bluuebunny/crossref_metadata_2025 huggingface dataset:
Manganese: a new contrast agent for lung imaging?
Authors: Gobbo Oliviero L. , Zurek Magdalena , Tewes Frederic , Ehrhardt Carsten , Crémillieux Yannick
Published: September 2012

Lung parenchyma remains one of the most difficult tissues to be imaged by means of magnetic resonance imaging (MRI). Several MRI techniques are routinely used for lung imaging. However, manganese‐enhancement MRI (MEMRI) technique has not been associated with pulmonary MRI. Here, we evaluated T1‐enhancement in the rat lung after a manganese instillation, using a 4.7 T magnet with a radial ultrashort echo time sequence. Our data showed that the signal intensity was increased in lungs receiving a manganese solution compared with a control solution to the lungs. MR signal enhancements above 30% were measured in lung parenchyma following 200 µl instillation of a 1 mm manganese chloride solution. MEMRI, therefore, may be a useful novel tool for enhancing signal intensity and image contrast in lung tissue. Copyright © 2012 John Wiley & Sons, Ltd.
Optical imaging of progenitor cell homing to patient‐derived tumors
Authors: Newton Isabel G. , Plaisted Warren C. , Messina‐Graham Steven , Abrahamsson Schairer Annelie E. , Shih Alice Y. , Snyder Evan Y. , Jamieson Catriona H. M. , Mattrey Robert F.
Published: September 2012

Capitalizing on cellular homing to cancer is a promising strategy for targeting malignant cells for diagnostic, monitoring and therapeutic purposes. Murine C17.2 neural progenitor cells (NPC) demonstrate a tropism for cell line‐derived tumors, but their affinity for patient‐derived tumors is unknown. We tested the hypothesis that NPC accumulate in patient‐derived tumors at levels detectable by optical imaging. Mice bearing solid tumors after transplantation with patient‐derived leukemia cells and untransplanted controls received 106 fluorescent DiR‐labeled NPC daily for 1–4 days, were imaged, then sacrificed. Tissues were analyzed by immunofluorescence and flow cytometry to detect tumor cell engraftment (CD45) and NPC (FITC‐β galactosidase or DiR). Tumors consisted primarily of CD45‐positive cells and demonstrated mild fluorescence, corresponding to frequent clusters of FITC‐β gal‐positive cells. Both transplanted and control mice demonstrated the highest fluorescent signal in the spleens and other tissues of the reticuloendothelial activating system. However, only rare FITC‐β gal‐positive cells were detected in the mildly engrafted transplanted spleens and none in the control spleens, suggesting that their high DiR signal reflects the sequestration of DiR‐positive debris. The mildly engrafted transplanted kidneys demonstrated low fluorescent signal and rare FITC‐β gal‐positive cells whereas control kidneys were negative. Results indicate that NPC accumulate in tissues containing patient‐derived tumor cells in a manner that is detectable by ex vivo optical imaging and proportional to the level of tumor engraftment, suggesting a capacity to home to micrometastatic disease. As such, NPC could have significant clinical applications for the targeted diagnosis and treatment of cancer. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control
Authors: Stuth Eckehard A.E. , Stucke Astrid G. , Zuperku Edward J.
Published: September 2012

This article provides a comprehensive, up to date summary of the effects of volatile, gaseous, and intravenous anesthetics and opioid agonists on ventilatory control. Emphasis is placed on data from human studies. Further mechanistic insights are provided byin vivoandin vitrodata from other mammalian species. The focus is on the effects of clinically relevant agonist concentrations and studies using pharmacological, that is, supraclinical agonist concentrations are de‐emphasized or excluded. © 2012 American Physiological Society.Compr Physiol2:2281‐2367, 2012.
Solubility and metastable zone width of DL‐tartaric acid in aqueous solution
Authors: Zhang Xiang‐Yang , Wang Xiaofang , Hao Lin , Yang Xiaowu , Dang Leping , Wei Hongyuan
Published: September 2012

Solubility and metastable zone width (MSZW) of DL‐tartaric acid (DL‐TA) in aqueous solution have been determined. Solubility of DL‐TA was measured in the temperature range from 0 to 50 °C at atmospheric pressure by means of the conventional polythermal method using Turbidity Monitoring Technique, which was verified by a gravimetric method. The dissolution enthalpy and entropy of DL‐TA were then calculated from the solubility data using van't Hoff equation. Two approaches was used to estimate the nucleation kinetics from the measured metastable zone width data, the self‐consistent approach and the approach based on 3D nucleation. In addition, the metastable zone width slightly decreases with increasing agitation rate and was independent of working volume.
A redox proteomic investigation of oxidative stress caused by benzoylecgonine in the freshwater bivalve Dreissena polymorpha
Authors: Pedriali Alessandra , Riva Consuelo , Parolini Marco , Cristoni Simone , Sheehan David , Binelli Andrea
Published: September 2012

Drugs of abuse and their human metabolites have been recently recognized as emerging environmental contaminants. Notwithstanding the fact that these kinds of compounds share some features with pharmaceuticals, their ecotoxicology has not yet been extensively investigated, although some of their characteristics may potentially threaten aquatic ecosystems. One of the most abundant drugs found in rivers and wastewaters is benzoylecgonine (BE), the main metabolite of cocaine. We applied a redox proteomics approach to evaluate changes in the proteome of Dreissena polymorpha exposed to two different concentrations of BE (0.5 and 1 µg/l). Exposures were performed in vivo for a period of 14 days and the effect of oxidative stress on protein thiol and carbonyl groups in mussel gills were evaluated. One‐dimensional electrophoresis did not reveal a reduction in protein thiol content but showed a significant increase of protein carbonylation at both doses tested. Then, protein profiling using two‐dimensional gel electrophoresis was performed with subsequent matrix assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) and TOF/TOF with LIFT technique and linear ion trap combined with orbitrap mass spectrometer (LTQ‐Orbitrap). This yielded de novo protein sequences suitable for database searching. These preliminary results and protein identifications obtained suggest that BE causes oxidative stress. Oxidative modifications were detected in differing classes of proteins such as those of the cytoskeleton, energetic metabolism and stress response. Copyright © 2012 John Wiley & Sons, Ltd.
Sweat testing for the detection of atomoxetine from paediatric patients with attention deficit/ hyperactivity disorder: application to clinical practice
Authors: Marchei Emilia , Papaseit Esther , Garcia‐Algar Oscar , Bilbao Amaia , Farré Magí , Pacifici Roberta , Pichini Simona
Published: September 2012

Atomoxetine (ATX) is a selective norepinephrine reuptake inhibitor approved since 2002 for the treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents, and adults as an alternative treatment to methylphenidate. Within the framework of a project evaluating the use of alternative biological matrices for therapeutic monitoring of psychoactive drugs in paediatric and non‐paediatric individuals, the excretion of ATX and its principal metabolites has been recently studied in oral fluid and hair. The aim of this study was to describe the excretion profile of ATX and its metabolites 4‐hydroxyatomoxetine (4‐OH‐ATX) and N‐desmethylatomoxetine (N‐des‐ATX) in sweat following the administration of different dosage regimens (60, 40, 35, and 18 mg/day) of ATX to six paediatric patients. Sweat patches were applied to the back of each participant and removed at timed intervals. ATX and its metabolites were measured in patches using a previously validated liquid chromatography‐tandem mass spectrometric (LC‐MS/MS) method. Independently from the administered dose, ATX appeared in the sweat patches 1 h post administration and reached its maximum concentration generally at 24 h. Peak ATX concentrations ranged between 2.31 and 40.4 ng/patch and did not correlate with the administered drug dose, or with body surface area. Total ATX excreted in sweat ranged between 0.008 and 0.121 mg, corresponding to 0.02 and 0.3% of the administered drug. Neither 4‐OH‐ATX, nor N‐des‐ATX was detected in either of the collected sweat patches. Measuring ATX in sweat patches can provide information on cumulative drug use from patch application until removal. Copyright © 2012 John Wiley & Sons, Ltd.
Activated monocytes augment TRAIL‐mediated cytotoxicity by human NK cells through release of IFN‐γ
Authors: Sarhan Dhifaf , D'Arcy Padraig , Wennerberg Erik , Lidén Majken , Hu Jin , Winqvist Ola , Rolny Charlotte , Lundqvist Andreas
Published: September 2012

Natural killer (NK) cells are innate lymphocytes that are able to directly kill tumor cells through different mechanisms including ligation of TNF‐related apoptosis‐inducing ligand (TRAIL) receptors. Zoledronic acid (ZA) is a bisphosphonate known to upregulate the expression of TRAIL on human γδ T cells. Here, we investigated whether exposure to ZA would upregulate TRAIL expression on human NK cells and augment their cytotoxicity against tumor cells. When cocultured with monocytes, treatment with ZA and IL‐2 resulted in a significant upregulation of TRAIL expression on human NK cells (p = 0.002). Consequently, ZA‐primed NK cells were significantly more cytotoxic against TRAIL sensitive tumor cells (p < 0.0001). In the presence of ZA and IL‐2, monocytes produced high levels of IFN‐γ; when cultured in the presence of neutralizing antibodies to IFN‐γ, TRAIL expression and TRAIL‐mediated cytotoxicity of NK cells were significantly reduced. Furthermore, in tumor‐bearing SCID/Beige mice, a significant delayed tumor progression and prolonged survival was observed after infusion of ZA‐primed NK cells compared with that observed in mice infused with unprimed NK cells. These findings represent a novel approach to potentiate TRAIL‐mediated apoptosis by adoptively infused NK cells that could improve the outcome in patients with cancer.
Redox Activity in a Vanadium(V)–o‐Dioxolene Complex Is Modulated by Protonation State As Indicated by 51V Solid‐State NMR Spectroscopy and Density Functional Theory
Authors: Chatterjee Pabitra B. , Goncharov‐Zapata Olga , Hou Guangjin , Dmitrenko Olga , Polenova Tatyana , Crans Debbie C.
Published: September 2012

Most known vanadium(V) complexes with redox‐active o‐dioxolene ligands are non‐innocent. Since the vanadium(V) complex [VO(gsal)(HCat)] is innocent, its properties were investigated by 51V solid‐state NMR spectroscopy and density functional theory (DFT). The innocent ligand behavior manifested itself by the upfield isotropic chemical shift and large negative chemical shift anisotropy observed in the solid state. The electronic structure and NMR spectroscopic parameters of this complex were addressed by DFT calculations and found to be consistent with the NMR spectroscopic observations indicating that the complex is redox‐inactive. The observed increase in the HOMO–LUMO gap for the innocent complex is concomitant with the 51V NMR chemical shift of –460 ppm and consistent with the high redox stability of this molecule. The stabilization was traced to the overall charge of [VO(gsal)(HCat)] facilitated by the coordination of the minus‐one‐charged o‐dioxolene ligand and rendering the overall complex neutral. These studies suggest that protonation may prove to be an effective way in which vanadium(V) complexes with redox‐active ligands can be stabilized.
Proteomic analysis of prion diseases: Creating clarity or causing confusion?
Authors: Rubenstein Richard
Published: September 2012

Prion diseases, or transmissible spongiform encephalopathies, are progressive, fatal neurodegenerative diseases. There are both human and animal forms of the disease and all are associated with the conversion of a normal host‐coded cellular prion protein (PrPC) into an abnormal protease‐resistant isoform (PrPSc). Although methodologies are sensitive and specific for postmortem disease diagnosis, the use of PrPSc as a preclinical or general biomarker for surveillance is difficult, due to the fact that it is present in extremely small amounts in accessible tissues or body fluids such as blood, urine, saliva, and cerebrospinal fluid. Recently, amplification techniques have been developed, which have enabled increased sensitivity for PrPSc detection. However, it has recently been reported that proteinase K sensitive, pathological isoforms of PrP may have a significant role in the pathogenesis of some prion diseases. Accordingly, the development of new diagnostic tests that do not rely on PrPSc and proteinase K digestion is desirable. The search for biomarkers (other than PrPSc) as tools for diagnosis of prion diseases has a long history. Ideally biomarkers able to detect all transmissible spongiform encephalopathies, even at preclinical stages of infection are desirable but not yet possible due to the heterogeneity of the disease and lengthy disease progression. Recent advances in neuroproteomics have led to an overwhelming amount of information, which may offer insight on protein–protein interactions. While the amount of data obtained is impressive, the ability to relate it to the disease and validating its usefulness in diagnostic biomarker development remains a formidable challenge.
A model for spatio‐temporal clustering using multinomial probit regression: application to avalanche counts
Authors: Lavigne A. , Bel L. , Parent E. , Eckert N.
Published: September 2012

Although modeling complex environmental spatio‐temporal processes, separability between time and space effects is often assumed as a first approach, even though it may be unrealistic. Hence, the development of adapted non‐separable spatio‐temporal models is a challenging issue. In this work, we are interested in modeling avalanche counts over the whole French Alps, a large area that exhibits zones characterized by distinct climatic behaviors. We have at our disposal a data set of 405, 63‐year series of avalanche counts, one series for one township. We assume the series can be divided into several spatial clusters presenting specific temporal trends. On the latent layer of a hierarchical negative binomial‐lognormal structure, the clusters are characterized by independent temporal evolutions, modeled using smoothing splines. The clusters arise as the result of a multinomial probit regression, with spatial coordinates used as covariates. Inference is performed within the Bayesian hierarchical framework. The number of clusters is assessed using cross validation. The best score is obtained for a three‐cluster model, but other configurations also share some evidence. The first cluster is located in the east of the French Alps, whereas the others are located together in the west part of the French Alps. The three contrasted temporal trends corresponding to the three clusters result from regional climate change effects, interacting with a strong altitudinal control and data limitation. The proposed model could be used for analyzing various other climatic and environmental data sets. Copyright © 2012 John Wiley & Sons, Ltd.
Contaminants of emerging concern in municipal wastewater effluents and marine receiving water
Authors: Vidal-Dorsch Doris E. , Bay Steven M. , Maruya Keith , Snyder Shane A. , Trenholm Rebecca A. , Vanderford Brett J.
Published: September 2012

The occurrence and concentrations of contaminants of emerging concern (CECs) were investigated in municipal effluents and in marine receiving water. Final effluent from four large publicly owned treatment works (POTWs) and seawater collected near the respective POTW outfall discharges and a reference station were collected quarterly over one year and analyzed for 56 CECs. Several CECs were detected in effluents; naproxen, gemfibrozil, atenolol, and tris(1-chloro-2-propyl)phosphate were the compounds most frequently found and with the highest concentrations (>1 µg/L). Gemfibrozil and naproxen had the highest seawater concentrations (0.0009 and 0.0007 µg/L) and also were among the most frequently detected compounds. Effluent dilution factors ranged from >400 to approximately 1,000. Fewer CECs were detected and at lower concentrations in seawater collected from the reference station than at the outfall sites. Effluent concentrations for some CECs (e.g., pharmaceuticals) were inversely related to the degree of wastewater treatment. This trend was not found in seawater samples. Few temporal differences were observed in effluent or seawater samples. Effluent CEC concentrations were lower than those currently known for chronic toxicity thresholds. Nevertheless, the evaluation of potential chronic effects for CECs is uncertain because aquatic life toxicity thresholds have been developed for only a few CECs, and the effluent and seawater samples had compounds, such as nonylphenol, known to bioaccumulate in local fish. Additional data are needed to better understand the significance of CEC presence and concentrations in marine environments. Environ. Toxicol. Chem. 2012; 31: 2674–2682. © 2012 SETAC
Influence of carbon and lipid sources on variation of mercury and other trace elements in polar bears (Ursus maritimus)
Authors: Routti Heli , Letcher Robert J. , Born Erik W. , Branigan Marsha , Dietz Rune , Evans Thomas J. , McKinney Melissa A. , Peacock Elizabeth , Sonne Christian
Published: September 2012

In the present study, the authors investigated the influence of carbon and lipid sources on regional differences in liver trace element (As, Cd, Cu, total Hg, Mn, Pb, Rb, Se, and Zn) concentrations measured in polar bears (Ursus maritimus) (n = 121) from 10 Alaskan, Canadian Arctic, and East Greenland subpopulations. Carbon and lipid sources were assessed using δ13C in muscle tissue and fatty acid (FA) profiles in subcutaneous adipose tissue as chemical tracers. A negative relationship between total Hg and δ13C suggested that polar bears feeding in areas with higher riverine inputs of terrestrial carbon accumulate more Hg than bears feeding in areas with lower freshwater input. Mercury concentrations were also positively related to the FA 20:1n-9, which is biosynthesized in large amounts in Calanus copepods. This result raises the hypothesis that Calanus glacialis are an important link in the uptake of Hg in the marine food web and ultimately in polar bears. Unadjusted total Hg, Se, and As concentrations showed greater geographical variation among polar bear subpopulations compared with concentrations adjusted for carbon and lipid sources. The Hg concentrations adjusted for carbon and lipid sources in Bering–Chukchi Sea polar bear liver tissue remained the lowest among subpopulations. Based on these findings, the authors suggest that carbon and lipid sources for polar bears should be taken into account when one is assessing spatial and temporal trends of long-range transported trace elements. Environ. Toxicol. Chem. 2012; 31: 2739–2747. © 2012 SETAC
Integrated coastal effects study: Synthesis of findings
Authors: Bay Steven M. , Vidal-Dorsch Doris E. , Schlenk Daniel , Kelley Kevin M. , Maruya Keith A. , Gully Joseph R.
Published: September 2012

Municipal wastewater discharges constitute a major source of contaminants of emerging concern (CECs) to coastal waters, yet uncertainty exists regarding their linkage to adverse biological effects such as endocrine disruption. Limited information is available concerning the types and fate of CECs discharged to the Southern California Bight (SCB) from municipal wastewater and their potential for ecological impacts. The present study investigated the impacts of CECs from ocean wastewater discharges on SCB fish. Concentrations of CECs were measured in effluents from four major municipal wastewater dischargers. Seawater, sediment, and hornyhead turbot (Pleuronichthys verticalis) from the discharge sites and a reference area were collected and analyzed for chemical and biological indicators. Low concentrations of pharmaceuticals, personal care products, and industrial and commercial compounds were measured in effluent. Some CECs were also detected in sediment, seawater, and fish livers near the outfalls, confirming exposure to CECs. Fish plasma hormone analyses suggested the presence of physiological effects, including a reduced stress response, altered estrogen synthesis or estrogenic exposure, and reduced thyroxine. Most fish responses were found at all sites and could not be directly associated with effluent discharges. However, concentrations of thyroxine were lower at all discharge sites relative to the reference, and estradiol concentrations were lower at three of the four outfall sites. The physiological responses found were not associated with adverse impacts on fish reproduction or populations. Interpretation of molecular and physiological measurements in field organisms such as those used in the present study is challenging because of a lack of information on baseline conditions and uncertain linkages to apical endpoints such as survival and reproduction. Environ. Toxicol. Chem. 2012; 31: 2711–2722. © 2012 SETAC
Evaluation of reproductive endocrine status in hornyhead turbot sampled from Southern California's urbanized coastal environments
Authors: Reyes Jesus A. , Vidal-Dorsch Doris E. , Schlenk Daniel , Bay Steven M. , Armstrong Jeffrey L. , Gully Joseph R. , Cash Curtis , Baker Michael , Stebbins Timothy D. , Hardiman Gary , Kelley Kevin M.
Published: September 2012

As part of a regionwide collaboration to determine the occurrence of contaminants and biological effects in coastal ecosystems offshore of urban southern California, the present study characterized the reproductive endocrinology of an indigenous flatfish, the hornyhead turbot (Pleuronichthys verticalis), and compared groups sampled from different study sites representing varying degrees of pollution to screen for potential endocrine disruptive effects. Turbot were sampled from locations near the coastal discharge sites of four large municipal wastewater treatment plants (WWTPs) located between Los Angeles and San Diego, California, USA, and were compared with fish sampled from three far-field reference locations in the region. Despite environmental presence of both legacy contaminants and contaminants of emerging concern and evidence for fish exposure to several classes of contaminants, both males and females generally exhibited coordinated seasonal reproductive cycles at all study sites. Patterns observed included peaks in sex steroids (17β-estradiol, testosterone, 11-ketotestosterone) in the spring and low levels in the fall, changes corresponding to similarly timed gonadal changes and plasma vitellogenin concentrations in females. Comparisons between fish captured at the different study sites demonstrated some regional differences in plasma levels of estrogens and androgens, indicative of location-associated effects on the endocrine system. The observed differences, however, could not be linked to the ocean discharge locations of four of the largest WWTPs in the world. Environ. Toxicol. Chem. 2012; 31: 2689–2700. © 2012 SETAC
Previous international experience, cross‐cultural training, and expatriates' cross‐cultural adjustment: Effects of cultural intelligence and goal orientation
Authors: Koo Moon Hyoung , Kwon Choi Byoung , Shik Jung Jae
Published: September 2012

Although various antecedents of expatriates' cross‐cultural adjustment have been addressed, previous international experience, predeparture cross‐cultural training, and cultural intelligence (CQ) have been most frequently examined. However, there are few attempts that explore the effects of these antecedents simultaneously or consider the possible influencing variables that can impact cross‐cultural adjustment. In addition, empirical findings on the effects of these antecedents are somewhat mixed. Hence, there is a need for integrative studies exploring the mechanism of cross‐cultural adjustment to deepen understanding of how previous international experience, predeparture cross‐cultural training, and CQ affect expatriates' cross‐cultural adjustment. In this regard, we considered CQ as a variable that mediates the influences of previous international experience (work and nonwork) and predeparture cross‐cultural training (length and comprehensiveness) on cross‐cultural adjustment. Additionally, an expatriate's goal orientation was considered as a moderating variable that influences the effects of previous international experience and predeparture cross‐cultural training on CQ. Results using a sample of 190 Korean expatriates partially supported the hypotheses. The mediating effect of CQ and moderating effect of goal orientation were partially supported. The previous international nonwork rather than work experience and comprehensiveness rather than length of predeparture cross‐cultural training were more positively related to CQ. The theoretical contributions, practical implications for human resource development (HRD) practitioners, limitations, and suggestions for future research are discussed.
The impact of managerial coaching on learning outcomes within the team context: An analysis
Authors: Hagen Marcia , Gavrilova Aguilar Mariya
Published: September 2012

This study investigates the relationship between coaching expertise, project difficulty, and team empowerment on team learning outcomes within the context of a high‐performance work team. Variables were tested using multiple regression analysis. The data were analyzed for two groups—team leaders and team members—using t‐tests, factor analysis, as well as correlation, regression, and commonality analyses. The results indicate that the independent variable project difficulty explained the most variance in team learning outcomes for team leaders whereas coaching expertise and team empowerment explained the most variance in team learning outcomes for team members. Practical implications include the selection and training of team leaders in managerial coaching and the development of challenging projects in situations where team learning is highly important. Theoretical implications include providing further empirical support for leadership theories, and coaching theory in particular.
Anti‐Stokes fluorescence from endogenously formed protoporphyrin IX – Implications for clinical multiphoton diagnostics
Authors: Kantere Despina , Guldbrand Stina , Paoli John , Goksör Mattias , Hanstorp Dag , Wennberg Ann‐Marie , Smedh Maria , Ericson Marica B.
Published: September 2012

Multiphoton imaging based on two‐photon excitation is making its way into the clinics, particularly for skin cancer diagnostics. It has been suggested that endogenously formed protoporphyrin IX (PpIX) induced by aminolevulinic acid or methylaminolevulinate can be applied to improve tumor contrast, in connection to imaging of tissue autofluorescence. However, previous reports are limited to cell studies and data from tissue are scarce. No report shows conclusive evidence that endogenously formed PpIX increases tumor contrast when performing multiphoton imaging in the clinical situation. We here demonstrate by spectral analysis that two‐photon excitation of endogenously formed PpIX does not provide additional contrast in superficial basal cell carcinomas. In fact, the PpIX signal is overshadowed by the autofluorescent background. The results show that PpIX should be excited at a wavelength giving rise to one‐photon anti‐Stokes fluorescence, to overcome the autofluorescent background. Thus, this study reports on a plausible method, which can be implemented for clinical investigations on endogenously formed PpIX using multiphoton microscopy (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Expression of CD81, SR‐BI and LDLR in lymphocytes and monocytes from patients with classic and occult hepatitis C virus infection
Authors: Roque‐Cuéllar M. Carmen , Sánchez Berta , García‐Lozano José Raúl , Garrido‐Serrano Antonio , Sayago Manuel , Praena‐Fernández Juan Manuel , Núñez‐Roldán Antonio , Aguilar‐Reina José
Published: September 2012

CD81, the scavenger receptor‐BI (SR‐BI) and the low‐density lipoprotein receptor (LDLR) are involved in peripheral blood mononuclear cells (PBMCs) hepatitis C virus (HCV) entry. To investigate if these molecules are altered by HCV, 20 controls and 66 patients: 37 untreated and 29 sustained virological responders, were studied. CD81 and LDLR expression, measured the percentage of cells expressing the HCV‐receptors and their mean fluorescence intensity (MFI), was analyzed on lymphocytes and monocytes, as well as SR‐BI on monocytes by flow cytometry. RNA was extracted from PBMCs and detection of the HCV‐RNA positive and negative strands was performed by strand‐specific RT‐PCR. A statistically significant increase of CD81 expression was observed on lymphocytes, a higher percentage of LDLR on lymphocytes and monocytes, as well as SR‐BI on monocytes was found in the patients as compared to the controls (P < 0.05 in all cases). Untreated patients showed a higher percentage of LDLR+ lymphocytes than sustained virological responders (P = 0.025). Nineteen sustained virological responders bore the HCV‐RNA positive strand in PBMCs; nine of them the negative strand too. Sustained virological responders with occult infection and viral replication, showed a higher expression of LDLR on lymphocytes (P < 0.05) and a higher LDLR MFI on monocytes (P = 0.011) than those without viral replication. In conclusion, HCV exposure modifies expression levels of the receptors studied, being LDLR related with HCV replication, not only in the classic but also in the occult infection. J. Med. Virol. 84:1727–1736, 2012. © 2012 Wiley Periodicals, Inc.
Enterovirus 71 blocks selectively type I interferon production through the 3C viral protein in mice
Authors: Lee Yi‐Ping , Wang Ya‐Fang , Wang Jen‐Ren , Huang Szu‐Wei , Yu Chun‐Keung
Published: September 2012

Type I interferons (IFNs) represent an essential innate defense mechanism for controlling enterovirus 71 (EV 71) infection. Mice inoculated with EV 71 produced a significantly lower amount of type I IFNs than those inoculated with poly (I:C), adenovirus type V, or coxsackievirus B3 (CB3). EV 71 infection, however, mounted a proinflammatory response with a significant increase in the levels of serum and brain interleukin (IL)‐6, monocyte chemoattractant protein‐1, tumor necrosis factor, and IFN‐γ. EV 71 infection abolished both poly (I:C)‐ and CB3‐induced type I IFN production of mice. Such effect was not extended to other enteroviruses including coxsackievirus A24, B2, B3, and echovirus 9, as mice infected with these viruses retained type I IFN responsiveness upon poly (I:C) challenge. In addition, EV 71‐infected RAW264.7 cells produced significantly lower amount of type I IFNs than non‐infected cells upon poly (I:C) stimulation. The inhibitory effect of EV 71 on type I IFN production was attributed to the viral protein 3C, which was confirmed using over‐expression systems in both mice and RAW264.7 cells. The 3C over‐expression, however, did not interfere with poly (I:C)‐induced proinflammatory cytokine production. These findings indicate that EV 71 can hamper the host innate defense by blocking selectively type I IFN synthesis through the 3C viral protein. J. Med. Virol. 84:1779–1789, 2012. © 2012 Wiley Periodicals, Inc.
Identification of prohibitin as a Chikungunya virus receptor protein
Authors: Wintachai Phitchayapak , Wikan Nitwara , Kuadkitkan Atichat , Jaimipuk Thitigun , Ubol Sukathida , Pulmanausahakul Rojjanaporn , Auewarakul Prasert , Kasinrerk Watchara , Weng Wen‐Yu , Panyasrivanit Mingkwan , Paemanee Atchara , Kittisenachai Suthathip , Roytrakul Sittiruk , Smith Duncan R.
Published: September 2012

Chikungunya virus (CHIKV) has recently re‐emerged causing millions of infections in countries around the Indian Ocean. While CHIKV has a broad host cell range and productively infects a number of different cell types, macrophages have been identified as a potential viral reservoir serving to increase the duration of symptoms. To date no CHIKV interacting protein has been characterized and this study sought to identify CHIKV binding proteins expressed on target cell membranes. Two‐dimensional virus overlay identified prohibitin (PHB) as a microglial cell expressed CHIKV binding protein. Co‐localization, co‐immunoprecipitation as well as antibody and siRNA mediated infection inhibition studies all confirmed a role for PHB in mediating internalization of CHIKV into microglial cells. PHB is the first identified CHIKV receptor protein, and this study is evidence that PHB may play a role in the internalization of multiple viruses. J. Med. Virol. 84:1757–1770, 2012. © 2012 Wiley Periodicals, Inc.
Common temperature signal in four well‐replicated tree growth series from northern Fennoscandia
Authors: Lindholm M. , Aalto T. , Grudd H. , Mccarroll D. , Ogurtsov M. , Jalkanen R.
Published: September 2012

Four Nordic temperature proxies based on tree growth at the northern timberline – ring‐width from Sweden and Finland, maximum latewood density from Sweden, and height increment from Finland – were compared. Three indexing methods were used to enhance the low (centennial and above), medium (decadal‐to‐multidecadal) and high (decadal‐to‐interannual) frequencies. The proxies are shown to have a strong temperature signal (common variance) at the interannual‐to‐multidecadal scale, while the multidecadal‐to‐centennial trends are less coherent, perhaps reflecting intra‐regional differences in growing conditions but more likely due to the more noisy regional curve standardization method used to retain the longest trends. Various methods of combining the four proxy series were explored and tested by comparison with four long temperature records from northern Fennoscandia. Only relatively high‐frequency, spline‐indexed series produced consistently positive verification statistics as a reconstruction model for summer temperature using all four proxies. Copyright © 2012 John Wiley & Sons, Ltd.
Total phenolics content, anthocyanins, and dietary fiber content of apple pomace powders produced by vacuum‐belt drying
Authors: Yan Huitong , Kerr William L
Published: September 2012

Background

Apple pomace is a waste material from apple juice processing, and contains significant amounts of dietary fiber and phytochemicals. Many of these compounds may be degraded post‐pressing and during drying operations. Continuous vacuum‐belt drying (VBD) was studied as a means of drying and maintaining quality of apple pomace. The color and chemical properties of samples dried by vacuum‐belt drying at different temperatures were evaluated including total phenolics content (TPC), monomeric anthocyanins (TMA) and dietary fiber content (TDF).

Results

VBD powders were pale golden yellow, and those dried at 80°C did not differ in L*, a* and b* values from freeze‐dried powders. VBD pomace had 44.9 to 51.9 g gallic acid equivalents kg−1 TPC, with greatest retention for pomace dried at 80 and 95°C. TPC for pomace dried at 80 or 95°C was not significantly different from that for freeze‐dried pomace. TMA levels (74.0 mg C3G kg−1, where C3G is cyanidine 3‐O‐glucoside equivalents) were highest in pomace vacuum dried at 80°C. TDF ranged from 442 to 495 g kg−1 in vacuum‐dried pomace and was not significantly different from TDF of freeze‐dried poamce (480 g kg−1).

Conclusion

In all cases, TPC, TMA and TDF were higher in VBD pomace than in freeze‐dried whole apple, while VBD pomace prepared at 80 or 95°C had fiber and phytochemical levels similar to freeze‐dried powders. © 2012 Society of Chemical Industry
Ionic liquid‐based vortex‐assisted dispersive liquid–liquid microextraction of organophosphorus pesticides in apple and pear
Authors: Zhang Lijin , Chen Fang , Liu Shaowen , Chen Biyu , Pan Canping
Published: September 2012

An ionic liquid‐based vortex‐assisted dispersive liquid–liquid microextraction (DLLME) was developed for the analysis of trace amounts of six organophosphorus pesticides (OPPs) in apple and pear coupled with high‐performance liquid chromatography. During the DLLME, the effect of some experimental factors including extraction solvent and its volume, dispersion solvent and its volume, vortex time, salt addition, and pH on the extraction procedure were investigated. Under the chosen extraction conditions, the analytes were enriched more than 300‐fold and the limits of detections were greatly dropped to 0.061–0.73 μg/kg. The linearity relationship was observed in the range of 2–100 μg/kg with the correlation coefficients (R2) ranging from 0.9967 to 0.9983. The relative standard deviations varied from 2.3 to 5.7% (n = 6). Mean recovery values of the OPPs were in the range of 69.8–109.1% with a relative standard deviation lower than 7.0%. Based on these above, it could be concluded that 1‐octyl‐3‐methylimidazolium hexafluorophosphate ([C8MIM][PF6]) was a good extraction solvent and the proposed [C8MIM][PF6]‐based vortex‐assisted DLLME method was suitable for the effective extraction of the OPPs in apple and pear.
Dry fractionation
Authors: Dijkstra Albert J.
Published: September 2012

With the increase in palm oil production, the dry fractionation process has also gained in importance, both in comparison with other fractionation processes and in terms of the number of tonnes per annum. This has been assisted by the development of far less labour‐intensive processes and improved understanding of the physical chemistry involved. This new insight indicates that temperature uniformity in a crystalliser is not necessary, which opens the door to continuous crystallisation. Combining this continuous crystallisation with a proven continuous separation system such as the conical sieve centrifuge could well lead to a fully continuous dry fractionation process. It is not there yet but likely to arrive.
Impaired growth, hematopoietic colony formation, and ribosome maturation in human cells depleted of Shwachman–Diamond syndrome protein SBDS
Authors: Sezgin Gulay , Henson Adrianna L. , Nihrane Abdallah , Singh Sharon , Wattenberg Max , Alard Pascale , Ellis Steven R. , Liu Johnson M.
Published: September 2012

Background

Shwachman–Diamond syndrome (SDS), associated with SBDS mutations, is characterized by pancreatic exocrine dysfunction and marrow failure. Sdo1, the yeast ortholog of SBDS, is implicated in maturation of the 60S ribosomal subunit, with delayed export of 60S‐like particles from the nucleoplasm when depleted. Sdo1 is needed for release of the anti‐subunit association factor Tif6 from 60S subunits, and Tif6 may not be recycled to the nucleus when Sdo1 is absent.

Methods

To clarify the role of SBDS in human ribosome function, TF‐1 erythroleukemia and A549 lung carcinoma cells were transfected with vectors expressing RNAi against SBDS.

Results

Growth and hematopoietic colony forming potential of TF‐1 knockdown cells were markedly hindered when compared to controls. To analyze the effect of SBDS on 60S subunit maturation in A549 cells, subunit localization was assessed by transfection with a vector expressing a fusion between human RPL29 and GFP: we found a higher percentage of SBDS‐depleted cells with nuclear localization of 60S subunits. Polysome analysis of TF‐1 knockdown cells showed a decrease in free 60S and 80S subunits. We also analyzed the levels of eIF6 (human ortholog of Tif6) following near‐complete knockdown of SBDS in TF‐1 cells and found an approximately 20% increase in the amount of eIF6 associated with the 60S subunit.

Conclusions

We conclude that knockdown of SBDS leads to growth inhibition and defects in ribosome maturation, suggesting a role for wild‐type SBDS in nuclear export of pre‐60S subunits. Furthermore, knockdown of SBDS may interfere with eIF6 recycling. Pediatr Blood Cancer 2013;60:281–286. © 2012 Wiley Periodicals, Inc.
A novel mutation in the SerpinC1 gene presenting as unprovoked neonatal cerebral sinus venous thrombosis in a kindred
Authors: Kumar Riten , Moharir Mahendranath , Yau Ivanna , Williams Suzan
Published: September 2012

Antithrombin (AT) deficiency has been associated with an increased risk of pediatric cerebral sinus venous thrombosis (CSVT); but few cases of neonatal CSVT have been reported. We describe two half‐siblings who presented with seizures in the first week of life and were found to have extensive CSVT with associated parenchymal and intraventricular hemorrhage. Both infants were found to have type 1 AT deficiency. Sequencing of the SerpinC1 gene revealed a novel heterozygous mutation on exon 5 (c.1009C > T p.Q337X). Both infants were treated with anticoagulation and had recanalization of the dural sinuses on follow up imaging. Pediatr Blood Cancer 2013; 60: 133–136. © 2012 Wiley Periodicals, Inc.
Two cases of localized neuroblastoma with multiple segmental chromosomal alterations and metastatic progression
Authors: Morales La Madrid Andres , Nall Melanie Beglin , Ouyang Karen , Minor Agata , Raca Gordana , Kent Paul , Miller Ira , Schleiermacher Gudrun , Janoueix‐Lerosey Isabelle , Cohn Susan L.
Published: September 2012

Surgery alone is curative for most children with localized MYCN‐non‐amplified neuroblastoma. However, 10–15% will develop recurrent loco‐regional disease, and very rarely, patients will relapse metastatically. Currently, it is not possible to predict which child with localized, MYCN‐non‐amplified neuroblastoma will develop disseminated disease. We report two children who presented with favorable biology, localized neuroblastoma and subsequently relapsed with metastatic disease after treatment with surgery. Whole‐genome DNA copy number analyses performed on the diagnostic tumors identified 15 (case 1) and 8 (case 2) segmental chromosomal alterations. Further analysis of the prognostic value of whole‐genome analysis in children with localized neuroblastoma is warranted. Pediatr Blood Cancer 2013;60:332–335. © 2012 Wiley Periodicals, Inc.
Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis
Authors: Gort Laura , Granell M. Reyes , Fernández Gema , Carreto Práxedes , Sanchez Aurora , Coll M. José
Published: September 2012

Objective

Nonimmune hydrops fetalis (NIHF) is defined by the excessive fluid accumulation in more than one foetal compartments and body cavities because of nonimmune reasons. It has been described that 14 lysosomal diseases may be causative of NIHF. The aim of this study was to design a fast protocol to investigate the most frequent lysosomal diseases that are reported that may cause NIHF.

Method

We analysed the glycosaminoglycans excretion in the amniotic fluid supernatant and four different lysosomal enzymatic activities in the amniotic cultured cells of the different NIHF amniotic fluids we received.

Results

We investigated 30 NIHF cases, using this fast protocol. We detected two cases of NIHF because of lysosomal diseases, which represent 6.6%. We diagnosed one case of mucopolysaccharidosis type VII and one case of Gaucher disease.

Conclusion

The fast protocol we designed analyses seven of the most frequent lysosomal pathologies that have been described that may cause NIHF, with only five different determinations, which make the analysis of NIHF fast, cost‐effective and without need of too much amniotic fluid. We believe this protocol may be useful for the analysis of lysosomal diseases in NIHF. © 2012 John Wiley & Sons, Ltd.
Pediatric chronic lower respiratory disorders: Microbiological and immunological phenotype
Authors: Bugin S. , Lunardi F. , Bertuola F. , Snijders D. , Bottecchia L. , Perissinotto E. , Calabrese F. , Barbato A.
Published: September 2012

The role of infectious agents in children with recurrent/chronic lower respiratory disorders (R/CLRDs) is not clear, whereas it has been largely studied in acute respiratory diseases. The purpose of the study was to evaluate the frequency of infections, in particular viral infections, in children with R/CLRDs correlating their presence with clinical/biohumoral parameters.

Eighty children affected by R/CLRDs underwent bronchoscopy and analysis of bronchoalveolar lavage (BAL) for cells, mediators (eosinophil cationic protein—ECP, interleukin—IL‐8, tumor necrosis factor—TNFα) and pathogens (viruses and bacteria).

Viral genomes were detected in 50/80 (62.5%) children. Rhinovirus, the principal detected virus (26/50, 52%), occurred more frequently in male children. Higher percentages of BAL neutrophils and IL‐8 values were detected in virus positive than negative children.

ECP values resulted significantly higher in the children with rhinovirus than in those with other viruses. No other statistically significant correlation between viral findings and clinical/biohumoral data were found.

Respiratory viruses, especially rhinovirus, seem to play an important role in children with R/CLRDs. They are associated with changes in BAL cellularity and inflammatory cytokines. Further studies are needed to confirm the persistence of viruses in these patients and to identify eventual therapeutic strategies. Pediatr Pulmonol. 2013; 48:780–788. © 2012 Wiley Periodicals, Inc.
Delayed radical prostatectomy for intermediate‐risk prostate cancer is associated with biochemical recurrence: Possible implications for active surveillance from the SEARCH database
Authors: Abern Michael R. , Aronson William J. , Terris Martha K. , Kane Christopher J. , Presti Joseph C. , Amling Christopher L. , Freedland Stephen J.
Published: September 2012

INTRODUCTION

Active surveillance (AS) is increasingly accepted as appropriate management for low‐risk prostate cancer (PC) patients. It is unknown whether delaying radical prostatectomy (RP) is associated with increased risk of biochemical recurrence (BCR) for men with intermediate‐risk PC.

METHODS

We performed a retrospective analysis of 1,561 low and intermediate‐risk men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated with RP between 1988 and 2011. Patients were stratified by interval between diagnosis and RP (≤3, 3–6, 6–9, or >9 months) and by risk using the D'Amico classification. Cox proportional hazard models were used to analyze BCR. Logistic regression was used to analyze positive surgical margins (PSM), extracapsular extension (ECE), and pathologic upgrading.

RESULTS

Overall, 813 (52%) men were low‐risk, and 748 (48%) intermediate‐risk. Median follow‐up among men without recurrence was 52.9 months, during which 437 men (38.9%) recurred. For low‐risk men, RP delays were unrelated to BCR, ECE, PSM, or upgrading (all P > 0.05). For intermediate‐risk men, however, delays >9 months were significantly related to BCR (HR: 2.10, P = 0.01) and PSM (OR: 4.08, P < 0.01). Delays >9 months were associated with BCR in subsets of intermediate‐risk men with biopsy Gleason score ≤3 + 4 (HR: 2.51, P < 0.01), PSA ≤ 6 (HR: 2.82, P = 0.06), and low tumor volume (HR: 2.59, P = 0.06).

CONCLUSIONS

For low‐risk men, delayed RP did not significantly affect outcome. For men with intermediate‐risk disease, delays >9 months predicted greater BCR and PSM risk. If confirmed in future studies, this suggests delayed RP for intermediate‐risk PC may compromise outcomes. Prostate 73: 409–417, 2013. © 2012 Wiley Periodicals, Inc.