bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity
Authors: Liu Baohui , Lin Xi , Yang Xiangsheng , Dong Huimin , Yue Xiaojing , Andrade Kelsey C. , Guo Zhentao , Yang Jian , Wu Liquan , Zhu Xiaonan , Zhang Shenqi , Tian Daofeng , Wang Junmin , Cai Qiang , Chen Qizuan , Mao Shanping , Chen Qianxue , Chang Jiang 
Published: June 2015

AbstractActivation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. Identification of RND3 as a novel factor in GBM genesis was demonstrated in vitro by cell experiments and in vivo by a GBM xenograft model. We found that RND3 expression was significantly decreased in human glioblastoma. The levels of RND3 expression were inversely correlated with Notch activity, tumor size, and tumor cell proliferation, and positively correlated with patient survival time. We demonstrated that RND3 functioned as an endogenous repressor of the Notch transcriptional complex. RND3 physically interacted with NICD, CSL, and MAML1, the Notch transcriptional complex factors, promoted NICD ubiquitination, and facilitated the degradation of these cofactor proteins. We further revealed that RND3 facilitated the binding of NICD to FBW7, a ubiquitin ligase, and consequently enhanced NICD protein degradation. Therefore, Notch transcriptional activity was inhibited. Forced expression of RND3 repressed Notch signaling, which led to the inhibition of glioblastoma cell proliferation in vitro and tumor growth in the xenograft mice in vivo. Downregulation of RND3, however, enhanced Notch signaling activity, and subsequently promoted glioma cell proliferation. Inhibition of Notch activity abolished RND3 deficiency‐mediated GBM cell proliferation. We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis.
Using a nano‐flare probe to detect RNA in live donor cells prior to somatic cell nuclear transfer
Authors: Fu Bo , Ren Liang , Liu Di , Ma Jian‐zhang , An Tie‐zhu , Yang Xiu‐qin , Ma Hong , Guo Zhen‐hua , Zhu Meng , Bai Jing 
Published: June 2015

AbstractMany transgenes are silenced in mammalian cells (donor cells used for somatic cell nuclear transfer [SCNT]). Silencing correlated with a repressed chromatin structure or suppressed promoter, and it impeded the production of transgenic animals. Gene transcription studies in live cells are challenging because of the drawbacks of reverse‐transcription polymerase chain reaction and fluorescence in situ hybridization. Nano‐flare probes provide an effective approach to detect RNA in living cells. We used 18S RNA, a housekeeping gene, as a reference gene. This study aimed to establish a platform to detect RNA in single living donor cells using a Nano‐flare probe prior to SCNT and to verify the safety and validity of the Nano‐flare probe in order to provide a technical foundation for rescuing silenced transgenes in transgenic cloned embryos. We investigated cytotoxic effect of the 18S RNA–Nano‐flare probe on porcine fetal fibroblasts, characterized the distribution of the 18S RNA–Nano‐flare probe in living cells and investigated the effect of the 18S RNA–Nano‐flare probe on the development of cloned embryos after SCNT. The cytotoxic effect of the 18S RNA–Nano‐flare probe on porcine fetal fibroblasts was dose‐dependent, and 18S RNA was detected using the 18S RNA–Nano‐flare probe. In addition, treating donor cells with 500 pM 18S RNA–Nano‐flare probe did not have adverse effects on the development of SCNT embryos at the pre‐implantation stage. In conclusion, we established a preliminary platform to detect RNA in live donor cells using a Nano‐flare probe prior to SCNT.
Preparation of Highly Active Nickel Catalysts Supported on Mesoporous Nanocrystalline γ‐Al2O3 for Methane Autothermal Reforming
Authors: Sepehri Soodeh , Rezaei Mehran 
Published: June 2015

AbstractAutothermal reforming (ATR) of methane was carried out over nanocrystalline Al2O3‐supported Ni catalysts with various Ni loadings. Mesoporous nanocrystalline γ‐Al2O3 powder with high specific surface area was prepared by the sol‐gel method and employed as support for the nickel catalysts. The prepared samples were characterized by X‐ray diffraction, Brunauer‐Emmett‐Teller, temperature‐programmed reduction, temperature‐programmed hydrogenation, and scanning electron microscopy techniques. It is demonstrated that the methane conversion increased with increasing in Ni content and that the catalyst with 25 wt % Ni exhibited the highest activity and a stable catalytic performance in the ATR process, with a low degree of carbon formation. Furthermore, the effects of the reaction temperature, the calcination temperature, the steam/CH4 and O2/CH4 ratios, and the gas hourly space velocity on the catalytic performance of the 25 % Ni/Al2O3 catalyst were investigated.
Full Superstructure for Multiobjective Optimization of Multicolumn Chromatography for Ternary Separations
Authors: Agrawal Gaurav , Kawajiri Yoshiaki 
Published: June 2015

AbstractIn the past decades, many multicolumn chromatographic processes have been proposed and studied for multicomponent continuous separation. In this study, the optimal operation for ternary multicolumn chromatographic separation is obtained from a full superstructure which embeds many different operations. A multiobjective optimization problem was solved to analyze the trade‐off between the throughput and the purity of the target component. It was found that the throughput of the optimal operation found from the full superstructure is significantly higher than that of the generalized full cycle scheme in our former publication in 2012.
Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine‐Containing Dipeptides
Authors: Gutiérrez Alejandro , Marzo Isabel , Cativiela Carlos , Laguna Antonio , Gimeno M. Concepción 
Published: June 2015

AbstractSeveral gold(I) complexes with cysteine‐containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh3)] gives the gold‐dipeptide‐phosphine species. Starting from these formally gold(I) thiolate–dipeptide phosphine complexes with the general formula [Au(SR)(PR3)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non‐proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC50 values in the very low micromolar range. Structure–activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents.
ChemInform Abstract: Metal‐Free Csp3—N Bond Cleavage of Amides Using tert‐Butyl Hydroperoxide as Oxidant.
Authors: Guo Shengmei , Zhu Zheng , Lu Lin , Zhang Wenbiao , Gong Jiuhan , Cai Hu 
Published: June 2015

AbstractThe C—N bond cleavage of dimethyl acetamide (II) under oxidative conditions is demonstrated.
A randomized phase 2 study comparing EC or CMF versus nab‐paclitaxel plus capecitabine as adjuvant chemotherapy for nonfrail elderly patients with moderate to high‐risk early breast cancer (ICE II‐GBG 52)
Authors: von Minckwitz Gunter , Conrad Bettina , Reimer Toralf , Decker Thomas , Eidtmann Holger , Eiermann Wolfgang , Hackmann John , Möbus Volker , Marmé Frederik , Potenberg Jochem , Stickeler Elmar , Simon Eike , Thomssen Christoph , Huober Jens , Denkert Carsten , Alfer Joachim , Jackisch Christian , Nekljudova Valentina , Burchardi Nicole , Loibl Sibylle ,   for the German Breast Group Investigators
Published: June 2015

BACKGROUNDAlthough greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane‐based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients.METHODSPatients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either human epidermal growth factor receptor 2 (HER2)‐positive, hormone receptor‐negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI‐1 or any stage pT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m2, methotrexate at a dose of 40 mg/m2, and 5‐fluorouracil at a dose of 600 mg/m2 iv on days 1 plus 8 every 29 days) versus 6 cycles of nab‐paclitaxel and capecitabine (nPX) (nab‐paclitaxel at a dose of 100 mg/m2 iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m2 orally on days 1‐14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events.RESULTSThirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P<.001) with 1 and 5 deaths observed during treatment, respectively. Grade 3 to 5 adverse events were more frequent among patients treated with EC/CMF (90.9%) than among those treated with nPX (64.8%) (P<.001), with hematological toxicities being more frequent with EC/CMF (88.4% vs 22.3%; P<.001), but nonhematological toxicities (hand‐foot syndrome, diarrhea, mucositis, fatigue, sensory neuropathy, thromboembolisms, and metabolic disorders) being more frequent with nPX (58.5% vs 18.7%; P<.001). None of the geriatric scores (Charlson comorbidity index, Vulnerable Elders Survey [VES‐13], Instrumental Activities of Daily Living [IADL], and G8) independently predicted grade 3 to 5 toxic events or treatment discontinuations. No differences in survival between the treatment groups were observed after 22.8 months.CONCLUSIONSCompared with EC/CMF, treatment with nPX led to more treatment discontinuations and nonhematological toxicities in elderly patients with moderate or high‐risk breast cancer. Cancer 2015;121:3639–3648. © 2015 American Cancer Society.
Type 2 diabetes mellitus and risk of gallbladder cancer: a systematic review and meta‐analysis of observational studies
Authors: Gu Jun , Yan Shiyan , Wang Baochan , Shen Feng , Cao Haixia , Fan Jiangao , Wang Yuqin 
Published: June 2015

AbstractAimsIncreasing evidence suggests that a history of type 2 diabetes mellitus (type 2 DM) may be involved in the development of various sites of cancer. However, the association with risk of gallbladder cancer remains unclear.MethodsWe identified studies by a literature search of MEDLINE and EMBASE through 31 August 2014 and by searching the reference lists of pertinent articles. All data were independently extracted by two investigators using a standardized data abstraction tool. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated with a random effects model.ResultsA total of 20 studies (eight case‐control studies and 12 cohort studies) were included in this meta‐analysis. Analysis of these 20 studies found that compared with non‐diabetic individuals, diabetic individuals had an increased risk of gallbladder cancer (SRR = 1.56, 95% CI: 1.36–1.79). There was evidence of moderate heterogeneity among these studies (p = 0.010 and I2 = 43.5%). This increased risk relationship is independent of smoking, body mass index and a history of gallstones. However, whether or not controlled for, alcohol use may be one of the potential confounders that significantly affect the association between type 2 DM and the risk of gallbladder cancer. Diabetic women and men had a similarly increased risk of gallbladder cancer associated with type 2 DM.ConclusionsThese findings of this systematic review indicate that compared with non‐diabetic individuals, both men and women with type 2 DM had an increased risk of gallbladder cancer. Copyright © 2015 John Wiley & Sons, Ltd.
Parasitic helminths and their beneficial impact on type 1 and type 2 diabetes
Authors: Berbudi Afiat , Ajendra Jesuthas , Wardani Ajeng P.F. , Hoerauf Achim , Hübner Marc P. 
Published: June 2015

SummaryIt is estimated that by the year 2035 almost 600 million people will suffer from diabetes. In the case of type 2 diabetes, the strongest increase of diabetes incidence occurs in developing and newly industrialized countries. This increase correlates not only with a progressing sedentary lifestyle and nutritional changes, but also environmental changes. Similarly, the increase of type 1 diabetes incidence in industrialized countries over the past decades cannot be explained by genetic factors alone, suggesting that environmental changes are also involved. One such environmental change is a reduced exposure to pathogens because of improved hygiene. Parasitic helminths modulate the immune system of their hosts and induce type 2 as well as regulatory immune responses. As pro‐inflammatory immune responses are crucial for the onset of both type 1 and type 2 diabetes, helminth‐induced immunomodulation may prevent diabetes onset and ameliorate insulin sensitivity. Several epidemiological studies in human and experimental animal models support such a protective effect of helminths for autoimmune diabetes. Recent studies further suggest that helminths may also provide such a beneficial effect for type 2 diabetes. In this review we summarize studies that investigated parasitic helminths and helminth‐derived products and their impact on both type 1 and type 2 diabetes highlighting potential protective mechanisms. Copyright © 2015 John Wiley & Sons, Ltd.
Effects of deforestation and weather on diurnal frost heave processes on the steep mountain slopes in south central Japan
Authors: Ueno Kenichi , Kurobe Kousei , Imaizumi Fumitoshi , Nishii Ryoko 
Published: June 2015

AbstractFreezing and thawing processes play an important role for the gravitational transport of surface materials on steep mountain slopes in Japan. The effects of deforestation on frost heave activity were observed through the 2012/2013 winter season in Ikawa University Forest, a southern mountainous area in central Japan (1180–1310 m above sea level). During periods without snow cover, needle ice development prevailed at a clear‐cut site, and the downslope sediment movement of upper soil was 10 to 15 cm through the winter season. At a non‐cut site, rise and fall in the ground surface level prevailed on a weekly scale, with no evident downslope movements at the surface; ice lens formation in the soil layer is assumed. Abrupt changes in the radiation budget, such as the strengthening of nighttime radiative cooling and increases in daytime direct insolation, induced frequent development/deformation of needle ice at the clear‐cut site. In snow‐free periods, the day‐to‐day variability in needle ice growth length and in nighttime averaged net radiation showed significant correlations; cloudy weather with warmer and moist air intrusion associated with synoptic disturbances prevented the occurrence of needle ice. Namely, day‐to‐day weather changes directly affected the mass movement of the upper soil after deforestation. Shallow snow cover occurred discontinuously through the winter and is likely an important factor in keeping the soil moisture sufficiently high in the upper soil layer for initiating needle ice during snow‐free periods. We also discuss contributions of coastal extratropical cyclone activities providing both snow cover and cloudy weather in the southern mountain areas of central Japan to the intra‐seasonal variability in frost heave and its indirect effect on soil creep and landslides on the deforested steep slopes. Copyright © 2015 John Wiley & Sons, Ltd.
The effect of sulfate on selenate bioaccumulation in two freshwater primary producers: A duckweed (Lemna minor) and a green alga (Pseudokirchneriella subcapitata)
Authors: Lo Bonnie P. , Elphick James R. , Bailey Howard C. , Baker Josh A. , Kennedy Christopher J. 
Published: June 2015

Abstract

Predicting selenium bioaccumulation is complicated because site-specific conditions, including the ionic composition of water, affect the bioconcentration of inorganic selenium into the food web. Selenium tissue concentrations were measured in Lemna minor and Pseudokirchneriella subcapitata following exposure to selenate and sulfate. Selenium accumulation differed between species, and sulfate reduced selenium uptake in both species, indicating that ionic constituents, in particular sulfate, are important in modifying selenium uptake by primary producers. Environ Toxicol Chem 2015;34:2841–2845. © 2015 SETAC
Modeling the transport of organic chemicals between polyethylene passive samplers and water in finite and infinite bath conditions
Authors: Tcaciuc A. Patricia , Apell Jennifer N. , Gschwend Philip M. 
Published: June 2015

Abstract

Understanding the transfer of chemicals between passive samplers and water is essential for their use as monitoring devices of organic contaminants in surface waters. By applying Fick's second law to diffusion through the polymer and an aqueous boundary layer, the authors derived a mathematical model for the uptake of chemicals into a passive sampler from water, in finite and infinite bath conditions. The finite bath model performed well when applied to laboratory observations of sorption into polyethylene (PE) sheets for various chemicals (polycyclic aromatic hydrocarbons, polychlorinated biphenyls [PCBs], and dichlorodiphenyltrichloroethane [DDT]) and at varying turbulence levels. The authors used the infinite bath model to infer fractional equilibration of PCB and DDT analytes in field-deployed PE, and the results were nearly identical to those obtained using the sampling rate model. However, further comparison of the model and the sampling rate model revealed that the exchange of chemicals was inconsistent with the sampling rate model for partially or fully membrane-controlled transfer, which would be expected in turbulent conditions or when targeting compounds with small polymer diffusivities and small partition coefficients (e.g., phenols, some pesticides, and others). The model can be applied to other polymers besides PE as well as other chemicals and in any transfer regime (membrane, mixed, or water boundary layer–controlled). Lastly, the authors illustrate practical applications of this model such as improving passive sampler design and understanding the kinetics of passive dosing experiments. Environ Toxicol Chem 2015;34:2739–2749. © 2015 SETAC
It is time to develop ecological thresholds of toxicological concern to assist environmental hazard assessment
Authors: Belanger Scott E. , Sanderson Hans , Embry Michelle R. , Coady Katie , DeZwart Dick , Farr Brianna A. , Gutsell Steve , Halder Marlies , Sternberg Robin , Wilson Peter 
Published: June 2015

Abstract

The threshold of toxicological concern (TTC) concept is well established for assessing human safety of food-contact substances and has been reapplied for a variety of endpoints, including carcinogenicity, teratogenicity, and reproductive toxicity. The TTC establishes an exposure level for chemicals below which no appreciable risk to human health or the environment is expected, based on a de minimis value for toxicity identified for many chemicals. Threshold of toxicological concern approaches have benefits for screening-level risk assessments, including the potential for rapid decision-making, fully utilizing existing knowledge, reasonable conservativeness for chemicals used in lower volumes (low production volume chemicals (e.g., &lt; 1 t/yr), and reduction or elimination of unnecessary animal tests. Higher production volume chemicals (&gt;1 t/yr) would in principle always require specific information because of the presumed higher exposure potential. The TTC approach has found particular favor in the assessment of chemicals used in cosmetics and personal care products, as well as other chemicals traditionally used in low volumes. Use of the TTC in environmental safety is just beginning, and initial attempts are being published. Key questions focus on hazard extrapolation of diverse taxa across trophic levels, importance of mode of action, and whether safe concentrations for ecosystems estimated from acute or chronic toxicity data are equally useful and in what contexts. The present study provides an overview of the theoretical basis for developing an ecological (eco)-TTC, with an initial exploration of chemical assessment and boundary conditions for use. An international collaboration under the International Life Sciences Institute Health and Environmental Sciences Institute has been established to address challenges related to developing and applying useful eco-TTC concepts. Environ Toxicol Chem 2015;34:2864–2869. © 2015 SETAC