bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic acid reduces linoleic acid induced monocyte chemoattractant protein‐1 expression via PPARγ and nuclear factor‐κB pathway in retinal pigment epithelial cells
Authors: Fang I‐Mo , Yang Chang‐Hao , Yang Chung‐May 
Published: July 2014

ScopeTo investigate whether docosahexaenoic acid (DHA) could inhibit linoleic acid (LA) induced monocyte chemoattractant protein (MCP)‐1 expression in human retinal pigment epithelial (RPE) cells.Methods and resultsARPE‐19 cells were pretreated with DHA and then exposed to LA. The expression of MCP‐1 and PPARγ was examined using RT‐PCR and Western blot analysis. LA at 10, 25, or 50 μM induced expression of MCP ARPE‐19 cells in a dose‐dependent manner (p < 0.05). DHA at 50 and 100 μM effectively inhibited LA‐induced MCP‐1 expression and production (p < 0.05) and NF‐κB activation. In addition, the culture medium from LA‐stimulated ARPE‐19 cells could induce tube formation in choroidal endothelial cells (RF6A), whereas 100 μM DHA inhibited tube formation. DHA at 100 μM increased the expression and activity of PPARγ (p < 0.05). Pretreatment with PPARγ inhibitor (GW9662) abolished the inhibitory effect of DHA (100 μM) on LA‐induced IκB degradation, p65 translocation, and MCP‐1 expression in ARPE‐19 cells (p < 0.05), as well as tube formation in RF6A.ConclusionDHA reduced LA‐induced MCP‐1 expression via a PPARγ‐ and NF‐κB‐dependent pathway in ARPE‐19 cells. These results suggest the molecular mechanisms underlying the beneficial effects of increased consumption of DHA and reduced consumption of LA on age‐related macular degeneration.
Phenylpropenoic acid glucoside augments pancreatic beta cell mass in high‐fat diet‐fed mice and protects beta cells from ER stress‐induced apoptosis
Authors: Mathijs Iris , Da Cunha Daniel A. , Himpe Eddy , Ladriere Laurence , Chellan Nireshni , Roux Candice R. , Joubert Elizabeth , Muller Christo , Cnop Miriam , Louw Johan , Bouwens Luc 
Published: July 2014

ScopeA major goal of diabetes therapy is to identify novel drugs that preserve or expand pancreatic beta cell mass. Here, we examined the effect of a phenylpropenoic acid glucoside (PPAG) on the beta cell mass, and via which mechanism this effect is established.Methods and resultsMice were fed a high‐fat and fructose‐containing diet to induce obesity and hyperglycemia. PPAG treatment protected obese mice from diet‐induced hyperglycemia and resulted in a tripling of beta cell mass. The effect of the phytochemical on beta cell mass was neither due to increased proliferation, as determined by Ki67 immunostaining, nor to neogenesis, which was assessed by genetic lineage tracing. TUNEL staining revealed suppressed apoptosis in PPAG‐treated obese mice. In vitro, PPAG protected beta cells from palmitate‐induced apoptosis. It protected beta cells against ER stress by increasing expression of antiapoptotic B‐cell lymphoma 2 (BCL2) protein without affecting proapoptotic signals.ConclusionsWe identified an antidiabetic phytochemical that protects pancreatic beta cells from ER stress and apoptosis induced by high‐fat diet/lipotoxicity. At the tissue level, this led to a tripling of beta cell mass. At the molecular level, the protective effect of the phytochemical was mediated by increasing BCL2 expression in beta cells.
Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention
Authors: Beaver Laura M. , Buchanan Alex , Sokolowski Elizabeth I. , Riscoe Allison N. , Wong Carmen P. , Chang Jeff H. , Löhr Christiane V. , Williams David E. , Dashwood Roderick H. , Ho Emily 
Published: July 2014

ScopeEpidemiological studies provide evidence that consumption of cruciferous vegetables, like broccoli, can reduce the risk of cancer development. Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that induces anti‐proliferative and pro‐apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for this cancer‐specific cytotoxicity remain unclear.Methods and resultsWe utilized RNA sequencing and determined the transcriptomes of normal prostate epithelial cells, androgen‐dependent prostate cancer cells, and androgen‐independent prostate cancer cells treated with SFN. SFN treatment dynamically altered gene expression and resulted in distinct transcriptome profiles depending on prostate cell line. SFN also down‐regulated the expression of genes that were up‐regulated in prostate cancer cells. Network analysis of genes altered by SFN treatment revealed that the transcription factor Specificity protein 1 (Sp1) was present in an average of 90.5% of networks. Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells and Sp1 may be an important mediator of SFN‐induced changes in expression.ConclusionOverall, the data show that SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti‐cancer agent.
Hop‐derived prenylflavonoids are substrates and inhibitors of the efflux transporter breast cancer resistance protein (BCRP/ABCG2)
Authors: Tan Kee W. , Cooney Janine , Jensen Dwayne , Li Yan , Paxton James W. , Birch Nigel P. , Scheepens Arjan 
Published: July 2014

ScopeHops (Humulus lupulus L.) produce unique prenylflavonoids that exhibit interesting bioactivities. This study investigates the interactions between selected prenylflavonoids and breast cancer resistance protein (BCRP/ABCG2), an efflux transporter important for xenobiotic bioavailability and multidrug resistance (MDR).Methods and resultsABCG2‐inhibitory activity of xanthohumol (XN), isoxanthohumol (IX), 6‐prenylnaringenin (6‐PN), 8‐prenylnaringenin (8‐PN), and 6,8‐diprenylnarigenin (6,8‐diPN) was evaluated using mitoxantrone accumulation and vesicular transport assays. XN, IX, and 8‐PN were tested for a substrate‐type relationship with ABCG2 using ATPase and bidirectional transport assays. The prenylflavonoids exhibited significant ABCG2‐inhibitory activities in mitoxantrone accumulation and vesicular transport assays. In the ATPase assay, XN, IX, and 8‐PN inhibited baseline and sulfasalazine‐stimulated ATPase activities with IC50 of 2.16–27.0 μM. IX and 8‐PNalso displayed bell‐shaped activation curves in Ko143‐suppressed membranes, indicating a substrate‐type relationship. For IX, efflux ratios of 1.25 ± 0.21 and 9.18 ± 0.56 were observed in wild type and ABCG2‐overexpressing MDCKII cell monolayers, respectively. The latter was reduced to 1.25 ± 0.15 in the presence of the ABCG2‐specific inhibitor Ko143, demonstrating an ABCG2‐mediated efflux of IX. Additionally, evidence was shown for the involvement of ABCG2 in the efflux of 8‐PN and/or its sulfate conjugate.ConclusionPrenylflavonoids are potent inhibitors of ABCG2 and therefore implicated in ABCG2‐mediated food/herb‐drug interactions and MDR. ABCG2‐mediated efflux of prenylflavonoids may represent one mechanism that regulates prenylflavonoid bioavailability.
Selection and evaluation of optimal two‐dimensional CAIPIRINHA kernels applied to time‐resolved three‐dimensional CE‐MRA
Authors: Weavers Paul T. , Borisch Eric A. , Riederer Stephen J. 
Published: July 2014

PurposeTo develop and validate a method for choosing the optimal two‐dimensional CAIPIRINHA kernel for subtraction contrast‐enhanced MR angiography (CE‐MRA) and estimate the degree of image quality improvement versus that of some reference acceleration parameter set at R ≥ 8.MethodsA metric based on patient‐specific coil calibration information was defined for evaluating optimality of CAIPIRINHA kernels as applied to subtraction CE‐MRA. Evaluation in retrospective studies using archived coil calibration data from abdomen, calf, foot, and hand CE‐MRA exams was accomplished with an evaluation metric comparing the geometry factor (g‐factor) histograms. Prospective calf, foot, and hand CE‐MRA studies were evaluated with vessel signal‐to‐noise ratio (SNR).ResultsRetrospective studies show g‐factor improvement for the selected CAIPIRINHA kernels was significant in the feet, moderate in the abdomen, and modest in the calves and hands. Prospective CE‐MRA studies using optimal CAIPIRINHA show reduced noise amplification with identical acquisition time in studies of the feet, with minor improvements in the hands and calves.ConclusionA method for selection of the optimal CAIPIRINHA kernel for high (R ≥ 8) acceleration CE‐MRA exams given a specific patient and receiver array was demonstrated. CAIPIRINHA optimization appears valuable in accelerated CE‐MRA of the feet and to a lesser extent in the abdomen. Magn Reson Med 73:2234–2242, 2015. © 2014 Wiley Periodicals, Inc.
Deformable registration for quantifying longitudinal tumor changes during neoadjuvant chemotherapy
Authors: Ou Yangming , Weinstein Susan P. , Conant Emily F. , Englander Sarah , Da Xiao , Gaonkar Bilwaj , Hsieh Meng‐Kang , Rosen Mark , DeMichele Angela , Davatzikos Christos , Kontos Despina 
Published: July 2014

PurposeTo evaluate DRAMMS, an attribute‐based deformable registration algorithm, compared to other intensity‐based algorithms, for longitudinal breast MRI registration, and to show its applicability in quantifying tumor changes over the course of neoadjuvant chemotherapy.MethodsBreast magnetic resonance images from 14 women undergoing neoadjuvant chemotherapy were analyzed. The accuracy of DRAMMS versus five intensity‐based deformable registration methods was evaluated based on 2,380 landmarks independently annotated by two experts, for the entire image volume, different image subregions, and patient subgroups. The registration method with the smallest landmark error was used to quantify tumor changes, by calculating the Jacobian determinant maps of the registration deformation.ResultsDRAMMS had the smallest landmark errors (6.05 ± 4.86 mm), followed by the intensity‐based methods CC‐FFD (8.07 ± 3.86 mm), NMI‐FFD (8.21 ± 3.81 mm), SSD‐FFD (9.46 ± 4.55 mm), Demons (10.76 ± 6.01 mm), and Diffeomorphic Demons (10.82 ± 6.11 mm). Results show that registration accuracy also depends on tumor versus normal tissue regions and different patient subgroups.ConclusionsThe DRAMMS deformable registration method, driven by attribute‐matching and mutual‐saliency, can register longitudinal breast magnetic resonance images with a higher accuracy than several intensity‐matching methods included in this article. As such, it could be valuable for more accurately quantifying heterogeneous tumor changes as a marker of response to treatment. Magn Reson Med 73:2343–2356, 2015. © 2014 Wiley Periodicals, Inc.
Phase‐field modeling and simulation of fracture in brittle materials with strongly anisotropic surface energy
Authors: Li Bin , Peco Christian , Millán Daniel , Arias Irene , Arroyo Marino 
Published: July 2014

SummaryCrack propagation in brittle materials with anisotropic surface energy is important in applications involving single crystals, extruded polymers, or geological and organic materials. Furthermore, when this anisotropy is strong, the phenomenology of crack propagation becomes very rich, with forbidden crack propagation directions or complex sawtooth crack patterns. This problem interrogates fundamental issues in fracture mechanics, including the principles behind the selection of crack direction. Here, we propose a variational phase‐field model for strongly anisotropic fracture, which resorts to the extended Cahn‐Hilliard framework proposed in the context of crystal growth. Previous phase‐field models for anisotropic fracture were formulated in a framework only allowing for weak anisotropy. We implement numerically our higher‐order phase‐field model with smooth local maximum entropy approximants in a direct Galerkin method. The numerical results exhibit all the features of strongly anisotropic fracture and reproduce strikingly well recent experimental observations. Copyright © 2014 John Wiley & Sons, Ltd.
The proper generalized decomposition for the simulation of delamination using cohesive zone model
Authors: Metoui S. , Pruliere E. , Ammar A. , Dau F. , Iordanoff I. 
Published: July 2014

ABSTRACTThe use of cohesive zone models is an efficient way to treat the damage especially when the crack path is known a priori. It is the case in the modeling of delamination in composite laminates. However, the simulations using cohesive zone models are expensive in a computational point of view. When using implicit time integration or when solving static problems, the non‐linearity related to the cohesive model requires many iteration before reaching convergence. In explicit approaches, an important number of iterations are also needed because of the time step stability condition. In this article, a new approach based on a separated representation of the solution is proposed. The proper generalized decomposition is used to build the solution. This technique coupled with a cohesive zone model allows a significant reduction of the computational cost. The results approximated with the proper generalized decomposition are very close the ones obtained using the classical finite element approach. Copyright © 2014 John Wiley & Sons, Ltd.
Novel structural modeling and mesh moving techniques for advanced fluid–structure interaction simulation of wind turbines
Authors: Bazilevs Y. , Korobenko A. , Deng X. , Yan J. 
Published: July 2014

SummaryIn this paper, we target more advanced fluid–structure interaction (FSI) simulations of wind turbines than reported previously. For this, we illustrate how the recent advances in isogeometric analysis of thin structures may be used for efficient structural mechanics modeling of full wind turbine structures, including tower, nacelle, and blades. We consider both horizontal axis and vertical axis wind turbine designs. We enhance the sliding–interface formulation of aerodynamics, previously developed to handle flows about mechanical components in relative motion such as rotor–tower interaction to allow nonstationary sliding interfaces. To accommodate the nonstationary sliding interfaces, we propose a new mesh moving technique and present its mathematical formulation. The numerical examples include structural mechanics verification for the new offshore wind turbine blade design, FSI simulation of a horizontal axis wind turbine undergoing yawing motion as it turns into the wind and FSI simulation of a vertical axis wind turbine. The FSI simulations are performed at full scale and using realistic wind conditions and rotor speeds. Copyright © 2014 John Wiley & Sons, Ltd.
Protein interactomics based on direct molecular fishing on paramagnetic particles: Practical realization and further SPR validation
Authors: Ivanov Alexis S. , Medvedev Alexei , Ershov Pavel , Molnar Andrey , Mezentsev Yury , Yablokov Evgeny , Kaluzhsky Leonid , Gnedenko Oksana , Buneeva Olga , Haidukevich Irina , Sergeev Gennadiy , Lushchyk Aliaksandr , Yantsevich Alexey , Medvedeva Marina , Kozin Sergey , Popov Igor , Novikova Svetlana , Zgoda Victor , Gilep Andrey , Usanov Sergey , Lisitsa Andrey , Archakov Alexander 
Published: July 2014

There is increasing evidence that proteins function in the cell as integrated stable or temporally formed protein complexes, interactomes. Previously, using model systems we demonstrated applicability of direct molecular fishing on paramagnetic particles for protein interactomics (Ershov et al. Proteomics, 2012, 12, 3295). In the present study, we have used a combination of affinity‐based molecular fishing and subsequent MS for investigation of human liver proteins involved in interactions with immobilized microsomal cytochrome b5 (CYB5A), and also transthyretin and BSA as alternative affinity ligands (baits). The LC−MS/MS identification of prey proteins fished on these baits revealed three sets of proteins: 98, 120, and 220, respectively. Comparison analysis of these sets revealed only three proteins common for all the baits. In the case of paired analysis, the number of common proteins varied from 2 to 9. The binding capacity of some identified proteins has been validated by a SPR‐based biosensor. All the investigated proteins effectively interacted with the immobilized CYB5A (Kd values ranged from 0.07 to 1.1 μM). Results of this study suggest that direct molecular fishing is applicable for analysis of protein–protein interactions (PPI) under normal and pathological conditions, in which altered PPIs are especially important.
Giving voice to cancer patients: assessing non‐specific effects of an integrative oncology therapeutic program via short patient narratives
Authors: Keshet Yael , Schiff Elad , Samuels Noah , Ben‐Arye Eran 
Published: July 2014

AbstractObjectiveThe aim of this study was to assess patient perspectives regarding non‐specific effects of a complementary medicine (CM) consultation and intervention within an integrative oncology setting.MethodsPatients undergoing chemotherapy in a community‐based oncology service were referred by oncology healthcare providers to an integrative oncology physician trained in CM‐oriented supportive care. Assessment of concerns and well‐being was made using the Measure Yourself Concerns and Wellbeing questionnaire, at baseline and after 3 months of CM treatments, which were designed to improve quality of life (QoL) outcomes. Patients were asked to describe the most important aspects of the integrative treatment process. Free‐text narratives were examined using content analysis with ATLAS.Ti software for systematic coding.ResultsOf 152 patients' narratives analyzed, 44% reported an experience of patient‐centered care, including CM practitioners' approach of togetherness, uniqueness, and the invoking of an internal process. CM practitioner approach was experienced within a context of an enhanced sense of confidence; gaining a different perspective; and acquiring emotional resilience and empowerment.ConclusionsShort patient narratives should be considered for patient‐reported outcomes, expressing perspectives of both effects and experience of care. CM may promote patient QoL‐related outcomes through non‐specific effects, enhancing patient‐centered care. The benefits of CM dependent on general therapeutic incidental aspects (i.e., common factors) warrant attention regarding non‐specific components of treatment. Copyright © 2014 John Wiley & Sons, Ltd.
Metacognitive aspects influence subjective well‐being in parents of children with cancer
Authors: Toffalini Enrico , Veltri Alessia , Cornoldi Cesare 
Published: July 2014

AbstractObjectiveResearch suggests that metacognitive beliefs may be involved in psychological distress and even in the pathogenesis of emotional disorders. The present research is a first attempt to investigate how certain metacognitive aspects operate as favorable or adverse factors influencing subjective well‐being (SWB) in the parents of children with cancer.MethodThirty parents of children being treated for cancer completed questionnaires on their metacognitive beliefs (Metacognition Questionnaire), sensitivity to autobiographical memory, and self‐reported measures of positive and negative affect (Positive and Negative Affect Schedule). Results in the study group were compared with those obtained from 36 control parents of children being treated for acute, not life‐threatening illnesses (hospitalized control group) and from 30 control parents of healthy children (healthy control group).ResultsParents in both the study group and the hospitalized control group reported less SWB than the healthy control group. Most important, metacognitive aspects explained up to 77% of the variance in SWB in parents of children with cancer, as opposed to only 23% in hospitalized control group and 33% in the healthy control group.ConclusionDifferent metacognitive aspects have a crucial role—both negative and positive—in SWB of parents of children with cancer. It is suggested that the psychological support for parents coping with a child suffering from oncological disease should assess such aspects and try to address them in clinical practice. Copyright © 2014 John Wiley & Sons, Ltd.
Engineering deamidation‐susceptible asparagines leads to improved stability to thermal cycling in a lipase
Authors: Bhanuramanand K. , Ahmad Shoeb , Rao N. M. 
Published: July 2014

AbstractAt high temperatures, protein stability is influenced by chemical alterations; most important among them is deamidation of asparagines. Deamidation kinetics of asparagines depends on the local sequence, solvent, pH, temperature, and the tertiary structure. Suitable replacement of deamidated asparagines could be a viable strategy to improve deamidation‐mediated loss in protein properties, specifically protein thermostability. In this study, we have used nano RP‐HPLC coupled ESI MS/MS approach to identify residues susceptible to deamidation in a lipase (6B) on heat treatment. Out of 15 asparagines and six glutamines in 6B, only five asparagines were susceptible to deamidation at temperatures higher than 75°C. These five positions were subjected to site saturation mutagenesis followed by activity screen to identify the most suitable substitutions. Only three of the five asparagines were found to be tolerant to substitutions. Best substitutions at these positions were combined into a mutant. The resultant lipase (mutC) has near identical secondary structure and improved thermal tolerance as compared to its parent. The triple mutant has shown almost two‐fold higher residual activity compared to 6B after four cycles at 90°C. MutC has retained more than 50% activity even after incubation at 100°C. Engineering asparagines susceptible to deamidation would be a potential strategy to improve proteins to withstand very high temperatures.
Engineering of an isolated p110α subunit of PI3Kα permits crystallization and provides a platform for structure‐based drug design
Authors: Chen Ping , Deng Ya‐Li , Bergqvist Simon , Falk Matthew D. , Liu Wei , Timofeevski Sergei , Brooun Alexei 
Published: July 2014

AbstractPI3Kα remains an attractive target for the development of anticancer targeted therapy. A number of p110α crystal structures in complex with the nSH2‐iSH2 fragment of p85 regulatory subunit have been reported, including a few small molecule co‐crystal structures, but the utilization of this crystal form is limited by low diffraction resolution and a crystal packing artifact that partially blocks the ATP binding site. Taking advantage of recent data on the functional characterization of the lipid binding properties of p110α, we designed a set of novel constructs allowing production of isolated stable p110α subunit missing the Adapter Binding Domain and lacking or featuring a modified C‐terminal lipid binding motif. While this protein is not catalytically competent to phosphorylate its substrate PIP2, it retains ligand binding properties as indicated by direct binding studies with a pan‐PI3Kα inhibitor. Additionally, we determined apo and PF‐04691502 bound crystal structures of the p110α (105‐1048) subunit at 2.65 and 2.85 Å, respectively. Comparison of isolated p110α(105‐1048) with the p110α/p85 complex reveals a high degree of structural similarity, which validates suitability of this catalytically inactive p110α for iterative SBDD. Importantly, this crystal form of p110α readily accommodates the binding of noncovalent inhibitor by means of a fully accessible ATP site. The strategy presented here can be also applied to structural studies of other members of PI3KIA family.