bluuebunny/crossref_metadata_2025 huggingface dataset:
Point‐of‐Care Platelet Function Testing Predicts Bleeding in Patients Exposed to Clopidogrel Undergoing Coronary Artery Bypass Grafting: Verify Pre‐Op TIMI 45—A Pilot Study
Authors: Reed Grant W. , Kumar Amit , Guo Jianping , Aranki Sary , Shekar Prem , Agnihotri Arvind , Maree Andrew O. , McLean Dalton S. , Rosenfield Kenneth , Cannon Christopher P.
Published: February 2015

Background

Guidelines recommend delaying coronary artery bypass grafting (CABG) for 5 days after discontinuing clopidogrel. However, platelet function may recover quicker in certain individuals.

Hypothesis

We hypothesized that perioperative measurement of platelet function with a point‐of‐care P2Y12 inhibitor assay could predict bleeding during CABG in patients exposed to clopidogrel.

Methods

Verify Pre‐Op TIMI 45 was a prospective pilot study of 39 patients on clopidogrel who subsequently underwent CABG. Preoperative on‐treatment platelet reactivity was assessed with VerifyNow P2Y12 Reaction Units (PRU), with higher PRU indicating more reactive platelets. Outcomes were stratified by PRU quartiles, as well as prespecified cutpoints for the lowest quartile (PRU 173), a cutpoint for major bleeding determined by the Youden index using receiver operator curve analysis (PRU 207), and clopidogrel resistance (PRU 230).

Results

Patients in higher PRU quartiles experienced smaller decreases in hemoglobin and hematocrit (P < 0.05 for all comparisons), less major bleeding (P = 0.021), and less major or minor bleeding (P = 0.003). Patients above the PRU 207 and 230 cutpoints had less chest‐tube output (P = 0.041 and P = 0.012, respectively), less major bleeding (P = 0.005 and P = 0.036, respectively), and less major or minor bleeding (P = 0.013 and P < 0.001, respectively). By receiver operator curve analysis, preoperative PRU ≤ 207 discriminated between patients with and without major bleeding during surgery (area under the curve: 0.76, 95% confidence interval: 0.59‐0.94, P = 0.018).

Conclusions

In this pilot study, we found that point‐of‐care platelet function assessment could predict bleeding in patients recently exposed to clopidogrel undergoing CABG.
Time Series Models for Air Pollution Modelling Considering the Shift to Natural Gas in a Turkish City
Authors: Taşpınar Fatih
Published: February 2015

Fossil fuel utilization for residential heating is still a major source of fine particulate matter (PM10) and sulphur dioxide (SO2), despite the increasing consumption of natural gas in some cities in Turkey. In the present study, PM10 and SO2 air pollution and residential natural gas consumption (RNGC) were modelled by various multi‐parameter time series modelling methods (TSMs). To estimate short‐term pollution levels considering the future estimates of RNGC and meteorological factors, a time series dataset was designed for the years 2007–2013. Factor analysis was also performed to aid in the selection of variables for constructing TSMs. The error measures and coefficient of determination (R2) were used to evaluate forecasting accuracy of the models constructed. In the short‐term estimation of RNGC, PM10, and SO2 for 2014–2015, temperature dependent ARIMAX(1,1,2) (R2 = 0.944) and RNGC and meteorological factors dependent SARIMAX(0,1,1)(1,1,0)12 (R2 = 0.761) and ARIMAX(1,1,0) (R2 = 0.698) models, respectively, yielded the best fitting scores and accuracy measures. The models performed well in reflecting the time series data and thus, could be utilized in energy planning for sustainable development concerning environmental decision making and short‐term air quality forecasting for public health.
Ligand‐Biased and Probe‐Dependent Modulation of Chemokine Receptor CXCR3 Signaling by Negative Allosteric Modulators
Authors: Bernat Viachaslau , Brox Regine , Heinrich Markus R. , Auberson Yves P. , Tschammer Nuska
Published: February 2015

Over the last decade, functional selectivity (or ligand bias) has evolved from being a peculiar phenomenon to being recognized as an essential feature of synthetic ligands that target G protein‐coupled receptors (GPCRs). The CXC chemokine receptor 3 (CXCR3) is an outstanding platform to study various aspects of biased signaling, because nature itself uses functional selectivity to manipulate receptor signaling. At the same time, CXCR3 is an attractive therapeutic target in the treatment of autoimmune diseases and cancer. Herein we report the discovery of an 8‐azaquinazolinone derivative (N‐{1‐[3‐(4‐ethoxyphenyl)‐4‐oxo‐3,4‐dihydropyrido[2,3‐d]pyrimidin‐2‐yl]ethyl}‐4‐(4‐fluorobutoxy)‐N‐[(1‐methylpiperidin‐4‐yl)methyl]butanamide, 1 b) that can inhibit CXC chemokine 11 (CXCL11)‐dependent G protein activation over β‐arrestin recruitment with 187‐fold selectivity. This compound also demonstrates probe‐dependent activity, that is, it inhibits CXCL11‐ over CXCL10‐mediated G protein activation with 12‐fold selectivity. Together with a previously reported biased negative allosteric modulator from our group, the present study provides additional information on the molecular requirements for allosteric modulation of CXCR3.
Role mining based on cardinality constraints
Authors: Li Ruixuan , Li Huaqing , Gu Xiwu , Li Yuhua , Ye Wei , Ma Xiaopu
Published: February 2015

Role mining was recently proposed to automatically find roles among user‐permission assignments using data mining technologies. However, the current studies about role mining mainly focus on how to find roles, without considering the constraints that are essentially required in role‐based access control systems. In this paper, we present a role mining algorithm with constraints, especially for the cardinality constraints. We illustrate it is essential for role mining to take cardinality constraints into account, and introduce the concepts of the cardinality constraints of roles and permissions. We further propose a role mining algorithm to generate roles based on these two kinds of cardinality constraints. The algorithm uses graph theory to model the role mining problem and maps the relation of two roles to the relation of graph elements. We set an optimization goal for role mining and employ graph optimization theory to find roles that satisfy the aforementioned cardinality constraints. We carry out the experiments to evaluate our approach. The experimental results demonstrate the rationality and effectiveness of the proposed algorithm. Copyright © 2015 John Wiley & Sons, Ltd.
Production of Renewable Hexanols from Mechanocatalytically Depolymerized Cellulose by Using Ir‐ReOx/SiO2 catalyst
Authors: Liu Sibao , Okuyama Yasuyo , Tamura Masazumi , Nakagawa Yoshinao , Imai Akio , Tomishige Keiichi
Published: February 2015

Invited for this month′s cover is the group of Keiichi Tomishige at Tohoku University, Sendai (Japan). The image shows that in a biphasic reaction system (n‐decane+H2O) high yields of hexanols can be produced from mechanocatalytically depolymerized cellulose. The Full Paper itself is available at 10.1002/cssc.201403010
Quantification of cells with specific phenotypes I: Determination of CD4+ cell count per microliter in reconstituted lyophilized human PBMC prelabeled with anti‐CD4 FITC antibody
Authors: Stebbings Richard , Wang Lili , Sutherland Janet , Kammel Martin , Gaigalas Adolfas K. , John Manuela , Roemer Bodo , Kuhne Maren , Schneider Rudolf J. , Braun Michael , Engel Andrea , Dikshit Dinesh K. , Abbasi Fatima , Marti Gerald E. , Paola Sassi Maria , Revel Laura , Kim Sook‐Kyung , Baradez Marc‐Olivier , Lekishvili Tamara , Marshall Damian , Whitby Liam , Jing Wang , Ost Volker , Vonsky Maxim , Neukammer Jörg
Published: February 2015

A surface‐labeled lyophilized lymphocyte (sLL) preparation has been developed using human peripheral blood mononuclear cells prelabeled with a fluorescein isothiocyanate conjugated anti‐CD4 monoclonal antibody. The sLL preparation is intended to be used as a reference material for CD4+ cell counting including the development of higher order reference measurement procedures and has been evaluated in the pilot study CCQM‐P102. This study was conducted across 16 laboratories from eight countries to assess the ability of participants to quantify the CD4+ cell count of this reference material and to document cross‐laboratory variability plus associated measurement uncertainties. Twelve different flow cytometer platforms were evaluated using a standard protocol that included calibration beads used to obtain quantitative measurements of CD4+ T cell counts. There was good overall cross‐platform and counting method agreement with a grand mean of the laboratory calculated means of (301.7 ± 4.9) μL−1 CD4+ cells. Excluding outliers, greater than 90% of participant data agreed within ±15%. A major contribution to variation of sLL CD4+ cell counts was tube to tube variation of the calibration beads, amounting to an uncertainty of 3.6%. Variation due to preparative steps equated to an uncertainty of 2.6%. There was no reduction in variability when data files were centrally reanalyzed. Remaining variation was attributed to instrument specific differences. CD4+ cell counts obtained in CCQM‐P102 are in excellent agreement and show the robustness of both the measurements and the data analysis and hence the suitability of sLL as a reference material for interlaboratory comparisons and external quality assessment. © 2015 The Authors. Published by Wiley Periodicals, Inc.
Quantification of cells with specific phenotypes II: Determination of CD4 expression level on reconstituted lyophilized human PBMC labelled with anti‐CD4 FITC antibody
Authors: Wang L. , Stebbings R. , Gaigalas A. K. , Sutherland J. , Kammel M. , John M. , Roemer B. , Kuhne M. , Schneider R. J. , Braun M. , Engel A. , Dikshit D. , Abbasi F. , Marti G. E. , Sassi M. , Revel L. , Kim S. K. , Baradez M. , Lekishvili T. , Marshall D. , Whitby L. , Jing W. , Ost V. , Vonsky M. , Neukammer J.
Published: February 2015

This report focuses on the characterization of CD4 expression level in terms of equivalent number of reference fluorophores (ERF). Twelve different flow cytometer platforms across sixteen laboratories were utilized in this study. As a first step the participants were asked to calibrate the fluorescein isothiocyanate (FITC) channel of each flow cytometer using commercially available calibration standard consisting of five populations of microspheres. Each population had an assigned value of equivalent fluorescein fluorophores (EFF denotes a special case of the generic term ERF with FITC as the reference fluorophore). The EFF values were assigned at the National Institute of Standards and Technology (NIST). A surface‐labelled lyophilized cell preparation was provided by the National Institute of Biological Standards and Control (NIBSC), using human peripheral blood mononuclear cells (PBMC) pre‐labeled with a FITC conjugated anti‐CD4 monoclonal antibody. Three PBMC sample vials, provided to each participant, were used for the CD4 expression analysis. The PBMC are purported to have a fixed number of surface CD4 receptors. On the basis of the microsphere calibration, the EFF value of the PBMC samples was measured to characterize the population average CD4 expression level of the PBMC preparations. Both the results of data analysis performed by each participant and the results of centralized analysis of all participants' raw data are reported. Centralized analysis gave a mean EFF value of 22,300 and an uncertainty of 750, corresponding to 3.3% (level of confidence 68%) of the mean EFF value. The next step will entail the measurement of the ERF values of the lyophilized PBMC stained with labels for other fluorescence channels. The ultimate goal is to show that lyophilized PBMC is a suitable biological reference cell material for multicolor flow cytometry and that it can be used to present multicolor flow cytometry measurements in terms of ABC (antibodies bound per cell) units. © 2015 International Society for Advancement of Cytometry
Th17 cytokines in non‐melanoma skin cancer
Authors: McAllister Florencia , Kolls Jay K.
Published: February 2015

T‐helper‐type 17 cytokines have been implicated in epithelial cancer progression at mucosal sites. In this issue of the European Journal of Immunology, Nardinocchi et al. [Eur. J. Immunol. 2015. 45: 922–931] show that the Th17 cytokines IL‐17 and IL‐22 can both signal to nonmelanoma skin cancer cells, inducing both cellular proliferation and enhanced migration of human basal cell carcinoma and squamous cell carcinoma cell lines in vitro. These cytokines were also shown to exacerbate tumor growth in mice injected with the squamous cell carcinoma line, CAL27. Thus, IL‐17 and IL‐22 may be key factors in skin cancer progression and may provide novel prognostic markers in nonmelanoma skin cancer.
Fabrication of Single‐Layer Graphitic Carbon Nitride and Coupled Systems for the Photocatalytic Degradation of Dyes under Visible‐Light Irradiation
Authors: Rong Xinshan , Qiu Fengxian , Zhao Hao , Yan Jie , Zhu Xiaolu , Yang Dongya
Published: February 2015

A coupled system for the photocatalytic degradation of rhodamine B (RhB) was realized by a CdS/SL g‐C3N4 (SL g‐C3N4 = single‐layer graphitic carbon nitride) photocatalyst under visible‐light irradiation. SL g‐C3N4 was fabricated by the ultrasonic exfoliation of bulk g‐C3N4. Two series of CdS/SL g‐C3N4 and CdS/g‐C3N4 photocatalysts with different CdS content were prepared by a hydrothermal process. The photocatalysts were characterized by Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), UV/Vis diffuse reflection spectroscopy (DRS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), X‐ray photoelectron spectroscopy (XPS), and transient photocurrent measurements. Compared with those of pure bulk g‐C3N4, CdS, and SL g‐C3N4, the samples of the CdS/SL g‐C3N4 photocatalyst series exhibited enhanced photocatalytic activities and excellent photostabilities under visible‐light irradiation. With an optimum CdS content of 33.3 % and a reaction time of 120 min, the RhB degradation efficiency reached 99.55 % under visible‐light irradiation. From a first‐order model, the rate constant (k) of the 33.3 % CdS/SL g‐C3N4 photocatalyst is up to 13.59, 6.10, and 4.54 times those of bulk g‐C3N4, SL g‐C3N4, and CdS, respectively. On the basis of the corresponding energy band positions, a mechanism for enhanced photocatalytic activity is proposed. Owing to the excellent performance of the CdS/SL g‐C3N4 series, a visible‐light‐responsive and environmentally friendly photocatalyst for the degradation of dyes was obtained.
Enzyme‐assisted formation of hybrid biopolymer hydrogels incorporating active phenolic nanospheres
Authors: Petkova Petya , Francesko Antonio , Tzanov Tzanko
Published: February 2015

Advances in development of nanocomposite gels that provide localized delivery of pharmaceuticals for treatment of chronic wounds are being highly pursued. To design such materials, the use of natural polymers is recommendable due to their intrinsic biocompatibility and biodegradability. Moreover, the use of biocatalytic approaches for composite assembling is preferred compared to harsh chemical cross‐linking reagents. In this study, HRP catalyzed cross‐linking of hydrogels from aqueous solution of thiolated chitosan to in situ incorporated sonochemically synthesized epigallocatechin gallate nanospheres (EGCG NSs). The potential of the generated NSs for chronic wound treatment was evaluated by assessing their antibacterial properties and inhibitory effect on myeloperoxidase and collagenase—major enzymes of inflamed chronic wounds. The EGCG NSs displayed better antibacterial and antienzymatic properties compared to the EGCG in solution. Also, the NSs were incorporated into hydrogels without affecting their integrity and were released intact in a sustained manner (during 6 days). The cytotoxicity assay confirmed the compatibility of the hybrid material with human fibroblasts that suffered less than 10% decrease in viability during 24 h. Release of functional phenolic NSs and good compatibility of the composite hydrogel with cells suggested its potential application in chronic wound management.
Toxicity of Cúspide 480SL® spray mixture formulation of glyphosate to aquatic organisms
Authors: Currie Zachary , Prosser Ryan S. , Rodriguez-Gil Jose Luis , Mahon Kim , Poirier Dave , Solomon Keith R.
Published: February 2015

In 2011, an alternative formulation of glyphosate (Cúspide 480SL®) was chosen to replace Roundup-SL®, Fuete-SL®, and Gly-41® for the control of Erythroxylum coca, the source of cocaine, in Colombia. Cúspide 480SL contains the active ingredient glyphosate isopropylamine (IPA) salt, which is the same active ingredient used in previous formulations. However, Cúspide 480SL contains an alkyl polyglycoside surfactant rather than the polyethoxylated tallow amine (POEA) surfactant used in other formulations and known to be more toxic to nonprimary producing aquatic organisms than glyphosate itself. An adjuvant, Cosmo-Flux F411, and water also are added to the spray mixture before application. Aquatic ecosystems adjacent to the target coca fields might be exposed to the spray mix, placing aquatic organisms at risk. Because no toxicity data were available for spray mixture on aquatic organisms, acute toxicity tests were conducted on aquatic plants, invertebrates, and fish, by using the Cúspide 480SL spray mix as described on the label. Based on the median effective concentration (EC50) values for similar organisms, the spray mixture was less toxic to aquatic organisms than formulations previously used for the control of coca (i.e., Roundup-SL, Fuete-SL, and Gly-41). A physical effect induced by Cosmo-Flux F411 was observed in Daphnia magna, Ceriodaphnia dubia, and Hyalella azteca, causing the invertebrates to be trapped in an oily film that was present at the surface of the water. However, a hazard assessment for the Cúspide 480SL spray mix, using estimated worst-case exposure scenario concentrations and EC50 values from the toxicity tests, indicated de minimis hazard for the tested aquatic animals, with hazard quotients all <<1. Environ Toxicol Chem 2015;34:1178–1184. © 2015 SETAC
Quantifying natural variability as a method to detect environmental change: Definitions of the normal range for a single observation and the mean of m observations
Authors: Barrett Timothy J. , Hille Kelly A. , Sharpe Rainie L. , Harris Katherine M. , Machtans Hilary M. , Chapman Peter M.
Published: February 2015

The normal range has been defined as the range that encloses 95% of reference values; in practice this range has been defined as the reference mean ± 2 standard deviations (SD). When sample sizes are small and reference data are not normally distributed, the mean ± 2 SDs do not enclose 95% of data values. Prediction intervals (PI) calculated using sample statistics are used in the present study to define the normal range for a single observation and the mean of m observations. The PIs provide confidence limits for the next randomly selected observation (or mean of m observations) from a population. The PIs are defined using normally distributed reference data; normality can typically be achieved with transformations of the data. Covariates can be used to explain some of the variability in the reference distribution, increasing the ability to detect change. When assumptions of normality are not met, alternative methods of defining the normal range are provided. The normal range can be used to quantify natural variability and assess change from the reference distribution. It can be used as an early warning indicator of change in environmental monitoring to identify the need for further investigation. Environ Toxicol Chem 2015;34:1185–1195. © 2015 SETAC
Geochemical characteristics and depositional environment of the Middle Permian mudstones from central Qiangtang Basin, northern Tibet
Authors: Hu Junjie , Li Qi , Li Juan , Huang Jing , Ge Dongsheng
Published: February 2015

Geochemical characteristics of the Middle Permian mudstones from the Longge Formation in the Jiaomuri area, central uplift zone of Qiangtang Basin have been analysed to constrain their provenance, tectonic setting, depositional redox condition and palaeoclimate. Based on the geochemical parameters like CIA, PIA, ICV values and Th/U, K/Rb ratios indicate that the source rocks were affected by low degree weathering conditions. The U/Th, V/Cr, Ni/Co, V/Sc ratios and Uau, C‐values of samples suggest that the mudstones were formed in an oxic environment, with arid palaeoclimate. Bulk‐rock geochemistry analysis indicates that they are mainly arkose and subarkose, derived from dominantly andesitic rocks, probably a mixing of felsic and mafic provenance. The CIA, PIA and ICV values of these samples suggest that the Longge mudstones are compositionally immature and related to moderate weathering. The tectonic discrimination diagrams, as well as critical trace and REE characteristic parameters imply an oceanic arc or continental arc setting for the depositional basin of mudstones from the Longge Formation, probably back‐arc basin. This study supports an occurrence of archipelagic oceanic basins in the Jiaomuri area in the Middle Permian, which provides evidence for the research of the Longmu Co–Shuanghu–Lancangjiang Suture. Copyright © 2015 John Wiley & Sons, Ltd.
Shear Stress Modulates Resistin‐Induced CC Chemokine Ligand 19 Expression in Human Aortic Endothelial Cells
Authors: Yu Hong‐Ren , Sung Mao‐Ling , Kuo Hsing‐Chun , Lin Chi‐Hui , Chen Cheng‐Nan
Published: February 2015

Resistin may be an important link between obesity and diabetes. Recent studies have suggested an association between resistin and atherogenic processes. In addition, CCL19 is highly expressed in human atherosclerotic lesions. The interplays among resistin, CCL19, and shear stress in regulating vascular endothelial function are not clearly understood. In the present study, resistin stimulation induced dose‐ and time‐dependent CCL19 expression in human aortic endothelial cells (HAECs). By using neutralizing antibody and small interfering (si)RNA, we demonstrated that toll‐like receptor 4 (TLR4) is critical for resistin‐induced CCL19 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that resistin increased NF‐κB‐DNA binding activities in ECs. Inhibition of NF‐κB activation by specific siRNA blocked the resistin‐induced CCL19 promoter activity and expression. Preshearing of ECs for 12 h at 20 dyn/cm2 inhibited the resistin‐induced NF‐κB activation and CCL19 expression. Our findings serve to elucidate the molecular mechanisms underlying the resistin induction of CCL19 expression in ECs and the shear‐stress protection against this induction. J. Cell. Physiol. 230: 2120–2127, 2015. © 2015 Wiley Periodicals, Inc.
A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice
Authors: Bethel Monique , Barnes Calvin L.T. , Taylor Amanda F. , Cheng Ying‐Hua , Chitteti Brahmananda R. , Horowitz Mark C. , Bruzzaniti Angela , Srour Edward F. , Kacena Melissa A.
Published: February 2015

Emerging data suggest that megakaryocytes (MKs) play a significant role in skeletal homeostasis. Indeed, osteosclerosis observed in several MK‐related disorders may be a result of increased numbers of MKs. In support of this idea, we have previously demonstrated that MKs increase osteoblast (OB) proliferation by a direct cell–cell contact mechanism and that MKs also inhibit osteoclast (OC) formation. As MKs and OCs are derived from the same hematopoietic precursor, in these osteoclastogenesis studies we examined the role of the main MK growth factor, thrombopoietin (TPO) on OC formation and bone resorption. Here we show that TPO directly increases OC formation and differentiation in vitro. Specifically, we demonstrate the TPO receptor (c‐mpl or CD110) is expressed on cells of the OC lineage, c‐mpl is required for TPO to enhance OC formation in vitro, and TPO activates the mitogen‐activated protein kinases, Janus kinase/signal transducer and activator of transcription, and nuclear factor‐kappaB signaling pathways, but does not activate the PI3K/AKT pathway. Further, we found TPO enhances OC resorption in CD14+CD110+ human OC progenitors derived from peripheral blood mononuclear cells, and further separating OC progenitors based on CD110 expression enriches for mature OC development. The regulation of OCs by TPO highlights a novel therapeutic target for bone loss diseases and may be important to consider in the numerous hematologic disorders associated with alterations in TPO/c‐mpl signaling as well as in patients suffering from bone disorders. J. Cell. Physiol. 230: 2142–2151, 2015. © 2015 Wiley Periodicals, Inc.
Epigenetic Regulation of miR‐29s Affects the Lactation Activity of Dairy Cow Mammary Epithelial Cells
Authors: Bian Yanjie , Lei Yu , Wang Chunmei , Wang Jie , Wang Lina , Liu Lili , Liu Lixin , Gao Xuejun , Li Qingzhang
Published: February 2015

Milk is important for human nutrition, and enhanced milk quality has become a major selection criterion for the genetic improvement of livestock. Epigenetic modifications have been shown to be involved in mammary gland development; but the mechanisms underlying their effects remain unknown. MicroRNAs are involved in the regulation of milk synthesis and in mammary gland development. Our study is the first to investigate the roles of miR‐29s and epigenetic regulation in dairy cow mammary epithelial cells (DCMECs). Our results show that miR‐29s regulate the DNA methylation level by inversely targeting both DNMT3A and DNMT3B in DCMECs. The inhibition of miR‐29s caused global DNA hypermethylation and increased the methylation levels of the promoters of important lactation‐related genes, including casein alpha s1 (CSN1S1), E74‐like factor 5 (ElF5), peroxisome proliferator‐activated receptor gamma (PPARγ), sterol regulatory element binding protein‐1 (SREBP1), and glucose transporter 1 (GLUT1). The inhibition of miR‐29s reduced the secretion of lactoprotein, triglycerides (TG) and lactose by DCMECs. Moreover, the treatment of DCMECs with 5‐aza‐2′‐deoxycytidine (5‐Aza‐dC) decreased the methylation levels of the miR‐29b promoter and increased the expression of miR‐29b. The link between miR‐29s and DNMT3A/3B enhances our understanding of the roles of miRNAs in mammary gland function, and our data will inform more experimentally oriented studies to identify new mechanisms of regulating lactation. We present new insights regarding the epigenetic regulation of lactation performance. Improved understanding of the molecular basis of lactation will aid in the development of strategies for optimizing milk quality in dairy cows and modifying the lactation performance of offspring. J. Cell. Physiol. 230: 2152–2163, 2015. © 2015 Wiley Periodicals, Inc.
Extracellular Ca2+ Promotes Odontoblastic Differentiation of Dental Pulp Stem Cells via BMP2‐Mediated Smad1/5/8 and Erk1/2 Pathways
Authors: Li Shiting , Hu Jing , Zhang Gang , Qi Wei , Zhang Ping , Li Pengfei , Zeng Yong , Zhao Wenfeng , Tan Yinghui
Published: February 2015

Ca2+ is the main element of many pulp capping materials that are used to promote the regeneration of tertiary dentin, but the underlying molecular mechanism is not clear. In this study, we found that Ca2+ increased the expression of the odontoblastic differentiation marker gene DSPP and promoted odontoblastic differentiation and mineralization of DPSCs, but inhibited ALP activity. Ca2+ increases the expression of endogenous BMP2, which activates the Smad1/5/8 pathway and promotes the Smad1‐Runx2 and Runx2‐DSPP interaction in DPSCs. Inhibition of Smad1/5/8 with dorsomorphin partially blocked Runx2 activity; however, inhibition of the BMP2 receptor with Noggin nearly fully suppressed Runx2 activity. These results indicate that Ca2+ promotes cell differentiation mainly via BMP2‐mediated Smad‐dependent and Smad‐independent pathways. We then determined that the phosphorylation level of Erk1/2, but not JNK or p38, was significantly increased as a result of Ca2+ stimulation. Blockage of Erk1/2 was found to inhibit Runx2 activity, indicating that Ca2+ triggers the Erk1/2 pathway, which subsequently regulates Runx2 activity. In addition, inhibition of Erk1/2 differentially attenuated the phosphorylation levels of Smad1/5/8 and Smad2/3. Collectively, this study demonstrates that Ca2+ activates the BMP2‐mediated Smad1/5/8 and Erk1/2 pathways in DPSCs and that Smad1/5/8 and Erk1/2 signaling converge at Runx2 to control the odontoblastic differentiation of DPSCs. J. Cell. Physiol. 230: 2164–2173, 2015. © 2015 Wiley Periodicals, Inc.
RETRACTED: Environmental Disruption of Circadian Rhythm Predisposes Mice to Osteoarthritis‐Like Changes in Knee Joint
Authors: Kc Ranjan , Li Xin , Voigt Robin M. , Ellman Michael B. , Summa Keith C. , Vitaterna Martha Hotz , Keshavarizian Ali , Turek Fred W. , Meng Qing‐Jun , Stein Gary S. , van Wijnen Andre J. , Chen Di , Forsyth Christopher B. , Im Hee‐Jeong
Published: February 2015

Circadian rhythm dysfunction is linked to many diseases, yet pathophysiological roles in articular cartilage homeostasis and degenerative joint disease including osteoarthritis (OA) remains to be investigated in vivo. Here, we tested whether environmental or genetic disruption of circadian homeostasis predisposes to OA‐like pathological changes. Male mice were examined for circadian locomotor activity upon changes in the light:dark (LD) cycle or genetic disruption of circadian rhythms. Wild‐type (WT) mice were maintained on a constant 12 h:12 h LD cycle (12:12 LD) or exposed to weekly 12 h phase shifts. Alternatively, male circadian mutant mice (ClockΔ19 or Csnk1etau mutants) were compared with age‐matched WT littermates that were maintained on a constant 12:12 LD cycle. Disruption of circadian rhythms promoted osteoarthritic changes by suppressing proteoglycan accumulation, upregulating matrix‐degrading enzymes and downregulating anabolic mediators in the mouse knee joint. Mechanistically, these effects involved activation of the PKCδ‐ERK‐RUNX2/NFκB and β‐catenin signaling pathways, stimulation of MMP‐13 and ADAMTS‐5, as well as suppression of the anabolic mediators SOX9 and TIMP‐3 in articular chondrocytes of phase‐shifted mice. Genetic disruption of circadian homeostasis does not predispose to OA‐like pathological changes in joints. Our results, for the first time, provide compelling in vivo evidence that environmental disruption of circadian rhythms is a risk factor for the development of OA‐like pathological changes in the mouse knee joint. J. Cell. Physiol. 230: 2174–2183, 2015. © 2015 Wiley Periodicals, Inc.
The SRE Motif in the Human PNPLA3 Promoter (−97 to −88 bp) Mediates Transactivational Effects of SREBP‐1c
Authors: Liang Hua , Xu Jing , Xu Fen , Liu Hongxia , Yuan Ding , Yuan Shuhua , Cai Mengyin , Yan Jinhua , Weng Jianping
Published: February 2015

Patatin‐like phospholipase domain containing 3 (PNPLA3) is a non‐secreted protein primarily expressed in liver and adipose tissue. Recently, numerous genetic studies have shown that PNPLA3 is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD). However, the mechanism involved in transcriptional regulation of the PNPLA3 gene remains unknown. We performed a detailed analysis of the human PNPLA3 gene promoter and identified two novel cis‐acting elements (SRE and NFY binding motifs) located at −97/−88 and −26/−22 bp, respectively. Overexpression of SREBP‐1c in HepG2 cells significantly increased PNPLA3 promoter activity. Mutation of either of the putative SRE or NFY binding motifs blocked the transactivation effects of SREBP‐1c on the promoter. Overexpression of SREBP‐1c and NFY together increased PNPLA3 promoter activity twice as much as that of SREBP‐1c or NFY expression alone. This result suggests that SREBP‐1c and NFY synergistically transactivate the human PNPLA3 gene. The ability of SREBP‐1c and NFY to bind these cis‐elements was confirmed using gel shift analysis. Putative SRE and NFY motifs also mediated synergistic insulin‐induced transactivation of the PNPLA3 promoter in HepG2 cells. Additionally, the ability of SREBP‐1c to bind to the PNPLA3 promoter was increased by insulin in a dose‐dependent manner. Moreover, the treatment of HepG2 cells with the PI3K inhibitor LY294002 led to reduced insulin promoter‐activating ability accompanied by a decrease in PNPLA3 and SREBP‐1c protein expression. These results demonstrate that SREBP‐1c is a direct activator of the human PNPLA3 gene and insulin transactivates the PNPLA3 gene via the PI3K‐SREBP‐1c/NFY pathway in HepG2 cells. J. Cell. Physiol. 230: 2224–2232, 2015. © 2015 Wiley Periodicals, Inc.
Test–retest reliability of diffusion measures in cerebral white matter: A multiband diffusion MRI study
Authors: Duan Fei , Zhao Tengda , He Yong , Shu Ni
Published: February 2015

Background

To investigate the test–retest (TRT) reliability of the diffusion measures in cerebral white matter obtained from the diffusion MRI dataset acquired with multiband acceleration.

Methods

With the multiband diffusion MRI dataset with two repeated scanning sessions, the TRT reliability of diffusion measures (fractional anisotropy [FA], mean diffusivity [MD], primary diffusivity [PD] and transverse diffusivity [TD]) was investigated through several fully automated analysis methods, including two voxel‐level analyses (voxel‐based analysis [VBA] and tract‐based spatial statistics [TBSS]) and an atlas ROI‐based analysis. The reproducibility was assessed by the intra‐class correlation coefficient (ICC).

Results

Our results demonstrated moderate to high reproducibility (ICC > 0.4) of diffusion measures from the multiband EPI sequence with different analysis approaches. Across different measures, FA exhibited the highest reproducibility (mean ICC = 0.70), while MD showed the lowest reliability (mean ICC = 0.55) (P = 0.006). Additionally, ICCs varied across different tract ROIs: Commissural tracts showed higher reproducibility than other categories of tracts (projection, association and brainstem), while the brainstem tracts exhibited the poorest reliability (P = 0.004).

Conclusion

Our findings suggest a potential utility of the multiband EPI sequence for exploring individual differences of cerebral white matter and provide reference for future white matter studies. J. Magn. Reson. Imaging 2015;42:1106–1116.
Norovirus infections and seroprevalence of genotype gii.4‐specific antibodies in a spanish population
Authors: Carmona‐Vicente Noelia , Fernández‐Jiménez Manuel , Ribes Juan M. , Téllez‐Castillo Carlos J. , Khodayar‐Pardo Parisá , Rodríguez‐Diaz Jesús , Buesa Javier
Published: February 2015

Genotype II.4 noroviruses (NoVs) are a leading cause of epidemic acute gastroenteritis in children and adults worldwide. The prevalence of different NoV genotypes causing outbreaks and sporadic cases of acute gastroenteritis in the region of Valencia, Spain, during a 4‐year period (2008–11) was investigated. NoVs were detected in 42 out of 55 (76.3%) outbreaks and in 26 out of 332 (7.8%) sporadic cases of acute gastroenteritis. Genogroup GII strains were predominant in outbreaks and sporadic cases. Different genotype GII.4 variants were found (Yerseke_2006a, Den Haag_2006b, Apeldoorn_2007, and New Orleans_2009), with the latter variant detected most frequently (35.3%). A recombinant P domain of the NoV GII.4 Apeldoorn_2007 variant was produced in Escherichia coli and used as the coating antigen in an enzyme immunoassay to survey the IgG antibody seroprevalence against NoV GII.4 in a Spanish population. Baculovirus‐expressed virus‐like particles (VLPs) of NoV GII.4 Den Haag_2006b variant were also produced and used as antigen to compare seroreactivity. Of the 434 serum specimens analyzed, 429 (98.6%) had antibodies against the P domain. The comparison of reactivities of 30 serum samples to the NoV GII.4 P polypeptide and VLP showed reproducible results with a correlation coefficient of r = 0.794. Titers of antibodies to the P domain increased gradually and significantly with age, reaching the highest levels at the age group of 41–50 years. These results confirm the high prevalence of NoV GII.4 infections in Valencia from early childhood. J. Med. Virol. 87:675–682, 2015. © 2015 Wiley Periodicals, Inc.
Localization of the kinesin adaptor proteins trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal and cortical neurons
Authors: Loss Omar , Stephenson F. Anne
Published: February 2015

Neuronal function requires regulated anterograde and retrograde trafficking of mitochondria along microtubules by using the molecular motors kinesin and dynein. Previous work has established that trafficking kinesin proteins (TRAKs),TRAK1 and TRAK2, are kinesin adaptor proteins that link mitochondria to kinesin motor proteins via an acceptor protein in the mitochondrial outer membrane, etc. the Rho GTPase Miro. Recent studies have shown that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons by virtue of its binding to both kinesin and dynein motor proteins, whereas TRAK2 controls mitochondrial transport in dendrites resulting from its binding to dynein. This study further investigates the subcellular localization of TRAK1 and TRAK2 in primary cultures of hippocampal and cortical neurons by using both commercial antibodies and anti‐TRAK1 and anti‐TRAK2 antibodies raised in our own laboratory (in‐house). Whereas TRAK1 was prevalently localized in axons of hippocampal and cortical neurons, TRAK2 was more prevalent in dendrites of hippocampal neurons. In cortical neurons, TRAK2 was equally distributed between axons and dendrites. Some qualitative differences were observed between commercial and in‐house‐generated antibody immunostaining. © 2015 Wiley Periodicals, Inc.
The kinetics of the inhibition of acrylamide by glycine in potato model systems
Authors: Zhu Yuchen , Wang Pengpu , Wang Fei , Zhao Mengyao , Hu Xiaosong , Chen Fang
Published: February 2015

BACKGROUND

Acrylamide (AA) is a potential carcinogen which widely exists in heat‐processed foods. The addition of glycine (Gly) has been shown to reduce the formation of AA. The objective of this work was to investigate the kinetics of the inhibition of AA by Gly in both asparagine (Asn)/glucose (Glc) and Asn/Glc/Gly potato model systems during heating at 160 °C, 180 °C, and 200 °C.

RESULTS

The simplified two consecutive first‐order kinetic model fitted well to the changes of AA in both systems. No significant difference in rate constant (kF) and apparent activation energy (EaF) was observed for AA formation between the two systems (P > 0.05). Whereas EaE and only kE at 200 °C for AA elimination in the Asn/Glc/Gly system was significantly higher than Asn/Glc system (P < 0.05). The elimination reaction between Gly and AA was confirmed by the identification of their major reaction product 2‐((3‐amino‐3‐oxopropyl)amino)acetic acid in the Asn/Glc/15 N‐Gly system.

CONCLUSION

The reduction of AA by Gly is predominantly attributed to the elimination reaction between Gly and AA. © 2015 Society of Chemical Industry
Cadmium sulfide nanoparticles as a novel coating for solid‐phase microextraction
Authors: Wang Licheng , Tang Sheng , Wang Shuai , Liang Xiaojing , Guo Yong
Published: February 2015

CdS nanoparticles coated on a stainless‐steel wire for solid‐phase microextraction was prepared. Scanning electron microscopy showed that the CdS nanoparticles clustered together to form a porous structure and X‐ray diffraction confirmed that the CdS nanoparticles were the wurtzite phase. Coupled to gas chromatography with flame ionization detection, the extraction abilities of the fiber for polycyclic aromatic hydrocarbons were examined by the headspace method. The parameters of adsorption time, adsorption temperature, salt concentration, desorption time, and desorption temperature were investigated and optimized. For the method, wide linearity and low limits of detection from 5 to 15 ng/L were obtained. The relative standard deviations for single‐fiber repeatability and fiber‐to‐fiber reproducibility were less than 10.2 and 12.6%, respectively. The enrichment factors were from 1155.6 to 3905.4, showing the fiber has good extraction capacity for polycyclic aromatic hydrocarbons. Moreover, the fiber can be used more than 50 times, exhibiting good stability. The established method was also used to analyze the polycyclic aromatic hydrocarbons in two real samples, and the recoveries from 82.7 to 114.2% further proved the reliability of the method.
Development of a selective sorbent for the solid‐phase extraction of terbuthylazine in olive oil samples: A molecular imprinting strategy
Authors: Garcia Raquel , Martins Nuno , Carreiro Elisabete P. , Simões Marco , Carrott Maria M. L. Ribeiro , Carrott Peter J. M. , Burke Anthony J. , Cabrita Maria João
Published: February 2015

Aiming to implement an analytical methodology that is highly selective for the extraction and quantification of terbuthylazine from olive oil, we successfully achieved: (i) the development of a molecularly imprinted polymer by bulk polymerization using terbuthylazine as template molecule, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross‐linker, and dichloromethane as porogen; (ii) characterization of the imprinting material using Fourier transform infrared spectroscopy, thermogravimetric analysis, nitrogen adsorption at 77 K, and scanning electron microscopy; (iii) their molecular recognition for the template molecule using high‐performance liquid chromatography, and (iv) optimization of a solid‐phase extraction procedure using as sorbent the synthesized molecularly imprinted polymer for the selective extraction and clean‐up of terbuthylazine from spiked organic olive oil and further quantification of the pesticide levels by high‐performance liquid chromatography. The suitability of the implemented analytical methodology was demonstrated, as concentrations of terbuthylazine below the tolerated maximum residue limits in the spiked organic olive oil samples could be satisfactorily analyzed with good precision/accuracy with high recovery rates (96%). Overall, the implemented methodology has proven to be reliable and robust and is highly promising in the field of sample preparation, particularly for the isolation/preconcentration of terbuthylazine in complex food samples.
A study on wear and worn surfaces of grey cast iron affected by a novel silicate additive
Authors: Zeng Zhu , Tian Bin
Published: February 2015

A novel aluminium silicate hydroxide additive has shown excellent anti‐wear effect in practical applications and has been mainly studied on steels in laboratory conditions. In this paper, the pin‐on‐disk sliding wear tests were carried out to investigate the wear and worn surfaces of grey cast iron with additives in different concentration. It was found that the silicate additive showed an obvious anti‐wear effect and a reliable duration, reduced the number of pits and cracks on the worn surfaces and improved the nanohardness of the worn surfaces of grey cast iron disks by 72%. Furthermore, Raman spectroscopy displayed that the carbon structure of the worn surface of grey cast iron disks with the additive had an obvious transformation from nanocrystalline graphite to amorphous carbon. Copyright © 2015 John Wiley & Sons, Ltd.
Light emitting diode‐generated blue light modulates fibrosis characteristics: Fibroblast proliferation, migration speed, and reactive oxygen species generation
Authors: Mamalis Andrew , Garcha Manveer , Jagdeo Jared
Published: February 2015

Background and Objective

Blue light is part of the visible light spectrum that does not generate harmful DNA adducts associated with skin cancer and photoaging, and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light‐emitting diode (LED) red and infrared light inhibits proliferation of skin fibroblasts. Moreover, different wavelengths of light can produce different biological effects. Furthermore, the effects of LED blue light (LED‐BL) on human skin fibroblasts are not well characterized. This study investigated the effects of LED‐BL on human skin fibroblast proliferation, viability, migration speed, and reactive oxygen‐species (ROS) generation.

Methods and Materials

Irradiation of adult human skin fibroblasts using commercially‐available LED‐BL panels was performed in vitro, and modulation of proliferation and viability was quantified using the trypan blue dye exclusion assay, migratory speed was assessed using time‐lapse video microscopy, and intracellular ROS generation was measured using the dihydrorhodamine flow cytometry assay. Statistical differences between groups were determined by ANOVA and Student's t‐test.

Results

Human skin fibroblasts treated with LED‐BL fluences of 5, 10, 15, 30, and 80 J/cm2 demonstrated statistically significant dose‐dependent decreases in relative proliferation of 8.4%, 29.1%, 33.8%, 51.7%, and 55.1%, respectively, compared to temperature and environment matched bench control plates, respectively. LED‐BL fluences of 5, 30, 45, and 80 J/cm2 decreased fibroblast migration speed to 95 ± 7.0% (P = 0.64), 81.3 ± 5.5% (P = 0.021), 48.5 ± 2.7% (P < 0.0001), and 32.3 ± 1.9% (P < 0.0001), respectively, relative to matched controls. LED fluences of 5, 10, 30, and 80 J/cm2 resulted in statistically significant increases in reactive oxygen species of 110.4%, 116.6%, 127.5%, and 130%, respectively, relative to bench controls.

Conclusion

At the fluences studied, LED‐BL can inhibit adult human skin dermal fibroblast proliferation and migration speed, and is associated with increased reactive oxygen species generation in a dose‐dependent manner without altering viability. LED‐BL has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation. Lasers Surg. Med. 47:210–215, 2015. © 2015 Wiley Periodicals, Inc.
The Role of Matrix Compliance on Cell Responses to Drugs and Toxins: Towards Predictive Drug Screening Platforms
Authors: Zustiak Silviya Petrova
Published: February 2015

Since the birth of tissue engineering, it has been redefined to include not only the development of tissues for clinical use, but also in vitro models for the study of tissue physiology and pathology. Great strides have been accomplished in the design of in vitro tissue models, yet one area in which they are underrepresented, but where they can have an immediate impact, is the development of platforms for drug screening. By providing more in vivo‐like cell environments, such models could address the growing concerns about drug failures due to lack of efficacy or unexpected side effects. This review aims to address the interface between substrate compliance and cell responsiveness to toxins and drugs since compliance has been established as a major determinate of overall cell fate. Here, results from 2D substrates and 3D matrices are discussed. Additionally, examples of biomaterial‐based high‐throughput stiffness assays in drug screening are presented.
Defined Polymeric Materials for Gene Delivery
Authors: He Dongsheng , Wagner Ernst
Published: February 2015

For successful gene therapy, the delivery of the curative genetic information into target cells is the main hurdle and the development of efficient and safe gene delivery carriers the crucial challenge. Polymeric materials have been widely investigated as gene delivery agents, generating first promising results. However, the heterogeneity and polydispersity of polymers and lack of site specific modifications make it difficult to achieve accurate structure‐activity relationship studies. Moreover it will hamper manufacturing of highly defined materials which could be used in clinical development. Therefore, polymers with precise chemical structure are required. In this review, we focus on the current design of defined polymeric materials for gene transfer. We first discuss the barriers for gene delivery, and then provide examples which illustrate defined polymeric vectors, including dendrimers, peptide carriers, and sequence‐defined oligoaminoamides.