, 0·261 h–1 from the liver to the plasma and 0·267 h–1 from the stomach to the plasma. The delay in the liver was 0·714 h. Gamma camera imaging provides data for use in compartmental modelling of 75Se-SeMet absorption and metabolism in humans. In clinical settings, the obtained rate constants and the delay in the liver may be useful variables for quantifying reduced intestinal absorption capacity or liver function.
Harnessing values to save the rhinoceros: insights from Namibia
Authors: Muntifering Jeff R. , Linklater Wayne L. , Clark Susan G. , !Uri-≠Khob Simson , Kasaona John K. , /Uiseb Kenneth , Du Preez Pierre , Kasaona Kapoi , Beytell Petrus , Ketji Jermain , Hambo Boas , Brown Matthew A. , Thouless Chris , Jacobs Shayne , Knight Andrew T. 
Published: September 2015

AbstractThe rate at which the poaching of rhinoceroses has escalated since 2010 poses a threat to the long-term persistence of extant rhinoceros populations. The policy response has primarily called for increased investment in military-style enforcement strategies largely based upon simple economic models of rational crime. However, effective solutions will probably require a context-specific, stakeholder-driven mix of top-down and bottom-up mechanisms grounded in theory that represents human behaviour more realistically. Using a problem-oriented approach we illustrate in theory and practice how community-based strategies that explicitly incorporate local values and institutions are a foundation for combating rhinoceros poaching effectively in specific contexts. A case study from Namibia demonstrates how coupling a locally devised rhinoceros monitoring regime with joint-venture tourism partnerships as a legitimate land use can reconcile individual values represented within a diverse stakeholder group and manifests as both formal and informal community enforcement. We suggest a social learning approach as a means by which international, national and regional governance can recognize and promote solutions that may help empower local communities to implement rhinoceros management strategies that align individual values with the long-term health of rhinoceros populations.
How to prove that your therapy is effective, even when it is not: a guideline
Authors: Cuijpers P. , Cristea I. A. 
Published: September 2015

Aims.Suppose you are the developer of a new therapy for a mental health problem or you have several years of experience working with such a therapy, and you would like to prove that it is effective. Randomised trials have become the gold standard to prove that interventions are effective, and they are used by treatment guidelines and policy makers to decide whether or not to adopt, implement or fund a therapy.Methods.You would want to do such a randomised trial to get your therapy disseminated, but in reality your clinical experience already showed you that the therapy works. How could you do a trial in order to optimise the chance of finding a positive effect?Results.Methods that can help include a strong allegiance towards the therapy, anything that increases expectations and hope in participants, making use of the weak spots of randomised trials (risk of bias), small sample sizes and waiting list control groups (but not comparisons with existing interventions). And if all that fails one can always not publish the outcomes and wait for positive trials.Conclusions.Several methods are available to help you show that your therapy is effective, even when it is not.
CPI motif interaction is necessary for capping protein function in cells
Authors: Edwards Marc , McConnell Patrick , Schafer Dorothy A. , Cooper John A. 
Published: September 2015

AbstractCapping protein (CP) has critical roles in actin assembly in vivo and in vitro. CP binds with high affinity to the barbed end of actin filaments, blocking the addition and loss of actin subunits. Heretofore, models for actin assembly in cells generally assumed that CP is constitutively active, diffusing freely to find and cap barbed ends. However, CP can be regulated by binding of the ‘capping protein interaction’ (CPI) motif, found in a diverse and otherwise unrelated set of proteins that decreases, but does not abolish, the actin-capping activity of CP and promotes uncapping in biochemical experiments. Here, we report that CP localization and the ability of CP to function in cells requires interaction with a CPI-motif-containing protein. Our discovery shows that cells target and/or modulate the capping activity of CP via CPI motif interactions in order for CP to localize and function in cells.
Corrected placement of Mus-Rattus fossil calibration forces precision in the molecular tree of rodents
Authors: Kimura Yuri , Hawkins Melissa T. R. , McDonough Molly M. , Jacobs Louis L. , Flynn Lawrence J. 
Published: September 2015

AbstractTime calibration derived from the fossil record is essential for molecular phylogenetic and evolutionary studies. Fossil mice and rats, discovered in the Siwalik Group of Pakistan, have served as one of the best-known fossil calibration points in molecular phylogenic studies. Although these fossils have been widely used as the 12 Ma date for theMus/Rattussplit or a more basal split, conclusive paleontological evidence for the nodal assignments has been absent. This study analyzes newly recognized characters that demonstrate lineage separation in the fossil record of Siwalik murines and examines the most reasonable nodal placement of the diverging lineages in a molecular phylogenetic tree by ancestral state reconstruction. Our specimen-based approach strongly indicates that Siwalik murines of theKarnimataclade are fossil members of the Arvicanthini-Otomyini-Millardini clade, which excludesRattusand its relatives. Combining the new interpretation with the widely accepted hypothesis that theProgonomysclade includesMus, the lineage separation event in the Siwalik fossil record represents theMus/Arvicanthissplit. Our test analysis on Bayesian age estimates shows that this new calibration point provides more accurate estimates of murine divergence than previous applications. Thus, we define this fossil calibration point and refine two other fossil-based points for molecular dating.
Baclofen mediates neuroprotection on hippocampal CA1 pyramidal cells through the regulation of autophagy under chronic cerebral hypoperfusion
Authors: Liu Li , Li Chang-jun , Lu Yun , Zong Xian-gang , Luo Chao , Sun Jun , Guo Lian-jun 
Published: September 2015

AbstractGABA receptors play an important role in ischemic brain injury. Studies have indicated that autophagy is closely related to neurodegenerative diseases. However, during chronic cerebral hypoperfusion, the changes of autophagy in the hippocampal CA1 area, the correlation between GABA receptors and autophagy and their influences on hippocampal neuronal apoptosis have not been well established. Here, we found that chronic cerebral hypoperfusion resulted in rat hippocampal atrophy, neuronal apoptosis, enhancement and redistribution of autophagy, down-regulation of Bcl-2/Bax ratio, elevation of cleaved caspase-3 levels, reduction of surface expression of GABAA receptor α1 subunit and an increase in surface and mitochondrial expression of connexin 43 (CX43) and CX36. Chronic administration of GABAB receptors agonist baclofen significantly alleviated neuronal damage. Meanwhile, baclofen could up-regulate the ratio of Bcl-2/Bax and increase the activation of Akt, GSK-3β and ERK which suppressed cytodestructive autophagy. The study also provided evidence that baclofen could attenuate the decrease in surface expression of GABAA receptor α1 subunit and down-regulate surface and mitochondrial expression of CX43 and CX36, which might enhance protective autophagy. The current findings suggested that, under chronic cerebral hypoperfusion, the effects of GABAB receptors activation on autophagy regulation could reverse neuronal damage.
The arsenic hyperaccumulating Pteris vittata expresses two arsenate reductases
Authors: Cesaro Patrizia , Cattaneo Chiara , Bona Elisa , Berta Graziella , Cavaletto Maria 
Published: September 2015

AbstractEnzymatic reduction of arsenate to arsenite is the first known step in arsenate metabolism in all organisms. Although the presence of one mRNA arsenate reductase (PvACR2) has been characterized in gametophytes of P. vittata, no arsenate reductase protein has been directly observed in this arsenic hyperaccumulating fern, yet. In order to assess the possible presence of arsenate reductase in P. vittata, two recombinant proteins, ACR2-His6 and Trx-His6-S-Pv2.5–8 were prepared in Escherichia coli, purified and used to produce polyclonal antibodies. The presence of these two enzymes was evaluated by qRT-PCR, immunoblotting and direct MS analysis. Enzymatic activity was detected in crude extracts. For the first time we detected and identified two arsenate reductase proteins (PvACR2 and Pv2.5–8) in sporophytes and gametophytes of P. vittata. Despite an increase of the mRNA levels for both proteins in roots, no difference was observed at the protein level after arsenic treatment. Overall, our data demonstrate the constitutive protein expression of PvACR2 and Pv2.5–8 in P. vittata tissues and propose their specific role in the complex metabolic network of arsenic reduction.
PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex
Authors: Alves Maria M. , Fuhler Gwenny M. , Queiroz Karla C.S. , Scholma Jetse , Goorden Susan , Anink Jasper , Arnold Spek C. , Hoogeveen-Westerveld Marianne , Bruno Marco J. , Nellist Mark , Elgersma Ype , Aronica Eleonora , Peppelenbosch Maikel P. 
Published: September 2015

AbstractTuberous sclerosis complex (TSC) is caused by inactivating mutations in eitherTSC1orTSC2and is characterized by uncontrolled mTORC1 activation. Drugs that reduce mTOR activity are only partially successful in the treatment of TSC, suggesting that mTOR-independent pathways play a role in disease development. Here, kinome profiles of wild-type andTsc2−/−mouse embryonic fibroblasts (MEFs) were generated, revealing a prominent role for PAK2 in signal transduction downstream of TSC1/2. Further investigation showed that the effect of the TSC1/2 complex on PAK2 is mediated through RHEB, but is independent of mTOR and p21RAC. We also demonstrated that PAK2 over-activation is likely responsible for the migratory and cell cycle abnormalities observed inTsc2−/−MEFs. Finally, we detected high levels of PAK2 activation in giant cells in the brains of TSC patients. These results show that PAK2 is a direct effector of TSC1-TSC2-RHEB signaling and a new target for rational drug therapy in TSC.
Charge transfer and electronic doping in nitrogen-doped graphene
Authors: Joucken Frédéric , Tison Yann , Le Fèvre Patrick , Tejeda Antonio , Taleb-Ibrahimi Amina , Conrad Edward , Repain Vincent , Chacon Cyril , Bellec Amandine , Girard Yann , Rousset Sylvie , Ghijsen Jacques , Sporken Robert , Amara Hakim , Ducastelle François , Lagoute Jérôme 
Published: September 2015

AbstractUnderstanding the modification of the graphene’s electronic structure upon doping is crucial for enlarging its potential applications. We present a study of nitrogen-doped graphene samples on SiC(000"Equation missing") combining angle-resolved photoelectron spectroscopy, scanning tunneling microscopy and spectroscopy and X-ray photoelectron spectroscopy (XPS). The comparison between tunneling and angle-resolved photoelectron spectra reveals the spatial inhomogeneity of the Dirac energy shift and that a phonon correction has to be applied to the tunneling measurements. XPS data demonstrate the dependence of the N 1s binding energy of graphitic nitrogen on the nitrogen concentration. The measure of the Dirac energy for different nitrogen concentrations reveals that the ratio usually computed between the excess charge brought by the dopants and the dopants’ concentration depends on the latter. This is supported by a tight-binding model considering different values for the potentials on the nitrogen site and on its first neighbors.
Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells
Authors: Kim Seong-Hoon , Ryu Hye Guk , Lee Juhyun , Shin Joon , Harikishore Amaravadhi , Jung Hoe-Yune , Kim Ye Seul , Lyu Ha-Na , Oh Eunji , Baek Nam-In , Choi Kwan-Yong , Yoon Ho Sup , Kim Kyong-Tai 
Published: September 2015

AbstractMany mitotic kinases have been targeted for the development of anti-cancer drugs and inhibitors of these kinases have been expected to perform well for cancer therapy. Efforts focused on selecting good targets and finding specific drugs to target are especially needed, largely due to the increased frequency of anti-cancer drugs used in the treatment of lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell survival. We found that ursolic acid (UA) inhibits the catalytic activity of VRK1 via direct binding to the catalytic domain of VRK1. UA weakens surveillance mechanisms by blocking 53BP1 foci formation induced by VRK1 in lung cancer cells and possesses synergistic anti-cancer effects with DNA damaging drugs. Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients.
Illusory Tactile Motion Perception: An Analog of the Visual Filehne Illusion
Authors: Moscatelli Alessandro , Hayward Vincent , Wexler Mark , Ernst Marc O. 
Published: September 2015

AbstractWe continually move our body and our eyes when exploring the world, causing our sensory surfaces, the skin and the retina, to move relative to external objects. In order to estimate object motion consistently, an ideal observer would transform estimates of motion acquired from the sensory surface into fixed, world-centered estimates, by taking the motion of the sensor into account. This ability is referred to as spatial constancy. Human vision does not follow this rule strictly and is therefore subject to perceptual illusions during eye movements, where immobile objects can appear to move. Here, we investigated whether one of these, the Filehne illusion, had a counterpart in touch. To this end, observers estimated the movement of a surface from tactile slip, with a moving or with a stationary finger. We found the perceived movement of the surface to be biased if the surface was sensed while moving. This effect exemplifies a failure of spatial constancy that is similar to the Filehne illusion in vision. We quantified this illusion by using a Bayesian model with a prior for stationarity, applied previously in vision. The analogy between vision and touch points to a modality-independent solution to the spatial constancy problem.
CRISPR/Cas9-Assisted Transformation-Efficient Reaction (CRATER), a novel method for selective transformation
Authors: Rothschild L. J. , Greenberg D. T. , Takahashi J. R. , Thompson K. A. , Maheshwari A. J. , Kent R. E. , McCutcheon G. , Shih J. D. , Calvet C. , Devlin T. D. , Ju T. , Kunin D. , Lieberman E. , Nguyen T. , Tran F. G. , Xiang D. , Fujishima K. 
Published: September 2015

AbstractThe CRISPR/Cas9 system has revolutionized genome editing by providing unprecedented DNA-targeting specificity. Here we demonstrate that this system can be applied to facilitate efficient plasmid selection for transformation as well as selective gene insertion into plasmid vectors by cleaving unwanted plasmid byproducts after restriction enzyme digestion and ligation. Using fluorescent and chromogenic proteins as reporters, we demonstrate that CRISPR/Cas9 cleavage excludes unwanted ligation byproducts and increases transformation efficiency of desired inserts from 20% up to 97% ± 3%. This CRISPR/Cas9-Assisted Transformation-Efficient Reaction (CRATER) protocol is a novel, inexpensive, and convenient method for obtaining specific cloning products.
Divergence or convergence: paradoxes in corporate governance?
Authors: Chhillar Palka , Lellapalli Ramana Venkata 
Published: September 2015

Purpose– This review paper aims to compare the various dimensions in the finance literature pertaining to the Anglo-Saxon Model (Stockholder Model) prevalent in the USA and the UK with the German Model (Stakeholder Model) of corporate governance prevalent in Germany and continental Europe. The present study identifies different strands of research on the various dimensions of these models, along with aspects of governance in emerging economies and the phenomenon of the convergence of these governance mechanisms.Design/methodology/approach– The literature review on corporate governance models has been carried out on the themes of internal and external governance mechanisms. The review considers agency theory along with principal–principal (PP) conflicts as the fundamental blocks explaining the need for governance structures.Findings– The traditional models of governance, along with the incorporation of PP conflicts, will result in a hybrid model inculcating the best of both the traditional models. However, convergence in the true sense may not be possible owing to fundamental differences pertaining to cultural, economic, legal and socio-economic aspects of the firm.Originality/value– This paper proposes a framework incorporating the interplay of managerial talent and controlling shareholders to understand the governance system that may be applicable for firms in emerging economies.