bluuebunny/crossref_metadata_2025 huggingface dataset:
A simulation‐based framework for risk assessment and probabilistic sensitivity analysis of base‐isolated structures
Authors: Taflanidis Alexandros A. , Jia Gaofeng
Published: April 2011

A versatile, simulation‐based framework for risk assessment and probabilistic sensitivity analysis of base‐isolated structures is discussed in this work. A probabilistic foundation is used to address the various sources of uncertainties, either excitation or structural, and to characterize seismic risk. This risk is given, in this stochastic setting, by some statistics of the system response over the adopted probability models and stochastic simulation is implemented for its evaluation. An efficient, sampling‐based approach is also introduced for establishing a probabilistic sensitivity analysis to identify the importance of each of the uncertain model parameters in affecting the overall risk. This framework facilitates use of complex models for the structural system and the excitation. The adopted structural model explicitly addresses nonlinear characteristics of the isolators and of any supplemental dampers, and the effect of seismic pounding of the base to the surrounding retaining walls. An efficient stochastic ground motion model is also discussed for characterizing future near‐fault ground motions and relating them to the seismic hazard for the structural site. An illustrative example is presented that emphasizes the results from the novel probabilistic sensitivity analysis and their dependence on seismic pounding occurrences and on addition of supplemental dampers. Copyright © 2011 John Wiley & Sons, Ltd.
Environmental fractionation of PCBs and PBDEs during particle transport as recorded by sediments in coastal waters
Authors: Grant Paul B.C , Johannessen Sophia C , Macdonald Robie W , Yunker Mark B , Sanborn Michael , Dangerfield Neil , Wright Cynthia , Ross Peter S
Published: April 2011

The Strait of Georgia (British Columbia, Canada) is a hydrologically complex inland sea with a rich abundance and diversity of species of aquatic life. Marine sediments, as both a sink for hydrophobic contaminants and a potential source for aquatic food webs, were collected from 41 sites throughout the 6,900-km2 Strait of Georgia. The congener-specific concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), including BDE-209, were measured. Urban harbors represented hotspots for both PCBs and PBDEs, whereas PBDEs were also found at high concentrations near municipal outfalls. Patterns of PCB distribution were consistent with historical point source emissions in urban areas and environmental distillation toward lighter profiles in remote sites over time. The single congener BDE-209 dominated the PBDEs, accounting for 52% of the average total concentration. However, nonurban deep-water sediment PBDE profiles were both heavier and had higher concentration-weighted average log KOW (octanol–water partition coefficient) values compared to shallow samples (percent BDE-209 of total PBDE, 66 versus 32%; log KOW, 9.5 versus 8.2, respectively). Collectively, our results suggest that although source signals largely explain PCB and PBDE hotspots in the Strait of Georgia, the combination of physicochemical properties and environmental processes drive divergent compositional fates for the PCBs and the heavier PBDEs in the sediments of the Strait of Georgia. Environ. Toxicol. Chem. 2011; 30:1522–1532. © 2011 SETAC
Unsteady hydromagnetic flow of a reactive variable viscosity third‐grade fluid in a channel with convective cooling
Authors: Chinyoka T. , Makinde O. D.
Published: April 2011

This paper examines the combined effects of a transverse magnetic field and variable viscosity on unsteady flow of a reactive third‐grade electrically conducting fluid and heat transfer in a channel with convective cooling at the surface. It is assumed that the fluid has small electrical conductivity and the electromagnetic force produced is very small. The coupled nonlinear partial differential equations governing the problem are derived and solved numerically using a semi‐implicit finite‐difference scheme. Both numerical and graphical results are presented and physical aspects of the problem are discussed with respect to various parameters embedded in the system. It is in general noted that those parameters that increase/decrase one flow quantity (velocity or temperature) also lead to the increase/decrease respectively of the other quantity. Copyright © 2011 John Wiley & Sons, Ltd.
Anode Current Collecting Efficiency of Tubular Anode‐supported Solid Oxide Fuel Cells
Authors: Bai Y. , Wang C. , Jin C. , Liu J.
Published: April 2011

Anode current collection points (ACCPs) were fabricated on the outside surface of a tubular anode‐supported solid oxide fuel cell (SOFC). The ACCPs were distributed axially along the SOFC tube with the distance between every adjacent two ACCPs the same. The effect of collecting current with different number of ACCPs on the performance of the SOFC was studied. It was found that with the same effective area, using more ACCPs to collect the current leads to better performance, while with a SOFC with a determined total surface area, there is an optimum number of ACCPs to be made and used considering the area occupied by the ACCPs themselves.
Quality of life lost due to non‐fatal road traffic injuries
Authors: Cubí‐Mollá Patricia , Herrero Carmen
Published: April 2011

The objective of this paper is to evaluate the effect of a non‐fatal road crash on the health‐related quality of life of injured people. A new approach based on the cardinalization of categorical Self‐Assessed Health valuations is suggested. Health losses have been estimated by using different Time Trade‐off and Visual Analogue Scale tariffs, in order to assess the robustness of the results. The methodology is based on the existing literature about treatment effects. Our main contribution focuses on evaluating the loss of health up to 1 year after the non‐fatal accident, for those who are non‐institutionalized, which aids the appropriate estimation of the aggregated health losses in quality‐of‐life terms. Copyright © 2011 John Wiley & Sons, Ltd.
Down-regulation of phosphatase and tensin homolog by hepatitis C virus core 3a in hepatocytes triggers the formation of large lipid droplets
Authors: Clément Sophie , Peyrou Marion , Sanchez-Pareja Andrea , Bourgoin Lucie , Ramadori Pierluigi , Suter David , Vinciguerra Manlio , Guilloux Kevin , Pascarella Stephanie , Rubbia-Brandt Laura , Negro Francesco , Foti Michelangelo
Published: April 2011

Abstract:

Hepatitis C virus (HCV) perturbs the host's lipid metabolism and often results in hepatic steatosis. In nonalcoholic fatty liver disease, the intrahepatic down-regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a critical mechanism leading to steatosis and its progression toward fibrosis and hepatocellular carcinoma. However, whether an HCV infection triggers the formation of large lipid droplets through PTEN-dependent mechanisms is unknown. We assessed PTEN expression in the livers of patients infected with HCV genotype 1 or 3 with or without steatosis. The role of PTEN in the HCV-induced biogenesis of lipid droplets was further investigated in vitro with hepatoma cells transduced with the HCV core protein of genotype 1b or 3a. Our data indicate that PTEN expression was down-regulated at the posttranscriptional level in steatotic patients infected with genotype 3a. Similarly, the in vitro expression of the HCV genotype 3a core protein (but not 1b), typically leading to the appearance of large lipid droplets, down-regulated PTEN expression by a mechanism involving a microRNA-dependent blockade of PTEN messenger RNA translation. PTEN down-regulation promoted in turn a reduction of insulin receptor substrate 1 (IRS1) expression. Interestingly, either PTEN or IRS1 overexpression prevented the development of large lipid droplets, and this indicates that the down-regulation of both PTEN and IRS1 is required to affect the biogenesis of lipid droplets. However, IRS1 knockdown per se did not alter the morphology of lipid droplets, and this suggests that other PTEN-dependent mechanisms are involved in this process. Conclusion: The down-regulation of PTEN and IRS1 is a critical event leading to the HCV genotype 3a–induced formation of large lipid droplets in hepatocytes. (HEPATOLOGY 2011;)
Co‐delivery of anti‐vascular endothelial growth factor siRNA and doxorubicin by multifunctional polymeric micelle for tumor growth suppression
Authors: Huang Hong‐Yi , Kuo Wei‐Ti , Chou Ming‐Ju , Huang Yi‐You
Published: April 2011

Nonviral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multifunctional nanomicelles for both drug and gene delivery application. Polyethylenimine (PEI) was modified by grafting stearic acid (SA) and further formulated to polymeric micelles (PEI‐SA) with positive surface charge for gene delivery evaluation. Our results showed that PEI‐SA micelles provided high siRNA binding efficiency and exhibited low cytotoxicity compared with unmodified PEI. siRNA delivered by PEI‐SA carriers also demonstrated significantly higher cellular uptake efficiency and stability even in the presence of serum proteins when compared with free siRNA. The post‐transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI‐SA/siRNA. In the animal intratumoral model study, the combination of co‐delivering doxorubicin and vascular endothelial growth factor (VEGF) siRNA delivered by PEI‐SA micelles showed a promising effect on anti‐tumor growth. The amphiphilic structure of PEI‐SA micelles provides advantages for multifunctional tasks; such that hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and hydrophobic core can serve as a payload for hydrophobic drugs, making it truly a promising multifunctional vehicle for both genetic and chemotherapy application. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Chitosan implants in the rat spinal cord: Biocompatibility and biodegradation
Authors: Kim Howard , Tator Charles H. , Shoichet Molly S.
Published: April 2011

Biomaterials are becoming increasingly popular for use in spinal cord repair, but few studies have investigated their long‐term biocompatibility in central nervous system tissue. In this study, chitosan was compared with two commercial materials, degradable polyglycolide (vicryl and polyglactin 910) and nondegradable expanded poly(tetrafluoroethylene) (Gore‐Tex and ePTFE), in terms of host tissue response and biodegradation in the rat spinal cord in two different spinal cord implantation models. In an uninjured model, implants were placed in the spinal cord intrathecal space for up to 6 months. At 1 month, vicryl implants elicited an elevated macrophage/microglia response compared to chitosan and Gore‐Tex, which subsided in all groups by 6 months. Fibrous encapsulation was observed for all three materials. At 6 months, the in vivo degradation of vicryl was complete, while Gore‐Tex showed no signs of degradation, as assessed by mass loss and SEM. Chitosan implants showed evidence of chain degradation at 6 months as demonstrated by differential hematoxylin and eosin staining; however, this did not result in mass loss. In the second model, implants were placed directly into the spinal cord for up to 12 months. This resulted in increased immune and inflammatory responses but did not alter degradation profiles. The same trends observed for the materials in the intrathecal space were mirrored in the spinal cord tissue. These results demonstrate that chitosan is a relatively inert biomaterial that does not elicit a chronic immune response and is suitable for long‐term applications for repair of the spinal cord. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Three‐dimensional glass‐derived scaffolds for bone tissue engineering: Current trends and forecasts for the future
Authors: Baino Francesco , Vitale‐Brovarone Chiara
Published: April 2011

Biomaterials used in regenerative medicine are often designed to act as 3D porous templates (scaffolds) able to support and promote the growth and repair of natural tissues. Some types of glasses have a great potential for making bone tissue engineering scaffolds, as they can bond to host bone, stimulate bone cells toward osteogenesis, and resorb at the same time as the bone is repaired. This review article highlights the evolution of glass‐based scaffolds for bone tissue engineering; specifically, the features, limitations, and advantages of the different types of glass‐derived scaffolds proposed in the literature (macroporous glass‐ceramic, sol–gel glass, composite, graded, hybrid, and hierarchical implants) are critically examined, discussed, and compared. Future directions for the research are also suggested, highlighting the promise of multifunctional systems able to combine bone regeneration and drug release abilities, the increasing role of nondestructive advanced imaging techniques, such as X‐ray microtomography, for scaffolds investigation and the potential of stem cells incorporation into scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Efficiency of random search procedures along the silicon cluster series: Sin (n = 5–10, 15, and 20)
Authors: Avaltroni Fabrice , Corminboeuf Clemence
Published: April 2011

The efficiency of the simplest isomeric search procedure consisting in random generation of sets of atomic coordinates followed by density functional theory geometry optimization is tested on the silicon cluster series (Si5–
10,
15,
20). Criteria such as yield, isomer distributions and recurrences are used to clearly establish the performance of the approach with respect to increasing cluster size. The elimination of unphysical candidate structures and the use of distinct box shapes and theoretical levels are also investigated. For the smaller Sin (n = 5–10) clusters, the generation of random coordinates within a spherical box is found to offer a reasonable alternative to more complex algorithms by allowing straightforward identification of every known low‐lying local minima. The simple stochastic search of larger clusters (i.e. Si15 and Si20) is however complicated by the exponentially increasing number of both low‐ and high‐lying minima leading to rather arbitrary and non‐comprehensive results. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011
The effect of iron and copper impurities on the wettability of sphalerite (110) surface
Authors: Simpson Darren J. , Bredow Thomas , Chandra Anand P. , Cavallaro Giuseppe P. , Gerson Andrea R.
Published: April 2011

The effect of impurities in the zinc sulfide mineral sphalerite on surface wettability has been investigated theoretically to shed light on previously reported conflicting results on sphalerite flotation. The effect of iron and copper impurities on the sphalerite (110) surface energy and on the water adsorption energy was calculated with the semi‐empirical method modified symmetrically orthogonalized intermediate neglect of differential overlap (MSINDO) using the cyclic cluster model. The effect of impurities or dopants on surface energies is small but significant. The surface energy increases with increasing surface iron concentration while the opposite effect is reported for increasing copper concentration. The effect on adsorption energies is much more pronounced with water clearly preferring to adsorb on an iron site followed by a zinc site, and copper site least favorable. The theoretical results indicate that a sphalerite (110) surface containing iron is more hydrophilic than the undoped zinc sulfide surface. In agreement with the literature, the surface containing copper (either naturally or by activation) is more hydrophobic than the undoped surface. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011
Being homeless and the use and nonuse of services: a qualitative study
Authors: Ogden Jane , Avades Talin
Published: April 2011

Eight homeless people were interviewed about their experiences of health and social services. Three themes emerged: responsibility, identity, and feeling trapped. Although some felt they were responsible for their own situation and avoided help, most turned to formal channels for help, but professionals were often seen as offering unwanted labels and as being rule bound. In contrast, peers were considered more understanding but colluded with their problems. Participants also expressed feeling trapped within the homeless system. Therefore, by locating responsibility for change with others, they were left feeling stigmatized, but by turning to their peers, their situation remained the same. © 2011 Wiley Periodicals, Inc.
Limiting attrition in longitudinal research on homeless adolescents: what works best?
Authors: Hobden Karen , Curtis Forney Jason , Wyszacki Durham Kathleen , Toro Paul
Published: April 2011

The effectiveness of five tracking strategies (collateral contacts, Internet databases, driver's records, letters, and community visits) used in attempting to locate homeless and housed adolescents 4.5 years after they were first contacted was examined and compared. The study sample comprised 401 adolescents (252 homeless and 149 matched housed) from 8 counties in Southeast Michigan. Homelessness was defined as sleeping in a shelter, at a friend's home without parental permission, or on the streets for at least 1 night within 1 month before initial contact. We successfully located and interviewed 85% (n=340) of our sample at the 4.5‐year time point. The most effective tracking procedure was collateral contact, which was important in locating 43% of participants in this study, followed by Internet databases (18%), community visits (11%), driver's records (6%), and letters (6%). © 2011 Wiley Periodicals, Inc.
TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation
Authors: Gobbi Giuliana , Di Marcantonio Daniela , Micheloni Cristina , Carubbi Cecilia , Galli Daniela , Vaccarezza Mauro , Bucci Giovanna , Vitale Marco , Mirandola Prisco
Published: April 2011

PKC isoenzymes play central roles in various cellular signalling pathways, participating in a variety of protein phosphorylation cascades that regulate/modulate cellular structure and gene expression. It has been firmly established that several isoforms of PKC have a role in the regulation of tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) activity. Our interest in probing the role of the epsilon isoform of PKC in the colonic cell differentiation stems from the discovery that PKCε and TRAIL are involved in the differentiation of other cell types like hematopoietic stem cells. Although the role of PKCε and TRAIL in the gastrointestinal system is unclear, it has been observed that PKCε has oncogenic activity in colon epithelial cells (CEC), while TRAIL increases the death of intestinal epithelial cells during inflammation. Here we demonstrate a reciprocal expression of PKCε and TRAIL in human colon mucosa: CECs at the bottom of the colonic crypts show high levels of PKCε, being negative for TRAIL expression. On the contrary, luminal CECs are positive for TRAIL, while negative for PKCε. Indeed, TRAIL‐ and butyrate‐induced differentiation of the human colorectal cancer cell line HT29 requires the decrease of PKCε expression, whose absence in turn increases cell sensitivity to TRAIL‐induced apoptosis. Moreover, TRAIL preferentially promotes HT29 differentiation into goblet cells. Taken together, this data demonstrate that TRAIL and PKCε must be reciprocally regulated to ensure physiological CEC differentiation starting from the stem cell pool, and that the down‐regulation of PKCε is however critical for the differentiation and apoptosis of cancer cells. J. Cell. Physiol. 227: 630–638, 2012. © 2011 Wiley Periodicals, Inc.
Emerging strategies for the early detection and prevention of head and neck squamous cell cancer
Authors: Dasgupta Santanu , Dash Rupesh , Das Swadesh K. , Sarkar Devanand , Fisher Paul B.
Published: April 2011

Despite significant improvements in therapeutic protocols, head and neck squamous cell carcinoma (HNSCC) remains a major health problem worldwide. The 5‐year post‐therapeutic survival rate is among the lowest of the major cancers with loco‐regional relapse being the main cause of death. Moreover, in most instances, the quality of life of the afflicted patient is severely compromised. The poor prognosis for HNSCC is primarily due to disease detection at advanced stages. Accordingly, development of early detection and preventive strategies are essential. Recent advances in our understanding of the molecular biology and etiology of HNSCC should facilitate development of improved intervention and therapeutic approaches. The present review discusses the potential role of such factors for developing preventive and early diagnostic strategies for HNSCC management. J. Cell. Physiol. 227: 467–473, 2012. © 2011 Wiley Periodicals, Inc.
The roles of integrin β4 in Vascular Endothelial Cells
Authors: Wang Li , Dong ZhiWu , Zhang Yun , Miao JunYing
Published: April 2011

Integrin heterodimers play diverse and important roles in physiological and pathological processes, such as cell adhesion, migration, proliferation, differentiation, angiogenesis, and tumor progression, via the outside‐in and/or inside‐out signaling pathways. Aberrant functions of integrins have been implicated in the causation and intervention of multiple diseases. Integrin β4, a laminin‐5 (LN5) receptor, mainly locates in the adhesion structure of hemidesmosome (HD). Most of the previous researches concentrated on the role of integrin β4 in cancer and cancer therapy, and a few focused on the physiological roles of normal mammalian cells. Recently, accumulating data reveal that integrin β4 participates in cell death, macroautophagy (hereafter autophagy), senescence, and differentiation regulations in various cell types including human umbilical vein endothelial cells (HUVECs), mesenchymal stem cells, and mouse neural cells, implying the key roles of integrin β4 in the physiological alteration of mammalian cells. Thus, the elucidation of integrin β4‐mediated signaling may undoubtedly contribute to novel therapeutic strategies for various human diseases, such as vascular and neural disorders. We have reviewed the roles of integrin β4 in neural cells. In the present review we will discuss the recent research progress in the inherent functions and pharmacological modulation of integrin β4 in vascular endothelial cells. J. Cell. Physiol. 227: 474–478, 2012. © 2011 Wiley Periodicals, Inc.
Nuclear γ‐tubulin associates with nucleoli and interacts with tumor suppressor protein C53
Authors: Hořejší Barbora , Vinopal Stanislav , Sládková Vladimíra , Dráberová Eduarda , Sulimenko Vadym , Sulimenko Tetyana , Vosecká Věra , Philimonenko Anatoly , Hozák Pavel , Katsetos Christos D. , Dráber Pavel
Published: April 2011

γ‐Tubulin is assumed to be a typical cytosolic protein necessary for nucleation of microtubules from microtubule organizing centers. Using immunolocalization and cell fractionation techniques in combination with siRNAi and expression of FLAG‐tagged constructs, we have obtained evidence that γ‐tubulin is also present in nucleoli of mammalian interphase cells of diverse cellular origins. Immunoelectron microscopy has revealed γ‐tubulin localization outside fibrillar centers where transcription of ribosomal DNA takes place. γ‐Tubulin was associated with nucleolar remnants after nuclear envelope breakdown and could be translocated to nucleoli during mitosis. Pretreatment of cells with leptomycin B did not affect the distribution of nuclear γ‐tubulin, making it unlikely that rapid active transport via nuclear pores participates in the transport of γ‐tubulin into the nucleus. This finding was confirmed by heterokaryon assay and time‐lapse imaging of photoconvertible protein Dendra2 tagged to γ‐tubulin. Immunoprecipitation from nuclear extracts combined with mass spectrometry revealed an association of γ‐tubulin with tumor suppressor protein C53 located at multiple subcellular compartments including nucleoli. The notion of an interaction between γ‐tubulin and C53 was corroborated by pull‐down and co‐immunoprecipitation experiments. Overexpression of γ‐tubulin antagonized the inhibitory effect of C53 on DNA damage G2/M checkpoint activation. The combined results indicate that aside from its known role in microtubule nucleation, γ‐tubulin may also have nuclear‐specific function(s). J. Cell. Physiol. 227: 367–382, 2012. © 2011 Wiley Periodicals, Inc.
Lysyl hydroxylase 3 is secreted from cells by two pathways
Authors: Wang Chunguang , Ristiluoma Marja‐Maija , Salo Antti M. , Eskelinen Sinikka , Myllylä Raili
Published: April 2011

Lysyl hydroxylase 3 (LH3) is a post‐translational modification enzyme with lysyl hydroxylase (LH), collagen galactosyltransferase (GT), and glucosyltransferase (GGT) activities. The active sites responsible for LH and GT/GGT activities of LH3 are localized separately in the carboxy‐ and the amino‐terminal parts of the molecule, respectively. LH3 is found both intracellularly in the ER, as well as extracellularly in serum, the extracellular space and on cell surfaces, and is the only secreted LH isoform. In order to determine whether the activities of LH3 play a role in the secretion, we created various LH3 and mutant expression constructs and over‐expressed the proteins in COS‐7 and HT‐1080 cells. Our data indicate that while the LH active site mediates retention of LH3 in the ER, the GGT active site is required for the secretion of LH3 into the extracellular space. Moreover, Brefeldin A treatment and cholesterol depletion of the cells revealed that the secretion of LH3 from the ER to the extracellular space occurs via two secretory pathways, which generate two glycoforms. LH3 molecules found in the cell medium are secreted through the Golgi complex, and the secretion is dependent on LH3 glycosyltransferase activity. LH3 found on the cell surface bypasses the Golgi complex. J. Cell. Physiol. 227: 668–675, 2012. © 2011 Wiley Periodicals, Inc.
Dynamic redistribution of calcium sensitive potassium channels (hKCa3.1) in migrating cells
Authors: Schwab Albrecht , Nechyporuk‐Zloy Volodymyr , Gassner Birgit , Schulz Christoph , Kessler Wolfram , Mally Sabine , Römer Michael , Stock Christian
Published: April 2011

Calcium‐sensitive potassium channels (KCa3.1) are expressed in virtually all migrating cells. Their activity is required for optimal cell migration so that their blockade leads to slowing down. KCa3.1 channels must be inserted into the plasma membrane in order to elicit their physiological function. However, the plasma membrane of migrating cells is subject to rapid recycling by means of endo‐ and exocytosis. Here, we focussed on the endocytic internalization and the intracellular transport of the human isoform hKCa3.1. A hKCa3.1 channel construct with an HA‐tag in the extracellularly located S3‐S4 linker was transfected into migrating transformed renal epithelial MDCK‐F cells. Channel internalization was visualized and quantified with immunofluorescence and a cell‐based ELISA. Movement of hKCa3.1 channel containing vesicles as well as migration of MDCK‐F cells were monitored by means of time lapse video microscopy. hKCa3.1 channels are endocytosed during migration. Most of the hKCa3.1 channel containing vesicles are moving at a speed of up to 2 µm/sec in a microtubule‐dependent manner towards the front of MDCK‐F cells. Our experiments indicate that endocytosis of hKCa3.1 channels is clathrin‐dependent since they colocalize with clathrin adaptor proteins and since it is impaired when a C‐terminal dileucine motif is mutated. The C‐terminal dileucine motif is also important for the subcellular localization of hKCa3.1 channels in migrating cells. Mutated channels are no longer concentrated at the leading edge. We therefore propose that recycling of hKCa3.1 channels contributes to their characteristic subcellular distribution in migrating cells. J. Cell. Physiol. 227: 686–696, 2012. © 2011 Wiley Periodicals, Inc.
Regulation of inositol 1,4,5‐trisphosphate receptor function during mouse oocyte maturation
Authors: Wakai Takuya , Vanderheyden Veerle , Yoon Sook‐Young , Cheon Banyoon , Zhang Nan , Parys Jan B. , Fissore Rafael A.
Published: April 2011

At the time of fertilization, an increase in the intracellular Ca2+ concentration ([Ca2+]i) underlies egg activation and initiation of development in all species studied to date. The inositol 1,4,5‐trisphosphate receptor (IP3R1), which is mostly located in the endoplasmic reticulum (ER) mediates the majority of this Ca2+ release. The sensitivity of IP3R1, that is, its Ca2+ releasing capability, is increased during oocyte maturation so that the optimum [Ca2+]i response concurs with fertilization, which in mammals occurs at metaphase of second meiosis. Multiple IP3R1 modifications affect its sensitivity, including phosphorylation, sub‐cellular localization, and ER Ca2+ concentration ([Ca2+]ER). Here, we evaluated using mouse oocytes how each of these factors affected IP3R1 sensitivity. The capacity for IP3‐induced Ca2+ release markedly increased at the germinal vesicle breakdown stage, although oocytes only acquire the ability to initiate fertilization‐like oscillations at later stages of maturation. The increase in IP3R1 sensitivity was underpinned by an increase in [Ca2+]ER and receptor phosphorylation(s) but not by changes in IP3R1 cellular distribution, as inhibition of the former factors reduced Ca2+ release, whereas inhibition of the latter had no impact. Therefore, the results suggest that the regulation of [Ca2+]ER and IP3R1 phosphorylation during maturation enhance IP3R1 sensitivity rendering oocytes competent to initiate oscillations at the expected time of fertilization. The temporal discrepancy between the initiation of changes in IP3R1 sensitivity and acquisition of mature oscillatory capacity suggest that other mechanisms that regulate Ca2+ homeostasis also shape the pattern of oscillations in mammalian eggs. J. Cell. Physiol. 227: 705–717, 2012. © 2011 Wiley Periodicals, Inc.
Vitamin A metabolism in benign and malignant melanocytic skin cells: Importance of lecithin/retinol acyltransferase and RPE65
Authors: Amann Philipp M. , Luo Chonglin , Owen Robert W. , Hofmann Claudia , Freudenberger Muriel , Schadendorf Dirk , Eichmüller Stefan B. , Bazhin Alexandr V.
Published: April 2011

Disturbance in vitamin A metabolism seems to be an important attribute of cancer cells. Retinoids, particularly retinoic acid, have critical regulatory functions and appear to modulate tumor development and progression. The key step of vitamin A metabolism is the esterification of all‐trans retinol, catalyzed by lecithin/retinol acyltransferase (LRAT). In this work, we show that malignant melanoma cells are able to esterify all‐trans retinol and subsequently isomerize all‐trans retinyl esters (RE) into 11‐cis retinol, whereas their benign counterparts—melanocytes are not able to catalyze these reactions. Besides, melanoma cell lines express lecithin/retinol acyltranseferase both at the mRNA and protein levels. In contrast, melanocytes do not express this enzyme at the protein level, but mRNA of lecithin/retinol acyltransefrase could still be present at mRNA level. RPE65 is expressed in both melanocytic counterparts, and could be involved in the subsequent isomerization of RE produced by lecithin/retinol acyltransefrase to 11‐cis retinol. Cellular retinol‐binding protein 2 does not appear to be involved in the regulation of all‐trans retinol esterification in these cells. Expression of LRAT and RPE65 can be modulated by retinoids. We propose that the post‐transcriptional regulation of lecithin/retinol acyltransefrase could be involved in the differential expression of this enzyme. Besides, activities of LRAT and RPE65 may be important for removal of all‐trans retinal which is the substrate for retinoic acid production in skin cells. Consequently, the decreasing cellular amount of retinoic acid and its precursor molecules could result in a change of gene regulation. J. Cell. Physiol. 227: 718–728, 2012. © 2011 Wiley Periodicals, Inc.
The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2
Authors: Hamada Shin , Satoh Kennichi , Hirota Morihisa , Kanno Atsushi , Umino Jun , Ito Hiromichi , Masamune Atsushi , Kikuta Kazuhiro , Kume Kiyoshi , Shimosegawa Tooru
Published: April 2011

Pancreatic cancer is one of the life‐threatening cancers due to the difficulty in the curative surgery and resistance against conventional therapeutic strategies. Recent studies indicated that cancer stem cells, which exist as a small number of cells within the entire cancer tissue, contribute to the disease progression. Cancer stem cells reveal resistance against conventional chemotherapy, which is derived from the high‐expression of multiple transporter genes. Our previous study demonstrated the aggravating role of the homeobox gene MSX2 as an inducer of epithelial‐mesenchymal transition, and MSX2 turned out to correlate with the chemoresistance in the current study. Comprehensive analysis of the MSX2‐target gene has identified ABCG2 as the responsible gene. Since previous studies reported the pivotal role of ABCG2 as a determining factor of cancer stem cells, the detailed regulatory mechanism of ABCG2 expression by MSX2 was investigated. As a result, the MSX2 expression level in each cell line well correlated with the ABCG2 expression level, and alteration of the MSX2 expression level by over‐expression or siRNA‐based knockdown affected the ABCG2 expression accordingly. Finally, we identified the functional cooperation of MSX2 and SP1 in the transcriptional regulation of ABCG2 via the SP1 binding elements within the ABCG2 promoter. These findings clarified the intriguing regulatory mechanism of the cancer stem cell‐related gene, and will delineate a novel therapeutic target in pancreatic cancer. J. Cell. Physiol. 227: 729–738, 2012. © 2011 Wiley Periodicals, Inc.
Insulin‐like growth factor 1 stimulation of androgen receptor activity requires β1A integrins
Authors: Sayeed Aejaz , Alam Naved , Trerotola Marco , Languino Lucia R.
Published: April 2011

Despite the findings that β1 integrins play a vital role in the regulation of cell proliferation and survival, the mechanisms through which they operate and lead to cancer progression remain elusive. Previously, our laboratory has shown that β1A integrins support insulin‐like growth factor 1 (IGFI)‐mediated mitogenic and transforming activities. Here, we report that β1A integrins regulate basal levels of IGF‐IR, although they are not critical for maintaining cancer cell morphology. Upon transfection of β1A siRNA and consequent downregulation of IGF‐IR, we show inhibition of anchorage‐independent growth of prostate cancer cells, a function which is dependent on IGF‐IR expression. In addition, we demonstrate that IGFI‐mediated activation of androgen receptor (AR), known to occur in prostate cancer cells, requires expression of β1A integrins as evaluated by luciferase reporter assays and immunoblotting analysis. Since β1A integrin levels are increased by R1881 or dihydrotestosterone (DHT), our results imply that β1A integrins support an androgen‐enhanced feedback loop that regulates the expression of IGF‐IR. β1A integrins also regulate inducible levels of IGF‐IR in cells stimulated by androgen or by a combination of androgen and IGFI, as evaluated by flow cytometric analysis and immunoblotting. Furthermore, upon transfection of β1A siRNA and consequent downregulation of IGF‐IR, neither activation of AKT, an effector of IGF‐IR, nor AR levels are affected. We conclude that β1A integrin expression is critical for maintaining the regulatory crosstalk between IGF‐IR and AR. J. Cell. Physiol. 227: 751–758, 2012. © 2011 Wiley Periodicals, Inc.
The switch from pRb/p105 to Rb2/p130 in DNA damage and cellular senescence
Authors: Helmbold Heike , Galderisi Umberto , Bohn Wolfgang
Published: April 2011

Cellular senescence is a response to genotoxic stress that results in an irreversible cell cycle arrest. Activation of this pathway relies on the activity of the retinoblastoma proteins and proteins of the DNA damage response cascade. Here, we discuss the functional relevance of the switch from pRb/p105 to Rb2/p130 that becomes apparent when cells enter senescent arrest. J. Cell. Physiol. 227: 508–513, 2012. © 2011 Wiley Periodicals, Inc.
Seawater at the nanoscale: marine gel imaged by atomic force microscopy
Authors: Radić Tea Mišić , Svetličić Vesna , Žutić Vera , Boulgaropoulos Beate
Published: April 2011

The present study introduces atomic force microscopy (AFM) as a tool for characterization of marine gel network and marine biopolymers self‐assembly, not accessible by other techniques. AFM imaging of marine gel samples collected in summers 2003 and 2004 in the northern Adriatic Sea provided insight into molecular organization of gel network and associations between polysaccharide fibrils in the network. Initial stages of biopolymers self‐assembly were visualized by AFM in a phytoplankton bloom experiment performed in the same aquatorium. Based on AFM imaging and differential scanning calorimetry, the marine gel is characterized as a thermoreversible physical gel and the dominant mode of gelation as crosslinking of polysaccharide fibrils by hydrogen bonding which results in helical structures and their associations. Direct deposition of whole seawater on freshly cleaved mica followed by rinsing was the procedure that caused the least impact on the original structures of biopolymer assemblies in seawater. Copyright © 2011 John Wiley & Sons, Ltd.
Unraveling lipid/protein interaction in model lipid bilayers by Atomic Force Microscopy
Authors: Alessandrini Andrea , Facci Paolo
Published: April 2011

The current view of the biological membrane is that in which lipids and proteins mutually interact to accomplish membrane functions. The lateral heterogeneity of the lipid bilayer can induce partitioning of membrane‐associated proteins, favoring protein–protein interaction and influence signaling and trafficking. The Atomic Force Microscope allows to study the localization of membrane‐associated proteins with respect to the lipid organization at the single molecule level and without the need for fluorescence staining. These features make AFM a technique of choice to study lipid/protein interactions in model systems or native membranes. Here we will review the technical aspects inherent to and the main results obtained by AFM in the study of protein partitioning in lipid domains concentrating in particular on GPI‐anchored proteins, lipidated proteins, and transmembrane proteins. Whenever possible, we will also discuss the functional consequences of what has been imaged by Atomic Force Microscopy. Copyright © 2011 John Wiley & Sons, Ltd.
Nuclear delivery mechanism of herpes simplex virus type 1 genome
Authors: Liashkovich Ivan , Hafezi Wali , Kühn Joachim M , Oberleithner Hans , Shahin Victor
Published: April 2011

Herpes simplex virus type 1 (HSV‐1) is a widespread human pathogen infecting more than 80% of the population worldwide. Its replication involves an essential, poorly understood multistep process, referred to as uncoating. Uncoating steps are as follows: (1) The incoming capsid pinpoints the nuclear pore complex (NPC). (2) It opens up at the NPC and releases the highly pressurized viral genome. (3) The viral genome translocates through the NPC. In the present review, we highlight recent advances in this field and propose mechanisms underlying the individual steps of uncoating. We presume that the incoming HSV‐1 capsid pinpoints the NPC by hydrophobic interactions and opens up upon binding to NPC proteins. Genome translocation is initially pressure‐driven. Copyright © 2011 John Wiley & Sons, Ltd.
Intragastric approach for submucosal tumors located near the Z‐line: A hybrid laparoscopic and endoscopic technique
Authors: Shim Jung Ho , Lee Han Hong , Yoo Han Mo , Jeon Hae Myung , Park Cho Hyun , Kim Jun Gi , Song Kyo Young
Published: April 2011

Background

The present study was designed to evaluate the feasibility and impact of the “intragastric” approach to laparoscopic wedge resection as a surgical option for the treatment of suspected small sized gastric submucosal tumors (SMTs) located at the level of Z‐line.

Methods

We reviewed six patients who underwent laparoscopic intragastric resection of a suspected gastric SMT. In all cases, tumor mass was located just below the Z‐line. The patients' clinicopathologic characteristics and surgical outcomes were prospectively recorded and reviewed.

Results

All six patients were underwent successfully laparoscopic wedge resection by the intragastric approach using a balloon‐type trocar. No case was required open conversion. The mean operation time was 128 min, and the mean hospital stay was 4 days. Five cases were proven to have leiomyoma, and one case was found to have gastrointestinal stromal tumor with low risk. The mean tumor size was 2.7 cm.

Conclusion

Laparoscopic resection through the “intragastric” approach is a safe and feasible option for gastric SMTs located at the level of Z‐line. J. Surg. Oncol. 2011; 104:312–315. © 2011 Wiley‐Liss, Inc.
A COSMO‐RS based QSPR model for the lubricity of biodiesel and petrodiesel components
Authors: Masuch K. , Fatemi A. , Murrenhoff H. , Leonhard K.
Published: April 2011

The development of a new, optimised fuel is a process in which various necessary fuel properties have to be taken into account. For an inclusion of candidates not synthesised yet into the design process, a fully predictive model relying on nothing but the molecular structure is mandatory for each relevant property. One of the most important aspects for the design of a fuel is its lubricity. In this study, the predictive method conductor‐like screening model for realistic solvation (COSMO‐RS) for the calculation of thermodynamic mixture properties is adopted for deriving a quantitative structure–property relationship for the lubricity of fuel components. COSMO‐RS calculates molecular descriptors (sigma moments) based on quantum chemical calculations. These descriptors are adapted to describe the underlying phenomena causing the film formation ability and lubricity of the fuel. The lubricity is assessed via high‐frequency reciprocating rig measurements taken from literature. The molecular descriptors and experimental data are evaluated via statistical methods in order to find the most influential molecular descriptors. Copyright © 2011 John Wiley & Sons, Ltd.
Human papillomavirus vaccine: Widening the scope for cancer prevention
Authors: No Jae Hong , Kim Mi‐Kyung , Jeon Yong‐Tark , Kim Yong‐Beom , Song Yong‐Sang
Published: April 2011

Human papillomavirus (HPV) is the necessary cause of cervical cancer. The HPV oncoproteins E6 and E7 have crucial roles in various steps of carcinogenesis, inducing degradation of p53 and destabilization of pRb. Several clinical trials show that recombinant HPV vaccines are safe and effective in preventing persistent infection of HPV and associated anogenital lesions. Although most clinical studies to date have investigated the effectiveness of HPV vaccines in young female subjects, elderly females and males may also be candidates for HPV vaccines. Prophylactic HPV vaccination may be an ideal preventive method for other HPV‐associated cancers in addition to cervical carcinoma. Carcinogenesis by HPV, efficacy trials of currently available HPV vaccines, and the possible roles of HPV vaccines in the prevention of HPV‐associated cancers are reviewed in this article. © 2011 Wiley‐Liss, Inc.
Redox modulation of p53: Mechanisms and functional significance
Authors: Kim Do‐Hee , Kundu Joydeb Kumar , Surh Young‐Joon
Published: April 2011

The tumor suppressor protein p53 functions as a stress‐responsive transcription factor. In response to oxidative, nitrosative, and electrophilic insults, p53 undergoes post‐translational modifications, such as oxidation and covalent modification of cysteines, nitration of tyrosines, acetylation of lysines, phosphorylation of serine/threonine residues, etc. Because p53 plays a vital role in the transcriptional regulation of genes encoding proteins involved in a wide spectrum of biochemical processes including DNA repair, cell‐cycle regulation, and programmed cell death, the redox‐modification of p53 appears to be an important determinant of cell fate. This review highlights the redox regulation of p53 and its consequences on cellular function. © 2011 Wiley‐Liss, Inc.
Antioxidant‐rich coffee reduces DNA damage, elevates glutathione status and contributes to weight control: Results from an intervention study
Authors: Bakuradze Tamara , Boehm Nadine , Janzowski Christine , Lang Roman , Hofmann Thomas , Stockis Jean‐Pierre , Albert Franz W. , Stiebitz Herbert , Bytof Gerhard , Lantz Ingo , Baum Matthias , Eisenbrand Gerhard
Published: April 2011

Epidemiological and experimental evidence increasingly suggests coffee consumption to be correlated to prevention or delay of degenerative diseases connected with oxidative cellular stress. In an intervention study comprising 33 healthy volunteers, we examined DNA‐protective and antioxidative effects exerted in vivo by daily ingestion of 750 mL of freshly brewed coffee rich in both green coffee bean constituents as well as roast products. The study design encompassed an initial 4 wk of wash‐out, followed by 4 wk of coffee intake and 4 wk of second wash‐out. At the start and after each study phase blood samples were taken to monitor biomarkers of oxidative stress response. In addition, body weight/composition and intake of energy/nutrients were recorded. In the coffee ingestion period, the primary endpoint, oxidative DNA damage as measured by the Comet assay (±FPG), was markedly reduced (p<0.001). Glutathione level (p<0.05) and GSR‐activity (p<0.01) were elevated. Body weight (p<0.01)/body fat (p<0.05) and energy (p<0.001)/nutrient (p<0.001–0.05) intake were reduced. Our results allow to conclude that daily consumption of 3–4 cups of brew from a special Arabica coffee exerts health beneficial effects, as evidenced by reduced oxidative damage, body fat mass and energy/nutrient uptake.
Morphology enabled dipole inversion (MEDI) from a single‐angle acquisition: Comparison with COSMOS in human brain imaging
Authors: Liu Tian , Liu Jing , de Rochefort Ludovic , Spincemaille Pascal , Khalidov Ildar , Ledoux James Robert , Wang Yi
Published: April 2011

Magnetic susceptibility varies among brain structures and provides insights into the chemical and molecular composition of brain tissues. However, the determination of an arbitrary susceptibility distribution from the measured MR signal phase is a challenging, ill‐conditioned inverse problem. Although a previous method named calculation of susceptibility through multiple orientation sampling (COSMOS) has solved this inverse problem both theoretically and experimentally using multiple angle acquisitions, it is often impractical to carry out on human subjects. Recently, the feasibility of calculating the brain susceptibility distribution from a single‐angle acquisition was demonstrated using morphology enabled dipole inversion (MEDI). In this study, we further improved the original MEDI method by sparsifying the edges in the quantitative susceptibility map that do not have a corresponding edge in the magnitude image. Quantitative susceptibility maps generated by the improved MEDI were compared qualitatively and quantitatively with those generated by calculation of susceptibility through multiple orientation sampling. The results show a high degree of agreement between MEDI and calculation of susceptibility through multiple orientation sampling, and the practicality of MEDI allows many potential clinical applications. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.