bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression profiling in the cerebral cortex of patients with cirrhosis with and without hepatic encephalopathy
Authors: Görg Boris , Bidmon Hans-Jürgen , Häussinger Dieter
Published: January 2013

Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is seen as the clinical manifestation of a low-grade cerebral edema associated with oxidative-nitrosative stress. However, comprehensive data on HE-associated molecular derangements in the human brain are lacking. In the present study, we used a whole human genome microarray approach for gene expression profiling in

post mortem

brain samples from patients with cirrhosis with or without HE and controls without cirrhosis. Altered expression levels were found for a total of 1,012 genes in liver cirrhosis patients without and with HE, and HE-characteristic gene expression changes were identified. Genes with altered expression pattern in HE were related to oxidative stress, microglia activation, receptor signaling, inflammatory pathways, cell proliferation, and apoptosis. Despite an up-regulation of genes associated with microglia activation,

pro

-inflammatory cytokine messenger RNA profiles remained unchanged in the brains of patients with liver cirrhosis and HE compared with controls. Interestingly, many genes counteracting

pro

-inflammatory signaling and inflammatory cytokine expression were up-regulated in the cerebral cortex of patients with liver cirrhosis and HE.

Conclusion

: Pathogenetic mechanisms of HE deduced from cell culture and animal experiments, such as oxidative stress, altered Zn2+ homeostasis and microglia activation also apply to human brain from patients with liver cirrhosis and HE. The study also revealed a not-yet recognized increased expression of genes antagonizing proinflammatory signaling and inflammatory cytokine expression.
BTB/POZ domain-containing protein 7: Epithelial-mesenchymal transition promoter and prognostic biomarker of hepatocellular carcinoma
Authors: Tao Yi-Ming , Huang Jin-Lin , Zeng Shan , Zhang Sai , Fan Xue-Gong , Wang Zhi-Ming , Yang Hui-Xiang , Yuan Xiao-Hua , Wang Pu , Wu Fan , Luo Jia , Zeng De-Yu , Shen Hong
Published: January 2013

Epithelial-mesenchymal transition (EMT) is a critical step in the metastasis of hepatocellular carcinoma (HCC). BTB/POZ domain-containing protein 7 (BTBD7) regulates EMT-associated proteins implicated in HCC progression. However, the role(s) of BTBD7 in HCC have not been identified. Using highly metastatic HCC HCCLM3 cells, immortalized L02 hepatocytes, metastatic HCC animal models, and three independent cohorts of HCC patient specimens, we aimed to determine the involvement of BTBD7 in HCC metastasis. We show that BTBD7 messenger RNA and protein was highly expressed in HCC cells and tumor tissues, with such expression being associated with: enhanced cell motility, venous invasion, and poor prognosis. BTBD7 promoted HCC angiogenesis and metastasis

in vitro

and

in vivo

, but did not influence cell proliferation or colony formation. BTBD7 enhancement of HCC invasion and EMT phenotype occurred through activation of a RhoC-Rock2-FAK-signaling pathway, resulting in matrix metalloproteinase-2/9 production and microvessel formation. Applying a predictive risk score model, Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of HCC clinical outcome.

Conclusion

: The present study identifies BTBD7 as a novel candidate prognostic factor and a potential therapeutic target of HCC.
Nitrate dynamics in a rural headwater catchment: measurements and modelling
Authors: Smethurst Philip J. , Petrone Kevin C. , Langergraber Günter , Baillie Craig C. , Worledge Dale , Nash David
Published: January 2013

This study was designed to improve our understanding of, and mechanistically simulate, nitrate (NO3) dynamics in a steep 9.8 ha rural headwater catchment, including its production in soil and delivery to a stream via surface and subsurface processes. A two‐dimensional modelling approach was evaluated for (1) integrating these processes at a hillslope scale annually and within storms, (2) estimating denitrification, and (3) running virtual experiments to generate insights and hypotheses about using trees in streamside management zones (SMZs) to mitigate NO3 delivery to streams. Total flow was mathematically separated into quick‐ and slow‐flow components; the latter was routed through the HYDRUS software with a nitrogen module designed for constructed wetlands. Flow was monitored for two years. High surface‐soil NO3 concentrations started to be delivered to the stream via preferential subsurface flow within two days of the storm commencing. Groundwater NO3‐N concentrations decreased from 1.0 to less than 0.1 mg l−1 from up‐slope to down‐slope water tables, respectively, which was attributed to denitrification. Measurements were consistent with the flushing of NO3 mainly laterally from surface soil during and following each storm. The model accurately accounted for NO3 turnover, leading to the hypotheses that denitrification was a minor flux (<3 kg N ha−1) compared to uptake (98−127 kg N ha−1), and that SMZ trees would reduce denitrification if they lowered the water table. This research provides an example of the measurement and modelling of NO3 dynamics at a small‐catchment scale with high spatial and temporal resolution. Copyright © 2013 John Wiley & Sons, Ltd.
Hydrological response of a humid agroforestry catchment at different time scales
Authors: Palleiro L. , Rodríguez‐Blanco M. L. , Taboada‐Castro M. M. , Taboada‐Castro M. T.
Published: January 2013

Using data collected at the Mero catchment during three hydrological years (2005/06–2007/08), an analysis of rainfall–runoff relationships was performed at annual, seasonal, monthly, and event scales. At annual scale, the catchment showed low runoff coefficients (23–35%), due to high water storage capacity soils as well as high runoff inter‐annual variability. Rainfall variability was the main responsible for the differences in the inter‐annual runoff. At seasonal and monthly scales, there was no simple relationship between rainfall and runoff. Seasonal dynamics of rainfall and potential evapotranspiration in conjunction with different rainfall distribution during the study years could be the key factors explaining the complex relationship between rainfall and runoff at monthly and seasonal scale. At the event scale, the results revealed that the hydrological response was highly dependent on initial conditions and, to a lesser extent, on rainfall amount. The shapes of the different hydrographs, regardless of the magnitude, presented similar characteristics: a moderate rise and a prolonged recession, suggesting that subsurface flow was the dominant process in direct runoff. Moreover, all rainfall–runoff events had a higher proportion of baseflow than of direct runoff. A cluster‐type analysis discriminated three types of events differentiated mainly by rainfall amount and antecedent rainfall conditions. The study highlights the role of the antecedent rainfall and the need for caution in extrapolating relationships between rainfall amount and hydrological response of the catchment. Copyright © 2013 John Wiley & Sons, Ltd.
Investigating the influence of minor hydraulic structures on modeling flood events in lowland areas
Authors: Hailemariam Freegzi Mehari , Brandimarte Luigia , Dottori Francesco
Published: January 2013

Flood inundation models have been recognized to be a valuable tool to reproduce flow dynamics in a given area and support decision‐making processes on flood management measures. In many cases, in the simulation of flood events, only the main river channel and the associated structures are represented within the model. However, during flood events involving lowland areas, the minor drainage network – and the associated hydraulic structures – may have an important role in conveying flow and determining which areas will be flooded. The objective of this study is to investigate whether – and to what extent – small hydraulic structures in drainage networks have an influence in flooding on lowland areas.

The case study for this research is the 1990 flood event which occurred in the lowland plain of the Reno River, in Northern Italy. The study area is mainly used for agricultural purposes and has a drainage system with several small bridges and culverts.

The influence of the minor hydraulic structures on flood dynamics was analyzed through a combined use of one‐dimensional (1D) and two‐dimensional (2D) hydraulic models. First, a number of detailed and simplified approaches to represent hydraulic structures in the computational grids were analyzed by means of the HECRAS 1D model. Second, these approaches were implemented and tested in several 2D simulations of the flood event. The simulated inundation extents and flood levels were then compared with the observed data and with each other. The analysis of results showed that simplified schematizations were sufficient to obtain good model predictions of peak inundation extent and flood levels, at least for the present case study. Moreover, the influence of the structures on the peak flood inundation extent and flood levels was found to be limited, whereas it showed to be more significant during the drainage phase of the flood. Copyright © 2013 John Wiley & Sons, Ltd.
Water balance analysis for the Tonle Sap Lake–floodplain system
Authors: Kummu M. , Tes S. , Yin S. , Adamson P. , Józsa J. , Koponen J. , Richey J. , Sarkkula J.
Published: January 2013

The Tonle Sap Lake of Cambodia is the largest freshwater body of Southeast Asia, forming an important part of the Mekong River system. The lake has an extremely productive ecosystem and operates as a natural floodwater reservoir for the lower Mekong Basin, offering flood protection and assuring the dry season flow to the Mekong Delta. In light of the accelerating pace of water resources development within the Mekong Basin and the anticipation of potentially significant hydrological impacts, it is critical to understand the overall hydrologic regime of Tonle Sap Lake. We present here a detailed water balance model based on observed data of discharges from the lake's tributaries, discharge between Mekong and the lake through the Tonle Sap River, precipitation, and evaporation. The overland flow between the Mekong and lake was modelled with the EIA 3D hydrodynamic model. We found that majority (53.5%) of the water originates from the Mekong mainstream, but the lake's tributaries also play an important role contributing 34% of the annual flow, while 12.5% is derived from precipitation. The water level in the lake is mainly controlled by the water level in the Mekong mainstream. The Tonle Sap system is hence very vulnerable, from a water quantity point of view, to possible changes in the Mekong mainstream and thus, development activities in the whole Mekong basin. From a biogeochemical point of view, the possible changes in the lake's own catchment are equally important, together with the changes in the whole Mekong Basin. Based on our findings, we recommend of continuing the monitoring programmes in lake's tributaries and urgently starting of groundwater measurement campaign within the floodplain, and including the groundwater modelling to be part of the hydrodynamic models applied for the lake. Copyright © 2013 John Wiley & Sons, Ltd.
The hazard communication of fragrance allergens must be improved
Authors: Klaschka Ursula
Published: January 2013

Contact allergy is a global health problem that could be alleviated considerably if the general public could reduce contact to sensitizers. Efficient hazard communication would be a valuable instrument to achieve this. What do current regulations concerning fragrance sensitizers in cosmetic products in Europe contribute? For example, there are bans and restrictions according to the Cosmetic Regulation, there is the “26 allergens rule” that requires that the names of some allergenic fragrance ingredients are listed on the containers, there is labeling and classification of hazardous products according to Regulation 1272/2008, and there is the regulation concerning the registration, evaluation, authorization and restriction of chemicals (REACH). Do these regulations increase consumer protection by suitable hazard communication instruments? Four main problems were identified. First, according to the 26 allergens rule, consumers carry a very large part of the responsibility for risk reduction management. They need to be capable and motivated to recognize the names of strong allergens listed in the ingredient list and decide for themselves whether they want to run the risk or not, provided that they are aware of their responsibility. Second, cosmetic products do not need to be classified and labeled like other consumer goods, according to the European Commission Regulation 1272/2008, if they contain hazardous substances. Third, some pictograms for hazardous substances, for example, the exclamation mark for sensitizers, are not well understood by the majority of the general public. Fourth, very often, the design of cosmetic containers implies health and well being, even if the respective products contain sensitizers or other hazardous substances. Against this background, the following improvements are proposed: 1) the 26 allergens rule needs revision, 2) the exception for cosmetic products from labeling and classification should be abolished, 3) a new self-explanatory pictogram for skin sensitizers and skin irritants should become mandatory for consumer products containing allergens, and 4) packaging of products containing hazardous substances should not be allowed to be attractive and evoke feelings that the products were harmless. Labeling of consumer products can be a very efficient tool for risk communication, however, the addressees must be sufficiently trained to understand the system and know the consequences of their behavior. Transparent labeling will increase the credibility of manufacturers and can lead to a subsequent improved risk management with a benefit for all stakeholders. Integr Environ Assess Manag 2013;9:358–362. © 2013 SETAC
The practicalities and pitfalls of establishing a policy-relevant and cost-effective soil biological monitoring scheme
Authors: Faber Jack H , Creamer Rachel E , Mulder Christian , Römbke Jörg , Rutgers Michiel , Sousa J Paulo , Stone Dorothy , Griffiths Bryan S
Published: January 2013

A large number of biological indicators have been proposed over the years for assessing soil quality. Although many of those have been applied in monitoring schemes across Europe, no consensus exists on the extent to which these indicators might perform best and how monitoring schemes can be further optimized in terms of scientific and policy relevance. Over the past decade, developments in environmental monitoring and risk assessment converged toward the use of indicators and endpoints that are related to soil functioning and ecosystem services. In view of the proposed European Union (EU) Soil Framework Directive, there is an urgent need to identify and evaluate indicators for soil biodiversity and ecosystem services. The recently started integrated project, Ecological Function and Biodiversity Indicators in European Soils (EcoFINDERS), aims to address this specific issue within the EU Framework Program FP7. Here, we 1) discuss how to use the concept of ecosystem services in soil monitoring, 2) review former and ongoing monitoring schemes, and 3) present an analysis of metadata on biological indicators in some EU member states. Finally, we discuss our experiences in establishing a logical sieve approach to devise a monitoring scheme for a standardized and harmonized application at European scale. Integr Environ Assess Manag 2013; 9: 276–284. © 2013 SETAC
Pulsed radiofrequency treatment for idiopathic trigeminal neuralgia: A retrospective analysis of the causes for ineffective pain relief
Authors: Luo F. , Meng L. , Wang T. , Yu X. , Shen Y. , Ji N.
Published: January 2013

We retrospectively analyzed the reasons for ineffective pain relief in patients with idiopathic trigeminal neuralgia (TN) who had undergone pulsed radiofrequency (PRF) treatment guided by computed tomography scan. We found that intraoperative PRF output voltage and electrical field intensity was significantly higher (p < 0.05) in the group who had received effective treatment than in the ineffective group. These findings suggest that optimizing PRF parameters and increasing the intraoperative output voltage (electric field intensity) may therefore, provide better pain relief in patients with TN.
Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23–related hypophosphatemia, dental anomalies, and ectopic calcification
Authors: Rafaelsen Silje Hjorth , Ræder Helge , Fagerheim Anne Kristine , Knappskog Per , Carpenter Thomas O , Johansson Stefan , Bjerknes Robert
Published: January 2013

Fibroblast growth factor 23 (FGF23) plays a crucial role in renal phosphate regulation, exemplified by the causal role of PHEX and DMP1 mutations in X-linked hypophosphatemic rickets and autosomal recessive rickets type 1, respectively. Using whole exome sequencing we identified compound heterozygous mutations in family with sequence similarity 20, member C (FAM20C) in two siblings referred for hypophosphatemia and severe dental demineralization disease. FAM20C mutations were not found in other undiagnosed probands of a national Norwegian population of familial hypophosphatemia. Our results demonstrate that mutations in FAM20C provide a putative new mechanism in human subjects leading to dysregulated FGF23 levels, hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis of the long bones in the absence of rickets.
Validation of a Free Phenytoin Assay on Cobas c501 Analyzer Using Calibrators From Cobas Integra Free Phenytoin Assay by Comparing its Performance With Fluorescence Polarization Immunoassay for Free Phenytoin on the TDx Analyzer
Authors: Dasgupta Amitava , Davis Bonnette , Chow Loretta
Published: January 2013

For many years, fluorescence polarization immunoassay (FPIA) on the TDx analyzer has been used for determination of free phenytoin concentration. Recently Abbott Laboratories decided to discontinue the TDx analyzer and related assays on this analyzer. Free phenytoin assay is also available from Roche Diagnostics for application on the Cobas Integra analyzer (fluorescence polarization assay) but not on Cobas c510 analyzer. Free phenytoin calibrators from the Cobas Integra free phenytoin assay and the reagents from the KIMSphenytoin assay were used for the determination of free phenytoin on the Cobas c501 analyzer. The intra‐run and inter‐run precisions were both <7.2%. The assay was linear from 0.2 to 4 μg/ml. The free phenytoin assay on the Cobas c501 was compared with the FPIAassay on the TDx analyzer using sera from 25 patients receiving phenytoin (phenytoin concentration between 0.3 and 3.7 μg/ml). The following regression equation was observed: y = 0.9899 x + 0.0408 (r = 0.98, n = 25). In conclusion, the free phenytoin assay on the Cobas c501 analyzer is a valid alternative to free phenytoin assay on the TDx analyzer. J. Clin. Lab. Anal. 27:1–4, 2013. © 2012 Wiley Periodicals, Inc.
The combination of surface enhanced Raman spectroscopy and an ionic liquid as a model system to study the adhesion interface between sulfur and brass
Authors: Baert Kitty , Breugelmans Tom , Buytaert Guy , Brabant Johan Van , Hubin Annick
Published: January 2013

The adhesion of steel cord to rubber is very important for the quality of reinforced rubber products, e.g. tyres. Therefore, steel cord is often plated with brass, which will lead to CuxS bonds after reaction with sulfur compounds in the rubber. A unique in‐situ analytical method has been developed to investigate the sulfur–brass interface: the sulfuring process has been simulated via a heating process in a water‐free transparent ionic liquid with added sulfur and the reaction at the brass‐coated steel cord has been monitored in real time with Raman spectroscopy. The grown CuxS film seems to be similar to the layers at the steel cord interface in real rubber materials. The model system can also be used to perform electrochemical measurements at the same time. The thickness of the CuxS layer has been estimated from the measured current during a cathodic stripping process. Copyright © 2013 John Wiley & Sons, Ltd.
Influence of pre‐slaughtering feed restriction on muscle characteristics of farmed sea bass (Dicentrarchus labrax L.) during cold storage
Authors: Sáez María I , Navarro Ginés , García‐Mesa Sergio , Martínez Tomás F , García‐Gallego Manuel , Suárez María D
Published: January 2013

BACKGROUND

This paper deals with the consequences of dietary restriction or complete starvation before slaughtering on the biochemical and textural characteristics of sea bass muscle.

RESULTS

Results showed that only severe feed restriction influenced negatively total body and individual organ weights, and these animals showed lower condition factor as well. Neither moderate feed restriction (up to 50% of the standard ration) kept for 30 days nor total starvation up to 12 days caused significant effects on fish weight and fillet yield. Muscle lipid content was lower in feed‐restricted fish, although this parameter was not altered by starvation time. Differences between the two feeding strategies studied were observed in muscle textural and biochemical parameters, and the results point to an influence of the nutritional status on the post‐mortem evolution of collagen and myofibrillar proteins, although firmness was not modified.

CONCLUSIONS

Moderate feed restriction prior to slaughtering could be advisable in sea bass culture, given that no detrimental effects on fish quality or fish performance were noticed, whereas substantial amounts of feed can be saved. © 2013 Society of Chemical Industry
Effect of alkali and oxidative treatments on the physicochemical, pasting, thermal and morphological properties of corn starch
Authors: Spier Franciela , Zavareze Elessandra da Rosa , Marques e Silva Ricardo , Elias Moacir Cardoso , Dias Alvaro Renato Guerra
Published: January 2013

Background

Few studies on starch modifications using different chemical agents are available in the literature, and no reports were found on the combined effect of oxidation and alkaline treatment of corn starch. Thus this work evaluated the physicochemical, pasting, morphological, cystallinity and thermal properties of chemically modified corn starch, after either the isolated or combined action of alkaline (sodium hydroxide) and oxidative (sodium hypochlorite) treatments.

Results

The highest values for the sum of carbonyl and carboxyl and enzymatic hydrolysis occurred in starches submitted to oxidative treatment at high active chlorine concentrations. The alkali treatment in isolation modified the pasting properties, reduced the paste temperature and increased the peak viscosity, breakdown, final viscosity and setback of starches. Starch modified by the action of sodium hypochlorite and hydroxide in combination presented more severe damage on granule surfaces.

Conclusion

The results show that corn starch modified by the combined action of oxidative and alkaline treatments should be studied more, especially at the concentration limit of sodium hydroxide where gelatinization occurs. Under these conditions the effect of oxidation can be more intense and thus allow the production of starches with different properties and an increase in their industrial applications. © 2013 Society of Chemical Industry
Beavers (Castor fiber) in the Past: Holocene Archaeological Evidence for Beavers in Romania
Authors: Bejenaru L. , Stanc S. , Popovici M. , Balasescu A.
Published: January 2013

Archaeological beaver (Castor fiber) remains from Romanian sites dating from the Mesolithic to the Middle Ages are described in terms of their frequencies (based on the number of identified specimens), morphology and size. A summary of previous archaeozoological studies in the geographical and historical regionalization of the Romanian territory (i.e. Banat, Dobrudja, Moldavia, Muntenia, Oltenia and Transylvania) shows that temporal and regional variation characterizes the assemblages. The data also reveal that beaver hunting contributed little to local economies, although some spatial and temporal variations are apparent and are here compared with the evidence from the historical record. In addition, univariate, bivariate and geometric morphometric analyses are employed to examine different anatomical elements. Studies of the lower third molar (M3) reveal that there is a statistically significant intraspecific variability between the Neolithic and Iron Age populations, situated also in different regions, Muntenia and Moldavia, respectively. Copyright © 2013 John Wiley & Sons, Ltd.
Online discussion of drug side effects and discontinuation among breast cancer survivors
Authors: Mao Jun J. , Chung Annie , Benton Adrian , Hill Shawndra , Ungar Lyle , Leonard Charles E. , Hennessy Sean , Holmes John H.
Published: January 2013

Purpose

While patients often use the internet as a medium to search for and exchange health‐related information, little is known about the extent to which patients use social media to discuss side effects related to medications. We aim to understand the frequency and content of side effects and associated adherence behaviors discussed by breast cancer patients related to using aromatase inhibitors (AIs), with particular emphasis on AI‐related arthralgia.

Methods

We performed a mixed methods study to examine content related to AI associated side effects posted by individuals on 12 message boards between 2002 and 2010. We quantitatively defined the frequency and association between side effects and AIs and identified common themes using content analysis. One thousand randomly selected messages related to arthralgia were coded by two independent raters.

Results

Among 25 256 posts related to AIs, 4589 (18.2%) mentioned at least one side effect. Top‐cited side effects on message boards related to AIs were joint/musculoskeletal pain (N = 5093), hot flashes (1498), osteoporosis (719), and weight gain (429). Among the authors posting messages who self‐reported AI use, 12.8% mentioned discontinuing AIs, while another 28.1% mentioned switching AIs. Although patients often cited severe joint pain as the reason for discontinuing AIs, many also offered support and advice for coping with AI‐associated arthralgia.

Conclusion

Online discussion of AI‐related side effects was common and often related to drug switching and discontinuation. Physicians should be aware of these discussions and guide patients to effectively manage side effects of drugs and promote optimal adherence. Copyright © 2013 John Wiley & Sons, Ltd.
Improving the mechanical properties of laser‐sintered polyamide 12 through incorporation of carbon nanotubes
Authors: Bai Jiaming , Goodridge Ruth D. , Hague Richard J.M. , Song Mo
Published: January 2013

Well‐dispersed nanocomposite powder with spherical morphology and suitable particle size for processing by laser sintering was successfully produced by coating polyamide 12 (PA12) powder particles with carbon nanotubes (CNTs). Flexural, impact, and tensile test specimens produced by laser sintering the PA12–CNT powder showed no distortion and good definition. The density of the PA12–CNT laser‐sintered parts was higher than that of neat PA12, which the authors propose is mainly due to higher laser absorption by the CNT particles. Compared to the laser‐sintered PA12 parts, PA12–CNT parts showed enhanced flexural, impact, and tensile properties without sacrificing elongation at break. This enhancement may be attributed to the good dispersion of the CNT in the PA12 matrix and denser laser‐sintered parts. Considering the low weight percentage of CNT used (0.1 wt%), it would seem that the method used in this work is a cost efficient and effective way to produce polymer nanocomposite powders for laser sintering, while maintaining the optimum powder morphology for the laser sintering process and enhancing the mechanical properties of the laser‐sintered part. POLYM. ENG. SCI., 2013. © 2013 Society of Plastics Engineers
Personality Traits and Body Weight Measures: Concurrent and Across–Time Associations
Authors: Armon Galit , Melamed Samuel , Shirom Arie , Shapira Itzhak , Berliner Shlomo
Published: January 2013

We tested the possibility that the five–factor model of personality is associated with three measures of body weight and with changes in their levels over time and that these associations are gender specific. The study was conducted at two points of time, Time 1 (2664 participants) and Time 2 (1492 participants), over approximately 4 years, controlling for gender, age, education, and having a chronic disease. Body weight was assessed by body mass index, waist circumference, waist–to–hip ratio, and the five–factor model by Saucier's Mini–Markers. Cross–sectional regression results indicated that conscientiousness was negatively associated with the three body weight measures, whereas neuroticism and extraversion were positively associated with the three body weight measures. The longitudinal regression results indicate that extraversion was associated with an increase in two of the body weight measures. Neuroticism was associated with increase in all three body weight measures and more strongly for women than for men. Openness was associated with a decrease in all three body weight measures for women, but this association was not significant for men. These findings help identify personality traits that lead to risk of weight gain and point to the modifying role of gender. Copyright © 2013 John Wiley & Sons, Ltd.
Identification of complex relationship between protein kinases and substrates during the cell cycle of HeLa cells by phosphoproteomic analysis
Authors: Yang Xing‐Lin , Li Qing‐Run , Ning Zhi‐Bin , Zhang Yan , Zeng Rong , Wu Jia‐Rui
Published: January 2013

Each phase of eukaryotic cell cycle is tightly controlled by multicomponent regulatory networks based on complex relationships of protein phosphorylation. In order to better understand the relationships between kinases and their substrate proteins during the progression of cell cycle, we analyzed phosphoproteome of HeLa cells during G1, S, and G2/M phases of cell cycle using our developed quantitative phosphoproteomic approaches. A total of 4776 high‐confidence phosphorylation sites (phosphosites) in 1177 proteins were identified. Bioinformatics analysis for predicting kinase groups revealed that 46 kinase groups could be assigned to 4321 phosphosites. The majority of phosphoproteins harboring two or more phosphosites could be phosphorylated by different kinase groups, in which nine major kinase groups accounted for more than 90% phosphosites. Further analyses showed that approximately half of the examined two phosphosite combinations were correlatively regulated, regardless of whether the kinase groups were same or not. In general, the majority of proteins containing correlated phosphosites had solely co‐regulated or counter‐regulated phosphosites, and co‐regulation was significantly more frequent than counter‐regulation, suggesting that the former may be more important for regulating the cell cycle. In conclusion, our findings provide new insights into the complex regulatory mechanisms of protein phosphorylation networks during eukaryotic cell cycle.
Quantitative measurements of N‐linked glycoproteins in human plasma by SWATH‐MS
Authors: Liu Yansheng , Hüttenhain Ruth , Surinova Silvia , Gillet Ludovic CJ , Mouritsen Jeppe , Brunner Roland , Navarro Pedro , Aebersold Ruedi
Published: January 2013

SWATH‐MS is a data‐independent acquisition method that generates, in a single measurement, a complete recording of the fragment ion spectra of all the analytes in a biological sample for which the precursor ions are within a predetermined m/z versus retention time window. To assess the performance and suitability of SWATH‐MS‐based protein quantification for clinical use, we compared SWATH‐MS and SRM‐MS‐based quantification of N‐linked glycoproteins in human plasma, a commonly used sample for biomarker discovery. Using dilution series of isotopically labeled heavy peptides representing biomarker candidates, the LOQ of SWATH‐MS was determined to reach 0.0456 fmol at peptide level by targeted data analysis, which corresponds to a concentration of 5–10 ng protein/mL in plasma, while SRM reached a peptide LOQ of 0.0152 fmol. Moreover, the quantification of endogenous glycoproteins using SWATH‐MS showed a high degree of reproducibility, with the mean CV of 14.90%, correlating well with SRM results (R2 = 0.9784). Overall, SWATH‐MS measurements showed a slightly lower sensitivity and a comparable reproducibility to state‐of‐the‐art SRM measurements for targeted quantification of the N‐glycosites in human blood. However, a significantly larger number of peptides can be quantified per analysis. We suggest that SWATH‐MS analysis combined with N‐glycoproteome enrichment in plasma samples is a promising integrative proteomic approach for biomarker discovery and verification.
Quantifying molecular partition of cell‐penetrating peptide–cargo supramolecular complexes into lipid membranes: optimizing peptide‐based drug delivery systems
Authors: Freire João Miguel , Veiga Ana Salomé , de la Torre Beatriz G. , Andreu David , Castanho Miguel A. R. B.
Published: January 2013

One of the major challenges in the drug development process is biodistribution across epithelia and intracellular drug targeting. Cellular membrane heterogeneity is one of the major drawbacks in developing efficient and sustainable drug delivery systems, which brings the need to study their interaction with lipids in order to unravel their mechanisms of action and improve their delivery capacities. Cell penetrating peptides (CPPs) are able to translocate almost any cell membrane carrying cargo molecules. However, different CPP use different entry mechanisms, which are often concentration‐dependent and cargo‐dependent. Being able to quantify the lipid affinity of CPP is of obvious importance and can be achieved by studying the partition extent of CPP into lipid bilayers. The partition constant (Kp) reflects the lipid–water partition extent. However, all currently available methodologies are only suitable to determine the partition of single molecules into lipid membranes or entities, being unsuitable to determine the partition of bimolecular or higher order supramolecular complexes. We derived and tested a mathematical model to determine the Kp of supramolecular CPP‐cargo complexes from fluorescence spectroscopy data, using DNA oligomers as a model cargo. As a proof‐of‐concept example, the partition extent of two new membrane active peptides derived from dengue virus capsid protein (DENV C protein) with potential CPP properties, in both scenarios (free peptide and complexed with a molecular cargo), were tested. We were able to identify the lipid affinity of these CPP:DNA complexes, thus gaining valuable insights into better CPP formulations. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Introduction of histidine units using benzotriazolide activation
Authors: Bajaj Kiran , Panda Siva S. , Ibrahim Mohamed A. , El‐Feky Said A. , Katritzky Alan R.
Published: January 2013

Nα‐Boc‐Nim‐(4‐toluenesulfonyl‐l‐histidylbenzotriazole) enables convenient acylation of N‐, O‐, S‐, and C‐nucleophiles with no detectable racemization. We report efficient syntheses of novel histidine‐containing di‐, tri‐, and tetra‐peptides and models for the preparation of potentially biologically active histidine N‐, O‐, S‐, and C‐conjugates. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Electron spin resonance of the Yb 4f‐moment in Yb(Rh1−xFex)2Si2
Authors: Sichelschmidt J. , Jeevan H. S. , Mchalwat M. , Gegenwart P.
Published: January 2013

The electron spin resonance (ESR) signal of the heavy‐fermion metal YbRh2Si2 is investigated in terms of its dependence on the partial substitution of Rh by Fe. This non‐isovalent substitution gives rise to a chemical pressure and also leads to a reduction of the conduction electron density of states (hole doping). The values and anisotropy of the ESR parameters are comparable with those of Yb(Rh1−x Cox)2Si2 for Fe‐contents up to at least 10%. This result provides additional evidence that the Kondo interaction allows narrow ESR spectra in a heavy fermion compound. The absence of an ESR signal for 30% Fe content points towards a distribution of different crystal electric field symmetries at the Yb‐sites, leading to a dominating disorder‐related broadening.
Activation of AMP‐activated Protein Kinase and Phosphorylation of Glycogen Synthase Kinase3 β Mediate Ursolic Acid Induced Apoptosis in HepG2 Liver Cancer Cells
Authors: Son Hyun‐Soo , Kwon Hee Young , Sohn Eun Jung , Lee Jang‐Hoon , Woo Hong‐Jung , Yun Miyong , Kim Sung‐Hoon , Kim Young‐Chul
Published: January 2013

Despite the antitumour effect of ursolic acid observed in several cancers, the underlying mechanism remains unclear. Thus, in the present study, the roles of AMP‐activated protein kinase (AMPK) and glycogen synthase kinase 3 beta (GSK3β) were examined in ursolic acid induced apoptosis in HepG2 hepatocellular carcinoma cells. Ursolic acid significantly exerted cytotoxicity, increased the sub‐G1 population and the number of ethidium homodimer and terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling positive cells in HepG2 cells. Also, ursolic acid enhanced the cleavages of poly‐ADP‐ribose polymerase (PARP) and caspase3, attenuated the expression of astrocyte elevated gene (AEG1) and survivin in HepG2 cells. Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells. Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells. Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased AEG‐1 induced by ursolic acid in HepG2 cells. Overall, our findings suggest that ursolic acid induced apoptosis in HepG2 cells via AMPK activation and GSK3β phosphorylation as a potent chemopreventive agent. Copyright © 2013 John Wiley & Sons, Ltd.
A System's Mean Time To Repair Allocation Method Based on the Time Factors
Authors: Dong Zhou , Chuan Lv , Yongxiang Li , Zhiqi Guo
Published: January 2013

The aim of the maintenance allocation is to allocate the maintenance time to the subsystems reasonably and accurately. Traditional mean time to repair (MTTR) allocation methods are widely used in the industry. However, there are many deficiencies in practical application, which is inconsistent with the purpose of the maintenance allocation. To allocate the MTTR more precisely and reasonably, a better model is needed. The aim of this paper is to develop a maintenance allocation model, which can improve the applicability and operability, and solve the residue problem that exists in maintenance allocation. A case study is used to demonstrate how the model can be applied in practice. Copyright © 2013 John Wiley & Sons, Ltd.
Determination of bromadiolone and brodifacoum in human hair by liquid chromatography/tandem mass spectrometry and its application to poisoning cases
Authors: Zhu Lin , Yan Hui , Shen Baohua , Shi Yan , Shen Min , Xiang Ping
Published: January 2013

RATIONALE

Bromadiolone and brodifacoum, two common anticoagulant rodenticides, are involved in the majority of anticoagulant rodenticide poisoning cases in humans in China. Hair analysis can provide long‐term information on drug exposure. A method using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed and validated for the measurement of bromadiolone and brodifacoum in human hair.

METHODS

A 1 mL aliquot of a phosphate buffer solution (pH 6.8) was added to 20 mg of pulverized hair followed by ultrasonication and liquid‐liquid extraction. Liquid chromatography was performed using a C18 column with a mobile phase gradient of ammonium acetate (10 mM) and methanol. A tandem mass spectrometer in multiple reaction monitoring mode with a negative electrospray ionization source was employed for detection. Warfarin‐d5 was used as an internal standard for both analytes.

RESULTS

The limits of detection (LODs) for bromadiolone and brodifacoum were 0.010 and 0.025 ng/mg, respectively. The calibration curves for both analytes were linear from 0.025 to 1 ng/mg. The accuracy ranged from 90.3 to 109.3%, and the intra‐day and inter‐day imprecisions were less than 15%.

CONCLUSIONS

The established method was found effective when applied to the analyses of bromadiolone or brodifacoum in five cases, indicating that segmental hair analysis could be useful for clinical and forensic purposes by identifying the time of ingestion. Copyright © 2013 John Wiley & Sons, Ltd.
Collision‐induced dissociation of aflatoxins
Authors: Tóth Katalin , Nagy Lajos , Mándi Attila , Kuki Ákos , Mézes Miklós , Zsuga Miklós , Kéki Sándor
Published: January 2013

RATIONALE

The aflatoxin mycotoxins are particularly hazardous to health when present in food. Therefore, from an analytical point of view, knowledge of their mass spectrometric properties is essential. The aim of the present study was to describe the collision‐induced dissociation behavior of the four most common aflatoxins: B1, B2, G1 and G2.

METHODS

Protonated aflatoxins were produced using atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) combined with high‐performance liquid chromatography (HPLC). For the tandem mass spectrometry (MS/MS) experiments nitrogen was used as the collision gas and the collision energies were varied in the range of 9–44 eV (in the laboratory frame).

RESULTS

The major APCI‐MS/MS fragmentations of protonated aflatoxins occurred at 30 eV collision energy. The main fragmentation channels were found to be the losses of a series of carbon monoxide molecules and loss of a methyl radical, leading to the formation of radical‐type product ions. In addition, if the aflatoxin molecule contained an ether‐ or lactone‐oxygen atom linked to a saturated carbon atom, loss of a water molecule was observed from the [M + H]+ ion, especially in the case of aflatoxins G1 and G2.

CONCLUSIONS

A relatively small modification in the structure of aflatoxins dramatically altered the fragmentation pathways and this was particularly true for aflatoxins B1 and B2. Due to the presence of a C = C double bond connected to the ether group in aflatoxin B1 no elimination of water was observed but, instead, formation of radical‐type product ions occurred. Fragmentation of protonated aflatoxin B1 yielded the most abundant radical‐type cations. Copyright © 2013 John Wiley & Sons, Ltd.
Genomics and epigenomics of colorectal cancer
Authors: Schweiger Michal‐Ruth , Hussong Michelle , Röhr Christina , Lehrach Hans
Published: January 2013

Colorectal cancer is one of the most common cancer types worldwide and accounts for approximately 600,000 deaths annually. Work over the last decades has uncovered a number of tumor‐suppressor and oncogenes which are frequently mutated and might thus be responsible for the malignant transformation. However, only with the development of new high‐throughput technologies systematic analyses of the genome and epigenomes became feasible. While data generation has increased exponential, we are now faced with new challenges to transform these data into useful models that help predicting the outcome of genomic aberrations and to develop novel diagnostic and therapeutic strategies. As a basis for the modeling it is essential to understand and integrate current knowledge. We review previous and current ideas in colorectal cancer development and focus on a pathway oriented view. We show that colorectal cancer is a multilayer complex disease affecting the genome as well as the epigenome with direct consequences on the gene and microRNA (miRNA) expression signatures. The goal is to illustrate the current principles of colorectal cancer pathogenesis and to illustrate the need for elaborate computer modeling systems. WIREs Syst Biol Med 2013, 5:205–219. doi: 10.1002/wsbm.1206

This article is categorized under:

Analytical and Computational Methods > Analytical Methods

Laboratory Methods and Technologies > Genetic/Genomic Methods

Translational, Genomic, and Systems Medicine > Therapeutic Methods

Translational, Genomic, and Systems Medicine > Translational Medicine
How Many Contralateral Papillary Thyroid Carcinomas Can Be Missed?
Authors: Lee Kwan Ju , Cho Yun Jung , Kim Jeong Goo , Lee Dong Ho
Published: January 2013

Background

When surgeons decide to perform lobectomy as the treatment of papillary thyroid carcinomas (PTCs), they must consider the possibility of contralateral cancer. We wanted to determine the incidence of bilateral PTCs (bPTCs) and analyze their characteristics. We also wanted to determine how many patients with bPTC were missed preoperatively.

Methods

From January 2007 to May 2011, a total of 466 patients with PTC who were treated by total thyroidectomy at a single institution were enrolled. Patients were divided into two groups based on bilaterality. The patients with bPTCs were further investigated regarding the preoperative presence of the contralateral tumor.

Results

Bilaterality was seen in 29.8 % of PTC patients. In all, 36.8 % of PTCs ≥1 cm, and 25.7 % were papillary thyroid microcarcinomas (PTMCs). The presence of PTC in the contralateral lobe was missed in 15.8 % of bPTCs and in 21.3 % of bPTMCs. The rates of preoperatively nondetected contralateral cancer were 4.7 and 5.5 % for PTCs and PTMCs, respectively. Tumor size and multifocality were factors associated with bilaterality (p = 0.014 and p < 0.001, respectively).

Conclusions

Bilaterality is found more frequently when the tumor is large. Multifocality also can help predict the possibility of bilaterality. Therefore, total thyroidectomy may be necessary for patients with a multifocal or large tumor. It should be noted that the presence of a contralateral cancer is missed in 4.7 and 5.5 % of patients with preoperatively diagnosed unilateral PTC and PTMC, respectively.
Allocleaning behavior by the sentinel crab Macrophthalmus banzai: a case of mutual cooperation
Authors: Fujishima Yurika , Wada Keiji
Published: January 2013

The macrophthalmid crab Macrophthalmus banzai performs allocleaning behavior, in which an individual feeds off the carapace or walking legs of a conspecific male or female. Cleaning continues until the recipient (‘cleanee’) rejects the cleaning or the cleaner ceases cleaning. In cases where the recipient did not reject the cleaning, the cleanee often retreated to its own burrow site after the cleaner ceased cleaning, allowing the cleaner to feed on its territory. We suggest that this is mutual cooperation, in which the cleaner assists the recipient to clean the body surface, and the recipient in return provides a feeding ground for the cleaner. Using field observation, we explored the factors responsible for the retreat of the cleanee in response to the cleaning behavior. Factors influencing the retreat of the cleanee were the time of the cleaning incident relative to low tide, the cleanee’s position relative to its own burrow, and the duration of the cleaning bout. The third factor showed that retreat was more common when the cleaning was thorough, which suggests that allocleaning is a form of mutual cooperation in M. banzai.
Localization of Rab proteins to peroxisomes: A proteomics and immunofluorescence study
Authors: Gronemeyer Thomas , Wiese Sebastian , Grinhagens Sören , Schollenberger Lukas , Satyagraha Ari , Huber Lukas A. , Meyer Helmut E. , Warscheid Bettina , Just Wilhelm W.
Published: January 2013

Rab10 and Catalase colocalize by fluorescence microscopy (View interaction)