bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic Gold(I) N‐heterocyclic Carbene Complexes with Phosphane Ligands as Potent Enzyme Inhibitors
Authors: Rubbiani Riccardo , Salassa Luca , de Almeida Andreia , Casini Angela , Ott Ingo
Published: March 2014

Organometallic gold complexes with N‐heterocyclic carbene (NHC) ligands have been demonstrating promising properties as novel anticancer agents. Gold(I) NHC complexes containing different phosphanes as secondary ligands were shown to trigger strong cytotoxic effects in cancer cells, and their effective uptake into the cells was quantified by atomic absorption spectroscopy. Moreover, the new compounds strongly inhibited the activity of the seleno‐enzyme thioredoxin reductase (TrxR) and of the zinc‐finger enzyme poly(ADP‐ribose) polymerase 1 (PARP‐1). In the case of TrxR inhibition, their activity depended clearly on the size of the alkyl/aryl residues of phosphorus atoms. Density functional theory (DFT) calculations showed that the AuP bond of the triphenylphosphane complex [AuI(NHC)(PPh3)]I had a lower bond dissociation energy compared to trialkylphosphane complexes [AuI(NHC)(PR3)]I, indicating a higher kinetic reactivity of this particular compound. In fact, [AuI(NHC)(PPh3)]I triggered an enhanced inhibitory activity against PARP‐1.
Quantitative chemical exchange saturation transfer (qCEST) MRI – RF spillover effect‐corrected omega plot for simultaneous determination of labile proton fraction ratio and exchange rate
Authors: Sun Phillip Zhe , Wang Yu , Dai ZhuoZhi , Xiao Gang , Wu Renhua
Published: March 2014

Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute proteins and peptides as well as microenvironmental properties. However, the complexity of the CEST MRI effect, which varies with the labile proton content, exchange rate and experimental conditions, underscores the need for developing quantitative CEST (qCEST) analysis. Towards this goal, it has been shown that omega plot is capable of quantifying paramagnetic CEST MRI. However, the use of the omega plot is somewhat limited for diamagnetic CEST (DIACEST) MRI because it is more susceptible to direct radio frequency (RF) saturation (spillover) owing to the relatively small chemical shift. Recently, it has been found that, for dilute DIACEST agents that undergo slow to intermediate chemical exchange, the spillover effect varies little with the labile proton ratio and exchange rate. Therefore, we postulated that the omega plot analysis can be improved if RF spillover effect could be estimated and taken into account. Specifically, simulation showed that both labile proton ratio and exchange rate derived using the spillover effect‐corrected omega plot were in good agreement with simulated values. In addition, the modified omega plot was confirmed experimentally, and we showed that the derived labile proton ratio increased linearly with creatine concentration (p < 0.01), with little difference in their exchange rate (p = 0.32). In summary, our study extends the conventional omega plot for quantitative analysis of DIACEST MRI. Copyright © 2014 John Wiley & Sons, Ltd.
Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy
Authors: Ali Towhid , Nakajima Takahito , Sano Kohei , Sato Kazuhide , Choyke Peter L. , Kobayashi Hisataka
Published: March 2014

A new type of monoclonal antibody (mAb)‐based, highly specific phototherapy (photoimmunotherapy; PIT) that uses a near‐infrared (NIR) phthalocyanine dye, IRDye700DX (IR700) conjugated with an mAb, has recently been described. NIR light exposure leads to immediate, target‐selective necrotic cell death. However, tumor shrinkage takes several days to occur, making it difficult to detect earlier changes in the tumor. In this study, Panitumumab targeting the epidermal growth factor receptor (EGFR1) conjugated to IR700 was used to treat EGFR‐expressing A431 tumor cells and in vivo xenografts. PIT was performed at varying doses of NIR light (10, 30, 50 and 100 J cm−2) in xenograft tumors in mice. Indocyanine green (ICG) dynamic imaging was evaluated for monitoring cytotoxic effects for the first hour after PIT. Our results demonstrated a statistical difference (p < 0.05) in ICG intensity between control and PIT treated tumors in the higher light exposure groups (50 J cm−2: 2.94 ± 0.35 vs 5.22 ± 0.92, p = 0.02; and 100 J cm−2: 3.56 ± 0.96 vs 5.71 ± 1.43, p = 0.008) as early as 20 min post ICG injection. However, no significant difference (p > 0.05) in ICG intensity between control and PIT treated tumors was evident in the lower light exposure group at any time points up to 60 min (10 J cm−2: 1.92 ± 0.49 vs 1.71 ± 0.3, p = 0.44; and 30 J cm−2: 1.57 ± 0.35 vs 2.75 ± 0.59, p = 0.07). Similarly, the retention index (background to corrected uptake ratio of ICG) varied with light exposure. In conclusion, ICG may serve as a potential indicator of acute cytotoxic effects of mAb‐IR700‐induced PIT even before morphological changes can be seen in targeted tumors. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Absolute MR thermometry using nanocarriers
Authors: Deckers Roel , Sprinkhuizen Sara M. , Crielaard Bart J. , Ippel Johannes H. , Boelens Rolf , Bakker Chris J. G. , Storm Gert , Lammers Twan , Bartels Lambertus W.
Published: March 2014

Accurate time‐resolved temperature mapping is crucial for the safe use of hyperthermia‐mediated drug delivery. We here propose a magnetic resonance imaging temperature mapping method in which drug delivery systems serve not only to improve tumor targeting, but also as an accurate and absolute nano‐thermometer. This method is based on the temperature‐dependent chemical shift difference between water protons and the protons in different groups of drug delivery systems. We show that the chemical shift of the protons in the ethylene oxide group in polyethylene glycol (PEG) is temperature‐independent, whereas the proton resonance of water decreases with increasing temperature. The frequency difference between both resonances is linear and does not depend on pH and physiological salt conditions. In addition, we show that the proton resonance of the methyl group in N‐(2‐hydroxypropyl)‐methacrylamide (HPMA) is temperature‐independent. Therefore, PEGylated liposomes, polymeric mPEG‐b‐pHPMAm‐Lac2 micelles and HPMA copolymers can provide a temperature‐independent reference frequency for absolute magnetic resonance (MR) thermometry. Subsequently, we show that multigradient echo MR imaging with PEGylated liposomes in situ allows accurate, time‐resolved temperature mapping. In conclusion, nanocarrier materials may serve as highly versatile tools for tumor‐targeted drug delivery, acting not only as hyperthermia‐responsive drug delivery systems, but also as accurate and precise nano‐thermometers. Copyright © 2014 John Wiley & Sons, Ltd.
Bifunctional Gd(III) and Tb(III) chelates based on a pyridine–bis(iminodiacetate) platform, suitable optical probes and contrast agents for magnetic resonance imaging
Authors: Laurent Sophie , Vander Elst Luce , Galaup Chantal , Leygue Nadine , Boutry Sébastien , Picard Claude , Muller Robert. N.
Published: March 2014

To study the physicochemical properties of lanthanide complexes derived from a bifunctional chelating agent based on a PMN‐tetraacetic acid moiety {PMN‐tetraacetic acid (1): [2,6‐pyridinediylbis(methylene nitrilo)‐tetraacetic acid]}, 4‐carboxylic acid substituted pyridine derivative (2) was synthesized. This ligand forms heptadentate (N3O4) Ln(III) complexes (Ln = Gd, Eu, Tb), with two water molecules completing the inner coordination sphere of the metal. The parameters that govern the relaxivity of the Gd(III) complex and the luminescence of Eu(III) and Tb(III) complexes were obtained by 17O and 1H NMR studies and time‐resolved fluorescence experiments, respectively. The gadolinium and terbium complexes show interesting properties either for MRI or FOR optical imaging; that is, for the Gd complex, a high proton relaxivity (r1 = 6.4 s−1 mm−1 at 20 MHz) with short water residence time (τM = 38.5 ns); for the Tb complex, a luminescence lifetime of 1.22 ms at room temperature and a luminescence quantum yield of 10%. The kinetic stability of these complexes toward blood protein, cation or bioactive oxyanion was also examined. The Gd(2)(H2O)2 complex does not interact with human serum albumin, but undergoes a transmetalation reaction with Zn(II) in a phosphate buffer solution (pH 7.4), rather similar to that of Gd–DTPA–BMA(H2O). On the other hand, as observed for Eu and Tb complexes, these chelates do not form ternary complexes with bidentate anions such as l‐lactate, citrate or carbonate. Finally, a phosphatidylserine‐specific hexapeptide (TLVSSL) was grafted on Gd or Tb chelates, and the Gd–peptide conjugate was used in vitro for targeting apoptotic cells. Copyright © 2014 John Wiley & Sons, Ltd.
Disparities of cancer incidence in Michigan's American Indians: Spotlight on breast cancer
Authors: Roen Emily L. , Copeland Glenn E. , Pinagtore Noel L. , Meza Rafael , Soliman Amr S.
Published: March 2014

BACKGROUND

In American Indians (AIs), cancer is a leading cause of mortality, yet their disease burden is not fully understood due to unaddressed racial misclassification in cancer registries. This study describes cancer trends among AIs in Michigan, focusing on breast cancer, in a linked data set of Indian Health Service (IHS), tribal, and state cancer registry data adjusted for misclassification.

METHODS

AI status was based on reported race and linkage to IHS data and tribal registries. Data with complete linkage on all incident cancer cases in Michigan from 1995 to 2004 was used to calculate age‐standardized incidence estimates for invasive all‐site and female breast cancers stratified by racial group. For female breast cancers, stage‐ and age‐specific incidence and percent distributions of early‐ versus late‐stage cancers and age of diagnosis were calculated.

RESULTS

More than 50% of all AI cases were identified through IHS and/or tribal linkage. In the linked data, AIs had the lowest rates of all‐sites and breast cancer. For breast cancers, AI women had a greater late‐stage cancer burden and a younger mean age of diagnosis as compared to whites. Although the age‐specific rate for whites was greater than for AI women in nearly all age groups, the difference in hazard ratio increased with increasing age.

CONCLUSIONS

Our state‐specific information will help formulate effective, tailored cancer prevention strategies to this population in Michigan. The data linkages used in our study are crucial for generating accurate rates and can be effective in addressing misclassification of the AI population and formulating cancer prevention strategies for AI nationwide. Cancer 2014;120:1847–1853. © 2014 American Cancer Society.
Octreotide long‐acting repeatable use among elderly patients with carcinoid syndrome and survival outcomes: A population‐based analysis
Authors: Shen Chan , Shih Ya‐Chen Tina , Xu Ying , Yao James C.
Published: March 2014

BACKGROUND

Octreotide long‐acting repeatable (LAR) is indicated for the treatment of carcinoid syndrome and diarrhea related to VIPoma, and may delay tumor growth in patients with neuroendocrine tumors (NETs). To the authors' knowledge, the pattern of octreotide LAR use in clinical practice and its impact on survival outcomes has not been well documented.

METHODS

Using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database, the authors identified patients with NET aged ≥ 65 years who were diagnosed between July 1999 and December 2007. Patients with US Food and Drug Administration‐approved indications for octreotide LAR were identified from Medicare claims. Multivariate logistic regression was performed to ascertain factors associated with octreotide LAR use, whereas the Cox proportional hazards model was used to evaluate the impact of octreotide LAR on survival.

RESULTS

Among those with Food and Drug Administration‐approved indications, 245 of 4848 patients with distant‐stage disease (51%) and 81 of 807 patients with local/regional disease (10%) initiated treatment with octreotide LAR within 6 months of diagnosis. Multivariate logistic regression indicated that among those with distant‐stage disease, older age (≥ 80 years vs 65‐69 years) (odds ratio [OR], 0.43; 95% confidence interval [95% CI], 0.23‐0.81), female sex (OR, 0.62; 95% CI, 0.40‐0.97), and living in the South (vs Northeast) (OR, 0.36; 95% CI, 0.18‐0.72) were associated with a lower likelihood of using octreotide LAR. The multivariate proportional hazards model showed that octreotide LAR provided a significant 5‐year survival benefit for patients with distant‐stage disease (hazards ratio, 0.61; P ≤ .001), whereas this survival benefit was not shown for the patients with local/regional stage (hazards ratio, 0.88; P = .563).

CONCLUSIONS

The results of this retrospective study suggest a possible survival benefit for the use of octreotide LAR in elderly patients with distant‐stage NET with carcinoid syndrome. The results of the current study also suggest that octreotide LAR is underused in this population despite recommended guidelines. Cancer 2014;120:2039–2049. © 2014 American Cancer Society.
Distribution of microsomal prostaglandin E synthase‐1 in the mouse brain
Authors: Eskilsson Anna , Tachikawa Masanori , Hosoya Ken‐ichi , Blomqvist Anders
Published: March 2014

Previous studies in rats have demonstrated that microsomal prostaglandin E synthase‐1 (mPGES‐1) is induced in brain vascular cells that also express inducible cyclooxygenase‐2, suggesting that such cells are the source of the increased PGE2 levels that are seen in the brain following peripheral immune stimulation, and that are associated with sickness responses such as fever, anorexia, and stress hormone release. However, while most of what is known about the functional role of mPGES‐1 for these centrally evoked symptoms is based on studies on genetically modified mice, the cellular localization of mPGES‐1 in the mouse brain has not been thoroughly determined. Here, using a newly developed antibody that specifically recognizes mouse mPGES‐1 and dual‐labeling for cell‐specific markers, we report that mPGES‐1 is constitutively expressed in the mouse brain, being present not only in brain endothelial cells, but also in several other cell types and structures, such as capillary‐associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. Regional differences were seen with particularly prominent labeling in autonomic relay structures such as the area postrema, the subfornical organ, the paraventricular hypothalamic nucleus, the arcuate nucleus, and the preoptic area. Following immune stimulation, mPGES‐1 in brain endothelial cells, but not in other mPGES‐1‐positive cells, was coexpressed with cyclooxygenase‐2, whereas there was no coexpression between mPGES‐1 and cyclooxygenase‐1. These data imply a widespread synthesis of PGE2 or other mPGES‐1‐dependent products in the mouse brain that may be related to inflammation‐induced sickness symptom as well as other functions, such as blood flow regulation. J. Comp. Neurol. 522:3229–3244, 2014. © 2014 Wiley Periodicals, Inc.
Variations in microanatomy of the human cochlea
Authors: Avci Ersin , Nauwelaers Tim , Lenarz Thomas , Hamacher Volkmar , Kral Andrej
Published: March 2014

The human cochlea shows considerable interindividual variability in size and morphology. In order to develop atraumatic cochlear implant (CI) electrodes, high‐precision details of the variability of human anatomy are required. Sixteen human temporal bones were cut around the cochlea in blocks of approximately 3.5 × 3.5 cm. The bones were scanned by using a Skyscan 1173 micro‐computed tomography (μCT) device. Mimics software (Materialise, Leuven, Belgium) was used to segment out the scala tympani (ST) from the μCT images. A three‐dimensional surface model of the segmented area was generated for each cochlea. Cross‐sectional images were taken and analyzed by custom‐designed software in MATLAB. Comparison of different STs showed large variability in cross‐sectional diameter (CSD), vertical trajectory, and height of the ST. Relative standard deviations of the CSD were between 9 and 15%. Heights measured at the center of the ST exceeded those in the modiolar and lateral regions of the scala. At the lateral region, the height decreased significantly at the beginning of the second turn. In the vertical trajectory, critical anatomic features were observed, such as dips, vertical jumps, and peaks. Rosenthal's canal (RC) extended to between 560 and 650°. We found a correlation between the length of the RC and that of the ST. The ST was segmented and the internal dimensions measured by using μCT. We observed large dimensional variability between different STs. These differences could have considerable implications for approaches to the design of CI arrays, especially in terms of their ability to preserve residual hearing during insertion of the electrode array. J. Comp. Neurol. 522:3245–3261, 2014. © 2014 Wiley Periodicals, Inc.
Derivatization and Multidimensional Gas‐Chromatographic Resolution of α‐Alkyl and α‐Dialkyl Amino Acid Enantiomers
Authors: Meinert Cornelia , Meierhenrich Uwe J.
Published: March 2014

The quantitative resolution of amino acid enantiomers is crucial to a number of fields of bioanalytical chemistry, including food and plant analysis, metabolomics, medicinal chemistry, and archeochemistry. The enantioselective analysis of α‐dialkyl amino acids, however, has proven more difficult than for proteinaceous α‐protonated amino acids. Herein, the development of an analytical method capable of base‐line resolving enantiomers of α‐alkyl and α‐dialkyl amino acids in two chromatographic dimensions is reported. It was found that enantiomers of α‐dialkyl amino acids can be readily resolved with the use of an enantioselective Chirasil‐Val stationary phase in the first chromatographic dimension and a polyethylene glycol stationary phase in the second dimension. These data offer new possibilities for the enantioselective resolution and precise quantification of non‐biological α‐dialkyl amino acids. This methodology will subsequently be applied particularly towards enantioselective analyses of samples relevant for understanding of the origin of homochirality on Earth such as meteorites, comets, and interstellar ices.
1,8‐Cineole: Chemical and Biological Oxidation Reactions and Products
Authors: Azerad Robert
Published: March 2014

The products of chemical and biological oxidation (hydroxy, oxo, and acid derivatives) of 1,8‐cineole (3,3‐dimethyl‐2‐oxabicyclo[2.2.2]octane) are reviewed with a focus on the diverse regio‐ and stereoselectivities obtained from this meso monoterpenic compound abundantly present in eucalyptus leaves. Physical properties (melting‐point and specific rotation values) as well as 1H and 13C NMR spectroscopic data of oxidized derivatives have been exhaustively compiled with particular attention on the clarification of some literature inconsistencies owing to different carbon numbering and stereochemical denominations. Analytical and synthetic methods, and formation as metabolites by plants, microorganisms, and animals are also reviewed together with their presently known biological activities.
Equimolar Carbon Absorption by Potassium Phthalimide and In Situ Catalytic Conversion Under Mild Conditions
Authors: Zhang Shuai , Li Yu‐Nong , Zhang Ya‐Wei , He Liang‐Nian , Yu Bing , Song Qing‐Wen , Lang Xian‐Dong
Published: March 2014

Potassium phthalimide, with weak basicity, is an excellent absorbent for rapid carbon dioxide capture with almost equimolar absorption. This process is assumed to proceed through the potassium carbamate formation pathway, as supported by NMR spectroscopy, an in situ FTIR study, and computational calculations. Both the basicity and nucleophilicity of phthalimide salts have a crucial effect on the capture process. Furthermore, the captured carbon dioxide could more easily be converted in situ into value‐added chemicals and fuel‐related products through carbon capture and utilization, rather than going through a desorption process.
Putting an eye on cytological specimens: An audit of the clinical impact of thyroid fine‐needle aspiration in different health care settings
Authors: Pereira Bernardo Dias , Gerhard Renê , Schmitt Fernando
Published: March 2014

There is published evidence showing less cost‐benefit approaches in the evaluation of thyroid nodules. We performed an institutional audit of the cytologic diagnosis of thyroid fine‐needle aspiration (FNA) in an attempt to perceive the clinical impact of this technique on the management of thyroid nodules and to compare it in two different types of health care: Primary Care Medicine and Endocrinology.

We performed a retrospective analysis to the electronic records of patients referred from General Practitioners (GP) and Endocrinologists (E) for thyroid FNA between 2010 and 2012. Request forms for cytological reports where retrieved for analysis of clinical and cytological data.

The database search retrieved 1655 patients (female gender: 88.2%; GP references: 51.8%). Preprocedure clinical information was available from 157 out of 2005 nodules (7.8%). Significant differences in cytological diagnosis were seen in “Nondiagnostic” (GP: 11.6%; E: 7.5%, χ2 = 0.002) and “Benign” categories (GP: 75%; E: 81.8%, χ2 < 0.001). The main potential cause of “Nondiagnostic” samples was nodules smaller than one centimeter (total: 14 cases; GP: 7; E: 7). Reasons to request FNA for these nodules were provided in 6 out of 27 cases (GP: 0/16; E: 6/11, P < 0.001). The rate of insufficient samples was inversely correlated with nodule size (τ = −0.242, P = 0.001).

When evaluating thyroid nodules, clinicians should take into account the limitations of FNA, the international recommendations for better cost‐benefit approaches and the importance of a well‐informed cytopathologist for better cytological diagnostic results. Diagn. Cytopathol. 2014;42:1009–1012. © 2014 Wiley Periodicals, Inc.
The Role of Sdf‐1α signaling in Xenopus laevis somite morphogenesis
Authors: Leal Marisa A. , Fickel Sarah R. , Sabillo Armbien , Ramirez Julio , Vergara Hernando Martínez , Nave Ceazar , Saw Daniel , Domingo Carmen R.
Published: March 2014

Background: Stromal derived factor‐1α (sdf‐1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis, and in embryogenesis. The sdf‐1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway et al., 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf‐1α is conserved in Xenopus laevis. Results: Using a morpholino approach, we demonstrate that knockdown of sdf‐1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf‐1α or cxcr4 leads to the near absence of β‐dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf‐1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. Conclusion: Our results show that sdf‐1α signaling regulates somite cell migration, rotation, and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf‐1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog. Developmental Dynamics 243:509–526, 2014. © 2013 Wiley Periodicals, Inc.
Genes that regulate morphogenesis and growth of the temporomandibular joint: A review
Authors: Hinton Robert J.
Published: March 2014

Compared with the joints of the limbs, our understanding of the genes that regulate development and growth in the temporomandibular joint (TMJ) is fairly limited. Because the morphogenesis of the secondary cartilage and other intra‐articular structures in the TMJ occurs later and in a different manner than in the limbs, the genetic control of TMJ development might reasonably be assumed to differ from that in the limbs. However, studies of the specific genes regulating TMJ morphogenesis and growth have only begun to appear in the literature within the last decade. This review attempts to survey and interpret the existing knowledge on this topic and to suggest fruitful avenues of investigation for the future. Studies to date using knockout and over‐expression of candidate genes suggest that a developmental hierarchy of joint structures exists, with condyle development primary. A hierarchy of gene expression also exists: Runx2 and Sox9 expression is critical for condylar cartilage formation. Several of the other genes discussed in this report may regulate TMJ morphogenesis by affecting Sox9 and Runx2 expression and control the ihh‐PTHrP axis by means of these genes. Developmental Dynamics 243:864–874, 2014. © 2014 Wiley Periodicals, Inc.
Spatial and temporal genetic structure of a river‐residentAtlantic salmon (Salmo salar) after millennia of isolation
Authors: Sandlund Odd Terje , Karlsson Sten , Thorstad Eva B. , Berg Ole Kristian , Kent Matthew P. , Norum Ine C. J. , Hindar Kjetil
Published: March 2014

The river‐residentSalmo salar(“småblank”) has been isolated from otherAtlantic salmon populations for 9,500 years in upperRiverNamsen,Norway. This is the onlyEuropeanAtlantic salmon population accomplishing its entire life cycle in a river. Hydropower development during the last six decades has introduced movement barriers and changed more than 50% of the river habitat to lentic conditions. Based on microsatellites andSNPs, genetic variation within småblank was only about 50% of that in the anadromousAtlantic salmon within the same river. The genetic differentiation (FST) between småblank and the anadromous population was 0.24. This is similar to the differentiation between anadromousAtlantic salmon inEurope andNorthAmerica. Microsatellite analyses identified three genetic subpopulations within småblank, each with an effective population sizeNeof a few hundred individuals. There was no evidence of reduced heterozygosity and allelic richness in contemporary samples (2005–2008) compared with historical samples (1955–56 and 1978–79). However, there was a reduction in genetic differentiation between sampling localities over time.SNPdata supported the differentiation of småblank into subpopulations and revealed downstream asymmetric gene flow between subpopulations. In spite of this, genetic variation was not higher in the lower than in the upper areas. The meta‐population structure of småblank probably maintains genetic variation better than one panmictic population would do, as long as gene flow among subpopulations is maintained. Småblank is a unique endemic island population of Atlantic salmon. It is in a precarious situation due to a variety of anthropogenic impacts on its restricted habitat area. Thus, maintaining population size and avoiding further habitat fragmentation are important.
A Heterobimetallic FeIIIMnII Complex of an Unsymmetrical Dinucleating Ligand: A Structural and Functional Model Complex for the Active Site of Purple Acid Phosphatase of Sweet Potato
Authors: Das Biswanath , Daver Henrik , Singh Amrendra , Singh Reena , Haukka Matti , Demeshko Serhiy , Meyer Franc , Lisensky George , Jarenmark Martin , Himo Fahmi , Nordlander Ebbe
Published: March 2014

The heterodinuclear mixed‐valence complex [FeMn(ICIMP)(OAc)2Cl] (1) {H2ICIMP = 2‐(N‐carboxylmethyl)‐[N‐(N‐methylimidazolyl‐2‐methyl)aminomethyl]‐[6‐(N‐isopropylmethyl)‐[N‐(N‐methylimidazolyl‐2‐methyl)]aminomethyl‐4‐methylphenol], an unsymmetrical N4O2 donor ligand} has been synthesized and fully characterized by several spectroscopic techniques as well as by X‐ray crystallography. The crystal structure of the complex reveals that both metal centers in 1 are six‐coordinate with the chloride ion occupying the sixth coordination site of the MnII ion. The phenoxide moiety of the ICIMP ligand and both acetate ligands bridge the two metal ions of the complex. Mössbauer spectroscopy shows that the iron ion in 1 is high‐spin FeIII. Two quasi‐reversible redox reactions for the complex, attributed to the FeIIIMnII/FeIIMnII (at –0.67 V versus Fc/Fc+) and FeIIIMnII/FeIIIMnIII (at 0.84 V), were observed by means of cyclic voltammetry. Complex 1, with an FeIII–MnII distance of 3.58 Å, may serve as a model for the mixed‐valence oxidation state of purple acid phosphatase from sweet potato. The capability of the complex to effect organophosphate hydrolysis (phosphatase activity) has been investigated at different pH levels (5.5–11) by using bis(2,4‐dinitrophenyl)phosphate (BDNPP) as the substrate. Density functional theory calculations indicate that the substrate coordinates to the MnII ion. In the transition state, a hydroxide ion that bridges the two metal ions becomes terminally coordinated to the FeIII ion and acts as a nucleophile, attacking the phosphorus center of BDNPP with the concomitant dissociation of the leaving group.
Structures Self‐Assembled from Anionic Graphene and Cationic Manganese Porphyrin: Characterization and Application in Artificial Photosynthesis
Authors: Kaplan Amir , Korin Eli , Bettelheim Armand
Published: March 2014

Carboxylic‐rich graphene oxide (CGO) and MnIII tetrakis(N‐methyl‐4‐pyridinio)porphyrin (MnTMPyP) form self‐assembled leaf‐like structures. These were obtained through electrostatic and π–π stacking interactions, as indicated by the redshift of the metalloporphyrin Soret band throughout the pH range of 6–12. Voltammetry and XPS measurements confirmed that CGO does not significantly affect the chemical environment of the metal ion in MnTMPyP. However, the effect of CGO is apparent when determining by rotating ring disk electrode (RRDE) voltammetry the ability of CGO‐MnIVTMPyP films to catalyze water oxidation and evolve oxygen. The amount of O2 evolved at pH 10 and 1.6 V versus Ag/AgCl is 50 % higher than that of MnTMPyP films. When used for the photoelectrochemical oxidation of water, CGO‐MnTMPyP films on iron/hematite foams exhibited substantial activity, as evidenced by the current density (0.54 mA/cm2 at 1.23 V vs. NHE) and incident photons to current efficiency (IPCE; 9.0 % at 1.43 V vs. NHE) measured at pH 10.
Electrospun Polyaniline/Poly(ethylene oxide) Composite Nanofibers Based Gas Sensor
Authors: Li Changling , Chartuprayoon Nicha , Bosze Wayne , Low Karen , Lee Kyu Hwan , Nam Jin , Myung Nosang V.
Published: March 2014

Camphor‐10‐sulfonic acid (HCSA) doped polyaniline (PANI)/poly(ethylene oxide) (PEO) composite nanofibers with different compositions (12 to 52 wt.% of PANI) were synthesized by an electrospinning method and their properties including optical, electrical and sensing were systematically investigated. FT‐IR shows that an increase of IR absorbance ratios of aromatic CC stretching vibration of benzenoid rings of PANI to COC symmetric vibrational modes of PEO confirmed that the PANI content in nanofiber mats increased proportionally with increase in PANI content in electrospinning solution. The band gap of PANI was determined to be 2.5 eV using UV‐Vis spectroscopy. The electrical conductivities of the nanofibers increased with an increase in the PANI content in the nanofibers. Additionally, the sensitivity toward NH3 increased as the PANI content increased, but branched nanofibers reduced sensing response. The humidity sensitivity changed from positive to negative as the PANI content increased. The electron transport mechanism was studied by measuring the temperature dependence electrical resistivity. The negative temperature coefficient of resistance revealed a semiconducting behavior for the PANI/PEO nanofibers. The activation energy, calculated by Arrhenius plot, increased as the PANI content decreased. The power law indicated that electrons were being transported in a three dimensional matrix, and the longer hopping distance required more hopping energy for electron transport.
Phenolic characterization and antimicrobial activity of folk medicinal plant extracts for their applications in olive production
Authors: Boiteux Joana , Vargas Carolina Soto , Pizzuolo Pablo , Lucero Gabriela , Silva María Fernanda
Published: March 2014

Phytophthora spp is important in plant pathology due to the importance of the diseases it causes. In olive trees, severe damages are caused by the disease known as “dry branch” occasioned by Phytophthora nicotianae, P. citrophthora and P. palmivora. Much effort has been made to find efficient methods of control, with a low negative impact on environment. In this regard, treatment with plant extracts is a valid strategy. The aims of the present study are (i) to determine the polyphenol composition of extracts of Thymus vulgaris, Origanum vulgare, Matricaria recutita, and Larrea divaricata by CZE, (ii) correlate the analytical composition of these extracts with the inhibition on the mycelial growth, and (iii) determine the individual antimicrobial activity of the most active ingredients. A simple methodology was developed for the determination of catechin, naringenin, cinnamic acid, syringic acid, chlorogenic acid, apigenin, vanillic acid, luteolin, quercetin, and caffeic acid in plant extracts by CZE. The extraction of phenolic compounds in extract was performed by a miniaturized solid phase extraction using a home‐made minicolumn packed with suitable filtering material (C18, 50 mg). The optimized analyses conditions were: 30 mM boric acid buffer, pH 9.50; capillary, 57 cm full length, 50 cm effective length, 75 μm id, hydrodynamic injection 30 mbar, 2 s; 25 kV; 25°C, detection by UV absorbance at 290 nm. Sample results suggest that phenolic composition seems to have a great influence on inhibition of pathogens. The highest inhibitions of mycelial growth were observed for cinnamic acid and naringenin.
Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing
Authors: Coutelle Oliver , Hornig‐Do Hue‐Tran , Witt Axel , Andree Maria , Schiffmann Lars M , Piekarek Michael , Brinkmann Kerstin , Seeger Jens M , Liwschitz Maxim , Miwa Satomi , Hallek Michael , Krönke Martin , Trifunovic Aleksandra , Eming Sabine A , Wiesner Rudolf J , Hacker Ulrich T , Kashkar Hamid
Published: March 2014

In the normal quiescent vasculature, only 0.01% of endothelial cells (ECs) are proliferating. However, this proportion increases dramatically following the angiogenic switch during tumor growth or wound healing. Recent evidence suggests that this angiogenic switch is accompanied by a metabolic switch. Here, we show that proliferating ECs increasingly depend on mitochondrial oxidative phosphorylation (OxPhos) for their increased energy demand. Under growth conditions, ECs consume three times more oxygen than quiescent ECs and work close to their respiratory limit. The increased utilization of the proton motif force leads to a reduced mitochondrial membrane potential in proliferating ECs and sensitizes to mitochondrial uncoupling. The benzoquinone embelin is a weak mitochondrial uncoupler that prevents neoangiogenesis during tumor growth and wound healing by exhausting the low respiratory reserve of proliferating ECs without adversely affecting quiescent ECs. We demonstrate that this can be exploited therapeutically by attenuating tumor growth in syngenic and xenograft mouse models. This novel metabolic targeting approach might be clinically valuable in controlling pathological neoangiogenesis while sparing normal vasculature and complementing cytostatic drugs in cancer treatment.
Mild expression differences of MECP2 influencing aggressive social behavior
Authors: Tantra Martesa , Hammer Christian , Kästner Anne , Dahm Liane , Begemann Martin , Bodda Chiranjeevi , Hammerschmidt Kurt , Giegling Ina , Stepniak Beata , Castillo Venzor Aracely , Konte Bettina , Erbaba Begun , Hartmann Annette , Tarami Asieh , Schulz‐Schaeffer Walter , Rujescu Dan , Mannan Ashraf U , Ehrenreich Hannelore
Published: March 2014

The X‐chromosomal MECP2/Mecp2 gene encodes methyl‐CpG‐binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype‐based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3′UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele‐specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain‐expressed, species‐conserved miR‐511 binds to MECP2 3′UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior.
The role of vegetation in the retention of fine sediment and associated metal contaminants in London's rivers
Authors: Gibbs Helen M. , Gurnell Angela M. , Heppell Catherine M. , Spencer Kate L.
Published: March 2014

Many urban rivers receive significant inputs of metal‐contaminated sediments from their catchments. Restoration of urban rivers often creates increased slack water areas and in‐channel vegetation growth where these metal‐contaminated sediments may accumulate. Quantifying the accumulation and retention of these sediments by in‐channel vegetation in urban rivers is of importance in terms of the planning and management of urban river restoration schemes and compliance with the Water Framework Directive.

This paper investigates sediment properties at four sites across three rivers within Greater London to assess the degree to which contaminated sediments are being retained. Within paired restored and unrestored reaches at each site, four different bed sediment patch types (exposed unvegetated gravel, sand, and silt/clay (termed ‘fine’) sediments, and in‐channel vegetated sediments) were sampled and analysed for a range of metals and sediment characteristics. Many samples were found to exceed Environment Agency guidelines for copper (Cu), lead (Pb) and zinc (Zn) and Dutch Intervention Values for Cu and Zn.

At all sites, sediments accumulating around in‐channel vegetation were similar in calibre and composition to exposed unvegetated fine sediments. Both bed sediment types contained high concentrations of pseudo‐total and acetic acid extractable metal concentrations, potentially due to elevated organic matter and silt/clay content, as these are important sorbtion phases for metals. This implies that the changed sediment supply and hydraulic conditions associated with river restoration may lead to enhanced retention of contaminated fine sediments, particularly around emergent plants, frequently leading to the development of submerged and emergent landforms and potential river channel adjustments.

High pseudo‐total metal concentrations were also found in gravel bed sediments, probably associated with iron (Fe) and manganese (Mn) oxyhydroxides and discrete anthropogenic metal‐rich particles.

These results highlight the importance of understanding the potential effects of urban river restoration upon sediment availability and channel hydraulics and consequent impacts upon sediment contaminant dynamics and storage. Copyright © 2014 John Wiley & Sons, Ltd.
Rock slope instability and erosion: toward improved process understanding
Authors: Krautblatter Michael , Moore Jeffrey R.
Published: March 2014

Rock slopes in a range of environments are among the landscape elements most sensitive to climate change, the latter affecting rock mass properties, altering slope boundary conditions, and changing geosystem configurations. Major climate‐dependent influences promoting destabilization include stress redistribution with changing glacial ice extents, degradation of mountain permafrost, altered slope hydrology and weathering environments, loading and unloading due to deposition and erosion, and changes in the spectrum of magnitude and frequency of driving forces. In steep bedrock terrain, erosional processes control slope morphology by modulating rates of: (i) weathering in response to climate and pre‐disposition, (ii) rock slope retreat in response to magnitude and frequency of detachment, and (iii) channel incision or valley infilling in response to variable sediment supply. Modelling landscape evolution and anticipating natural hazards in these environments thus requires deeper insights into the processes driving rock slope instability and erosion. This special issue emphasizes new understanding of rock slope processes through a collection of manuscripts at the forefront of research in the field. Copyright © 2014 John Wiley & Sons, Ltd.
Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity
Authors: Maynard Samuel K. , Edwards Peter , Wheeler James R.
Published: March 2014

Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single-stage designs. Environ Toxicol Chem 2014;33:1578–1583. © 2014 The Authors. Published on behalf of SETAC by Wiley Periodicals, Inc.
QoS‐driven spectrum sharing game in cognitive radio systems: a variational inequality approach
Authors: Poulakis Marios I. , Vassaki Stavroula , Panagopoulos Athanasios D. , Constantinou Philip
Published: March 2014

Cognitive radio (CR) technology aspires to the efficient usage of the limited and underutilised radio spectrum resources. Constituting a flexible and intelligent network, the unlicensed secondary users (SUs) may coexist with the licensed primary users (PUs), under the prerequisite not to disturb their communication. A spectrum interweave CR system is considered, where SUs coexist with a single PU pair in a fading environment. The SUs are allowed to transmit their data ‘peacefully’, only with the absence of PU's transmission, by exploiting spectrum holes of the licensed band. A quality of service (QoS)‐driven spectrum sharing scheme is proposed. Specifically, the problem of licensed spectrum sharing among SUs is formulated as a novel non‐cooperative game with a view of maximising the effective capacity of each SU that has specific delay QoS requirements, subject to the coupled constraint of the available bandwidth. Because this game constitutes a generalised Nash equilibrium problem, we apply the variational inequality framework to solve it. The variational solution is proven to be unique, and it is obtained through a distributed iterative algorithm. The performance of the proposed scheme is evaluated through numerical simulations, and the results confirm the importance of incorporating the delay QoS factor in spectrum sharing studies. Copyright © 2014 John Wiley & Sons, Ltd.
Interleukin‐1 beta enhances endocytosis of glial glutamate transporters in the spinal dorsal horn through activating protein kinase C
Authors: Yan Xisheng , Yadav Ruchi , Gao Mei , Weng Han‐Rong
Published: March 2014

Excessive activation of glutamate receptors in spinal dorsal horn neurons is a key mechanism leading to abnormal neuronal activation in pathological pain conditions. Previous studies have shown that activation of glutamate receptors in the spinal dorsal horn is enhanced by impaired glial glutamate transporter functions and proinflammatory cytokines including interleukin‐1 beta (IL‐1β). In this study, we for the first time revealed that spinal glial glutamate transporter activities in the neuropathic animals are attenuated by endogenous IL‐1β. Specifically, we demonstrated that nerve injury results in an increased expression of IL‐1β and activation of PKC in the spinal dorsal horn as well as suppression of glial glutamate uptake activities. We provided evidence that the nerve‐injury induced suppression of glial glutamate uptake is at least in part ascribed to endogenous IL‐1β and activation of PKC in the spinal dorsal horn. IL‐1β reduces glial glutamate transporter activities through enhancing the endocytosis of both GLT‐1 and GLAST glial glutamate transporters. The IL‐1β induced trafficking of glial glutamate transporters is through the calcium/PKC signaling pathway, and the dynamin‐dependent endocytosis, which is dependent on the integrity of actin filaments. The signaling pathway regulating glial glutamate transporters revealed in this study provides novel targets to attenuate aberrant activation of glutamate receptors in the spinal dorsal horn, which could ultimately help the development of analgesics. GLIA 2014;62:1093–1109
Cost‐effectiveness Analysis and Insurance Coverage: Solving a Puzzle
Authors: Pauly Mark
Published: March 2014

The conventional model for the use of cost‐effectiveness analysis for health programs involves determining whether the cost per unit of effectiveness of the program is lower than some socially determined maximum acceptable cost per unit of effectiveness. If a program is better by this criterion, the policy implication is that it should be implemented by full coverage of its cost by insurance; if not, the program should not be implemented. This paper examines the unanswered question of how cost‐effectiveness analysis should be performed and interpreted when insurance coverage may involve cost sharing. It explores the question of how cost sharing should be related to the magnitude of a cost‐effectiveness ratio. A common view that cost sharing should vary inversely with program cost‐effectiveness is shown to be incorrect. A key issue in correct analysis is whether there is heterogeneity in marginal effectiveness of care that cannot be perceived by the social planner but is known by the demander. It is possible that some programs that would fail the social efficiency test at full coverage will be acceptable with positive cost sharing. Combining individual and social preferences affects both the choice of programs and the extent of cost sharing. Copyright © 2014 John Wiley & Sons, Ltd.