bluuebunny/crossref_metadata_2025 huggingface dataset:
Starting a new life: Sperm PLC‐zeta mobilizes the Ca2+ signal that induces egg activation and embryo development
Authors: Nomikos Michail , Swann Karl , Lai F. Anthony
Published: November 2011

We have discovered that a single sperm protein, phospholipase C‐zeta (PLCζ), can stimulate intracellular Ca2+ signalling in the unfertilized oocyte (‘egg’) culminating in the initiation of embryonic development. Upon fertilization by a spermatozoon, the earliest observed signalling event in the dormant egg is a large, transient increase in free Ca2+ concentration. The fertilized egg responds to the intracellular Ca2+ rise by completing meiosis. In mammalian eggs, the Ca2+ signal is delivered as a train of long‐lasting cytoplasmic Ca2+ oscillations that begin soon after gamete fusion and persist beyond the completion of meiosis. Sperm PLCζ effects Ca2+ release from egg intracellular stores by hydrolyzing the membrane lipid PIP2 and consequent stimulation of the inositol 1,4,5‐trisphosphate (InsP3) receptor Ca2+‐signalling pathway, leading to egg activation and early embryogenesis. Recent advances have refined our understanding of how PLCζ induces Ca2+ oscillations in the egg and also suggest its potential dysfunction as a cause of male infertility.
Updating risk prediction tools: A case study in prostate cancer
Authors: Ankerst Donna P. , Koniarski Tim , Liang Yuanyuan , Leach Robin J. , Feng Ziding , Sanda Martin G. , Partin Alan W. , Chan Daniel W. , Kagan Jacob , Sokoll Lori , Wei John T. , Thompson Ian M.
Published: November 2011

Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision‐making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [‐2]proPSA measured on an external case–control study performed in Texas, U.S.. Recent state‐of‐the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network.
Development of thermostable Candida antarctica lipase B through novel in silico design of disulfide bridge
Authors: Le Quang Anh Tuan , Joo Jeong Chan , Yoo Young Je , Kim Yong Hwan
Published: November 2011

Lipase B from Candida antarctica (CalB) is a versatile biocatalyst for various bioconversions. In this study, the thermostability of CalB was improved through the introduction of a new disulfide bridge. Analysis of the B‐factors of residue pairs in CalB wild type (CalB‐WT) followed by simple flexibility analysis of residues in CalB‐WT and its designated mutants using FIRST server were newly proposed to enhance the selective power of two computational tools (MODIP and DbD v1.20) to predict the possible disulfide bonds in proteins for the enhancement of thermostability. Five residue pairs (A162‐K308, N169‐F304, Q156‐L163, S50‐A273, and S239C‐D252C) were chosen and the respective amino acid residues were mutated to cysteine. In the results, CalB A162C‐K308C showed greatly improved thermostability while maintaining its catalytic efficiency compared to that of CalB‐WT. Remarkably, the temperature at which 50% of its activity remained after 60‐min incubation (T) of CalB A162C_K308C was increased by 8.5°C compared to that of CalB‐WT (55 and 46.5°C, respectively). Additionally, the half‐life at 50°C of CalB A162C‐K308C was 4.5‐fold higher than that of CalB‐WT (220 and 49 min, respectively). The improvement of thermostability of CalB A162C‐K308C was elucidated at the molecular level by molecular dynamics (MD) simulation. Biotechnol. Bioeng. 2012; 109:867–876. © 2011 Wiley Periodicals, Inc.
Neutral Nickel Oligo‐ and Polymerization Catalysts: The Importance of Alkyl Phosphine Intermediates in Chain Termination
Authors: Heyndrickx Wouter , Occhipinti Giovanni , Minenkov Yury , Jensen Vidar R.
Published: November 2011

An unconventional chain termination reaction has been explored for the SHOP (Shell higher olefin process)‐type, anilinotropone, and salicylaldiminato nickel‐based oligo‐ and polymerization catalysts by using density functional theory (DFT). Starting from the tetracoordinate alkyl phosphine complex, the termination reaction was found to involve a rearrangement of the alkyl chain to form a pentacoordinate β‐agostic complex, β‐hydride elimination, and olefinic chain dissociation and to compete with propagation at sufficiently high phosphine concentration and/or basicity. It provides the first complete and convincing mechanistic rationale for the decreasing chain lengths observed upon increasing phosphine concentration and basicity. The unconventional reaction was found to be a major termination pathway for the SHOP‐type catalyst and is very unlikely to lead to branching and olefin isomerization, which is critical for explaining why the SHOP catalyst, in contrast to the anilinotropone and salicylaldiminato catalysts, tends to lead to the oligomerization of ethylene to form linear α‐olefins. Based on our results we have proposed a new and extended catalytic cycle for the SHOP‐type ethylene oligomerization catalyst. Finally, the importance of the new termination reaction for the SHOP‐type catalyst suggests that this reaction may also operate with other ethylene oligomerization nickel catalysts. This prediction was confirmed for a pyrazolonatophosphine catalyst, for which the new termination route was found to be even more facile, which explains the short oligomers produced by this catalyst.
Remarkably Selective Recognition of Iodobenzene Derivatives by a Macrocyclic Bis‐PtII Metallohost
Authors: Trokowski Robert , Akine Shigehisa , Nabeshima Tatsuya
Published: November 2011

We designed and synthesized self‐assembled bis‐PtII dimer 1⋅4 BF4 with quino[8,7‐b][1,10]phenanthroline as an extended π‐face contact area, which acts as the first artificial receptor with high affinity toward iodinated aromatic compounds significantly based on noncovalent iodine⋅⋅⋅aromatic‐plane interactions in a “side‐on” fashion. Despite their structural similarity to a previously reported metallohost 24+ that bears 2,2′:6′,2′′‐terpyridine units, a dramatic change in selectivity toward substituted benzene derivatives was observed for 14+. 1H NMR spectroscopic titration revealed a high affinity of 14+ towards haloarenes, with exceptionally large association constants for 2‐iodophenol (Ka=16 000 M−1) and 1,2‐diiodobenzene (Ka=21 000 M−1), which are 93‐ and 140‐fold higher, respectively, than the values obtained for 24+. In addition, 14+ showed a remarkably high affinity and selectivity toward 2,6‐diiodophenol (Ka=35 000 M−1), which is an important substructure of the thyroid hormone T4. X‐ray crystallography and theoretical calculations strongly suggest that “side‐on” iodine⋅⋅⋅aromatic‐plane interactions and π–π stacking contribute to the strong 1,2‐diiodobenzene and 2,6‐diiodophenol binding. The results obtained here give unique and valuable insight into the nature of halogen atom interactions in their “side‐on” region with an electropositive aromatic plane, which may provide useful guidance for designing artificial receptors for iodinated biomolecules.
Clinical Impact of Off‐Label Cardiac Resynchronization Therapy in End‐Stage Heart Failure Patients on Continuous Intravenous Inotrope
Authors: Hara Masahiko , Mizuno Hiroya , Mizote Isamu , Nakatani Daisaku , Asano Yoshihiro , Sakata Yasushi , Nanto Shinsuke , Komuro Issei
Published: November 2011

Background:

Potential benefits of off‐label cardiac resynchronization therapy (CRT) in end‐stage heart failure (EHF) patients have not been fully investigated.

Hypothesis:

Some EHF patients who are dependent on intravenous inotropes can benefit from CRT.

Methods:

We retrospectively enrolled 14 EHF patients who were dependent on intravenous inotropes at the time of CRT implantation. Mean duration of inotropic support was 51 ± 47 days before CRT device implantation. To identify the efficacy of CRT, we assessed the successful withdrawal rate from inotropic support and survival estimates after device implantation. We also tried to identify possible predictors for withdrawal by comparing patient demographics between successful withdrawal (SW) and nonwithdrawal (NW) groups.

Results:

Successful withdrawal was achieved in 9 (64%) of 14 patients 46 ± 33 days after CRT device implantation. Event‐free survival was longer in the SW group than in the NW group (810 ± 169 days vs 114 ± 34 days; P = 0.007). In addition, patients in the SW group showed a higher previous surgery rate (89% vs 20%; P = 0.010) and a lower grade of mitral regurgitation (median, 0 vs 2; P = 0.010) than those in the NW group.

Conclusions:

Our retrospective data showed potential benefits of CRT among EHFpatients. Treatment of mitral regurgitation might be an essential qualification for managing EHF patients with CRT. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Mortality Trends for Non–ST‐segment Elevation Myocardial Infarction (NSTEMI) in the United States from 1988 to 2004
Authors: Movahed Mohammed Reza , John Jooby , Hashemzadeh Mehrnoosh , Hashemzadeh Mehrtash
Published: November 2011

Background:

Non–ST‐segment myocardial infarction (NSTEMI) is one of the major causes of hospital admissions. Mortality trend in patients with NSTEMI over the years has not been studied well. The goal of this study is to explore age‐adjusted long‐term mortality trends from NSTEMI in the United States using a very large database.

Methods:

We used the National Inpatient Sample (NIS) database, a component of the Health Care Cost and Utilization (HCUP) project, for this study. International Classification of Disease, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes were used to identify NSTEMI cases in patients >40 years old. Age‐adjusted mortality rates for NSTEMI cases were calculated by multiplying the age‐specific mortality rates of NSTEMI by age‐specific weights.

Results:

A total of 1,400,234 patients above the age of 40 years were identified. The mean age of this cohort was 77.1±10.7 years, with a total of 179,361 deaths being reported over this 16‐year period. Among patients who died, 51.2% were men and 48.8% were women. The age‐adjusted mortality from NSTEMI declined from 1988 (727 per 100,000) to 2004 (305 per 100,000) until the middle of the decade when mortality from NSTEMI started leveling off. Total mortality decreased from 29.6% in 1988 to 11.3% in 2004.

Conclusions:

Our analysis showed a significant reduction in the age‐adjusted and total mortality for NSTEMI over the years studied. The cause of this trend is not known but most likely reflects advancement in the treatment of patients with acute coronary syndrome. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Effects of hue, saturation, and brightness on color preference in social networks: Gender‐based color preference on the social networking site Twitter
Authors: Fortmann‐Roe Scott
Published: November 2011

Account information for over 1 million Twitter users was downloaded and analyzed to determine color preference. Blues were found to be the most preferred color, whereas greens were least preferred. Distinct gender‐specific differences were found. Males preferred blues to a greater extent than females, whereas females preferred magentas to a much greater extent than males. Males preferred darker colors to a greater extent than women. Density plots within hue, saturation, and brightness space summarize the distribution of color choices and illustrate color preferences for both males and females. © 2011 Wiley Periodicals, Inc. Col Res Appl, 38, 196–202, 2013.
Influence of mechanical defects on the crystal lattice of silicon
Authors: Jauß T. , Danilewsky A.N. , Wittge J. , Cröll A. , Garagorri J. , Elizalde R. M. , Allen D. , McNally P.
Published: November 2011

To examine the impact of mechanical defects on the crystal lattice of silicon, controlled damage was applied to silicon wafers by a nanoindendation method. With increasing loads of 1, 5 and 50 N, the area with micro‐cracks and strain around the indents increases. The damage is characterised by high resolution diffractometry using a conventional X‐ray tube. Spatially resolved rocking curves were recorded across the indents and analysed with respect to full width at half maximum. From reciprocal space maps the amount of strain and tilt around the indents is separated. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A mapping forwarding approach for supporting mobility in networks with identifier/locator separation
Authors: Qiu Feng , Luo Hongbin , Li Xiaoqian , Xue Miao , Dong Ping , Zhang Hongke
Published: November 2011

The identifier/locator separation has been widely recognized as a feasible solution for addressing the current Internet's routing scaling problem. Moreover, such a separation solution in terms of mobility can keep connection survivability and support global seamless roaming. A critical challenge in supporting efficient mobility is how to update the identifier‐to‐locator mappings of mobile nodes (MNs). In this paper, we propose a mapping forwarding (MF) scheme for location management in the identifier/locator separation architecture. In the MF scheme, a tunnel router (xTR) is selected as an agent of an MN and keeps the MN's identifier‐to‐locator mapping invariable by setting up an MF chain. As long as the MN is managed by the same xTR, the MN's mapping stored in the xTR of each correspondent node of the MN does not need to be updated, thus reducing the location update signaling cost. Meanwhile, the unchanged mapping assures the correct forwarding of packets, which reduces mobility‐related disruption and enhances the location management's reliability. In addition, for the handoff in two MF chains, we propose a data‐triggered update scheme that can achieve route optimization. To evaluate the proposed MF scheme, we establish two analytical models and formulate the blocking probability and the total protocol cost. The performance results show how the blocking probability changes under various parameters and how the MF scheme can effectively reduce the blocking probability compared with the location management scheme without the MF strategy. Meanwhile, our analysis demonstrates that the MF scheme has a lower overhead when the mobility rate is high. Copyright © 2011 John Wiley & Sons, Ltd.
Reducing code wastage in orthogonal variable spreading factor‐based wideband code division multiple access networks
Authors: Saini Davinder , Gupta Ankit , Joshi Aditi
Published: November 2011

Most third‐generation and beyond wideband code division multiple access networks use the orthogonal variable spreading factor code tree for channelization codes. The codes in this code tree are limited and the performance of a wireless network depends upon the code assignment for new calls. In this paper, we introduce a term called ‘wastage capacity’, which gives us the amount of wastage caused when a code (single or multiple) with a data rate higher than the rate of the incoming call is assigned to it. We suggest two methods to keep wastage capacity below an arbitrary threshold value or zero. In the first method, we devised an algorithm in which wastage up to a certain threshold would be tolerated and the minimum rakes to get this wastage capacity were identified. In the second approach, we reduced the wastage capacity to zero irrespective of the number of rakes at the expense of higher cost and complexity. Copyright © 2011 John Wiley & Sons, Ltd.
Zeranol: doping offence or mycotoxin? A case‐related study
Authors: Thevis Mario , Fußhöller Gregor , Schänzer Wilhelm
Published: November 2011

Zeranol ((7R,11S)‐7,15,17‐trihydroxy‐11‐methyl‐12‐oxabicyclo[12.4.0]octadeca‐1(14),15,17‐trien‐13‐one, also referred to as 7α‐zearalanol, Ralone®, Frideron®, Ralgro®, etc.) is a semi‐synthetic estrogenic veterinary drug with growth‐promoting properties. Its use regarding animal husbandry has been prohibited in the European Union since 1981 and, due to its anabolic effects, it is further recognized as a banned substance in sport. Numerous studies were conducted concerning the identification of the illicit application of zeranol to domestic livestock. These studies also considered the natural occurrence of zeranol as a metabolite of the mycotoxin zearalenone and the issue of differentiating both scenarios, i.e. illegal use or unintended contamination. Human sports drug testing authorities are facing comparable challenges since the deliberate misuse of the (for human application non‐approved) drug should be discriminated from adverse analytical findings resulting from the biotransformation of the mycotoxin zearalenone possibly ingested with contaminated food. The active drug (zeranol), its major human metabolites (zearalanone, 7β‐zearalanol) and the mycotoxin (zearalenone) plus its major and unique metabolic products (α‐zearalenol, β‐zearalenol) have been monitored in routine doping controls by means of validated gas chromatography‐(tandem) mass spectrometry (GC‐(MS/)MS) methods since 1996, and between 2005 and 2010 four samples providing suspicious signals were detected. In agreement with literature data, in vitro metabolism studies demonstrated the metabolic pathway from zearalenone towards zeranol (and common metabolites). In contrast, an administration study urine sample (collected after oral application of 20 mg of zeranol) yielded only ultra‐trace amounts of zearalenone and its characteristic metabolites, which supported the assumption that a mycotoxin contamination caused the finding of zeranol in the doping control specimens rather than a misuse of the anabolic agent. Copyright © 2011 John Wiley & Sons, Ltd.
A Quest for Ligand‐Unsupported Li+–π Interactions in Mono‐, Di‐, and Tritopic Lithium Arylborates
Authors: Franz Daniel , Haghiri Ilkhechi Alireza , Bolte Michael , Lerner Hans‐Wolfram , Wagner Matthias
Published: November 2011

The lithium salts of selected mono‐, di‐, and tritopic arylborates have been synthesized and their solid‐state structures have been analyzed by X‐ray crystallography with focus on the occurrence of Li+–aryl π interactions. The solvated salts of the monotopic arylborate [Li(thf)4][(p‐BrC6H4)BPh3] as well as the ditopic borates [Li(12‐crown‐4)2]2[p‐C6H4(BMe3)2] and [Li(tetraglyme)]2[p‐C6H4(BPh3)2] exist as solvent‐separated ion pairs in the crystal lattice. The attachment of two moderately coordinating monohydridoborate functionalities on a benzene ring leads to Li+–hydride interactions. In the case of [Li(thf)3]2[p‐C6H4{9‐BBN(H)}2] [9‐BBN(H) = 9‐borabicyclo[3.3.1]nonane], this additional attractive force is not sufficient to promote Li+–aryl π interactions, however, the 1,2‐dimethoxyethane (DME) solvate [Li(dme)2]2[p‐C6H4{9‐BBN(H)}2] shows a remarkably short contact between the Li+ cation and the adjacent phenylene ipso carbon atom [Li–C 2.366(2) Å]. The targeted structural motif ofLi+–arene η6 coordination was finally observed in the solid‐state structures of the tritopic borates [{Li(12‐crown‐4)2}2Li(thf)][1,3,5‐C6H3(BMe3)3] and [{Li(thf)2}2Li][1,3,5‐C6H3(BH3)3]. In the latter complex, an extensive network of Li–H–B bonds is observed in addition to the Li+–π interaction.
Impact of frying on key fatty acid ratios of canola oil
Authors: Talpur Muhammad Younis , Sherazi Syed Tufail Hussain , Mahesar Sarfaraz Ahmed , Naz Saba , Kara Huseyin
Published: November 2011

The study was carried out to investigate the changes in saturated (SFA), monoene (MUFA), trans (TFA), and polyunsaturated (PUFA) fatty acids and the key fatty acid ratios (SFA/UFA, cis PUFA/SFA, C18:2/C16:0 and C18:3/C16:0) during potato chips frying in canola oil using single bounce attenuated total reflectance FTIR (SB‐ATR‐FTIR) spectroscopy. The data obtained from GC‐FID were used as reference. The calibration of main fat groups and their key fatty acid ratios were developed by partial least square (PLS) regression coefficients using 4000 to 650 cm−1 spectral range. FTIR PLS regression for the predicted SFA, MUFA, TFA, and PUFA were found 0.999, 0.998, 0.998, and 0.999, respectively, whereas for SFA/UFA, cis PUFA/SFA, C18:2/C16:0 and C18:3/C16:0 the regression coefficients were 0.991, 0.997, 0.996, and 0.994, respectively. We conclude that FTIR‐PLS could be used for rapid and accurate assessment of changes in the main fat groups and their key fatty acid ratios ratio during the frying process.

Practical applications: FTIR‐ATR method is very simple, rapid, and environmentally friendly. No sample preparation is required and one drop of oil is enough for FTIR analysis. The proposed method could be applied for quick determination of key fatty acid ratios in the food processing industry.
Serine‐Based Bis‐quat Gemini Surfactants: Synthesis and Micellization Properties
Authors: Goreti Silva S. , Fernandes Ricardo F. , Marques Eduardo F. , do Vale M. Luísa C.
Published: November 2011

The synthesis of novel cationic gemini surfactants based on serine, with long lipophilic alkyl chains and a spacer linked to the nitrogen atom of the amino acid residue by amine linkages, is described. The most efficient synthetic pathway involves introduction of the spacer into the monomeric precursors, N‐alkyl derivatives, by reductive amination of dialdehydes followed by methylation and deprotection. Characterization of the basic micellization properties of the new compounds was carried out by tensiometry and conductimetry. These surfactants present enhanced interfacial properties compared to the monomeric analogues, and show improved performance, namely lower critical micelle concentration (cmc), lower surface tension at cmc and increased micellar ionization, with respect to conventional bis‐quaternary ammonium salts (bis‐quats).
Looking for a Robust, Synthetic, Fully‐Extended (2.05‐Helical) Peptide Structure – Effect of Terminal Groups
Authors: Formaggio Fernando , Crisma Marco , Peggion Cristina , Moretto Alessandro , Venanzi Mariano , Toniolo Claudio
Published: November 2011

The incorporation of α‐amino acids with a quaternary α‐carbon atom into a peptide provides a tool to effectively restrict the available range of its backbone conformations. Specifically, under favorable conditions, Cα,α‐diethylglycine (Deg) homopeptides are known to preferentially adopt the fully‐extended (2.05‐helical) structure, which is characterized by the longest possible separation between two adjacent α‐amino acid Cα atoms. We have investigated the influence of the nature of the N‐ and/or C‐terminal protecting (or blocking) groups on the relative stabilities of the fully‐extended conformation vs. the competing, shorter 310‐helical structure in a synthetic Deg homopeptide series.
The development of the UHV a.c. arresters
Authors: Wang Bao‐shan , Wang Shao‐wu , Xiong Yi , Wang Xiao‐ning , Tang Lin , Zuo Zhong‐qiu
Published: November 2011

Ultra‐high voltage (UHV) systems require good insulation and high reliability. UHV a.c. system metal‐oxide surge arrester (UHV MOA) is an important protective equipment, which used to limit the system overvoltage, to lower the level of insulation, and to increase operational reliability. The technical level of the UHV MOA has a significant impact on the safety and reliability, as well as the investment levels of the UHV project. The successful development of the UHV MOA is one of the most important achievements in arrester area. Before the completion of the China UHV a.c. demonstration project, UHV MOA has not been used commercially abroad, so the arrester standards were not involved of the UHV level. This paper details the development of the UHV MOA, including the design of technical parameters, equipment development, test, and so on. Copyright © 2011 John Wiley & Sons, Ltd.
Improved total variation diminishing schemes for advection simulation on arbitrary grids
Authors: Hou J. , Simons F. , Hinkelmann R.
Published: November 2011

The requirements for flux limiter functions preserving total variation diminishing (TVD) are derived based on a 1D nonuniform grid, and a new TVD region is determined to fit arbitrary 1D grids. Some second‐order TVD schemes called improved TVD schemes are developed, such as modified Van Leer scheme, modified Van Albada scheme, and modified SUPERBEE scheme. Then, they are extended to 2D grids. Because the element sizes and face positions are taken into account, good behaviors are observed in the implementations in both 1D and 2D cases for pure advection simulation. That is, good conservation, better monotonicity, and higher accuracy are maintained by the improved TVD schemes compared with the present ones deduced from uniform grids, and they keep superiorities even when implemented on poor grids. Among all the improved TVD schemes, the modified SUPERBEE is only recommended for poor 1D grids, but the modified Van Leer scheme can suit both poor 1D and 2D grids. Copyright © 2011 John Wiley & Sons, Ltd.
Expression of cancer‐testis antigens MAGE‐A4 and MAGE‐C1 in oral squamous cell carcinoma
Authors: Montoro José Raphael de Moura Campos , Mamede Rui Celso Martins , Neder Serafini Luciano , Saggioro Fabiano Pinto , Figueiredo David Livingstone Alves , Silva Wilson Araújo da , Jungbluth Achim A. , Spagnoli Giulio Cesare , Zago Marco Antônio
Published: November 2011

Background

Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer‐testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE‐A4 (melanoma antigen) and MAGE‐C1 are expressed in carcinoma of the oral cavity and are related with survival.

Methods

This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE‐A4 and MAGE‐C1. Fisher's exact test and log‐rank test were used to evaluate the results.

Results

The expression of the MAGE‐A4 and MAGE‐C1 were 56.5% and 47.8% without statistical difference in studied variables and survival.

Conclusion

The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Plasma epstein‐barr virus DNA concentration and clearance rate as novel prognostic factors for metastatic nasopharyngeal carcinoma
Authors: Hsu Cheng‐Lung , Chang Kai‐Ping , Lin Chien‐Yu , Chang Hsien‐Kun , Wang Cheng‐Hsu , Lin Tung‐Liang , Liao Chun‐Ta , Tsang Ngan‐Ming , Lee Li‐Yu , Chan Sheng‐Chieh , Ng Shu‐Hang , Li Hsin‐Pai , Chang Yu‐Sun , Wang Hung‐Ming
Published: November 2011

Background

To investigate the pretreatment copy number and the clearance rate of plasma Epstein‐Barr virus (EBV) DNA as novel prognostic outcome markers for metastatic nasopharyngeal carcinoma (NPC).

Methods

Seventy‐three patients with metastatic NPC were treated at outpatient department. Plasma EBV DNA concentrations and half‐life values of plasma viral clearance rates, were determined by real‐time quantitative polymerase chain reaction.

Results

Treatment response evaluated after 3 to 6 months of treatment showed that the overall response rate was 53.5%. The pretreatment plasma EBV DNA concentrations and the half‐life of plasma EBV DNA clearance rates had significant effects on treatment response and overall survival prediction. In the chemotherapy regimen, gemcitabine plus cisplatin had a better treatment outcome than the cisplatin plus oral UFT and calcium folinate–based regimens.

Conclusions

The pretreatment plasma EBV DNA copy number and their clearance rates are significant predictors for NPC treatment outcome. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Cryogun cryotherapy for oral leukoplakia
Authors: Lin Hung‐Pin , Chen Hsin‐Ming , Cheng Shih‐Jung , Yu Chuan‐Hang , Chiang Chun‐Pin
Published: November 2011

Background

Our previous study showed that cotton‐swab cryotherapy is an alternative treatment modality for oral leukoplakia.

Methods

This study used liquid nitrogen spray with a cryogun (cryogun cryotherapy) to treat 60 oral leukoplakia lesions.

Results

Complete regression was achieved in all 60 oral leukoplakia lesions after cryogun cryotherapy. We found that 60 oral leukoplakia lesions treated with cryogen cryotherapy needed significantly fewer mean treatments (3.1 ± 1.3) to achieve complete regression than 60 previously reported oral leukoplakia lesions treated with cotton‐swab cryotherapy (mean, 6.3 ± 3.8 treatments). Oral leukoplakia lesions on oral mucosal sites other than the tongue, <2 cm2, with epithelial dysplasia, or with a surface keratin thickness <55 μm required significantly fewer cryogun cryotherapy treatments to achieve complete regression.

Conclusions

For treatment of oral leukoplakia, the cryogun cryotherapy needed fewer mean treatments to achieve complete regression of the lesions than the cotton‐swab cryotherapy. Head Neck, 2012
Quantitative analysis of free flap volume changes in head and neck reconstruction
Authors: Yamaguchi Kazuaki , Kimata Yoshihiro , Onoda Satoshi , Mizukawa Nobuyoshi , Onoda Tomoo
Published: November 2011

Background

The purpose of this study was to determine whether free flap volume decreases or increases in the long‐term postoperative period.

Methods

We used a retrospective analysis of 17 patients to measure muscle and fat volume in free flap with 3‐dimensional (3D) images using the AZE Virtual Place Lexus64.

Results

Seventeen patients underwent free flap reconstruction with rectus abdominis musculocutaneous flaps (n = 11) or anterolateral thigh flaps (n = 6). Median follow‐up was 28.9 months (range, 2.1–48.4 months). Total flap volume was significantly decreased in flaps including ≥40% muscle (p = .011). Mean final muscle volume was 50% at an average of 12 months. Final fat volume was significantly higher for cases with no evidence of disease (mean, 116.7%) than for died‐of‐the‐disease cases (mean, 70.3%; p = .007).

Conclusion

Use of free flaps with a high ratio of fat to muscle is sustainable and can gain volume over time, as transplanted fat can increase depending on host condition. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Endoplasmic reticulum-tethered transcription factor cAMP responsive element-binding protein, hepatocyte specific, regulates hepatic lipogenesis, fatty acid oxidation, and lipolysis upon metabolic stress in mice
Authors: Zhang Chunbin , Wang Guohui , Zheng Ze , Maddipati Krishna Rao , Zhang Xuebao , Dyson Gregory , Williams Paul , Duncan Stephen A. , Kaufman Randal J. , Zhang Kezhong
Published: November 2011

cAMP responsive element-binding protein, hepatocyte specific (CREBH), is a liver-specific transcription factor localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here, we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the liver. Under the normal chow diet, CrebH knockout mice display a modest decrease in hepatic lipid contents, but an increase in plasma triglycerides (TGs). After having been fed an atherogenic high-fat (AHF) diet, massive accumulation of hepatic lipid metabolites and significant increase in plasma TG levels were observed in the CrebH knockout mice. Along with the hypertriglyceridemia phenotype, the CrebH null mice displayed significantly reduced body-weight gain, diminished abdominal fat, and increased nonalcoholic steatohepatitis activities under the AHF diet. Gene-expression analysis and chromatin-immunoprecipitation assay indicated that CREBH is required to activate the expression of the genes encoding functions involved in de novo lipogenesis, TG and cholesterol biosynthesis, FA elongation and oxidation, lipolysis, and lipid transport. Supporting the role of CREBH in lipogenesis and lipolysis, forced expression of an activated form of CREBH protein in the liver significantly increases accumulation of hepatic lipids, but reduces plasma TG levels in mice. Conclusion: All together, our study shows that CREBH plays a key role in maintaining lipid homeostasis by regulating the expression of the genes involved in hepatic lipogenesis, FA oxidation, and lipolysis under metabolic stress. The identification of CREBH as a stress-inducible metabolic regulator has important implications in the understanding and treatment of metabolic disease. (Hepatology 2012)
Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense
Authors: Teltschik Zora , Wiest Reiner , Beisner Julia , Nuding Sabine , Hofmann Claudia , Schoelmerich Juergen , Bevins Charles L. , Stange Eduard F. , Wehkamp Jan
Published: November 2011

Liver cirrhosis is associated with bacterial translocation (BT) and endotoxemia. Most translocating bacteria belong to the common intestinal microbiota, suggesting a breakdown of intestinal barrier function. We hypothesized that diminished mucosal antimicrobial host defense could predispose to BT. Two rodent models of portal hypertension with increased BT were used, CCl4-induced ascitic cirrhosis and 2-day portal vein–ligated (PVL) animals. BT was assessed by standard microbiological techniques on mesenteric lymph nodes. Total RNA was isolated systematically throughout the intestinal tract, and expression of Paneth cell α-cryptdins and β-defensins was determined by real-time quantitative polymerase chain reaction (qPCR). To determine functional consequences, mucosal antimicrobial activity was assessed with a fluorescence-activated cell sorting assay. BT was detectable in 40% of rats with cirrhosis. Compared with the group without BT, these animals exhibited diminished intestinal Paneth cell α-cryptdin 5 and 7 expression. In contrast, PVL was associated with BT in all animals but did not affect antimicrobial peptides. The decrease in Paneth cell antimicrobials was most pronounced in the ileum and the coecum. Other antimicrobials showed no changes or even an induction in the case of BT at different sites. Antimicrobial activity toward different commensal strains was reduced, especially in the distal ileum and the cecum in experimental cirrhosis with BT (excluding PVL). Conclusion: Compromised Paneth cell antimicrobial host defense seems to predispose to BT in experimental cirrhosis. Understanding this liver–gut axis including the underlying mechanisms could help us to find new treatment avenues. (Hepatology 2012)
Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment
Authors: Harrington Patrick R. , Zeng Wen , Naeger Lisa K.
Published: November 2011

Boceprevir- and telaprevir-based treatments for chronic hepatitis C virus (HCV) infection use specific response-guided therapy (RGT) guidelines. Eligibility for shortened treatment duration is based on achieving undetectable HCV RNA early during treatment. It is unclear whether a detected HCV RNA level that is below the assay lower limit of quantitation (detectable/BLOQ) is comparable to an undetectable HCV RNA level for RGT decision making. We analyzed data from boceprevir and telaprevir clinical trials to obtain a comprehensive understanding of the frequency and clinical relevance of detectable/BLOQ HCV RNA measurements. In Phase 3 trials P05216 (boceprevir), C216 (telaprevir), and 108 (telaprevir), detectable/BLOQ levels were reported for approximately 10%-20% of all on-treatment HCV RNA measurements. In P05216 and C216, subjects with detectable/BLOQ HCV RNA, on average, had a reduced sustained virologic response (SVR) rate compared with subjects with undetectable HCV RNA at the same on-treatment timepoint. At key RGT timepoints (week 8 for boceprevir, week 4 for telaprevir), subjects with detectable/BLOQ HCV RNA had an approximately 20% lower SVR rate compared with subjects with undetectable HCV RNA, and this difference widened for later on-treatment timepoints. A similar trend was observed for Study 108, but the differences in SVR rates were modest, potentially explained by a higher frequency of reported detectable/BLOQ results. Analyses of Phase 2 boceprevir and telaprevir trials indicated subjects with detectable/BLOQ HCV RNA at RGT timepoints benefited from extended treatment duration. Conclusion: During boceprevir- and telaprevir-based treatment, subjects with detectable/BLOQ HCV RNA had a reduced virologic response compared with subjects with undetectable HCV RNA. Eligibility for shortened treatment duration should be based on achieving undetectable HCV RNA (i.e., HCV RNA not detected) at RGT decision timepoints. (Hepatology 2012)
Family history of liver cancer and hepatocellular carcinoma
Authors: Turati Federica , Edefonti Valeria , Talamini Renato , Ferraroni Monica , Malvezzi Matteo , Bravi Francesca , Franceschi Silvia , Montella Maurizio , Polesel Jerry , Zucchetto Antonella , La Vecchia Carlo , Negri Eva , Decarli Adriano
Published: November 2011

Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti–hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random-effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta-analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03).

Conclusion :

A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk. (Hepatology 2011)
Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation
Authors: Embade Nieves , Fernández-Ramos David , Varela-Rey Marta , Beraza Naiara , Sini Marcella , de Juan Virginia Gutiérrez , Woodhoo Ashwin , Martínez-López Nuria , Rodríguez-Iruretagoyena Begoña , Bustamante Francisco Javier , de la Hoz Ana Belén , Carracedo Arkaitz , Xirodimas Dimitris P. , Rodríguez Manuel S. , Lu Shelly C. , Mato José M. , Martínez-Chantar María L.
Published: November 2011

Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy. (Hepatology 2012)
Assessing the investigation of streamflow source areas through uncertainty evaluation of numerical experiments in small catchments
Authors: Soria Freddy , Kazama So
Published: November 2011

This study proposes an algorithm to identify streamflow source areas through the interpretation of the predictive uncertainty analysis of streamflow generation. The method interprets model‐free variance‐based sensitivity indices and response surfaces to track the spatiotemporal evolution of streamflow source areas that define the components of a single rainfall‐runoff event‐driven hydrograph. Under a Monte Carlo framework, a distributed model was used to investigate (at daily resolution) a mountainous catchment with simple terrain in Japan and (at monthly resolution) a mountainous Andean watershed with complex terrain. Results suggest that for simple terrains, integrative river discharge observations at the outlet describe, to a great extent, most states of the catchment runoff response. However, for the time steps during which rainfall strikes, the validity of the observations at the outlet is restricted to the main stream. In the watershed with simple terrain, permanently saturated areas were found in the low lands and the riparian areas (slope gradients from 1% to 10%). The storage zones are on the headwaters (slope gradients up to 23%). Transitional zones cover the remaining areas. In complex terrains, the role of the topographic slope gradients is more relevant than the topology for the streamflow source areas delineation. In the Andean watershed, the dominating processes are in the headwaters, where the slope gradients are gentle (from 3% to 20%), and wetlands act as transient water reservoirs. In conclusion, the transferability of information at different spatiotemporal scales between catchments with heterogeneous topography and complex terrain seems unlikely. Copyright © 2011 John Wiley & Sons, Ltd.
Exploring frataxin function
Authors: Busi Maria V. , Gomez‐Casati Diego F.
Published: November 2011

Frataxin is a nuclear‐encoded mitochondrial protein highly conserved in prokaryotes and eukaryotes. Its deficiency was initially described as the phenotype of Friedreich's ataxia, an autosomal recessive disease in humans. Although several functions have been described for frataxin, that is, involvement in Fe‐S cluster and heme synthesis, energy conversion and oxidative phosphorylation, iron handling and response to oxidative damage, its precise function remains unclear. Although there is a general consensus on the participation of frataxin in the maintenance of cellular iron homeostasis and in iron metabolism, this protein may have other specific functions in different tissues and organisms. © 2011 IUBMB IUBMB Life, 2011.
1α,25(OH)2D3‐dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells
Authors: Buitrago Claudia G. , Arango Nadia S. , Boland Ricardo L.
Published: November 2011

We previously reported that 1α,25‐dihydroxy‐vitamin D3 [1α,25(OH)2D3] induces non‐transcriptional rapid responses through activation of Src and MAPKs in the skeletal muscle cell line C2C12. In the present study we investigated the modulation of Akt by the secosteroid hormone in C2C12 cells at proliferative stage (myoblasts) and at early differentiation stage. In proliferating cells, 1α,25(OH)2D3 activates Akt by phosphorylation in Ser473 in a time‐dependent manner (5–60 min). When these cells were pretreated with methyl‐beta‐cyclodextrin to disrupt caveolae microdomains, hormone‐induced activation of Akt was suppressed. Similar results were obtained by siRNA silencing of caveolin‐1 expression, further indicating that hormone effects on cell membrane caveolae are required for downstream signaling. PI3K and p38 MAPK, but not ERK1/2, participate in 1α,25(OH)2D3 activation of Akt in myoblasts. The involvement of p38 MAPK in Akt phosphorylation by the hormone probably occurs through MAPK‐activated protein kinase 2 (MK2), which is activated by the steroid. In addition, the participation of Src in Akt phosphorylation by 1α,25(OH)2D3 was demonstrated using the inhibitor PP2 and antisense oligodeoxynucleotides that suppress Src expression. We also observed that PI3K participates in hormone‐induced proliferation. During the early phase of C2C12 cell differentiation 1α,25(OH)2D3 also increases Akt phosphorylation and activates Src. Of relevance, Src and PI3K are involved in Akt activation and in MHC and myogenin increased expression by 1α,25(OH)2D3. Altogether, these data suggest that 1α,25(OH)2D3 upregulates Akt through Src, PI3K, and p38 MAPK to stimulate myogenesis in C2C12 cells. J. Cell. Biochem. 113: 1170–1181, 2012. © 2011 Wiley Periodicals, Inc.
Upregulation of recepteur d'origine nantais tyrosine kinase and cell invasiveness via early growth response‐1 in gastric cancer cells
Authors: Lee Ko E. , Park Jung S. , Khoi Pham N. , Joo Young E. , Lee Young H. , Jung Young D.
Published: November 2011

Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in carcinogenesis of epithelial tumors. RON expression was induced by the tumor promoter, phorbol 12‐myristate 13‐acetate (PMA), in gastric adenocarcinoma AGS cells. Studies with deleted and site‐directed mutagenesis of Egr‐1 promoter and with expression vectors encoding Egr‐1 confirmed that Egr‐1 is essential for RON expression. In addition, AGS cells pretreated with PMA showed remarkably enhanced invasiveness, which was partially abrogated by siRNA‐targeted RON and Egr‐1. These results suggest that tumor promoter induces RON expression via Egr‐1, which, in turn, stimulates cell invasiveness in AGS cells. J. Cell. Biochem. 113: 1217–1223, 2012. © 2011 Wiley Periodicals, Inc.