bluuebunny/crossref_metadata_2025 huggingface dataset:
The negative costimulatory molecule PD‐1 modulates the balance between immunity and tolerance via miR‐21
Authors: Iliopoulos Dimitrios , Kavousanaki Melina , Ioannou Marianna , Boumpas Dimitrios , Verginis Panayotis
Published: March 2011

Disruption of the programmed death‐1 (PD‐1) pathway leads to breakdown of peripheral tolerance and initiation of autoimmunity. The molecular pathways that mediate this effect remain largely unknown. We report here that PD‐1 knockout (PD‐1−/−) mice develop more severe and sustained Ag‐induced arthritis (AIA) than WT animals, which is associated with increased T‐cell proliferation and elevated levels of IFN‐γ and IL‐17 secretion. MicroRNA analysis of Ag‐specific CD4+ T cells revealed a significant upregulation of microRNA 21 (miR‐21) in PD‐1−/− T cells compared with WT controls. In addition, PD‐1 inhibition, via siRNA, upregulated miR‐21 expression and enhanced STAT5 binding in the miR‐21 promoter area. Computational analysis confirmed that miR‐21 targets directly the expression of programmed cell death 4 (PDCD4) and overexpression of miR‐21 in cells harboring the 3′UTR of PDCD4 resulted in reduced transcription and PDCD4 protein expression. Importantly, in vitro delivery of antisense‐miR‐21 suppressed the Ag‐specific proliferation and cytokine secretion by PD‐1−/− T cells, whereas adoptive transfer of Ag‐specific T cells, overexpressing miR‐21, induced severe AIA. Collectively, our data demonstrate that breakdown of tolerance in PD‐1−/− mice activates a signaling cascade mediated by STAT5, miR‐21, and PDCD4 and establish their role in maintaining the balance between immune activation and tolerance.
Ruthenium–Porphyrin Complexes Induce Apoptosis by Inhibiting the Generation of Intracellular Reactive Oxygen Species in the Human Hepatoma Cell Line (HepG2)
Authors: Liu Yanan , Zhang Xiaonian , Zhang Rong , Chen Tianfeng , Wong Yum‐Shing , Liu Jie , Zheng Wen‐Jie
Published: March 2011

Two ruthenium(II)–porphyrin complexes, [(3‐Py)Ru(phen)2(tmopp)] [1; phen = phenanthroline, tmopp = 5,10,15,20‐tetrakis(4‐methoxyphenyl)porphyrin] and [(4‐Py)Ru(phen)2(tmopp)] (2), have been synthesized and characterized for the first time. It was found that the two ruthenium(II)–porphyrin complexes show significant antitumor activity in HepG2 cells. Flow cytometric analysis showed that complex 1 arrested the cell cycle in the G0/G1 phase and induced apoptosis in HepG2 cells. Fluorescence microscopy and flow cytometric analyses demonstrated that the generation of intracellular reactive oxygen species (ROS) was significantly inhibited in cells treated with either complex. The total antioxidant capacity of the complexes was detected by a 2,2′‐azinobis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) assay; this showed that both complexes are good free‐radical scavengers. Ruthenium(II)–porphyrin complex 1 also was found to scavenge hydroxy radicals, as measured by the Fenton system. These data demonstrate that ruthenium(II)–porphyrin complexes exhibit antioxidant properties, probably through the involvement of a direct scavenging effect on a hydroxy radical. Taken together, the findings show that ruthenium(II)–porphyrin complexes induce apoptosis in HepG2 cells by inhibiting the generation of ROS and are potential anticancer therapeutic agents.
Spectroscopic, Structural and DFT Study of the Responses of Carbonylmetal Crown Ether Complexes to Alkali Metal Cations
Authors: Stephenson G. Richard , Anson Christopher E. , Creaser Colin S. , Daul Claude A.
Published: March 2011

FTIR spectra of tricarbonyl(η6‐benzo‐15‐crown‐5)chromium(0) (1) in the presence of lithium, sodium and potassium perchlorate salts in methanol show different responses in the Cr–CO vibrational region of the spectrum. Data from the symmetric (νsym) and antisymmetric (νasym) Cr–CO vibrational stretching modes have been analysed by principal component analysis (PCA) to generate a factor score plot that provides a visual representation of these differential responses. X‐ray crystallographic data for the sodium perchlorate complex 1·Na+ and dimensions from DFT‐derived structures of 1·Li+, 1·Na+ and 1·K+ indicate that binding M+ in the crown causes electron density and structural changes in the [O(4)–C(9)–C(4)–O(8)]Cr–C(1)=O(1) sections of 1, which vary depending on the nature of the cation. This suggests a mode of action in which Li+ associates with a more compact O(4)–C(9)–C(4)–O(8), while Na+ and K+ differ crucially in the extent of σ and π contributions to their effect on νsym and νasym. A comparison of the FTIR data from 1, tricarbonyl(η6‐1‐phenyl‐1‐aza‐15‐crown‐5)chromium(0) (2) and tricarbonyl(η6‐2‐phenyl‐15‐crown‐5)chromium(0) (3) with a wider range of cations (NH4+, Li+, Na+, K+, Rb+, Cs+, Mg2+, Ba2+) and anions (AcO–, BPh4–, Br–, C1O4–, I–, SCN–), showed that 1 and 3 both responded significantly to the different metal cations, but 2 did not. The relative cation differentiation of 1, 2 and 3 was measured using the parameter ΔR(cation), and ratios of ΔN(cation) values [calculated from ΔR(cation)] distinguished different effects in the FTIR spectra of 1 and 3 for different pairs of cations.
Intermolecular Hydrogen–Fluorine Interaction in Dimolybdenum Triply Bonded Complexes Modified by Fluorinated Formamidine Ligands for the Construction of 2D‐ and 3D‐Networks
Authors: Krackl Sebastian , Inoue Shigeyoshi , Driess Matthias , Enthaler Stephan
Published: March 2011

The formamidines ArNHC(H)=N–Ar [Ar = Ph (2a), 4‐F‐Ph (2b), 3,5‐F2Ph (2c) and 2,6‐F2Ph (2d) and R = 2,3,5‐F3Ph (2e), 3,4,5‐F3Ph (2f), F5Ph (2g) and 4‐CF3Ph (2h)] were synthesized and the influence of the introduction of a fluorine or a trifluoromethyl group into the aryl unit on the solid‐state structures was investigated. On comparing the experimental data, only marginal differences in the geometrical and electronic features of the diverse substituted species were detected. DFT calculations and X‐ray crystallography of 2d–2g revealed that the E‐syn‐configuration corresponded to the thermodynamically most stable motif of all of the examined formamidines. However, in their solid‐state, these ligands showed a range of H···F interactions, which varied depending on the number and position of the fluorine atoms on the aryl group and thus led to interesting solid‐state structures. Moreover, compounds 2 were used for the synthesis of the new heteroleptic dimolybdenum triply‐bonded complexes, Mo2[(2a–2c; 2e–f)–H]2(OtBu)4 (3a–3c; 3e–3f). X‐ray crystallography of complexes 3c and 3f revealed two different isomers in the solid state: in trans‐3c the two formamidines are in one plane, while in cis‐3c and cis‐3f they are next to each other. The DFT calculations showed only a small distinction in energy between the configurations, which led us to assume that the different configurations were induced by the crystal packing. The specific H···F interactions provided by the different formamidines led to a two‐dimensional arrangement for trans‐3c and a three‐dimensional network for cis‐3c and cis‐3f.
Li2Sr4[Si2N5]N – A Layered Lithium Nitridosilicate Nitride
Authors: Lupart Saskia , Pagano Sandro , Oeckler Oliver , Schnick Wolfgang
Published: March 2011

The quaternary alkaline earth nitridosilicate nitride Li2Sr4[Si2N5]N has been synthesized at 900 °C using liquid lithium as fluxing agent in weld‐shut tantalum ampoules. The structure of Li2Sr4[Si2N5]N {space group I$\bar {4}$m2 [no. 119, a = 751.46(11), c = 1508.9(3) pm, Z = 4, R1 = 0.049, wR2 = 0.135, 499 data, 41 parameters]} is built up from vertex sharing [SiN4] tetrahedra forming layers which can be derived from the apophyllite structure type. According to the condensation degree of κ = 2:5 discrete N3– ions which are coordinated by five Sr2+ and one Li+ site occur besides the silicate layers in the crystal structure. The electronic structure and chemical bonding in Li2Sr4[Si2N5]N has been analyzed by Madelung calculations (MAPLE) and DFT (VASP) calculations.
N‐(Di)icosyl‐Substituted Benzo[a]phenoxazinium Chlorides: Synthesis and Evaluation as Near‐Infrared Membrane Probes
Authors: Naik Sarala , Alves Carla M. A. , Coutinho Paulo J. G. , Gonçalves M. Sameiro T.
Published: March 2011

Five benzo[a]phenoxazinium chlorides containing alkyl chains with twenty carbon atoms at the 5‐ or 9‐positions of the tetracyclic ring were efficiently synthesised and characterised by UV/Vis and NIR spectroscopy. The absorption and emission maxima in ethanol occur in the range 627–641 nm and 645–676 nm, respectively, with quantum yields varying from 0.14 to 0.38. Preliminary photophysical studies with these fluorochromophores in zwitterionic [2,3‐bis(palmitoyloxy)propyl‐2‐(trimethylammonio)ethyl phosphate, DPPC] and cationic (N,N‐dimethyl‐N‐octadecyloctadecan‐1‐aminium bromide, DODAB) vesicles were carried out. The results showed that the new benzo[a]phenoxazinium derivatives are able to detect the gel to liquid‐crystalline lipid phase transition through variations in either the extent of H‐aggregation or in the acid–base equilibrium.
Ionizing Power of Aprotic Solvents
Authors: Streidl Nicolas , Mayr Herbert
Published: March 2011

Rate constants for the heterolysis reactions (SN1) of a series of chloro‐diarylmethanes in aprotic solvents (dimethyl sulfoxide (DMSO), acetonitrile, carboxamides, etc.) have been determined conductometrically in the presence of amines or triphenylphosphane, which trap the intermediate ion‐pairs and suppress ion recombination. The operation of SN2 mechanisms can be excluded because the observed first‐order rate constants become almost independent of the nature of the nucleophilic additive when a certain concentration of nucleophile is exceeded. The heterolysis rate constants are used to calculate nucleofugality parameters Nf and sf for chloride in aprotic solvents according to the linear free‐energy relationship lg k (25 °C) = sf(Nf + Ef). Ionizing powers YBnCl of these solvents were calculated according to the Winstein–Grunwald equation. Because the heterolysis rate constants in aprotic solvents correlate only poorly with dielectric constants or empirical solvent parameters such as Gutmann's acceptor numbers or ETN values, the most common solvent polarity parameters do not reliably predict ionization rates in aprotic solvents.
Facile Access to 3,5‐Dihalogenated Pyrazoles by Sydnone Cycloaddition and their Versatile Functionalization by Pd‐Catalyzed Cross‐Coupling Processes
Authors: Delaunay Thierry , Es‐Sayed Mazen , Vors Jean‐Pierre , Monteiro Nuno , Balme Geneviève
Published: March 2011

The 1,3‐dipolar cycloaddition of diversely N‐substituted 4‐iodosydnones with 3‐halopropiolates produces easily separable mixtures of dihalogenated pyrazolylcarboxylic esters at a preparative scale level, with the 3,5‐dihalogenopyrazole regioisomers always predominating. Further decarboxylation of the major isomers provided the corresponding 3,5‐dihalogenopyrazoles with a free C‐4 position. These were found to be valuable scaffolds for the elaboration of unsymmetrically 1,3,5‐trisubstituted pyrazole derivatives by site‐selective Pd‐catalyzed cross‐coupling reactions. Notably, the flexible and site‐selective introduction of different (hetero)aryl, vinyl, or alkyl substituents at the C‐5 and C‐3 positions of the pyrazole core could be achieved through sequential Suzuki‐type reactions with various boron compounds. Furthermore, the Suzuki coupling sequence could be amenable to a one‐pot procedure that enables rapid generation of the targeted compounds.
Intercalation of Tetrathiafulvalene between the Two Plates of a Copper(I)‐Complexed [4]Rotaxane
Authors: Sauvage Jean‐Pierre , Trolez Yann , Canevet David , Sallé Marc
Published: March 2011

The ability of a cyclic copper(I)‐complexed [4]rotaxane to act as a receptor towards organic electron donors has been studied. In particular, tetrathiafulvalene (TTF), which is a flat and electron‐rich molecule, forms a relatively stable complex with the rotaxane host. 1H NMR spectroscopic measurements strongly suggest that the coordination mode involves intercalation of the TTF motif between the two electron‐poor plates of the [4]rotaxane. By contrast, extended TTF (exTTF), which possesses π‐donating ability similar to that of TTF but which is a significantly bulkier molecule due to a concave structure, was not able to form any detectable complex. This observation tends to indicate that the recognition site of the [4]rotaxane receptor is rigid and can not adapt to thick substrates.
Voltammetric Determination of Both Concentration and Diffusion Coefficient by Combinational Use of Regular and Microelectrodes
Authors: Zhang Hua , Aoki Koichi , Chen Jingyuan , Nishiumi Toyohiko , Toda Hirokazu , Torita Eiji
Published: March 2011

Two Pt disks with 1.6 and 0.1 mm diameter, whose sizes were accurately evaluated, were applied to voltammetric diffusion‐controlled currents to determine the concentrations of redox species. Since voltammetric peak currents at a regular electrode, Ip, and limiting currents at a microelectrode, IL, are proportional to D1/2 and D, respectively, the ratio Ip2/IL is independent of the diffusion coefficient but dependents on the concentration. We used this fact to determine the concentrations of ferrocenyl derivatives, hemin, hexacyanoferrate(II), dioxygen gas and hydrogen gas. New insights are not only the absolute determination of concentrations but also the sensitive detection of adsorption of electrochemical products which blocked the voltammetric currents.
A New Voltammetric Sensor Based on a Glassy Carbon Electrode Modified with 8‐Hydroxyquinoline‐5‐sulfonic Acid
Authors: Brunetti Barbara , Desimoni Elio
Published: March 2011

The preparation and characterization of a new modified glassy carbon electrode (GCE) obtained by cycling the potential in a 8‐hydroxyquinoline‐5‐sulfonic acid (HQSA) solution is presented. The influence of the deposition parameters on analytical performance is evaluated along with the comparison with the behavior of an activated GCE obtained by the same electrochemical treatment but in absence of HQSA. The modification by HQSA leads to improved electrochemical performances with respect to those of a bare or activated GCE. This is shown by applying the proposed electrode to the determination of some species of pharmaceutical and alimentary interest.
Enhanced Electroanalytical Sensitivity via Interface Miniaturisation: Ion Transfer Voltammetry at an Array of Nanometre Liquid–Liquid Interfaces
Authors: Scanlon Micheál D. , Arrigan Damien W. M.
Published: March 2011

The benefit of miniaturization towards the nanoscale of electroanalytical systems was evaluated by assessment of the sensitivity of the response. Ion transfer voltammetry across the interface between two immiscible electrolyte solutions (ITIES) was employed as the basis for detection of nonredoxactive ions. The analytical sensitivity increased on miniaturisation of the interface from millimetre‐, to micrometre‐, to nanometre‐scale, with an improvement in sensitivity of more than three orders of magnitude. This is due to the enhanced mass transport via convergent diffusion as the size of the ITIES is minimised. These results illustrate the benefit of miniaturisation of electrochemical detection methods to the nanoscale.
Non‐canonical functions of the tuberous sclerosis complex‐Rheb signalling axis
Authors: Neuman Nicole A. , Henske Elizabeth Petri
Published: March 2011

The protein products of the tuberous sclerosis complex (TSC) genes, TSC1 and TSC2, form a complex, which inhibits the small G‐protein, Ras homolog enriched in brain (Rheb). The vast majority of research regarding these proteins has focused on mammalian Target of Rapamycin (mTOR), a target of Rheb. Here, we propose that there are clinically relevant functions and targets of TSC1, TSC2 and Rheb, which are independent of mTOR. We present evidence that such non‐canonical functions of the TSC‐Rheb signalling network exist, propose a standard of evidence for these non‐canonical functions, and discuss their potential clinical and therapeutic implications for patients with TSC and lymphangioleiomyomatosis (LAM).
Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children
Authors: Ruiz-Extremera Ángeles , Muñoz-Gámez José Antonio , Salmerón-Ruiz María Angustias , de Rueda Paloma Muñoz , Quiles-Pérez Rosa , Gila-Medina Ana , Casado Jorge , Martín Ana Belén , Sanjuan-Nuñez Laura , Carazo Ángel , Pavón Esther José , Ocete-Hita Esther , León Josefa , Salmerón Javier
Published: March 2011

The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV−ve), with 128 children, and 33 were HCV-RNA−ve/HCV antibody+ve, with 43 children. The infants were tested for HCV-RNA at birth and at regular intervals until the age of 6 years. IL28B (single nucleotide polymorphism rs12979860) was determined in the mothers and children. HCV-VT was assumed when children presented HCV-RNA+ve in two subsequent blood samples. HCV-VT-infected infants were categorized as: (1) transient viremia with posterior HCV-RNA−ve and without serum-conversion; (2) persistent infection with serum-conversion. Of the 31 mothers with CC polymorphism, 19 (61%) were HCV-RNA+ve, whereas among the 68 mothers with non-CC polymorphism, 56 (82%) were HCV-RNA+ve. In all, 26 of 128 (20%) infants born to the HCV-RNA+ve mothers acquired HCV infection, but only 9 (7%) were chronically infected. The rate of HCV-VT was higher among the mothers with higher HCV viremia. No HCV-VT was detected in the HCV-RNA−ve women. Neither the mothers' nor the childrens' IL-28 status was associated with an increased risk of HCV-VT. The factors influencing viral clearance among the infected children were genotype non-1 and genotype CC of IL28B. In logistic regression, child CC polymorphism was the only predictor of HCV-clearance in HCV genotype-1. Conclusion: High maternal viral load is the only predictive factor of HCV-VT. IL28B plays no role in HCV-VT, but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype-1 among infected children. (HEPATOLOGY 2011;)
Electrostatic modifications of the human leukocyte antigen-DR P9 peptide-binding pocket and susceptibility to primary sclerosing cholangitis
Authors: Hov Johannes R. , Kosmoliaptsis Vasilis , Traherne James A. , Olsson Marita , Boberg Kirsten M. , Bergquist Annika , Schrumpf Erik , Bradley Andrew J. , Taylor Craig J. , Lie Benedicte A. , Trowsdale John , Karlsen Tom H.
Published: March 2011

The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC ( P = 1.2 × 10−32 and P = 1.8 × 10−22 in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket.

Conclusion:

The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DRβ chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;)
Re‐expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer
Authors: Ieda Junji , Yokoyama Shozo , Tamura Koichi , Takifuji Katsunari , Hotta Tsukasa , Matsuda Kenji , Oku Yoshimasa , Nasu Toru , Kiriyama Shigehisa , Yamamoto Naoyuki , Nakamura Yasushi , Shively John E. , Yamaue Hiroki
Published: March 2011

Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is known to be downregulated at the transcriptional level in adenoma and carcinoma. Recent reports have shown that CEACAM1 is overexpressed at protein level in colorectal cancer and correlated with clinical stage. The reason why colorectal cancer cells re‐expressed CEACAM1 remains unclear. The aim of our study was to clarify the implication of CEACAM1 re‐expression in colorectal cancer. Immunohistochemical analyses were conducted with CEACAM1 long (CEACAM1‐L) or short (CEACAM1‐S) cytoplasmic domain‐specific antibodies on clinical samples from 164 patients with colorectal cancer. The risk factors for metastasis and survival were calculated for clinical implication of CEACAM1 re‐expression. Invasion chamber and wound healing assays were performed for the effect of CEACAM1 expression on invasion and migration of colorectal cancer cells. CEACAM1‐L and CEACAM1‐S stained with greater intensity at the invasion front than at the luminal surface of tumors. Differences between the long and short cytoplasmic isoform expression levels were observed at the invasion front. Multivariate analysis showed that CEACAM1‐L dominance was an independent risk factor for lymph node metastasis, hematogenous metastasis and short survival. The Kaplan–Meier evaluation demonstrated that CEACAM1‐L dominance was associated with shorter survival time (p < 0.0001). In the invasion chamber and wound healing assays, CEACAM1‐L promoted invasion and migration. Re‐expression of CEACAM1 is observed at the invasion front of colorectal cancer. CEACAM1‐L dominance is associated with metastasis and shorter survival of the patients with colorectal cancer. CEACAM1‐L dominance is important for colorectal cancer cells invasion and migration.
Mechanism of cell death mediated by a BF2‐chelated tetraaryl‐azadipyrromethene photodynamic therapeutic: Dissection of the apoptotic pathway in vitro and in vivo
Authors: O'Connor Aisling E. , Mc Gee Margaret M. , Likar Yury , Ponomarev Vladimir , Callanan John J. , O'shea Donal F. , Byrne Annette T. , Gallagher William M.
Published: March 2011

Photodynamic therapy (PDT) is an established treatment modality for cancer. ADPM06 is an emerging non‐porphyrin PDT agent which has been specifically designed for therapeutic application. Recently, we have demonstrated that ADPM06‐PDT is well tolerated in vivo and elicits impressive complete response rates in various models of cancer when a short drug‐light interval is applied. Herein, the mechanism of action of ADPM06‐PDT in vitro and in vivo is outlined. Using a drug and light combination that reduces the clonogenicity of MDA‐MB‐231 cells by >90%, we detected a well‐orchestrated apoptotic response accompanied by the activation of various caspases in vitro. The generation of reactive oxygen species (ROS) upon photosensitizer irradiation was found to be the key instigator in the observed apoptotic response, with the endoplasmic reticulum (ER) found to be the intracellular site of initial PDT damage, as determined by induction of a rapid ER stress response post‐PDT. PDT‐induced apoptosis was also found to be independent of p53 tumor suppressor status. A robust therapeutic response in vivo was demonstrated, with a substantial reduction in tumor proliferation observed, as well as a rapid induction of apoptosis and initiation of ER stress, mirroring numerous aspects of the mechanism of action of ADPM06 in vitro. Finally, using a combination of 18F‐labeled 3′‐deoxy‐3′‐fluorothymidine (18F‐FLT) nuclear and optical imaging, a considerable decrease in tumor proliferation over 24‐hr in two models of human cancer was observed. Taken together, this data clearly establishes ADPM06 as an exciting novel PDT agent with significant potential for further translational development.
Hemin, an iron‐binding porphyrin, inhibits HIF‐1α induction through its binding with heat shock protein 90
Authors: Lee Jung Min , Lee Woo Hyung , Kay Hee Yeon , Kim Eun‐sook , Moon Aree , Kim Sang Geon
Published: March 2011

Hypoxia and growth factor stimulation induce hypoxia‐inducible factor‐1α (HIF‐1α), conferring upon cancer cells the ability to adapt to microenvironments and enhance proliferation, angiogenesis and metastasis. Hemin, an iron‐binding porphyrin, has been used to treat porphyria attacks, particularly in acute intermittent porphyria. Although the anti‐inflammatory and antitumor effects of hemin were reported, no information is available regarding its effect on HIF‐1α. Our study investigated whether hemin and other protoporphyrin compounds have the ability to inhibit HIF‐1α activity, and if so, what is the molecular basis of inhibition. Hemin treatment prevented CoCl2‐induced HIF‐1α expression. HIF‐1α inhibition by hemin resulted from an increase in its facilitated ubiquitination and degradation, as shown by the experimental results using cychloheximide treatment and ubiquitination assays. Consistently, hemin repressed HIF‐1α‐dependent gene transactivation. Intriguingly, hemin directly impeded the binding between heat shock protein 90 (HSP90) and HIF‐1α, which was reversed by the addition of an excess amount of ATP required for HSP90 activity. In addition, hemin decreased the expression of client proteins of HSP90. Thus, the inhibition of HIF‐1α activity by hemin might result from its interaction with HSP90. Moreover, treatment of protoporphyrin IX, ZnPP or Co(III)PP, but not Mn(III)PP, inhibited HIF‐1α induction, indicating that protoporphyrin ring in association with the nature of binding metal leads to HSP90 inhibition. In an in vivo model, hemin treatment inhibited not only the formation of new vessels but also cancer cell proliferation and migration/invasion, supporting the notion that hemin may be applied to the prevention and/or treatment of angiogenesis and/or cancer metastasis.
Potential mechanism of interleukin‐8 production from lung cancer cells: An involvement of EGF–EGFR–PI3K–Akt–Erk pathway
Authors: Zhang Yong , Wang Linyan , Zhang Miaomiao , Jin Meiling , Bai Chunxue , Wang Xiangdong
Published: March 2011

Tumor inflammatory microenvironment is considered to play the role in the sensitivity of tumor cells to therapies and prognosis of lung cancer patients. Interleukin‐8 (IL‐8) is one of critical chemo‐attractants responsible for leukocyte recruitment, cancer proliferation, and angiogenesis. The present study aimed at investigating potential mechanism of IL‐8 production from human non‐small cell lung cancer (NSCLC) SPC‐A1 cells. We initially found that EGF could directly stimulate IL‐8 production, proliferation, and bio‐behaviors of lung cancer cells through the activation of EGFR, PI3K, Akt, and Erk signal pathway. EGF‐stimulated IL‐8 production, phosphorylation of Akt and Erk, and cell proliferation and movement could be inhibited by EGFR inhibitor (Erlotinib), PI3K inhibitor (GDC‐0941 BEZ‐235 and SHBM1009), and ERK1/2 inhibitor (PD98059). Our data indicate that IL‐8 production from lung cancer cells could be initiated by their own produced factors, leading to the recruitment of inflammatory cells in the cancer tissue, and the formation of inflammatory microenvironment. Thus, it seems that the signal pathway of EGFR–PI3K–Akt–Erk can be the potential target of therapies for inflammatory microenvironment in lung cancer. J. Cell. Physiol. 227: 35–43, 2012. © 2011 Wiley Periodicals, Inc.
Alteration of G1/S transition regulators influences recurrences in head and neck squamous carcinomas
Authors: Canzonieri Vincenzo , Barzan Luigi , Franchin Giovanni , Vaccher Emanuela , Talamini Renato , Sulfaro Sandro , Baldassarre Gustavo
Published: March 2011

Head‐Neck Squamous Cell Carcinoma (HN‐SCC) is a clinically challenging disease associated with a high mortality rate. The chemo‐radiotherapy treatments that aim to preserve the organ represent the current gold standard therapy for advanced laryngeal disease, reserving surgery only for non‐responsive or relapsed cases. Despite these aggressive approaches, local persistent or recurrent disease remains the primary cause of treatment failure but we still do not have known factors and/or markers able to predict the outcome of the disease and in particular the risk of local relapse. Here we address this point on a series of 54 cases of HN‐SCC for whom the presence of local relapse was known. Using immunohistochemistry (IHC) analysis to evaluate protein expression and localization in the recurrence free and recurrence positive samples, we studied the expression of key cell cycle regulators including p53, p16, p27, pRB, Cyclin D1, Cyclin D3, and Stathmin. Overall by analyzing seven different cell cycle regulators we can hypothesize that the alteration of G1/S regulation represents a fundamental event in the onset/progression of HN‐SCC cancers and that the associate use of Cyclin D1/p16 expression should be considered as a possible biomarker toward the identification of those patients that will probably develop a recurrent disease and thus should benefit of a more aggressive treatment. J. Cell. Physiol. 227: 233–238, 2012. © 2011 Wiley Periodicals, Inc.
Rhinovirus contamination of surfaces in homes of adults with natural colds: Transfer of virus to fingertips during normal daily activities
Authors: Winther B. , McCue K. , Ashe K. , Rubino J. , Hendley J.O.
Published: March 2011

Multiple surfaces contaminated with rhinovirus were detected in hotel rooms by reverse transcriptase‐polymerase chain reaction (RT‐PCR) following occupancy by a cold sufferer. Whether infectious rhinovirus contaminates surfaces in homes and is transferred from surfaces to fingertips through normal activities is not known. Nasal secretions from 30 subjects with new colds were tested for rhinovirus genome by RT‐PCR; infectious rhinovirus was sought with tissue cultures. Each subject identified 10 sites in their home touched during the preceding 24 hr. Samples from sites were tested for rhinovirus by RT‐PCR and cell culture. Later, each subject's mucus (stored at −70°C) was deposited on surfaces for testing transfer to fingertips through daily life activities such as flipping a light switch, touching the telephone keypad, and holding the telephone handset. Nasal secretions from 16/30 subjects were positive for rhinovirus by RT‐PCR; 66 (41%) of 160 surfaces in homes were positive. Contaminated surfaces included doorknobs (6 positive/18 tested), refrigerator door handles (8/14), TV remote controls (5/10), and bathroom faucets (8/10). Five (19%) of 26 RT‐PCR positive sites from culture positive subjects were positive in cell culture. Nasal mucus from six culture positive subjects was deposited on objects. Infectious rhinovirus was detected on 22% of fingertips following contact with objects contaminated for 1 hr; transfer dropped to 3% after 24 hr of contamination, and 0% after 48 hr. Infectious rhinovirus found on surfaces in homes of people with colds can be transferred to fingertips, but infectivity of virus in mucus declines by 24 hr after deposition. J. Med. Virol. 83:906–909, 2011. © 2011 Wiley‐Liss, Inc.
Expression profiles of genes associated with viral entry in HCV‐infected human liver
Authors: Nakamuta M. , Fujino T. , Yada R. , Aoyagi Y. , Yasutake K. , Kohjima M. , Fukuizumi K. , Yoshimoto T. , Harada N. , Yada M. , Kato M. , Kotoh K. , Taketomi A. , Maehara Y. , Nakashima M. , Enjoji M.
Published: March 2011

Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV‐infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR‐BI), claudin‐1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL‐cholesterol (LDL‐C) and HCV core antigen were also evaluated, and expression of claudin‐1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin‐1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up‐regulated in HCV‐infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin‐1, occludin versus claudin‐1, and CD81 versus SR‐BI in HCV‐infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL‐C (P = 0.0147), with their levels negatively correlated to LDLR (P = 0.0270 and P = 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin‐1 and occludin was increased in HCV‐infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin‐1 in HCV‐infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV‐infected and normal livers. J. Med. Virol. 83:921–927, 2011. © 2011 Wiley‐Liss, Inc.
Hepatitis C virus sequences from different patients confirm the existence and transmissibility of subtype 2q, a rare subtype circulating in the metropolitan area of Barcelona, Spain
Authors: Martró Elisa , Valero Ana , Jordana‐Lluch Elena , Saludes Verónica , Planas Ramón , González‐Candelas Fernando , Ausina Vicente , Bracho Maria Alma
Published: March 2011

The hepatitis C virus (HCV) has been classified into six genotypes and more than 70 subtypes with distinct geographical and epidemiological distributions. While 18 genotype 2 subtypes have been proposed, only 5 have had their complete sequence determined. The aim of this study was to characterize HCV isolates from three patients from the Barcelona metropolitan area of Spain for whom commercial genotyping methods provided discordant results. Full‐length genome sequencing was carried out for 2 of the 3 patients; for the third patient only partial NS5B sequences could be obtained. The generated sequences were subjected to phylogenetic, recombination, and identity analyses. Sequences covering most of the HCV genome (9398 and 9566 nt in length) were obtained and showed a 90.3% identity to each other at the nucleotide level, while both sequences differed by 17.5–22.6% from the other fully sequenced genotype 2 subtypes. No evidence of recombination was found. The NS5B phylogenetic tree showed that sequences from the three patients cluster together with the only representative sequence of the provisionally designed 2q subtype, which also corresponds to a patient from Barcelona. Phylogenetic analysis of the full coding sequence showed that subtype 2q was more closely related to subtype 2k. The results obtained in this study suggest that subtype 2q now meets the requirements for confirmed designation status according to consensus criteria for HCV classification and nomenclature, and its epidemiological value is ensured as it has spread among several patients in the Barcelona metropolitan area. J. Med. Virol. 83:820–826, 2011. © 2011 Wiley‐Liss, Inc.
In‐soil biodegradation of palm mat geotextiles
Authors: Kugan R. , Sarsby R. W.
Published: March 2011

The tensile strength properties of Buriti palm mat geotextiles (manufactured in Brazil using low‐tech, ‘cottage‐industry’ manufacturing techniques) have been investigated with a view to using them as engineering fabrics for soil reinforcement. The rate at which the physical properties of the vegetable fibre geotextiles decline once they have been buried in soil is a key issue. Geotextiles have been buried for various time periods in a sandy soil, under both fully and partially saturated conditions, before being tested to quantify any change in tensile strength with time. It has been found that partially saturated soil is a more aggressive environment than fully saturated soil. The Buruti palm mats retained approximately 40per cent of their initial strength after burial for 1 year in fully saturated soil, but there was total loss of strength after only 9 months when mats were buried in partially saturated soil. The strength retained under fully saturated conditions is inversely proportional to the square‐root of time whilst for partially saturated conditions the strength is directly proportional to the inverse of time. The palm mat geotextiles would not have sufficient durability for use in major ground strengthening applications but they do have potential for prolonging the life of unbound roads. Copyright © 2011 John Wiley & Sons, Ltd.
Anti‐ship missile defense for a naval task group
Authors: Karasakal Orhan , Özdemirel Nur Evin , Kandiller Levent
Published: March 2011

In this study, we present a new formulation for the air defense problem of warships in a naval task group and propose a solution method. We define the missile allocation problem (MAP) as the optimal allocation of a set of surface‐to‐air missiles (SAMs) of a naval task group to a set of attacking air targets. MAP is a new treatment of an emerging problem fostered by the rapid increase in the capabilities of anti‐ship missiles (ASMs), the different levels of air defense capabilities of the warships against the ASM threat, and new technology that enables a fully coordinated and collective defense. In addition to allocating SAMs to ASMs, MAP also schedules launching of SAM rounds according to shoot‐look‐shoot engagement policy or its variations, considering multiple SAM systems and ASM types. MAP can be used for air defense planning under a given scenario. As thorough scenario analysis would require repetitive use of MAP, we propose efficient heuristic procedures for solving the problem. © 2011 Wiley Periodicals, Inc. Naval Research Logistics, 2011
Numerical analysis of a transient eddy current axisymmetric problem involving velocity terms
Authors: Bermúdez Alfredo , Reales Carlos , Rodríguez Rodolfo , Salgado Pilar
Published: March 2011

The aim of this article is to analyze a transient axisymmetric electromagnetic model involving velocity terms in the Ohm's law. To this end, we introduce a time‐dependent weak formulation leading to a degenerate parabolic problem and establish its well posedness.We propose a finite‐element method for space discretization and prove well posedness and error estimates. Then, we combine it with a backward Euler time discretization and prove stability and error estimates. Finally, numerical results assessing the performance of the method are reported. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2011
The role of filler type in the photo‐oxidation behaviour of micro‐ and nano‐filled polypropylene
Authors: Morreale Marco , Dintcheva Nadka Tzankova , La Mantia Francesco Paolo
Published: March 2011

The rising interest in polymer nanocomposites leads also to an increasing concern for their photo‐oxidation resistance. The main properties and photo‐oxidation behaviour of polypropylene‐based microcomposites and nanocomposites were investigated. The results show that the use of nanosized calcium carbonate may lead to a higher photo‐oxidation rate than that of pristine polypropylene, in a way that is comparable to organo‐modified nanoclays. It is also observed that nanosized calcium carbonate causes higher photodegradation rates than microsized calcium carbonate. The main reasons for the increased photo‐oxidation rates when using organo‐modified nanoclays include the presence of iron ions, the degradation of the organo‐modifier and the formation of acidic sites on nanoclay layers, while in the case of calcium carbonate the main reasons are related to the achieved morphology and structure. The presence of calcium carbonate, especially when nanosized, significantly modifies the distribution of photo‐oxidation products in comparison to clay‐filled nanocomposites. Copyright © 2011 Society of Chemical Industry
Empirically valid strategies to improve social and emotional competence of preschool children
Authors: McCabe Paul C. , Altamura Michelle
Published: March 2011

Research over the past few decades has highlighted the importance of social and emotional competence in preschool children on later academic, social, and psychological outcomes. Children who are socially and emotionally competent have increased socialization opportunities with peers, develop more friends, have better relationships with their parents and teachers, and enjoy more academic and social successes. Children who lack social and emotional competence are at risk for reduced socialization opportunities, rejection, withdrawal, behavioral disturbance, and achievement problems. Intervention programs that target social–emotional development in preschool are ideally situated to bolster these skills before the problems exacerbate. In this paper, research on the importance of social and emotional competence in young children is reviewed as it relates to immediate and long‐term outcomes. Assessments of social and emotional development and behavioral adjustment are briefly reviewed, followed by a review of intervention programs with demonstrated empirical efficacy. Although preliminary evidence supports the utility of these intervention programs, additional research on short‐ and long‐term efficacy is recommended, and more programs designed specifically for early childhood are needed. © 2011 Wiley Periodicals, Inc.
Comparative effect of integrated pest management and farmers' standard pest control practice for managing insect pests on cabbage (Brassica spp.)
Authors: Reddy Gadi VP
Published: March 2011

BACKGROUND: Studies were conducted on experimental cabbage plantings in 2009 and on experimental and commercial plantings in 2010, comparing farmers' current chemical standard pesticide practices with an integrated pest management (IPM) program based on the use of neem (Aza‐Direct) and DiPel (Bacillus thuringiensis). In experimental plantings, the IPM program used six or eight applications of neem and DiPel on a rotational basis. The standard‐practice treatments consisted of six or eight applications of carbaryl and malathion or control treatment.

RESULTS: The IPM treatments reduced pest populations and damage, resulting in a better yield than with the standard chemical or control treatment. When IPM treatment included three applications of neem plus three applications of DiPel (on a rotational basis in experimental fields), it again reduced the pest population and damage and produced a better yield than the standard practice. The lower input costs of the IPM program resulted in better economic returns in both trials.

CONCLUSIONS: The IPM components neem and DiPel are suitable for use in an IPM program for managing insect pests on cabbage (Brassica spp.). Copyright © 2011 Society of Chemical Industry
Crystal growth and electric properties of lead‐free NBT‐BT at compositions near the morphotropic phase boundary
Authors: Zhang Qinhui , Zhao Xiangyong , Sun Renbing , Luo Haosu
Published: March 2011

Lead‐free piezoelectric materials such as Na0.5Bi0.5TiO3‐BaTiO3 (NBBT) solid solution have been paid increasing attention from an environmental perspective. In this paper, a series of NBBT single crystals with compositions near the morphotropic phase boundary (MPB) were grown by the top‐seeded solution growth (TSSG) method. The compositional dependence of crystalline structure was investigated by high‐resolution X‐ray diffraction (XRD). In addition, the dielectric, piezoelectric and ferroelectric (FE) properties of NBBT crystals were also investigated. Excellent piezoelectric properties of NBBT crystals, especially large thickness coupling factors kt, were obtained near the MPB, which are more than or close to the performances of PZT ceramics. Moreover, the performances of NBBT crystals can be further enhanced by doping. Finally, the domain configurations of NBBT96/4 crystal were studied preliminarily.

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Impedance spectroscopy analysis for high‐Tc BaTiO3‐(Bi1/2Na1/2)TiO3 lead‐free PTCR ceramics
Authors: Leng Senlin , Zheng Liaoying , Li Guorong , Zeng Jiangtao , Yin Qingrui , Xu Zhijun , Chu Ruiqing
Published: March 2011

The ac impedance measurement was used to investigate the yttrium (Y)‐doped 0.99BaTiO3‐0.01Bi1/2Na1/2TiO3 (0.99BT‐0.01BNT) lead‐free positive temperature coefficient of resistivity (PTCR) ceramics in the frequency range from 40 Hz to 2 MHz and in the temperature range from room temperature to 240 °C. The resistivity and capacitance of each electrical component can be obtained from the complex impedance and electric modulus spectroscopy. These obtained data were discussed and compared with directly experimental measured results. In addition, the surface acceptor‐state density and depletion layer thickness were calculated. The grain‐boundary potential barrier of the samples was also estimated according to the Heywang model, the value was between 0.17 and 0.55 eV in the temperature range of 150–240 °C.
Thermal conductivity of Gd2Zr2O7 thin films using thermal‐impedance method
Authors: Kim J. W. , Jeong G. E. , Yang Ho‐Soon
Published: March 2011

Pyrochlore‐structured rare‐earth materials have been of interest recently as thermal‐barrier coating materials because they show low thermal conductivity due to the oxygen vacancy. This study reports the preparation and thermal characterization of Gd2Zr2O7 films deposited on YSZ and Al2O3 substrates. Since the thermal properties of Gd2Zr2O7 and YSZ are not obviously different, the thermal‐impedance method (the extended 3ω method) is used to study the films in this work. Gd2Zr2O7 thin films of various thicknesses are deposited using a pulsed laser deposition method. The thermal conductivity of Gd2Zr2O7 thin films exhibits a dependence on film thickness. The thickness‐dependent thermal conductivity is ascribed to the interfacial thermal resistance between the Gd2Zr2O7 film and substrates. The interfacial resistance is obtained by fitting the thickness‐dependent thermal conductivity with the effective thermal‐conductivity equation.
Fabrication of ordered silicon nanopillars and nanowires by self‐assembly and metal‐assisted etching
Authors: Boarino Luca , Imbraguglio Dario , Enrico Emanuele , De Leo Natascia , Celegato Federica , Tiberto Paola , Pugno Nicola , Amato Giampiero
Published: March 2011

Silicon nanowires (SiNWs) and nanopillars have been obtained by metal‐assisted etching (MAE), starting from silver thin films deposited by thermal evaporation and sputtering on silicon substrates. Different deposition methods and thickness are strongly affecting spatial distribution and shapes of the extruded silicon nanostructures. The paper reports a study of distribution and morphology, as a function of silver thickness, deposition conditions and etching times. The application of polystyrene soft masks obtained by self‐assembly and the sputter‐etching by Ar ions allow the formation of regular indentations in the silver thin films, giving origin to a regular distribution of extruded pillars and wires during the following etching in HF:H2O2:H2O. The aqueous etching and the use of silver still influence the homogeneity of the etching result on large area and introduce a modulation in the etching front, so affecting thickness homogeneity. Work is in progress to replicate these former results with gold and different etching solutions.

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SEM microphoto of ordered SiNWs obtained by MAE and polystyrene nanosphere self‐assembly.