bluuebunny/crossref_metadata_2025 huggingface dataset:
Nrf2, but not β‐catenin, mutation represents an early event in rat hepatocarcinogenesis
Authors: Zavattari Patrizia , Perra Andrea , Menegon Silvia , Kowalik Marta Anna , Petrelli Annalisa , Angioni Maria Maddalena , Follenzi Antonia , Quagliata Luca , Ledda‐Columbano Giovanna Maria , Terracciano Luigi , Giordano Silvia , Columbano Amedeo
Published: March 2015

Hepatocellular carcinoma (HCC) develops through a multistage process, but the nature of the molecular changes associated with the different steps, the very early ones in particular, is largely unknown. Recently, dysregulation of the NRF2/KEAP1 pathway and mutations of these genes have been observed in experimental and human tumors, suggesting their possible role in cancer development. To assess whether Nrf2/Keap1 mutations are early or late events in HCC development, we investigated their frequency in the rat Resistant Hepatocyte model, consisting of the administration of diethylnitrosamine followed by a brief exposure to 2‐acetylaminofluorene. This model enables the dissection of all stages of hepatocarcinogenesis. We found that Nrf2/Keap1 mutations were present in 71% of early preneoplastic lesions and in 78.6% and 59.3% of early and advanced HCCs, respectively. Mutations of Nrf2 were more frequent, missense, and located in the Nrf2‐Keap1 binding region. Mutations of Keap1 occurred at a much lower frequency in both preneoplastic lesions and HCCs and were mutually exclusive with those of Nrf2. Functional in vitro and in vivo studies showed that Nrf2 silencing inhibited the ability of tumorigenic rat cells to grow in soft agar and to form tumors. Unlike Nrf2 mutations, those of Ctnnb1, which are frequent in human HCC, were a later event as they appeared only in fully advanced HCCs (18.5%). Conclusion: In the Resistant Hepatocyte model of hepatocarcinogenesis the onset of Nrf2 mutations is a very early event, likely essential for the clonal expansion of preneoplastic hepatocytes to HCC, while Ctnnb1 mutations occur only at very late stages. Moreover, functional experiments demonstrate that Nrf2 is an oncogene critical for HCC progression and development. (Hepatology 2015;62:851‐862)
The receptor tyrosine kinase EphB2 promotes hepatic fibrosis in mice
Authors: Mimche Patrice N. , Brady Lauren M. , Bray Christian F. , Lee Choon M. , Thapa Manoj , King Thayer P. , Quicke Kendra , McDermott Courtney D. , Mimche Sylvie M. , Grakoui Arash , Morgan Edward T. , Lamb Tracey J.
Published: March 2015

Beyond the well‐defined role of the Eph (erythropoietin‐producing hepatocellular) receptor tyrosine kinases in developmental processes, cell motility, cell trafficking/adhesion, and cancer, nothing is known about their involvement in liver pathologies. During blood‐stage rodent malaria infection we have found that EphB2 transcripts and proteins were up‐regulated in the liver, a result likely driven by elevated surface expression on immune cells including macrophages. This was significant for malaria pathogenesis because EphB2
–/– mice were protected from malaria‐induced liver fibrosis despite having a similar liver parasite burden compared with littermate control mice. This protection was correlated with a defect in the inflammatory potential of hepatocytes from EphB2
–/– mice resulting in a reduction in adhesion molecules, chemokine/chemokine receptor RNA levels, and infiltration of leukocytes including macrophages/Kupffer cells, which mediate liver fibrosis during rodent malaria infections. These observations are recapitulated in the well‐established carbon tetrachloride model of liver fibrosis in which EphB2–/–
carbon tetrachloride–treated mice showed a significant reduction of liver fibrosis compared to carbon tetrachloride–treated littermate mice. Depletion of macrophages by clodronate‐liposomes abrogates liver EphB2 messenger RNA and protein up‐regulation and fibrosis in malaria‐infected mice. Conclusion: During rodent malaria, EphB2 expression promotes malaria‐associated liver fibrosis; to our knowledge, our data are the first to implicate the EphB family of receptor tyrosine kinases in liver fibrosis or in the pathogenesis of malaria infection. (Hepatology 2015;62:900–914)
Increased effect of IMiDs by addition of cytokine‐induced killer cells in multiple myeloma
Authors: Bullok Katharina F. , Sippel Christoph , Schmidt‐Wolf Ingo G.H.
Published: March 2015

Immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide and pomalidomide, represent the basic principle of multiple myeloma treatment. However, the development of resistance is a limiting factor. Over the last years, the efficient application of cytokine‐induced killer (CIK) cells has been reported as an alternative strategy to treat hematological neoplasms. In this study, we tested for a potential synergistic effect by combining the IMiDs thalidomide, lenalidomide and pomalidomide with CIK cells in different myeloma cell lines in vitro. Myeloma cells tested with CIK cells were significantly reduced. In the combination, myeloma cells were significantly reduced compared with cells only tested with IMiDs but not to the cells tested with CIK cells. Otherwise, the number of CIK cells was significantly reduced when treated with IMiDs. Because IMiDs are active in patients with myeloma, these results lead to the expectation that combination of IMiDs and CIK cells achieve better results in the treatment of multiple myeloma compared with the single use of IMiDs. Therefore, further examinations in an in vivo setting are necessary to have a closer look on the cellular interactions. Copyright © 2015 John Wiley & Sons, Ltd.
4‐Methyl‐5‐(4‐methylphenyl)‐4,5‐dihydrooxazol‐2‐amine (4,4′‐DMAR, 4,4′‐dimethylaminorex): availability, prevalence of use, desired effects and acute toxicity
Authors: Glanville James , Dargan Paul I. , Wood David M.
Published: March 2015

Objective

4‐Methyl‐5‐(4‐methylphenyl)‐4,5‐dihydrooxazol‐2‐amine (4,4′‐dimethylaminorex (4,4′‐DMAR)) is a derivative of the controlled substances aminorex and 4‐methylaminorex marketed as a potential novel psychoactive substance. This paper brings together the published scientific and ‘grey’ literature to understand 4,4′‐DMAR as a novel psychoactive substance.

Methods

Searches of the published scientific and ‘grey’ literature, using the keywords ‘4‐methyl‐euphoria’, ‘4‐methyl‐U4Euh’, ‘4‐M‐4‐MAR’, ‘4,4‐dimethylaminorex’, ‘4,4′‐DMAR’, ‘para‐methyl‐4‐aminorex’ and ‘Serotoni’, were undertaken to identify information on the availability, prevalence of use and desired/unwanted effects of 4,4′‐DMAR.

Results

No studies have reported the prevalence of use of 4,4′‐DMAR. Internet snapshot studies in April and May 2014 showed availability of 4,4′‐DMAR from one and two Internet suppliers respectively. Price decreased with increasing purchase amounts from €12/g for a 1‐g purchase to €2.20/g for a 100‐g purchase in April 2014. Internet discussion fora suggest that the desired and unwanted effects of 4,4′‐DMAR are similar to those seen with other sympathomimetic drugs such as 3,4‐methylenedioxy‐methamphetamine and mephedrone, although the duration of unwanted effects and ‘comedown’ appear to be longer. Unwanted effects were reported at doses of 5–200 mg, which overlaps with the reported doses (10–200 mg) associated with desired effects. 4,4′‐DMAR has been detected, along with other drugs, in 27 deaths in Europe; the contribution of the 4,4′‐DMAR in these deaths has not been established.

Conclusions

Currently, there appears to limited availability of 4,4′‐DMAR; therefore, use is likely to be low. Its desired and unwanted effects appear similar to other sympathomimetic recreational drugs such as methylenedioxy‐methamphetamine or mephedrone. Copyright © 2015 John Wiley & Sons, Ltd.
The safety of serotonin–noradrenaline reuptake inhibitors (SNRIs) in pregnancy and breastfeeding: a comprehensive review
Authors: Bellantuono Cesario , Vargas Marianna , Mandarelli Gabriele , Nardi Bernardo , Martini Maria Giulia
Published: March 2015

Objective

The present study provides a comprehensive review of the existing literature on the safety of serotonin–noradrenaline reuptake inhibitors (SNRIs) in pregnancy and lactation.

Methods

Studies published in English, reporting the use of SNRIs in pregnant and/or breastfeeding women, were identified by searching MEDLINE/Pubmed, PsycINFO, and EMBASE.

Results

Twenty‐nine studies were included in the review. Altogether, the initial evidence coming from the reviewed studies suggests a lack of association between SNRIs and an increased risk of major congenital malformations. Conversely, exposure to SNRIs seems to be significantly associated with an increased risk of some perinatal complications. No neonatal adverse events emerged, so far, in the few studies concerning the safety of SNRIs during breastfeeding.

Conclusions

Available data suggest that venlafaxine is relatively safe during pregnancy, in particular as far as major malformations are concerned, whereas considering the small number of studies published, no definitive conclusions can be drawn on its safety during breastfeeding. Because of the few studies so far published, the safety of duloxetine during pregnancy and breastfeeding remains to be well established. Copyright © 2015 John Wiley & Sons, Ltd.
Non‐small cell lung cancer is characterized by dramatic changes in phospholipid profiles
Authors: Marien Eyra , Meister Michael , Muley Thomas , Fieuws Steffen , Bordel Sergio , Derua Rita , Spraggins Jeffrey , Van de Plas Raf , Dehairs Jonas , Wouters Jens , Bagadi Muralidhararao , Dienemann Hendrik , Thomas Michael , Schnabel Philipp A. , Caprioli Richard M. , Waelkens Etienne , Swinnen Johannes V.
Published: March 2015

Non‐small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)‐based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non‐malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non‐malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D‐imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D‐imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development.
Expression of mucin 1 possessing a 3′‐sulfated core1 in recurrent and metastatic breast cancer
Authors: Ideo Hiroko , Hinoda Yuji , Sakai Kohei , Hoshi Ikue , Yamamoto Shigeru , Oka Masaaki , Maeda Kazunari , Maeda Noriko , Hazama Shoichi , Amano Junko , Yamashita Katsuko
Published: March 2015

Breast cancer is the most frequent cancer threatening the lives of women between the ages of 30 and 64. The cancer antigen 15‐3 assay (CA15‐3) has been widely used for the detection of breast cancer recurrence; however, its sensitivity and specificity are inadequate. We previously found that the breast cancer cell line YMBS secretes mucin 1 possessing 3′‐sulfated core1 (3Score1‐MUC1) into the medium. Therefore, we here evaluated whether 3Score1‐MUC1 is secreted into the blood streams of breast cancer patients, and whether it can serve as an improved breast cancer marker. We developed a lectin‐sandwich immunoassay, called Gal4/MUC1, using a 3′‐sulfated core1‐specific galectin‐4 and a MUC1 monoclonal antibody. Using the Gal4/MUC1 assay method, we found that 3Score1‐MUC1 was profoundly expressed in the blood streams of patients with recurrent and/or metastatic breast cancer. The positive ratio of the Gal4/MUC1 assay was higher than that of the CA15‐3 assay in both primary (n = 240) and relapsed (n = 43) patients, especially in the latter of which the positive ratio of Gal4/MUC1 was 86%. whereas that of CA15‐3 was 47%. Furthermore, serum Gal4/MUC1 levels could more sensitively reflect the recurrence of primary breast cancer patients after surgery. Therefore, the Gal4/MUC1 assay should be an excellent alternative to the CA15‐3 tumor marker for tracking the recurrence and metastasis of breast cancer.
Synthesis and Inhibition Study of Bicyclic Iminosugar‐Based Alkaloids, Scaffolds, and Libraries towards Glucosidase
Authors: Cheng Wei‐Chieh , Guo Chih‐Wei , Lin Cheng‐Kun , Jiang Yu‐Ruei
Published: March 2015

A small library of bicyclic iminosugar‐based alkaloids and scaffolds possessing a polyhydroxylated pyrrolidine and a varied ring skeleton have been synthesized. Through rapid diversification of the scaffold via an amide coupling with random carboxylic acids, structurally diverse bicyclic iminosugar‐based libraries were prepared with substituent diversity, core diversity, and configurational diversity. This discovery process allowed us to efficiently sieve out potent and specific glycosidase inhibitors, and a bicyclic, conformationally restricted iminosugar was demonstrated to be more potent than the monocyclic ones in this study. The most potent and selective inhibitor discovered was found to have a Ki value of 71 nM against α‐glucosidase.
Recent Advances in Rechargeable Magnesium Battery Technology: A Review of the Field’s Current Status and Prospects
Authors: Park Min‐Sik , Kim Jae‐Geun , Kim Young‐Jun , Choi Nam‐Soon , Kim Jeom‐Soo
Published: March 2015

The demand for new energy storage systems to be employed in large‐scale electrical energy storage systems (EESs) has grown recently, particularly for green energy storage and grid‐supporting applications. Rechargeable Mg batteries are promising candidates for such applications because of their good safety characteristics and raw materials’ abundance. Recent progress in the field is noticeable, but further efforts are required to support the successful implementation of rechargeable Mg batteries. We address progress in the development of rechargeable Mg batteries and problems to be resolved in future research, briefly summarize the most recent advances in the development of rechargeable Mg batteries, from a materials perspective, and cover progress on each of the major components of Mg batteries: the electrolyte, the cathode material, and the anode material. We provide a practical guideline for further development of self‐sustainable rechargeable Mg batteries as a future power source.
Claudin clusters as determinants of epithelial barrier function
Authors: Markov Alexander G. , Aschenbach Jörg R. , Amasheh Salah
Published: March 2015

Claudins are tetraspan tight junction proteins which have been attributed to primarily determine epithelial barrier function in a wide variety of different organs and tissues. Among this protein family with currently 27 members, single claudins contribute in an organ‐ and tissue‐specific manner to defined properties such as cation‐, anion‐ or water‐selective pore functions, sealing functions or ambiguous functions. As the size of tight junction strand particles visualized by freeze‐fracture electron microscopy have a diameter of approximately 10 nm, multimeric assembly of tight junction proteins appears to be a basic principle for barrier formation. Moreover, expression patterns of different tissues showed that single claudins appear to specifically co‐localize with other claudins, which indicates a cluster formation within tight junction strand particles with a fixed stoichiometry. This review provides a critical view on the current understanding of tight junction protein co‐localization within strands. We analyze how tissue specific differences of claudin functions could be dependent on their specific partners for barrier formation. Furthermore, a model of claudin clusters as structural and functional units within tight junction strands is provided. © 2015 IUBMB Life, 67(1):29–35, 2015
Detection and characterization of nonspecific, sparsely populated binding modes in the early stages of complexation
Authors: Cardone Antonio , Bornstein Aaron , Pant Harish C. , Brady Mary , Sriram Ram , Hassan Sergio A.
Published: March 2015

A method is proposed to study protein–ligand binding in a system governed by specific and nonspecific interactions. Strong associations lead to narrow distributions in the proteins configuration space; weak and ultraweak associations lead instead to broader distributions, a manifestation of nonspecific, sparsely populated binding modes with multiple interfaces. The method is based on the notion that a discrete set of preferential first‐encounter modes are metastable states from which stable (prerelaxation) complexes at equilibrium evolve. The method can be used to explore alternative pathways of complexation with statistical significance and can be integrated into a general algorithm to study protein interaction networks. The method is applied to a peptide–protein complex. The peptide adopts several low‐population conformers and binds in a variety of modes with a broad range of affinities. The system is thus well suited to analyze general features of binding, including conformational selection, multiplicity of binding modes, and nonspecific interactions, and to illustrate how the method can be applied to study these problems systematically. The equilibrium distributions can be used to generate biasing functions for simulations of multiprotein systems from which bulk thermodynamic quantities can be calculated. © 2015 Wiley Periodicals, Inc.
Reservations about the Conclusions of the Interdivisional (APA Divisions 12 & 29) Task Force on Evidence‐Based Therapy Relationships: What Do We Know, What Don't We Know?
Authors: Kazantzis Nikolaos , Cronin Timothy J. , Norton Peter J. , Lai Jerry , Hofmann Stefan G.
Published: March 2015

We offer a critical and constructive appraisal of the conclusions provided by the Interdivisional (American Psychological Association [APA] Divisions 12 & 29) Task Force on Evidence‐Based Therapy Relationships. We highlight problems in overlapping terminology and definitions, as well as problems in the conduct of its meta‐analyses (i.e., duplication of studies between reviews, inappropriate study inclusion, and use of measures of specific constructs for the calculation of effects for multiple relationship elements). On this basis, we express reservation about the conclusions offered by the APA Task Force. This special issue explores whether there are other therapeutic relationship elements that warrant consideration and further study. We were particularly interested in those elements that showed promise based on empirical or theoretical grounds, and in each article, we asked for an account of how the case formulation would guide the methods of adaptation for each individual client, and how the element would contribute to clinically relevant changes.
The Analyst's Authenticity: “If You See Something, Say Something”
Authors: Goldstein George , Suzuki Jessica Y.
Published: March 2015

The history of authenticity in psychoanalysis is as old as analysis itself, but the analyst's authenticity in particular has become an increasingly important area of focus in recent decades. This article traces the development of conceptions of analytic authenticity and proposes that the analyst's spontaneous verbalization of his or her unformulated experience in session can be a potent force in the course of an analysis. We acknowledge that although analytic authenticity can be a challenging ideal for the analyst to strive for, it contains the power to transform the experience of the patient and the analyst, as well as the meaning of their work together. Whether it comes in the form of an insight‐oriented comment or a simple acknowledgment of things as they seem to be, a therapist's willingness to speak aloud something that has lost its language is a powerful clinical phenomenon that transcends theoretical orientation and modality.
Updated clinical practice guidelines for the management of biliary tract cancers: revision concepts and major revised points
Authors: Yoshitomi Hideyuki , Miyakawa Shuichi , Nagino Masato , Takada Tadahiro , Miyazaki Masaru
Published: March 2015

Background

In 2008, the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery (JSHBPS) launched the clinical practice guideline for the management of biliary tract cancers. JSHBPS decided to revise these guidelines for distribution of updated points concerning the treatment of biliary tract cancers.

Methods

To make clearer recommendations, we introduced the concepts of Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, in which the strength of recommendations are decided considering not only quality of evidence, but also balance of benefits and harms/burdens, patients’ preferences, and cost benefits.

Results

We emphasize the importance of the dynamic contrast enhanced multiple row detector CT (MDCT) in the diagnosis of biliary tract and gallbladder carcinomas. For biliary drainage, we suggest to perform endoscopic approaches instead of percutaneous approach to avoid complications. Regarding the surgical treatments, we included new clinical questions about the importance of combined vascular resection, intraoperative histological examination of the bile duct resection margin, and the combined extrahepatic bile duct resection for the gallbladder carcinoma. We also discussed details about premalignant lesions and non‐neoplastic lesions in pathology section.

Conclusion

With this major revision, we expect that the Japanese standards of treatments of these diseases are recorded and reported in the universal language.
Temporal assessment of pancreatic blood flow and perfusion following secretin stimulation using noninvasive MRI
Authors: Cox Eleanor F. , Smith Janette K. , Chowdhury Abeed H. , Lobo Dileep N. , Francis Susan T. , Simpson John
Published: March 2015

Purpose

To dynamically quantify pancreatic perfusion and flow within the arteries supplying the pancreas in response to secretin stimulation.

Materials and Methods

Twelve healthy male subjects were scanned at 1.5T with arterial spin labeling to measure tissue perfusion and phase contrast magnetic resonance imaging (MRI) to measure vessel flow. Superior mesenteric (SMA), gastroduodenal (GDA), common hepatic (HA), and splenic (SA) arterial flow and pancreatic perfusion were serially measured for 50 minutes following 1 IU/kg intravenous secretin. The significance of differences between timepoints was tested using a repeated measures one‐way analysis of variance (ANOVA).

Results

Baseline blood flow (mean ± SEM or median [IQR]) for SMA, HA, SA, and GDA was 7.6 ± 1.3, 4.0 ± 0.5, 8.2 ± 0.8, and 0.9 (0.8–1.4) ml/s, respectively. Baseline pancreatic perfusion was 200 ± 25 ml/100g/min. Blood flow increased in the SMA (234%, P < 0.0001) and GDA (155%, P = 0.015) immediately after secretin injection. Reduced HA blood flow was observed after 10 minutes (P = 0.066) with no change in SA flow (P = 0.533). Increased pancreatic perfusion was maintained for 40 minutes after injection with a maximal increase at 5 minutes (16.8%, P = 0.025).

Conclusion

Intravenous secretin resulted in significant temporal changes in pancreatic perfusion and arterial blood flow. J. Magn. Reson. Imaging 2015;42:1233–1240.
Characterization of ice‐nucleating bacteria using on‐line electron impact ionization aerosol mass spectrometry
Authors: Wolf R. , Slowik J. G. , Schaupp C. , Amato P. , Saathoff H. , Möhler O. , Prévôt A. S. H. , Baltensperger U.
Published: March 2015

The mass spectral signatures of airborne bacteria were measured and analyzed in cloud simulation experiments at the AIDA (Aerosol Interaction and Dynamics in the Atmosphere) facility. Suspensions of cultured cells in pure water were sprayed into the aerosol and cloud chambers forming an aerosol which consisted of intact cells, cell fragments and residual particles from the agar medium in which the bacteria were cultured. The aerosol particles were analyzed with a high‐resolution time‐of‐flight aerosol mass spectrometer equipped with a newly developed PM2.5 aerodynamic lens. Positive matrix factorization (PMF) using the multilinear engine (ME‐2) source apportionment was applied to deconvolve the bacteria and agar mass spectral signatures. The bacteria mass fraction contributed between 75 and 95% depending on the aerosol generation, with the remaining mass attributed to agar. We present mass spectra of Pseudomonas syringae and Pseudomonas fluorescens bacteria typical for ice‐nucleation active bacteria in the atmosphere to facilitate the distinction of airborne bacteria from other constituents in ambient aerosol, e.g. by PMF/ME‐2 source apportionment analyses. Nitrogen‐containing ions were the most salient feature of the bacteria mass spectra, and a combination of C4H8N+ (m/z 70) and C5H12N+ (m/z 86) may be used as marker ions. Copyright © 2015 John Wiley & Sons, Ltd.
In situ analysis of soybeans and nuts by probe electrospray ionization mass spectrometry
Authors: Petroselli Gabriela , Mandal Mridul K. , Chen Lee C. , Hiraoka Kenzo , Nonami Hiroshi , Erra‐Balsells Rosa
Published: March 2015

The probe electrospray ionization (PESI) is an ESI‐based ionization technique that generates electrospray from the tip of a solid metal needle. In the present work, we describe the PESI mass spectra obtained by in situ measurement of soybeans and several nuts (peanuts, walnuts, cashew nuts, macadamia nuts and almonds) using different solid needles as sampling probes. It was found that PESI‐MS is a valuable approach for in situ lipid analysis of these seeds. The phospholipid and triacylglycerol PESI spectra of different nuts and soybean were compared by principal component analysis (PCA). PCA shows significant differences among the data of each family of seeds. Methanolic extracts of nuts and soybean were exposed to air and sunlight for several days. PESI mass spectra were recorded before and after the treatment. Along the aging of the oil (rancidification), the formation of oxidated species with variable number of hydroperoxide groups could be observed in the PESI spectra. The relative intensity of oxidated triacylglycerols signals increased with days of exposition. Monitoring sensitivity of PESI‐MS was high. This method provides a fast, simple and sensitive technique for the analysis (detection and characterization) of lipids in seed tissue and degree of oxidation of the oil samples. Copyright © 2015 John Wiley & Sons, Ltd.
Quantitation of ortho‐cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic‐UHPLC‐MS/MS
Authors: Johnson Darryl , Carter Melissa D. , Crow Brian S. , Isenberg Samantha L. , Graham Leigh Ann , Erol H. Akin , Watson Caroline M. , Pantazides Brooke G. , van der Schans Marcel J. , Langenberg Jan P. , Noort Daan , Blake Thomas A. , Thomas Jerry D. , Johnson Rudolph C.
Published: March 2015

Tri‐ortho‐cresyl phosphate (ToCP) is an anti‐wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver‐activated metabolite 2‐(o‐cresyl)‐4H‐1,3,2‐benzodioxaphosphoran‐2‐one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho‐cresyl phosphoserine (oCP‐BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic‐UHPLC‐MS/MS method for the quantitation of unadducted BChE and the long‐term CBDP biomarker, oCP‐BChE, in human serum. The method has a reportable range from 2.0 ng/ml to 150 ng/ml, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥85%) and precision (RSD ≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP‐BChE adduct was stable for at least 72 h at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Adsorptive parameters and influence of hot geometries on the SER(R) S spectra of methylene blue molecules adsorbed on gold nanocolloidal particles
Authors: Dutta Roy Sannak , Ghosh Manash , Chowdhury Joydeep
Published: March 2015

The vibrational signatures of methylene blue (MB) dye molecule have been reported. Complete vibrational assignments of the molecule are presented for the first time. Concentration‐dependent surface enhanced resonance Raman scattering [SER(R) S] spectra of the molecule have been investigated. Fluorescence spectroscopic technique has been applied to explore the concentration of the probe molecule actually adsorbed on the gold nanocolloidal (AuNC) surface. The free energy of adsorption and saturated concentration of MB molecules on AuNC surface are also estimated. Gigantic enhancements ~105–1013 orders of magnitude have been recorded for the enhanced Raman bands in the SER(R) S spectra. The possible orientation of the molecule on the AuNC surface and their probable protrusions within the hot spots have been suggested. The hot geometries and correlation between the plasmonic behavior of the nanoparticles and enhancement efficiencies of the SER(R) S band have been mapped with the aid of three‐dimensional finite difference time domain (3D‐FDTD) simulations. Application of soft lithographic technique to engineer the pattern formation of hetero dimeric spherical aggregates will be an interesting field of study in future to enhance the detection limit of this and similar types of dye molecules. Copyright © 2015 John Wiley & Sons, Ltd.
A quarter‐century demographic analysis of the Caribbean coral, Orbicella annularis, and projections of population size over the next century
Authors: Edmunds P. J.
Published: March 2015

In this study, size‐based matrix models for the reef‐building coral Orbicella annularis at 14‐m depth on the Tektite reef in St. John, U.S. Virgin Islands, were used to: (1) explore the demography of changing coral cover over 25 yr, (2) test for spatial homogeneity in demographic properties through a contrast with a previous study (at Yawzi Point, Edmunds and Elahi 2007), and (3) evaluate the potential for future population stability. During three, five year intervals from 1988 to 2002, St. John was affected by hurricanes and bleaching, yet coral cover at Tektite increased from 33% to 49%; from 2002 to 2007, it declined to 27%; and from 2010 to 2013, it stabilized at ∼ 28%. Over a quarter‐century, colonies > 50 cm2 became rare, the abundance of colonies ≤ 50 cm2 increased from 58% (1988) to 92% (2013), and population density doubled to 67 colonies m‐2 by 2013. Population growth (λ) was greater at Tektite (1.152 ≥ λ ≥ 1.018) than Yawzi Point (0.679 ≥ λ ≥ 0.586), and while population size at Tektite declined due to bleaching and disease in 2005 (λ = 0.753 over 2003–2008), it recovered between 2008 and 2013 (λ = 0.966); the population at Yawzi Point declined from 1988 to 2003 without signs of recovery. Projections suggest a continuation of recent conditions could allow O. annularis at Tektite to retain ∼ 9% cover after 100 yr, but with a return to the rates of growth and survival of 1993–1998, it could attain coverage similar to that of 1988 (33%) in ∼ 15 yr.
Intertidal zone particulate organic carbon redistribution by low‐tide rainfall
Authors: Chen Si , Torres Raymond , Goñi Miguel A.
Published: March 2015

We present field data and data from the literature to highlight the effects of low‐tide rainfall on particulate organic carbon (POC) redistribution in intertidal landscapes. The POC exchanges reported from disparate but related studies were standardized to a storm‐induced exchange rate (gPOC m−2 mmRain−1) and compared. Results show that these intertidal areas have a characteristic response to rainfall with an average flux of 0.040 ± 0.038 gPOC m−2 mmRain−1. Further, low‐tide rainfall can entrain and redistribute 7–54% of annual sedimentary POC accumulation, or 12–75% of annual POC export, based on current outwelling assessments. Finally, we provide a conceptual model describing the variability of rainfall‐driven POC exchange through the hierarchical structure of intertidal landscapes and how observations of POC flux can be expected to change across the intertidal landscape. This information should be used to guide sampling strategies for continued intertidal zone rainfall work.
Assessing carbon and nutrient inputs in a spring‐fed estuary using fluorescence spectroscopy and discriminatory classification
Authors: Arellano Ana R. , Coble Paula G.
Published: March 2015

Environmental and chemical properties were investigated in water samples collected at sites in Kings Bay, Florida, within its springshed, and in the adjacent Crystal River, in an attempt to discover the cause of observed increases in nitrogen and nuisance filamentous algae over the past 40 yr. Colored dissolved organic matter (CDOM) was characterized by excitation emission matrix and absorption spectroscopy. Subsequent parallel factor analysis (PARAFAC) identified five recurring peaks: two terrestrial humic (C‐type), two marine humic (M‐type), and one protein‐like component. Optical and environmental parameters used for discriminant analysis included fluorescence maximum intensity (Fmax), emission maximum (Emmax), absorption coefficient [aCDOM (λ)], spectral slope (S), PARAFAC components, total nitrogen (TN), dissolved inorganic nitrogen, dissolved organic nitrogen, ratio of TN to Fmax (TN : F), total phosphate, and salinity. Canonical analysis of principal (CAP) coordinates indicated that 82% of the samples could be accurately categorized on the basis of their site of origin. Northern Kings Bay sites were characterized by a protein‐like component associated with wastewater, as well as DIN concentrations in excess of the United States Environmental Protection Agency limit of 0.35 mg NO3 L−1. Two distinct M‐type humic components were identified: partially photobleached component that was found in the brackish water and unbleached component found in meteoric groundwater. We propose that the latter can be utilized as a groundwater marker. Our results provide a model by which meteoric and subterranean estuary groundwater sources may be uncovered through the use of multiple environmental parameters combined with PARAFAC components in multivariate analyses.
Toward autonomous measurements of photosynthetic electron transport rates: An evaluation of active fluorescence‐based measurements of photochemistry
Authors: Silsbe Greg M. , Oxborough Kevin , Suggett David J. , Forster Rodney M. , Ihnken Sven , Komárek Ondřej , Lawrenz Evelyn , Prášil Ondřej , Röttgers Rüdiger , Šicner Michal , Simis Stefan G.H. , Van Dijk Mark A. , Kromkamp Jacco C.
Published: March 2015

This study presents a methods evaluation and intercalibration of active fluorescence‐based measurements of the quantum yield (
) and absorption coefficient (
) of photosystem II (PSII) photochemistry. Measurements of
,
, and irradiance (E) can be scaled to derive photosynthetic electron transport rates (
), the process that fuels phytoplankton carbon fixation and growth. Bio‐optical estimates of
and
were evaluated using 10 phytoplankton cultures across different pigment groups with varying bio‐optical absorption characteristics on six different fast‐repetition rate fluorometers that span two different manufacturers and four different models. Culture measurements of
and the effective absorption cross section of PSII photochemistry (
, a constituent of
) showed a high degree of correspondence across instruments, although some instrument‐specific biases are identified. A range of approaches have been used in the literature to estimate
and are evaluated here. With the exception of ex situ
estimates from paired
and PSII reaction center concentration (
) measurements, the accuracy and precision of in situ
methodologies are largely determined by the variance of method‐specific coefficients. The accuracy and precision of these coefficients are evaluated, compared to literature data, and discussed within a framework of autonomous
measurements. This study supports the application of an instrument‐specific calibration coefficient (
) that scales minimum fluorescence in the dark (
) to
as both the most accurate in situ measurement of
, and the methodology best suited for highly resolved autonomous
measurements.© 2014 Association for the Sciences of Limnology and Oceanography
Apathy in Parkinson's disease: A systematic review and meta‐analysis
Authors: den Brok Melina G.H.E. , van Dalen Jan Willem , van Gool Willem A. , Moll van Charante Eric P. , de Bie Rob M.A. , Richard Edo
Published: March 2015

Apathy is a frequently reported neuropsychiatric symptom in Parkinson's disease (PD), but its prevalence and clinical correlates are debated. We aimed to address these issues by conducting a systematic review and meta‐analysis. Embase, Medline/PubMed, and PsychINFO databases were searched for relevant studies. Data were extracted by two independent observers, using predefined extraction forms tailored specifically to the research question. From 1,702 titles and abstracts, 23 studies were selected. Meta‐analysis showed a prevalence of apathy in PD of 39.8% (n = 5,388, 905% CI 34.6‐45.0%). Apathy was associated with higher age (3.3 years, 95% CI = 1.7‐4.9), lower mean Mini‐Mental State Evaluation (MMSE) score (−1.4 points, 95% CI = −2.1 to −0.8), an increased risk of co‐morbid depression (relative risk [RR] = 2.3, 95% CI = 1.9‐2.8), higher Unified Parkinson's Disease Rating Scale (UPDRS) motor score (6.5 points, 95% CI = 2.6‐10.3), and more severe disability (Hedges‐G = 0.5, 95% CI = 0.3‐0.6). Half of the patients with apathy had concomitant depression (57.2%, 95% CI = 49.4‐64.9%), and this estimate was similar after exclusion of patients with cognitive impairment (52.5%, 95% CI = 42.2%‐62.8%). In conclusion, we found that apathy affects almost 40% of patients with PD. Several factors influence reported prevalence rates, contributing to the considerable heterogeneity in study results. Half of patients with apathy do not suffer from concomitant depression or cognitive impairment, confirming its status as a separate clinical syndrome in PD. The pervasiveness of apathy in PD warrants research into its treatment, although different underlying pathophysiological mechanisms may require different treatment strategies. Treatment of apathy could improve patient quality of life, reduce caregiver burden, alleviate disability by increasing motivation for self‐care, and reduce cognitive impairment by improving executive functioning. © 2015 International Parkinson and Movement Disorder Society
Reachable workspace reflects dynamometer‐measured upper extremity strength in facioscapulohumeral muscular dystrophy
Authors: Han Jay J. , De Bie Evan , Nicorici Alina , Abresch Richard T. , Bajcsy Ruzena , Kurillo Gregorij
Published: March 2015

Introduction: It is not known whether a reduction in reachable workspace closely reflects loss of upper extremity strength in facioscapulohumeral muscular dystrophy (FSHD). In this study we aimed to determine the relationship between reachable workspace and quantitative upper extremity strength measures. Methods: Maximal voluntary isometric contraction (MVIC) testing of bilateral elbow flexion and shoulder abduction by hand‐held dynamometry was performed on 26 FSHD and 27 control subjects. In addition, Kinect sensor‐based 3D reachable workspace relative surface areas (RSAs) were obtained. Loading (500‐g weight) effects on reachable workspace were also evaluated. Results: Quantitative upper extremity strength (MVIC of elbow flexion and shoulder abduction) correlated with Kinect‐acquired reachable workspace RSA (R = 0.477 for FSHD, P = 0.0003; R = 0.675 for the combined study cohort, P < 0.0001). Progressive reduction in RSA reflected worsening MVIC measures. Loading impacted the moderately weak individuals the most with additional reductions in RSA. Conclusions: Reachable workspace outcome measure is reflective of upper extremity strength impairment in FSHD. Muscle Nerve 52: 948–955, 2015
Motion control of the rabbit ankle joint with a flat interface nerve electrode
Authors: Park Hyun‐Joo , Durand Dominique M.
Published: March 2015

Introduction: A flat interface nerve electrode (FINE) has been shown to improve fascicular and subfascicular selectivity. A recently developed novel control algorithm for FINE was applied to motion control of the rabbit ankle. Methods: A 14‐contact FINE was placed on the rabbit sciatic nerve (n = 8), and ankle joint motion was controlled for sinusoidal trajectories and filtered random trajectories. To this end, a real‐time controller was implemented with a multiple‐channel current stimulus isolator. Results: The performance test results showed good tracking performance of rabbit ankle joint motion for filtered random trajectories and sinusoidal trajectories (0.5 Hz and 1.0 Hz) with <10% average root‐mean‐square (RMS) tracking error, whereas the average range of ankle joint motion was between −20.0 ± 9.3° and 18.1 ± 8.8°. Conclusions: The proposed control algorithm enables the use of a multiple‐contact nerve electrode for motion trajectory tracking control of musculoskeletal systems. Muscle Nerve 52: 1088–1095, 2015
Utility of electromyographic fatigue threshold during treadmill running
Authors: Crozara Luciano F. , Castro Alex , De Almeida Neto Antonio F. , Laroche Dain P. , Cardozo Adalgiso C. , Gonçalves Mauro
Published: March 2015

Introduction: We investigated 2 different methods for determining muscle fatigue threshold by electromyography (EMG). Methods: Thirteen subjects completed an incremental treadmill running protocol for EMG fatigue threshold (EMGFT) determination based on the critical power concept (EMGFT1) and the breakpoint in the linear relationship between EMG amplitude and exercise intensity (EMGFT2). Then, both the EMGFT1 and EMGFT2 were tested in a continuous treadmill running protocol. EMG was recorded from the rectus femoris (RF), vastus lateralis (VL), biceps femoris (BF), and lateral gastrocnemius (LG) muscles. Results: For BF, EMGFT2 was higher than EMGFT1, and EMGFT1 for BF was lower than EMGFT1 for LG. EMG of RF was higher at EMGFT2 than at EMGFT1, and LG EMG was lower at EMGFT2. Conclusions: EMGFT can be determined during a single treadmill running test, and EMGFT1 may be the most appropriate method to estimate the muscle fatigue threshold during running. Muscle Nerve 52: 1030–1039, 2015
Correction of B1‐inhomogeneities for relaxation‐compensated CEST imaging at 7 T
Authors: Windschuh Johannes , Zaiss Moritz , Meissner Jan‐Eric , Paech Daniel , Radbruch Alexander , Ladd Mark E. , Bachert Peter
Published: March 2015

Chemical exchange saturation transfer (CEST) imaging of endogenous agents in vivo is influenced by direct water proton saturation (spillover) and semi‐solid macromolecular magnetization transfer (MT). Lorentzian fit isolation and application of the inverse metric yields the pure CEST contrast AREX, which is less affected by these processes, but still depends on the measurement technique, in particular on the irradiation amplitude B1 of the saturation pulses. This study focuses on two well‐known CEST effects in the slow exchange regime originating from amide and aliphatic protons resonating at 3.5 ppm or −3.5 ppm from water protons, respectively. A B1‐correction of CEST contrasts is crucial for the evaluation of data obtained in clinical studies at high field strengths with strong B1‐inhomogeneities. Herein two approaches for B1‐inhomogeneity correction, based on either CEST contrasts or Z‐spectra, are investigated. Both rely on multiple acquisitions with different B1‐values. One volunteer was examined with eight different B1‐values to optimize the saturation field strength and the correction algorithm. Histogram evaluation allowed quantification of the quality of the B1‐correction. Finally, the correction was applied to CEST images of a patient with oligodendroglioma WHO grade 2, and showed improvement of the image quality compared with the non‐corrected CEST images, especially in the tumor region. Copyright © 2015 John Wiley & Sons, Ltd.
Neurocognitive evaluation of long term survivors of atypical teratoid rhabdoid tumors (ATRT): The Canadian registry experience
Authors: Lafay‐Cousin Lucie , Fay‐McClymont Taryn , Johnston Donna , Fryer Chris , Scheinemann Katrin , Fleming Adam , Hukin Juliette , Janzen Laura , Guger Sharon , Strother Douglas , Mabbott Donald , Huang Annie , Bouffet Eric
Published: March 2015

Background

Because atypical teratoid rhabdoid tumor(ATRT) is a rare disease of infancy carrying a grim prognosis, focus on long‐term outcome, especially neurocognitive remained very limited. With new era of multimodality therapy, an increasing proportion of patients are now long‐term survivors.

Procedure

Retrospective review of neuropsychological (NP) status of survivors from the Canadian ATRT registry.

Results

Among 77 patients diagnosed between 1995–2012, 16(22%) were survivors. Formal NP assessments were available in eight patients. Partial information on academic achievement was available on three additional patients. There were four girls and seven boys diagnosed at a median age of 27.5 months. Seven patients underwent complete resection and three had metastatic disease. All but one received sequential high dose chemotherapy. Five patients received intrathecal chemotherapy. Three patients underwent radiation. Median age at time of formal NP assessment was 7.6 years (3.9–9.8). Full Scale Intellectual Quotient (FSIQ) ranged from less than 50–119 (mean 78). Simple expressive and receptive language appeared relatively preserved. Three recently diagnosed patients (median time assessment from diagnosis 2.6 years (1.6–4.7)) had average to high average FSIQ, academic and visual spatial skills, visual, and verbal memory. Five other patients diagnosed earlier and tested at a median time of 4.9 years (3.3–8.3) post‐diagnosis had a FSIQ ranging from <50 to 71. Approximately 50% of their scores were in the impaired range.

Conclusion

Overall this cohort appears significantly impaired at school age despite the absence of systematic radiotherapy. Larger series focusing on neurocognitive outcome are needed in the current context where treatment strategies include adjuvant radiation. Pediatr Blood Cancer 2015;62:1265–1269. © 2015 Wiley Periodicals, Inc.