bluuebunny/crossref_metadata_2025 huggingface dataset:
Water productivity of poultry production: the influence of different broiler fattening systems
Authors: Krauß Michael , Keßler Jens , Prochnow Annette , Kraatz Simone , Drastig Katrin
Published: February 2015

With the expected increase in poultry meat consumption water use will increase as well. The objective of this study is to quantify the effects of fattening systems on the water productivity in broiler chicken production with consideration given to conditions in Germany. Four fattening systems were analyzed in terms of water use for feed production, drinking, cleaning, and the parent stock. The fattening systems differed in intensity, ranging from fast fattening with a fattening period of 30 days and a carcass weight of 1.1 kg to slow fattening with a period up to 46 days and a carcass weight of 2.1 kg. During the fattening period the broiler chicken were fed with performance‐linked feed. The water productivity of the feed components varied from 0.4 kg dry mass per m3 water input for soybean meal to 1.8 kg dry mass per m3 water input for maize. In all fattening systems the water input for feed production accounted for 90 to 93% of the total water input. The share for the parent stock was 7 to 10%, while drinking and cleaning water accounted for less than 1%. For all fattening systems the water productivity was 0.3 kg carcass weight per m3 water input, 2.8 MJ food energy per m3 water input and 57 g food protein per m3 water input. The shorter fattening period and lower feed demand in the more intensive fattening systems were juxtaposed to the higher carcass weight and higher water productivity of the feed components in the more extensive systems.
Estimating and Forecasting Large Panels of Volatilities with Approximate Dynamic Factor Models
Authors: Luciani Matteo , Veredas David
Published: February 2015

We introduce an approximate dynamic factor model for modeling and forecasting large panels of realized volatilities. Since the model is estimated by means of principal components and low‐dimensional maximum likelihood, it does not suffer from the curse of dimensionality. We apply the model to a panel of 90 daily realized volatilities pertaining to S&P 100 from January 2001 to December 2008. Results show that our model is able to capture the stylized facts of panels of volatilities (comovements, clustering, long memory, dynamic volatility, skewness and heavy tails), and that it performs fairly well in forecasting, in particular in periods of turmoil, in which it outperforms standard univariate benchmarks. Copyright © 2015 John Wiley & Sons, Ltd.
Bridging the gap between climate models and impact studies: the FORESEE Database
Authors: Dobor L. , Barcza Z. , Hlásny T. , Havasi Á. , Horváth F. , Ittzés P. , Bartholy J.
Published: February 2015

Studies on climate change impacts are essential for identifying vulnerabilities and developing adaptation options. However, such studies depend crucially on the availability of reliable climate data. In this study, we introduce the climatological database called FORESEE (Open Database for Climate Change Related Impact Studies in Central Europe), which was developed to support the research of and adaptation to climate change in Central and Eastern Europe: the region where knowledge of possible climate change effects is inadequate. A questionnaire‐based survey was used to specify database structure and content. FORESEE contains the seamless combination of gridded daily observation‐based data (1951–2013) built on the E‐OBS and CRU TS datasets, and a collection of climate projections (2014–2100). The future climate is represented by bias‐corrected meteorological data from 10 regional climate models (RCMs), driven by the A1B emission scenario. These latter data were developed within the frame of the ENSEMBLES FP6 project. Although FORESEE only covers a limited area of Central and Eastern Europe, the methodology of database development, the applied bias correction techniques, and the data dissemination method, can serve as a blueprint for similar initiatives.
Exploring the brain's structural connectome: A quantitative stroke lesion‐dysfunction mapping study
Authors: Kuceyeski Amy , Navi Babak B. , Kamel Hooman , Relkin Norman , Villanueva Mark , Raj Ashish , Toglia Joan , O'Dell Michael , Iadecola Costantino
Published: February 2015

The aim of this work was to quantitatively model cross‐sectional relationships between structural connectome disruptions caused by cerebral infarction and measures of clinical performance. Imaging biomarkers of 41 ischemic stroke patients (72.0 ± 12.0 years, 20 female) were related to their baseline performance in 18 cognitive, physical and daily life activity assessments. Individual estimates of structural connectivity disruption in gray matter regions were computed using the Change in Connectivity (ChaCo) score. ChaCo scores were utilized because they can be calculated using routinely collected clinical magnetic resonance imagings. Partial Least Squares Regression (PLSR) was used to predict various acute impairment and activity measures from ChaCo scores and patient demographics. Statistical methods of cross‐validation, bootstrapping and multiple comparisons correction were implemented to minimize over‐fitting and Type I errors. Multiple linear regression models based on lesion volume and lateralization information were constructed for comparison. All models based on connectivity disruption had lower Akaike Information Criterion and almost all had better goodness‐of‐fit values (R2: 0.26–0.92) than models based on lesion characteristics (R2: 0.06–0.50). Confidence intervals of PLSR coefficients identified brain regions important in predicting each clinical assessment. Appropriate mapping of eloquent functions, that is, language and motor, and replication of results across pathologies provided validation of this method. Models of complex functions provided new insights into brain‐behavior relationships. In addition to the potential applications in prognostication and rehabilitation development, this quantitative approach provides insight into the structural networks underlying complex functions like activities of daily living and cognition. Quantitative analysis of big data will be invaluable in understanding complex brain‐behavior relationships. Hum Brain Mapp 36:2147–2160, 2015. © 2015 Wiley Periodicals, Inc.
Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF‐1
Authors: Belmadani Abdelhak , Ren Dongjun , Bhattacharyya Bula J. , Rothwangl Katharina B. , Hope Thomas J. , Perlman Harris , Miller Richard J.
Published: February 2015

We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the “subhippocampal zone,” SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology. © 2015 Wiley Periodicals, Inc.
Synthesis and Structure of a Ternary Copper(II) Complex with Mixed Ligands of Diethylenetriamine and Picrate: DNA/Protein‐Binding Property and In Vitro Anticancer Activity Studies
Authors: Shi Ya‐Ning , Zheng Kang , Zhu Ling , Li Yan‐Tuan , Wu Zhi‐Yong , Yan Cui‐Wei
Published: February 2015

Based on the importance of the design and synthesis of transition metal complexes with noncovalent DNA/protein‐binding abilities in the field of metallo pharmaceuticals, a new mononuclear ternary copper(II) complex with mixed ligands of diethylenetriamine (dien) and picrate anion (pic), identified as [Cu(dien)(pic)](pic), was synthesized and characterized by elemental analysis, molar conductivity measurement, infrared spectrum, electronic spectral studies, and single‐crystal X‐ray diffractometry. The structure analysis reveals that the copper(II) complex crystallizes in the monoclinic space group P21/c, and the copper(II) ion has a distorted square pyramidal coordination geometry. A two‐dimensional supramolecular structure is formed through hydrogen bonds. The DNA/bovine serum albumin (BSA)‐binding properties of the complex are explored, indicating that the complex can interact with herring sperm DNA via intercalation mode and bind to BSA responsible for quenching of tryptophan fluorescence by static quenching mechanism. The in vitro anticancer activity shows that the copper(II) complex is active against the selected tumor cell lines.
Mitochondrial DNA Oxidative Damage Contributes to Cardiomyocyte Ischemia/Reperfusion‐Injury in Rats: Cardioprotective Role of Lycopene
Authors: Yue Rongchuan , Xia Xuewei , Jiang Jiahui , Yang Dezhong , Han Yu , Chen Xiongwen , Cai Yue , Li Liangpeng , Wang Wei Eric , Zeng Chunyu
Published: February 2015

Mitochondrial (mt) dysfunction and oxidative stress are involved in the pathogenesis of ischemia/reperfusion (I/R)‐injury. Lycopene, a lipophilic antioxidant found mainly in tomatoes and in other vegetables and fruits, can protect mtDNA against oxidative damage. However, the role of mtDNA in myocardial I/R‐injury is unclear. In the present study, we aimed to determine if and how lycopene protects cardiomyocytes from I/R‐injury. In both in vitro and in vivo studies, I/R‐injury increased mt 8‐hydroxyguanine (8‐OHdG) content, decreased mtDNA content and mtDNA transcription levels, and caused mitochondrial dysfunction in cardiomyocytes. These effects of I/R injury on cardiomycoytes were blocked by pre‐treatment with lycopene. MtDNA depletion alone was sufficient to induce cardiomyocyte death. I/R‐injury decreased the protein level of a key activator of mt transcription, mitochondrial transcription factor A (Tfam), which was blocked by lycopene. The protective effect of lycopene on mtDNA was associated with a reduction in mitochondrial ROS production and stabilization of Tfam. In conclusion, lycopene protects cardiomyocytes from the oxidative damage of mtDNA induced by I/R‐injury. J. Cell. Physiol. 230: 2128–2141, 2015. © 2015 Wiley Periodicals, Inc.
Alpha‐Lipoic Acid Promotes Osteoblastic Formation in H2O2‐Treated MC3T3‐E1 Cells and Prevents Bone Loss in Ovariectomized Rats
Authors: Fu Chao , Xu Dong , Wang Chang‐Yuan , Jin Yue , Liu Qi , Meng Qiang , Liu Ke‐Xin , Sun Hui‐Jun , Liu Mo‐Zhen
Published: February 2015

Alpha‐lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. Recently, accumulating evidences has indicated the relationship between oxidative stress and osteoporosis (OP). Some studies have investigated the possible beneficial effects of ALA on OP both in vivo and in vitro; however, the precise mechanism(s) underlying the bone‐protective action of ALA remains unclear. Considering this, we focused on the anti‐oxidative capacity of ALA to exert bone‐protective effects in vitro and in vivo. In the present study, the effects of ALA on osteoblastic formation in H2O2‐treated MC3T3‐E1 pre‐osteoblasts and ovariectomy (OVX)‐induced bone loss in rats were investigated. The results showed that ALA promoted osteoblast differentiation, mineralization and maturation and inhibited osteoblast apoptosis, thus increasing the OPG/receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL) ratio and leading to enhanced bone formation in vitro and inhibited bone loss in vivo. Further study revealed that ALA exerted its bone‐protective effects by inhibiting reactive oxygen species (ROS) generation by down‐regulating Nox4 gene expression and protein synthesis and attenuating the transcriptional activation of NF‐κB. In addition, ALA might exert its bone‐protective effects by activating the Wnt/Lrp5/β‐catenin signaling pathway. Taken together, the present study indicated that ALA promoted osteoblastic formation in H2O2‐treated MC3T3‐E1 cells and prevented OVX‐induced bone loss in rats by regulating Nox4/ROS/NF‐κB and Wnt/Lrp5/β‐catenin signaling pathways, which provided possible mechanisms of bone‐protective effects in regulating osteoblastic formation and preventing bone loss. Taken together, the results suggest that ALA may be a candidate for clinical OP treatment. J. Cell. Physiol. 230: 2184–2201, 2015. © 2015 Wiley Periodicals, Inc.
LB‐1 Exerts Antitumor Activity in Pancreatic Cancer by Inhibiting HIF‐1α and Stat3 Signaling
Authors: Niu Fei , Li Yan , Lai Fang‐Fang , Ni Lin , Ji Ming , Jin Jing , Yang Han‐Ze , Wang Chao , Zhang Dong‐Ming , Chen Xiao‐Guang
Published: February 2015

Hypoxia is widely present in pancreatic cancer and subsequently causes the overexpression of hypoxia‐inducible factor‐1α (HIF‐1α) and signal transducer and activator of transcription‐3 (Stat3). HIF‐1α and Stat3 function cooperatively to regulate a number of downstream genes that are implicated in tumorigenesis. Thus, inhibition of HIF‐1α and Stat3 is a potential therapeutic strategy for pancreatic cancer. In this study, we explored how LB‐1, a novel triptolide (LA) derivative, exerted its antitumor effect through blockade of HIF‐1α and Stat3 signaling. Our data showed that LB‐1 was able to inhibit the proliferation and colony formation of Mia‐PaCa2 and SW1990 cells. LB‐1 suppressed HIF‐1α protein accumulation by promoting its proteasome degradation and reducing transactivation. Moreover, the silence of HIF‐1α by shRNA partially prevented the proliferation inhibition triggered by LB‐1. As expected, LB‐1 also decreased Stat3 protein accumulation and blocked the physical interactions between HIF‐1α/p300/phosphor‐Stat3 (p‐Stat3) at the pharmacological concentration to reduce VEGF expression, thereby hypoxia‐induced angiogenesis. In the Mia‐PaCa2 nude xenograft model, therapeutic treatment with LB‐1 significantly inhibited tumor growth and had minimal systemic toxicity compared to the mother drug LA. Furthermore, in accordance with in vitro results, HIF‐1α activation and Stat3 expression in tumors were blocked by LB‐1 through mTOR‐dependent pathway. Taken together, these results illustrate that, as a potent inhibitor of HIF‐1α and Stat3 signaling, LB‐1 exhibits antitumor effect and could be potentially used to treat pancreatic cancer. J. Cell. Physiol. 230: 2212–2223, 2015. © 2015 Wiley Periodicals, Inc.
Wnt5a Induces Collagen Production by Human Periodontal Ligament Cells Through TGFβ1‐Mediated Upregulation of Periostin Expression
Authors: Hasegawa Daigaku , Wada Naohisa , Maeda Hidefumi , Yoshida Shinichiro , Mitarai Hiromi , Tomokiyo Atsushi , Monnouchi Satoshi , Hamano Sayuri , Yuda Asuka , Akamine Akifumi
Published: February 2015

Wnt5a, a member of the noncanonical Wnt proteins, is known to play important roles in the development of various organs and in postnatal cell functions. However, little is known about the effects of Wnt5a on human periodontal ligament (PDL) cells. In this study, we examined the localization and potential function of Wnt5a in PDL tissue. Immunohistochemical analysis revealed that Wnt5a was expressed predominantly in rat PDL tissue. Semi‐quantitative reverse‐transcription polymerase chain reaction and Western blotting analysis demonstrated that human PDL cells (HPDLCs) expressed Wnt5a and its receptors (Ror2, Fzd2, Fzd4, and Fzd5). Removal of occlusal pressure by extraction of opposing teeth decreased Wnt5a expression in rat PDL tissue, and the expression of Wnt5a and its receptors in HPDLCs was upregulated by exposure to mechanical stress. Stimulation with Wnt5a significantly enhanced the proliferation and migration of HPDLCs. Furthermore, Wnt5a suppressed osteoblastic differentiation of HPDLCs cultivated in osteogenic induction medium, while it significantly enhanced the expression of PDL‐related genes, such as periostin, type‐I collagen, and fibrillin‐1 genes, and the production of collagen in HPDLCs cultivated in normal medium. Both knockdown of periostin gene expression by siRNA and inhibition of TGFβ1 function by neutralizing antibody suppressed the Wnt5a‐induced PDL‐related gene expression and collagen production in HPDLCs. Interestingly, in HPDLCs cultured with Wnt5a, TGFβ1 neutralizing antibody significantly suppressed periostin expression, while periostin siRNA had no effect on TGFβ1 expression. These results suggest that Wnt5a expressed in PDL tissue plays specific roles in inducing collagen production by PDL cells through TGFβ1‐mediated upregulation of periostin expression. J. Cell. Physiol. 9999: 2647–2660, 2015. © 2015 Wiley Periodicals, Inc.
TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes
Authors: Chen Jicui , Ren Jianmin , Jing Qingping , Lu Sumei , Zhang Yuchao , Liu Yuantao , Yu Cong , Gao Peng , Zong Chen , Li Xia , Wang Xiangdong
Published: February 2015

TSH/TSHR signaling plays a role in the regulation of lipid metabolism in adipocytes. However, the precise mechanisms are not known. In the present study, we determined the effect of TSH on fatty acid synthase (FASN) expression, and explored the underlying mechanisms. In vitro, TSH reduced FASN expression in both mRNA and protein levels in mature adipocytes and was accompanied by protein kinase A (PKA) activation, cAMP‐response element binding protein (CREB) phosphorylation, as well as extracellular signal‐regulated kinase 1/2 (ERK1/2) and c‐Jun NH2‐terminal kinase (JNK) activation. TSH‐induced downregulation of FASN was partially abolished by inhibition of PKA and ERK, but not JNK. TSHR and FASN expression in visceral tissue was significantly increased in C57BL/6 mice with diet‐induced obesity compared with control animals, whereas thyroid TSHR expression was normal. These findings suggest that activation of TSHR directly inhibits FASN expression in mature adipocytes, possibly mediated by PKA and ERK. In obese animals, this function of TSHR seems to be counteracted. The precise mechanisms need further investigation. J. Cell. Physiol. 230: 2233–2239, 2015. © 2015 Wiley Periodicals, Inc.
Concise Review: The Role of Oxygen in Hematopoietic Stem Cell Physiology
Authors: Jež Mojca , Rožman Primož , Ivanović Zoran , Bas Tuba
Published: February 2015

Molecular dioxygen, O2, is an important element in cellular microenvironment in vivo, and often overlooked in standard in vitro and ex vivo cell culture systems. Molecular oxygen is the ultimate electron acceptor in oxidative cellular respiration, and also a signal that regulates cell fate through concentration gradients. Recent advances in physiology of oxygen and adult stem cell research have shown that apart from being important for oxidative phosphorylation, thus energy metabolism, oxygen is also important as a signaling molecule and an integral part of the stem cell niche. This review article covers the influence of physiologically relevant oxygen levels on adult stem cells through highlighting the research on the effect of oxygen concentration on hematopoietic stem cell maintenance, proliferation and differentiation. This is important particularly to understand the embryonic and adult stem cell biology and physiology. The new discoveries in this field will help to further improve current tissue engineering and clinical applications. In addition, understanding the relationship between oxygen and stemness is invaluable for the advanced treatments of neoplastic diseases. Authors believe that in the future, active and programmed dynamic of oxygen levels will be routinely used for the programmed in vitro and ex vivo expansion of different adult stem cell types and tissue regeneration purposes. J. Cell. Physiol. 230: 1999–2005, 2015. © 2015 Wiley Periodicals, Inc.
Evaluation of remediation processes for explosive‐contaminated soils: kinetics and Microtox® bioassay
Authors: Oh Seok‐Young , Yoon Hyun‐Su , Jeong Tae‐Yong , Kim Sang Don
Published: February 2015

BACKGROUND

Soils and sediments near military sites where training regularly occurs are vulnerable to contamination from toxic nitro explosives such as 2,4,6‐trinitrotoluene (TNT) and hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX). In order to clean up the explosive‐contaminated soils, several options have been investigated and evaluated as ex situ remediation processes, including alkaline hydrolysis, subcritical water degradation, zero‐valent iron (Fe(0)) reduction, and Fe(0)‐assisted Fenton oxidation. The kinetics of the remediation processes were evaluated and the toxicity of treated solutions determined using the Microtox® bioassay.

RESULTS

Kinetically, using four remediation methods, explosives were rapidly degraded in contaminated soils. Under optimal conditions, more than 99% of explosives were destroyed. However, the Microtox® bioassay showed that after degradation of explosives by alkaline hydrolysis, treated solutions did not show any decrease in toxicity, suggesting that hydrolytic products may still be toxic. Similarly, the Fe(0) reduction process did not significantly aid removal of toxicity due to the toxicity of reduction products. In contrast, subcritical water degradation and Fe(0)‐assisted Fenton oxidation markedly reduced the toxicity of explosives. When a toxic metal (e.g. Pb in shooting ranges) co‐existed with explosives, toxicity still remained after complete degradation of the explosives by subcritical water degradation or Fe(0)‐assisted Fenton oxidation, indicating that additional treatment may be needed.

CONCLUSIONS

Results suggest that, besides removal/degradation of toxic explosives, reduction of toxicity after treatment should be evaluated to select a practical option to remediate explosive‐contaminated soils. © 2015 Society of Chemical Industry
Enhanced biodegradation of aged petroleum hydrocarbons in soils by glucose addition in microbial fuel cells
Authors: Li Xiaojing , Wang Xin , Wan Lili , Zhang Yueyong , Li Nan , Li Desheng , Zhou Qixing
Published: February 2015

BACKGROUND

Bioelectrochemical remediation of soils contaminated by petroleum hydrocarbons has received increasing attention as an effective approach to remove pollution with simultaneous electricity generation.

RESULTS

Here, glucose was added as a co‐substrate in this system. The charge output of soil microbial fuel cells (MFCs) was enhanced by 262%, and the total petroleum hydrocarbon degradation rate increased by 200%. According to the increased dehydrogenase and polyphenol oxidase activities, the exogenetic glucose substantially activated hydrocarbon degradation bacteria (such as Alcanivorax). The Shannon–Wiener Index and richness of soil microbial community decreased after glucose addition, indicating that a selective enrichment of specific communities was imposed by glucose. Correlation analysis showed the biodiversity in soil far from the cathode was mainly determined by the concentration of petroleum hydrocarbons, while that in soil close to the cathode was dominated by the current.

CONCLUSION

This study demonstrated that an exogenetic carbon source enhanced the bioelectrochemically assisted degradation of aged petroleum hydrocarbons in saline soils, providing an effective approach to remove contaminations from soil in barren areas or extreme environments. © 2015 Society of Chemical Industry
Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase‐deficient astrocytes
Authors: Pajęcka Kamilla , Nissen Jakob D. , Stridh Malin H. , Skytt Dorte M. , Schousboe Arne , Waagepetersen Helle S.
Published: February 2015

Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100–500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2‐deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels of extracellular glutamate independently of the GDH expression level. Moreover, increased intracellular glutamate content was observed in the GDH‐deficient cells after a 2‐hr incubation in the presence of 100 µM glutamate. It is significant that GDH‐deficient cells exhibited an increased utilization of glucose in the presence of 250 and 500 µM glutamate, monitored as an increase in the accumulation of tritiated 2‐deoxyglucose‐6‐phosphate. These findings underscore the importance of the expression level of GDH for the ability to utilize glutamate as an energy source fueling its own energy‐requiring uptake. © 2015 Wiley Periodicals, Inc.
Electromembrane‐surrounded solid‐phase microextraction coupled to ion mobility spectrometry for the determination of nonsteroidal anti‐inflammatory drugs: A rapid screening method in complicated matrices
Authors: Abedi Hamid , Ebrahimzadeh Homeira
Published: February 2015

A new robust method of electromembrane‐surrounded solid‐phase microextraction coupled to ion mobility mass spectrometry was applied for nonsteroidal anti‐inflammatory drugs determination in complex matrices. This is the first time that a graphene/polyaniline composite coating is applied in electromembrane‐surrounded solid‐phase microextraction method. The homemade graphene/polyaniline composite is characterized by a high electrical conductivity and thermal stability. The variables affecting electromembrane‐surrounded solid‐phase microextraction, including extraction time; applied voltage and pH were optimized through chemometric methods, central composite design, and response surface methodology. Under the optimized conditions, limits of detection of 0.04 and 0.05 ng/mL were obtained for mefenamic acid and ibuprofen, respectively. The feasibility of electromembrane‐surrounded solid‐phase microextraction followed by ion mobility mass spectrometry was successfully confirmed by the extraction and determination of low levels of ibuprofen and mefenamic acid in human urine and plasma samples and satisfactory results were obtained.
Acrylamide‐functionalized graphene micro‐solid‐phase extraction coupled to high‐performance liquid chromatography for the online analysis of trace monoamine acidic metabolites in biological samples
Authors: Yang Xiaoting , Hu Yufei , Li Gongke , Zhang Zhuomin
Published: February 2015

Monoamine acidic metabolites in biological samples are essential biomarkers for the diagnosis of neurological disorders. In this work, acrylamide‐functionalized graphene adsorbent was successfully synthesized by a chemical functionalization method and was packed in a homemade polyether ether ketone micro column as a micro‐solid‐phase extraction unit. This micro‐solid‐phase extraction unit was directly coupled to high‐performance liquid chromatography to form an online system for the separation and analysis of three monoamine acidic metabolites including homovanillic acid, 5‐hydroxyindole‐3‐acetic acid, and 3,4‐dihydroxyphenylacetic acid in human urine and plasma. The online system showed high stability, permeability, and adsorption capacity toward target metabolites. The saturated extraction amount of this online system was 213.1, 107.0, and 153.4 ng for homovanillic acid, 5‐hydroxyindole‐3‐acetic acid, and 3,4‐dihydroxyphenylacetic acid, respectively. Excellent detection limits were achieved in the range of 0.08–0.25 μg/L with good linearity and reproducibility. It was interesting that three targets in urine and plasma could be actually quantified to be 0.94–3.93 μg/L in plasma and 7.15–19.38 μg/L in urine. Good recoveries were achieved as 84.8–101.4% for urine and 77.8–95.1% for plasma with the intra‐ and interday relative standard deviations less than 9.3 and 10.3%, respectively. This method shows great potential for online analysis of trace monoamine acidic metabolites in biological samples.
In vivo 1HMRSI of glycine in brain tumors at 3T
Authors: Ganji Sandeep K. , Maher Elizabeth A. , Choi Changho
Published: February 2015

Purpose

MR spectroscopic imaging (SI) of glycine (Gly) in the human brain is challenging due to the interference of the abundant neighboring J‐coupled resonances. Our aim is to accomplish reliable imaging of Gly in healthy brain and brain tumors using an optimized MR sequence scheme at 3 tesla.

Methods

Two‐dimensional 1H SI was performed with a point‐resolved spectroscopy scheme. An echo time of 160 ms was used for separation between Gly and myo‐inositol signals. Data were collected from eight healthy volunteers and 14 subjects with gliomas. Spectra were analyzed with the linear combination model using numerically calculated basis spectra. Metabolite concentrations were estimated with reference to creatine in white matter (WM) regions at 6.4 molar concentrations (mM).

Results

From a linear regression analysis with respect to the fractional gray matter (GM) content, the Gly concentrations in pure GM and WM in healthy brains were estimated to be 1.1 and 0.3 mM, respectively. Gly was significantly elevated in tumors. The tumor‐to‐contralateral Gly concentration ratio was more extensive with higher grades, showing ∼10‐fold elevation of Gly in glioblastomas.

Conclusion

The Gly level is significantly different between GM and WM in healthy brains. Our data indicate that SI of Gly may provide a biomarker of brain tumor malignancy. Magn Reson Med 75:52–62, 2016. © 2015 Wiley Periodicals, Inc.
MRICEST at 1T with large µeffLn3+ complexes T m3+‐HPDO3A: An efficient MRI pH reporter
Authors: Rancan Giaime , Delli Castelli Daniela , Aime Silvio
Published: February 2015

Purpose

Chemical exchange saturation transfer (CEST) sensitivity relies on the prototropic exchange rate kex between the agent and the “bulk” water protons. To exploit large kex, a large frequency separation (Δω) between the pools of exchanging protons is necessary. For this reason, high magnetic fields are preferred. Herein it is shown that the use of paramagnetic CEST agents based on lanthanide (III) ions with large effective magnetic moments allows the carrying out of CEST experiments at the relatively low field strength of 1 tesla (T).

Methods

Measurements were performed on a 1T MR‐scanner using continuous wave (cw)‐presaturation with a spin echo sequence. ParaCEST complexes have been synthetized by mixing the ligand and Ln(III)Cl3 in a stoichiometric ratio at room temperature and pH 7.

Results

Different lanthanide chelates were investigated (Tm‐, Dy‐, Yb‐, Eu‐HPDO3A, and Eu‐DOTAMGly). Ratiometric (Tm‐HPDO3A) and selective detection (Eu‐DOTAMGly and Tm‐HPDO3A) experiments have been proven feasible in vivo.

Conclusion

In vitro experiments demonstrated the feasibility of the CEST methodology at 1T for nearly every paraCEST candidate under investigation, except for Eu‐HPDO3A. Among the studied compounds, Tm‐HPDO3A proved suitable for the application of a ratiometric method for assessing pH both in vitro and in vivo. Magn Reson Med 75:329–336, 2016. © 2015 Wiley Periodicals, Inc.
Safety of valproic acid in patients with chronic obstructive pulmonary disease: a population‐based cohort study
Authors: Antoniou Tony , Yao Zhan , Camacho Ximena , Mamdani Muhammad M. , Juurlink David N. , Gomes Tara
Published: February 2015

Purpose

Valproic acid is an anticonvulsant that also inhibits histone deacetylase (HDAC), a property that could worsen pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The clinical significance of this property is unknown. We therefore compared the risk of COPD exacerbation in older patients with COPD commencing treatment with either valproic acid or phenytoin, an anticonvulsant that does not affect HDAC.

Methods

We conducted a population‐based retrospective cohort study of Ontario residents with COPD aged 66 years or older who started treatment with valproic acid or phenytoin between 1 April 1993 and 30 November 2012. The primary outcome was a hospital admission or emergency department visit for a COPD exacerbation within 240 days of drug initiation. A secondary outcome examined initiation of oral corticosteroids in the outpatient setting.

Results

During the study period, we identified 4596 COPD patients who commenced valproic acid and 8478 who commenced phenytoin. Following multivariable adjustment, valproic acid did not increase the risk of the primary outcome (adjusted hazard ratio 1.00, 95% confidence interval 0.79 to 1.26). Although valproic acid was associated with a lower risk of initiating oral corticosteroids in the first thirty days following commencement of anticonvulsant therapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21 to 0.49), no difference was observed during subsequent follow‐up.

Conclusion

Among older patients with COPD, treatment with valproic acid does not increase the risk of adverse pulmonary outcomes relative to phenytoin. These findings suggest that valproate‐induced HDAC inhibition is of little clinical relevance in this context. ">© 2015 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
Template–polymer commensurability and directed self‐assembly block copolymer lithography
Authors: Sunday Daniel F. , Ashley Elizabeth , Wan Lei , Patel Kanaiyalal C. , Ruiz Ricardo , Kline R. Joseph
Published: February 2015

Block copolymer directed self‐assembly (BCP) with chemical epitaxy is a promising lithographic solution for patterning features with critical dimensions under 20 nm. In this work, we study the extent to which lamellae‐forming poly(styrene‐b‐methyl methacrylate) can be directed with chemical contrast patterns when the pitch of the block copolymer is slightly compressed or stretched compared to the equilibrium pitch observed in unpatterned films. Critical dimension small angle X‐ray scattering complemented with SEM analysis was used to quantify the shape and roughness of the line/space features. It was found that the BCP was more lenient to pitch compression than to pitch stretching, tolerating at least 4.9% pitch compression, but only 2.5% pitch stretching before disrupting into dislocation or disclination defects. The more tolerant range of pitch compression is explained by considering the change in free energy with template mismatch, which suggests a larger penalty for pitch stretching than compressing. Additionally, the effect of width mismatch between chemical contrast pattern and BCP is considered for two different pattern transfer techniques. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 595–603
Screening protein isoforms predictive for cancer using immunoaffinity capture and fast LC‐MS in PRM mode
Authors: Lesur Antoine , Ancheva Lina , Kim Yeoun Jin , Berchem Guy , van Oostrum Jan , Domon Bruno
Published: February 2015

Purpose

We report an immunocapture strategy to extract proteins known to harbor driver mutations for a defined cancer type before the simultaneous assessment of their mutational status by MS. Such a method bypasses the sensitivity and selectivity issues encountered during the analysis of unfractionated complex biological samples.

Experimental design

Fast LC separations using short nanobore columns hyphenated with a high‐resolution quadrupole‐orbitrap mass spectrometer have been devised to take advantage of fast MS cycle times in conjunction with sharp chromatographic peak widths to accelerate the sample analysis throughput. Such an analytical platform is well suited to analyze simple protein mixtures obtained after immunoaffinity enrichment.

Results

After establishing the technical performance of the platform, the method was applied to the quantitative profiling of cellular Ras and EGFR protein isoforms, as well as serum amyloid A isoforms in plasma.

Conclusions and clinical relevance

Immunoaffinity purification combined with fast LC‐MS detection for the detection of driver mutations in tissue and tumor biomarkers in plasma samples can assist clinicians to select an optimal therapeutic intervention for patients.
Mass Dependent of Explosion Probability of RDX, Tetryl, and a PBX Powder in Drop Hammer Test
Authors: Wen Yushi , Long Xinping , Xiang Yong , Yu Shaojun , Dai Xiaogan , Li Ming
Published: February 2015

Series of Drop Weight Tests with varying sample mass of RDX, tetryl, and a PBX molding powder were carried out and the dramatic effects of sample mass on the explosion probability were obtained. The experimental results indicate that the explosion probability will firstly increase and subsequently decrease when the mass of sample reduces and also it shows the explosion probability is also related with the coverage area of the sample on the impact pillar. The explosion probability reached the maximum when the impact pillar was fully covered by the sample. A Dual‐factor‐competition Model is proposed in this work, which is able to predict the correlation between the explosion probability and sample mass. The response characteristic obtained can help to redesign the sensitivity test and provide a new way to distinguish the impact sensitiveness of insensitive explosives by reducing the sample mass.
Does deamidation cause protein unfolding? A top‐down tandem mass spectrometry study
Authors: Soulby Andrew J. , Heal Jack W. , Barrow Mark P. , Roemer Rudolf A. , O'Connor Peter B.
Published: February 2015

Deamidation is a nonenzymatic post‐translational modification of asparagine to aspartic acid or glutamine to glutamic acid, converting an uncharged amino acid to a negatively charged residue. It is plausible that deamidation of asparagine and glutamine residues would result in disruption of a proteins' hydrogen bonding network and thus lead to protein unfolding. To test this hypothesis Calmodulin and B2M were deamidated and analyzed using tandem mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer (FTICR‐MS). The gas phase hydrogen bonding networks of deamidated and nondeamidated protein isoforms were probed by varying the infra‐red multi‐photon dissociation laser power in a linear fashion and plotting the resulting electron capture dissociation fragment intensities as a melting curve at each amino acid residue. Analysis of the unfolding maps highlighted increased fragmentation at lower laser powers localized around heavily deamidated regions of the proteins. In addition fragment intensities were decreased across the rest of the proteins which we propose is because of the formation of salt‐bridges strengthening the intramolecular interactions of the central regions. These results were supported by a computational flexibility analysis of the mutant and unmodified proteins, which would suggest that deamidation can affect the global structure of a protein via modification of the hydrogen bonding network near the deamidation site and that top down FTICR‐MS is an appropriate technique for studying protein folding.
Effects of refuges on the evolution of resistance to transgenic corn by the western corn rootworm, Diabrotica virgifera virgiferaLeConte
Authors: Deitloff Jennifer , Dunbar Mike W , Ingber David A , Hibbard Bruce E , Gassmann Aaron J
Published: February 2015

BACKGROUND

Diabrotica virgifera virgifera LeConte is a major pest of corn and causes over a billion dollars of economic loss annually through yield reductions and management costs. Corn producing toxins derived from Bacillus thuringiensis (Bt) has been developed to help manage D. v. virgifera. However, previous studies have demonstrated the ability of this species to evolve resistance to Bt toxins in both laboratory and field settings.

RESULTS

We used an experimental evolution approach to test the refuge strategies for delaying resistance of D. v. virgifera to corn producing Bt toxin Cry34/35Ab1. In the absence of refuges, D. v. virgifera developed resistance to Bt corn after three generations of selection. In some cases, non‐Bt refuges reduced the level of resistance compared with the strain selected in the absence of refuges, but refuge strains did show reduced susceptibility to Bt corn compared with the unselected strain.

CONCLUSIONS

In this study, non‐Bt refuges delayed resistance to Bt corn by D. v. virgifera in some cases but not others. Combining the refuge strategy with pyramids of multiple Bt toxins and applying other pest management strategies will likely be necessary to delay resistance of D. v. virgifera to Bt corn. © 2015 Society of Chemical Industry
Characterization of gas phase iron phthalocyanine with X‐ray photoelectron and absorption spectroscopies
Authors: Bidermane Ieva , Lüder Johann , Totani Roberta , Grazioli Cesare , de Simone Monica , Coreno Marcello , Kivimäki Antti , Åhlund John , Lozzi Luca , Brena Barbara , Puglia Carla
Published: February 2015

Despite the numerous studies dedicated to phthalocyanine molecules adsorbed on surfaces, in monolayer or thin film, very few works have been focused on the characterization of vapors of these molecules. In this article we present the C 1s, N 1s and Fe 2p photoemission results as well as N K‐edge X‐ray absorption data of iron phthalocyanine (FePc) in gas phase. Presented comparison of X‐ray photoelectron spectroscopy and X‐ray absorption spectroscopy spectra of FePc films show a great similarity with the gas phase results, confirming the molecular character of thick films. The Fe 2p photoemission spectrum of the gas phase FePc, shown for the first time, can be considered as a fingerprint of the Fe(II) ionic state of the central metal of the iron phthalocyanine. The performed multiplet calculations for describing the Fe 2p XP spectrum indicate (aeb) state as the most probable ground state for thick film of iron phthalocyanine.
A regional forecast model evaluation of statistical rainfall properties using the CPOL radar observations in different precipitation regimes over Darwin, Australia
Authors: Nguyen Hanh , Protat Alain , Kumar Vickal , Rauniyar Surendra , Whimpey Michael , Rikus Lawrence
Published: February 2015

This study evaluates the ability of the regional high‐resolution version of the Australian Community Climate and Earth‐System Simulator (ACCESS‐A) model (horizontal resolution of 12 km, 50 height levels with a 37.5 km top) to simulate statistical rainfall properties during three monsoon seasons using the Darwin C‐band polarimetric (CPOL) radar observation as a reference. The comparison consists of characteristics of precipitation, including the total‐domain accumulated daily rainfall, the daily rain intensity and frequency and the probability distribution function of hourly rain rate. These characteristics are then binned using five large‐scale atmospheric regimes that represent the main weather states in that region to assess the ability of the model to reproduce the variability of the statistical rainfall properties as a function of these defined regimes. The main results are that although the model reproduces the accumulated daily rainfall amount reasonably well, albeit tending to slightly overestimate it, the mean rain rate is too weak, compensated by too large a rain frequency of occurrence. In terms of intensity the model tends to perform worse in the dry regimes but improves in the wet regimes, especially during the ‘Deep Westerly’ regime, when most of the monsoonal precipitation is produced. Probability distribution functions of rain rates reveal that although there are small differences amongst regimes, marked discrepancies are found between model and observations. The ACCESS‐A overestimates light rain rates, underestimates moderate to heavy rain rates and produces spurious very heavy rain rates that are not observed at all by the radar. The evaluation of the diurnal cycle of rainfall properties also reveals a general underestimate of rain rates, compensated by an overestimated rain frequency over the whole cycle, resulting in an overestimated amplitude and a wrong timing of the diurnal cycle. In all regimes, the overestimation of total‐domain daily rainfall and rain frequency is found to be due to an overestimation of low rain rates produced by the ACCESS‐A convective scheme, while the underestimation of mean rain rate is due to an underestimate of high rain rates and high rain rates frequency by the ACCESS‐A convective scheme.
TALEN‐mediated gene editing of the thrombospondin‐1 locus in axolotl
Authors: Kuo Tzu‐Hsing , Kowalko Johanna E. , DiTommaso Tia , Nyambi Mandi , Montoro Daniel T. , Essner Jeffrey J. , Whited Jessica L.
Published: February 2015

Loss‐of‐function genetics provides strong evidence for a gene's function in a wild‐type context. In many model systems, this approach has been invaluable for discovering the function of genes in diverse biological processes. Axolotls are urodele amphibians (salamanders) with astonishing regenerative abilities, capable of regenerating entire limbs, portions of the tail (including spinal cord), heart, and brain into adulthood. With their relatively short generation time among salamanders, they offer an outstanding opportunity to interrogate natural mechanisms for appendage and organ regeneration provided that the tools are developed to address these long‐standing questions. Here we demonstrate targeted modification of the thrombospondin‐1 (tsp‐1) locus using transcription‐activator‐like effector nucleases (TALENs) and identify a role of tsp‐1 in recruitment of myeloid cells during limb regeneration. We find that while tsp‐1‐edited mosaic animals still regenerate limbs, they exhibit a reduced subepidermal collagen layer in limbs and an increased number of myeloid cells within blastemas. This work presents a protocol for generating and genotyping mosaic axolotls with TALEN‐mediated gene edits.
Monolithic Graphene Trees as Anode Material for Lithium Ion Batteries with High C‐Rates
Authors: Jeong Seung Yol , Yang Sunhye , Jeong Sooyeon , Kim Ick Jun , Jeong Hee Jin , Han Joong Tark , Baeg Kang‐Jun , Lee Geon‐Woong
Published: February 2015

Monolithically structured reduced graphene oxide (rGO), prepared from a highly concentrated and conductive rGO paste, is introduced as an anode material for lithium ion batteries with high rate capacities. This is achieved by a mixture of rGO paste and the water‐soluble polymer sodium carboxymethylcellulose (SCMC) with freeze drying. Unlike previous 3D graphene porous structures, the monolithic graphene resembles densely branched pine trees and has high mechanical stability with strong adhesion to the metal electrodes. The structures contain numerous large surface area open pores that facilitate lithium ion diffusion, while the strong hydrogen bonding between the graphene layers and SCMC provides high conductivity and reduces the volume changes that occur during cycling. Ultrafast charge/discharge rates are obtained with outstanding cycling stability and the capacities are higher than those reported for other anode materials. The fabrication process is simple and straightforward to adjust and is therefore suitable for mass production of anode electrodes for commercial applications.