bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Polyphenolic Compounds from Black Tea for the Solid Phase Extraction and Determination of Trace Iron in Drinking Water
Authors: Farhadi Khalil , Maleki Ramin , Nikkhahi Yousef
Published: January 2010

A simple and selective solid phase extraction procedure for the trace analysis of iron(III) in water samples has been developed. Sodium dodecyl sulfate coated alumina, modified with polyphenolic compounds (extracted from black tea) was used for the extraction and preconcentration of iron(III) from water samples before determination by flame atomic absorption spectrometry. Due to the complexation reaction between iron(III) and polyphenol compounds, iron(III) was quantitatively extracted on the proposed sorbent and then eluted by 2.0 mL of HCl (1.0 mol/L). The effects of extraction parameters, such as pH and volume of sample solution, amount of polyphenolic compounds, type of eluting agent and the effect of interfering ions on the extraction of iron(III), were investigated. It was found that the proposed method had a good linear range (15.0–100.0 μg/L) and a low detection limit (10.0 μg/L). The procedure was successfully applied for iron determination in drinking water samples.
Development of an Advanced Biological Treatment System Using Bioaugmentation Technology for the Treatment of Eutrophic Drinking Water Resources
Authors: Meng Zhi‐Qi , Zhao Yi , Lu Zhen‐Mei , Min Hang , Shen Jin‐Wen , Xu Xiang‐Yang
Published: January 2010

Drinking water supplies around the world are increasingly at risk from eutrophication. However, many of the technologies developed in the laboratory to control water eutrophication have not been successfully applied in situ. To explore an in situ water treatment strategy for treating eutrophic drinking water resources, a laboratory system simulating a real river way was designed and used to treat raw eutrophic drinking water. The system included several removable modules and bioaugmentation technology to ensure the formation and maintenance of the biofilm, and enhance treatment efficiency. During operation of the system, the biofilm was successfully formed and maintained under a continuous hydraulic shock loading up to 14.4 m3 m–2 d–1, and the average removal rates of chlorophyll a, TN, and TP were 83.85, 53.44 and 70.78%, respectively. The biofilm had a high phosphorus storage capacity, even when phosphorus loading increased to 15–20 mg/L, the removal was constant at around 10 mg/L. Moreover, PCR‐DGGE analysis demonstrated that the bioaugmented bacteria, including Flavobacterium and Pseudomonas, successfully colonized the biofilm inside the system. Furthermore, the original community of microorganisms from the raw drinking water was maintained, which is an important aspect of the in situ treatment process. In conclusion, this strategy successfully treated raw eutrophic drinking water in the simulated river way. Its efficacy, low operation cost and application to water safety make this system a promising prospect for controlling eutrophication of drinking water resources.
Removal of Selenium by Adsorption onto Granular Activated Carbon (GAC) and Powdered Activated Carbon (PAC)
Authors: Wasewar Kailas L. , Prasad Basheshwar , Gulipalli Sekhararao
Published: January 2010

The present work involves the study of Se(IV) adsorption onto granular activated carbon (GAC) and powdered activated carbon (PAC). The adsorbents are coated with ferric chloride solution for the effective removal of selenium. The physico‐chemical characterization of the adsorbents is carried out using standard methods, e. g., proximate analysis, scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), thermo‐gravimetric (TGA) and differential thermal analysis (DTA), etc. The FTIR spectra of the GAC and PAC indicate the presence of various types of functional groups, e. g., free and hydrogen bonded OH groups, silanol groups (Si‐OH), alkenes, and CO group stretching from aldehydes and ketones on the surface of adsorbents. Batch experiments are carried out to determine the effect of various factors such as adsorbent dose (w), initial pH, contact time (t), and temperature (T) on the adsorption process. The optimum GAC and PAC dosage is found to be 10 g/L and 8 g/L, respectively, for Se(IV) removal with C0 = 100 mg/L. The percent removal of Se(IV) increases with increasing adsorbent concentration, while removal per unit weight of adsorbent increases with decreasing adsorbent concentration. Se(IV) adsorption onto both the GAC and PAC adsorbents is high at low pH values, and decreases with increased initial pH. The results obtained are analyzed by various kinetic models. The parameters of pseudo‐first order, pseudo‐second order kinetics, and Weber‐Morris intra particle kinetics are determined. It is seen that the sorption kinetics of Se(IV) onto GAC and PAC can be best represented by the pseudo‐second order kinetic model.
Pyrrolidine Derivatives as Plasmepsin Inhibitors: Binding Mode Analysis Assisted by Molecular Dynamics Simulations of a Highly Flexible Protein
Authors: Luksch Torsten , Blum Andreas , Klee Nina , Diederich Wibke E. , Sotriffer Christoph A. , Klebe Gerhard
Published: January 2010

Plasmepsins II (EC number: 3.4.23.39) and IV (EC number: 3.4.23.B14) are aspartic proteases present in the food vacuole of the malaria parasite Plasmodium falciparum and are involved in host hemoglobin degradation. A series of pyrrolidine derivatives, originally synthesized as HIV‐1 protease inhibitors, were tested for activity against plasmepsin (Plm). Inhibitors in the nanomolar range were discovered for the Plm II and IV isoforms. Detailed studies were carried out to identify putative binding modes that help to explain the underlying structure–activity relationships. Reasonable binding modes were generated for pyrrolidine‐3,4‐diester derivatives and a substituted 3,4‐diaminopyrrolidine inhibitor by using a crystal structure of inhibitor‐bound Plm II (PDB ID: 1LEE). Modeling studies indicated that the flap of available Plm crystal structures is not sufficiently opened to accommodate the 3,4‐bis(aminomethylene)pyrrolidines. Molecular dynamics simulations were performed to analyze the flexibility of the protein in greater detail, leading to a binding mode hypothesis for the 3,4‐bis(aminomethylene)pyrrolidines and providing further insight and general implications for the design of Plm II inhibitors.
High Energy Density Physics with Heavy Ion Beams and related Interaction Phenomena
Authors: Hoffmann D.H.H. , Tahir N.A. , Udrea S. , Rosmej O. , Meister C.V. , Varentsov D. , Roth M. , Schaumann G. , Frank A. , Blazevic A. , Ling J. , Hug A. , Menzel J. , Hessling Th. , Harres K. , Günther M. , El‐Moussati S. , Schumacher D. , Imran M.
Published: January 2010

High intensity particle beams from accelerators induce high energy density states in bulk matter. Due to the specific nature of the ion‐matter interaction a volume of matter is heated uniformly with low gradients of temperature and pressure in the initial phase, depending on the pulse structure of the beam with respect to space and time. We present an overview on recent results and developments of beam plasma, and beam matter interaction experiments with heavy ion and laser beams (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Resonant Penetration of a Circularly Polarized Femtosecond Laser Pulse Through Ultra‐Thin Foils
Authors: Bordyukh N.V. , Krainov V.P.
Published: January 2010

We develop the theory of penetration of an intense femtosecond laser pulse through ultra‐thin metal foils. When the electron excursion length in laser field exceeds the foil thickness we cannot use the hydrodynamic approach, i.e. there is no dielectric constant of the foil, and well known macroscopic Fresnel formulas are inapplicable. We solve the Vlasov selfconsistent equations for the electromagnetic field inside the foil collisionless plasma. In the case of the linearly polarized laser field such a problem has been solved recently. Our current goal is the circularly polarized laser field since the electron velocities in this case are much greater than that for linearly polarized field. We found that the resonance peaks in the penetrations of radiation through the foil appear at definite foil thicknesses (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stability of LiF Crystal in the Warm Dense Matter State
Authors: Stegailov V.V.
Published: January 2010

The finite temperature density functional theory approach is deployed for the description of the fcc LiF crystal in a two‐temperature warm dense matter state with hot electrons and cold lattice that is formed after ultrafast energy deposition. The lattice stability and the interatomic bonding at elevated electronic temperatures are studied (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantum Kinetic Approach to Time‐Resolved Photoionization of Atoms
Authors: Bonitz M. , Hochstuhl D. , Bauch S. , Balzer K.
Published: January 2010

Theoretical approaches to the photoionization of few‐electron atoms are discussed. These include nonequilibrium Greens functions and wave function based approaches. In particular, the Multiconfiguration Time‐Dependent Hartree‐Fock method is discussed and applied to model a one‐dimensional atom with four electrons. We compute ground state energies and the time‐dependent photoionization by the field a strong laser pulse with two different frequencies in the ultraviolet (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamic Properties of One‐Component Moderately Coupled Plasmas: The Mixed Löwner‐Nevanlinna‐Pick Approach
Authors: Arkhipov Yu.V. , Askaruly A. , Davletov A.E. , Tkachenko I.M.
Published: January 2010

Dynamic characteristics of strongly coupled one‐component plasmas are studied within the moment approach with local constraints, similar to that of Schur. The dynamic structure factor is modeled by the.rst three terms of its asymptotic decomposition at high frequencies and its values at a few interpolation points on the real axis. This makes the dynamic structure factor to be a non‐rational function whose extension onto the upper half‐plane of complex frequency is holomorphic with a nonnegative imaginary part and a continuous extension to the real axis. A free parameter of the non‐rational model function of the suggested Schur‐like algorithm is obtained from the Shannon entropy maximization procedure.

The results automatically satisfy not only the sum rules and other exact relations but, also, interpolate between the interpolation frequencies. A quantitative agreement is obtained with simulation data on the plasma dynamic properties. The method permits to take into account the energy dissipation processes so that the results of alternative theoretical approaches are included into the moment scheme and are complemented. The algorithm tested herewith can also be used in a broader setting (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Equation of State of Shock Compressed Hydrogen
Authors: Gryaznov V. K. , Iosilevskiy I. L. , Fortov V. E.
Published: January 2010

Model SAHA‐D based on chemical picture for equation of state of warm dense hydrogen is presented. Coulomb corrections are used via a modified pseudopotential model. Intense short‐range repulsion of neutral particles is described in simplified form (soft sphere model). The results of calculations of principal Hugoniots and double shock are compared with experiments and the first principle calculations. Asymptotic properties of the model at high temperature limit are considered (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermodynamic Functions of Dense Plasmas: Analytic Approximations for Astrophysical Applications
Authors: Potekhin A. Y. , Chabrier G.
Published: January 2010

We briefly review analytic approximations of thermodynamic functions of fully ionized nonideal electronion plasmas, applicable in a wide range of plasma parameters, including the domains of nondegenerate and degenerate, nonrelativistic and relativistic electrons, weakly and strongly coupled Coulomb liquids, classical and quantum Coulomb crystals. We present improvements to previously published approximations. Our code for calculation of thermodynamic functions based on the reviewed approximations is made publicly available (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Account of Atomic and Molecular Contributions in the Equation of‐State for a Weakly Non‐Ideal Hydrogen Plasmas
Authors: Starostin A. N. , Roerich V. C.
Published: January 2010

Convergent partition function for atomic and molecular bound states is derived for weakly non‐ideal hydrogen plasmas. Corrections due to charged‐neutral particles interactions are also described. These contributions have been realized in the model equation of state of hydrogen plasmas and the HEOS code. The physical model EOS also includes the Coulomb and diffraction corrections, contributions of the scattering states, electron and ion interactions, and the radiation pressure. The calculated dependences of the heat capacity, the ionization degree, and partial pressures are presented (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sec61α is required for dorsal closure during Drosophila embryogenesis through its regulation of Dpp signaling
Authors: Wang Xiaochen , Ward Robert E.
Published: January 2010

During dorsal closure in Drosophila, signaling events in the dorsalmost row of epidermal cells (DME cells) direct the migration of lateral epidermal sheets towards the dorsal midline where they fuse to enclose the embryo. A Jun amino‐terminal kinase (JNK) cascade in the DME cells induces the expression of Decapentaplegic (Dpp). Dpp signaling then regulates the cytoskeleton in the DME cells and amnioserosa to affect the cell shape changes necessary to complete dorsal closure. We identified a mutation in Sec61α that specifically perturbs dorsal closure. Sec61α encodes the main subunit of the translocon complex for co‐translational import of proteins into the ER. JNK signaling is normal in Sec61α mutant embryos, but Dpp signaling is attenuated and the DME cells fail to maintain an actinomyosin cable as epithelial migration fails. Consistent with this model, dorsal closure is rescued in Sec61α mutant embryos by an activated form of the Dpp receptor Thick veins. Developmental Dynamics 239:784–797, 2010. © 2010 Wiley‐Liss, Inc.
Wnt modulators in the biotech pipeline
Authors: Rey Jean‐Philippe , Ellies Debra L.
Published: January 2010

The original article to which this Erratum refers was published in Developmental Dynamics 239:102–114
A Theoretical Insight into the Mechanism of the Silver‐Catalysed Transsiliranation Reaction
Authors: Mayoral José Antonio , Rodríguez‐Rodríguez Sergio , Salvatella Luis
Published: January 2010

DFT calculations on a silver‐catalysed transsiliranation reaction (silylene transfer from a silirane to an alkene) have shown the key role of a silylenesilver ion in the catalyticcycle. Although the corresponding triflate‐bound species has previously been detected by NMR and IR spectroscopy, no significant silylene‐transfer activity is predicted for such a nonionised structure. Several experimental results can be explained by this new reaction mechanism.
PCR‐product microarray based on polyacrylic acid‐modified surface for SNP genotyping
Authors: Shi Xiaolong , Tang Chao , Zhou Dequan , Sun Jinxia , Lu Zuhong
Published: January 2010

PCR‐product microarray has great efficiency in SNP genotyping, mutation screening and epigenetic analyzing from a large number of samples. The current PCR‐product microarray technology is mostly based on the 3‐D gel microarray technologies due to its high loading capacity for PCR products, while there is little progress for PCR‐product microarray on planar glass, which gives low background and convenient fabrication. In this study, we improved the PCR‐product microarray on planar glass by employing a polyacrylic acid‐covered slide. The raw amino‐modified PCR products were simply precipitated with ethanol and directly spotted for DNA immobilization. Three detection methods of hybridization, solid‐single base extension and solid‐multiple bases elongation were carried out for single nucleotide variation identification on the PCR‐product microarray. The experimental results showed that the high immobilization yield for raw PCR product was achieved, and the high specificity and high ratio of S/N for genotyping on the microarray were obtained. SNP genotyping of cytochrome P450 2D6 gene in 30 individuals was successfully demonstrated. This study has significantly increased the performances of PCR‐product microarray, which could improve its applications in SNP genotyping and mutation screening in large number of individuals.
Immobilized pH gradients
Authors: Gianazza Elisabetta , Righetti Pier Giorgio
Published: January 2010

In this short review, we give an account of the steps through which the protocols for operation with IPGs were set up in the early '80s. One of the main achievements by our group was the development of a computer program, pH GRADIENT, for the calculation of pH, buffering power and ionic strength of a mixture of monoprotic buffers titrated within any pH span and for the linearization of the desired pH gradient. Using this program, in 1984 we could devise formulations for IPGs covering up to six pH units, which was the subject of a publication in Electrophoresis (volume 5, pages 88–97). This was the starting point for the use of IPGs for the resolution of protein samples of any composition and for their application as first dimension of 2‐DE separations. Currently IPGs are in common use in proteomics investigations, not only along classical protocols but also for sample prefractionation and in shotgun approaches. Much less frequently are they used for 1‐DE analytical applications, a field for which in recent years much attention has instead more often focused on capillary electrophoresis/IEF procedures.
CEC: Selected developments that caught my eye since the year 2000
Authors: Svec Frantisek
Published: January 2010

During the last decade, a number of new developments have emerged in the field of CEC. This paper focuses only on monolithic columns prepared from synthetic polymers. Monolithic columns have become a well‐established format of stationary phases for CEC immediately after their inception in the mid‐1990s. They are readily prepared in situ from liquid precursors. Also, the control over both porous properties and surface chemistries is easy to achieve. These advantages make the monolithic separation media an attractive alternative to capillary columns packed with particulate materials. Since the number of papers concerned with just this single topic of polymer‐based monolithic CEC columns is large, this overview describes only those approaches this author found interesting.
Separation of enantiomers with charged chiral selectors in CE
Authors: Chankvetadze Bezhan
Published: January 2010

In this short overview the major developments in separation of enantiomers with charged chiral selectors are summarized in CE. The advantages of charged chiral selectors in comparison with their uncharged analogues are emphasized from the viewpoints of higher flexibility, higher and alternative separation selectivity, as well as alternative chiral recognition mechanism.
Recent significant developments in detection and method development for the determination of inorganic ions by CE
Authors: Johns Cameron , Breadmore Michael C. , Macka Mirek , Ryvolová Markéta , Haddad Paul R.
Published: January 2010

CE has been available as a tool for almost 20 years, but it is only in the past several years that it has been implemented widely. This has been the result of some significant advances in the technique. These fall in the areas of indirect photometric detection (through the use of dyes as probes and LEDs as light sources), the introduction and establishment of capacitively‐coupled contactless conductivity detection (C4D) as a routine, sensitive and commercially available detection method, and in software capable of simulation of separations and the selection of optimal composition of the BGE. These developments are reviewed and their impact illustrated by reference to a case study involving the rapid separation and sensitive detection of 15 anions and 12 cations on a portable CE instrument. It is shown that C4D provides considerably superior detection sensitivity (by a factor of about 8 in comparison with optimised indirect photometry).
Automated comparative protein structure modeling with SWISS‐MODEL and Swiss‐PdbViewer: A historical perspective
Authors: Guex Nicolas , Peitsch Manuel C. , Schwede Torsten
Published: January 2010

SWISS‐MODEL pioneered the field of automated modeling as the first protein modeling service on the Internet. In combination with the visualization tool Swiss‐PdbViewer, the Internet‐based Workspace and the SWISS‐MODEL Repository, it provides a fully integrated sequence to structure analysis and modeling platform. This computational environment is made freely available to the scientific community with the aim to hide the computational complexity of structural bioinformatics and encourage bench scientists to make use of the ever‐increasing structural information available. Indeed, over the last decade, the availability of structural information has significantly increased for many organisms as a direct consequence of the complementary nature of comparative protein modeling and experimental structure determination. This has a very positive and enabling impact on many different applications in biomedical research as described in this paper.
Organic solvents in CE
Authors: Kenndler Ernst
Published: January 2010

In this contribution some fundamental aspects are discussed serving for a critical reflection and elucidation of the role of organic solvents in CE. The implications of the solvent on the parameters governing peak resolution are discussed based on the concepts describing migration and zone broadening in capillary zone electrophoresis. This discussion includes the solvent‐dependent influence of the ionic strength on the mobility. The role of the solvent on the plate number in case of the inevitable diffusional peak dispersion is outlined, and its effect on other peak broadening contributions is briefly examined. This paper also deals with the problems of conductance, applicable voltage and analysis time upon application of organic solvents, and tries to clarify some misunderstandings common in the literature.
DNA sequencing by CE
Authors: Karger Barry L. , Guttman András
Published: January 2010

Sequencing of human and other genomes has been at the center of interest in the biomedical field over the past several decades and is now leading toward an era of personalized medicine. During this time, DNA‐sequencing methods have evolved from the labor‐intensive slab gel electrophoresis, through automated multiCE systems using fluorophore labeling with multispectral imaging, to the “next‐generation” technologies of cyclic‐array, hybridization based, nanopore and single molecule sequencing. Deciphering the genetic blueprint and follow‐up confirmatory sequencing of Homo sapiens and other genomes were only possible with the advent of modern sequencing technologies that were a result of step‐by‐step advances with a contribution of academics, medical personnel and instrument companies. While next‐generation sequencing is moving ahead at breakneck speed, the multicapillary electrophoretic systems played an essential role in the sequencing of the Human Genome, the foundation of the field of genomics. In this prospective, we wish to overview the role of CE in DNA sequencing based in part of several of our articles in this journal.
Immobilization of acetylcholinesterase in nanofibrous PVA/BSA membranes by electrospinning
Authors: Moradzadegan Atousa , Ranaei‐Siadat Seyed‐Omid , Ebrahim‐Habibi Azadeh , Barshan‐Tashnizi Mohammad , Jalili Rouhollah , Torabi Seyed‐Fakhraddin , Khajeh Khosro
Published: January 2010

Electrospinning, a simple and versatile method to fabricate nanofibrous supports, has attracted continuous attention in the field of enzyme immobilization. In this study, acetylcholinesterase (AChE) has been successfully immobilized in PVA nanofibers via electrospinning of a mixture of AChE, BSA as an enzyme stabilizing additive and PVA. The maximum activity recovery of immobilized AChE was about 40%. In comparison with free enzyme, the immobilized AChE showed improved stability while retaining a considerable amount of activity at lower pH values. Moreover, the immobilized AChE retained >34% of its initial activity when stored at 30°C for 100 days and retained 70% of its initial activity after ten consecutive reactor batch cycles.
Quantification and potential aroma contribution of β‐ionone in marine salt
Authors: Silva Isabel , Rocha Sílvia M. , Coimbra Manuel A.
Published: January 2010

A methodology for quantification of β‐ionone in marine salt was developed using the headspace solid phase microextraction and gas chromatography–quadrupole mass spectrometry (HS–SPME/GC–qMS). Quantification of β‐ionone was achieved by linear regression from an analytical plot of pure standard using the target ion at m/z 177 by ion extraction chromatography (IEC). HS–SPME/GC–qMS combined with IEC mode allowed quantification of trace levels (ng/l) of β‐ionone in marine salt aqueous solutions. The methodology developed presented a good linearity (R2 = 0.981) for the range of concentrations used (16 a 568 ng/l) and a good reproducibility (15%), with limits of detection and quantification of 9 and 29 ng/l, respectively. This methodology was applied to marine salt from different geographical origins (Portugal, France, and Cape Verde). Estimated concentrations of β‐ionone in marine salt varied from 241 to 888 ng/kg of salt. The highest values were found for Aveiro, in Portugal, and Guérande, in France, in environments surrounded by a large number of plant and algae diversity. However, in Castro Marim and Tavira (in Algarve, South of Portugal), this compound was not found. According to the odour threshold of β‐ionone in water (30 ng/l), aqueous solutions with more than 100 g/l of marine salt can exhibit a violet odour. Similar conditions can occur in the ponds with higher levels of salinity of the traditional saltpans. This methodology proved to be a useful tool for screening and quantification of β‐ionone, a compound shown to present potential contribution to marine salt aroma. Copyright © 2010 John Wiley & Sons, Ltd.
A finite element immersed boundary method for fluid flow around rigid objects
Authors: Ilinca F. , Hétu J.‐F.
Published: January 2010

This paper proposes a new immersed boundary (IB) method for solving fluid flow problems in the presence of rigid objects which are not represented by the mesh. Solving the flow around objects with complex shapes may involve extensive meshing work that has to be repeated each time a change in the geometry is needed. Important benefit would be reached if we are able to solve the flow without the need of generating a mesh that fits the shape of the immersed objects. This work presents a finite element IB method using a discretization covering the entire domain of interest, including the volume occupied by immersed objects, and which produces solutions of the flow satisfying accurately the boundary conditions at the surface of immersed bodies. In other words the finite element solution represents accurately the presence of immersed bodies while the mesh does not. This is done by including additional degrees of freedom on interface cut elements which are then eliminated at element level. The boundary of immersed objects is defined using a level set function. Solutions are shown for various flow problems and the accuracy of the present approach is measured with respect to solutions obtained on body‐fitted meshes. Copyright © 2010 Crown in the right of Canada.
Increased Fructose Consumption Is Associated With Fibrosis Severity in Patients With Nonalcoholic Fatty Liver Disease
Authors: Abdelmalek Manal F. , Suzuki Ayako , Guy Cynthia , Unalp-Arida Aynur , Colvin Ryan , Johnson Richard J. , Diehl Anna Mae
Published: January 2010

The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency × amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (≥7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (

P

< 0.0001), male sex (

P

< 0.0001), hypertriglyceridemia (

P

< 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (

P

< 0.001), increased calorie intake (

P

< 0.0001), and hyperuricemia (

P

< 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (

P

< 0.05 for each). In older adults (age ≥ 48 years), daily fructose consumption was associated with increased hepatic inflammation (

P

< 0.05) and hepatocyte ballooning (

P

= 0.05).

Conclusion

: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD. Hepatology 2010
Forkhead Box P3+ Regulatory T Cell Underlies Male Resistance to Experimental Type 2 Autoimmune Hepatitis
Authors: Lapierre Pascal , Béland Kathie , Martin Caroline , Alvarez Fernando , Alvarez Fernando
Published: January 2010

Autoimmune hepatitis (AIH), like many autoimmune diseases, is most prevalent in young women. The immunological basis of this age and sex susceptibility bias was investigated in a murine model of AIH. Xenoimmunization of 7-week-old female C57BL/6 mice resulted in more severe AIH with higher levels of liver inflammation, serum alanine aminotransferase, specific T-cell cytotoxicity, and autoantibody than younger and older females. Vaccinated males developed minimal liver inflammation and higher percentages of CD4+CD25+FoxP3+ regulatory T cell in peripheral blood mononuclear cells, spleen, and liver than females. Regulatory T cells (Tregs) were virtually absent in liver-lymphocytes infiltrates of females. Castration of C57BL/6 mice, with or without 17β-estradiol supplementation, did not modify susceptibility in males, nor Treg numbers, suggesting minimal contribution of testosterone and estradiol to autoimmune hepatitis (AIH) susceptibility. Xenoimmunized

Aire

(+/0) mouse displayed similar AIH susceptibility, sex bias, and Tregs numbers as C57BL/6 mice, suggesting that susceptibility in females is not the result of less stringent thymic central tolerance. Autoreactive B cell response against formiminotransferase-cyclodeaminase correlated with disease activity, possibly linking B-cell autoreactivity and AIH pathogenesis.

Conclusion

: Peripheral tolerance and development of regulatory T cells after self-mimicking antigen exposure, and not sexual hormone nor central tolerance, are the main factors for susceptibility to AIH in females. Hepatology 2010
Atp8b1 and Abcb11 Analysis in 62 Children With Normal Gamma-Glutamyl Transferase Progressive Familial Intrahepatic Cholestasis (Pfic): Phenotypic Differences Between Pfic1 and Pfic2 and Natural History
Authors: Davit-Spraul Anne , Fabre Monique , Branchereau Sophie , Baussan Christiane , Gonzales Emmanuel , Stieger Bruno , Bernard Olivier , Jacquemin Emmanuel
Published: January 2010

Progressive familial intrahepatic cholestasis (PFIC) types 1 and 2 are characterized by normal serum gamma-glutamyl transferase (GGT) activity and are due to mutations in

ATP8B1

(encoding FIC1) and

ABCB11

(encoding bile salt export pump [BSEP]), respectively. Our goal was to evaluate the features that may distinguish PFIC1 from PFIC2 and ease their diagnosis. We retrospectively reviewed charts of 62 children with normal-GGT PFIC in whom a search for

ATP8B1

and/or

ABCB11

mutation, liver BSEP immunostaining, and/or bile analysis were performed. Based on genetic testing, 13 patients were PFIC1 and 39 PFIC2. The PFIC origin remained unknown in 10 cases. PFIC2 patients had a higher tendency to develop neonatal cholestasis. High serum alanine aminotransferase and alphafetoprotein levels, severe lobular lesions with giant hepatocytes, early liver failure, cholelithiasis, hepatocellular carcinoma, very low biliary bile acid concentration, and negative BSEP canalicular staining suggest PFIC2, whereas an absence of these signs and/or presence of extrahepatic manifestations suggest PFIC1. The PFIC1 and PFIC2 phenotypes were not clearly correlated with mutation types, but we found tendencies for a better prognosis and response to ursodeoxycholic acid (UDCA) or biliary diversion (BD) in a few children with missense mutations. Combination of UDCA, BD, and liver transplantation allowed 87% of normal-GGT PFIC patients to be alive at a median age of 10.5 years (1-36), half of them without liver transplantation.

Conclusion:

PFIC1 and PFIC2 differ clinically, biochemically, and histologically at presentation and/or during the disease course. A small proportion of normal-GGT PFIC is likely not due to

ATP8B1

or

ABCB11

mutations. (Hepatology 2010)
Determination of Immune Memory to Hepatitis B Vaccination Through Early Booster Response in College Students
Authors: Jan Chyi-Feng , Huang Kuo-Chin , Chien Yin-Chu , Greydanus Donald E. , Davies Dele H. , Chiu Tai-Yuan , Huang Li-Min , Chen Chien-Jen , Chen Ding-Shinn
Published: January 2010

The long-term protection of hepatitis B (HB) vaccination has been debated for years. The purpose here was to evaluate the kinetic changes of antibody to HB surface antigen (anti-HBs) and define immune memory of the HB vaccine among college students who had previously received full neonatal immunization against HB. In all, 127 college students aged 18-23 years born after July 1984 who had completed HB vaccination and were seronegative for all three HB viral markers, including HB surface antigen (HBsAg), antibody to HB core protein (anti-HBc), and anti-HBs, were recruited. They received three doses of HB vaccine at enrollment, 1 month and 6 months after enrollment. Their anti-HBs titers were assayed at enrollment, 7-10 days, 1 month, 6 months, and 7 months following the first dose of HB vaccine. The anti-HBs seroprotective rates for subjects 7-10 days, 1 month, 6 months, and 7 months postvaccination were 20.5%, 75.6%, 94.5%, and 99.2%, respectively. Those who were seroprotective at 7 to 10 days after one dose of HB vaccine booster developed significantly higher levels of anti-HBs at 1 and 6 months than those not developing seroprotective anti-HBs response at an earlier timepoint.

Conclusion:

At least one-quarter of HB vaccinees have lost their immune memory to the HB vaccine when entering college. Immune memory to HB vaccine was identified by early seroconversion, which was present in only 20% of vaccinees in the present study. To ensure higher than 90% anti-HBs seroconversion rates, at least 2 doses of HB booster vaccines are recommended for at-risk youths who received complete HB vaccinations in neonatal or infant periods but are seronegative for HBsAg, anti-HBs, and anti-HBc in adolescence. (Hepatology 2010;)
Hepatic Glycosphingolipid Deficiency and Liver Function in Mice
Authors: Jennemann Richard , Rothermel Ulrike , Wang Shijun , Sandhoff Roger , Kaden Sylvia , Out Ruud , van Berkel Theo J. , Aerts Johannes M. , Ghauharali Karen , Sticht Carsten , Gröne Hermann-Josef
Published: January 2010

Recent studies have reported that glycosphingolipids (GSLs) might be involved in obesity-induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin resistance accompanied by improved glycemic control and decreased liver steatosis in obese mice. In addition, pharmacologic GSL depletion altered hepatic secretory function. In those studies, ubiquitously acting inhibitors for GSL biosynthesis have been used to inhibit the enzyme Ugcg (UDP-glucose:ceramide glucosyltransferase), catalyzing the first step of the glucosylceramide-based GSL-synthesis pathway. In the present study a genetic approach for selective GSL deletion in hepatocytes was chosen to achieve complete inhibition of GSL synthesis and to avoid possible adverse effects caused by Ugcg inhibitors. Using the Cre/loxP system under control of the albumin promoter, GSL biosynthesis in hepatocytes and their release into the plasma could be effectively blocked. Deletion of GSL in hepatocytes did not change the quantity of bile excretion through the biliary duct. Total bile salt content in bile, feces, and plasma from mutant mice showed no difference as compared to control animals. Cholesterol concentration in liver, bile, feces, and plasma samples remained unaffected. Lipoprotein concentrations in plasma samples in mutant animals reached similar levels as in their control littermates. No alteration in glucose tolerance after intraperitoneal application of glucose and insulin appeared in mutant animals. A preventive effect of GSL deficiency on development of liver steatosis after a high-fat diet was not observed.

Conclusion

: The data suggest that GSL in hepatocytes are not essential for sterol, glucose, or lipoprotein metabolism and do not prevent high-fat diet-induced liver steatosis, indicating that Ugcg inhibitors exert their effect on hepatocytes either independently of GSL or mediated by other (liver) cell types. Hepatology 2010
Maternal behaviour and children's early emotion regulation skills differentially predict development of children's reactive control and later effortful control
Authors: Graziano Paulo A. , Keane Susan P. , Calkins Susan D.
Published: February 2010

The role of maternal behaviour and children's early emotion regulation skills in the development of children's reactive control, specifically behavioural impulsivity, and later effortful control was examined in a sample of 435 children. HLM analyses indicated significant growth in reactive control across the toddlerhood to early childhood period. Emotion regulation at age‐2 positively predicted initial levels of children's reactive control abilities while maternal overcontrol/intrusiveness predicted lower levels of reactive control growth. Maternal behaviours at age‐2 predicted children's effortful control abilities at age‐5.5. Emotion regulation did not predict effortful control abilities. Maternal behaviour and children's early emotion regulation skills may differentially facilitate the development of reactive and effortful control abilities. Copyright © 2010 John Wiley & Sons, Ltd.
Metronomic administration of the drug GMX1777, a cellular NAD synthesis inhibitor, results in neuroblastoma regression and vessel maturation without inducing drug resistance
Authors: Fuchs Dieter , Rodriguez Alejandro , Eriksson Sara , Christofferson Rolf , Sundberg Christian , Azarbayjani Faranak
Published: January 2010

High‐risk neuroblastoma is a rapidly growing tumor with a survival rate below 50%. A new treatment strategy is to administer chemotherapeutic drugs metronomically, i.e., at lower doses and frequent intervals. The aim of the study was to investigate the effects of GMX1777, a chemotherapeutic drug affecting cellular energy metabolism, in a mouse model for high‐risk neuroblastoma. Female SCID mice were injected s.c. with MYCN‐amplified human neuroblastoma cells and randomized to either treatment with GMX1777 or vehicle. In some animals, treatment was discontinued allowing tumor relapse. Treatment response was evaluated using the pediatric preclinical testing program (PPTP). Immunohistochemistry and qRT‐PCR was performed on tumor cryosections to investigate the microscopic and molecular changes in tumors in response to GMX1777. Despite an increase in vessel density, tumor regression and a high group response score according to PPTP criteria was induced by GMX1777 without inducing drug resistance. Treatment resulted in inhibition of tumor cell proliferation, vessel maturation, reduced hypoxia, increased infiltration of MHC class II negative macrophages and expansion of the nonvascular stromal compartment. Decreased stromal VEGF‐A and PDGF‐B mRNA in response to treatment together with the structural data suggest a “deactivation” or “silencing” of the tumor stroma as a paracrine entity. In conclusion, GMX1777 was highly efficient against high‐risk neuroblastoma xenografts through modulation of both the tumor cell and stromal compartment.
ADAM28 is a serological and histochemical marker for non‐small‐cell lung cancers
Authors: Kuroda Hiroaki , Mochizuki Satsuki , Shimoda Masayuki , Chijiiwa Miyuki , Kamiya Kazunori , Izumi Yotaro , Watanabe Masazumi , Horinouchi Hirohisa , Kawamura Masahumi , Kobayashi Koichi , Okada Yasunori
Published: January 2010

ADAM28 (a disintegrin and metalloproteinase 28) is over‐expressed in non‐small‐cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. The present study was aimed to develop an enzyme‐linked immunosorbent assay (ELISA) system for diagnosis and monitoring of NSCLC. Our ELISA specifically measured ADAM28, showing negligible cross‐reactivity with other metalloproteinases. The ADAM28 level in the NSCLC tissue was remarkably 36.9‐fold higher than that in the non‐neoplastic lung tissue (p < 0.001). The serum level was significantly 4.6‐fold higher in the NSCLC patients (5.41 ± 8.62 ng/ml; n = 102) than in the control subjects (1.17 ± 0.93 ng/ml; n = 20) (p < 0.001), and increased with progress of tumor stage (p < 0.001). The level was also significantly higher in the patients with recurrent carcinoma than the control (p < 0.001) and in the patients with lymph node metastasis than those without metastasis (p < 0.001). The sensitivity, false‐negative rate and AUC for ADAM28 were better than those for carcinoembryonic antigen. The combination of both assays improved the sensitivity, specificity, false‐positive and false‐negative rates for NSCLC. There was a positive correlation between the ADAM28 level measured by ELISA system and the degree of immunostaining in the lung adenocarcinomas with a size of ≤20 mm in diameter. The adenocarcinoma patients showing the high immunohistochemical reaction exhibited a poorer disease‐free survival than those with the lower immunoreactivity (n = 102; p < 0.05). These data demonstrate that our ELISA is specific and sensitive to monitor the levels of ADAM28 in the samples from NSCLC patients and suggest that ADAM28 is a useful serological and histochemical marker for NSCLC.
The novel human endogenous retrovirus‐related gene, psiTPTE22‐HERV, is silenced by DNA methylation in cancers
Authors: Liang Qiaoyi , Ding Jiayi , Xu Rongzhen , Xu Zefeng , Zheng Shu
Published: January 2010

The psiTPTE22 gene has been designated as a TPTE pseudogene. Our study found that the 5′ part of psiTPTE22 has no sequence similarity to TPTE and contains a 3.8‐kb human endogenous retrovirus (HERV) element. Because of the HERV element, the 5′ part of psiTPTE22 (psiTPTE22‐HERV) expresses independently as a gene. Comparison between the DNA sequences of humans and chimps indicated that psiTPTE22‐HERV is human specific. We identified 3 alternatively spliced transcript variants from psiTPTE22‐HERV by a PCR‐based strategy, which use the transcriptional termination signal contained in the HERV element. A 402‐nt ORF was contained in the 2 longer transcripts. Western blotting using antibodies produced with chemically synthesized peptide confirmed that a 15‐kDa protein was translated from this ORF. RT‐PCR results indicated that the ORF‐containing transcripts were mainly expressed in psiTPTE22‐HERV‐expressing samples. Real‐time quantitative RT‐PCR results showed that expression of the 402‐nt ORF was upregulated in normal tissues of kidney, liver, stomach, and lung but downregulated in corresponding tumor tissues. This gene is located near the centromere of chromosome 22 and has a high GC content around the promoter region. Bisulfite sequencing PCR results indicated that it is silenced in cancers by DNA methylation. The expression of psiTPTE22‐HERV can be recovered in cancer cells using DNA methylation and histone deacetylase inhibitors. These results suggest psiTPTE22‐HERV is regulated epigenetically by DNA methylation. Our study paved the way for further study on an interesting HERV‐related human‐specific gene, which is silenced in cancers by DNA methylation.
Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study
Authors: Almquist Martin , Bondeson Anne‐Greth , Bondeson Lennart , Malm Johan , Manjer Jonas
Published: January 2010

Previous studies indicate that calcium and its regulating hormones, i.e., parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD2 and 25OHD3), PTH and calcium using a nested case–control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD3, PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD3, and the OR for the 2nd, 3rd and 4th quartiles, as compared to the first, were 0.84 (0.60–1.15), 0.84 (0.60–1.17) and 0.93 (0.66–1.33). Serum calcium was positively associated with breast cancer in premenopausal women (OR for the 4th quartile = 3.10:1.33–7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th quartile = 1.94:1.12–3.37 and p for trend < 0.01). There was no association between baseline serum PTH and breast cancer risk.